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Bronchoalveolar Lavage As a Diagnostic Procedure: a Review of Known Cellular and Molecular Findings in Various Lung Diseases

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5019 Review Article Bronchoalveolar lavage as a diagnostic procedure: a review of known cellular and molecular findings in various lung diseases Kevin R. Davidson1, Duc M. Ha1,2,3, Marvin I. Schwarz1, Edward D. Chan1,2,4 1Division of Pulmonary Sciences & Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; 2Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA; 3Institute for Health Research, Kaiser Permanente Colorado, Aurora, Colorado, USA; 4National Jewish Health, Denver, Colorado, USA Contributions: (I) Conception and design: KR Davidson, ED Chan; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: None; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Edward D. Chan, MD. D509, Neustadt Building, National Jewish Health, 1400 Jackson St, Denver, Colorado 80206, USA. Email: [email protected]. Abstract: Bronchoalveolar lavage (BAL) is a commonly used procedure in the evaluation of lung disease as it allows for sampling of the lower respiratory tract. In many circumstances, BAL differential cell counts have been reported to be typical of specific lung disorders. In addition, more specific diagnostic tests including molecular assays such as polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay, special cytopathologic stains, or particular microscopic findings have been described as part of BAL fluid analysis. This review focuses on common cellular and molecular findings of BAL in a wide range of lung diseases. Since the performance of the first lung irrigation in 1927, BAL has become a common and important diagnostic tool. While some pulmonary disorders have a highly characteristic signature of BAL findings, BAL results alone often lack specificity and require interpretation along with other clinical and radiographic details. Development of new diagnostic assays is certain to reinforce the utility of BAL in the future. Our review of the BAL literature is intended to serve as a resource to assist clinicians in the care of patients with lung disorders. Keywords: Bronchoalveolar lavage (BAL); bronchoscopy; cell count differential; lung disease; pneumonitis; signature Submitted Jan 14, 2020. Accepted for publication Aug 12, 2020. doi: 10.21037/jtd-20-651 View this article at: http://dx.doi.org/10.21037/jtd-20-651 Introduction bronchoscope in 1927, the procedure of BAL has advanced to become safer and better tolerated (1,2). Development of Bronchoalveolar lavage (BAL) is a common and relatively the flexible bronchoscope in 1966 was a major breakthrough safe diagnostic procedure for the evaluation of patients as bronchoscopy and BAL are now typically performed with lung disease. It often provides valuable diagnostic under conscious sedation. BAL is frequently paired with information when clinical history, physical exam, routine other bronchoscopic procedures such as endobronchial or laboratory testing, pulmonary function testing and transbronchial biopsies, transbronchial needle aspiration, radiographic imaging are insufficient to reach a definitive bronchial brushings, and endobronchial ultrasound-guided diagnosis. Compared to sputum analysis, BAL allows for needle aspirations. The lavage fluid can be evaluated with a targeted sampling of the lower respiratory tract with less variety of analytical tests including cell counts and differential, microbial contamination from the upper aerodigestive tract. cytopathologic analysis, and cultures in addition to specific Since the first lung irrigation was performed through a rigid molecular and immunologic diagnostic tests. © Journal of Thoracic Disease. All rights reserved. J Thorac Dis 2020;12(9):4991-5019 | http://dx.doi.org/10.21037/jtd-20-651 4992 Davidson et al. BAL characteristics of lung disease BAL as a diagnostic procedure Additionally, more recent diagnostic techniques such as matrix-assisted laser desorption/ionization time-of-flight Several characteristics of BAL fluid have been recognized mass spectrometry (MALDI-TOF) and PCR coupled to to predict—with varying degrees of confidence—specific electrospray ionization mass spectrometry (PCR/ESI- lung disorders. For example, with compatible clinical MS) both show potential to provide rapid microbiologic history and imaging, a lymphocytic-predominant BAL is results of BAL fluid that will enable clinicians to target adequate to support a diagnosis of pulmonary sarcoidosis particular organisms far sooner than conventionally or hypersensitivity pneumonitis; or in a patient with possible (15,16). More recently, whole-genome sequencing, an acute alveolar opacification on chest imaging, the including real-time