*Drexel University College of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine
†Advanced Center for Lung and Thoracic Oncology, Eastern Regional Medical Center, Cancer Treatment Centers of America, Philadelphia, PA
Disclosure: There is no conflict of interest or other disclosures.
Reprints: Mark E. Lund, MD, Advanced Center for Lung and Thoracic Oncology, Eastern Regional Medical Center, Cancer Treatment Centers of America, 1331 East Wyoming Avenue, MOB Suite 3170, Philadelphia, PA 19124 (e-mail: firstname.lastname@example.org).
Received March 21, 2013
Accepted May 16, 2013
Primary bronchogenic carcinoma is the most common lethal cancer worldwide. Although the entity of postobstructive pneumonia is frequently encountered in patients with lung cancer, the current available literature is surprisingly sparse with respect to the epidemiology and specific management of this syndrome. In order to initiate appropriate antimicrobial therapy and improve the morbidity and mortality of lung cancer patients, accurate knowledge of the microbiology of these pneumonias is required. Useful clinical applications may also be found in studies which have examined both the microbiology1–2 of postobstructive pneumonias as well as the methods of data collection.1–5 In addition, there have been other studies examining airway colonization in patients with both chronic obstructive pulmonary disease (COPD) and obstructive lesions to better understand the microbiology and mechanisms leading to obstructive pneumonia.5–8
Postobstructive pneumonia was first described by McDonald et al9 as a radiographic opacification resulting from complete or partial airway obstruction by a pulmonary neoplasm. The obstruction is usually thought of as an intraluminal mass, but also commonly results from external compression from masses within adjacent lung parenchyma3 or other mediastinal structures.10 The opacification results from a combination of atelectasis, bronchiectasis, mucus plugging, and parenchymal inflammation1 with or without infection, which can be difficult to distinguish radiologically from the lung tumors which cause them.11
The clearance of inhaled particles is dependent upon an intact mucociliary escalator from the terminal bronchioles to the proximal large airways; thus an obstruction of a proximal airway can present as recurrent pneumonias in the same segment or lobe.12 Historically, nearly one half of patients with central tumors can present with peripheral lung collapse or obstructive pneumonia,13 but studies on the true incidence are limited. In 1 prospective study by Marrie14 of 1269 patients admitted for pneumonia, 23 cases of lung tumors were diagnosed and confirmed histologically. Of these 23 cases, nearly 40% of the patients had pneumonia as their first presenting symptom of pulmonary neoplasm. Additional support for this pathophysiology comes from a retrospective study of patients in Norway showing an increased incidence of lung cancer after hospitalization for pneumonia in comparison with the reference group. In fact, more than half of the lung cancers were first diagnosed within 3 months of the hospitalization.15 In patients with known lung cancer, pneumonia can be a considerable cause of morbidity and mortality,16 and occurs more frequently in patients with advanced disease.17
Central airway obstruction is most commonly due to a malignancy including more indolent tumors such as carcinoid; however, it may also be a complication of benign obstructing lesions including, papillomatosis secondary to HPV, intraluminal lipomas, and adenomas.18 Although all histologic cell types can result in obstruction, small cell carcinoma, and squamous cell carcinomas typically arise centrally and have a tendency to involve the central airways. Not surprisingly, studies have shown that postobstructive pneumonias were more commonly associated with squamous cell or small cell histology.3,17 Obstructive atelectasis complicates roughly 20% of patients with small cell lung cancer and presented with cough and dyspnea, symptoms that resolved with chemotherapy and/or radiation treatment.19 Metastatic disease from carcinomas of breast, colorectal, and renal origin can frequently involve the airways and manifest as progressive respiratory compromise and pulmonary infections in advanced disease.
The etiology of postobstructive lung consolidations, whether due to an actual infection in an area of retained secretions or to a noninfectious chemical pneumonitis from the secretions themselves, remains a matter of debate.1 Radiographic lung opacifications or infiltrates are often assumed to be infectious, but may also simply result from an area of retained secretions, as suggested by Burke and Fraser. They examined the histology of 50 patients undergoing resection for lung cancer with opacities on chest radiographs and found only 9 of 52 cases with evidence of recent or remote infection; 42 of the cases had histologic changes consistent with noninfectious causes.20 Some of the changes described included airway abnormalities such as bronchiectasis or bronchiolectasis with mucus plugging or parenchymal changes such as interstitial pneumonitis and fibrosis. Changes consistent with recent infection, defined as the presence of polymorphonuclear leukocytes and necrosis, were found in 6 of the tumors examined, and always within a background of peribronchiolar inflammatory changes. The authors concluded that the radiologic findings typically associated with infectious pneumonia were not truly infectious in nature.
