|Year : 2022 | Volume
| Issue : 3 | Page : 236-240
The diagnostic yield and characteristics of bronchoalveolar lavage in suspected nontuberculous mycobacterial pulmonary disease
Shigehisa Kajikawa1, Eisuke Fujishiro1, Toshio Kato1, Hiroyuki Tanaka1, Etsuro Yamaguchi1, Akihito Kubo2, Satoru Ito1
1 Department of Respiratory Medicine and Allergology, Aichi Medical University, Nagakute, Japan
2 Department of Respiratory Medicine and Allergology, Aichi Medical University; Department of Clinical Oncology, Aichi Medical University Hospital, Nagakute, Japan
|Date of Submission||05-Jun-2022|
|Date of Acceptance||17-Aug-2022|
|Date of Web Publication||12-Sep-2022|
Department of Respiratory Medicine and Allergology, Aichi Medical University, 1-1 Yazako-Karimata, Nagakute 480-1195
Source of Support: None, Conflict of Interest: None
Background: Bronchoalveolar lavage (BAL) has widely been used to manage respiratory diseases including respiratory infections. The aim of this study was to evaluate the diagnostic yield of BAL for detecting nontuberculous Mycobacterium (NTM). Methods: We retrospectively reviewed the records of 54 patients who underwent bronchoscopy due to suspected NTM pulmonary disease. Positive culture results of respiratory specimens were defined as NTM pulmonary disease. For BAL, two or three aliquots of 50 mL (total 100 or 150 mL) of sterile normal saline were instilled through bronchoscope. Results: NTM was detected in 31 of 54 (57.4%) patients. The detection rates were not different between the patients who underwent bronchoscopy with BAL (24 of 39, 61.5%) and those without (7 of 15, 46.7%) (P = 0.437). BAL fluid was mostly neutrophil dominant in both positive and negative NTM culture groups. In the subgroup analysis of 33 patients who underwent both the BAL and anti- glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody measurements, 12 of 19 (63.2%) positive Mycobacterium avium complex (MAC) culture patients and 8 of 14 (57.1%) negative MAC culture patients were positive for anti-GPL-core IgA antibody (seropositive) (P = 0.991). There was no severe complication related to BAL. Conclusions: The diagnostic yield of BAL with ≥100 mL sterile saline was not superior to that of bronchial wash or sputum aspiration in patients with suspected NTM pulmonary disease. Patients with seropositive but negative culture results for MAC suggest pseudonegative for pulmonary MAC disease.
Keywords: Anti-glycopeptidolipid-core immunoglobulin A antibody, bronchoalveolar lavage, bronchoscopy, Mycobacterium avium complex, nontuberculous mycobacteria
|How to cite this article:|
Kajikawa S, Fujishiro E, Kato T, Tanaka H, Yamaguchi E, Kubo A, Ito S. The diagnostic yield and characteristics of bronchoalveolar lavage in suspected nontuberculous mycobacterial pulmonary disease. Int J Mycobacteriol 2022;11:236-40
|How to cite this URL:|
Kajikawa S, Fujishiro E, Kato T, Tanaka H, Yamaguchi E, Kubo A, Ito S. The diagnostic yield and characteristics of bronchoalveolar lavage in suspected nontuberculous mycobacterial pulmonary disease. Int J Mycobacteriol [serial online] 2022 [cited 2022 Sep 28];11:236-40. Available from: https://www.ijmyco.org/text.asp?2022/11/3/236/355924
| Introduction|| |
The prevalence of pulmonary infection of nontuberculous Mycobacterium (NTM) infection is increasing worldwide including in Japan. Specifically, Mycobacterium avium complex (MAC) is the most common pathogen in pulmonary NTM disease. When sputum or induced sputum cannot be obtained, bronchoscopy is required. As a diagnostic tool using a bronchoscope for pulmonary NTM disease, the usefulness of bronchial wash using a small amount (e.g. 20 mL) of physiological saline and bronchial brushing, and biopsy has been reported.,,, Tomishima et al. recently reported that the diagnostic yield of bronchoscopy for NTM was 52.8% and not high enough.
