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| ORIGINAL ARTICLE |
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| Year : 2018 | Volume
: 7
| Issue : 2 | Page : 178-182 |
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Bronchial wash culture is less valuable in patients suspected to have nontuberculous mycobacteria lung disease for bilateral bronchiectasis with nodules
Keisuke Watanabe1, Masaharu Shinkai2, Masahiro Shinoda2, Takeshi Kaneko2
1 Department of Pulmonology, Yokohama City University Graduate School of Medicine; Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
2 Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| Date of Web Publication | 13-Jun-2018 |
Correspondence Address:
Keisuke Watanabe
Department of Pulmonology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama 236-0004
Japan
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijmy.ijmy_38_18
Backgrounds: Bronchiectasis (BE) with nodules on chest computed tomography (CT) is one of the radiological findings of nontuberculous mycobacteria (NTM) lung disease. However, the NTM lung disease is not diagnosed in some patients who undergo bronchoscopy, though their radiological findings show BE with nodules. We need the indicator to distinguish the patients who would not be given the diagnosis of NTM lung disease with bronchoscopy. Methods: We retrospectively reviewed the records of the patients who underwent bronchoscopy from January 2010 to July 2013 at our hospital because sputum test had not yielded the diagnosis of NTM lung disease or the patients had been unable to produce sputum, though their chest CT had shown BE with nodules. Results: A total of 36 patients were included in this study, and acid-fast bacterium (AFB) culture of bronchial wash was positive in 17 patients. More patients with negative culture in bronchial wash had AFB-negative culture with purulent sputum before bronchoscopy (37% vs. 0%, P = 0.008) and bilateral BE with nodules on chest CT (89% vs. 41%, P = 0.007). Multivariate analysis showed that bilateral BE with nodules on chest CT was the risk factor for the negative culture of AFB with bronchial wash (odds ratio: 0.149; 95% confidence interval: 0.024–0.913, P = 0.040). Conclusion: Patients with bilateral BE with nodules on chest CT have less possibility to have positive AFB culture from bronchial wash when sputum test was not diagnostic.
Keywords: Bronchoscopy, computed tomography, Mycobacterium avium, Mycobacterium intracellulare, nontuberculous mycobacteria
How to cite this article:
Watanabe K, Shinkai M, Shinoda M, Kaneko T. Bronchial wash culture is less valuable in patients suspected to have nontuberculous mycobacteria lung disease for bilateral bronchiectasis with nodules. Int J Mycobacteriol 2018;7:178-82 |
How to cite this URL:
Watanabe K, Shinkai M, Shinoda M, Kaneko T. Bronchial wash culture is less valuable in patients suspected to have nontuberculous mycobacteria lung disease for bilateral bronchiectasis with nodules. Int J Mycobacteriol [serial online] 2018 [cited 2021 Jul 25];7:178-82. Available from: https://www.ijmyco.org/text.asp?2018/7/2/178/234324 |
| Introduction | |  |
Nontuberculous mycobacteria (NTM) lung disease is common and has reported to increase worldwide.[1],[2],[3],[4],[5],[6] Bronchiectasis (BE) with nodules on chest computed tomography (CT) is one of the radiological findings of NTM lung disease.[7] However, there exists many differential diagnoses for BE with nodules on chest CT.[8] To make the diagnosis of NTM lung disease, bronchoscopy is needed for the patients who are suspected to have NTM lung disease, when they have negative sputum culture for acid-fast bacterium (AFB) or have no sputum. However, the NTM lung disease is not diagnosed in some patients who undergo bronchoscopy, though their radiological findings are compatible with NTM lung disease. Bronchoscopy is relatively safe, but complications occur to some extent,[9] and we must omit needless examination. Therefore, we need the indicator to distinguish the patients who would not be given the diagnosis of NTM lung disease with bronchoscopy. We retrospectively reviewed the records of the patients who had undergone bronchoscopy because sputum test had not yielded the diagnosis of NTM lung disease, though their CT had showed BE with nodules. Then, we compared the characteristics of the patients whose bronchial washing culture was positive for NTM and those whose bronchial washing culture was negative for NTM.
| Methods | | |
This study was approved by the Review Board of our hospital (NO. D1409007). Due to the retrospective nature of this study, written informed consent was waved.
We retrospectively reviewed the records of the patients who underwent bronchoscopy from January 2010 to July 2013. Inclusion criteria were as follows:
- The patients who were suspected to have NTM lung disease because of BE with nodules on chest CT
- No sputum or negative sputum culture for AFB
- Age older than 20 years old.
Patients who were known to be serologically positive for human immunodeficiency virus were excluded from the study.
