Pneumonia Mimics: Pearls and Pitfalls

Authors: Drew A. Long, BS (@drew2232, Vanderbilt University School of Medicine, US Army) and Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) & Justin Bright, MD (@JBright2021, Senior Staff Physician, Henry Ford Hospital)

It’s a busy day in the ED. You have a full waiting room and multiple patients who have been roomed but not seen. You force your exhaustion to the back of your mind as you see your next patient: a 52-year-old male with cough and shortness of breath for three days. He states he has felt warm at home, but he denies chest pain, abdominal pain, vomiting, and diarrhea. He has experienced several episodes of nausea.  His past medical history includes hypertension and hyperlipidemia.

His vital signs include HR 103, RR 24, BP 128/72, T 99.8, and SpO2 95% on room air. He has some crackles in the lower lung bases, but has an otherwise normal physical exam. You order a chest x-ray, which demonstrates a right lower lobe infiltrate. As you write the diagnosis of “pneumonia” on the discharge form and write a prescription for antibiotics, you pause. Is there something else you could be missing? Are there other diagnoses you should consider?

Background

Pneumonia is defined as an acute infection of the pulmonary alveoli.  Pneumonia can be life-threatening, most commonly in older patients with comorbidities or immunocompromised patients.  It is the 7^th leading cause of death in the U.S. and the number one cause of death from infectious disease in the U.S.¹   The annual incidence of community acquired pneumonia (CAP) ranges from 2 to 4 million, resulting in an estimated annual 500,000 hospitalizations.¹  Pneumonia is broken into several categories: community-acquired (CAP), hospital-acquired, healthcare-associated (HCAP), and ventilator-associated (VAP) (Table 1).

Table 1.  Classification of Pneumonia (Adapted from Maloney G, Anderson E, Yealy DM.  Tintinalli’s Emergency Medicine:  A Comprehensive Study Guide.  Chapter 65:  Pneumonia and Pulmonary Infiltrates.  McGraw Hill Professional 2016.  8^th ed.)

Pneumonia can be caused by bacteria, viruses, or fungi.  However, it is often challenging to differentiate between these in the ED, and many patients will not have an etiologic agent identified even after inpatient evaluation.   It is estimated that a microbial agent cannot be identified in nearly half of cases of CAP.¹ The “typical” pathogens in patients hospitalized with pneumonia include S. pneumoniae and H. influenza, with S. pneumoniae being the most common.  The “typical” pathogens are thought to account for about half of cases.¹ “Atypical” pathogens include Legionella, Mycoplasma, and Chlamydia.  The most common identified viral causes of pneumonia are influenza and parainfluenza viruses.  Fungal pneumonia is often associated with patients who are immunocompromised or possess other risk factors.^1,2

History and Physical Examination

The classic presentation of pneumonia is a cough productive of purulent sputum, shortness of breath, and fever.  The most common signs of pneumonia include cough (79%-91%), fever (up to 75%), increased sputum (up to 65%), pleuritic chest pain (up to 50%), and dyspnea (approximately 70%).³ There are many patterns of presentation with a variety of these symptoms and physical findings, making the diagnosis at times difficult. Elderly or debilitated patients in particular can present with non-specific complaints, such as altered mental status without the classic symptoms.^1,2 In addition, pneumonia may cause lightheadedness, malaise, weakness, headache, nausea/vomiting, joint pain, and rash.  The examination may reveal bronchial or decreased breath sounds, dullness on percussion, rales, rhonchi, or wheezing. This wide variation in symptoms and presentation provides potential for misdiagnosis, especially if other conditions are not considered.

The chest x-ray in patients with pneumonia can vary greatly.  Radiologic findings in pneumonia are used in conjunction with the physical exam to identify any area of consolidation.  The most common cause of pneumonia, S. pneumoniae, classically presents with a lobar infiltrate visualized on chest x-ray.  Other organisms, such as Staphylococcus aureus pneumonia can be seen on chest x-ray as extensive infiltration and effusion or empyema.  Klebsiella may present with diffuse, patchy infiltrates.  Other findings on chest x-ray found in various organisms include pleural effusions, basilar infiltrates, interstitial infiltrates, or abscesses.^1,2,4 However, each agent can present multiple ways on chest x-ray, and many patients may not demonstrate the classic radiographic findings, especially elderly and immunocompromised patients with weakened immune systems.

