Wednesday, July 2, 2008

Radiological Imaging in Pneumonia: Recent Innovations

Sat Sharma, MD, FRCPC Bruce Maycher, MD Gregg Eschun, MD

Curr Opin Pulm Med 13(3):159-169, 2007. © 2007 Lippincott Williams & Wilkins


Abstract and Introduction

Abstract
Purpose of Review: Pneumonia is one of the major infectious diseases responsible for significant morbidity and mortality throughout the world. Radiological imaging plays a prominent role in the evaluation and treatment of patients with pneumonia. This paper reviews recent innovations in the radiologic diagnosis and management of suspected pulmonary infections.
Recent Findings: Chest radiography is the most commonly used imaging tool in pneumonias because of availability and an excellent cost-benefit ratio. Computed tomography is mandatory in unresolved cases or when complications of pneumonia are suspected. A specific radiologic pattern can suggest a diagnosis in many cases. Bacterial pneumonias are classified into four main groups: community-acquired, aspiration, healthcare-associated and hospital-acquired pneumonia. The radiographic patterns of community-acquired pneumonia may be variable and are often related to the causative agent. Aspiration pneumonia involves the lower lobes with bilateral multicentric opacities. The radiographic patterns of healthcare-associated and hospital-acquired pneumonia are variable, most commonly showing diffuse multifocal involvement and pleural effusion.
Summary: Combination of pattern recognition with knowledge of the clinical setting is the best approach to the radiologic interpretation of pneumonia. Radiological imaging will narrow the differential diagnosis of direct additional diagnostic measures and serve as an ideal tool for follow-up examinations.

Introduction
Pneumonia is a major cause of morbidity and mortality in adult patients.[1] Bacterial pneumonia is the sixth most common cause of death in the USA.[2,3**] Bacterial pneumonias were previously classified into lobar pneumonia, bronchial pneumonia and acute interstitial pneumonia. This classic morphologic classification cannot help to predict the causative organism. The spectrum of organisms is ever increasing; continued escalation in the elderly population of our society and widespread use of antibiotics have changed patterns of bacterial pneumonias.[4] Therefore, most authors prefer a clinical classification of pneumonia: community-acquired pneumonia (CAP), aspiration pneumonia, healthcare-associated pneumonia (HCAP), nosocomial pneumonia [hospital acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP)]. The number of immunocompromised patients has dramatically increased because of the AIDS epidemic, cancer chemotherapy, and organ transplantation.[5,6] Over the last few years many viral infections, such as systemic acute respiratory syndrome and avian influenza, have become a significant threat to humans.[7**]

Diagnosis of pneumonia requires a combination of clinical assessment, radiological imaging, and appropriate microbiological tests.[3**] Plain chest radiography is an inexpensive test and is an important initial examination in all patients suspected of pneumonia.[8] Computed tomography (CT) is a valuable adjunct in negative or nondiagnostic chest radiography, unresolved pneumonias, and when complications are suspected.[9]

Imaging of Bacterial Pneumonia

Not only confirmatory of a diagnosis of pneumonia, radiological imaging can also be indicative of whether the pneumonia is community-acquired, aspiration-related or nosocomial.

Community-Acquired Pneumonia
CAP results in 500 000-1 million patients being hospitalized each year in the USA and carries high morbidity, mortality and cost.[1,2] Chest radiography is the reference standard for the diagnosis of CAP; however, its reliability is limited because of significant interobserver variability in interpretation.[10*] The etiology of CAP varies widely and is geographically influenced. The most common bacterial agents for CAP include Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. In a study by Lim et al.,[11] the most common agent producing CAP was Strep. pneumoniae in 48% of cases, followed by virus in 19%, C. pneumoniae in 13%, Haemophilus influenzae in 20%, and M. pneumoniae in 3%.

The usual radiologic imaging findings in CAP comprise an air-space consolidation in one segmental lobe, limited by the pleural surfaces (Fig. 1). Patterns of lobar pneumonia and bronchopneumonia were equally frequent in pneumococcal pneumonia.[12] A small pleural effusion is especially common and is often reactive. The CT scan may show additional ground glass attenuation, centrilobular nodules, bronchial wall thickening, and centrilobular branching structures.

