June 2023 Pulmonary Case of the Month: An Invisible Disease

Lewis J. Wesselius MD

Pulmonary Department

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 78-year-old man presented to the Emergency Department on April 7 for shortness of breath and weakness over the last 2 weeks. He was in good health prior to an outside hospitalization March 29-April 3 for pneumonia and a possible non-ST-elevation myocardial infarction (elevated troponins). He had a bronchoscopy during his recent outside hospitalization without specific pathogen identified but was treated with antibiotics and discharged on levofloxacin. Since his hospital discharge 4 days previously he feels weaker and increasingly short of breath. He is short of breath even walking around his home. He denies fever or a productive cough.

Past Medical History, Family History and Social History

• Atrial fibrillation, s/p ablation. On Eliquis.
• Prior renal cell carcinoma, s/p resection, no recurrence
• DM Type 2
• GERD
• OSA
• Essential tremor
• Never smoked

Medications

• Apixaban
• Aspirin
• Atorvastatin
• Flecanide
• Insulin
• Levofloxacin
• Lisinopril
• Pantoprazole
• Tamsulosin

Physical Examination

• General: The patient looks comfortable and is in no distress
• Vital Signs: BP 110/62 O2 Sat 94% on room air
• CVS: Heart sounds are regular
• Lungs: Clear to auscultation
• Abdomen: Soft, nontender, bowel sounds present
• Extremities: No edema
• Neuro: Alert and oriented
• Skin: Warm and dry, no rashes

Chest X-ray

A portable chest X-ray was performed (Figure 1).

Figure 1. Portable chest X-ray obtained in the emergency department.

Which of the following should be done next? Click on the correct answer to be directed to the second of six pages)

1. Arterial blood gases
2. Bronchoscopy
3. Thoracic CT scan
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. June 2023 Pulmonary Case of the Month: An Invisible Disease. Southwest J Pulm Crit Care Sleep. 2023;26(6):83-86. doi: https://doi.org/10.13175/swjpccs022-23 PDF

Case Report: The Importance of Screening for EVALI

Vanessa Josef MD, MS

George Tu, MD, FCCP

Department of Internal Medicine and Lung Center of Nevada

HCA MountainView Hospital

Las Vegas, Nevada, USA

Abstract

E-cigarette or vaping product use associated lung injury (EVALI) is an epidemic that has swept the United States by storm starting in Sept 2019. E-cigarettes or vaping was initially advertised as a “safer” alternative to smoking cigarettes when they entered the market in 2007. Only now are we are starting to see the complications of a not so harmless behavior. Many times, EVALI can present similar to community acquired pneumonia (CAP), which can cause a clinical conundrum when despite adequate antibiotic coverage, patients’ respiratory status tend to decline. Through our case report, we demonstrate and stress the importance of early screening for e-cigarette and vaping use in social history to increase clinical suspicion of EVALI and provide early intervention if a patient does not respond to CAP treatment, in hopes of identifying more cases of EVALI and igniting future research. 

Introduction

The recent outbreaks of E-cigarette or vaping product use associated lung injury (EVALI) in Sept 2019, has placed the spotlight on the dangers of vaping. EVALI is a form of acute or subacute lung injury whose pathogenesis is unknown and is thought to be a spectrum of disease, rather than a single process. It has many findings such as organizing pneumonia, diffuse alveolar damage or acute fibrinous pneumonitis that are bronchiocentric and accompanied by bronchiolitis (1). If not identified quickly, EVALI has led to non-invasive ventilation, intubation and mechanical ventilation and even death in, otherwise, healthy young adults (1). The CDC confirmed 57 deaths and 2,602 reported cases of EVALI throughout the United States from Aug 2019 to Jan 2020, all of whom were between the ages of 18-34 (2,3). The paucity of knowledge within the medical community with regards to the disease, its pathogenesis and targeted treatment puts clinicians at a disadvantage. We report a case of a 30-year-old male who presented to our hospital with complaints of flu-like symptoms who was initially thought to have community acquired pneumonia but was later diagnosed with EVALI in order to raise awareness, illustrate how crucial screening can affect patient outcome and the need for further investigations of this severe respiratory illness. 

Case Presentation

A 30-year-old Hispanic male with significant past medical history of intracranial hemorrhage secondary to arteriovenous malformation and craniotomy (2016) was admitted to our hospital in December 2019 after experiencing productive cough, subjective fevers, malaise, night sweats, dizziness, and fatigue for 3 days. He denied having any sick contacts or obtaining the flu vaccine, or any recent hospitalization. His admitting diagnosis was sepsis due to community acquired pneumonia and he was found to have acute renal failure which was pre-renal in nature.

Clinical findings on admission were as follows: body temperature 37°C, blood pressure 116/75mmHg, heart rate 129 beats/min, respiratory rate 18 breaths/min and oxygen saturation 99% on room air. Physical examination revealed diminished breath sounds on the right lower lobe upon auscultation. The patient’s breathing did not appear labored and he was able to speak full sentences. Laboratory tests revealed: white blood cell count of 13,000 x 10⁹/L with 88.8% neutrophils, BUN/creatinine was 29/1.59 (elevated compared to last admission in 2016), urine toxicology was positive for cannabinoids, urinalysis showed proteinuria of 100 and the rest of the biochemical testing were within normal ranges.

The initial chest x-ray (Figures 1 and 2) was read as interval development of interstitial type infiltrates in the perihilar and lower lobe distribution bilaterally, favoring pneumonia, compared to his pervious chest x-ray from 2016 which had no evidence of acute cardiopulmonary process (Figure 3).

Figures 1 and 2. Chest radiography (PA and lateral views) from the day of admission.

Figure 3. Chest radiograph from a previous admission in 2016 showing no acute cardiopulmonary process.

Sepsis bolus was given in the emergency department, blood cultures were drawn, and patient was started on ceftriaxone and azithromycin for community acquired pneumonia. Overnight, The patient spiked fever twice of 39°C at 2am and 4am the next morning. Antibiotics were broadened to vancomycin and piperacillin-tazobactam and blood cultures were repeated. Patient endorsed dyspnea and increased work of breathing requiring 2L nasal cannula. He remained tachycardic with his heart rate in the 110s despite adequate fluid resuscitation and antibiotic coverage. He also spiked an additional fever of 39.3°C at 8am. Arterial blood gas obtained showed pH 7.49, pCO₂ 33, pO₂ 70, HCO₃ 25 on 2L nasal cannula indicating acute hypoxic respiratory failure and respiratory alkalosis. Since renal function normalized, CT angiogram of the chest (Figure 4) was obtained. Although negative for pulmonary embolism, it showed extensive bilateral ground-glass lung opacities characteristic of pulmonary edema or pneumonia, noted predominantly in the lower and middle lung zones with sparing of the periphery.

Figure 4. CT angiography of the chest in lung windows, almost 24hrs after presentation to the emergency department.

Pulmonology was consulted. Upon further questioning it was discovered the patient has been vaping CBD oil and THC for about 5 years. He vapes approximately 1-2 dabbed cartridges per week which he normally obtains from a dispensary and his friends. The last time he vaped was 3 days prior to admission. He denied smoking tobacco, having a history of childhood asthma. He was started on methylprednisolone 40mg IV BID. Because his temperature became mildly elevated at 37.9°C in the afternoon, it was decided to take him for a bronchoalveolar lavage (BAL) the following day.

Respiratory viral panel, urine Legionella and urine Streptococcus pneumoniae, HIV 4^th generation screen, sputum culture and blood cultures were all negative. Procalcitonin was 3.88 ng/ml. BAL cytology revealed non-specific pulmonary macrophages, benign bronchial epithelial cells, and mucus. It was negative for fungal organisms, cytomegalovirus, Mycoplasma, tuberculosis, Pneumocystis jirovecii, Legionella, and malignant cells. Gram stain was negative as well. 

No other events occurred during the rest of his hospital course. Extensive counseling provided regarding cessation of vaping, which the patient expressed he will no longer do. His respiratory symptoms improved with the start of steroids and he was discharged on hospital day 6 with Augmentin and a 10-day prednisone taper.

Discussion

Currently, EVALI is a diagnosis of exclusion, rather than part of the initial screening for patients who present to the hospital with respiratory complaints. During our team’s initial assessment of the patient, vaping was not asked based off the reported history, imaging studies, and labs obtained by the emergency department because it appeared to be a straightforward case of sepsis secondary to community acquired pneumonia (CAP). However, despite adequate antibiotic coverage with ceftriaxone and azithromycin our patient continued to spike high fevers overnight. He did not have any risk factors for MRSA or Pseudomonas that would call for broad empiric coverage when he was first admitted based off the IDSA 2019 guidelines for treating CAP (7).

Despite sepsis fluid resuscitation, our patient remained tachycardic where his heart rate ranged between 110-120s. CT angiogram of the chest to rule out pulmonary embolism could not be done when he was admitted due to acute renal failure. A ventilation-perfusion scan would not be an appropriate study at the time due to patient’s abnormal chest x-ray. Thus, the details of the lung parenchyma could not be appreciated at the time of admission. With his continual fever spikes, we ordered the following labs to try and identify the type of infection, the possibility of a superimposed infection or resistance to the current antimicrobial regimen and if the patient was immunocompromised: flu antigens, urine Legionella and Streptococcus pneumoniae, respiratory viral panel (adenovirus, human metapneumovirus, influenza A & B, parainfluenza 1, 2 & 3, RSV, rhinovirus), HIV 4^th generation screen, sputum culture, procalcitonin and repeat blood cultures. That same morning, his antibiotics were broadened to vancomycin and piperacillin-tazobactam.

Since the patient endorsed increased work of breathing and required 2L nasal cannula when he was initially on room air when he first arrived, pulmonary embolism (PE) had to be ruled out. With his renal function back to normal, we were able to get the CT angiogram of the chest which was negative for PE but showed the largely affected parenchyma. Pulmonology was consulted because of the irregular findings and sudden decline. Based off the peripheral sparing which is characteristic for EVALI and his urine toxicology testing positive for cannabinoids, further questioning about his social history was obtained. The patient’s admission to vaping THC and CBD oil for several years and that he obtains his cartridges from dispensaries and his friends, increased the suspicion for EVALI. Based on the current literature and reports from the CDC, EVALI is largely associated with the use of THC and products obtained from informal sources such as family/friends, dealers or online sellers (1). Many times, these unregulated products contain vitamin E acetate, which is currently thought to be the culprit ingredient igniting the destruction of lung parenchyma (4). The answer remains unclear if the cause of EVALI is an inhalation injury and/or is there an intrinsic reaction sparked by the chemical reactions between the various products that causes tissue injury.

He was immediately started on methylprednisolone 40mg IV BID, based on the recommended dosing of intravenous steroids of 1mg/kg (6). However, the patient’s temperature started to rise again despite the initiation of empiric antibiotics and steroids on the same day. BAL was performed the next morning to rule out infection, malignancy or any other structural issues and only revealed non-specific pulmonary macrophages, benign bronchial epithelial cells, and mucus. The patient clinically improved with the continued regimen of vancomycin, piperacillin-tazobactam and methylprednisolone IV.

There have been notable case reports with regards to EVALI that illustrate its various presentations and some of the barriers that make it difficult to diagnose. Salzman et al. (8) presented a case of a 27-year-old Caucasian female who developed acute eosinophilic pneumonia associated with electronic cigarettes. CBC at the time of admission showed WBC of 24,400 with 47% eosinophils. Although she admitted to vaping both nicotine and THC products for at least three years, three months prior to admission, she was vaping exclusively JUUL pods with nicotine blueberry and mint flavors. Her symptoms were severe enough that she required a one day stay in the ICU. She was treated with oral prednisone 50mg daily for a total of 5 days and oral doxycycline 100mg BID with improvement in her symptoms. This brings up the question whether her prior vaping history already jeopardized her lung parenchyma thus putting her at higher risk for developing EVALI.

In Schmitz’ (9) case report of a 38-year-old obese female with fibromyalgia on chronic prednisone (20mg daily), she admits to having started vaping CBD oil one month prior to admission. On BAL she was found to have diffuse upper and lower airway erythema with significant coughing, elevated eosinophil count (59%) and foamy macrophages which is associated with EVALI. She was started on methylprednisolone 1000mg daily, without antibiotics and experienced rapid improvement within a couple of days.

Works and Stack (5) discussed the case of a 20-year-old male who had several hospital admissions due to complaints of productive cough, high grade fever, gastrointestinal symptoms of diarrhea/nausea and 20lb unintentional weight loss over 3 weeks. The patient initially was treated at another hospital with ceftriaxone, levofloxacin and azithromycin and did not complete the course of antibiotics because they left against medical advice since they did not experience any improvement. On admission, the patient was found to have a very high leukocytosis with WBC of 44,800 and was not started immediately on empiric antibiotics. Instead, he was started on prednisone 1mg/kg and Bactrim after the BAL failed to yield an infectious cause. The patient was also noted to have obtain his THC cartridges from an outside source, like our patient.

Panse’s (10) case of a 25-year-old male who previously smoked 1-2packs per day and quit 6 months prior to admission was not forthcoming about vaping. Both CT scans showed multifocal ground-glass opacities with features of small airway obstruction. He underwent bronchoscopy and transbronchial biopsy which did not provide enough information to make a diagnosis. A video-assisted thorascopic lung biopsy was performed and showed acute and organized lung injury with interstitial edema, type II pneumocyte hyperplasia, alveolar fibrin deposition, acute fibrinous pneumonitis, lipid-laden macrophages and foci of organizing pneumonia consistent with EVALI. This is a prime example of how omission of vaping history delays diagnosis, leads to invasive procedures and although it did not happen in this particular situation, can result in death (10). Unlike the patient in Panse’s case, our patient easily admitted to vaping. Non-disclosure of medically relevant information such as vaping, is a problem clinicians will run into especially since it is a key piece of information needed to diagnose EVALI. Many patients withhold information from their doctors, especially those that they may find embarrassing, feel that they will be judge or lectured, or not wanting to hear about associated harm. Quantifying how many patients are withholding information or how many cases are not being accounted for because the person does not want to admit they are vaping would be difficult.

Formal diagnostic criteria for EVALI has not been agreed upon which can be attributed to the various forms of lung injury. We were able to diagnose our patient based of the suggested criteria of e-cigarette or vaping in the previous 90 days, lung opacities on chest x-ray or CT, exclusion of infection, and the absence of alternative diagnosis (cardiac, neoplastic or rheumatologic) (1). In a case series by Kalininskiy et al. (12), the University of Rochester Medical Center (Rochester, New York, USA) created a clinical practice algorithm to allow for the rapid identification of suspected EVALI based on history, clinical presentation and chest imaging, which is similar to the CDC however it focuses on vaping activity from the past 30 days rather than 90 days.

Currently, the treatment of EVALI is empiric antibiotics for community acquired pneumonia, systemic glucocorticoids in those with worsening symptoms, and supportive therapy with supplemental oxygen (6). In our case, the patient improved with the combination of vancomycin, piperacillin-tazobactam and methylprednisolone. The efficacy of systemic glucocorticoids is still unknown (1). However, it still remains unclear whether it was the combination of those specific antibiotics in conjunction with steroids, the combination of vancomycin and piperacillin-tazobactam only or solely systemic glucocorticoids. Since CAP is more common, it should not be overlooked and go untreated. Further investigation needs to be done for more targeted therapy.

The long-term effects of EVALI in those who were treated are still not well known. It is currently recommended for repeat imaging to determine if the treatment regimen was successful. However, many patients are lost to follow-up, as was the case for our patient due to lack of insurance.

Our case report illustrates how crucial early identification of EVALI affects patient care. It is imperative clinicians screen for the disease to prevent further complications. We recommend the following screening criteria: although the population greatly affected by the EVALI epidemic have been predominantly males between the ages of 18-34 (37% of the cases reported to the CDC as of Jan 14, 2020 are age 18-24, and 24% are 25-34, with a 66% male predominance) it should include all those who vape or use e-cigarettes regardless of age or gender as illustrated with the aforementioned case reports (13). Patients who presents with respiratory symptoms, especially if they are similar to pneumonia, such as dyspnea, increased work of breathing, fevers/chills, productive cough, chest pain, pleurisy, hemoptysis, and noted hypoxemia should be asked more than just smoking history with regards to cigarettes. They should be asked about prior E-cigarettes usage or vaping in the past, when was the last use, what kind of products were used and were they concentrated/dabbed and where it was obtained. Clinical suspicion should be increased if patients admit to THC or CBD use, but nicotine, flavorings and additives should not be disregarded. Urine drug screen should be ordered if there is a strong clinical suspicion, and the patient is denying prior THC use. EVALI has also been associated with gastrointestinal symptoms of abdominal pain, diarrhea, and nausea/vomiting. It is important to rule out infectious causes, by asking about sick contacts, recent hospitalizations, history of HIV and use of immunologic agents that can cause one to be immunocompromised. Patients should be screened about airway diseases such as asthma, COPD, and interstitial lung disease since they could have already caused chronic changes to lung parenchyma. There is still so much that the medical community does not know about EVALI. Further investigations still need to be pursued to improve the medical community’s diagnosis and treatment of this serious respiratory epidemic.