 While it is tempting to diagnose pneumonia in a patient with a classic presentation (fever, cough, shortness of breath) and a supportive chest x-ray, what else should be considered?  As Table 2 shows, many conditions can be confused for pneumonia based on the history, physical exam, and radiographic findings.

Table 2.  Mimics of Pneumonia (Adapted from Marx JA.  Rosen’s Emergency Medicine:  Concepts and Clinical Practice and Maloney G, Anderson E, Yealy DM.  Tintinalli’s Emergency Medicine:  A Comprehensive Study Guide.  Chapter 65:  Pneumonia and Pulmonary Infiltrates.)

Unfortunately, many of these diagnoses are not even considered in a patient with a classic presentation for pneumonia until the patient fails to improve with initial antibiotic management.  Of the diagnoses listed in Table 2, several of these carry high potential for morbidity and mortality.  These include pulmonary embolism, endocarditis, vasculitis, acute decompensated heart failure, tuberculosis, primary lung cancer, and acute respiratory distress syndrome.  The remainder of this discussion will focus on differentiating each of these from pneumonia.

*Bonus: What can potentially assist providers? Ultrasound (US)!

US has demonstrated tremendous utility differentiating pneumonia from other conditions. X-ray has a sensitivity of 46-77% in diagnosing pneumonia. US findings with pneumonia include air bronchograms, b-lines, consolidations, pleural line abnormalities, and pleural effusions. Dynamic air bronchograms (those that move) are considered pathognomonic for pneumonia.  Positive likelihood ratios (LR) for these findings range from 15.6 to 16.8, with negative LR’s of 0.03 to 0.07.^5,6  Please see a prior emDocs.net post on the use of US in pneumonia: http://www.emdocs.net/ultrasound-for-pneumonia-in-the-ed/

Pulmonary Embolism

Pulmonary embolism (PE) occurs when a thrombus, most commonly from the venous system, embolizes to the pulmonary vasculature.^7,8 Like pneumonia, the clinical presentation of a PE can vary greatly, ranging from an asymptomatic patient to an ill-appearing, dyspneic patient.  PE can be easily confused with pneumonia, as the most common presenting symptom is dyspnea followed by pleuritic chest pain and cough.^8,9 Fever can also be present in pulmonary embolism. The most common symptoms and their frequency are shown in Table 3.

Table 3.  Signs and Symptoms Of Pulmonary Embolism (adapted from Stein PD, Beemath A, Matta F, et al.  Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. Am J Med. 2007;120(10):871.)

A PE most commonly has non-specific chest x-ray findings (atelectasis, pleural effusion, peripheral infarct/consolidation, elevated hemidiaphragm) or is normal.²  That being said, while a normal chest x-ray is helpful in distinguishing PE from pneumonia, a normal chest x-ray does not definitively exclude pneumonia or pulmonary embolism.  Hampton’s Hump (peripheral wedge-shaped opacity with base against pleural surface) and Westermark’s Sign (focus of oligemia and vessel collapse distal to the PE) are classic findings in the PE radiograph, but they lack sensitivity.

The important aspect of not missing PE is first considering it. As the presentation of PE is nonspecific, clinical gestalt and risk stratification are useful. Evaluate the patient for signs/symptoms of PE including shortness of breath with pleuritic chest pain, tachypnea, and leg swelling in the setting of risk factors such as recent travel history, prior history of thrombosis, family history of thrombosis, or history of cancer.  If signs and/or symptoms are present and concerning, do not hesitate to begin the workup for PE.

In PE, US may reveal RV strain with dilated RV and free wall hypokinesis and normal RV apical contractility (McConnell Sign). On short axis view, the LV will appear “D” shaped, with RV bowing into the LV due to elevated right-sided pressures.^10-12

Endocarditis

Endocarditis is most commonly caused by a bacterial agent, with a one-year mortality of 40%.¹³ The most common symptoms are intermittent fever (85%) and malaise (80%).¹  Additionally, endocarditis can present with dyspnea, chest pain, cough, headache, weakness, and myalgias.  Infective endocarditis (IE) can easily be confused with pneumonia in a patient presenting with fever and dyspnea or chest pain.  Risk factors for IE are shown below in Table 4.  Diagnosis includes the Duke Criteria. A patient with flu-like symptoms (cough, myalgias, etc.) with the risk factors shown in Table 4, warrants further evaluation for IE. ^13-17