Figure 1. (click image to zoom) Right upper-lobe consolidation in a patient with community-acquired pneumonia


Mycoplasma pneumonia is common in children, adolescents, and adults below 40 years of age. The incidence of this infection varies but increases during epidemics. The radiographic appearances are variable; however, two main clinical and radiographic groups are identified.[13,14] One pattern is that of unilateral or bilateral air-space disease with a lobar or segmental distribution; the other pattern is a diffuse bilateral reticular nodular infiltrate. Studies have shown no predominant radiographic pattern and more frequent involvement of lung bases. C. pneumoniae has similar radiographic appearance to M. pneumoniae. L. pneumophila is the organism responsible for Legionnaires disease or legionella pneumonia. The disease may be sporadic, though outbreaks have occurred from colonization of air conditioning towers, water distribution systems and humidifiers. Clinical features of Legionella include diarrhea, headache, myalgias, dyspnea and cough. The radiographic findings consist of segmental peripheral consolidations[15] (Fig. 2). There may also be lobar involvement. Bilateral disease is seen in more than half of the patients.

Figure 2. (click image to zoom) Bilateral, multilobar consolidations of community-acquired Legionella pneumonia led to acute respiratory failure


CAP may contain unusual patterns. Round pneumonia resembling a pulmonary mass may occasionally be observed, especially in children.[16] Rapid growth, signs of infection, and resolution over time point to this pattern. Diffuse and bilateral infiltrates are especially seen in patients with chronic obstructive pulmonary disease and CAP. Sometimes these patients develop a linear pattern which could be difficult to distinguish from other etiologies.[17]

Aspiration Pneumonia
Inhalation of oropharyngeal or gastric contents into the larynx and lower respiratory tract causes aspiration pneumonia. Inhalation of sterile gastric contents leads to aspiration pneumonitis. Aspiration pneumonia may also be caused by inhalation of oropharyngeal material colonized with bacteria (Fig. 3). The predisposing features are either disturbance of consciousness or swallowing difficulties. The radiographic appearance is variable. The most common pattern is that of bilateral and multicentric opacities; a perihilar and basal distribution may be evident, particularly in the right lung.[18]

Figure 3. (click image to zoom) Aspiration pneumonia in a patient with dysphagia


Healthcare-Associated Pneumonia
HCAP is a unique entity and differs from CAP, and in many ways is similar to nosocomial pneumonia, either HAP or VAP. HCAP differs from CAP in both its bacteriology and outcomes, and thus therapy for these two groups should probably be approached differently, but similarly to those with HAP and VAP. The guideline definition for HCAP includes the following: hospitalization for ≥2 days in the preceding 90 days; residence in a nursing home or extended-care facility; home infusion therapy; long-term dialysis within 30 days; home wound care; and exposure to family members infected with multiply drug-resistant pathogens.[19] The mortality rate of HCAP patients (19.8%) was similar to that of HAP patients, but was higher than that of CAP patients (10%) and lower than that of VAP patients (29.3%).[20] In addition, the length of hospital stay increased progressively for CAP, HCAP, HAP, and VAP patients, and, in parallel with this, hospital costs increased for each of the four groups in the same order. The patients with HCAP were recommended to be treated for potential multiply drug-resistant pathogens, including resistant Gram-negative organisms and methicillin-resistant Staphylococcus aureus.

Nosocomial Pneumonia: Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia
HAP occurs 48 h after hospital admission or within 48 h of discharge from the hospital. The most common organisms responsible for HAP include aerobic Gram-negative bacilli (Enterobacteria, Escherichia coli, Pseudomonas aeruginosa) and Gram-positive cocci (S. aureus, Strep. pneumoniae). Quite often, HAP is deemed polymicrobial. Multiple risk factors that predispose to HAP include age, severity of the underlying disease, length of hospitalization, and invasive procedures.[21-23] Pneumonias are frequently encountered in intensive care units (ICUs) in patients on mechanical ventilation and are associated with high mortality (10-50%).[24] Interestingly, VAP occurring in the first 5 days of ventilation is usually due to Strep. pneumoniae, H. influenzae, M. catarrhalis and, occasionally, anaerobes; in contrast, VAP acquired after 5 days of ventilation commonly is secondary to P. aeruginosa, Acinetobacter or Enterobacter species, or methicillin-resistant S. aureus. The radiographic patterns are quite variable: HCAP and HAP are most likely bilateral with diffuse or multilobar consolidation. Pleural effusions are not uncommonly an associated abnormality[25] (Fig. 4).