Disclaimer

This research was supported (in whole or in part) by HCA and/or an HCA affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA or any of its affiliated entities.

References

1. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin - final report. N Engl J Med. 2020 Mar 5;382(10):903-16. [CrossRef] [PubMed]
2. Centers for Disease Control. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. January 17, 2020.Available at: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#key-facts (accessed 3/10/20).
3. Ellington S, Salvatore PP, Ko J, et al. Update: product, substance-use, and demographic characteristics of hospitalized patients in a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury - United States, August 2019-January 2020. MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):44-9. [CrossRef] [PubMed]
4. Blount BC, Karwowski MP, Shields PG, et al. Vitamin E acetate in bronchoalveolar-lavage fluid associated with EVALI. N Engl J Med. 2020 Feb 20;382(8):697-705. [CrossRef] [PubMed]
5. Works K, Stack L. E‐cigarette or vaping product‐use‐associated lung injury (EVALI): A case report of a pneumonia mimic with severe leukocytosis and weight loss. JACEP Open. 2020;1-3. [CrossRef]
6. Triantafyllou GA, Tiberio PJ, Zou RH, et al. Vaping-associated acute lung injury: a case series. Am J Respir Crit Care Med. 2019 Dec 1;200(11):1430-1. [CrossRef] [PubMed]
7. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. [CrossRef] [PubMed]
8. Salzman GA, Alqawasma M, Asad H. Vaping associated lung injury [EVALI]: an explosive United States epidemic. Mo Med. 2019 Nov-Dec;116(6):492-6. [PubMed]
9. Schmitz ED. Severe respiratory disease associated with vaping: a case report. Southwest J Pulm Crit Care. 2019;19[3]:105-9.[CrossRef]
10. Panse PM, Feller FF, Butt YM, Gotway MB. February 2020 imaging case of the month: an emerging cause for infiltrative lung abnormalities. Southwest J Pulm Crit Care. 2020;20(2):43-58. [CrossRef]
11. Levy AG, Scherer AM, Zikmund-Fisher BJ, Larkin K, Barnes GD, Fagerlin A. Prevalence of and factors associated with patient nondisclosure of medically relevant information to clinicians. JAMA Netw Open. 2018 Nov 2;1(7):e185293. [CrossRef] [PubMed]
12. Kalininskiy A, Bach CT, Nacca NE, Ginsberg G, Marraffa J, Navarette KA, McGraw MD, Croft DP. E-cigarette, or vaping, product use associated lung injury (EVALI): case series and diagnostic approach. Lancet Respir Med. 2019 Dec;7(12):1017-26. [CrossRef] [PubMed]
13. Centers for Disease Control. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. February 5, 2020. Available at:  https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#map-cases (accessed 3/10/20).

Cite as: Josef V, Tu G. Case report: the importance of screening for EVALI. Southwest J Pulm Crit Care. 2020;20(3)87-94. doi: https://doi.org/10.13175/swjpcc012-20 PDF 

Intralobar Bronchopulmonary Sequestration: A Case and Brief Review

Uddalak Majumdar, MD¹ 

Payal Sen, MD²

Akshay Sood, MD²

¹Cleveland Clinic Foundation, Cleveland, OH USA

²Univeristy of New Mexico, Albuquerque, NM USA

Abstract

Objective: Bronchopulmonary sequestration is a rare congenital abnormality of the lower respiratory tract, seen mostly in children but often in adults. The term implies a mass of lung tissue that has no function and lacks normal communication with the rest of the tracheobronchial tree.

Case: A 40-year-old man presented with acute onset of left flank pain for 4 hours. He was born in Yemen and emigrated to the US in 1998; at that time, he had been tested for tuberculosis which was negative. In this admission, he met systemic inflammatory response (SIRS) criteria and had basilar crackles in the left lower lobe of the lung. CT scan revealed a cavitary lesion with air-fluid level in the left lower lobe airspace. There was systemic arterial blood supply to this region arising off the celiac axis. He was diagnosed with an infected intralobar bronchopulmonary sequestration and underwent video-assisted thoracoscopic wedge resection. On follow up 3 months later, he was doing well.

Discussion: Pulmonary sequestration is a rare congenital anomaly of a mass of lung tissue, which can have cystic changes and is a very important differential diagnosis of cavities in the lung. Confirmation of diagnosis is by visualization of a systemic vessel supplying sequestrated pulmonary, and this is accomplished by contrast-enhanced CT scan, MRI or invasive angiography. 

Conclusion: The delay in diagnosis in our patient was due to falling prey to anchoring and availability biases and chasing the diagnosis of tuberculosis in a patient from Yemen with a lower lobe cavitation.

Case

History of Present Illness: A 40-year-old man with a past medical history of atrial fibrillation presented to the hospital with acute onset of left flank pain for 4 hours, fevers and chills. The pain was sharp and stabbing, pleuritic, non-radiating, and was severe with an intensity of 10/10. He denied extraneous activity or trauma earlier in the day, denied substernal pain, cough, night sweats, weight loss or change in urinary habits. He was born in Yemen and emigrated to the US in 1998; at that time, he was tested for tuberculosis (TB) which was negative. He was known to have a cavitary lesion in left lower lobe since 2005, and had undergone extensive evaluation (imaging, sputum and PPD) which showed no form of tuberculosis. He denied taking prophylactic TB treatment. Annual PPD testing had always been negative.

The patient worked on a ship, which travelled in the Great Lakes on the US-Canada border. He was a current smoker with a 20-pack-year smoking history. He lived at home with his wife and children. There was no history of IV drug use, prior imprisonment or homelessness. He denied being in contact with anyone with TB while in Yemen. He was sexually active with his wife and had no other sexual partners. He denied history of sexually transmitted infections.

Physical Examination:

Vital Signs: Temp – 38.3 degrees Fahrenheit, Pulse- 111/minute, RR- 18/min, BP- 151/66 mm Hg. Spo2- 90 % on Room Air.

Basilar crackles and rhonchi in the left lower lobe of the lung. No cervical or inguinal lymphadenopathy. Rest of the physical exam was normal.

Significant Laboratory Findings:

WBC elevated at 15,500/mm³ with 65 percent Neutrophils.

Lactate - 1.1 mmol/dL

Radiography:

Chest x-ray was done while in the emergency department, which revealed left basilar sub-segmental atelectasis (Figure 1).

Fig.1. Chest x-ray showing left basilar sub-segmental atelectasis without focal consolidation, large pleural effusion or pneumothorax.

Initial CT scan of abdomen and pelvis was done to rule out renal/ureteral stone. It showed a left lower lobe airspace consolidation with bronchiectasis and bronchiolectasis and a cavitary lesion with air-fluid level (Figure 2). 

Figure 2. Representative images from the CT scan in lung windows showing left lower lobe airspace consolidation concerning for an acute on chronic process.

C-reactive protein and erythrocyte sedimentation rate were normal, CRP and ESR- normal; blood cultures revealed no growth; procalcitonin 0.4 ng/mL (normal <0.15); anti-nuclear antibody – negative; Aspergillus antigen – negative; urine Legionella antigen – negative; Streptococcus pneumoniae antigen – positive.

Sputum Gram stain and acid-fast bacilli culture/stain could not be obtained because the patient did not produce any sputum.

Subsequently CT chest with IV contrast was done which showed findings compatible with a pneumonia within a left lower lobe intrapulmonary sequestration. (Figure 3).

Figure 3. Representative images from the thoracic CT chest with IV contrast. The left lower lobe demonstrates a 69 x 83 mm heterogeneous fluid collection with multiple locules of air. There was systemic arterial blood supply to this region arising off the celiac axis (arrows).

The patient was diagnosed with an infected intralobar bronchopulmonary sequestration. He was treated initially with intravenous fluids and piperacillin-tazobactam. He underwent video-assisted thoracoscopic wedge resection of infected bronchopulmonary sequestration in left lower lobe and ligation of the systemic feeding vessels from the celiac artery. Pathologic examination revealed a fibrotic lung with areas of centrilobular emphysema, bronchiolectasis, mucus pooling and microscopic honeycomb changes. Findings also showed an elastic artery, with features most suggestive of intralobar sequestration. His symptoms completely resolved after his operation.

Discussion

Bronchopulmonary sequestration is a rare congenital abnormality of the lower respiratory tract, seen mostly in children but often in adults, like in our patient (1). In 1946, Pryce coined the term "pulmonary sequestration" to describe a disconnected bronchopulmonary mass or cyst with an anomalous arterial supply (2). The term implies a mass of lung tissue that has no function and lacks normal communication with the rest of the tracheobronchial tree. This mass of non-functional lung tissue receives blood supply from the systemic circulation (3). The exact etiology is unknown and is thought to be an embryologic process error in foregut budding (4), although some have indicated a non-congenital acquired process in intralobar sequestration.

Sequestration may be intra- or extralobar based on its relation with the normal lung lobes. An intralobar sequestration (ILS), like the name suggests, is located within a normal lobe, lacks its own visceral pleura (5) and also has aberrant connections to bronchi, and lung parenchyma, or even the gastrointestinal tract, and often presents with recurrent infections (6,7). Compared to ILS, an extralobar sequestration (ELS) is located outside the normal lung and has its own visceral pleura (8), with the rare occurrence of infectious complications (9). About 75% of BPS is intralobar while 25% is extralobar (10). Bronchopulmonary sequestration is often associated with other congenital abnormalities like congenital diaphragmatic hernia, vertebral anomalies, congenital heart disease, pulmonary hypoplasia, colonic duplication, and congenital pulmonary airway malformation (11). 

Clinically, pulmonary sequestration is latent until infection leads to symptoms (12). Symptoms, like that of any pathological lung condition depend on the type, size, and location of the lesion. Sepsis and extracardiac shunting are common complications of untreated sequestration. Hemoptysis can also be a presentation. The mechanism of pneumonia is post-obstructive and usually recurrence of pneumonia leads to diagnosis. Recurrent pneumonia especially in the lower lobes should always include intralobar sequestration in the differential diagnoses. But the pathophysiology of infection and/or hemoptysis when ILS is not connected to airway is a mystery. Sometimes there is a partial or anatomically abnormal connection to the tracheobronchial tree, which can lead to poor mucus clearance, plugging and recurrent infection.

The mainstay of diagnosis is pre-operative imaging and post-operative histopathology of the resected specimen. The pathognomonic imaging characteristic is systemic vascular supply of the affected area of the lung (intra or extra-lobar), which is seen in about 80% of CT scans. Recurrent infection can lead to cystic areas within the mass (clusters of “ring shadows” on X-ray) (13). The surrounding normal lung may have air trapping and show emphysematous changes. Radiologic signs of BPS are a spectrum and represent the chronic and recurrent inflammation of the sequestrated lung: recurrent focal airspace disease, a parenchymal mass, a cavitary consolidation or mass, cystic lesions, localized bronchiectasis or adjacent emphysema. Bronchoscopy has little role in the management of BPS, which needs to be kept in mind by clinicians investigating cystic lung lesions. Identifying the systemic feeding vessel also helps with surgical planning.  

Symptomatic patients are treated with surgical excision; surgery is curative and is associated with minimal morbidity (14). Surgery is urgent in patients with significant respiratory distress but may be an elective procedure in adults or older children with less symptoms (15, 16). 

For asymptomatic patients of any age, management depends on how ‘high risk’ they are considered for developing complications. High risk patients are those with large lesions occupying >20 percent of the hemithorax, bilateral or multifocal cysts, or those with pneumothorax. In these patients, surgical resection is preferred to observation (17). On the other hand, in asymptomatic patients without these high-risk characteristics, either elective surgical resection or conservative management with observation are reasonable options (18). 

Apart from surgery, even embolization of the anomalous arterial supply has been reported to result in a complete resolution of symptoms and imaging changes to a certain in some cases (19). Since identification of vascular supply during surgery may be difficult during surgery, presurgical embolization may reduce risk of vascular complications (19). Embolization also has a more important role in hemoptysis and heart failure from shunting.

Conclusions

• Pulmonary sequestration is a rare congenital anomaly of a mass of lung tissue without a normal connection to the tracheobronchial tree and a systemic vascular supply.
• Presentation in adults is due to complication of the mass, undiagnosed in childhood. 
• Sequestrated lung can have cystic changes and is a very important differential diagnosis of the cavitation. 
• Confirmation of diagnosis is by visualization of a systemic vessel supplying sequestrated pulmonary, and this is usually accomplished by contrast-enhanced CT scan, MRI or invasive angiography.

Teaching points

This is a case of adult presentation of congenital pulmonary malformation and represents a delay in diagnosis, even though the patient’s symptoms started 10 years ago. The delay was due to falling prey to anchoring and availability biases and chasing the diagnosis of TB ten years ago in a patient from Yemen with a lower lobe cavitation. 

The feeding vessel from the celiac axis can only be demonstrated via a contrast enhanced CT, and thus, when in doubt, we should always get angiography by contrast-enhanced-CT or MRI or by invasive angiography. Had it been thought of and done 10 years ago, the patient would’ve been diagnosed and treated earlier.

Disclosure Statement

Drs. Majumdar, Sen and Sood have no conflicts of interest or financial ties to disclose.

References

1. Landing BH, Dixon LG. Congenital malformations and genetic disorders of the respiratory tract (larynx, trachea, bronchi, and lungs). Am Rev Respir Dis. 1979 Jul;120(1):151-85. [CrossRef] [PubMed]
2. John PR, Beasley SW, Mayne V. Pulmonary sequestration and related congenital disorders. A clinico-radiological review of 41 cases. Pediatric radiology. Pediatr Radiol. 1989;20(1-2):4-9. [CrossRef] [PubMed]
3. Van Raemdonck D, De Boeck K, Devlieger H, et al. Pulmonary sequestration: a comparison between pediatric and adult patients. Eur J Cardiothorac Surg. 2001 Apr;19(4):388-95. [CrossRef] [PubMed]
4. Gezer S, Taştepe I, Sirmali M, Findik G, Türüt H, Kaya S, Karaoğlanoğlu N, Cetin G. Pulmonary sequestration: a single-institutional series composed of 27 cases. J Thorac Cardiovasc Surg. 2007 Apr;133(4):955-9. [CrossRef] [PubMed]
5. Shanti CM, Klein MD. Cystic lung disease. Semin Pediatr Surg. 2008 Feb;17(1):2-8. [CrossRef] [PubMed]
6. Stocker JT, Drake RM, Madewell JE. Cystic and congenital lung disease in the newborn. Perspect Pediatr Pathol. 1978;4:93-154. [PubMed]
7. Schwartz MZ, Ramachandran P. Congenital malformations of the lung and mediastinum--a quarter century of experience from a single institution. J Pediatr Surg. 1997 Jan;32(1):44-7. [CrossRef] [PubMed]
8. Abbey P, Das CJ, Pangtey GS, Seith A, Dutta R, Kumar A. Imaging in bronchopulmonary sequestration. Send to J Med Imaging Radiat Oncol. 2009 Feb;53(1):22-31. [CrossRef] [PubMed]
9. Houda el M, Ahmed Z, Amine K, Amina BS, Raja F, Chiraz H. Antenatal diagnosis of extralobar pulmonary sequestration. Pan Afr Med J. 2014;19:54. [CrossRef] [PubMed]
10. Frazier AA, Rosado de Christenson ML, Stocker JT, Templeton PA. Intralobar sequestration: radiologic-pathologic correlation. Radiographics. 1997 May-Jun;17(3):725-45. [CrossRef] [PubMed]
11. Kravitz RM. Congenital malformations of the lung. Pediatr Clin North Am. 1994 Jun;41(3):453-72. [CrossRef] [PubMed]
12. Hang JD, Guo QY, Chen CX, Chen LY. Imaging approach to the diagnosis of pulmonary sequestration. Acta Radiol. 1996 Nov;37(6):883-8. [CrossRef] [PubMed]
13. Hernanz-Schulman M. Cysts and cystlike lesions of the lung. Radiol Clin North Am. 1993 May;31(3):631-49. [PubMed]
14. Samuel M, Burge DM. Management of antenatally diagnosed pulmonary sequestration associated with congenital cystic adenomatoid malformation. Thorax. 1999 Aug;54(8):701-6. [CrossRef] [PubMed]
15. Haller JA, Jr., Golladay ES, Pickard LR, Tepas JJ, 3rd, Shorter NA, Shermeta DW. Surgical management of lung bud anomalies: lobar emphysema, bronchogenic cyst, cystic adenomatoid malformation, and intralobar pulmonary sequestration. Ann Thorac Surg. 1979 Jul;28(1):33-43. [CrossRef] [PubMed]
16. Al-Bassam A, Al-Rabeeah A, Al-Nassar S, Al-Mobaireek K, Al-Rawaf A, Banjer H, et al. Congenital cystic disease of the lung in infants and children (experience with 57 cases). Eur J Pediatr Surg. 1999 Dec;9(6):364-8. [CrossRef] [PubMed]
17. Parikh DH, Rasiah SV. Congenital lung lesions: Postnatal management and outcome. Semin Pediatr Surg. 2015 Aug;24(4):160-7. [CrossRef] [PubMed]
18. Singh R, Davenport M. The argument for operative approach to asymptomatic lung lesions. Semin Pediatr Surg. 2015 Aug;24(4):187-95. [CrossRef] [PubMed]
19. Eber E. Adult outcome of congenital lower respiratory tract malformations. Swiss Med Wkly. 2006 Apr 15;136(15-16):233-40. [PubMed]

Cite as: Majumdar U, Sen P, Sood A. Intralobar bronchopulmonary sequestration: A case and brief review. Southwest J Pulm Crit Care. 2018;16(6):343-9. doi: https://doi.org/10.13175/swjpcc075-18 PDF

Necrotizing Pneumonia: Diagnosis and Treatment Options

Brian D. Skidmore, BS¹ and Veronica A. Arteaga, MD²

¹College of Medicine and ²Department of Medical Imaging

Banner-University Medical Center

University of Arizona

Tucson, AZ USA

Abstract

We present the case of a patient who was initially diagnosed with community-acquired pneumonia that was later discovered to have necrotizing changes. The case illustrates the challenges in diagnosing necrotizing pneumonia and the preferred treatment methods.

