Nontuberculous Mycobacteria Lung Research Articles

Building size and disinfectant type influence the detection and concentration of Mycobacterium spp. in hot water plumbing

The number of nontuberculous mycobacteria (NTM) lung disease cases is increasing in the United States (US). This respiratory disease is primarily caused by three NTM species: Mycobacterium avium, M. intracellulare, and M. abscessus. Since disease transmission could occur through water aerosolization, this study investigated these three species' occurrence (sporadic and persistent) in hot water samples collected from residences (n = 70) and office buildings (n = 30) across the US. A longitudinal survey design was used. Three quantitative Polymerase Chain Reaction (qPCR) assays were used to measure the mycobacterial species in the water samples. Additionally, the water's disinfectant residual was measured. A structure's age and square footage were evaluated to predict mycobacterial contamination. Also, the seasonal occurrence of each species was assessed by structure type. Residences had a 43 % (30/70), and office buildings had a 77 % (23/30) detection frequency of one or more Mycobacterium spp. in their hot water. The age of the structure influenced M. intracellulare detection frequency but not M. avium and M. abscessus. The structure's square footage affected M. avium and M. intracellulare detection frequency but not M. abscessus. In chlorinated water, M. intracellulare was detected 1.4× more often in office buildings' hot water than in chloraminated water. In chloraminated water, the Mycobacterium spp. were detected 2–2.5× more often in residences, while M. avium and M. abscessus were detected 1.5–2.3× more often in office buildings, compared to chlorinated water. Each Mycobacterium spp. had a different trend associated with the type of structure and disinfectant. Further research is needed to better understand NTM occurrence in the built environment to improve public health.

Multiparameter immunoprofiling for the diagnosis and differentiation of progressive versus nonprogressive nontuberculous mycobacterial lung disease-A pilot study.

Clinical prediction of nontuberculous mycobacteria lung disease (NTM-LD) progression remains challenging. We aimed to evaluate antigen-specific immunoprofiling utilizing flow cytometry (FC) of activation-induced markers (AIM) and IFN-γ enzyme-linked immune absorbent spot assay (ELISpot) accurately identifies patients with NTM-LD, and differentiate those with progressive from nonprogressive NTM-LD. A Prospective, single-center, and laboratory technician-blinded pilot study was conducted to evaluate the FC and ELISpot based immunoprofiling in patients with NTM-LD (n = 18) and controls (n = 22). Among 18 NTM-LD patients, 10 NTM-LD patients were classified into nonprogressive, and 8 as progressive NTM-LD based on clinical and radiological features. Peripheral blood mononuclear cells were collected from patients with NTM-LD and control subjects with negative QuantiFERON results. After stimulation with purified protein derivative (PPD), mycobacteria-specific peptide pools (MTB300, RD1-peptides), and control antigens, we performed IFN-γ ELISpot and FC AIM assays to access their diagnostic accuracies by receiver operating curve (ROC) analysis across study groups. Patients with NTM-LD had significantly higher percentage of CD4+/CD8+ T-cells co-expressing CD25+CD134+ in response to PPD stimulation, differentiating between NTM-LD and controls. Among patients with NTM-LD, there was a significant difference in CD25+CD134+ co-expression in MTB300-stimulated CD8+ T-cells (p <0.05; AUC-ROC = 0.831; Sensitivity = 75% [95% CI: 34.9-96.8]; Specificity = 90% [95% CI: 55.5-99.7]) between progressors and nonprogressors. Significant differences in the ratios of antigen-specific IFN-γ ELISpot responses were also seen for RD1-nil/PPD-nil and RD1-nil/anti-CD3-nil between patients with nonprogressive vs. progressive NTM-LD. Our results suggest that multiparameter immunoprofiling can accurately identify patients with NTM-LD and may identify patients at risk of disease progression. A larger longitudinal study is needed to further evaluate this novel immunoprofiling approach.

