Bronchoalveolar lavage as a diagnostic procedure: a review of known cellular and molecular findings in various lung diseases
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:

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


Bronchoalveolar lavage (BAL) is a common and relatively safe diagnostic procedure for the evaluation of patients with lung disease. It often provides valuable diagnostic information when clinical history, physical exam, routine laboratory testing, pulmonary function testing and radiographic imaging are insufficient to reach a definitive diagnosis. Compared to sputum analysis, BAL allows for targeted sampling of the lower respiratory tract with less microbial contamination from the upper aerodigestive tract.

Since the first lung irrigation was performed through a rigid bronchoscope in 1927, the procedure of BAL has advanced to become safer and better tolerated (1,2). Development of the flexible bronchoscope in 1966 was a major breakthrough as bronchoscopy and BAL are now typically performed under conscious sedation. BAL is frequently paired with other bronchoscopic procedures such as endobronchial or transbronchial biopsies, transbronchial needle aspiration, bronchial brushings, and endobronchial ultrasound-guided needle aspirations. The lavage fluid can be evaluated with a variety of analytical tests including cell counts and differential, cytopathologic analysis, and cultures in addition to specific molecular and immunologic diagnostic tests.

BAL as a diagnostic procedure

Several characteristics of BAL fluid have been recognized to predict—with varying degrees of confidence—specific lung disorders. For example, with compatible clinical history and imaging, a lymphocytic-predominant BAL is adequate to support a diagnosis of pulmonary sarcoidosis or hypersensitivity pneumonitis; or in a patient with an acute alveolar opacification on chest imaging, the presence of significant BAL eosinophils can indicate acute eosinophilic pneumonia with a fair degree of certainty (3-6). However, in most instances, although the cell differential findings on BAL often lack specificity, they still may be useful in excluding certain disorders such as diffuse alveolar hemorrhage, eosinophilic lung diseases, and to a lesser degree, certain infections, thus narrowing the differential diagnosis (7). The differential cell count may even be normal in many pulmonary disorders such as chronic obstructive pulmonary disease, asthma, or some cases of drug-induced pneumonitis (8,9). Creating greater complexity, the BAL cell count differential may evolve over time depending on the stage of the disease process such as in hypersensitivity pneumonitis and cases of acute respiratory distress syndrome (ARDS) (10,11). Nevertheless, the BAL cell count and differential pattern often assists clinicians in supporting a particular diagnosis or excluding others, thereby providing helpful clues in challenging cases and improving diagnostic accuracy. In some circumstances, no characteristic cell count and differential patterns are discernable either because of variability of cell counts seen in the disease process or limited data on BAL cell counts reported in the literature. Transbronchial biopsy and especially surgical lung biopsy retain a prominent role in the formal diagnosis of several lung diseases where BAL findings are nondiagnostic (12,13).

BAL is often performed to obtain respiratory samples in suspected infections for microbiologic culture and analysis when patients are unable to expectorate sputum even after attempt at sputum induction. However, after the initiation of antibiotics, even BAL loses sensitivity for many bacterial pathogens and becomes insensitive for fastidious microbes (14). Newer diagnostic techniques including polymerase chain reaction (PCR) and other molecular assays enhance the role of BAL for identifying specific microbial infections. Among immunocompromised patients who are vulnerable to a wider range of pathogens and may not exhibit classic symptoms or radiographic findings, BAL is particularly useful; e.g., for the diagnosis of pneumocystis pneumonia. Additionally, more recent diagnostic techniques such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and PCR coupled to electrospray ionization mass spectrometry (PCR/ESI-MS) both show potential to provide rapid microbiologic results of BAL fluid that will enable clinicians to target particular organisms far sooner than conventionally possible (15,16). More recently, whole-genome sequencing, including real-time metagenomic sequencing, of BAL fluid has been used to diagnose and manage viral, bacterial, and fungal pneumonias in critically ill patients with and without immunosuppression (17,18). In addition, shotgun sequencing of BAL fluid has been used to characterize the metagenomics and microbiome of the respiratory tract of lung transplant recipients (19) and patients with chronic lung diseases (20). As whole-genome sequencing becomes more readily available in clinical laboratories, its role in the analysis of BAL fluid will likely increase.