Case Presentation

History of Present Illness

The patient is a 51-year old woman who presents with right upper lobe pneumonia and a failed outpatient regimen of levofloxacin. She returned one week after being seen in the emergency department with worsening dyspnea, productive cough, and fever in addition to new symptoms of right chest pain and post-tussive emesis. The chest pain is stabbing in quality and constantly present. She denied any calf pain/swelling, previous history of deep venous thrombosis, or long trips or travels.

Physical Exam

Upon admission, blood pressure was 103/56 with a pulse of 114 and respiratory rate of 18. Her temperature was 38.1 °C (100.5 °F) but spiked at 39.5 °C (103.1 °F) and her SpO₂ was 94.0% on room air. Her breathing was unlabored and her lungs were clear to auscultation bilaterally except for crackles in the right upper lung field. The remainder of the exam was unremarkable.

Laboratory and Imaging

A chest radiograph was initially obtained and showed a right upper lobe consolidation consistent with community-acquired pneumonia (Figure 1).

Figure 1. Chest radiograph showing right upper lobe consolidation with possible volume loss.

One week later, a contrast-enhanced chest CT was performed and revealed a heterogeneously enhancing right upper lobe consolidation with cavitation and foci of air diagnostic of necrotizing pneumonia (Figure 2).

Figure 2. Contrast-enhanced chest CT showing right upper lobe pneumonic consolidation with peripheral enhancement, central necrosis, and small foci of air.

Laboratory studies revealed a markedly elevated C-reactive protein of 16.61 mg/dL and a white blood cell count of 18,000 cells/ μL. In addition, the red blood cell count, hemoglobin, and hematocrit were all reduced with values of 3,390,000 cells/ μL, 10.0 g/dL, and 31.0% respectively.

Hospital Course

A chest CT was ordered and the patient was diagnosed with necrotizing pneumonia. She was given IV vancomycin and piperacillin-tazobactam as empiric therapy. Tylenol was administered for fever management and steroids were deferred because her CURB-65 score for pneumonia severity was 0.

Attention was then given to identifying the infectious agent. Blood and respiratory cultures were obtained and a TB test was ordered. The cultures showed no growth and the TB test was negative. A bronchoalveolar lavage showed a highly neutrophilic cell count, however no pathogen was ever identified.

Given improvement with empiric therapy, during her hospital course she was discharged on oral amoxicillin and clavulanate until follow up with pulmonary in outpatient 6 weeks later. Imaging at that time showed post inflammatory changes and no evidence of infection.

Discussion

Necrotizing pneumonia is a rare complication of bacterial lung infections affecting 4% of all patients with community-acquired pneumonia (1). The infection can be patchy, segmental, or involve the entire lung. While the pathogenesis of necrotizing pneumonia is not clearly defined, most studies indicate that it is either an inflammatory response to toxins produced by the pathogen or it is the result of associated vasculitis and venous thrombosis. Patients typically present with common symptoms of pneumonia such as fever, cough, shortness of breath, and chest pain but can also rapidly develop hemoptysis, septic shock, and respiratory failure as the necrosis progresses (2). Because necrotizing pneumonia is associated with increased morbidity and mortality, it is important to distinguish it from non-necrotizing cases (3).

The diagnosis of necrotizing pneumonia may be difficult to make because of its similar presentation to non-necrotizing pneumonias and the limitations of standard chest radiographs. Chest radiographs may show an area of consolidation but are limited in identifying the extent of parenchymal disease (Figure 1) (2). Therefore, contrast-enhanced chest CT is an optimal exam for diagnosing necrotizing pneumonia. Disease may first appear as an in-homogeneously enhancing consolidation with focal areas of low attenuation (Figure 2).  Foci of air may subsequently develop in these areas of hypo-enhancing necrotic tissue indicating cavitation (4).

Laboratory studies may also be helpful in diagnosing necrotizing pneumonia. When compared to pneumonias without a necrotizing component, patients with necrotizing pneumonia show more elevated white blood cell counts and inflammatory markers (1). In one study, patients with necrotizing pneumonia had an average WBC count of 14,970/μL, an average ESR of 70 mm/h, and an average CRP of 18.8 mg/dL. Average values for patients with non-necrotizing pneumonia were significantly lower at 10,130/μL, 48 mm/h, and 11.4 mg/dL respectively (p<0.001) (3). These changes are also evident in the presented case with elevated WBC and CRP values of 18,000/μL and 16.61 mg/dL.

Necrotizing pneumonia is initially treated with intravenously administered broad-spectrum antibiotics that should target pathogens that commonly cause necrotizing changes. The most common microbes are Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae, however several other bacteria species may also cause necrosis (Table 1) (2).

Transition to oral antibiotics may be considered for patients that show improvement (1). A more focused treatment plan should be initiated once a specific pathogen is identified, however this is only accomplished in approximately 26% of cases (3).

Surgical resection may also be considered for patients who show no progress on antibiotic therapy and continue to decline. However the optimal timing and indications for surgery are not clearly defined. The extent of the resection should always be as conservative as possible and commonly involves debridement or segmentectomy of the damaged tissue. In cases where the parenchyma is extensively affected, lobectomy or pneumonectomy may be required (2).

References

1. Nicolaou EV, Bartlett AH. Necrotizing pneumonia. Pediatr Ann. 2017;1;46(2):e65-e68. [CrossRef] [PubMed]
2. Tsai YF, Ku YH. Necrotizing pneumonia: a rare complication of pneumonia requiring special consideration. Curr Opin Pulm Med. 2012;18(3):246-52. [CrossRef] [PubMed]
3. Seo H, Cha SI, Shin KM, et al. Clinical relevance of necrotizing change in patients with community-acquired pneumonia. Respirology. 2017;22(3):551-8. [CrossRef] [PubMed]
4. Walker CM, Abbott GF, Greene RE, Shepard JO, Vummidi D, Digumarthy SR. Imaging Pulmonary Infection: Classic Signs and Patterns. AJR Am J Roentgenol. 2014;202(3) 479-92. [CrossRef] [PubMed]

Cite as: Skidmore BD, Arteaga VA. Necrotizing pneumonia: diagnosis and treatment options. Southwest J Pulm Crit Care. 2017;15(6):274-7. doi: https://doi.org/10.13175/swjpcc137-17 PDF

October 2017 Pulmonary Case of the Month

Eric A. Jensen, MD

Department of Radiology

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 56-year-old woman presented with 3 days of non-productive cough, low-grade fever and severe right-sided pleuritic chest pain.

Past Medical History, Social History and Family History

She was diagnosed with coccidioidomycosis 5 years previously. She reports that she has had pneumonia every 6 to 12 months since her diagnosis with valley fever. She does not smoke. Family history is noncontributory.

Physical Examination

Her vital signs were unremarkable and she was afebrile but did cough frequently during the examination. Her lungs were clear and the rest of the physical examination was unremarkable.

Chest Radiography

She brings in two prior chest x-rays, one from 2011 (Figure 1, Panels A & B) and another from 2012 (Figure 1, Panel C).

Figure 1. Chest radiograph from 2011 (A & B) and from 2012 (C).

Which of the following best describes the chest x-rays? (Click on the correct answer to proceed to the second of five pages)

1. A repeat chest x-ray should be performed
2. A right lower lobe mass is present which appears to have enlarged from 2011 to 2012
3. There is a right lower posterior lung density
4. 1 and 3
5. All of the above

Cite as: Jensen EA. October 2017 pulmonary case of the month. Southwest J Pulm Crit Care. 2017;15(4):125-30. doi: https://doi.org/10.13175/swjpcc115-17 PDF

June 2017 Pulmonary Case of the Month

Robert Horsley, MD

Lewis J. Wesselius, MD 

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 61-year-old woman presented to the emergency department for 3 days of fevers up to 102º F, malaise, and progressive shortness of breath. Her symptoms started immediately after he last naltrexone injection for alcohol use disorder.

Past Medical History, Social History and Family History

• Alcohol use disorder
• Treated with monthly naltrexone injections, received 3 doses total, and gabapentin
• No other previous medical issues
• Nonsmoker

Physical Examination

• Vital signs: Pulse 100, BP 108/90, respiratory rate 34, SpO2 93% 10L non-rebreathing mask
• Cyanotic on room air
• Lungs clear

Radiography

A portable chest x-ray was performed in the emergency department (Figure 1).

Figure 1. AP chest radiograph taken in the emergency department.

A thoracic CT scan was performed (Figure 2).

Figure 2. Representative images from thoracic CT in lung windows.

Laboratory

• CBC showed a white blood cell count of 12,000 cells/mcL.
• The differential showed a left shift.
• Lactate was 5.2 mmol/L

Which of the following is (are) true? (Click on the correct answer to proceed to the second of five pages)

1. A lactate level of 5.2 can be a normal finding in a critically ill patient
2. Her symptoms are likely an allergic reaction to naltrexone
3. The most likely diagnosis is an atypical pneumonia
4. 1 and 3
5. All of the above

Cite as: Horsley R, Wesselius LJ. June 2107 pulmonary case of the month. Southwest J Pulm Crit Care. 2017;14(6):255-61. doi: https://doi.org/10.13175/swjpcc063-17 PDF

November 2016 Pulmonary Case of the Month

November 2016 Pulmonary Case of the Month

Anjuli M. Brighton, MB, BCh, BAO

Tania Jain, MBBS

Alan H. Bryce, MD

Ramachandra R. Sista, MD

Robert W. Viggiano, MD

Lewis J. Wesselius, MD

Pulmonary and Hematology/Oncology Departments

Mayo Clinic Arizona

Scottsdale, AZ USA

Pulmonary Case of the Month CME Information

Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive 0.25 AMA PRA Category 1 Credits™ for each case they complete. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity. 

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours

Lead Author(s): Anjuli M. Brighton, MB.  All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.

Learning Objectives:
As a result of this activity I will be better able to:

1. Correctly interpret and identify clinical practices supported by the highest quality available evidence.
2. Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
4. Will integrate new treatment options in discussing available treatment alternatives for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine at Banner University Medical Center Tucson

Current Approval Period: January 1, 2015-December 31, 2016

Financial Support Received: None

History of Present Illness

Our patient is a 76-year-old gentleman  who was referred based on an abnormal CT scan. He has a history of metastatic melanoma and had begun immunotherapy with pembrolizumab 10 months prior to admission. He had low grade fevers and chills and some dyspnea on exertion and dry cough. He also had a 6-8 pound weight loss over 4 weeks.

PMH, SH and FH

He has a history of hairy cell leukemia since 2009; squamous and basal cell cancers; and diabetes on insulin. He is a retired commercial banker and has a 15 pack-year smoking history.

Physical Examination

Physical examination showed and SpO2 of 90% on room air. His lungs were clear. He had numerous depigmented lesions on his skin.

Radiography

A thoracic CT scan was performed (Figure 1) and compared to a scan done 3 months prior which was considered unremarkable.

Figure 1. Video of representative images of contrast-enhanced thoracic CT scan in lung windows.

Which of the following best describe the CT scan? (Click on the correct answer to proceed to the second of four pages)

1. Normal
2. Mosaic pattern of lung attenuation
3. Numerous bronchial-associated ground glass opacities
4. Numerous pulmonary nodules
5. Numerous pulmonary nodules with a halo sign

Cite as: Brighton AM, Jain T, Bryce AH, Sista RR, Viggiano RW, Wesselius LJ. November 2016 pulmonary case of the month. Southwest J Pulm Crit Care. 2016:13(5):191-5. doi: http://dx.doi.org/10.13175/swjpcc098-16 PDF

October 2016 Pulmonary Case of the Month

Coya T Lindberg, BS¹

Ryan R Nahapetian, MD²

F Zahra Aly, MD, PhD, FRCPath³

¹University of Arizona College of Medicine Tucson, Tucson, AZ

²Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Arizona, Tucson, AZ

³Brody School of Medicine at East Carolina University, NC

Pulmonary Case of the Month CME Information

Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive 0.25 AMA PRA Category 1 Credits™ for each case they complete. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity. 

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours

Lead Author(s): Coya Lindberg, BS.  All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.

Learning Objectives:
As a result of this activity I will be better able to:

1. Correctly interpret and identify clinical practices supported by the highest quality available evidence.
2. Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
4. Will integrate new treatment options in discussing available treatment alternatives for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine at Banner University Medical Center Tucson

Current Approval Period: January 1, 2015-December 31, 2016

Financial Support Received: None

A 49-year-old man presented with chest discomfort to an outside medical facility in Arizona. He was previously healthy and had no chronic medical diseases. Physical examination was unremarkable and he was afebrile. A chest X-ray was performed (Figure  1).

Figure 1. Initial chest x-ray

Which of the following is most likely? (Click on the correct answer to proceed to the second of five panels)

1. There is a large right chest mass
2. There is a loculated pleural effusion in the minor fissure
3. There is a right ventricular aneurysm
4. There is right lower lobe consolidation
5. There is right middle lobe consolidation

Cite as: Lindberg CT, Nahapetian RR, Aly FZ. October 2016 pulmonary case of the month. Southwest J Pulm Crit Care. 2016;13(4):152-8. doi: http://dx.doi.org/10.13175/swjpcc096-16 PDF

September 2016 Pulmonary Case of the Month

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

Pulmonary Case of the Month CME Information

Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive 0.25 AMA PRA Category 1 Credits™ for each case they complete. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity. 

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours

Lead Author(s): Lewis J. Wesselius, MD.  All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.

Learning Objectives:
As a result of this activity I will be better able to:

1. Correctly interpret and identify clinical practices supported by the highest quality available evidence.
2. Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
4. Will integrate new treatment options in discussing available treatment alternatives for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine at Banner University Medical Center Tucson

Current Approval Period: January 1, 2015-December 31, 2016

Financial Support Received: None

History of Present Illness

The patient is a 52 year-old woman with prior renal transplant in 1998 due to complications of pre-eclampsia. She had a recent decline in renal function leading to re-transplant on June 23 of this year. She was admitted to the hospital on July 8th with ventricular tachycardia. Treatment with amiodarone was begun with no further ventriuclar tachycardia. She is also taking usual anti-rejection medications.

Past Medical History, Social History and Family History

Other than the renal transplantation she has no other significant past medical history and has never smoked. Family history is noncontributory.

Physical Examination

Physical examination was unremarkable other than the surgical wounds associated with her renal transplants.

Radiography

Her chest x-ray is shown in Figure 1.

Figure 1. Admission chest radiograph.