Non-tuberculous mycobacteria lung disease due to Mycobacterium chimaera in a 67-year-old man treated with immune checkpoint inhibitors for lung adenocarcinoma: infection due to dysregulated immunity?

Immune checkpoint inhibitors (ICIs) are drugs growingly employed in cancer immunotherapy which have significantly improved the prognosis of several tumours. ICIs act by restoring the “exhausted” immune system and increasing the number of T cells active against pathogens losing tolerogenic signalling, which has been linked to an increased risk of infectious events. We present the case of a 67-year-old man with locally advanced lung adenocarcinoma treated with the anti-PD-L1 durvalumab. Three months after immunotherapy started, an apparent radiological progression was found with elements suggesting a parenchymal superinfection associated with weight loss, asthenia, and sputum emission. A bronchoalveolar lavage resulted positive for Mycobacterium chimaera, and treatment with amikacin iv (for eight weeks) and daily azithromycin, ethambutol, and rifampicin was started. Thirteen months after treatment started, the patient is alive with a stable lung condition. The case highlights the risk of non-tuberculous mycobacteria lung disease (NTM-LD) in patients receiving ICIs treatment. We hypothesise that durvalumab induced an exaggerated immune response toward the mycobacteria, leading to immunopathology and overt clinical manifestations. Clinicians should be aware of this possibility in patients receiving ICIs developing new signs/symptoms related to the respiratory tract, especially in countries with a high prevalence of NTM-LD.

Molecular Characterization of Mycobacterium species Isolates from Patients with Pulmonary Tuberculosis in Sabah, Malaysia

Tuberculosis (TB) is one of the deadliest diseases worldwide, caused by members of Mycobacterium tuberculosis complex (MTBC), commonly by Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis. In Malaysia, Sabah is one of the states of public health concern with the highest TB cases. Clinical presentations of TB and non-tuberculous mycobacteria (NTM) lung disease are similar, and mycobacteria appear to be identical under standard diagnosis with sputum smear microscopy, causing difficulty to diagnose TB. Identification of Mycobacterium species is essential for effective management of mycobacterial diseases treatment and their control strategy. Thus, this study aimed to identify the Mycobacterium species from suspected TB patients in Sabah using molecular methods. Sputum samples (n=595) were screened with GeneXpert MTB/RIF (Xpert), and positive TB samples (n=67) were processed and cultured in BACTEC MGIT. Forty-five isolates were successfully recovered in MGIT and characterisation of the mycobacterial isolates using PCR and/or sequencing with rpoB, RD9, hsp65, and 16S rRNA genes confirmed the presence of Mtb in 41 samples, and four non-mycobacteria, i.e. Microbacterium laevaniformans, Streptomyces sp., Streptomyces misionensis and Gordonia sp. These non-mycobacteria isolates showed negative results when tested directly with Xpert. In conclusion, Mtb is the predominant species of MTBC circulating in Sabah. The presence of non-mycobacteria in this study was due to bacterial contamination in MGIT, not bacterial cross-reactivity in Xpert, implying the high sensitivity and specificity of Xpert for diagnosis of TB.

Mycobacterial skin infection.

Purpose of reviewThe aim of this article is to review the most recent evidences concerning mycobacterial skin infections, limiting the period of literature research to 2020--2021.Recent findingsMycobacterial skin infections include a heterogeneous group of cutaneous diseases.Cutaneous tuberculosis is usually the result of hematogenous dissemination or spread from underlying foci and it must be distinguished from tuberculids, resulting from the immunological reaction to Mycobacterium tuberculosis antigens. Leprosy prevalence was drastically reduced after introduction of multidrug therapy in the 1980 s, but cases are still reported due to underdiagnosis, and animal and environmental reservoirs. Recent advances concentrate in the diagnostic field. Specific guidelines for the treatment of nontuberculous mycobacteria skin infections are missing and surgical procedures may be required. Prognosis is better as compared to nontuberculous mycobacteria lung disease. Rapid laboratory-confirmed diagnosis of Buruli ulcer may be achieved by the IS2404 PCR. Among new drugs, telacebec is promising in terms of potency, shorter duration and tolerability in animal studies. A clinical trial in humans is planned.SummaryMycobacterial cutaneous lesions are nonpathognomonic and clinical suspicion must be confirmed by culture or molecular detection. Long-course multidrug treatment is required based on susceptibility tests. Surgical intervention may also be required. Rehabilitation and psychosocial support reduce long-term physical and mental consequences mostly in Buruli ulcer and leprosy.

