Nontuberculous mycobacteria in bronchiectasis: Prevalence and patient characteristics.

The aim of the current study was to investigate the prevalence and clinical associations of nontuberculous mycobacteria (NTM) in a well-characterised cohort of patients with adult-onset bronchiectasis. The sputum of all patients attending a tertiary referral bronchiectasis clinic between April 2002 and August 2003 was examined for mycobacteria as part of an extensive diagnostic work-up. NTM-positive patients subsequently had further sputa examined. A modified bronchiectasis scoring system was applied to all high-resolution computed tomography (HRCT) scans from NTM-positive patients, and a matched cohort without NTM. Out of 98 patients attending the clinic, 10 had NTM in their sputum on first culture; of those, eight provided multiple positive cultures. Three patients were treated for NTM infection. A higher proportion of NTM-positive than -negative patients were subsequently diagnosed with cystic fibrosis (two out of nine versus two out of 75). On HRCT scoring, more patients in the NTM-positive group had peripheral mucus plugging than in the NTM-negative group. In the current prospective study of a large cohort of patients with bronchiectasis, 10% cultured positive for nontuberculous mycobacteria in a random clinic sputum sample. Few clinical parameters were helpful in discriminating between groups, except for a higher prevalence of previously undiagnosed cystic fibrosis and of peripheral mucus plugging on high-resolution computed tomography in the nontuberculous mycobacteria group.     

Prevalence of gastroesophageal reflux disease in patients with nontuberculous mycobacterial lung disease

BACKGROUND: Knowledge of the relationship between respiratory disorders and gastroesophageal reflux disease (GERD) is increasing. However, the association between GERD and pulmonary disease caused by nontuberculous mycobacteria (NTM) has not been studied in detail. We investigated the prevalence of GERD in patients with the nodular bronchiectatic form of NTM lung disease. METHODS: Fifty-eight patients with the nodular bronchiectatic form of NTM lung disease underwent ambulatory 24-h esophageal pH monitoring. Of the 58 patients, 27 patients were identified as having Mycobacterium avium complex infection (15 with Mycobacterium intracellulare and 12 with M avium), and 31 patients had Mycobacterium abscessus pulmonary infection. RESULTS: The prevalence of GERD in patients with the nodular bronchiectatic form of NTM lung disease was 26% (15 of 58 patients). Only 27% (4 of 15 patients) had typical GERD symptoms. No statistically significant differences were found between patients with GERD and those without GERD with regard to age, sex, body mass index, or pulmonary function test results. However, patients with GERD were more likely to have a sputum smear that was positive for acid-fast bacilli (12 of 15 patients, 80%), compared with patients without GERD (19 of 43 patients, 44%) [p = 0.033]. In addition, bronchiectasis and bronchiolitis were observed in more lobes in patients with GERD than in patients without GERD (p = 0.008 and p = 0.005, respectively). CONCLUSIONS: Patients with the nodular bronchiectatic form of NTM lung disease have a high prevalence of increased esophageal acid exposure, usually without typical GERD symptoms.     

Bronchiectasis and nontuberculous mycobacterial disease

Over the last 30 years it has become increasingly clear that nontuberculous mycobacterial (NTM) lung infections and bronchiectasis are closely related disorders. Although incontrovertible proof is lacking, there is a growing consensus of opinion that NTM lung disease characterized by nodules and bronchiectasis (nodular/bronchiectatic NTM lung disease) may be a consequence of preexisting bronchiectasis that predisposes to NTM infection and disease. To use published diagnostic guidelines effectively, physicians must become familiar with the disease-causing potential of individual NTM species. Essentially all NTM patients have bronchiectasis, so optimal overall patient management requires successful therapeutic strategies for both NTM infection and bronchiectasis.     