What should be done at this time? (Click on the correct answer to proceed to the second of four panels)

1. Discontinue the amiodarone
2. Empiric antibiotics
3. Plasma brain naturetic peptide (BNP)
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. September 2016 pulmonary case of the month. Southwest J Pulm Crit Care. 2016;13(3):101-7. doi: http://dx.doi.org/10.13175/swjpcc086-16 PDF

August 2016 Pulmonary Case of the Month

Anjuli M. Brighton, MB, BCh, BAO

Kathryn E. Williams, MB, BCh, BAO

Lewis J. Wesselius, MD

Pulmonary Department

Mayo Clinic Arizona

Scottsdale, AZ USA

Pulmonary Case of the Month CME Information

Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive 0.25 AMA PRA Category 1 Credits™ for each case they complete. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity. 

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours

Lead Author(s): Anjuli M. Brighton, MB.  All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.

Learning Objectives:
As a result of this activity I will be better able to:

1. Correctly interpret and identify clinical practices supported by the highest quality available evidence.
2. Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
4. Will integrate new treatment options in discussing available treatment alternatives for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine at Banner University Medical Center Tucson

Current Approval Period: January 1, 2015-December 31, 2016

Financial Support Received: None

History of Present Illness

The patient is 54-year-old man with type 1 diabetes mellitus admitted for diabetic ketoacidosis (DKA). He complained of somnolence, nausea and vomiting and right foot pain. He had been admitted 2 weeks earlier for right foot gangrene. He had been receiving daptomycin for his right foot gangrene.

PMH, SH and FH

He had a previous history of osteomyelitis, perianal abscess, maxillary abscess, Candida esophagitis, transient ischemic attack, and peripheral vascular disease. He had previous amputations along with thrombectomy/ embolectomy/bypass. He was a former Marine and construction worker with ongoing cigarette use. Family history was noncontributory.

Physical Examination

• Febrile to 38.2ºC
• Crackles bilaterally
• Transmetatarsal stump with dry gangrene

Radiography

An admission chest x-ray was performed (Figure 1).

Figure 1. Admission portable AP of chest.

Which of the following are appropriate at this time? (Click on the correct answer to proceed to the second of four panels)

1. Blood and wound cultures
2. Empiric antibiotics including coverage for Staphylococcus aureus
3. Intravenous insulin and fluids
4. Serially monitor renal function and electrolytes
5. All of the above

Cite as: Brighton AM, Williams KE, Wesselius LJ. August 2016 pulmonary case of the month. Southwest J Pulm Crit Care. 2016;13(2):40-5. doi: http://dx.doi.org/10.13175/swjpcc070-16  PDF 

Interval Development of Multiple Sub-Segmental Pulmonary Embolism in Mycoplasma Pneumoniae Bronchiolitis and Pneumonia

Peter V. Bui¹

Sapna Bhatia²

Ali I. Saeed²

¹Department of Internal Medicine

²Division of Pulmonary, Critical Care, and Sleep Medicine

The University of New Mexico

Albuquerque, NM, USA

Abstract

Introduction: Cases of pulmonary embolism (PE) concurrent with Mycoplasma pneumoniae infection are rare in the medical literature. We describe a patient with M. pneumoniae bronchiolitis and pneumonia who developed multiple right-sided, sub-segmental PE.

Case Description: A 54-year-old man presented following one week of respiratory and constitutional symptoms. He was admitted for respiratory distress and started on ceftriaxone, azithromycin, and oseltamivir. Because of a lack of clinical improvement, antibiotics were escalated to vancomycin and piperacillin-tazobactam. M. pneumoniae IgM and IgG serologies returned positive, and antibiotics were narrowed to azithromycin, with clinical improvement and gradual decrease in supplemental oxygen requirement. One week into the hospitalization, the patient abruptly developed an increased oxygen requirement. Computed tomography angiography (CTA) of the chest found stable M. pneumoniae bronchiolitis and pneumonia and the interval development of multiple right-sided, sub-segmental PE. He was treated with unfractionated and then low-molecular-weight heparin as a bridge to warfarin, azithromycin, and a prednisone taper. In the outpatient setting, repeat CTA revealed resolution of M. pneumoniae infection and PE. 

Discussion: Although the mechanism and association are unclear, other case reports have proposed that M. pneumoniae infection promotes hypercoagulability or a prothrombotic state, predisposing patients to thromboembolism. In a patient with M. pneumoniae infection who develops sudden respiratory distress or failure despite appropriate treatment, clinicians should have a high suspicion for PE, and a CTA should be considered as part of further evaluation.

Introduction

Mycoplasma pneumoniae is one of thirteen Mycoplasma species isolated from humans and less commonly causes lower respiratory tract infections, of which atypical pneumonia occurs at higher rates (1). These lower respiratory tract infections have been reported to present similarly to other disease processes such as asthma and pulmonary embolism (PE) (2, 3). M. pneumoniae pneumonia typically has a benign course with low mortality. A study by von Baum et al. found a mortality of 0.7% in patients with M. pneumoniae pneumonia, with the deaths occurring in hospitalized patients (4). Despite this low mortality, rare complications may contribute to morbidity and mortality, although to what degree, if any, is unclear. A case report in the medical literature describes a PE and a hypercoagulable state associated with M. pneumoniae pneumonia in an adult during the peri-infectious period (5). We present a case with radiographic evidence of the interval development of multiple segmental PE in a patient with M. pneumoniae bronchiolitis and pneumonia.

Case Description

A 54-year-old man with a 15-pack-year smoking history, positive purified protein derivative treated with isoniazid, occupational exposures including asbestos and dust, and a current history of ethanol abuse presented to the emergency department with a one-week history of a productive cough with yellow sputum, weakness, shortness of breath, and dyspnea on exertion. He also noticed diffuse papular cutaneous lesions over his back.

In the emergency department, he was hypoxic with a need for supplemental oxygen. Cardiopulmonary examination was unremarkable. Initial laboratory studies including complete blood count, chemistry panel, and hepatic function panel were notable for a leukocytosis of 13.6 k/μL with a neutrophilia of 83%, aspartate transaminase of 108 units/L, alanine transaminase of 152 units/L, alkaline phosphatase of 175 units/L, and total bilirubin of 1.5 mg/dL, and creatine kinase of 563 units/L. Conventional chest radiograph (Figure 1) showed a left lower lobe infiltrate.

Figure 1. Conventional chest radiograph on day zero of the hospitalization. The images show a left lower lobe infiltrate.

The patient was admitted to the hospital and started on ceftriaxone and azithromycin for community-acquired pneumonia as well as oseltamivir over concerns for influenza.

During the initial hospitalization, the patient required supplemental oxygen for hypoxia with a rapid increase in fractional inspired oxygen (F_iO₂) to maintain oxygen saturation above 90%. Because of a lack of clinical improvement, antibiotics were broadened to include vancomycin and piperacillin-tazobactam. Since he continued to require a F_iO₂ of 60% on day four of the hospitalization, additional workup for atypical bacterial, viral, and fungal pathogens were performed after consultation with pulmonology. Acid-fast bacillus cultures and stains were negative. Sputum cultures were not obtained. An arterial blood gas prior to evaluation by Pulmonology found a pH of 7.42, partial pressure of carbon dioxide of 38 mmHg, partial pressure of oxygen of 86 mmHg, HCO₃ of 24 mmol/L, and F_iO₂ of 95%. Computed tomography (CT) of the chest (Figure 2) showed extensive bronchiolitis with focal areas of consolidation involving bilateral lower lobes.

Figure 2. Computed tomography of the chest on day four of the hospitalization. The image shows an extensive bronchiolitis with focal areas of consolidation involving bilateral lower lobes.

Oseltamivir was discontinued after the respiratory viral panel returned negative. Broad spectrum antibiotics were narrowed to azithromycin after M. pneumoniae IgM and IgG serologies returned positive. His oxygen requirement gradually improved over the next two days, and he was transitioned to nasal cannula.

On day seven of his hospitalization, the patient suddenly developed moderate respiratory distress with an increase in oxygen requirement. CT angiography (CTA) of the chest (Figure 3) done at this juncture showed unchanged parenchymal findings with interval development of multiple sub-segmental pulmonary emboli in the right lung.

Figure 3. Computed tomography angiography of the chest on day five of the hospitalization. The images show unchanged parenchymal findings with interval development of multiple sub-segmental pulmonary emboli in the right lung (see white arrows in Figure 3A).

Doppler ultrasound found no evidence of deep venous thrombosis (DVT) in both lower extremities. He was subsequently started on therapeutic anticoagulation with unfractionated heparin and then low-molecular-weight heparin as a bridge to warfarin. The patient subsequently improved on a 14-day course of azithromycin 500 mg orally once daily and 3-month tapered course of prednisone 60 mg orally once daily for M. pneumoniae infection, a 3-month course of warfarin for the PE, and supplemental oxygen. During follow-up in the outpatient setting, CTA of the chest showed the infection and PE to have resolved, and all therapies related to the infection and PE were discontinued.

Discussion

We herein describe a case of M. pneumoniae bronchiolitis and pneumonia complicated by right-sided PE. The reported occurrences of venous thromboembolism (VTE) during M. pneumoniae infection are limited to case reports. In our review of the literature, we found one case of M. pneumoniae infection associated with PE in the adult population. Ascer et al. (5) presented the case of a 28-year-old male with right-sided pneumonia and right-sided PE who was found to have antiphospholipid antibodies. For the PE, this patient was successfully treated with recombinant tissue-type and plasminogen activator and heparin and was discharged with hydroxychloroquine sulphate, aspirin, and warfarin. However, Ascer did not publish additional follow up for this seemingly prothrombotic state. In a case without PE, Senda et al. (6) reported on a 21-year-old patient with a left middle cerebral artery embolus and DVT in bilateral femoral veins in the setting of a M. pneumoniae infection. This patient had a transient increase in prothrombin time, partial thromboplastin time, fibrin/fibrinogen degradation products, thrombin-antithrombin III-complex, antiphospholipid antibodies, and IgM anticardiolipin antibodies and decrease in protein C activity.

The pediatric medical literature has additional case reports linking M. pneumoniae to PE. Brown et al. (7) described a 6-year-old male child with M. pneumoniae pneumonia, right-sided ileofemoral thrombosis, and right-sided PE found to have anticardiolipin IgG and IgM antibodies, lupus anticoagulant, and acquired activated protein C resistance. This prothrombotic state subsequently resolved after treatment of the infection with antibiotics and the PE with unfractionated heparin and then dalteparin. In another case report, during workup for a 13-year-old male child with right-sided PE in the setting of a left lower lobe M. pneumoniae pneumonia, Graw-Panzer et al. (8) found lupus anticoagulant, anticardiolipin IgG and IgM antibodies, and an underlying protein S deficiency. The transient prothrombotic markers returned to normal levels during subsequent follow-up for his acute illness.

M. pneumoniae pulmonary infections have been reported in the pediatric medical literature to be associated with an underlying hypercoagulability. Creagh et al. (9) reported on a left femoral vein thrombosis in a 10-year-old female with M. pneumoniae pneumonia who was found to have type I familial antithrombin III deficiency. In another case report of two children describing splenic infarcts associated with M. pneumoniae pneumonia, Witmer et al. (10) found elevated D-dimer, lupus anticoagulant, and elevated anticardiolipin and β2-glycoprotein antibodies that resolved following successful treatment of the infection with antibiotics and a three-month course of anticoagulation and, in one patient, an additional course of aspirin (10). No specific etiology was found for the infarctions, but Witmer et al. attributed the infarctions to possible thrombosis. Other case reports in the pediatric literature that found antiphospholipid antibodies include a patient with cardiac thrombus and internal carotid artery occlusion (11, 12). However, in their report of right popliteal artery thrombosis in a 5-year-old male child with M. pneumoniae pneumonia and right popliteal artery thrombosis, Joo et al. (13) did not find abnormalities in their limited hypercoagulability workup.

Our lack of hypercoagulability workup limits comparison with the available medical literature. We did not perform a hypercoagulability workup because the patient did not meet any Wells criteria and did not have a family history of hypercoagulability. Based on the available case reports, the underlying pathophysiology can be inferred to be related to a transient formation of antiphospholipid antibodies during a M. pneumoniae infection. Additionally, the thromboembolism can be expected to occur within a short period of time following the onset of symptoms. The rate that hypercoagulability occurs in infected patients and the practical clinical relevance of such a prothrombotic state without or without an inherited or congenital deficiency are unknown at this time. These questions would benefit from further investigation.

An alternative interpretation is a preexisting hypercoagulability may predispose patients to M. pneumoniae infection, which can exacerbate the hypercoagulability, further increasing the risk of VTE. This interpretation may be relevant for the patients of Graw-Panzer et al. (8) and Creagh et al. (9) who had underlying hypercoagulable conditions and subsequently suffered M. pneumoniae infection and then developed VTE. The Worcester Venous Thromboembolism study found an association between infection and VTE, and Rosendaal’s review of the literature found an association between hypercoagulability and increased risk of thrombosis (14-16). With the available case reports and epidemiological studies, this alternative interpretation has not been elucidated.

In this report, we described the interval development of PE in a patient with M. pnuemoniae bronchiolitis and pneumonia. The mechanism for the hypercoagulability during M. pneumoniae infection is unclear. A CTA of the chest should be obtained if a patient with M. pneumonia infection fails to show clinical improvement or suddenly develops clinical worsening of his or her respiratory status, so as to exclude PE. However, clinicians should take into account that Mycoplasma pneumonia may present with the symptoms of PE (3).

Acknowledgements

We would like to acknowledge Cecelia Kieu for assisting in the preparation of the figures for this manuscript.

References

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Cite as: Bui PV, Bhatia S, Saeed AI. Interval development of multiple sub-segmental pulmonary embolism in Mycoplasma pneumoniae bronchiolitis and pneumonia. Southwest J Pulm Crit Care. 2015;11(6):277-83. doi: http://dx.doi.org/10.13175/swjpcc152-15 PDF 

Safety and Complications of Bronchoscopy in an Adult Intensive Care Unit

Aarthi Ganesh, MBBS¹

Nirmal Singh, MBBS, MPH²

Gordon E. Carr, MD¹

¹Department of Pulmonary & Critical Care

²Department of Internal Medicine

University of Arizona

Tucson, Arizona

Abstract

Background: Bronchoscopy is a common procedure performed in adult intensive care units (ICU). However, very few studies report the safety and complications of the bronchoscopy and related procedures performed on critically ill patients. The primary aim of this study was to determine the incidence of complications following ICU bronchoscopy.

Methods: We conducted a retrospective chart review of patients admitted to an adult ICU and underwent bronchoscopy with or without bronchoalveolar lavage (BAL) and other bronchoscopic procedures. Data included patient demographics, APACHE II score, hemodynamics, comorbidities, type of ventilation and procedure performed. Data from BAL, including cellular differential and microbiology, were also collected.

Results: We identified 120 patient charts between November 2011 to March 2012. The most common procedure was bronchoscopy with BAL (62%) to evaluate for pneumonia (58%). Other procedures included transbronchial biopsy, APC and cryotherapy, balloon and stent placement, endobronchial biopsy and EBUS. Complications occurred in 18% of the patients, with hypoxia being the most common (7.5%). No deaths occurred related to the procedures. Nine percent of patients who had BAL or inspection had complications compared to 29% who underwent other procedures. Subgroup analysis conducted on patients undergoing BAL revealed significantly higher neutrophil counts (p=0.001) and higher APACHE II score (p=0.02) among those with BAL positive for bacteria and co-infection.

Conclusion: Bronchoscopy with BAL and inspection is relatively safe procedure even in critically ill patients. However, other interventional bronchoscopic procedures should be performed with caution in the ICU.

Abbreviations:

ICU: Intensive care unit

BAL: Bronchoalveolar lavage

EBUS: Endobronchial Ultrasound

APC: Argon Plasma Coagulation

SBP: Systolic Blood Pressure

CI: Confidence Interval

IP: Interventional pulmonary

MAP: Mean arterial pressure

SD: Standard deviation

CHF: Congestive heart Failure

COPD: Chronic Obstructive Pulmonary Disease

ILD: Interstitial Lung Disease

ET: Endotracheal

Introduction

Fiberoptic bronchoscopy is a commonly performed procedure in the medical intensive care unit (ICU). Prior studies have indicated that bronchoscopy is generally safe, making it a relatively low-risk procedure in appropriately selected ICU patients (1-3). Most prior studies reporting the safety of bronchoscopy were performed in early 1990s. The rates of complications or adverse events in these earlier studies ranged from 2% to 40% (2,4-6). The primary aim of this study was to assess the incidence of complications in ICU patients undergoing bronchoscopy in the contemporary era.