The technique by which BAL is performed, while similar globally, may have geographic variations depending on the institution and region of the world (21). In the United States and Europe, there are efforts to standardize the collection of BAL according to consensus guidelines (13,22,23). The bronchoscope is advanced distally into the bronchopulmonary segment of interest until it occludes the bronchus, thereby “wedging” the scope. Sequential aliquots of normal saline totaling at least 100 mL (and no more than 300 mL) should be instilled and at least 30% returned for optimal sampling. A minimum 5 mL (and ideally 10–20 mL) is needed for cellular analysis (13). Strict safety standards are advised including the use of sedatives and anesthetics and diligent monitoring of patients’ vital signs, respirations, and oxygenation during the procedure (24). BAL fluid should be collected in a labeled sterile container and transported expediently to the laboratory for analysis (21). Depending on laboratory capabilities, differential cell counts are performed by flow cytometry or manually after filtration or cytocentrifugation techniques (25).

Topical anesthetics such as lidocaine are administered universally in the upper airway, larynx, and lower respiratory tree to provide comfort and decrease cough. Theoretically, there have been concerns that high levels of topical anesthetics could reduce the sensitivity of microbial cultures from the BAL (26). This appears to be true of bronchial washings, but not of BAL (27). Such discrepancy is accounted for by the much higher volumes of sterile saline used during BAL in comparison to bronchial washings, thereby diluting the concentration of any residual topical anesthetic.

The objectives here are to compile available BAL data categorized by different classes of lung diseases and also to highlight lung disorders where insufficient BAL data exist. We performed comprehensive searches on PubMed to find available data on particular BAL profiles for a given disease using the keywords of BAL, lung lavage, and the names of specific disorders. A further goal is to provide clinicians with a succinct and referenced resource to aid in the evaluation of patients who undergo BAL albeit we acknowledge that in some resource-poor countries, many of the specific molecular tests may not be readily available. The data assembled are focused on the particular patterns of BAL cellularity seen within each disease state. In many cases, there were few published studies and when present, often limited to case reports and series. Not surprisingly, we found very few published articles on BAL data of rare lung diseases or pulmonary toxicities associated with recently developed medications.

The BAL data are organized into the following categories: healthy subjects (Table 1), airways diseases (Table 2), cystic lung diseases (Table 3), pulmonary vasculitides (Table 4), interstitial lung diseases (Table 5), occupational and environmental lung diseases (Table 6), radiation-induced pneumonitis (Table 7), infectious pneumonias (Tables 8-12), drug-induced pneumonitis (Table 13), and miscellaneous lung diseases (Table 14). For infectious pneumonias, we focused primarily on microbiologic and molecular diagnostic testing available. Additionally, we tabulated diseases characterized by particular BAL cell differential (eosinophilic, lymphocytic, or neutrophilic predominance) (Table 15), diffuse alveolar hemorrhage (DAH) due to non-infectious and infectious causes (Table 16), foamy alveolar macrophages (Table 17), and a tabulation of disorders in which a signature of BAL cellular findings may be diagnostic or relatively so (Table 18). Abbreviations in the tables are defined at the bottom of Table 18. We have elected not to discuss cytologic analysis of BAL to diagnose primary lung cancer or metastatic disease in detail in the scope of this paper.

Table 1
Table 1 Healthy subjects
Full table
Table 2
Table 2 Airway diseases
Full table
Table 3
Table 3 Cystic lung diseases
Full table
Table 4
Table 4 Pulmonary vasculitides*
Full table
Table 5
Table 5 Interstitial lung diseases
Full table
Table 6
Table 6 Occupational & environmental lung diseases
Full table
Table 7
Table 7 Radiation-induced pneumonitis
Full table
Table 8
Table 8 Infectious pneumonia: viruses
Full table
Table 9
Table 9 Infectious pneumonia: bacteria
Full table
Table 10
Table 10 Infectious pneumonia: fungi
Full table
Table 11
Table 11 Infectious pneumonia: parasites
Full table
Table 12
Table 12 Infectious pneumonia: mycobacteria
Full table
Table 13
Table 13 Drug-induced pneumonitis
Full table
Table 14
Table 14 Miscellaneous lung diseases
Full table
Table 15
Table 15 Diseases characterized by particular BAL cell differential
Full table
Table 16
Table 16 Diffuse alveolar hemorrhage
Full table
Table 17
Table 17 Diseases with foamy alveolar macrophages
Full table
Figure 1 Visual detection of foamy macrophages. (A) Giemsa stain and (B) Periodic acid-Schiff (PAS) stain of BAL from a patient with pulmonary alveolar proteinosis demonstrating the “ghosts” of the foamy vacuoles [Figure modified from (298)]. A Wright-Giemsa stain is also a “negative stain” and will also accomplish the same visual effect. (C) Oil Red O stain of the BAL from a patient with electronic cigarette/vaping-associated lung injury (EVALI) showing lipid-filled vacuoles within an alveolar macrophage. Magnification: 1,000×. BAL, bronchoalveolar lavage.
Table 18
Table 18 Diagnostic or highly suggestive BAL cellular phenotypes
Full table