Sputum appearance was evaluated according to the classification of Miller.[10] Transbronchial lung biopsy (TBLB) was performed from the segment where heavy small nodular opacities existed. The presence of granuloma was judged by the pathologists at our hospital who were independent of our study. Bronchial washing was performed after TBLB. Twenty milliliters sterile saline was injected into the segmental or subsegmental bronchus which TBLB was performed. Gram stains and the culture for AFB, other bacteria, and fungi were performed with the specimen of bronchial wash. The specimen of bronchial wash was screened with Auramine O for AFB smear testing, and positive for AFB was confirmed with Ziehl–Neelsen staining. Liquid culture medium (Bactec MGIT 960 apparatus; Becton Dickinson, Franklin, New Jersey, USA) was used for AFB culture. NTM was identified by DNA hybridization assay (DDH Mycobacteria assay; Kyokuto Pharmaceuticals Co., Tokyo, Japan).
The diagnosis of NTM lung disease was made with the diagnostic criteria of NTM lung disease proposed by ATS.[11]
Statistical analysis
Data were presented as mean ± standard division, if not otherwise specified. SPSS statistics version 19.0 (IBM, Armonk, New York, USA) was used for statistical analyses. The comparison was made with the t-test or Mann–Whitney U-test for continuous variable. The categorical variable was compared with Pearson's Chi-square test or Fisher's exact test. Multivariate analysis was performed by logistic regression analysis for the factors which showed P < 0.1 by univariate analysis. Statistical significance was set at P < 0.05 and all tests were two tailed.
| Results | | |
Thirty-six patients were included in this study. [Table 1] shows the characteristics of the patients. Twenty-seven patients were female and mean age was 67.5 ± 7.0 years old. Twenty-four patients had bilateral BE with nodules on chest CT. Twenty-four patients had a negative culture for AFB with sputum and 12 were unable to produce sputum. Of 24 patients whose sputum culture was negative for AFB, seven patients had purulent sputum. About the underlying disease, six patients (17%) had collagen vascular diseases, five patients (14%) had active malignancy, four patients (11%) had diabetes, and two patients (6%) had chronic respiratory diseases. Three patients (8%) received immunosuppressant.
[Table 2] shows the results of TBLB and bronchial wash culture. Thirty-two patients underwent TBLB and five patients (16%) had granuloma with TBLB. All patients underwent bronchial wash. AFB smear with bronchial wash was positive in seven patients (19%), and AFB culture was positive in 17 patients (47%). Of those with positive bronchial wash culture for AFB, 15 patients (88%), two patients (12%), and one patient (6%) had positive bronchial wash culture for Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium kansasii, respectively. One patient had positive results for both M. avium and M. intracellulare. All the patients with positive bronchial wash culture for AFB met the criteria for NTM lung disease proposed by ATS.[11]
[Table 3] shows the comparison with the patients having AFB-positive culture and those having AFB-negative culture in bronchial wash. Body mass index (BMI), white blood cell, C-reactive protein, erythrocyte sedimentation rate, and underlying conditions did not differ between two groups. However, more patients with negative culture in bronchial wash had AFB-negative culture with purulent sputum before bronchoscopy (37% vs. 0%, P = 0.008) and bilateral BE with nodules on chest CT (89% vs. 41%, P = 0.007). Logistic regression was performed for bilateral BE with nodules on chest CT, AFB-negative culture with purulent sputum before bronchoscopy, and C reactive protein. Bilateral BE with nodules on chest CT was the risk factor for the negative culture of AFB with bronchial wash (odds ratio [OR]: 0.149; 95% confidence interval [CI]: 0.024–0.913, P = 0.040) [Table 4]. | Table 3: Comparison with the patients having acid-fast bacillus positive culture and those having acid-fast bacillus negative culture in bronchial wash
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 | Table 4: Logistic regression for predicting positive culture in bronchial wash
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All the patients who had AFB-negative culture in bronchial wash did not meet the diagnostic criteria of NTM lung disease proposed by ATS11 during the follow-up period (median follow-up period was 18.9 months).