Table 4.  Risk factors for IE

One of the most important aspects to not miss is the patient with multiple infiltrates on chest x-ray, as a dreaded complication of IE is septic emboli.  This has been described in 13 to 44% of patients with IE.^18,19 Septic emboli can lead to damage in the systemic or pulmonary artery circulation, depending on left vs. right-sided disease.  Specifically, embolization can lead to stroke, paralysis, blindness, ischemia of the extremities, splenic or renal infarction, pulmonary emboli, or an acute myocardial infarction.¹⁸ In particular, septic emboli from the right heart to the pulmonary arteries can lead to a toxic-appearing patient with fever and shortness of breath.  Again, the chest x-ray may demonstrate multiple infarcts or consolidations. This patient may originally be worked up for pneumonia.  In the patient with IE risk factors described above and multiple consolidations/infarcts on chest x-ray, strongly consider IE and obtain multiple blood cultures and echocardiogram.  US may reveal valvular vegetation(s) and/or regurgitation.

Vasculitis (Systemic Lupus Erythematosus)

A vasculitis that often manifests with pulmonary involvement is systemic lupus erythematosus (SLE).  SLE is an autoimmune disorder that leads to inflammation of multiple organ systems.  Pulmonary involvement is common and has been observed in up to 93% of patients with SLE.^20,21 Lung involvement in SLE often manifests as pleurisy, coughing, and/or dyspnea.^21-23 The most common respiratory condition among patients with SLE is pleuritis, thought to be due to autoantibodies damaging the pleura itself.¹ Pneumonitis may also occur in the setting of SLE. Patients with acute lupus pneumonitis present with a rapid onset of fever, cough, and dyspnea, with elevation of serum antinuclear antibodies and anti-DNA antibodies.^22,23

Patients with SLE (either diagnosed or undiagnosed) and lung involvement should be worked up for infection.  Since patients with SLE are often immunosuppressed due to immunomodulatory therapy and the disease itself, they are at a much higher risk of infection with both typical and opportunistic agents.  The patient with extrapulmonary features of SLE (e.g. malar rash, oral ulcers, polyserositis, renal insufficiency, cytopenia, thrombophilia, lymphadenopathy, splenomegaly, or arthritis) and signs of lung involvement warrants treatment for infection and worsening vasculitis. Consultation with rheumatology and the ICU is recommended due to the potential for rapid decompensation.

Diffuse alveolar hemorrhage (DAH) is one of the most life-threatening conditions in SLE. Diffuse alveolar damage is a more common presentation in patients who already have a documented history of lupus and rarely presents as the initial manifestation of lupus.  These patients present with severe shortness of breath, hemoptysis, and diffuse patchy infiltrates on chest x-ray. Patients often require intubation, ICU admission, and high dose steroids.^24-26

Heart Failure Exacerbation

A patient with heart failure exacerbation can present similarly to a patient with pneumonia, particularly if a patient has undiagnosed heart failure.  Patients with acute decompensated heart failure most commonly present with cough, shortness of breath, fatigue, and/or peripheral edema.  The history and physical exam may be enough to differentiate a heart failure exacerbation from pneumonia.  A history of orthopnea and/or paroxysmal nocturnal dyspnea leading up to the patient’s presentation is sensitive and specific for heart failure.  Furthermore, many of these patients will have a cardiac history, history of cardiac procedures, and comorbid conditions for CHF (such as diabetes, hypertension, hyperlipidemia, or a history of smoking).  Physical exam may reveal an S3 or S4 heart sound, elevated jugular venous pressures, lower extremity edema, and crackles indicating interstitial pulmonary edema on auscultation of the lungs.  These patients often have nonspecific EKGs showing left-ventricular hypertrophy, bundle branch block, or signs of a previous MI such as prominent Q waves or T wave inversions.  BNP will more likely be elevated in CHF exacerbations, though sepsis from pneumonia can also increase BNP.^1,27

The chest x-ray findings in CHF may include prominent interstitial markings, cardiomegaly, and pleural effusions.²

US in the setting of CHF will reveal b-lines in 3 or more lung fields bilaterally, which has a +LR of 20. The IVC will often reveal significant distension, with 2-2.5cm in size and < 50% collapse. Echocardiogram may reveal depressed contractility if systolic dysfunction is present.²⁸

Tuberculosis

Tuberculosis (TB) is currently the world’s second leading infectious cause of death.¹ The lungs are the major site for infection with Mycobacterium tuberculosis.  TB can occur in multiple forms, including primary TB, reactivation TB, laryngeal TB, endobronchial TB, lower lung field TB infection, and tuberculoma.²⁹ As TB affects the lungs and can present with fever, cough, or dyspnea, it is often misdiagnosed as viral or bacteria pneumonia.  There are a wide array of nonspecific signs and symptoms associated with the multiple forms of TB, shown in Table 5.³⁰

Table 5.  Symptoms and Signs of Tuberculosis (Adapted from Barnes PF, et al:  Chest roentgenogram in pulmonary TB: new data on an old test. Chest. 94:316, 1988.)