Figure 4. (click image to zoom) Nosocomial left lower-lobe pneumonia of polymicrobial etiology developed in a patient recovering from total colectomy


Since these patients may also concurrently or otherwise have atelectasis, pulmonary infarction, pulmonary edema or acute respiratory distress syndrome, portable chest radiography is of limited value. The radiographic signs are nonspecific and the most reliable feature is the presence of air bronchogram. There is poor agreement between radiologists on interpretation of these films. Additionally, radiographic technique and other clinical factors influence interpretation of films. The role of chest radiographs in hospitalized patients is to rule out pneumonia when the radiographs are normal.[22,23] CT scanning may be helpful when chest radiographs are inconclusive, especially in patients with acute respiratory distress syndrome.[25]

Complications of Bacterial Pneumonia
CAP and nosocomial pneumonia are associated with multiple complications, especially in immunocompromised patients. The presence of cavitation is suggestive of a bacterial disease rather than viral or Mycoplasma pneumonia. The most common organisms associated with cavitation include S. aureus, Gram-negative bacteria, and anaerobes[12,17] (Fig. 5).

Figure 5. (click image to zoom)Left lower-lobe cavitation in a patient with nosocomial Gram-negative (Pseudomonas) pneumonia


Pulmonary gangrene is a rare form of cavitation that produces necrotization and subsequently a large cavity formation; this commonly occurs secondary to thrombosis of the pulmonary vessels. Pneumococcus and Klebsiella, as well as Aspergillus, are the most common agents in immunocompetent patients and immunocompromised hosts.[26] Staphylococcal infection is associated with pneumatocele, a cystic space that may be single or multiple and may enlarge, which is commonly seen in children.[12,17]

Lobar enlargement with bulging or ballooning of intralobar fissure is commonly associated with Klebsiella pneumonia, which is seen more commonly in alcoholics, affects upper lobes and is a common cause of the well known 'bulging fissure sign'.[27]

Approximately 20-60% of hospitalized patients with bacterial pneumonia develop parapneumonic pleural effusions. Most of these effusions are reactive and resolve with the antibiotic therapy. However, in 5-10% of cases, the effusions become complicated and progress to emphysema.[27] Decubitus film should be obtained and if the pleural fluid layers are greater than 10 mm, thoracentesis is recommended. If the patient is not showing improvement with therapy, consider repeating the chest X-ray in 12-24 h to see if the pleural effusion is increasing. Such patients may need to undergo a repeat thoracentesis in some instances.

Viral Pneumonia

Numerous viruses may cause lower-respiratory-tract infections in adults. These include influenza virus, adenovirus, measles virus, Hanta virus, Varicella-Zoster virus, and cytomegalovirus. The manifestations vary depending on whether the host is normal or immunocompromised. The viruses result in pathological findings of tracheobronchitis, bronchiolitis, and pneumonia. Parenchymal involvement initially occurs in the lung adjacent to the terminal bronchioles and respiratory bronchioles; however, extension throughout the lobule may occur. Rapidly progressive pneumonia may be seen in elderly and immunocompromised patients.[28,29]

Tracheobronchitis is not usually associated with radiologic abnormalities, whereas bronchiolitis causes partial airway obstruction and results in hyperinflation as well as poorly defined nodular opacities.

Viral pneumonia has a radiologic pattern consisting of poorly defined nodules, air-space nodules (of 4-10 mm), patchy areas of peribronchial ground glass opacity, and air-space consolidation. Hyperinflation is also commonly present because of the associated bronchiolitis. Pneumonia could progress as seen by the rapid confluence of consolidation leading to diffuse alveolar damage, which consists of homogenous or patchy unilateral or bilateral air-space consolidation and ground-glass opacity or poorly defined centrilobular nodules[29] (Fig. 6).