Bronchoalveolar lavage (BAL) has widely been used to manage respiratory diseases including respiratory infections.,, This method involves wedging the bronchus and washing the lesion with ≥100 mL of physiological saline.,, Because the amount of saline is more than that in the bronchial wash, one can expect that BAL has an advantage in the detection of NTM. Moreover, it is relatively easy to perform BAL when the suspected NTM infection is located in the middle lobe or lingula. Iwasaki et al. reported positive culture results of BAL fluid (BALF) in 9 of 25 patients (36%) with suspected MAC infection. However, the utility of BAL in the diagnosis of pulmonary NTM infection is unknown. The aim of this study was to evaluate the utility of the BAL in patients with suspected NTM pulmonary disease.
| Methods|| |
This study was approved by our institutional review board (approval No. 2021-039). The requirement for written informed consent was waived due to the retrospective design of the study.
Patients and study design
Medical records of consecutive patients who were suspected of having pulmonary NTM infection and underwent diagnostic bronchoscopy in the Department of Respiratory Medicine and Allergology, Aichi Medical University Hospital, from September 2017 to August 2020 were retrospectively reviewed. Data from 54 patients who underwent bronchoscopy for the detection of NTM were analyzed. All patients had been asked to expectorate sputum but the diagnosis of pulmonary NTM infection had not been made.
Bronchoscopy and bronchoalveolar lavage
Bronchoscopy was performed using a video bronchoscope (BFp-260F or BF1T-260; Olympus, Tokyo, Japan) under local anesthesia using 2% lidocaine and conscious sedation using intravenous injection of midazolam as needed. Sputum in the airways was aspirated through a bronchoscope. For bronchial wash, we wedged the segmental or subsegmental bronchus with abnormal shadows on chest CT, injected sterile normal saline (≤50 mL), and aspirated the lavage fluid through a bronchoscope. For BAL, two or three aliquots of 50 mL (total 100 or 150 mL) of sterile normal saline were instilled and gently suctioned back with a 50 mL plastic syringe. Then, the remaining fluid and secretions in the lung and airways were aspirated using a specimen container. For the processing of BALF, the volume of recovered fluid was measured. For the analysis of microbiology, samples were examined by Ziehl–Neelsen and fluorescent stains for Mycobacterium and Gram stains for other bacteria. The culture period of Mycobacterium was up to 8 weeks.
Clinical data were collected from electronic medical records. The CT findings were interpreted by two specialized pulmonologists (H. T. and T. K.), and the presence of four major abnormalities, bronchiectasis, micronodular opacity, nodule, and cavity, was assessed [Table 1]. The levels of serum immunoglobulin A (IgA) antibody against the glycopeptidolipid (GPL)-core antigen of MAC were measured using a commercial enzyme immunoassay kit. The cutoff value of >0.7 U/mL was judged to be positive for anti-GPL-core IgA antibodies. Although this method is not included in the diagnostic criteria of pulmonary MAC disease, the serodiagnosis would help clinicians manage patients with suspected pulmonary MAC disease. Adverse events during the bronchoscopy were also assessed according to the method in a previous survey by the Japan Society for Respiratory Endoscopy.
|Table 1: Characteristics of patients who underwent bronchoscopy with or without bronchoalveolar lavage|
Click here to view
Data are expressed as means ± standard deviation or median interquartile range. A Chi-square test, Fisher's exact test, t-test, or Mann–Whitney U-test were used to evaluate statistical significance. Statistical analyses were conducted using StatMate V (ATMS Co., Ltd., Tokyo, Japan). P <0.05 was considered statistically significant.
| Results|| |
Patient characteristics and microbiological results
The demographic and characteristics of all 54 patients are shown in [Table 1]. Thirty-one patients (57.4%) were diagnosed with NTM pulmonary disease according to the positive culture of samples obtained by bronchoscopy or sputum after the bronchoscopy. The culture results for acid-fast bacteria were as follows: M. avium (n = 18), M. intracellulare (n = 10), M. abscessus (n = 2), and not specified (n = 1). Other pathogens including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella spp., Pseudomonas aeruginosa, Streptococcus constellatus, Nocardia spp., and Candida spp., were detected in 11 patients.
Comparisons of characteristics of patients who underwent bronchoalveolar lavage and bronchial wash or aspiration
Bronchoscopic examinations involved BAL in 39 patients (72.2%), bronchial wash in 11 patients (20.4%), and endobronchial sputum aspiration without bronchial wash or BAL in four patients (7.4%). The characteristics of patients who underwent bronchoscopy with BAL (n = 39) and without (n = 15) are compared in [Table 1]. Among underlying diseases, paranasal sinusitis was significantly more frequent in patients without BAL than in those with BAL (26.7 vs. 5.1%, P = 0.044). There was no significant difference in the detection rate of NTM between the groups (with BAL 61.5%, without BAL 46.7%, P = 0.495).