Methods

The study was approved by the Institutional Review Board at the University of Arizona. We conducted a retrospective chart review of patients, 18 years or older, admitted to the adult medical intensive care unit, who underwent bronchoscopy with or without bronchoalveolar lavage (BAL) and other bronchoscopic procedures from November 1, 2011 to March 31, 2012. The other bronchoscopic procedures included transbronchial biopsies, endobronchial ultrasound (EBUS) guided biopsy, argon plasma coagulation (APC) and cryotherapy, balloon dilatation with stenting, and endobronchial biopsy. We excluded patients with incomplete charts, and patients who had bronchoscopy as a part of percutaneous tracheostomy procedure. Data included patient demographics, APACHE II scores, hemodynamics, co-morbidities, type of ventilation, type of procedure performed and the complications. Sedation used in the procedures included propofol or midazolam with fentanyl for analgesia. BAL results, including cellular differential and microbiology studies, were also collected. We used pre-specified definitions to assess for complications. We defined hypotension as reduction in systolic blood pressure (SBP) by >20 mm Hg or when a patient required vasopressors to maintain a mean arterial pressure (MAP) > 60 mm Hg during or after the procedure. Hypoxia was defined by drop in saturation to < 90% or when the FiO2 requirement increased by > 20% for more than 2 hours after the procedure. Hemorrhage was indicated as per the procedure note by the bronchoscopist or when the note indicated use of epinephrine or when additional procedures needed to be performed to control the bleeding. During the procedure all the patients FiO2 was increased but was turned down to their previous ventilatory settings unless there was significant hypoxia.

Statistical analysis was performed using STATA/IC 13.1 (StataCorp LP, Texas). Numerical variables are expressed as mean ± standard deviation (SD). Ninety-five percent confidence intervals (CIs) were calculated where appropriate. Univariate comparisons between patients who did and did not develop complications were calculated using a χ2 test or Fischer's exact test for categorical variables and a 2-sample t test for continuous variables applying central limit theorem. All statistical testing was two-tailed with significance level set at the alpha level of ≤0.05.

Results

We identified 140 patients who underwent ICU bronchoscopy during the study period. Eighteen patients were excluded due to incomplete information. Two charts were excluded as the bronchoscopy was performed for percutaneous tracheostomy. Table 1 shows the baseline characteristics of patients undergoing ICU bronchoscopy.

Table 1. Baseline Characteristics of Patients Prior to Bronchoscopy

Key: CAD: Coronary Artery Disease

        CHF: Congestive Heart Failure

        COPD: Chronic obstructive pulmonary disease

        FiO2: Oxygen required

        ILD: Interstitial Lung Disease

        MAP: Mean arterial pressure

        NM Disease: Neuromuscular disease

Sixty-nine percent of the patients were male and average age was 52 ± 16 years. The average APACHE II score was 18 ± 6 with a median of 18 and 88% of the patients were intubated and mechanically ventilated. The mean percentage oxygen (FiO2) requirement in the patients prior to the procedure was 63% ± 26. Sixty-three percent of the patients were immunocompromised, likely related to the large proportion of lung transplant recipients in our study population. Fifty-four percent also had chronic lung disease including chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Other common co-morbidities included cardiovascular disease including congestive heart failure (CHF) and arrhythmias, malignancy and neuromuscular diseases. Table II shows the indications for ICU bronchoscopy. The most common indication for the procedure was to evaluate for pneumonia or infiltrate in 87 cases (72%), followed by atelectasis/ collapse/ secretions in 19 cases (15.8%) (Table 2).

Table 2. Indications For Procedures

Other indications included tracheal or airway diseases, which included tracheal stenosis, upper airway obstruction, tracheal mass and bronchopleural fistula in 11 (8%) and hemoptysis (2%). The most common procedures performed were bronchoscopy with BAL in 75 (62%) and inspection in 31 (26%) (Table 3).

Table 3. Procedures

Key:  APC: Argon plasma coagulation

         BAL: Bronchoalveolar lavage

         Cryo: Cryotherapy

         EBUS: Endobronchial ultrasound

         ET: Endotracheal tube

Other procedures included transbronchial biopsy, APC and cryotherapy, balloon and stent placement, endobronchial biopsy and EBUS.

Table 4 shows the complications resulting from ICU bronchoscopy in this study population.

Table 4. Complications

Twenty two complications occurred during or within 2 hours after the procedure (18%), with hypoxia being the most common (7.5%). Hypoxia in two patients occurred secondary to hemorrhage. Pneumothorax was seen in one patient who underwent transbronchial biopsy with no fluoroscopic guidance. Hypotension which needed treatment with fluids or vasopressors occurred in 5.8% and hemorrhage in 3.3%. Hemorrhage was unrelated to coagulopathy in the patients. Significant bradycardia requiring treatment with atropine occurred in one patient. No deaths were reported related to the procedures. None of the procedures had to be terminated secondary to the complications. More adverse events were seen among the patients who underwent other bronchoscopic procedures (29%) than those undergoing BAL or inspection only (9%), though this was not statistically significant (p = 0.07).

As depicted in Table 5, none of the complications were significantly affected by the underlying comorbidities or the APACHE scores.

Table 5. Patient Characteristics Stratified by Complications

Key: BAL: Bronchoalveolar lavage

       MAP: Mean Arterial Pressure

Complications were not significantly associated with the amount of oxygen required (FiO2) and the mode of ventilation which the patients were on prior to the procedure. Similarly, neither the mean arterial pressure before the procedure or coagulopathy influenced the rate of complications. Hospital mortality was not different in the group with or without complications.

Figure 1 and Table 6 show the BAL cell differential.

Figure 1. BAL differential in culture with normal respiratory flora (0), bacteria (1), Viral (2), Fungal (3) and Co-infection (4). Each bar represents the differential in percentage.

Key: BAL: Bronchoalveolar lavage

          BAL N: Neutrophil count in BAL (in percentage)

          BAL L: Lymphocyte count in BAL (in percentage)

          BAL M: Macrophages count in BAL (in percentage)

          BAL E: Eosinophils count in BAL (in percentage)

Table 6. Bronchoalveolar Lavage Differential

Patients found to have bacterial pneumonia or mixed viral and bacterial infection had significantly higher neutrophil counts (mean BAL neutrophil count 82% for bacterial infection, and 80% for co-infections) than other patients (p=0.001) (Figure 2).

Figure 2. Neutrophil predominance in bacterial pneumonia. KEY: BAL-N: Bronchoalveolar lavage, neutrophil differential (in percentage).

These patients also had a higher APACHE II score (p=0.02). Hospital mortality was higher among those with BAL positive for bacteria (p= 0.012). Mortality was also significantly higher among patients with underlying malignancy (p= 0.002).

Discussion

In our study of 120 ICU bronchoscopies, we found a complication rate of 18%. No deaths were observed in this study. Hypoxia was the most common adverse event in our study, occurring in 9 procedures (7.5%) as has been noticed in the previous studies. Introduction of a bronchoscope through an endotracheal (ET) tube is known to cause airway obstruction resulting in increasing intra-tracheal pressures and variation in respiratory physiology (6). Almost all the patients who were mechanically ventilated had a size 7.5 - 8.5 ET tube or had tracheostomy in place. As in prior studies, BAL performed for evaluation of pneumonia and atelectasis were the two most common indications of the procedure (72% and 15.8% respectively) in our study (1-7). Even though bronchoscopy has not shown to be routinely superior to chest physiotherapy, certain subset of patient population may benefit from it (3,8,9). Improvement in oxygenation has been shown to occur in certain earlier studies (10,11).

Hypotension is also a known complication occurring during bronchoscopy. Our study had 7 events (5.8%) of hypotension needing vasopressor or fluid infusion. This was likely related to the sedation. Hypertension was observed in one case and bradycardia requiring treatment was seen in one. Cardiovascular abnormalities associated with bronchoscopy is generally related to the sympathetic surge happening during the procedure and the hypoxia (12-14). Per earlier studies, the complication rate of transbronchial biopsies in mechanically ventilated patients range between 0-15% (15,16,17). But it is relatively safe in comparison to open lung biopsy.

With the advent of newer technology, there has been an increase in the number of other bronchoscopic interventional pulmonary (IP) procedures, including endobronchial ablative therapies such as APC and cryotherapy. Endobronchial lesions occupying more than 50% of the airway lumen can alter the airway physiology and result in hypoxia, ventilation perfusion mismatch and hence respiratory failure. Use of ablative therapies can potentially reverse this (18). APC has been an useful tool to remove endobronchial lesions and relieve obstruction. It has been shown to be efficient and relatively safe in outpatient setting, but APC on mechanically ventilated patients has not been very well studied (19). APC in mechanically ventilated patient requires decrease in the FiO2 to less than or equal to 40%. Complications related to IP procedures performed specifically in patients requiring mechanical ventilation are difficult to assess  from the available literature (20). However, given the complexity of these cases and underlying illness, usually the complications are minor. In our study, interventional bronchoscopy procedures like APC, cryotherapy was to relieve airway obstruction which was the cause of mechanical ventilation. In our study, APC case was associated with hemorrhage. The balloon dilatation and stenting which was performed for a case of tracheal stenosis arising from malignancy. This was not associated with any complications related to the procedure in our study. Further study is needed to refine our understanding of the risks of advanced bronchoscopic techniques in ICU patients.

Procedures like EBUS are usually not done in critically ill patients. There are no studies which have looked into the use of and complications of performing EBUS in critically ill patients. Bhaskar et al. (21) report the use of esophageal access for mediastinal sampling through EBUS in ICU patients for the reason of causing hypoxia and changes in airway physiology with the EBUS scope in airway. Our study had one patient who had an EBUS for lung mass and this was not associated with any complications.

Subgroup analysis in our study showed the presence of neutrophilic predominance with neutrophil count of >80% in the BAL differential in patients diagnosed with bacterial infections and co-infections compared to those with viral/ fungal or mixed flora (p=0.001). This was similar to results from earlier studies (22,23). Neutrophilic pleocytosis in BAL fluid is frequently found in patients with pneumonia. As the neutrophil count is higher in bacterial pneumonia, it can indicate towards a differential of bacterial pneumonia even prior to the final microbiology results. Hence BAL differential may be complimentary to final culture results and maybe helpful to initiate or discontinue antibiotics in critically ill patients. Mortality among critically ill patients with bacterial pneumonia was higher compared to others (p=0.012). These patients tend to be sicker with higher APACHE II scores.

The weaknesses of the study includes the fact that it was retrospective chart review. The total number is small, and the number of the IP procedures performed is even smaller. Hence it is important that more studies should be conducted looking into the safety and complications of IP procedures in critically ill patients.

Conclusion

Our study looked into the fiberoptic bronchoscopy with BAL and inspection as well as other therapeutic procedures done in the critically ill patients. It indicates that even in critically ill patients, bronchoscopy with inspection and BAL is safe. Other interventional pulmonary procedures may have more complications. Even though the number of IP procedures performed in the study is low, the evidence of slightly more number of complications with these procedures indicates the need for caution before attempting them in the critically ill patients.

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Cite as: Ganesh A, Singh N, Carr GE. Safety and complications of bronchoscopy in an adult intensive care unit. Southwest J Pulm Crit Care. 2015;11(4):156-66. doi: http://dx.doi.org/10.13175/swjpcc106-15 PDF

Pulmonary Hantavirus Syndrome: Case Report and Brief Review

Charles J. VanHook, MD

Britt Warner, PA

Angela Taylor, MD

Longmont United Hospital

Longmont, Colorado

A 31-year-old white man presented to the emergency department complaining of fever, headache, mild confusion, and muscle aches. Approximately three days earlier he had developed non-quantified fever and diffuse muscle aches and pains. He was employed as a feedlot worker. He had visited an urgent care center one day earlier and had been advised to increase his oral fluid intake and to use non-steroidal anti-inflammatory agents as needed. Upon arrival to the emergency department he was found to have a temperature of 103.6º Fahrenheit, blood pressure of 125/72 mm Hg, respiratory rate of 40 breaths per minute, and room-air oxygen saturation of 84% by pulse oximetry. Auscultation of the chest disclosed diffuse rales. Heart sounds were rapid and regular. Abdominal exam was benign. There was no skin rash. Central nervous exam demonstrated agitation and confusion, but was otherwise non-focal. Laboratory examination revealed a white blood count of 11.7 K/uL, hemoglobin of 21.5 g/DL, hematocrit of 66.8%, platelet count of 73 K/uL, partial thromboplastin time of 36 seconds, lactic acid of 2.4 mm/L, and procalcitonin of 43 ng/mL. Chest radiograph disclosed extensive bilateral infiltrates (Figure 1).

Figure 1. Chest x-ray showing bilateral infiltrates

The patient precipitously declined, with severe respiratory distress, and was emergently intubated. Despite aggressive measures, including mechanical ventilation with an FIO2 of 1.0 and PEEP of 18 cm H2O, vigorous intravenous intravenous fluid resuscitation with normal saline, and pressor support with intravenous norepinephrine and vasopressin, the patient developed refractory hypoxemia. This was followed by a bradycardic arrest and death 2 hours after presentation. Serology sent at the time of admission later returned as IgM positive for hantavirus, with subsequent testing positive for Sin Nombre IgM.

Hantaviruses are RNA viruses of the family Bunyaviridae that are transmitted to humans by contact with the saliva, urine, or feces of infected rodents, which serve as persistently infected hosts (1). Patients who work in proximity to rodents, such as animal trappers, farmers, and forestry workers are at highest risk for infection. In the Western Hemisphere, there are approximately 200 cases per year of Hantavirus Pulmonary Syndrome (HPS), which was first identified in the Four Corners area of the Southwestern United States in 1993 (2). In the United States, HPS is most commonly caused by the Sin Nombre subfamily of hantavirus. A two-week incubation period precedes a 3-6 day prodromal period during which fever and myalgia are prominent features. The cardiopulmonary phase of HPS follows, with the development of acute non-cardiogenic pulmonary edema and multi-organ dysfunction. Typical laboratory abnormalities are leukocytosis and thrombocytopenia. Elevations in hematocrit and partial thromboplastin time are strong predictors of mortality, which approaches 40%. Definitive diagnosis depends on the serologic identification of IgM antibody to hantavirus using ELISA technology.  Immunochromatographic technology may allow for same day diagnosis (3). Treatment is supportive, and varies with the severity of disease. It may include volume resuscitation, ventilatory support, and renal replacement therapy. There is no established anti-viral therapy for Hantavirus infection, although ribavirin is often used in Asia. Corticosteroids have also been used sporadically with some success, but their use remains controversial (3).

Although Hantavirus remains a rare disease, prodromal symptoms in a patient with associated epidemiologic risk factors should heighten clinical suspicion.

References

1. Lednicky JA. Hantavirus: A short review. Arch Pathol Lab Med. 2003;127:30-35. [PubMed]
2. Duchin JS, Koster FT, Peters CJ, Simpson GL, Tempest B, Zaki S, Ksiazek TG, Rollin PE, Nichol S, Umland E, Moolenaar RL, Reef SE, Nolte KB, Gallaher MM, Butler JC, Breiman RF. Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. N England J Med 1994;330:949-55 [CrossRef] [PubMed]
3. Bi Z, Formenty P, Roth C Hantavirus infection: A review and global update. J Infect Developing Countries. 2008;2(1):3-23. [CrossRef] [PubMed]

Cite as: VanHook CJ, Warner B, Taylor A. Pulmonary hantavirus syndrome: case report and brief review. Southwest J Pulm Crit Care. 2015;11(3):121-3. doi: http://dx.doi.org/10.13175/swjpcc122-15 PDF

Common Mistakes in Managing Pulmonary Coccidioidomycosis

 John N. Galgiani MD¹

Kenneth Knox MD^1,2

Craig Rundbaken DO³

John Siever MD⁴

¹Valley Fever Center for Excellence and ²Arizona Respiratory Center

University of Arizona College of Medicine, Tucson, Arizona;

³Arizona Institute of Respiratory Medicine, Sun City West, Arizona;

And

⁴Arizona Pulmonary Specialists, Phoenix, Arizona

Abstract

Coccidioidomycosis (Valley Fever) is a common disease in Arizona and certain other parts of the Southwestern United States. Despite this, there is a surprising lack of awareness, neglect in diagnosis, and inadequacy of management by many clinicians in these endemic regions.  This review discusses why early diagnosis of coccidioidal infection is valuable to patient care and offers a variety of management options that are particularly useful and others which often are of little value.

Introduction

Coccidioidomycosis (Valley Fever) should be a familiar and well-managed disease for Arizona primary care clinicians, and specialists in pulmonary medicine or infectious diseases. In many years it is the second most commonly reported infectious disease to the Arizona Department of Health Services. It also constitutes nearly a third of all community acquired pneumonias (CAP) in Phoenix and Tucson (1-3). Coccidioidal infections in Arizona are responsible for two-thirds of all infections reported in the United States (4). Despite its expected frequency, in primary care practices it is common not to consider the diagnosis or to order necessary testing. In one study from Maricopa County, serologic tests for Valley Fever were ordered in less than 20% of persons with CAP (5). Furthermore, when specialists are referred patients with newly diagnosed Valley Fever, their management strategies vary widely, frequently falling outside of treatment guidelines developed both by the American Thoracic Society and the Infectious Diseases Society of America (6, 7).