非结核分枝杆菌病50例临床分析

目的探讨非结核分枝杆菌病的临床特点和提高非结核分枝杆菌病的诊断和治疗水平。方法1999年8月—2006年3月间在北京胸科医院住院治疗的患者,痰培养分枝杆菌阳性、菌种鉴定为非结核分枝杆菌的50例患者,进行耐药试验并对其临床表现及治疗效果进行总结。结果非结核分枝杆菌肺病患者对一线抗结核药物均有不同程度的耐药,其中对异烟肼(H)、链霉素(S)耐药率最高,对丁胺卡那霉素(Am)、卡那霉素(Km)耐药率较低。结论非结核分枝杆菌肺病确诊靠菌种鉴定,早期给予合理的化疗方案可取得一定的效果。     

Lung disease due to the more common nontuberculous mycobacteria

As the prevalence of tuberculosis (TB) declines in the developed world, the proportion of mycobacterial lung disease due to nontuberculous mycobacteria (NTM) is increasing. It is not clear whether there is a real increase in prevalence or whether NTM disease is being recognized more often because of the introduction of more sensitive laboratory techniques, and that more specimens are being submitted for mycobacterial staining and culture as the result of a greater understanding of the role of NTM in conditions such as cystic fibrosis, posttransplantation and other forms of iatrogenic immunosuppression, immune reconstitution inflammatory syndrome, fibronodular bronchiectasis, and hypersensitivity pneumonitis. The introduction of BACTEC liquid culture systems (BD; Franklin Lakes, NJ) and the development of nucleic acid amplification and DNA probes allow more rapid diagnosis of mycobacterial disease and the quicker differentiation of NTM from TB isolates. High-performance liquid chromatography, polymerase chain reaction, and restriction fragment length polymorphism analysis have helped to identify new NTM species. Although treatment regimens that include the newer macrolides are more effective than the earlier regimens, failure rates are still too high and relapse may occur after apparently successful therapy. Moreover, treatment regimens are difficult to adhere to because of their long duration, adverse effects, and interactions with the other medications that these patients require. The purpose of this article is to review the common presentations of NTM lung disease, the conditions associated with NTM lung disease, and the clinical features and treatment of the NTM that most commonly cause lung disease.     

Bronchoscopy for the diagnosis of nontuberculous mycobacterial pulmonary disease: Specificity and diagnostic yield in a retrospective cohort study

BackgroundBronchoscopy is a recognized method for obtaining specimens for the diagnosis of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnostic properties remain to be elucidated. The aim of this study was to determine the specificity of bronchoscopy for the diagnosis of NTM-PD, and to examine the diagnostic yield of bronchoscopy for detecting nontuberculous mycobacteria (NTM) when patients cannot expectorate sputum with NTM.MethodsThis retrospective cohort study included 2657 patients who underwent bronchoscopy and mycobacterial culture between January 2004 and June 2018 in a tertiary care center in Tokyo, Japan. To examine the specificity of bronchoscopy, the first cohort comprised patients who underwent bronchoscopy for the diagnosis of lung cancer and mycobacterial culture. To investigate the diagnostic yield, patients with nodular bronchiectasis who underwent bronchoscopy for the diagnosis of NTM-PD were enrolled into the second cohort.ResultsIn total, 919 patients were diagnosed with lung cancer, 19 patients showed positive culture for NTM, and 14 patients showed findings for NTM-PD. Accordingly, the specificity was calculated as 900/905 (99.4%). In addition, NTM-PD was suspected before bronchoscopy in 199 patients; the diagnostic yield was 105/199 (52.8%). Four factors were associated with NTM-PD: upper lobe examination, absence of specific bacteria, absence of connective tissue disease, and a higher total computed tomography score.ConclusionsBronchoscopy has a high specificity for the diagnosis of NTM-PD. In addition, even when NTM is undetected in sputum, bronchoscopy may detect mycobacteria in approximately half of the patients suspected of having NTM-PD.     

Risk factors for pulmonary disease due to culture-positive M. tuberculosis or nontuberculous mycobacteria in South African gold miners.