Figure 6. (click image to zoom) Influenza pneumonia in a debilitated elderly patient who did not receive influenza vaccine


Hanta virus pulmonary syndrome is identified radiologically as interstitial edema with or without rapid progression to air-space disease. There is a central or bibasilar distribution along with pleural effusions, which are common findings. These radiographic abnormalities arise secondary to pulmonary capillary leak syndrome.[30**]

More recently, severe acute respiratory syndrome (SARS) outbreaks have been reported in China, Hong Kong, and Canada. The illness is characterized by its highly infectious nature, as well as rapid deterioration of clinical course and propensity to involve healthcare workers. Serial chest radiographs are the initial investigations of choice in diagnosing this condition. These have shown unilateral or bilateral peripheral pleural-based opacities, which range from ground-glass opacities to consolidation with a lower zone predominance.[31] In advanced cases, widespread opacification in both lungs was identified. Pleural effusion is typically absent. High-resolution CT demonstrates ground-glass opacity with or without thickening of the interlobular interstitium, consolidation, or a combination of both. High-resolution CT scanning is more sensitive than chest radiography and provides detailed characteristics of abnormalities recognized on chest radiographs. A chest CT scan may also play a role, not only in detection and in characterization of the disease but also in monitoring disease progression and response to treatment and in identification of complications.[32*] Pneumomediastinum may also occur and is a distinct complication of SARS.

Nonresolving Pneumonia

Patients with pneumonia typically note subjective improvement within 3-5 days of treatment, although radiologic recovery invariably lags behind. Slow resolution has been defined as the persistence of radiographic abnormalities for more than 1 month in a clinically improved patient.[33] Approximately 90% of patients under 50 years show radiographic resolution by 4 weeks, whereas only 30% of patients older than 50 improve. Other comorbid conditions, including underlying systemic disorders and the severity of pneumonia, generally will lead to slow resolution. In patients with nonresolving pneumonia, alternate diagnosis such as tuberculosis, fungal pneumonia, nocardia and actinomycosis, neoplastic disorders of bronchogenic carcinoma, lymphoma, sarcoidosis, and bronchoalveolar carcinoma should be considered (Fig. 7). Additionally, inflammatory disorders consisting of bronchiolitis obliterans organizing pneumonia, eosinophilic pneumonias, systemic vasculitis, and drug-induced lung diseases constitute a significant proportion.[34] Bronchiolitis obliterans organizing pneumonia presents radiographically as a peripheral, patchy alveolar or air-space process and could be indistinguishable from bacterial pneumonia (Fig. 8). Finally, pulmonary embolism and infarction may mimic pneumonia in up to 30% of the cases.[35*] Treatment failure of a presumed pneumonia should be further investigated by high-resolution CT scan (Fig. 9). Detection of parenchymal abnormalities, including emphysema, air-space disease, interstitial disease, and nodules, may narrow differential diagnosis further or suggest an alternate diagnosis.[36]

Figure 7. (click image to zoom) Nonresolving pneumonia investigated by computed-tomography scan and bronchoscopy turned out to be bronchoalveolar carcinoma

Figure 8. (click image to zoom) Bronchiolitis obliterans organizing pneumonia of idiopathic etiology

Figure 9. (click image to zoom) Clinical presentation of left-lower pneumonia proved to be pulmonary infarction on spiral computed-tomography scan


Integrating Clinical and Imaging Findings

Since most useful imaging modalities for the evaluation of patients with known or suspected pulmonary infection are chest radiography and CT scan, the images should be interpreted with clinical knowledge. These include patient's symptoms, level of dyspnea, presence of fever or leukocytosis, productive or nonproductive cough, duration of symptoms, and immune status of the patient. Geographic location of the patient, whether in the community, a nursing home or a hospital, is an important factor in categorizing pneumonias.[21,23]

Although extremely valuable, the clinical data and radiographic findings may fail to establish a definitive diagnosis of pneumonia. This occurs because fever may be associated with drug-induced pulmonary disease, acute eosinophilic pneumonia, bronchiolitis obliterans organizing pneumonia, and pulmonary vasculitis. Furthermore, pulmonary edema and hemorrhage may also result in localized pulmonary disease of lobar or segmental distribution. Difficulties may occur in differentiating acute respiratory distress syndrome from pneumonia, and especially when both illnesses may coexist. Chest radiography should be obtained whenever pneumonia is suspected in adults. This is an important tool for detection of new infiltrates and for monitoring therapeutic response.[11-14] Chest radiographs also have a role in assessing the extent of disease and detection of complications such as cavitation, abscess formation, pneumothorax, and pleural effusions.