There are reasons why a gap exists between medical practices and optimal management of patients with Valley Fever. Although the Arizona Board of Medical Examiners issues approximately a thousand new licenses each year, most recipients have neither received their doctorate nor postgraduate education in Arizona. As documented by the Arizona Department of Health Services, only 12% of surveyed Arizona clinicians graduated from an Arizona medical school, only 47% received house staff training in Arizona medical centers, and only 16% had received CME training in Valley Fever within the past year (8). Moreover, a large majority of Arizonans moved to this state relatively recently, previously lived outside of the coccidioidal endemic region, and are themselves unfamiliar with the disease. Finally, since so many persons eventually resolve their illness whether or not treated with antifungal drugs, some clinicians perceive coccidioidomycosis not to be a serious public health problem and not an important diagnosis to make.

In this article, we will first address the last of these causes for the inattention to coccidioidomycosis and provide the evidence that southwestern clinicians, especially within the Arizona counties of Maricopa, Pima, and Pinal, should include Valley Fever frequently in their differential of CAP and other pulmonary syndromes. We will then highlight a number of what we believe are commonly made mistakes in diagnosis and management of coccidioidal pneumonia and its pulmonary sequelae. Admittedly, this will occasionally involve areas of personal opinion, albeit formed over many years of practice within the Phoenix and Tucson, Arizona areas. We also acknowledge the possibility that we “have it wrong” and that some management strategies that we believe are mistakes are in fact better approaches than we give them credit. The real purpose of this review is to provoke increased discussion by our colleagues within the endemic region about what constitutes best practices and what are not necessary or even counter-productive for our patients.

What is “simple,” uncomplicated early coccidioidal infection and why should clinicians be concerned about it?

Coccidioidomycosis is an infection that results after inhaling one or more spores (arthroconidia) of either Coccidioides immitis (the species usually found in California) or Coccidioides posadasii (the species usually found in Arizona and every other endemic region other than California) (9). As few as one spore is lethal to mice in experimental coccidioidomycosis (10) and likely similarly low exposures are sufficient to cause infection in humans. Based on conversion rates and prevalence rates of coccidioidal delayed-type dermal hypersensitivity in Pima County and in Bakersfield school children, respectively (11, 12), the risk of infection is estimated to be approximately 3% per year although there is year-to-year variation as a result of weather patterns (13, 14). Also, it was found in 2007 that the median time of residence within Arizona for newly diagnosed coccidioidal infections was 12 years (15) which suggests approximately a 4% annual risk. Based on older epidemiology (16, 17), it is thought that a third of infections result in clinical illness sufficient to seek medical attention. If you apply these overall estimates to the resident populations of the highly endemic counties of Arizona and California and assume that a portion is already immune because of past infection, estimated new infections would be 150,000 and medically important illness would occur in 50,000 patients each year.

A common misconception among primary care clinicians is that coccidioidomycosis, as it presents to clinicians for care, is usually a mild and inconsequential illness. That many textbooks refer to the initial illness as a “flu-like” syndrome only helps to perpetuate this idea. In fact, all the evidence indicates that those seeking medical care for a documented coccidioidal infection have a very debilitating disease. Evidence from otherwise healthy college students indicates that they are twice as likely to drop a semester of study because of Valley Fever than for mononucleosis (18). More recently, the Arizona Department of Health Services found that i) Illness lasted an average of 6 months, ii)     75% of employed persons stopped working, half missed two or more weeks, and iii) 40% were hospitalized (15). It is simply not tenable to expect that patients seeking care because of early coccidioidomycosis will not be significantly impacted and that accurate diagnose is unnecessary.

Most clinical coccidioidomycosis presents as community acquired pneumonia (CAP), not as a mild “flu-like” illness. Signs and symptoms include cough, chest pain, fever and profuse night sweating, weight loss, and commonly profound fatigue. Occasional patients have peripheral blood eosinophilia, Erythema nodosum, or Erythema multiforme, any of which should heighten suspicion for Valley Fever within its endemic areas. However, most patients do not have these findings, and the most common complaints are not at all specific to coccidioidal pneumonia. In two prospective Arizona studies, CAP in ambulatory patients was due to coccidioidal infection as frequently as 29% of the time (2, 3). In these studies and also in an earlier study (19), it was not possible to differentiate with any degree of precision which patients had coccidioidomycosis from those with other types of pneumonia without specific laboratory testing.

Despite the high probability that Arizona patients with CAP are infected with Coccidioides spp., evidence indicates that most clinicians do not try to establish this diagnosis. In one study of two separate medical groups in Maricopa County, coccidioidal testing was done for patients with CAP in only 2% and 13%, respectively (5). As a result, many patients are treated needlessly with antibacterial drugs (2, 3, 5, 20). If illness is protracted, further evaluation may be undertaken to exclude the possibility of malignancy and may include bronchoscopy, percutaneous needle aspiration, or even thoracotomy. If coccidioidal infection had been considered early in the evaluation, many such invasive procedures might be avoided as unnecessary. The frequent lack of testing of CAP patients living in or visiting endemic regions for Valley Fever is a major deficiency in routine primary care of these patients and one that can easily be rectified by simple changes in practice patterns. The Arizona Department of Health Services, the Maricopa and Pima County Medical Societies, and the Arizona Chapter of the Infectious Diseases Society of America have all endorsed testing such patients with CAP for coccidioidomycosis.

Applying a pathogenic model of coccidioidomycosis to managing Valley Fever CAP.

How does infection cause illness? In general, the pulmonary illness evolves through three or four phases. Initially, fungal proliferation starts from the inhaled arthroconidium transforming into a mature spherule followed by multiple cycles of spherule rupture, each taking several days to complete. With each spherule rupture, hundreds of endospore progeny are released into the pulmonary tissue (21). A key concept is that it is spherule rupture and not the presence of the spherule itself which triggers an acute inflammatory response (21-24). It is the acute inflammation which produces the pulmonary symptoms, fever, night sweating, and weight loss. If fungal proliferation continues unchecked, it is the ongoing inflammation that produces tissue destruction, fibrosis, and pulmonary cavitation. That inflammation and tissue destruction are the result of ongoing rupture of spherules and not caused by the mere presence of spherules is a pivotal concept. In a second phase, effective cellular adaptive immunity is stimulated by the coccidioidal infection and this inhibits spherule rupture which in turn reduces and eventually eliminates the stimulus for acute inflammation. Although a growing literature implicates Th-1 mediated mechanisms (9, 25-29), the fine details have not been fully defined. In the third, convalescent phase, whatever damage was caused by the acute inflammatory process of the first and second phases resolves either by healing or fibrosis and the symptoms caused by the inflammation abate. For many patients, there follows a fourth phase which involves protracted fatigue and inanition which can dramatically interfere with return to a normal sense of well-being. It is distinguished by an absence of symptoms of ongoing inflammation or evidence of progressive tissue damage.

How long it takes for each of these phases to evolve varies widely among different patients and produces the clinical range of illness from subclinical infections that do not lead to an office visit to infections that produce serious illness, even life-threatening pulmonary failure. However, at the time of diagnosis, assessing patients with respect to where they fall along this evolution from active fungal proliferation to convalescence can be a useful means of arriving at an individualized management program.

Role of antifungal treatment in early coccidioidal infection. Early coccidioidal pneumonia will usually resolve eventually whether treated or not, and evidence is lacking as to whether antifungal treatment is useful for patients to hasten resolution of illness or to prevent subsequent complications. Because of these uncertainties, opinions vary widely regarding whether to treat all patients on the hope that treatment is beneficial or to only treat a subset of newly diagnosed patients with risk factors for complications, with more extensive pneumonia, or with a protracted course of illness. If treatment is begun, the usual dosage would be 200 – 400 mg per day of fluconazole and continued usually for three to six months and sometimes longer than a year, even in the absence of co-existing immunosuppression, diabetes (30), or evidence of complications (3, 31).

Considering the pathogenesis of coccidioidomycosis, the potential value of early antifungal drug treatment would be to reduce or eliminate fungal growth and consequent spherule rupture. The result of treatment would therefore be to assist in the evolution of the first and second phases of illness. How it might help in speeding up convalescence, is less clear. Importantly, for phase-four patients, those with protracted fatigue with no objective evidence of ongoing inflammation or tissue destruction, there is very little reason to expect that an antifungal drug would offer any benefit since in such patients fungal proliferation has already stopped. While a variety of supportive measures including physical therapy for reconditioning may be very helpful for these patients (see below), continued antifungal drug treatment seems inappropriate and even counterproductive.

Although the exact value of antifungal treatment is an unsettled issue, there is consensus that after coccidioidomycosis is diagnosed, additional diagnostic studies in search of an etiology can be curtailed and whatever antibacterial agents have been initiated prior to the accurate diagnosis can be stopped. These are immediate and very tangible benefits of early diagnosis whether or not an antifungal is used. Additionally, as evidence of ongoing inflammation decreases, antifungal treatment that might have been started can be reassessed and in many patients discontinued.

Role of coccidioidal serology tests in management. Detecting anti-coccidioidal antibodies is a valuable means of diagnosing coccidioidal infections (32, 33). Also, when coccidioidal serologic tests were originally described and all tests were done by a single research laboratory, there was a useful relationship established between severity of extrapulmonary infections and the magnitude of complement-fixing titers (34). Unfortunately, there is currently considerable variation in the quantitative results that are obtained from different laboratories as they conduct their testing. Even serial results obtained from the same laboratory may vary because of factors unrelated to actual changes in the clinical status of the patient. In general, once the diagnosis of coccidioidomycosis is established, further coccidioidal serology tests should be restricted to titration of complement fixing antibodies either by the originally described procedure or by its surrogate, quantitative immunodiffusion (32). Even then, results and their changes over time should be only one part of the overall evaluation of the patient’s clinical status and may well be discounted if they are inconsistent with the rest of the evaluation.

Strategies for avoiding common mistakes in managing early coccidioidal infections. One very common mistake in the management of early uncomplicated coccidioidal pneumonia is to concentrate on treatment with antifungal drugs to the neglect of patient education which often is more important to the overall success of management. Patients who receive a new diagnosis of Valley Fever often have many questions and concerns about what this will mean for them. Providing a clear description of what Valley Fever is and how it needs to be managed often is very helpful in reducing anxiety. The Arizona Department of Health Services has printed material about Valley Fever that they distribute free of charge to help with patient education (available at http://www.azdhs.gov/phs/oids/epi/valley-fever/index.htm), but it is likely that additional explanations tailored to the patient’s specific situation will also be valuable.

A second common mistake is to excessively follow a patient’s pulmonary process with repeated CT scans. Whether or not a CT scan of the chest was involved with the initial evaluation of the presenting illness, it is frequently possible to continue management without this imaging once the etiology is established. Often the higher resolution of CT scans in comparison to plain views of the chest is simply unnecessary to guide subsequent management since relatively small changes in the shape of pulmonary infiltrates and hilar nodes provide little useful insight into what next steps ought to be taken. For example, if a pulmonary nodule is so small that it cannot reliably be seen on plain films, there may be no benefit to tracking its size one way or another. Avoiding unnecessary CT scans reduces both radiation exposure and cost.

A third management issue frequently mishandled by both primary care clinicians and specialists alike is the very common complaint of fatigue in patients with coccidioidal pneumonia. In the first phases of illness where there is focal evidence of ongoing inflammation, fatigue is expected and handled as part of the overall illness. However, in what we termed the “fourth phase” above, where inflammatory markers have resolved and focal ongoing damage no longer exists, patients are frequently not adequately managed. In our experience, which is very consistent with published descriptions, Valley Fever can be responsible for protracted fatigue, even after all other signs of infection have resolved. For example, in his excellent 1956 monograph, Fiese (35) writes:

“Profound fatigability and lassitude may persist for months after an otherwise uneventful recovery. Such residual symptoms are often alarming to the patient who is aware of the serious complications. It is important that the physician remember the frequency of post-infection lassitude, so that he may reassure the patient who fears that his disease is becoming disseminated.”

This has been especially striking in patients who have never before had fatigue as a significant ongoing complaint. In addition, because of the lack of normal activity, patients invariably become deconditioned and may not know how to methodically recondition, which can compound the disability, leading to frustration and sometimes reactive depression. We would encourage clinicians to provide such patients medical recommendations to employers to allow time away or reduced workloads to facilitate recuperation. In addition, a logical adjunct to help with the reconditioning would be a referral to a physical therapist to establish baseline levels of strength and endurance, set goals, and to provide a structured plan to accelerate the process. Although there does not yet exist a literature addressing the specific methods most effective in a physical therapy rehabilitation program, general reconditioning strategies would be most appropriate.

A fourth management mistake involves an overly aggressive handling of effusions that sometimes occur with early coccidioidal infection. Parapneumonic effusions associated with coccidioidal pneumonia are frequent if looked for carefully (36). However, on occasion they are not small and may be noted in patients prior to diagnosing the pulmonary process as coccidioidomycosis. As it turns out, coccidioidal parapneumonic effusions are generally self-limited and do not normally need aggressive drainage or decortication (37) as would often be employed for bacterial pleural infections. As a result, without early diagnosis of the coccidioidal etiology, it is very likely that unnecessary procedures would be instituted. This is especially true in pediatric patients where early video assisted thoracic surgery (VATS) is increasingly used for bacterial empyemas (38).

The consequences of coccidioidal pneumonia: Their management and mismanagement.

Nodules. Approximately 5% of coccidioidal pulmonary infections leave a nodule, visible by plain radiographs, in the region of the infiltrate. Undoubtedly, this number is even higher with CT scans. Often coccidioidal nodules are asymptomatic and their appearance is indistinguishable from cancer, including increased metabolic activity on PET/CT scan (39, 40). One benefit of early diagnosis of coccidioidal pneumonia is that when the acute pneumonia evolves into a residual nodule, the etiology of the lesion is known and no further evaluation is necessary. In that regard, asking the patient about a past diagnosis of coccidioidal pneumonia and associated X-rays may establish that the nodule is benign.  However, the antecedent acute pneumonia is often not identified and the nodule is detected as an incidental finding. In such cases, the most important issue is to determine if the lesion is malignant and the approach to this should be the same whether coccidioidomycosis is or is not in the differential. Once it is determined that the asymptomatic nodule is due to coccidioidal infection, a common mistake is to initiate antifungal therapy. Treatment at this stage has no effect since its stability indicates that there is no fungal proliferation for an antifungal to inhibit. Periodic evaluation with plain radiographic views of the chest is reasonable but, as with the surveillance of acute coccidioidal pneumonia, in most cases follow-up with CT scans is unnecessary.

Fibrocavitary chronic coccidioidal pneumonia. Another occasional consequence of coccidioidal pneumonia is the development of a cavity, sometimes with surrounding fibrosis. Much of the time cavities are single, often very peripheral near the pleural surface, with little or no surrounding infiltrate (so called “thin-walled” cavity), and asymptomatic. Others have more surrounding infiltrate or an air-fluid level within the cavity, can over time involve additional segments of the lung, and can produce symptoms such as pleuritic pain, cough, and hemoptysis.

A common mistake is the overtreatment of asymptomatic thin-walled cavities. While such lesions may spontaneously close or expand, there is no evidence that treatment alters such cavities. Similarly, despite their peripheral nature, very few such cavities rupture into the pleural space (see below). While surgical removal is occasionally an appropriate management strategy, most asymptomatic cavities can safely be observed with periodic plain films of the chest without surgical intervention.

Management of symptomatic, complex, or expanding cavities may involve oral azoles such as fluconazole (41) or surgical resection (42). Formulating the selection and timing of these two options is highly individualized. However, we would underscore that surgical management is often technically more challenging than might appear from an examination of the radiographic images. In experienced hands, video assisted thoracoscopic surgery (VATS) is increasingly utilized (43). However, some situations still require more extensive thoracotomy. It is highly recommended that patients be referred to thoracic surgeons who are specifically experienced in resecting coccidioidal lesions.

Ruptured coccidioidal cavity. As indicated above, it is surprising how few coccidioidal cavities rupture, resulting in a bronchopleural fistula and collapse of the lung. Their occurrence is most frequently in otherwise healthy athletic males and about half the time it is the first clinical manifestation of the coccidioidal infection (44). Because rupturing spherules are inflammatory, cavity rupture results in a pyopneumothorax with an air-fluid level rather than a simple pneumothorax as would be typical of a spontaneous pneumothorax or a ruptured pulmonary bleb. Failure to make this distinction often results in a delay in diagnosis.