The aim of this study was to determine risk factors for disease due to nontuberculous mycobacteria (NTM) compared to those due to Mycobacterium tuberculosis in South African gold miners with pulmonary mycobacterial disease. A case/control study comparing tuberculosis and NTM cases amongst all patients with a positive sputum mycobacterial culture in 1995 was carried out. The 51 cases of disease due to NTM and 425 tuberculosis cases were similar with regard to age, education, home region, smoking habits and percentage of CD4 cells. After adjustment for confounders, those with NTM were more likely to have had previous tuberculosis treatment (odds ratio (OR) 3.61; 95% confidence interval (CI) 1.9-6.9), have worked longer underground (p-value for trend=0.05) or have evidence of silicosis (OR 12.6; 95% CI 2.2-71) and were less likely to drink regularly (OR 0.12; 95% CI 0.02-0.93) than patients with tuberculosis. In patients with disease due to NTM, 35.3% were human immunodeficiency virus-positive compared with 48.8% of tuberculosis patients (p=0.2) and an estimated 21% overall in the mines at the time of the study. Previous tuberculosis treatment, silicosis and duration of underground work are even more strongly associated with disease due to nontuberculous mycobacteria than with tuberculosis. Attempts to reduce the incidence of all pulmonary mycobacterial disease in this community should address recognized risk factors and ensure that those with tuberculosis are diagnosed, treated and cured.     

Diagnosis of nontuberculous mycobacterial disease in the era of surveillance chest CT scans

The radiologic surveillance of smokers with low-dose CT scan has led to a significant surge of radiologic incidental findings, including the detection of early stages of pulmonary infections including nontuberculous mycobacteria (NTM). This causes a state of overdiagnosis and potential overtreatment of NTM lung disease. Here we propose a new approach to NTM pulmonary disease in the era of increased CT scanning.     

非结核分支杆菌肺病24例临床分析

目的总结非结核分支杆菌(NTM)肺病的临床特点。方法回顾性分析我所1994年至2004年间收治的24例NTM肺病的临床特点。结果本组NTM肺病以老年患者多见,症状较轻,肺部病变范围广,耐药率高,治疗效果差,部分患者持续菌阳。结论NTM肺病治疗方案有待探讨。     

The expanding spectrum of Mycobacterium avium complex-associated pulmonary disease

Nontuberculous mycobacteria (NTM) are increasingly recognized as important pulmonary pathogens. Mycobacterium avium intracellulare complex (MAC) causes most lung infections due to NTM. Patients with preexisting lung disease or immunodeficiency are at greatest risk for developing MAC infection. The majority of MAC pulmonary cases, however, occur in immunocompetent elderly women in association with nodular infiltrates and bronchiectasis. More recently, pulmonary disease has also been described in immunocompetent patients after exposure to MAC-contaminated hot tubs. We describe a case of aggressive MAC lung disease in a young immunocompetent female patient without preexisting lung disease whose clinical and pathologic characteristics do not fit into any of these categories and may represent a unique manifestation of MAC lung disease.     

Nontuberculous mycobacteria. II: nested-cohort study of impact on cystic fibrosis lung disease

The prevalence of nontuberculous mycobacteria (NTM) is high (approximately 13%) in sputum of patients with cystic fibrosis (CF), but the impact on lung disease is unknown. We followed 60 incident NTM-positive and 99 culture-negative patients with CF for 15 months and assessed clinical impact of NTM by FEV1 and high-resolution computed tomography (HRCT) of the chest. Mycobacterium avium complex was seen in 75% of NTM-positive subjects. The annual rate of decline in FEV1 was not different among control versus NTM-positive subjects who did not, or did, meet American Thoracic Society microbiologic criteria for NTM disease (3 +/- 1, 3 +/- 2, and 5 +/- 2%, respectively). More subjects with three or more positive cultures for NTM had two or more characteristic findings on entry HRCT (60%, 9/15) as compared with subjects with two positive cultures or less (32%) or negative cultures (19%; p < 0.02). All subjects with three or more positive cultures and exit HRCTs (n = 6) showed progression of HRCT findings, whereas only 17% of subjects with two positive cultures or less had progression (p = 0.0006). In summary, no significant short-term effect on FEV1 was detected in patients with multiple positive NTM cultures, but an abnormal HRCT was predictive of progression. Patients with CF and multiple positive NTM cultures, characteristic HRCT findings, and progression of HRCT changes should be monitored closely and considered for antimycobacterial therapy.     