Results of bronchoalveolar lavage and bronchoalveolar lavage fluid findings
The characteristics of patients who underwent BAL with positive (n = 24) and negative (n = 15) NTM cultures are compared in [Table 2]. The body mass index of the positive NTM culture group was significantly lower than that of the negative NTM culture group (P = 0.047). Ratios of neutrophils and lymphocytes in the BALF were high, and ratios of alveolar macrophages were low in both groups.
|Table 2: Demographic characteristics of 39 patients who underwent bronchoalveolar lavage|
Click here to view
Results of anti-glycopeptidolipid-core immunoglobulin A antibody of Mycobacterium avium complex
In the subgroup analysis of 33 patients who underwent both the BAL and anti-GPL-core IgA antibody measurements, 12 of 19 (63.2%) positive MAC culture patients and 8 of 14 (57.1%) negative MAC culture patients were positive for the anti-GPL-core IgA antibody (seropositive) (P = 0.991). The sensitivity and specificity of the anti-GPL-core IgA antibody for MAC detection in patients who underwent BAL were 63.2% and 47.9%.
Complications during bronchoalveolar lavage
Additional intravenous midazolam for sedation was needed in two cases during BAL and one case during the bronchial wash. There was no severe complication including respiratory failure related to bronchoscopy.
| Discussion|| |
In the present study, the detection rates by BAL of NTM and MAC were 61.5% and 56.4%. Iwasaki et al. reported that among 25 patients who underwent BAL (50 mL of saline three times) due to suspected pulmonary MAC infection, 9 (36%) had positive BALF culture results. BAL is a useful procedure to detect pathogens and diagnose respiratory infectious diseases.,, This technique has an advantage in minimizing contamination by bacteria existing in the upper and lower airways in patients with bacterial pneumonia and ventilator-induced lung injury. Choo et al. investigated the diagnostic yield of BAL in 217 immunocompromised patients presenting with lung infiltrates and detected pathogens including Mycobacterium tuberculosis (n = 13), MAC (n = 1), and Mycobacterium abscessus (n = 1) in 132 (60.8%) patients. In our results, BALF was mostly neutrophil dominant in patients with positive NTM cultures, similar to the findings in bacterial pneumonia. Taken together, it is not likely that BAL is more beneficial for the diagnosis of NTM pulmonary disease than bronchial wash.
At our institution, bronchial wash was performed with ≤50 mL (mostly 20 mL) of saline. Matsumoto et al. performed bronchial wash with 50 mL of saline and evaluated the usefulness of polymerase chain reaction test for MAC. Sugihara et al. reported the usefulness of bronchial lavage with 20 mL of saline for the diagnosis of pulmonary MAC infection in patients with suspected NTM. In a report by Urabe et al., 20 or 40 mL of saline was injected after bronchial brushing., Bronchial wash through a bronchoscope has been used to diagnose pulmonary NTM disease.,,, However, there is no recommendation or strict guideline for the amount of injected saline during bronchial wash for the diagnosis of NTM.
One of the important major complications of bronchoscopy including BAL is respiratory failure. Pirozynski et al. reported that the desaturation during BAL depends on the instilled fluid volume. Choo et al. reported that the complication rate was 14.7% in immunocompromised patients, but no factor impacted the complication rate by multiple logistic regression. In our study, there was no severe complication. Thus, BAL as well as bronchial wash exhibited a relatively low degree of invasiveness in agreement with findings of the previous literature.,
This study has several limitations. Data were collected retrospectively from patients who underwent bronchoscopy. Performing either BAL or bronchial wash was decided by the bronchoscopy operator. The detection rates for NTM and MAC were not significantly different between the BAL (61.5% and 56.4%) and bronchial wash (54.5% and 45.5%), possibly due to the small numbers. Even when the cultures for Mycobacterium were negative, the possibility of pulmonary MAC infection cannot be ruled out specifically in patients with positive results for the anti-GPL-core IgA antibody.
| Conclusions|| |
Our results were unable to show any benefit of BAL over bronchial wash in patients with suspected pulmonary NTM infection. Underlying MAC infection cannot be ruled out in patients with positive for anti-GPL-core IgA antibodies but negative MAC culture results. Careful further investigation is required to establish a strategy for accurate and early diagnosis of NTM and MAC pulmonary diseases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Daley CL, Winthrop KL. Mycobacterium avium
complex: Addressing gaps in diagnosis and management. J Infect Dis 2020;222:S199-211.