CLINICAL FEATURES AND MICROBIOLOGY
The diagnosis of a postobstructive infection is, therefore, typically made on clinical grounds with the presentation of fever, chills, leukocytosis in association with respiratory symptoms such as cough, wheeze, and dyspnea. An isolated persistent cough is a frequent presenting symptom of lung cancer, and usually indicates airway involvement. Fever in the setting of an infiltrate associated with a tumor is more likely associated with an organism that can be isolated; however, some cancer patients without infection present with this symptoms. In a study done by Liao et al2 involving patients with cavitating lung tumors, microbes were isolated from 6 of 7 febrile patients versus 1 of 15 nonfebrile patients. In a similar study by Liaw et al,1 7 of 9 febrile patients with obstructive pneumonitis diagnosed radiographically had micro-organisms isolated as opposed to just 2 of 17 nonfebrile patients with similar radiographic findings.
The few studies that have examined the bacteriology of postobstructive pneumonias directly suggest that most of these infections are polymicrobial in nature. In 2 small studies, ultrasound-guided needle aspirations of lung tissue were cultured and then compared against sputum cultures. Anywhere from 30% to 55% of the aspirates were found to be polymicrobial and had little concordance with organisms isolated from sputum cultures.1–2 Owing to the small sample size, there was no predominant organism isolated, but rather a wide variety of bacteria including both aerobic and anaerobic species was reported from each study. A larger retrospective study done by Kohno et al17 also found that the majority of pneumonias were polymicrobial. The most common organisms isolated were Haemophilus influenza, Klebsiella pneumonia, Enterobacter cloacae, Acinetobacter spp., Pseudomonas aeruginosa, and Staphylococcus aureus (Table 1). Interestingly, there was a noticeable shift in infectious etiologies toward gram-positive rods over the duration of the 15-year study period, and a concomitant decrease in the rate of gram-negative bacteria, likely reflecting the growing role of third generation cephalosporins in Japan. These findings demonstrate the selective pressures provided by wide-spectrum antibiotics, especially when used in the setting of nonresolving pneumonias.
One may be able to extrapolate the microbiology of postobstructive pneumonias from studies of patients with underlying lung disease or airway stents who are chronically colonized. Multiple studies examining patterns of colonization in patients with COPD have shown an estimated incidence of 24% to 42%5,21 of patients are colonized with both potential pathogenic micro-organisms (PPMs) and non-pathogenic microorganisms (non-PPMs).
In COPD patients, the most commonly found PPMs are similar to the list of pathogens isolated from the postobstructive pneumonias. One study by Angrill et al7 described the colonization of patients with stable bronchiectasis and found the most common PPMs were H. influenza, P. aeruginosa, and Streptococcus pneumonia. Cabello and colleagues compared the airway colonization of a healthy patient, a patient with COPD, and a patient with bronchogenic carcinoma at their baseline health. The patients with the highest rates of colonization, as shown by protected specimen brush (PSB) samples, were those with COPD and bronchiectasis. H. influenza and Streptococcus pneumonia were the most common organisms which correlates with microbes associated with COPD exacerbations.
Interestingly, the vast majority of COPD patients with stable disease and those during exacerbations grew organisms classified as non-PPMs, the significance of which is not yet understood. Examples of these organisms include Capnocytophagia sputigena, Haemophilus parainfluenzae, Group D Streptococcus, and Streptococcus viridans.5,22 These bacteria can also be introduced to the lower airway through manipulation such as stent placement; however, no correlation has yet been found between their introduction and increased incidence of infection.22 A study of initial bacterial colonization of respiratory intensive care unit patients sought to identify the types of organisms cultured within 48 hours of admission from the pharynx, trachea, stomach, and rectum and found the vast majority of positive cultures to be non-PPM organisms. The most common were S. viridans, Staphylococcus spp. (coagulase negative), and Neisseria spp., and they were largely found in the pharyngeal swabs and tracheal aspirates. Nevertheless, no difference in mortality was seen between those colonized with non-PPMs and those without.23 Interestingly, these organisms can be found in PSB and bronchoalveolar lavage (BAL) samples of healthy individuals with no history of either smoking, COPD, or airway instrumentation.5
When patients with obstructive lesions causing extrinsic compression are treated with airway stents, the procedure itself can either introduce pathogens into the bronchial flora or the stent can become a nidus for bacterial colonization. A study by Noppen et al22 obtaining protected sputum brush samples before and 3 to 4 weeks after airway stent placement showed that insertion of an airway stent was associated with a doubling of positive PSB specimens to 71%. Interestingly, the investigators did not find a relationship between a history of postobstructive pneumonia and airway colonization before instrumentation, suggesting that mechanical obstruction rather than presence of an infection leads to airway colonization. Of the patients with pre-existing airway colonization, there were new organisms within their PSB samples compared with their previous samples. There was also an association between poststent colonization and a quantitative increase in secretions seen on follow-up bronchoscopy, suggesting that stents interfered with mucosal clearance mechanisms. Moreover, the stent itself may harbor bacteria within intraluminal irregularities, possibly becoming colonized similar to the way endotracheal tubes do in mechanically ventilated patients.22
ROLE OF BRONCHOSCOPY
Because of the mechanical nature of large airways obstruction, it can be difficult to obtain accurate information about the microbiology of postobstructive infections noninvasively. The most straightforward and readily available culture sources are expectorated or induced sputum cultures which can be misleading due to frequent oropharyngeal contamination.6 In various studies of postobstructive pneumonia, the sputum culture was considered to be noncontributory to either diagnosis or direction of treatment. Many patients with lung tumors develop postobstructive pneumonias on the background of COPD; however, there have been no formal investigations confirming the sputum purulence of those with postobstructive pneumonias.