CT Imaging Characteristics of Nontuberculous Mycobacteria Lung Disease, Active Tuberculosis and Multi-Drug Resistant Tuberculosis.

The differential diagnosis of nontuberculous mycobacteria (NTM) lung disease, active tuberculosis (ATB) and multi-drug resistant tuberculosis (MDR-TB) remains difficult. To explore the CT imaging characteristics of NTM lung disease, ATB and MDR-TB for differential diagnosis. Patients with NTM lung disease (n=200), ATB (n=200) and MDR-TB (n=200) who were examined and treated from August 2013 to May 2021 were included. Their chest CT imaging results were retrospectively analyzed, and the imaging characteristics were compared. The proportion of cases complicated with underlying lung disease, cough and hemoptysis was significantly higher in NTM group than those in ATB and MDR-TB groups (P<0.05). Compared with ATB and MDR-TB groups, NTM group had significantly more cases of nodule-bronchus dilation type, but significantly fewer cases of nodule-mass type and other types (P<0.05). In NTM group, the cases of thin-wall cavity, bronchiectasis and centrilobular nodules increased, but the detection rate of thick-wall cavity, lung consolidation, atelectasis, lung damage, lung volume reduction, intrapulmonary calcification, hilar and mediastinal lymph node calcification, acinar nodules, pleural thickening and pleural effusion declined compared with ATB and MDR-TB groups (P<0.05). The detection rates of lesions, cavities and bronchiectasis in the lingual lobe of left lung and middle lobe of right lung were significantly higher in NTM group than those in ATB and MDR-TB groups (P<0.05). The imaging characteristics of NTM lung disease are quite similar to those of ATB and MDR-TB, but they can be differentially diagnosed through the types of cavities and nodules, incidence rate of bronchiectasis, and differences in lung consolidation, lung damage, calcification, pleural thickening and pleural effusion.

A Mycobacterium tuberculosis NBTI DNA Gyrase Inhibitor Is Active against Mycobacterium abscessus.

ABSTRACTFluoroquinolones—the only clinically used DNA gyrase inhibitors—are effective against tuberculosis (TB) but are in limited clinical use for nontuberculous mycobacteria (NTM) lung infections due to intrinsic drug resistance. We sought to test alternative DNA gyrase inhibitors for anti-NTM activity. Mycobacterium tuberculosis gyrase inhibitors (MGIs), a subclass of novel bacterial topoisomerase inhibitors (NBTIs), were recently shown to be active against the tubercle bacillus. Here, we show that the MGI EC/11716 not only has potent anti-tubercular activity but is active against M. abscessus and M. avium in vitro. Focusing on M. abscessus, which causes the most difficult to cure NTM disease, we show that EC/11716 is bactericidal, active against drug-tolerant biofilms, and efficacious in a murine model of M. abscessus lung infection. Based on resistant mutant selection experiments, we report a low frequency of resistance to EC/11716 and confirm DNA gyrase as its target. Our findings demonstrate the potential of NBTIs as anti-M. abscessus and possibly broad-spectrum anti-mycobacterial agents.