| Discussion | | |
Almost 34% to 53% of the patients whose CT showed BE with nodules had the positive culture for M. avium-intracellulare complex (MAC).[8],[12],[13] However, these studies did not limit the patients whose sputum test had not yielded the diagnosis of NTM lung disease. In this study, 47% of the patients with BE with nodules had bronchial wash culture positive for AFB though their sputum test had not yielded the diagnosis of NTM lung disease. These data showed the usefulness of bronchoscopy for the patients who were suspected to have NTM lung disease because of BE and nodules on chest CT and whose sputum test had not yielded the diagnosis. However, in 53% patients, bronchoscopy was not diagnostic. If we can predict the patients who will have negative AFB culture with bronchial wash, fewer patients would receive needless examination. In this study, bilateral BE with nodules was the risk factor for negative AFB culture with bronchial wash. When the area of opacity is wide, the burden of NTM is heavy, and it was speculated that sputum culture is more likely to be positive in such cases. Thus, when the patients with bilateral BE with nodules have negative sputum culture of AFB, it might be controversial for NTM lung disease. They might have less possibility to have NTM lung disease, and other diagnoses should be considered for these patients. Moreover, purulent sputum is suitable for detecting the pathogen. The patients might have less possibility to have NTM lung disease, when they have negative AFB culture with purulent sputum, although OR of negative AFB culture with purulent sputum for predicting negative AFB culture with bronchial wash could not be calculated due to a small number of patients in this study.
Recently, the usefulness of serological test for MAC has been reported.[14],[15],[16],[17],[18],[19] The necessity of bronchoscopy to diagnose the MAC lung disease might decrease. However, the sensitivity is not adequate in some studies with 60% to 77%.[15],[17],[18] Especially, sensitivity of 43% is reported in rheumatoid arthritis patients.[19] It might be difficult to deny MAC lung disease with negative MAC antibody. In addition, to gain cultivated strain is important for two reasons other than diagnostic value. First, Clarithromycin (CAM) is the key drug of chemotherapy for M. avium and M. intracellulare and the choice of the regimen is depended on the susceptibility to CAM according to ATS guideline.[11] Second, M. avium lung disease and M. intracellular lung disease are different in prognosis and response to the multiagent chemotherapy.[20] It is important to identify which the patients have M. avium lung disease or M. intracellular lung disease to predict the prognosis and the treatment response. Besides, it is difficult to distinguish MAC lung disease from other NTM lung diseases completely from their CT findings.[21] Therefore, when serological test for MAC is negative, we could not rule out other NTM lung disease. Bronchoscopy is essential to gain cultivated strain for the patients who have no sputum or negative sputum culture and should be considered, if the patients have no contraindication.
Our study has some limitations. First, this is a retrospective study and the number of the patients is relatively small. 95% CI of OR of bilateral BE with nodules on chest CT for the positive culture of AFB with bronchial wash was wide. Besides, we could not calculate the OR of AFB-negative culture with purulent sputum before bronchoscopy for the positive culture of AFB with bronchial wash because no patients who had positive AFB culture with bronchial wash had purulent sputum before bronchoscopy. Moreover, this study is performed at single institution. A large, prospective study is needed. Second, we could not collect the data about environmental risk factors such as soil and water exposure because of retrospective nature. But, there exist controversial reports about the environmental risk factors of NTM lung diseases.[22],[23],[24] Moreover, we compared the underlying diseases, conditions, and BMI of the patients, and there existed no difference between the patients with positive AFB culture from bronchial wash and those with negative AFB culture from bronchial wash. Third, if we performed lung tissue AFB culture with TBLB specimen, we might detect NTM pathogen with the higher rate. However, one retrospective study reported that bronchial wash culture was more sensitive than TBLB culture.[25] Further, the study is needed to know whether routine AFB culture with TBLB specimen could improve the detection rate of NTM pathogen.