Morimoto K, Iwai K, Uchimura K, Okumura M, Yoshiyama T, Yoshimori K, et al
. A steady increase in nontuberculous mycobacteriosis mortality and estimated prevalence in Japan. Ann Am Thorac Soc 2014;11:1-8.
Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et al
. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367-416.
Urabe N, Sakamoto S, Ito A, Sekiguchi R, Shimanuki Y, Kanokogi T, et al
. Bronchial brushing and diagnosis of pulmonary nontuberculous mycobacteria infection. Respiration 2021;100:877-85.
Sugihara E, Hirota N, Niizeki T, Tanaka R, Nagafuchi M, Koyanagi T, et al
. Usefulness of bronchial lavage for the diagnosis of pulmonary disease caused by Mycobacterium avium
-intracellulare complex (MAC) infection. J Infect Chemother 2003;9:328-32.
Tanaka E, Amitani R, Niimi A, Suzuki K, Murayama T, Kuze F. Yield of computed tomography and bronchoscopy for the diagnosis of Mycobacterium avium
complex pulmonary disease. Am J Respir Crit Care Med 1997;155:2041-6.
Maekawa K, Naka M, Shuto S, Harada Y, Ikegami Y. The characteristics of patients with pulmonary Mycobacterium avium
-intracellulare complex disease diagnosed by bronchial lavage culture compared to those diagnosed by sputum culture. J Infect Chemother 2017;23:604-8.
Tomishima Y, Urayama KY, Kitamura A, Okafuji K, Jinta T, Nishimura N, et al
. Bronchoscopy for the diagnosis of nontuberculous mycobacterial pulmonary disease: Specificity and diagnostic yield in a retrospective cohort study. Respir Investig 2022;60:355-63.
Choo R, Naser NS, Nadkarni NV, Anantham D. Utility of bronchoalveolar lavage in the management of immunocompromised patients presenting with lung infiltrates. BMC Pulm Med 2019;19:51.
Hara K, Kohno S, Koga H. Invasive techniques for the diagnosis of respiratory infectious diseases. J Infect Chemother 1996;1:166-76.
Meduri GU, Baselski V. The role of bronchoalveolar lavage in diagnosing nonopportunistic bacterial pneumonia. Chest 1991;100:179-90.
Klech H, Hutter C. Clinical guidelines and indications for bronchoalveolar lavage (BAL): Report of the European Society of Pneumology Task Group on BAL. Eur Respir J 1990;3:937-76.
Haslam PL, Baughman RP. Report of ERS Task Force: Guidelines for measurement of acellular components and standardization of BAL. Eur Respir J 1999;14:245-8.
Iwasaki K, Matsuzawa Y, Wakabayashi H, Shioya M, Hayakawa S, Tatsuno I. Lower airway microbiota in patients with clinically suspected Mycobacterium avium
complex lung disease. Heliyon 2021;7:e07283.
Kitada S, Maekura R, Toyoshima N, Fujiwara N, Yano I, Ogura T, et al
. Serodiagnosis of pulmonary disease due to Mycobacterium avium
complex with an enzyme immunoassay that uses a mixture of glycopeptidolipid antigens. Clin Infect Dis 2002;35:1328-35.
Kitada S, Kobayashi K, Ichiyama S, Takakura S, Sakatani M, Suzuki K, et al
. Serodiagnosis of Mycobacterium avium
-complex pulmonary disease using an enzyme immunoassay kit. Am J Respir Crit Care Med 2008;177:793-7.
Kitada S. Application of a commercial serodiagnostic kit that measures the serum anti-glycopeptidolipid core IgA antibody in Mycobacterium avium
complex pulmonary disease. Respir Investig 2019;57:410-4.
Asano F, Aoe M, Ohsaki Y, Okada Y, Sasada S, Sato S, et al
. Deaths and complications associated with respiratory endoscopy: A survey by the Japan Society for Respiratory Endoscopy in 2010. Respirology 2012;17:478-85.
Matsumoto H, Tsuyuguchi K, Suzuki K, Tanaka E, Amitani R, Kuze F. Evaluation of Roche Amplicor PCR assay for Mycobacterium avium
complex in bronchial washing. Int J Tuberc Lung Dis 1998;2:935-40.
Urabe N, Sakamoto S, Sano G, Ito A, Homma S. Characteristics of patients with bronchoscopy-diagnosed pulmonary Mycobacterium avium
complex infection. J Infect Chemother 2018;24:822-7.
Pirozyński M, Sliwiński P, Zieliński J. Effect of different volumes of BAL fluid on arterial oxygen saturation. Eur Respir J 1988;1:943-7.
[Table 1], [Table 2]