Changing epidemiology of nontuberculous mycobacterial lung disease in South Korea

Abstract Objectives: Pulmonary nontuberculous mycobacteria (NTM) are increasing worldwide, but data from regions with an intermediate tuberculosis (TB) burden are insufficient, and the reason for the changing epidemiology of NTM lung disease is unclear. We investigated the trends of NTM lung disease at a tertiary hospital in Korea and evaluated the contribution of liquid culture systems. Methods: We conducted a retrospective observational study of mycobacterial cultures of respiratory specimens from 26,793 patients at Severance Hospital in South Korea from January 2006 to December 2010. Results: The recovery percent of Mycobacterium tuberculosis isolates was 5.9% in 2006 and 7.1% in 2010, and the recovery percent of NTM isolates was 2.0% in 2006 and 6.3% in 2010. The annual percent of NTM isolation has increased steadily every year (p for trend 相似文献   

Analysis of chronic necrotizing pulmonary aspergillosis (CNPA) cases complicated with non-tuberculous mycobacteriosis (NTM)

OBJECTIVE: To clarify the clinical feature of chronic necrotizing pulmonary aspergillosis (CNPA) complicated with non-tuberculous mycobacteriosis (NTM). SUBJECTS AND METHODS: Forty-one CNPA cases underlying NTM were analyzed according to their clinical backgrounds. RESULTS: Concerning the radiological type of prior NTM, CNPA cases were classified into two groups; 1) resembling pulmonary tuberculosis that usually shows cavitary lesion and 2) micronodule and bronchiectasis pattern, and more than half of cases (61.0%) were classified as the latter type. Average duration between prior NTM and CNPA was 1354 days. Isolation of Aspergillus spp. from sputum was 15 out of 41 (36.6%). Positive rates for Aspergillus galactomannan antigen and anti-aspergillus antibody were 58.5%, 46.3% respectively. With regard to subspecies of mycobacteria, M. avium was most frequent (82.9%). Since 6.8% of NTM cases develop CNPA within 10 years, careful observation of CNPA was required for the management of NTM.     

Vitamin D-receptor polymorphisms and non-tuberculous mycobacterial lung disease in Korean patients.

This study investigated the potential role of vitamin D-receptor (VDR) gene polymorphisms in susceptibility to lung disease caused by non-tuberculous mycobacteria (NTM). TaqI and FokI polymorphisms were compared in 124 patients and 127 controls. The genotype, allele and haplotype frequencies did not differ between patients and controls. TaqI and FokI polymorphisms of the VDR gene do not appear to be responsible for host susceptibility to NTM lung disease, at least in this Korean population. An association cannot, however, be completely ruled out, as only two single nucleotide polymorphisms of the VDR gene were studied in this report.     

Respiratory infections associated with nontuberculous mycobacteria in non-HIV patients.

The incidence of nontuberculous mycobacteria (NTM) pulmonary diseases in HIV-negative patients was studied prospectively from January 1, 2001 to December 31, 2003 by 32 sentinel sites distributed throughout France. In total, 262 patients who yielded NTM isolates from respiratory clinical specimens, met the bacteriological, radiological and clinical criteria established by the American Thoracic Society for NTM respiratory disease. Among the 262 NTM isolates, 234 were slow-growing mycobacteria (125 Mycobacterium avium-intracellulare complex (MAC), 66 M. xenopi, 34 M. kansasii) and 28 were rapidly growing mycobacteria (25 M. abscessus complex). In the Paris area, M. xenopi was the most frequently isolated species, followed by MAC. Most patients (>50%), except those with M. kansasii, had underlying predisposing factors such as pre-existing pulmonary disease or immune deficiency. Asthenia, weight loss, chronic cough and dyspnoea were the most common clinical symptoms. The classical radiological appearance of NTM infections was indistinguishable from that observed in patients with pulmonary tuberculosis. In summary, the incidence of nontuberculous mycobacteria pulmonary infections in HIV-negative patients was estimated at 0.74, 0.73 and 0.72 cases per 100,000 inhabitants in 2001, 2002 and 2003, respectively.     

Comparison of the incidence between tuberculosis and nontuberculous mycobacterial disease after gastrectomy

Purpose

Gastrectomy is a well-known risk factor for tuberculosis (TB). However, little data are available regarding the relationship between gastrectomy and the risk of nontuberculous mycobacterial (NTM) disease. Here, we investigated the incidence of TB and NTM lung disease in gastrectomized patients.

Method

New cases of TB and NTM lung infection or disease were examined among patients who had undergone gastrectomy due to gastric cancer from 2003 to 2009 at a tertiary referral hospital in South Korea. Annualized incidence rates for cases were compared with those of the general population.