Once diagnosed, it is possible that oral azole antifungal therapy with re-expansion of the lung using chest tubes may resolve the problem. However, very frequently this is not effective in closing the air-leak and surgical resection of the ruptured cavity is needed. As with surgical intervention of other coccidioidal pulmonary lesions, a surgeon familiar with managing such problems is preferred.

Diffuse coccidioidal pneumonia. Occasionally, the initial coccidioidal pneumonia is wide-spread, involving several areas of both lungs and requiring intensive care and ventilatory support (45). Most cases of diffuse reticulonodular coccidioidal pneumonia are the result of fungemia in a severely immunocompromised patient (46-48). In Arizona patients with untreated AIDS, with this pattern, the coccidioidal infection frequently co-existed with Pneumocystis spp. infection (49). Not appreciating this can lead to initiating steroids and pneumocystis treatment which if antifungals are not also begun will exacerbate the coccidioidal infection. Less frequently, a very similar radiographic appearance can occur in immunologically normal persons following high-inoculum infection such as can occur at archeology excavation sites (50, 51). In contrast to where fungemia is responsible, patients with high-inoculum infections do not usually have extrapulmonary infections and often respond very quickly to treatment.

New advocacy for improving the care of patients with coccidioidomycosis.

The Valley Fever Center for Excellence, established in 1996 at the University of Arizona, promotes education, research, and improved care for coccidioidomycosis. As part of its program it established in 2009 a clinical network which later was named the Valley Fever Alliance of Arizona Clinicians (VFAAC). This year, the VFAAC Board of Directors published a Valley Fever tutorial for primary care clinicians that is available on the Center’s website (https://www.vfce.arizona.edu/resources/pdf/Tutorial_for_Primary_care_Physicians.pdf) or by requesting a copy directly from the Center. The purpose of VFAAC is to link clinicians in Arizona who are interested in and experienced with coccidioidomycosis and to provide among them avenues of communication. Clinicians interested in becoming members of VFAAC can submit an application form which is reviewed and approved by the Board of Directors at one of its meetings held several times each year. Thus far VFAAC has expanded to over 125 clinicians. VFAAC membership is encouraged for any clinician licensed by the Boards of Medical Examiners, Osteopathic Examiners, Nursing, Physician Assistants, Behavior Health, Physical Therapy, or Occupational Therapy. Clinicians interested in learning more about VFAAC can contact the Valley Fever Center at vfever@email.arizona.edu.

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40. Reyes N, Onadeko OO, Luraschi-Monjagatta Mdel C, Knox KS, Rennels MA, Walsh TK, et al. Positron emission tomography in the evaluation of pulmonary nodules among patients living in a coccidioidal endemic region. Lung. 2014;192(4):589-93. [CrossRef] [PubMed]
41. Galgiani JN, Catanzaro A, Cloud GA, Johnson RH, Williams PL, Mirels LF, et al. Comparison of oral fluconazole and itraconazole for progressive, nonmeningeal coccidioidomycosis. A randomized, double-blind trial. Mycoses Study Group. Ann Intern Med. 2000;133(9):676-86. [CrossRef] [PubMed]
42. Jaroszewski DE, Halabi WJ, Blair JE, Coakley BJ, Wong RK, Parish JM, et al. Surgery for pulmonary coccidioidomycosis: a 10-year experience. Ann Thorac Surg. 2009;88(6):1765-72. [CrossRef] [PubMed]
43. Ashfaq A, Vikram HR, Blair JE, Jaroszewski DE. Video-assisted thoracoscopic surgery for patients with pulmonary coccidioidomycosis. J Thorac Cardiovasc Surg. 2014;148(4):1217-23. [CrossRef] [PubMed]
44. Cunningham RT, Einstein H. Coccidioidal pulmonary cavities with rupture. J Thorac Cardiovasc Surg. 1982;84:172-7. [PubMed]
45. Rosenstein NE, Emery KW, Werner SB, Kao A, Johnson R, Rogers D, et al. Risk factors for severe pulmonary and disseminated coccidioidomycosis: Kern County, California, 1995-1996. Clin Infect Dis. 2001;32(5):708-15. [CrossRef] [PubMed]
46. Bronnimann DA, Adam RD, Galgiani JN, Habib MP, Petersen EA, Porter B, et al. Coccidioidomycosis in the acquired immunodeficiency syndrome. Ann.Intern.Med. 1987;106:372-9. [CrossRef] [PubMed]
47. Fish DG, Ampel NM, Galgiani JN, Dols CL, Kelly PC, Johnson CH, et al. Coccidioidomycosis during human immunodeficiency virus infection. A review of 77 patients. Medicine (Baltimore). 1990;69:384-91. [CrossRef] [PubMed]
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Reference as: Galgiani JN, Knox K, Rundbaken C, Siever J. Common mistakes in managing pulmonary coccidioidomycosis. Southwest J Pulm Crit Care. 2015;10(5):238-49. doi: http://dx.doi.org/10.13175/swjpcc054-15 PDF

Editor's Note: For accompanying editorial see "Eliminating Mistakes in Managing Coccidioidomycosis" by Tim Kuberski.

May 2015 Pulmonary Case of the Month: Pneumonia with a Rash

Richard A. Robbins, MD

Phoenix Pulmonary and Critical Care Research and Education Foundation

Gilbert, AZ

History of Present Illness

A 77-year-old man underwent a thoracic CT scan  for follow up of a known thoracic aneurysm.  However, he had been feeling tired for about a week with a cough, night sweats and fever. He had no shortness of breath, wheezing or known history of lung disease.

Past Medical History, Social History and Family History

He has a history of hypertension and a known thoracic aortic aneurysm. There was a  surgical repair of his right clavicle after a motor vehicle accident. He is single and has lived in Arizona for over 50 years. He just returned from a trip to California where he visited Disneyland. He does not smoke. Family history is noncontributory.    

Current Medications

• Dutasteride
• Levothyroxine
• Atorvastatin

Physical Examination

His physical examination was reported as unremarkable. SpO2 was 95% on room air.

Radiography

Figure 1. Representative images from his thoracic CT scan showing a left lower lobe consolidation (red arrows). Panel A: coronal projection in lung windows. Panel B: axial view in lung windows.

Which of the following is appropriate at this time? (Click on the correct answer to proceed to the second of four panels)

1. Begin empiric antibiotics
2. Bronchoscopy with bronchoalveolar lavage
3. Sputum Gram stain and culture
4. 1 and 3
5. All of the above

Reference as: Robbins RA. May 2015 pulmonary case of the month: pneumonia with a rash. Southwest J Pulm Crit Care. 2015;10(5):203-7. doi: http://dx.doi.org/10.13175/swjpcc044-15 PDF 

September 2014 Pulmonary Case of the Month: A Case for Biblical Scholars

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 66-year-old man was seen in consultation. He had been followed since 1998 for bronchiectasis. He had a prior history of multiple skin infections with abscess formation requiring drainage beginning when he was in his 20's. He presented with increased recent sputum production, greenish in color.

PMH, FH, SH

He had a history of multiple skin infections, multiple pneumonias and osteomyelitis in addition to the bronchiectasis. There was a positive family history of coronary artery disease and childhood cancer in a sister. He had smoked cigars in the remote past, but none since the age of 25.

Physical Examination

•       General: short stature, scoliosis, SpO2 98% on RA.
•       Chest: few scattered crackles, no wheezes.
•       Cardiovascular: regular rate and rhythm with no murmur noted.
•       Extremities: No clubbing, cyanosis or edema.

Spirometry

      FVC 69% of predicted; FEV1 76% of predicted.

Which of the following should be performed at this time? (Click on the correct answer to proceed to the next panel)

1. Immunocompromised evaluation
2. Sputum culture
3. Thoracic CT scan
4. 1 and 3
5. All of the above

Reference as: Wesselius LJ. September 2014 pulmonary case of the month: a case for biblical scholars. Southwest J Pulm Crit Care. 2014;9(3):146-50. doi: http://dx.doi.org/10.13175/swjpcc108-14 PDF

March 2014 Pulmonary Case of the Month: The Cure May Be Worse Than the Disease

Sudheer Penupolu, MD 

Philip J. Lyng, MD

Lewis J. Wesselius, MD 

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 51 year old woman was seen with a chief complaint of gradually increasing shortness of breath. She was at baseline five months prior to presentation but noticed dyspnea on minimal exertion initially at a higher altitude, gradually progressing to dyspnea at rest. She was tried on 2 courses of antibiotics with no significant improvement. In addition to the dyspnea, she has some non productive cough but no fevers.

PMH, SH, FH

She had a renal transplant in 1997 for IgA disease and has a history of type II diabetes and hypertension.

She is a life long nonsmoker and has only occasional alcohol use. She is employed as a utility designer and has no exposure to any dusts, fumes or exotic animals.

Family history is noncontributory.

Medications

• Atenolol
• Lasix
• Prednisone 2 mg q daily
• Rosuvastatin
• Sirolimus 2 mg po q daily

There have been no changes in the doses in the past few years.

Physical Examination

Physical examination reveals no abnormalities and her lung auscultation is clear.

Laboratory

Her complete blood count (CBC), urinanalysis, liver function tests, and calcium were all within normal limits.

Radiology

An x-ray of the chest is shown in Figure 1. 

Figure 1. Initial PA chest radiograph.

Which of the below is the best interpretation of her chest x-ray?

1. Cardiomegaly
2. Left upper lobe consolidation
3. Normal
4. Right upper lobe consolidation
5. All of the above

Reference as: Penupolu S, Lyng PJ, Wesselius LJ. March 2014 pulmonary case of the month: the cure may be worse than the disease. Southwest J Pulm Crit Care. 2014;8(3):142-51. http://dx.doi.org/10.13175/swjpcc005-14 PDF

February 2013 Pulmonary Case of the Month: One Thing Leads to Another

Elijah Poulos, MD

Erica Peterson, MD

Robert A. Raschke, MD

Good Samaritan Regional Medical Center

Phoenix, AZ

History of Present Illness

A 63 year-old man from Minnesota with a history of sarcoidosis managed with low-dose prednisone (average 6 mg/day with periodic bursts) for the past 15 years was transferred to our hospital for a higher level of care.  Eight weeks prior to admission he was in Costa Rica for a 3 week vacation where he engulfed himself in local traditions, swam in marine and fresh water, slept in rural areas, ate unprocessed foods, wore no insect repellent and had no prophylactic vaccines or medications. He returned to northern Minnesota and visited his cabin where he noted numerous dog tics.

Four weeks prior to admission he developed intermittent fevers to 102°, rigors and drenching night sweats. Workup initiated in Minnesota was unrevealing. Specifically he had negative malaria smears, blood cultures, leptospirosis and hepatitis panels. Transaminases were elevated in the 100s. An empiric 1 week trial of doxycycline resulted in no improvement.

One week prior to admission he came to Arizona for a golfing trip. He noted ongoing fevers, chills, and sweats as before but now had a left conjunctival hemorrhage, lethargy, ataxia, dysarthria, jaundice and dyspnea. He was taken to the emergency room of another hospital where he was noted to have a fever of 104°, transaminitis, pancytopenia, and hypoglycemia. He was transferred to our care.

Physical Exam

Upon arrival, the patient was a well-nourished male who appeared fatigued, diaphoretic, and in mild respiratory distress. Vitals signs upon admission revealed a temperature 39.4° C, heart rate 118, blood pressure 111/70, respiratory rate 22, and oxygen saturation 93% on 2 liters via nasal cannula. Bibasilar crackles and diffuse wheezes were present on lung auscultation. A left conjunctival hemorrhage, mild jaundice, and upper extremity petechiae, purpura and bruising were present. Abdominal exam revealed hepatosplenomegaly.

Laboratory

CBC: WBC 1.4 X 10³ cells/mcL (47 segs, 29 bands, 5 NRBC, 4 metas, 5 myelos), Hgb 10.2 g/dL, and platelets 14 X 10³ cells/mcL. A peripheral smear was unremarkable except for pancytopenia.

Metabolic studies: BUN 41 mg/dL, creatinine 1.5 mg/dL, glucose 50 mg/dL, AST 362 U/L, ALT 227U/L, LDH 1100 U/L, total bilirubin 3.6 mg/dL, alkaline phosphatase 331 U/L..

Coagulation tests: Prothrombin time 18.2 secs, activated partial thromboplastin time (aPTT) 55 secs, fibrinogen 115 mg/dL, D-dimer 12.8 ng/ml D dimer units.

Lumbar puncture: 2 WBC, glucose 59 mg/dL, protein 56 mg/dL. Cultures were negative.

Miscellaneous: erythrocyte sedimentation rate (ESR) 13 mm/hr: C-reactive protein (CRP) 121 mg/L; ferritin >40,000 ng/ml; triglycerides 272 mg/dL.

ABG’s normal on 2L/min.

Radiography

Admission portable chest x-ray is shown in Figure 1.

Figure 1. Admission portable chest x-ray.

Which of the following is true?

1. A thoracic/abdominal CT scan is indicated
2. High-dose corticosteroids are indicated to suppress a  sarcoidosis flair
3. Open lung biopsy is indicated
4. Artesunic acid should be begun for malaria
5. Chloroquine should be begun for malaria

Reference as: Poulos E, Peterson E, Raschke RA. February 2013 pulmonary case of the month: one thing leads to another. Southwest J Pulm Crit Care. 2013;6(2):55-62. PDF

July 2012 Pulmonary Case of the Month: Pulmonary Infiltrates - Getting to the Heart of the Problem

Bridgett Ronan, MD

Robert Viggiano, MD

Lewis J. Wesselius, MD

Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 63 year old man was transferred from outside facility with ventricular tachycardia. He has a past history of ventricular tachycardia and had an intracardiac defibrillator (ICD) placed due to a low ejection fraction. The ICD had administered several shocks to the patient prior to admission.

His present medications included:

• Lisinopril 10 mg bid
• Diazepam 10 mg bid
• Amiodarone 400 mg daily
• Dutasteride 0.5 mg daily
• Tamsulosin 0.4 mg daily
• Dexlansoprazole 60 mg daily
• Levothyroxine 100 mcg daily

The patient underwent and electrophysiology (EP) procedure. He was intubated prior to the procedure. He developed sustained ventricular tachycardia when the ICD was turned off. Eleven cardioversions were required with an accumulated 108 seconds of ventricular tachycardia. He became hypotensive and received 6.2 L boluses of fluids and 5, 400 mg boluses of amiodarone and was placed on an amiodarone drip.

He remained intubated receiving mechanical ventilator after the EP procedure.

He was extubated after 2 days and was initially on oxygen at 6L/min nasal cannula. Over the next several days he developed increasing oxygen requirements and was treated with BiPAP and increasing oxygen.

PMH, SH and FH

As noted above he had a history of recurrent ventricular tachycardia and a dilated cardiomyopathy with an ejection fraction of 30-35%. In addition he had a history of paroxysmal atrial fibrillation, obstructive sleep apnea which resolved with weight loss, hypothyroidism and mild restriction on pulmonary function testing, possibly related to amiodarone or to kyphosis. He is a life-long nonsmoker.

Physical Examination

His vital signs included a Tmax of 38.8 C, heart rate of  79 beats/min, blood pressure of  113/67 mm Hg, respiratory rate of 38 breaths/min, and oxygen saturation of 94% on a 75% high flow mask. His weight had increased to 102 kg from 96.6 kg on admission.

Cardiovascular exam revealed an irregular rhythm but no murmur. There was jugular venous distention present. There was a trace of pedal edema but deeper pitting edema at the hips.

Pulmonary auscultation revealed bilateral rales with diminished breath sounds at the bases.

Chest X-ray

Admission and current chest x-ray are shown in Figure 1.

Figure 1. Admission chest x-ray (panel A) and current chest x-ray (panel B).

Laboratory Evaluation

Arterial blood gases showed a pH of 7.42, a pCO₂ of 39 and a pO₂ of 73 on 70% FiO₂. The white blood cell count (WBC) was elevated at 15.1X10³ cells/mm³.

Which of the following could explain the patient’s increased oxygen requirements?