Fiberoptic bronchoscopy has a central role in making the diagnosis of airways obstruction and malignancy and yields more accurate information about specific microbiology in cases of suspected postobstructive pneumonia. Bronchoscopy with PSB is considered the gold standard for diagnosis of pneumonia; however, there is no standardization for this procedure,8 nor is there an agreement on what constitutes a positive result. The majority of the studies define a positive culture for PSB as >102 CFUs and for BAL as >103 CFUs, but variation exists and the diagnostic yield would certainly be influenced by the cutoff point used. These studies were largely performed in COPD patients or perioperative patients undergoing pulmonary resection for cancer and additional studies are needed to see whether these results correlate with that found in postobstructive pneumonias.5,6,24,25 Although PSB and BAL may be able to provide a microbiological explanation for a nonresolving pneumonia, it may not lead to an improvement in mortality rate even when antimicrobial therapy is altered.26
The ability to sample a pulmonary lesion directly could be a significant advantage when sputum cultures are negative and the addition of endobronchial ultrasound has greatly enhanced the diagnostic utility of bronchoscopies.27,28 In patients who cannot tolerate bronchoscopy alternate imaging is required. In a retrospective study of 23 patients with nonresolving consolidation who underwent computed tomography-guided percutaneous biopsy, the diagnostic yield was 87%; only 20% of these samples had a positive culture and a diagnosis of postobstructive pneumonia.4 Several studies have examined the utility of ultrasound-guided aspiration1–3 and found the procedure clinically useful in tailoring antibiotics as well as for differentiating simple tumor necrosis from infectious consolidations with a very low incidence of pneumothorax. Advantages of ultrasound-guided techniques over computed tomography-guided biopsies include better visualization of peripheral lesions, and “real-time” monitoring of the needle position potentially leading to fewer complications, decreased cost, and bedside convenience.
The management of postobstructive pneumonia is not only dependent on appropriate antibiotic therapy, but also relief of the obstruction. Interventional bronchoscopy techniques, such as tumor debulking with Nd:YAG laser have shown promise for the treatment of proximal airway lesions while argon plasma anticoagulation and electrocautery have also been used safely and effectively for removal of airway lesions while providing good hemostasis.28 Bronchoplasty and airway stenting are also commonly used to restore airway patency with good results but also carry inherent risks. These and other methods of relieving obstruction should greatly increase the efficacy of antimicrobial therapy in postobstructive pneumonias. More data are required to determine the role these therapies should play in the care of these patients but initial studies have shown a hastened recovery and improved quality of life in patients who have received these interventions in the treatment of their postobstructive pneumonias.28
Postobstructive pneumonias present a difficult clinical situation in terms of diagnosis and treatment. Many of these nonresolving radiologic opacifications may not truly be infectious. For patient with malignancies complicating the airways obtaining accurate microbiological data remains a challenge. Much of the information we have for basing empiric antimicrobial therapy are extrapolated from at-risk populations such as those with COPD. Postobstructive pneumonias are most often polymicrobial, consisting of organisms isolated during both infection and with colonization; moreover, many are considered to be nonpathogenic and their presence in the distal airways is of unknown clinical significance. In addition, there are a number of patients from whom no organism can be isolated. With the emerging resistance patterns of gram-negative organisms in hospitalized patients as well as the use of interventional bronchoscopy techniques used to relieve central airways obstruction, further investigation into the microbiology of postobstructive pneumonias need to be conducted in order to determine the optimal management of this condition in cancer patients.
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