In differentiating TB from pneumonia, it is important to assess the patient for risk factors for TB.  The most commonly reported behavioral risk factor among patients with TB in the U.S. is substance abuse (including drugs, tobacco, and alcohol).³¹ Other risk factors include malnutrition, systemic disease (silicosis, malignancy, diabetes, renal disease, celiac disease, or liver disease), or patients who are immunocompromised or homeless.³²  Additionally, TB should be considered when a patient has a history of recent travel to an area where TB is endemic (Africa, the Middle East, Southeast and East Asia, and Central and South America).³³

 As TB has many forms, the chest x-ray in TB can vary and may not be all that helpful in differentiating TB from pneumonia.  In summary, TB should be suspected in a patient with vague symptoms who possesses risk factors for TB, particularly in patients who are homeless, immunosuppressed, have a history of drug use, or have recently traveled to a TB endemic area.

Primary Lung cancer

In 2012, lung cancer worldwide was the most common cancer in men and the third most common cancer in women.³⁴ In the U.S., lung cancer occurs in an estimated 225,000 patients every year and is responsible for over 160,000 deaths.³⁵ There are many risk factors for cancer, the most notorious of which is smoking.

A patient with a primary lung cancer can easily be confused with pneumonia due to the similarity of symptoms (Table 6).  What is key in primary lung cancer is these symptoms have a more insidious onset than the relatively more acute onset of symptoms in pneumonia. Furthermore, these symptoms will progress over time and may include symptoms less commonly seen in pneumonia (weight loss, bone pain, or voice hoarseness).

Table 6.  Symptoms of lung cancer at presentation.  (Modified from: Hyde, L, Hyde, CI. Chest 1974; 65:299-306 and Chute CG, et al. Cancer 1985; 56:2107-2111).

The chest x-ray in patients with lung cancer varies depending on the type and stage of cancer.  The chest x-ray in patients with a primary lung cancer may display a solitary nodule, an interstitial infiltrate, or may be normal.²

 If considering a primary lung malignancy in a patient whose presentation is consistent with pneumonia, more definitive imaging including CT of the chest may be warranted. Discussion with the oncology service is advised.

Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome (ARDS) is acute, diffuse, inflammatory lung injury that carries high rates of morbidity, ranging from 26 to 58%.^35,36 ARDS stems from diffuse alveolar damage and lung capillary endothelial injury, leading to increased capillary permeability and pulmonary edema.¹ This disease manifests with respiratory distress, with patients often displaying tachycardia, tachypnea, hypoxemia, and dyspnea.³⁷ Arterial blood gas analysis shows hypoxemia in addition to acute respiratory alkalosis and increased alveolar-arterial oxygen gradient (though ABG is usually not required in the ED).  A chest radiograph will typically reveal bilateral alveolar infiltrates, and classically, no cardiomegaly is seen.²

When considering ARDS, several factors come into play.  The diagnosis of ARDS is complicated, as the most common cause or ARDS is sepsis. Thus, ARDS may result from a prior pneumonia leading to sepsis. The patient with ARDS will appear sick and will likely require high levels of FiO2 or positive pressure ventilation if not intubated, while the severity of pneumonia varies greatly based on the patient and infectious microbe.  Risk factors such as sepsis, aspiration, and multiple transfusions are commonly seen with ARDS.³⁸ Other risk factors for ARDS include alcohol abuse, trauma, and smoke inhalation.  On physical exam, patients with ARDS often have diffuse crackles on auscultation of the lungs.  The chest x-ray shows more diffuse involvement than would be expected in a patient with pneumonia.² US will reveal b-lines in multiple lung fields.  If concerned for ARDS, be ready to intubate the patient for clinical course/oxygenation and admit to the ICU.