Results

This study included a total of 2,684 patients. New mycobacterial cases were found in 41 patients. Cases of TB and NTM lung infection were 35 (85 %) and 6 (15 %) including 2 NTM lung disease cases, respectively. Annualized crude incidence rates for TB, NTM lung infection, and NTM lung disease were 327/100,000, 56/100,000, and 19/100,000, respectively. The age-standardized incidence rate of TB was significantly higher in gastrectomized patients than in the general population. However, the standardized incidences of NTM lung infection and disease were not significantly different from those of non-gastrectomized patients. Patients with NTM lung infection frequently exhibited comorbid chronic lung disease, while those with TB were more frequently found to have fibronodular lesions on preoperative chest radiography.

Conclusions

Gastrectomy does not appear to increase the risk of NTM lung disease. However, NTM lung infection or disease should be considered as a differential diagnosis of pulmonary TB in gastrectomized patients accompanying chronic lung disease.     

Epidemiology and clinical significance of nontuberculous mycobacteria in patients negative for human immunodeficiency virus in Switzerland.

Over the last decades, the rate of isolation of tubercle bacilli has declined in the developed countries, while the incidence of infection with nontuberculous mycobacteria (NTM) has increased. In a retrospective study, we analyzed all cases of patients negative for human immunodeficiency virus (HIV) and from whom NTM were isolated in the Zurich area of Switzerland from 1983 to 1988. During the 6-year study period, 513 patients infected with NTM were identified, 34 of whom had clinically significant disease. The presentation of mycobacteriosis was found to be lung disease in 23 cases, soft-tissue disease in 10 cases, and disseminated disease in one case. The highest attack rate of pulmonary mycobacteriosis was 0.49% and was found in the group of patients 41-50 years old. During the 6-year period, the incidence of tuberculosis declined from 16.2 to 13.2 per 100,000 population, while the incidence of mycobacteriosis increased from 0.4 to 0.9 per 100,000 population. Clinically nonsignificant NTM isolates were found more frequently in patients with chronic lung diseases (P less than .01) and especially in patients with a history of tuberculosis (P less than .001).     

NRAMP1 gene polymorphism and susceptibility to nontuberculous mycobacterial lung diseases

STUDY OBJECTIVES: Pulmonary disease caused by nontuberculous mycobacteria (NTM) may occur in patients with no underlying lung disease and no known immunodeficiency. The purpose of this study was to evaluate a potential role for natural-resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms for human susceptibility to the NTM lung disease. DESIGN: A case-control study. SETTING: Tertiary university medical center. PARTICIPANTS: Forty-one adult patients with NTM lung disease (Mycobacterium avium complex infection, 18 patients; Mycobacterium abscessus infection, 23 patients) were included in the study population. The diagnosis of NTM lung disease was made when the patients fulfilled the diagnostic criteria published by the American Thoracic Society. All patients had findings on high-resolution CT scans, such as bilateral bronchiectasis combined with multiple small nodules and branching linear structures, that were characteristic of the nodular bronchiectatic form of NTM lung disease. Fifty healthy individuals were selected as control subjects. RESULTS: Heterozygotes at intron 4 (469 + 14G/C) [INT4], codon 543 in exon 15 (D543N), and 3' untranslated region (3'UTR) were observed at significantly higher frequencies in patients with NTM lung disease than in control subjects. The odds ratios (ORs) were 2.78 (95% confidence interval [CI], 1.12 to 6.89; p = 0.026) for INT4 G/C, 5.74 (95% CI, 1.48 to 22.30; p = 0.006) for D543 G/A, and 9.54 (95% CI, 2.49 to 36.53; p < 0.001) for 3'UTR TGTG+/del. Subjects who were heterozygous for two NRAMP1 polymorphisms in INT4 and D543N were particularly overrepresented among those with NTM lung disease, compared with those with the most common NRAMP1 genotype (OR, 10.88, 95% CI, 1.18 to 100.45; p = 0.035). There were no significant differences in the frequencies of INT4, D543N, and 3'UTR polymorphisms between the patients with M avium complex infection and those with M abscessus infection. CONCLUSIONS: These findings suggest that the NRAMP1 genetic polymorphisms are associated with human susceptibility to NTM lung disease.