| Conclusion | | |
In summary, patients with bilateral BE with nodules on CT are less likely to have the positive AFB culture from bronchial wash when sputum test was not diagnostic. A large, prospective study is needed to confirm our findings.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Lai CC, Tan CK, Chou CH, Hsu HL, Liao CH, Huang YT, et al. Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000-2008. Emerg Infect Dis 2010;16:294-6.  [ PUBMED] |
| 2. | Marras TK, Chedore P, Ying AM, Jamieson F. Isolation prevalence of pulmonary non-tuberculous mycobacteria in Ontario, 1997 2003. Thorax 2007;62:661-6. [ PUBMED] |
| 3. | Marras TK, Mendelson D, Marchand-Austin A, May K, Jamieson FB. Pulmonary nontuberculous mycobacterial disease, Ontario, Canada, 1998-2010. Emerg Infect Dis 2013;19:1889-91. [ PUBMED] |
| 4. | Park YS, Lee CH, Lee SM, Yang SC, Yoo CG, Kim YW, et al. Rapid increase of non-tuberculous mycobacterial lung diseases at a tertiary referral hospital in South Korea. Int J Tuberc Lung Dis 2010;14:1069-71. [ PUBMED] |
| 5. | Prevots DR, Shaw PA, Strickland D, Jackson LA, Raebel MA, Blosky MA, et al. Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems. Am J Respir Crit Care Med 2010;182:970-6. [ PUBMED] |
| 6. | Thomson RM; NTM working group at Queensland TB Control Centre and Queensland Mycobacterial Reference Laboratory. Changing epidemiology of pulmonary nontuberculous mycobacteria infections. Emerg Infect Dis 2010;16:1576-83. [ PUBMED] |
| 7. | Fujita J, Higa F, Tateyama M. Radiological findings of mycobacterial diseases. J Infect Chemother 2007;13:8-17. [ PUBMED] |
| 8. | Koh WJ, Lee KS, Kwon OJ, Jeong YJ, Kwak SH, Kim TS, et al. Bilateral bronchiectasis and bronchiolitis at thin-section CT: Diagnostic implications in nontuberculous mycobacterial pulmonary infection. Radiology 2005;235:282-8. |
| 9. | Jin F, Mu D, Chu D, Fu E, Xie Y, Liu T, et al. Severe complications of bronchoscopy. Respiration 2008;76:429-33. |
| 10. | Miller DL. A study of techniques for the examination of sputum in a field survey of chronic bronchitis. Am Rev Respir Dis 1963;88:473-83. [ PUBMED] |
| 11. | 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. [ PUBMED] |
| 12. | Swensen SJ, Hartman TE, Williams DE. Computed tomographic diagnosis of Mycobacterium avium-intracellulare complex in patients with bronchiectasis. Chest 1994;105:49-52. [ PUBMED] |
| 13. | Tanaka E, Amitani R, Niimi A, Suzuki K, Murayama T, Kuze F, et al. 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. |
| 14. | 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. [ PUBMED] |
| 15. | Kitada S, Levin A, Hiserote M, Harbeck RJ, Czaja CA, Huitt G, et al. Serodiagnosis of Mycobacterium avium complex pulmonary disease in the USA. Eur Respir J 2013;42:454-60. [ PUBMED] |
| 16. | Kitada S, Nishiuchi Y, Hiraga T, Naka N, Hashimoto H, Yoshimura K, et al. Serological test and chest computed tomography findings in patients with Mycobacterium avium complex lung disease. Eur Respir J 2007;29:1217-23. [ PUBMED] |
| 17. | Kobashi Y, Mouri K, Obase Y, Kato S, Oka M. Serological assay by use of glycopeptidolipid core antigen for Mycobacterium avium complex. Scand J Infect Dis 2013;45:241-9. [ PUBMED] |
| 18. | Shu CC, Ato M, Wang JT, Jou R, Wang JY, Kobayashi K, et al. Sero-diagnosis of Mycobacterium avium complex lung disease using serum immunoglobulin A antibody against glycopeptidolipid antigen in Taiwan. PLoS One 2013;8:e80473. [ PUBMED] |
| 19. | Watanabe M, Banno S, Sasaki K, Naniwa T, Hayami Y, Ueda R, et al. Serodiagnosis of Mycobacterium avium-complex pulmonary disease with an enzyme immunoassay kit that detects anti-glycopeptidolipid core antigen IgA antibodies in patients with rheumatoid arthritis. Mod Rheumatol 2011;21:144-9. |
| 20. | Koh WJ, Jeong BH, Jeon K, Lee NY, Lee KS, Woo SY, et al. Clinical significance of the differentiation between Mycobacterium avium and Mycobacterium intracellulare in M. avium complex lung disease. Chest 2012;142:1482-8. [ PUBMED] |
| 21. | Thomson RM, Yew WW. When and how to treat pulmonary non-tuberculous mycobacterial diseases. Respirology 2009;14:12-26. [ PUBMED] |
| 22. | Chan ED, Iseman MD. Underlying host risk factors for nontuberculous mycobacterial lung disease. Semin Respir Crit Care Med 2013;34:110-23. [ PUBMED] |
| 23. | Dirac MA, Horan KL, Doody DR, Meschke JS, Park DR, Jackson LA, et al. Environment or host?: A case-control study of risk factors for Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2012;186:684-91. [ PUBMED] |
| 24. | Maekawa K, Ito Y, Hirai T, Kubo T, Imai S, Tatsumi S, et al. Environmental risk factors for pulmonary Mycobacterium avium-intracellulare complex disease. Chest 2011;140:723-9. [ PUBMED] |
| 25. | Sekine A, Saito T, Satoh H, Morishita Y, Tsunoda Y, Tanaka T, et al. Limited value of transbronchial lung biopsy for diagnosing Mycobacterium avium complex lung disease. Clin Respir J 2017;11:1018-23. [ PUBMED] |
[Table 1], [Table 2], [Table 3], [Table 4]
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