Case resolution

As you return to this 52-year-old gentleman’s room with his prescription for antibiotics, you notice that he remains tachycardic, tachypneic, and hypoxic (HR 105, RR 24, SpO2 93%).  You perform a more complete review of systems and find out this gentleman has been experiencing pain in his right calf over the past week after returning from an overseas business trip.  On exam, you notice that his right lower extremity is slightly edematous compared to the left.  In addition to pneumonia, you decide to begin to work up this gentleman for a possible deep venous thrombosis and pulmonary embolism.  A chest CT reveals a large right-sided segmental PE.

Summary

Many potentially deadly conditions can be confused for pneumonia.  Unfortunately, many of these conditions are not considered until the patient fails to improve after treatment with antibiotics.  The following should be considered in a patient presenting with signs of pneumonia:

• Pulmonary embolism: suspect when a patient has signs/symptoms of PE including shortness of breath with pleuritic chest pain, tachypnea, and leg swelling in the setting of risk factors for DVT/PE.
• Endocarditis/septic emboli: consider in febrile patients with risk factors including history of IV drug use, poor dentition, structural heart disease, or the presence of a prosthetic valve. Septic emboli leading to pulmonary infarction can present with multiple infiltrates on chest x-ray.
• Systemic Lupus Erythematosus: pulmonary involvement is very common in lupus. Patients with SLE and lung involvement must always be evaluated for infection, and diffuse alveolar hemorrhage is a life-threatening complication.
• Heart Failure exacerbation: suspect in a patient with cardiac history and signs/symptoms of heart failure (orthopnea, PND, peripheral edema, elevated jugular venous distension, etc.).
• Tuberculosis: suspect in patients with risk factors for TB including substance abuse, malnutrition, systemic diseases, immunocompromise, or recent foreign travel.
• Lung cancer: suspect in patients with insidious onset of symptoms and in patients complaining of constitutional symptoms such as weight loss or fatigue.
• Acute Respiratory Distress Syndrome: suspect in toxic-appearing patients with white-out on chest x-ray who require high levels of FiO2 or positive pressure ventilation.

