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Bronchoalveolar Lavage and Opportunistic Pulmonary Infections

      Bronchoalveolar lavage has become an important clinical and investigational tool. Initially, it was used primarily for the assessment of patients with interstitial lung disease.
      • Hunninghake GW
      • Gadek JE
      • Kawanami O
      • Ferrans VJ
      • Crystal RG
      Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage.
      • Reynolds HY
      • Newball HH
      Analysis of proteins and respiratory cells obtained from human lungs by bronchial lavage.
      • Davis GS
      • Giancola MS
      • Costanza MC
      • Low RB
      Analyses of sequential bronchoalveolar lavage samples from healthy human volunteers.
      • Hunninghake GW
      • Kawanami O
      • Ferrans VJ
      • Young Jr, RC
      • Roberts WC
      • Crystal RG
      Characterization of the inflammatory and immune effector cells in the lung parenchyma of patients with interstitial lung disease.
      • Haslam PL
      • Turton CWG
      • Heard B
      • Lukoszek A
      • Collins JV
      • Salsbury AJ
      • Turner-Warwick M
      Bronchoalveolar lavage in pulmonary fibrosis: comparison of cells obtained with lung biopsy and clinical features.
      • Semenzato G
      • Chilosi M
      • Ossi E
      • Trentin L
      • Pizzolo G
      • Cipriani A
      • Agostini C
      • Zambello R
      • Marcer G
      • Gasparotto G
      Bronchoalveolar lavage and lung histology: comparative analysis of inflammatory and immunocompetent cells in patients with sarcoidosis and hypersensitivity pneumonitis.
      • Campbell DA
      • Poulter LW
      • Du Bois RM
      Immunocompetent cells in bronchoalveolar lavage reflect the cell populations in transbronchial biopsies in pulmonary sarcoidosis.
      • Paradis IL
      • Dauber JH
      • Rabin BS
      Lymphocyte phenotypes in bronchoalveolar lavage and lung tissue in sarcoidosis and idiopathic pulmonary fibrosis.
      In the past few years, the utility of bronchoalveolar lavage has been extended to the diagnosis of infectious lung disease, particularly in immunocompromised patients. The study by Martin and associates reported in this issue of the Proceedings (pages 549 to 557) reviews the Mayo Clinic experience with this procedure and further demonstrates the value of bronchoalveolar lavage in the assessment of immunocompromised patients.
      A point made by this study is that this diagnostic technique is associated with an acceptable morbidity in immunosuppressed and thrombocytopenic patients. No bleeding complications were noted (even in patients with very low platelet counts), and a minority of the patients (5 of 100) experienced a transient exacerbation of respiratory failure. Nine mechanically ventilated patients tolerated the procedure well. Stover and colleagues
      • Stover DE
      • Zaman MB
      • Hajdu SI
      • Lange M
      • Gold J
      • Armstrong D
      Bronchoalveolar lavage in the diagnosis of diffuse pulmonary infiltrates in the immunosuppressed host.
      similarly reviewed their results in 97 immunocompromised patients who underwent bronchoalveolar lavage for the evaluation of diffuse infiltrates. Eighteen patients were on assisted ventilation, and 35 had severe thrombocytopenia at the time of lavage. These investigators also reported no major complications associated with the procedure. Two patients with thrombocytopenia had an increased amount of blood in the lavage fluid; however, the hemorrhage did not persist. Among their patients, 50% had an increase in temperature after the procedure and a slight increase in infiltrates in the area of lavage, but blood cultures were consistently negative.
      Several studies have evaluated the safety of diagnostic bronchoalveolar lavage in patients with the acquired immunodeficiency syndrome (AIDS). In general, most patients with AIDS experience a transient elevation in temperature after lavage, but significant morbidity or mortality and episodes of serious hemorrhage are seldom associated with this procedure.