What is the outcome of patients admitted to hospital with a suspicion of CAP but a normal chest radiograph? Basi et al.[37] studied a population-based cohort of 2706 adults who were admitted with suspected pneumonia. They stratified patients by presence or absence of radiograph-confirmed pneumonia, and compared their characteristics and in-hospital mortality. Patients without radiographic confirmation of pneumonia had similar rates of positive sputum cultures (32 compared with 30%) and blood cultures (6 compared with 8%), and in-hospital mortality. Thus, absence of radiographic findings should not preclude clinical judgment and empiric antibiotics in these patients suffering from bacterial tracheobronchitis.

Pulmonary Computed-Tomography Scan
CT scanning is a useful adjunct to conventional radiography and provides excellent anatomical detail of the pattern and distribution of pulmonary processes. The findings of air-space disease, air-space nodules, ground-glass opacities, consolidation, air bronchograms, and centrilobular or perilobular distribution are seen better by CT than chest radiography.[12,17] Ground-glass opacification is a nonspecific CT-scan finding which may represent either alveolar or interstitial disease. The findings of interstitial disease reflect thickening by pulmonary edema, neoplasm, inflammation, or fibrosis of the normal interstitial structures. These are represented by CT-scan findings of septal thickening, bronchial-wall thickening, mosaic perfusion, bronchovascular-bundle thickening, interstitial nodules, and honeycombing.[12,17,38] The role of CT scanning is crucial in patients with nonrevealing or nondiagnostic findings, as well as for characterizing complications of pneumonia.

High-resolution CT scans obtained in 114 patients (58 immunocompetent, 56 immunocompromised) showed no or rare areas of air-space consolidation in patients with viral pneumonia and Pneumocystis carinii pneumonia (9%), in contrast to bacterial (85%), M. pneumoniae (79%), and fungal (75%) pneumonias.[38] Extensive symmetric bilateral areas of ground-glass attenuation were present in 95% patients with P. carinii pneumonia. Centrilobular nodules were present less commonly in bacterial pneumonia (17%) than in M. pneumoniae (96%), viral (78%), or fungal (92%) pneumonia.[38]

Strategies for Optimal Imaging Evaluation

In CAP, diagnosis and management often follow conventional chest radiography; other diagnostic procedures are rarely required. More than 90% of patients with segmental or lobar consolidation have either pneumococcal pneumonia or an atypical pneumonia caused by mycoplasma or a virus.[12-15] As a diagnostic strategy, the ordering of a chest X-ray to confirm a diagnosis of CAP in adults is recommended when patients have the following four clinical signs: fever, cough, sputum and coarse crackles.[8] Interobserver reliability of radiographic findings and the relationship to different causative pathogens in CAP was investigated by Boersma et al..[39**] Interobserver reliability was poor (κ < 0.4) for determining the main pattern of infiltrate and presence of air bronchogram, lymphadenopathy and thickening of bronchial walls. Interobserver reliability was fair to good (κ 0.4-0.7) or even excellent (κ >0.7) for determining the presence of pleural effusion, the extent of pneumonia and for identifying the lobes involved. M. pneumoniae was associated more often with patchy alveolar opacities than Strep. pneumoniae. Chlamydia spp. were associated with unilobar involvement (86%), especially when compared to M. pneumoniae and Strep. pneumoniae. Chest radiographs are of limited value in predicting the causative pathogen, but are of good use determining the extent of pneumonia and to detect complications such as parapneumonic effusion.

In nosocomial pneumonia, patchy bronchial pneumonia is the most common finding and is likely caused by Gram-negative pathogens, especially Pseudomonas or Klebsiella.[12,17] Aspiration pneumonia should always be suspected if the infiltrates are present bilaterally in the dependent or posterior portions of the lungs. A very high percentage of patients in medical ICU have abnormalities on chest radiographs. Studies on management and outcome efficacy to evaluate the role of routine chest radiography in ICU patients are required. Loeb et al.[40*] determined that the interrater agreement among radiologists for mobile chest radiographs in establishing the presence or absence of an infiltrate can be judged to be 'fair'. Treatment decisions need to include clinical findings and should not be made based on radiographic findings alone (Fig. 10).