BAL as a therapeutic procedure

BAL is almost exclusively used as a diagnostic tool. But a modified BAL—really more of a bronchial wash—using smaller aliquots of saline to help dislodge distal mucous plugs is likely the most common therapeutic use, especially in those with a secured airway (endotracheal tube or tracheostomy) but too debilitated to self-expectorate successfully. The best evidence for therapeutic use of BAL is for pulmonary alveolar proteinosis. In this instance, the BAL technique is modified with high volumes of sterile normal saline via a dual lumen endotracheal tube to perform a therapeutic whole lung lavage with removal of heavy lipoproteinaceous sediment from the lungs. This procedure was first described in 1963 with subsequent modifications in technique to optimize patient safety, yield of removed protein and therapeutic benefit (320). Other rare reports of therapeutic lung lavage have been described for exogenous lipoid pneumonia from milk aspiration (321) and another with kerosene aspiration (322) utilizing low volume segmental lavage with good radiographic resolution. In children with refractory Mycoplasma pneumoniae pneumonia complicated by atelectasis, therapeutic BAL was shown to significantly shorten the duration of illness, time to radiographic resolution, and length of hospital stay (323).


Since the first bronchial irrigation by Stitt in 1927, BAL has evolved to become an often-used diagnostic procedure throughout most of the world. With development of additional assays for microbial product (e.g., galactomannan for invasive fungal disease), immunostaining for organisms (e.g., direct fluorescent antibody for pneumocystis), and nucleic acid amplification tests for specific microbes, BAL for diagnosis of infectious disorders has made significant progress and will continue to advance further with new technologies. While differential cell count profiles and ancillary testing on BAL fluid may in themselves not be specific or diagnostic, in the proper clinical context, the BAL findings may be the deciding factor in making a confident diagnosis. For example, in a patient with home bird exposure, significant lymphocytosis on BAL and consistent imaging, a confident diagnosis of hypersensitivity pneumonitis can be made even in the absence of lung biopsy. Even when BAL results are non-diagnostic, their findings may help narrow the differential diagnosis. This review summarizes the vast array of additional characteristics and specific signature findings that can be a helpful aid to diagnosis. Herein, we present a current, succinct compilation of BAL data in a wide range of lung disease. In addition, we also listed those diseases and drug toxicities for which specific BAL data have not been reported.

In the future, it is likely that additional targeted diagnostics such as MALDI-TOF and PCR ES-M on BAL fluid will facilitate more rapid diagnosis of infectious pneumonia. Of particular interest is not only the ability to determine the etiology of infection but also to identify drug-resistant microbes. Such advances would transform the care of septic patients and also improve adherence to antibiotic stewardship. Additionally, genomic testing of BAL fluid may help clinicians differentiate patients with IPF from other forms of ILD as well as stratify patients with lung nodules into different risk groups for lung cancer. While surgical lung biopsy remains the gold standard for the diagnosis of various lung diseases, less invasive diagnostic techniques will become adopted if their yield becomes significantly more accurate. The ultimate goal would be to advance diagnostic techniques on BAL fluid to rival the sensitivity and specificity of the current gold standard of lung biopsy.


Funding: None.


Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at EDC serves as an unpaid editorial board member of Journal of Thoracic Disease. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See:


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Cite this article as: Davidson KR, Ha DM, Schwarz MI, Chan ED. Bronchoalveolar lavage as a diagnostic procedure: a review of known cellular and molecular findings in various lung diseases. J Thorac Dis 2020;12(9):4991-5019. doi: 10.21037/jtd-20-651

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