1. Pulmonary edema
2. Pneumonia
3. Amiodarone lung toxicity
4. A + B
5. A + C
6. All of the above

Reference as: Ronan B, Viggiano R, Wesselius LJ. July 2012 pulmonary case of the month: pulmonary infiltrates - getting to the heart of the problem. Southwest J Pulm Crit Care 2012;5:1-11. (click here for a PDF version of the case)

Relationship between the Veterans Healthcare Administration Hospital Performance Measures and Outcomes

Richard A. Robbins, M.D.¹

Richard Gerkin, M.D.²

Clement U. Singarajah, M.D.¹

¹Phoenix Pulmonary and Critical Care Medicine Research and Education Foundation and ²Banner Good Samaritan Medical Center, Phoenix, AZ

Reference as: Robbins RA, Gerkin R, Singarajah CU. Relationship between the Veterans Healthcare Administration hospital performance measures and outcomes. Southwest J Pulm Crit Care 2011;3:92-133. (Click here for PDF version of manuscript)

Abstract

Health care organizations have been using performance measures to compare hospitals. However, it is unclear if compliance with these performance measures results in better healthcare outcomes. We examined compliance with acute myocardial infarction, congestive heart failure, pneumonia and surgical process of care measures with traditional outcome measures including mortality rates, morbidity rates, length of stay and readmission rates using the Veterans Healthcare Administration Quality and Safety report. Disappointingly, increased compliance with the performance measures was not correlated with better outcomes with the single exception of improved mortality with higher rates of compliance with echocardiography. We also evaluated the hospital level of care and found that higher levels of complexity of care correlated with the acute myocardial infarction performance measure, but not with the congestive heart failure, pneumonia, or surgical process of care performance measures.  However, level of complexity of care strongly correlated with all cause mortality (p<0.001), surgical mortality (p=0.037) and surgical morbidity (p=0.01). These data demonstrate that compliance with the performance measures are not correlated with improved healthcare outcomes, and suggest that if measures are used to compare hospitals, different measures need to be developed.

Introduction

The Joint Commission recently released “Improving America’s Hospitals: The Joint Commission’s Annual Report on Quality and Safety 2011 (1).  In this report the results of hospital compliance with the Joint Commission’s performance measures are listed. The Joint Commission announced not only is compliance improving but identified 405 hospitals as their “Top Performers on Key Quality Measures Program”. In a letter at the beginning of the report Mark Chassin, President of the Joint Commission, said “This program is designed to be an incentive for better performance on accountability measures and to support organizations in their quest to do better”.

However, there have been several criticisms of the report. First, many hospitals which were recognized as top hospitals by US News & World Report, HealthGrades Top 50 Hospitals, or Thomson Reuters Top Cardiovascular Hospitals were not included (2). Small community hospitals were overrepresented and large academic medical centers were underrepresented in the report. Chassin commented that this should be "a wake-up call to larger hospitals to put more resources into these programs…”. This is surprising since teaching hospitals, which are usually large, urban hospitals, have previously been reported to have lower risk-adjusted mortality rates and lengths of stay (3). Second, it has been pointed out that many of the performance measures are not or only weakly associated with traditional outcomes such as mortality (4-7). Therefore, we compared the compliance with the Joint Commission performance measures compared to mortality rates, morbidity rates, length of stay and readmissions using the Nation’s largest healthcare system, the Department of Veterans Affairs. The results demonstrate that compliance with performance measures are not correlated with improved outcomes.

Methods

The study was approved by the Western IRB.

Process Performance Measures. We evaluated hospital performance based on publicly available data from the 2010 VHA Facility Quality and Safety Report (9). These measures evaluate quality of care for acute myocardial infarction, congestive heart failure, pneumonia and surgical care improvement program (SCIP) during fiscal year 2009. For each of the measures, a hospital’s performance is calculated as the proportion of patients who received the indicated care out of all the patients who were eligible for the indicated care. The quality indicators are based on, and in most cases identical to those used for the Joint Commission’s Hospital Compare (acute myocardial infarction-Appendix 1; congestive heart failure-Appendix 2; pneumonia-Appendix 3, surgical quality-Appendix 4). Data were also available for each component of the congestive heart failure quality measure (see Appendix 2) which was evaluated independently.

Disease specific mortality. Hospital-specific, risk-standardized rates of mortality within 30 days of discharge are reported for patients hospitalized with a principal diagnosis of heart attack, heart failure, and pneumonia. For each condition, the risk-standardized (also known as "adjusted" or "risk-adjusted") hospital mortality rate are calculated using mathematical models that use administrative data to adjust for differences in patient characteristics that affect expected mortality rates (10).

Surgical morbidity and mortality. VA’s Surgical Quality Improvement Program (VASQIP) monitors major surgical procedures performed at VHA facilities and tracks risk adjusted surgical complications (morbidity) and mortality rates. Patient data are collected at each facility by a specially trained nurse and entered into the VA’s electronic health record: detailed preoperative patient characteristics including chart-abstracted medical conditions, functional status, recent laboratory tests, information about the surgical procedure performed, and 30-day outcomes data.

The VASQIP program analyzes these patient data using mathematical models to predict an individual patient’s expected outcome based on the patient’s preoperative characteristics and the type and nature of the surgical procedure. Overall patient outcomes for major surgical procedures are expressed by comparing observed rates of mortality and morbidity to the expected rates for those patients undergoing the procedure as observed-to-expected (O/E) ratios. For example, if, based on patient characteristics, a facility expected 5 deaths following major surgery, but only 4 patients died, the O/E ratio would be reported as 0.8.

Medical Surgical Length of Stay (LOS). These data are the VA hospital average length of stay for patients who were discharged from acute medicine or surgery bed sections. It does not include patients discharged from observation beds or discharged from other areas of the hospital such as mental health.

Readmission rates. A readmission was defined as a patient who has had a recent hospital stay and needs to re-enter the hospital again within 30 days. These rates are not adjusted for patient characteristics that affected expected admission rates, so comparisons among hospitals should be interpreted with caution.

CHF readmissions were reported separately. CHF readmission is defined by patients who had an initial hospitalization for CHF and were readmitted at least once to acute care in the hospital within 30 days following discharge for CHF.

Hospital level of care. For descriptive purposes, hospitals were grouped into levels of care. These are classified into 4 levels: highly complex (level 1); complex (level 2); moderate (level 3), and basic (level 4). In general, level 1 facilities and some level 2 facilities represent large urban, academic teaching medical centers.

Correlation with Outcomes. Pearson’s correlation coefficient was used to assess the correlation of compliance with the performance measures and outcomes. Significance was defined as p<0.05. For comparisons among hospital levels, ANOVA or Kruskall-Wallis testing was done, as appropriate.

Results

Disease specific and all cause mortality rates compared to performance measures. Hospital-specific, risk-standardized rates of mortality within 30 days of discharge for patients hospitalized with a principal diagnosis of heart attack, heart failure, and pneumonia were compared to performance measure compliance. There was no correlation (Table 1, p>0.05 all conditions) but with an increased incidence of pneumonia actually weakly correlating with higher compliance with the pneumonia performance measures (Table 1, p=0.0411). Furthermore, there was no correlation between all cause mortality and the average of the three compliance measures (Table 1, p>0.05). Because each table is large, only the correlation coefficients are presented in the text. The table data on which the correlations are based are given at the end of the manuscript. (N=the number of hospitals. NA=not available).

Table 1. Disease Specific Mortality Correlated with Performance Measure Compliance

Correlation Coefficients	r value	N	p value
Acute Myocardial Infarction Mortality and AMI Performance Measure	0.0266	103	0.7897
Congestive Heart Failure Mortality and CHF Performance Measure	0.0992	123	0.2752
Pneumonia Mortality and Pneumonia Performance Measure	0.1844	123	0.0411
All Cause Mortality vs. Average of Performance Measures	0.1118	122	0.2202

Each component of the congestive heart failure performance measure was evaluated individually. Performance of echocardiography correlated with improved mortality (Table 2, p=0.0496) but there was no correlation with use of a angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at discharge, discharge instructions, nor smoking cessation advice (Table 2, p>0.05 all comparisons).

Table 2. Heart Failure Mortality Correlated with Compliance to Individual Heart Failure Performance Measures

Correlation Coefficients	r value	N	p
ACEI or ARB	-0.1007	112	0.2908
Smoking Cessation	0.0651	112	0.4953
Discharge Instructions	0.1411	111	0.1396
Echocardiography	-0.1860	112	0.0496

Surgical mortality and morbidity rates compared to surgical performance measures. There was no correlation between compliance with the surgical care improvement program (SCIP) and surgical mortality or morbidity (Table 3, p>0.05 both comparisons).

Table 3. Surgical Care Improvement Program (SCIP) Compliance Correlated with Observed/Expected (O/E) Morbidity/Mortality

Correlation Coefficients	r value	N	p value
O/E Mortality	0.0943	99	0.3530
O/E Morbidity	0.0031	99	0.9757

Length of Stay. None of the performance measures correlated with medical-surgical length of stay (Table 4, p>0.05 all comparisons).

Table 4. Length of Stay (LOS) Correlated with Performance Measure Compliance

Correlation Coefficients	r value	N	p value
LOS compared to AMI	0.1047	103	0.2926
LOS compared to CHF	-0.0178	123	0.8451
LOS compared to Pneumonia	-0.1679	123	0.0634
LOS compared to SCIP	-0.0404	106	0.6809
LOS compared to Average	0.0028	123	0.9755

Readmission rates. There was no correlation between all cause readmission rates and the acute myocardial infarction, congestive heart failure, pneumonia or surgical performance measures (Table 5, p>0.05 all comparisons). There was no correlation between heart failure readmission rate and the heart failure performance measure (data not shown, r=0.1525, p=0.0921).

Table 5. Readmission Rate Correlated with Performance Measure Compliance

Correlation Coefficients
	r value	N	p
AMI	0.1688	103	0.0883
CHF	0.1505	123	0.0966
Pneumonia	0.0581	123	0.5233
Average	0.1281	122	0.1597

Hospital level of care. Acute myocardial infarction performance measures inversely correlated with the hospital level of care, i.e., the higher the hospital complexity level, the better the compliance (Table 6, p=0.004). However, there was no correlation between congestive heart failure, pneumonia, surgical care improvement program or the average of the measures and the hospital level of care (Table 6).

Table 6. Hospital Level Correlated with Performance Measure Compliance

ANOVA	N	p
Acute Myocardial Infarction (AMI)	103	0.004
Congestive Heart Failure (CHF)	120	0.782
Community Acquired Pneumonia	120	0.296
Surgical Care Improvement Program (SCIP)	106	0.801
Average of Process of Care Measures	120	0.285

There was no correlation between the level of hospital care and the acute myocardial infarction, congestive heart failure, nor pneumonia mortality (Table 7, p>0.05 all comparisons). However, there was a strong correlation between all cause morality (p<0.001) and a correlation between surgical Observed/Expected mortality (Table 7, p=0.037) and surgical Observed/Expected morbidity (p=0.010).

Table 7. Hospital Level Correlated with Mortality and Surgical Morbidity

ANOVA	N	p
Acute Myocardial Infarction (AMI) Mortality	103	0.835
Congestive Heart Failure (CHF) Mortality	120	0.493
Pneumonia Mortality	120	0.547
All Cause Mortality	106	<0.001
Surgical O/E Mortality	99	0.037
Surgical O/E Morbidity	99	0.010

Discussion

These data from the Nation’s largest healthcare system demonstrate that increasing compliance of the performance measures prescribed by the Joint Commission does not affect disease specific mortality, all cause mortality, surgical mortality, surgical morbidity, length of stay or readmissions with the single exception of improved mortality correlating with increased compliance with performance of echocardiography. In contrast to the Joint Commission’s list of top hospitals which found smaller and rural hospitals to be overrepresented, we found that only the acute myocardial infarction performance measure correlated with a higher level of hospital care which represents mostly large, urban hospitals. We did find that all cause mortality and surgical morbidity highly correlated with the level of care. This would appear to differ from the Joint Commission’s list of top hospitals which tended to be small and rural, since VA hospitals with higher levels of care largely represent large urban, academic teaching medical centers.

There are multiple possible reasons for the lack of correlation between the performance measures and outcomes. Many of the outcomes are evidence based but several are not. For example, there are no randomized, multi-center studies evaluating the efficacy of discharge instructions, smoking cessation advice and pneumococcal vaccination. Studies with discharge instructions are retrospective, observational studies and have largely not shown improved outcomes (11,12). Several meta-analyses have failed to demonstrate the efficacy of pneumococcal vaccine in adults (13-15). Advice to quit smoking without follow up support or pharmacologic intervention has not been shown to lower smoking cessation rates (16). Mandating ineffective interventions such as these would not be expected to have a positive effect on outcomes. However, this is where most of the improvement in performance measure outcome has occurred (2).

Most of the interventions are grouped or bundled. Lack of compliance with any one of the bundle is taken as noncompliance with the whole. However, if the only difference between hospitals is noncompliance with an ineffective performance measure, there would not be any expected improvement in outcomes.

Many of the strongly evidence-based outcomes have very high compliance, usually exceeding 95% (9). It is possible that small improvements of 1 or 2% in effective performance measures might have too small an impact on outcomes to be detected even in large databases such as the Veterans Administration which examined 485,774 acute medical/surgical discharges in 2009.

The performance measures appear to avoid highly technical or costly interventions and often avoid interventions which have been shown positively affect outcomes. For example, beta blockers and spironolactone have been shown to be effective in heart failure but are not included in the congestive heart failure performance measures (17,18). Furthermore, carvedilol has been shown to be superior to metoprolol in improving survival (19). Why the performance measures include use of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker but not carvedilol and spironolactone is unclear.

Some of the performance measures may have caused inadvertent harm. For example, administration of antibiotics within 4 hours to patients with pneumonia was a previous performance measure. However, studies showed that this performance measurement led to administration of antibiotics in many patients who proved not to have pneumonia or another infectious disease, and a systematic review concluded that “evidence from observational studies fails to confirm decreased mortality with early administration of antibiotics in stable patients with [community acquired pneumonia]”  (20-22). The time has since been changed to 6 hours, but it is unclear if that it is any better than the initial 4 hour timing used (7).

We did not confirm the Joint Commission’s findings that the top hospitals are overrepresented by small, rural hospitals. We found no correlation between hospital level of complexity of care and performance measure compliance with the exception of acute myocardial infarction which was higher in hospitals with higher complexities of care. Although we found no correlation of the performance measures with any outcome measures, we did find a strong correlation between the hospital level of complexity of care and overall survival and surgical morbidity with the hospitals having the higher level of complexity having improved survival and decreased surgical morbidity. This would seem consistent with concept that volume of care correlates with outcomes.

It seems surprising that initiation of performance measures seem to go through such little scrutiny. In a 2005 editorial Angus and Abraham (23) addressed the issue of when there is sufficient evidence for a concept to be widely applied as a guideline or performance measure. Comparing guidelines to evaluation of novel pharmacologic therapies, they point out that promising phase II studies are insufficient for regulatory approval. Instead, one, and usually two, large multicenter phase III trials are necessary to confirm reliability. The same principle is echoed in evidence-based medicine, where grade A recommendations are based on two or more large, positive, randomized, and multicenter trials. This seems a reasonable suggestion. Perhaps what is needed is an independent Federal or private agency to review and approve performance measures, and as Angus and Abraham suggest, require at least two randomized, multicenter trials before implementation

The data presented in this manuscript do not support the usefulness of increasing compliance with the Veterans Administration’s (or the Joint Commission’s) performance measures in improving outcomes such as mortality, morbidity, length of stay or readmission rates. Until compliance with the performance measures results in improved outcomes, investment to improve these performance measures seems to be a poor utilization of resources. It suggests that oversight of regulatory agencies is needed in developing and implementing performance measures. If performance measures are to be used, new, clinically meaningful measures that correlate with outcomes need to be developed. 

References

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6. Fonarow GC, Yancy CW, Heywood JT; ADHERE Scientific Advisory Committee, Study Group, and Investigators. Adherence to heart failure quality-of-care indicators in US hosptials: analysis of the ADHERE Registry. Arch Int Med 2005;165: 1469-77.
7. Wachter RM, Flanders SA, Fee C, Pronovost PJ. Public reporting of antibiotic timing in patients with pneumonia: lessons from a flawed performance measure. Ann Intern Med 2008;149:29-32.
8. Stulberg JJ, Delaney CP, Neuhauser DV, Aron DC, Fu P, Koroukian SM.  Adherence to surgical care improvement project measures and the association with postoperative infections. JAMA. 2010;303:2479-85.
9. Available at: http://www.va.gov/health/docs/HospitalReportCard2010.pdf (accessed 9-28-11).
10. Ross JS, Maynard C, Krumholz HM, Sun H, Rumsfeld JS, Normand SL, Wang Y, Fihn SD. Use of administrative claims models to assess 30 day mortality among Veterans Health Administration hospitals. Medical Care 2010; 48: 652-658.
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19. Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, Torp-Pedersen C, Scherhag A, Skene A. Carvedilol Or Metoprolol European Trial Investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003;362:7-13.
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