      • Ognibene FP
      • Shelhamer J
      • Gill V
      • Macher AM
      • Loew D
      • Parker MM
      • Gelmann E
      • Fauci AS
      • Parrillo JE
      • Masur H
      The diagnosis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome using subsegmental bronchoalveolar lavage.
      • Broaddus C
      • Dake MD
      • Stulbarg MS
      • Blumenfeld W
      • Hadley WK
      • Golden JA
      • Hopewell PC
      Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome.
      • Stover DE
      • White DA
      • Romano PA
      • Gellene RA
      Diagnosis of pulmonary disease in acquired immune deficiency syndrome (AIDS): role of bronchoscopy and bronchoalveolar lavage.
      Similarly, bronchoalveolar lavage has been judged to be safe in patients who have undergone bone marrow transplantation.
      • Cordonnier C
      • Bernaudin J-F
      • Fleury J
      • Feuilhade M
      • Haioun C
      • Payen D
      • Huet Y
      • Atassi K
      • Vernant J-P
      Diagnostic yield of bronchoalveolar lavage in pneumonitis occurring after allogeneic bone marrow transplantation.
      At our institution, we routinely administer platelet transfusions to patients with thrombocytopenia (platelet counts of less than 50,000/mm3) during the procedure itself, and we also have observed no serious hemorrhagic complications. An important procedural point that is made by Martin and associates is that bronchoalveolar lavage should be limited to a single site in the lung. This approach apparently minimizes the risk of precipitating or exacerbating respiratory failure in this group of patients.
      The second major point made by the present study is that bronchoalveolar lavage is often an effective diagnostic tool in immunocompromised patients, particularly in the diagnosis of opportunistic infections. Pneumocystis carinii pneumonia was accurately diagnosed by use of bronchoalveolar lavage in 17 of the 18 confirmed cases (94%). Similar results have been obtained at other medical centers, and this sensitivity may be even further increased if transbronchial biopsy is also performed.
      • Stover DE
      • Zaman MB
      • Hajdu SI
      • Lange M
      • Gold J
      • Armstrong D
      Bronchoalveolar lavage in the diagnosis of diffuse pulmonary infiltrates in the immunosuppressed host.
      • Ognibene FP
      • Shelhamer J
      • Gill V
      • Macher AM
      • Loew D
      • Parker MM
      • Gelmann E
      • Fauci AS
      • Parrillo JE
      • Masur H
      The diagnosis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome using subsegmental bronchoalveolar lavage.
      • Broaddus C
      • Dake MD
      • Stulbarg MS
      • Blumenfeld W
      • Hadley WK
      • Golden JA
      • Hopewell PC
      Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome.
      • Stover DE
      • White DA
      • Romano PA
      • Gellene RA
      Diagnosis of pulmonary disease in acquired immune deficiency syndrome (AIDS): role of bronchoscopy and bronchoalveolar lavage.
      False-negative results may occur, however, and open-lung biopsy is still indicated if P. carinii pneumonia is strongly suspected clinically. The rapid, accurate detection of potentially pathogenic viruses in bronchoalveolar lavage fluid by the indirect immunofluorescent rapid shell vial technique (demonstrated in the studies by Martin and colleagues) is exciting and undoubtedly will be of increasing importance as more effective, safer antiviral agents become available.
      In this study, three of the four cases of fungal pneumonia were appropriately diagnosed by use of bronchoalveolar lavage; in contrast to other series, however, three false-positive diagnoses were also demonstrated. This important observation and our own experience suggest that, in some patients, the diagnosis of invasive fungal pulmonary infections may necessitate confirmatory studies in addition to bronchoalveolar lavage to justify treatment with potentially toxic therapeutic regimens. Studies of bronchoalveolar lavage fluid may also be useful in the diagnosis of fungal infection by other methods. Aspergillus antigen can be detected by radioimmunoassay in bronchoalveolar lavage specimens from patients with either invasive pulmonary aspergillosis or aspergillomas, and the presence of the antigen in the lavage fluid is relatively specific for these disorders.
      • Davis GS
      • Kelley J
      Invasive techniques for the diagnosis of respiratory infections.