Figure 10. (click image to zoom) Poor interobserver agreement for community-acquired pneumonia occurred in a patient with cardiomyopathy and sepsis


High-resolution CT scan can be useful in patients who have respiratory symptoms but normal results on chest films; additional information is needed on chest radiographic findings, or to look for concurrent parenchymal or pleural disease. CT scanning can also be quite beneficial in guiding diagnostic maneuvers such as bronchoscopy, bronchoalveolar lavage, or lung biopsy[35*,37,41*,42*] (Fig. 11). Despite the inability to make a specific diagnosis from a CT scan, it may be helpful in differentiating infectious from noninfectious acute parenchymal lung diseases.

Figure 11. (click image to zoom)Ventilator-associated pneumonia in a patient with acute respiratory distress syndrome is a difficult diagnosis thus requiring clinical and radiological correlation


Mobile Computed-Tomography Scanning

Making CT studies available at the point of care means that the severely ill patients face fewer of the dangers and usual difficulties involved with multiple transfers. Many patients in the ICUs are critically ill and physiologically unstable.[43] Intrahospital transport to the CT suite of the radiology department involves risks of further deterioration from physiological instability or technical mishaps that may result in aggravated secondary injuries and inability to deliver adequate therapeutic interventions. Furthermore, during infectious outbreaks, a CT service can be provided near the point of care to maintain strict isolation: this occurred during the SARS epidemic. Mobile CT scanners have become available only recently, thus experience with their use in ICU care is limited.[44] The newer mobile CT scanners can be easily moved and positioned close to the patient's bed. It is possible to scan with the patient resting on a nonmoving table or bed. To protect the staff and other patients in the ICU from radiation exposure, mobile lead shields are used.

The major limitation of the battery-powered mobile CT scanner is its lower heat-loading and X-ray tube power compared with that of state-of-the-art multidetector computerized axial tomography scanners. However, motion blurring caused by longer acquisition times is not a problem to render any study uninterpretable. Radiation dose, expressed as the CT dose index, remains a concern for the medical staff operating in the near vicinity; however, portable lead shielding may provide effective protection to healthcare workers. Although imaging of the lung parenchyma, pleural space and mediastinum may not be difficult, diagnosis of suspected pulmonary embolism obtained with a mobile CT scanner may be difficult. More research needs to be conducted to ascertain the quality of studies and the sensitivity and specificity of mobile thoracic scanning in various diseases.[45]

Conclusion

Radiology plays an important role in the diagnosis and management of patients with suspected pneumonia. Conventional chest radiography remains the first imaging procedure in the workup of patients. High-resolution CT scan is not recommended as an initial investigation but is valuable in patients with normal, equivocal, or nonspecific findings on chest radiograph. The CT scan may rarely provide a clue to the etiological agent, but could also be helpful in the differential diagnosis of infectious and noninfectious acute parenchymal lung disease.

Correspondence
Sat Sharma, MD, FRCPC, Associate Professor, Sections of Pulmonary and Critical Care Medicine, University of Manitoba, Site Director, Respiratory Medicine, St. Boniface General Hospital, BG034, 409 Tache Avenue, Winnipeg MB R2H 2A6, Canada Tel: +1 204 237 2217; fax: +1 204 231 1927; e-mail: ssharma@sbgh.mb.ca

Abbreviations
CAP = community-acquired pneumonia; CT = computed tomography; HAP = hospital-acquired pneumonia; HCAP = healthcare-associated pneumonia; ICU = intensive care unit; SARS = severe acute respiratory syndrome; VAP = ventilator-associated pneumonia.

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* of special interest
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Author
Sat Sharma, MD, FRCPC
Associate Professor, Sections of Pulmonary and Critical Care Medicine, University of Manitoba; Site Director, Respiratory Medicine, St. Boniface General Hospital, Winnipeg, Canada

Disclosure: Sat Sharma, MD, FRCPC, has disclosed no relevant financial relationships.


Bruce Maycher, MD
Department of Radiology, University of Manitoba, Winnipeg, Canada

Disclosure: Bruce Maycher, MD, has disclosed no relevant financial relationships.


Gregg Eschun, MD
Sections of Pulmonary and Critical Care Medicine, University of Manitoba, St. Boniface General Hospital, Canada

Disclosure: Gregg Eschun, MD, has disclosed no relevant financial relationships.


CME Author
Charles P. Vega, MD

1 comment:

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