References/Further Reading

1. Marx JA. Rosen’s Emergency Medicine:  Concepts and Clinical Practice.  Saunders 2014.  8^th
2. Maloney G, Anderson E, Yealy DM. Tintinalli’s Emergency Medicine:  A Comprehensive Study Guide.  Chapter 65:  Pneumonia and Pulmonary Infiltrates.  McGraw Hill Professional 2016.   8^th
3. Fine MJ, Stone RA, Singer DE et al. Processes and outcomes of care for patients with community-acquired pneumonia:  results from the Pneumonia Patient Outcomes Research Team (PORT) cohort study.  Arch Intern Med 159:  970, 1999.
4. Bartlett JG. Diagnostic approach to community-acquired pneumonia in adults.  UpToDate.  Jan 2016.
5. Hu QJ, Shen YC, Jia LQ, et al. Diagnostic performance of lung ultrasound in the diagnosis of pneumonia: a bivariate meta-analysis. Int J Clin Exp Med. 2014;7(1):115-21. [pubmed]
6. Chavez MA, Shams N, Ellington LE, et al. Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis. Respir Res. 2014;15:50. [pubmed]
7. Thompson BT. Overview of acute pulmonary embolism in adults.  UpToDate.  Jan 2016.
8. Thompson BT. Clinical presentation, evaluation, and diagnosis of the adult with suspected acute pulmonary embolism.  UpToDate.  Jan 2016.
9. Stein PD, Beemath A, Matta F, et al. Clinical characteristics of patients with acute pulmonary embolism:  data from PIOPED II.  Am J Med.  2007;120(10):871.
10. Perera, T. Mailhot, D. Riley, and D. Mandavia, “The RUSH exam: rapid ultrasound in Shock in the evaluation of the critically ill,” Emergency Medicine Clinics of North America, vol. 28, no. 1, pp. 29–56, 2010.
11. P. Borloz, W. J. Frohna, C. A. Phillips, and M. S. Antonis, “Emergency department focused bedside echocardiography in massive pulmonary embolism,” Journal of Emergency Medicine, vol. 41, no. 6, pp. 658–660, 2011.
12. Madan and C. Schwartz, “Echocardiographic visualization of acute pulmonary embolus and thrombolysis in the ED,” American Journal of Emergency Medicine, vol. 22, no. 4, pp. 294–300, 2004.
13. Murdoch DR, Corey GR, Hoen B. Clinical Presentation, Etiology and Outcome of Infective Endocarditis in the 21^st Century:  The International Collaboration on Endocarditis-Prospective Cohort Study.  Arch Intern Med.  2009 Mar 9;169(5):463-473.
14. Sexton DJ. Epidemiology, risk factors, and microbiology of infective endocarditis.  UpToDate.  Jan 2016.
15. Hill EE, Herijgers P, Claus P. Infective endocarditis:  changing epidemiology and predictors of 6-month mortality:  a prospective cohort study.  Eur Heart J.  2007;28(2):196.
16. Cantrell M, Yoshikawa TT. Infective endocarditis in the aging patient.  Gerontology.  1984;30(5):316.
17. Castillo FJ, Anguita M, Castillo JC, et al. Changes in the Clinical Profile, Epidemiology and Prognosis of Left-sided Native-valve Infective Endocarditis Without Predisposing Heart Conditions.  Rev Esp Cardiol (Engl Ed).  2015 May;68(5):445-8.  Epub 2015 Mar 16.
18. Spelman D, Sexton DJ. Complications and outcome of infective endocarditis.  UpToDate.  Jan 2016.
19. Steckelberg JM, Murphy JG, Ballard D, et al. Emboli in infective endocarditis:  the prognostic value of echocardiography.  Ann Intern Med.  1991;114(8):635.
20. Dellaripa PF, Danoff Sonye. Pulmonary manifestations of systemic lupus erythematosus in adults.  UpToDate.  Jan 2016.
21. King Jr. TE, Kim EJ, Kinder BW. Connective tissue diseases:  In:  Interstitial Lung Disease, 5^th, Schwartz MI, King TE Jr. (Eds), People’s Medical Publishing House-USA, Shelton, CT 2011.
22. Matthay RA, Schwarz MI, Petty TL, et al. Pulmonary manifestations of systemic lupus erythematosus:  review of twelve cases of acute lupus pneumonitis.  Medicine (Baltimore).  1975;54(5):397.
23. Wiedemann HP, Matthay RA. Pulmonary manifestations of systemic lupus erythematosus.  J Thorac Imaging.  1992;7(2):1.
24. Zamora MR, Warner ML, Tuder R, Schwarz MI. Diffuse alveolar hemorrhage and systemic lupus erythematosus.  Clinical presentation, histology, survival, and outcome.  Medicine (Baltimore).  1997;76(3):192. 
25. Andrade C, Mendonca T, Farinha F, et al. Alveolar hemorrhage in systemic lupus erythematosus:  a cohort review.  Lupus.  2016 Jan;25(1):75-85.  Epub 2015 Sep 18.
26. Collard HR, Schwarz MI. Diffuse alveolar hemorrhage. Clin Chest Med 2004;25:583–592, vii.
27. Borlaug BA. Clinical manifestations and diagnosis of heart failure with preserved ejection fraction.  UpToDate.  Jan 2016.
28. Ang S-H, Andrus P. Lung Ultrasound in the Management of Acute Decompensated Heart Failure. Current Cardiology Reviews. 2012;8(2):123-136.
29. Pozniak A. Clinical manifestations and complications of pulmonary tuberculosis.  UpToDate.  Jan 2016.
30. Barnes PF, et al: Chest roentgenogram in pulmonary TB:  new data on an old test.  94:316, 1988.
31. Oeltmann JE, Kammerer JS, Pevzner ES, Moonan PK. Tuberculosis and substance abuse in the United States, 1997-2006.  Arch Intern Med.  2009;169(2):189.
32. Horsburgh CR. Epidemiology of tuberculosis.  UpToDate.  Jan 2016.
33. World Health Organization. Global Tuberculosis Report 2014. http://www.who.int.proxy.library.vanderbilt.edu/tb/publications/global_report/en/.
34. World Cancer Research Fund International. Worldwide Data.  http://www.wcrf.org/int/cancer-facts-figures/worldwide-data.
35. MacCallum NS, Evans TW. Epidemiology of acute lung injury.  Curr Opin Crit Care.  2005;11(1):43.
36. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury.  N Engl J Med.  2005;353(16):1685.
37. Hansen-Flaschen J, Siegel MD. Acute respiratory distress syndrome:  Clinical features and diagnosis in adults.  UpToDate.  Jan 2016.
38. Siegel MD. Acute respiratory distress syndrome:  Epidemiology, pathophysiology, pathology, and etiology in adults.  UpToDate.  Jan 2016.