      • Andrews CP
      • Weiner MH
      Aspergillus antigen detection in bronchoalveolar lavage fluid from patients with invasive aspergillosis and aspergillomas.
      Significantly higher levels of oxalic acid (a known fermentation product of Aspergillus) have also been noted in lavage fluid from patients with invasive Aspergillus infections and have been advocated as a predictive factor for the presumptive diagnosis of invasive Aspergillus infections.
      • Benoit G
      • Feuilhade de Chauvin M
      • Cordonnier C
      • Astier A
      • Bernaudin J-F
      Oxalic acid level in bronchoalveolar lavage fluid from patients with invasive pulmonary aspergillosis.
      Originally, bronchoalveolar lavage was not considered useful in establishing a specific diagnosis of bacterial pneumonia, especially in immunocompromised patients, because oropharyngeal contamination may produce false-positive results. In the study by Martin and associates, however, the finding of pathogenic aerobic bacteria in the lower respiratory tract by bronchoalveolar lavage was often confirmed by similar bacteriologic findings from other corroborative tests.
      • Stover DE
      • Zaman MB
      • Hajdu SI
      • Lange M
      • Gold J
      • Armstrong D
      Bronchoalveolar lavage in the diagnosis of diffuse pulmonary infiltrates in the immunosuppressed host.
      The third point emphasized by these investigators is that bronchoalveolar lavage does not, in all cases, obviate the need for subsequent diagnostic open-lung biopsy. Nevertheless, the use of bronchoalveolar lavage does not delay performance of an open-lung biopsy by a clinically significant length of time if diagnostic information is not obtained. For this reason, bronchoalveolar lavage should be considered as an initial diagnostic procedure in immunocompromised patients with suspected infectious lung disease.

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        Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage.
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        • Newball HH
        Analysis of proteins and respiratory cells obtained from human lungs by bronchial lavage.
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        • Costanza MC
        • Low RB
        Analyses of sequential bronchoalveolar lavage samples from healthy human volunteers.
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        Characterization of the inflammatory and immune effector cells in the lung parenchyma of patients with interstitial lung disease.
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        • Turton CWG
        • Heard B
        • Lukoszek A
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        Bronchoalveolar lavage in pulmonary fibrosis: comparison of cells obtained with lung biopsy and clinical features.
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        • Zambello R
        • Marcer G
        • Gasparotto G
        Bronchoalveolar lavage and lung histology: comparative analysis of inflammatory and immunocompetent cells in patients with sarcoidosis and hypersensitivity pneumonitis.
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        Bronchoalveolar lavage in the diagnosis of diffuse pulmonary infiltrates in the immunosuppressed host.
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        • Parrillo JE
        • Masur H
        The diagnosis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome using subsegmental bronchoalveolar lavage.
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        Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome.
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        • White DA
        • Romano PA
        • Gellene RA
        Diagnosis of pulmonary disease in acquired immune deficiency syndrome (AIDS): role of bronchoscopy and bronchoalveolar lavage.
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        • Cordonnier C
        • Bernaudin J-F
        • Fleury J
        • Feuilhade M
        • Haioun C
        • Payen D
        • Huet Y
        • Atassi K
        • Vernant J-P
        Diagnostic yield of bronchoalveolar lavage in pneumonitis occurring after allogeneic bone marrow transplantation.
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        • Kelley J
        Invasive techniques for the diagnosis of respiratory infections.
        Clin Lab Med. June 1982; 2: 269-283
        • Andrews CP
        • Weiner MH
        Aspergillus antigen detection in bronchoalveolar lavage fluid from patients with invasive aspergillosis and aspergillomas.
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        • Feuilhade de Chauvin M
        • Cordonnier C
        • Astier A
        • Bernaudin J-F
        Oxalic acid level in bronchoalveolar lavage fluid from patients with invasive pulmonary aspergillosis.
        Am Rev Respir Dis. 1985; 132: 748-751