metagenomic sequencing, of BAL fluid presence of significant BAL eosinophils can indicate acute has been used to diagnose and manage viral, bacterial, eosinophilic pneumonia with a fair degree of certainty and fungal pneumonias in critically ill patients with and (3-6). However, in most instances, although the cell without immunosuppression (17,18). In addition, shotgun differential findings on BAL often lack specificity, they sequencing of BAL fluid has been used to characterize the still may be useful in excluding certain disorders such as metagenomics and microbiome of the respiratory tract of diffuse alveolar hemorrhage, eosinophilic lung diseases, lung transplant recipients (19) and patients with chronic and to a lesser degree, certain infections, thus narrowing lung diseases (20). As whole-genome sequencing becomes the differential diagnosis (7). The differential cell count more readily available in clinical laboratories, its role in the may even be normal in many pulmonary disorders such as analysis of BAL fluid will likely increase. chronic obstructive pulmonary disease, asthma, or some The technique by which BAL is performed, while cases of drug-induced pneumonitis (8,9). Creating greater similar globally, may have geographic variations depending complexity, the BAL cell count differential may evolve on the institution and region of the world (21). In the over time depending on the stage of the disease process United States and Europe, there are efforts to standardize such as in hypersensitivity pneumonitis and cases of acute the collection of BAL according to consensus guidelines respiratory distress syndrome (ARDS) (10,11). Nevertheless, (13,22,23). The bronchoscope is advanced distally into the the BAL cell count and differential pattern often assists bronchopulmonary segment of interest until it occludes the clinicians in supporting a particular diagnosis or excluding bronchus, thereby “wedging” the scope. Sequential aliquots others, thereby providing helpful clues in challenging cases of normal saline totaling at least 100 mL (and no more than and improving diagnostic accuracy. In some circumstances, 300 mL) should be instilled and at least 30% returned for no characteristic cell count and differential patterns are optimal sampling. A minimum 5 mL (and ideally 10–20 mL) discernable either because of variability of cell counts seen is needed for cellular analysis (13). Strict safety standards in the disease process or limited data on BAL cell counts are advised including the use of sedatives and anesthetics reported in the literature. Transbronchial biopsy and and diligent monitoring of patients’ vital signs, respirations, especially surgical lung biopsy retain a prominent role in and oxygenation during the procedure (24). BAL fluid the formal diagnosis of several lung diseases where BAL should be collected in a labeled sterile container and findings are nondiagnostic (12,13). transported expediently to the laboratory for analysis (21). BAL is often performed to obtain respiratory samples in Depending on laboratory capabilities, differential cell suspected infections for microbiologic culture and analysis counts are performed by flow cytometry or manually after when patients are unable to expectorate sputum even after filtration or cytocentrifugation techniques(25) . attempt at sputum induction. However, after the initiation Topical anesthetics such as lidocaine are administered of antibiotics, even BAL loses sensitivity for many bacterial universally in the upper airway, larynx, and lower pathogens and becomes insensitive for fastidious microbes (14). respiratory tree to provide comfort and decrease cough. Newer diagnostic techniques including polymerase chain Theoretically, there have been concerns that high levels reaction (PCR) and other molecular assays enhance the of topical anesthetics could reduce the sensitivity of role of BAL for identifying specific microbial infections. microbial cultures from the BAL (26). This appears to Among immunocompromised patients who are vulnerable be true of bronchial washings, but not of BAL (27). Such to a wider range of pathogens and may not exhibit classic discrepancy is accounted for by the much higher volumes of symptoms or radiographic findings, BAL is particularly sterile saline used during BAL in comparison to bronchial useful; e.g., for the diagnosis of pneumocystis pneumonia. washings, thereby diluting the concentration of any residual © Journal of Thoracic Disease. All rights reserved. J Thorac Dis 2020;12(9):4991-5019 | http://dx.doi.org/10.21037/jtd-20-651 Journal of Thoracic Disease, Vol 12, No 9 September 2020 4993 Table 1 Healthy subjects Smoking status Bronchoalveolar lavage fluid findings Healthy non-smokers
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