DNA Methylation Profiling for the Diagnosis and Prognosis of Patients with Nontuberculous Mycobacterium Lung Disease

The incidence of nontuberculous Mycobacterium (NTM) lung disease is rapidly increasing; however, its diagnosis and prognosis remain unclear while selecting patients who will respond to appropriate treatment. Differences in DNA methylation patterns between NTM patients with good or poor prognosis could provide important therapeutic targets. We used the Illumina MethylationEPIC (850k) DNA methylation microarray to determine the pattern between differentially methylated regions (DMRs) in NTM patients with good or poor prognosis (n = 4/group). Moreover, we merged and compared 20 healthy controls from previous Illumina Methylation450k DNA methylation microarray data. We selected and visualized the DMRs in the form of heatmaps, and enriched terms associated with these DMRs were identified by functional annotation with the “pathfinder” package. In total, 461 and 293 DMRs (|Log2 fold change| > 0.1 and P < 0.03) were more methylated in patients with four poor and four good prognoses, respectively. Furthermore, 337 and 771 DMRs (|Log2 fold change| > 0.08 and P < 0.001) were more methylated in eight NTM patients and 20 healthy controls, respectively. TGFBr1 was significantly less methylated, whereas HLA-DR1 and HLA-DR5 were more methylated in patients with poor prognosis (compared to those with good prognosis). LRP5, E2F1, and ADCY3 were the top three less-methylated genes in NTM patients (compared with the controls). The mTOR and Wnt signaling pathway-related genes were less methylated in patients with NTM. Collectively, genes related to Th1- cell differentiation, such as TGFBr1 and HLA-DR, may be used as biomarkers for predicting the treatment response in patients with NTM lung disease.

Distinguishing nontuberculous mycobacteria from Mycobacterium tuberculosis lung disease from CT images using a deep learning framework.

PurposeTo develop and evaluate the effectiveness of a deep learning framework (3D-ResNet) based on CT images to distinguish nontuberculous mycobacterium lung disease (NTM-LD) from Mycobacterium tuberculosis lung disease (MTB-LD).MethodChest CT images of 301 with NTM-LD and 804 with MTB-LD confirmed by pathogenic microbiological examination were retrospectively collected. The differences between the clinical manifestations of the two diseases were analysed. 3D-ResNet was developed to randomly extract data in an 8:1:1 ratio for training, validating, and testing. We also collected external test data (40 with NTM-LD and 40 with MTB-LD) for external validation of the model. The activated region of interest was evaluated using a class activation map. The model was compared with three radiologists in the test set.ResultPatients with NTM-LD were older than those with MTB-LD, patients with MTB-LD had more cough, and those with NTM-LD had more dyspnoea, and the results were statistically significant (p < 0.05). The AUCs of our model on training, validating, and testing datasets were 0.90, 0.88, and 0.86, respectively, while the AUC on the external test set was 0.78. Additionally, the performance of the model was higher than that of the radiologist, and without manual labelling, the model automatically identified lung areas with abnormalities on CT > 1000 times more effectively than the radiologists.ConclusionThis study shows the efficacy of 3D-ResNet as a rapid auxiliary diagnostic tool for NTB-LD and MTB-LD. Its use can help provide timely and accurate treatment strategies to patients with these diseases.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00259-021-05432-x.

The value of gene chip detection of bronchoalveolar lavage fluid in the diagnosis of nontuberculous mycobacterial lung disease.

Nontuberculous mycobacteria (NTM) are mycobacteria other than mycobacterium tuberculosis complex (MTBC) and mycobacterium leprae. NTM can cause infection in many human tissues and organs and is most commonly seen in the lungs. Clinically, the symptoms and signs of nontuberculous mycobacteria lung disease (NMLD) are very similar to those of tuberculosis (TB). Because most NTMs are resistant to conventional anti-TB drugs, the rapid diagnosis of NMLD is the key to treatment. This study aimed to use gene chip technology to examine bronchoalveolar lavage fluid (BALF) from NMLD patients to explore the value of this technique for the rapid diagnosis of NMLD in BALF. A retrospective analysis of 308 patients with NMLD treated at Fuzhou Pulmonary Hospital from January 2018 to June 2020 was performed. BALF was collected from the patients. Gene chip detection (Capital Bio Corporation, Chengdu, China) and BACTEC MGIT960 (Becton, Dickinson and Company, MD, USA) liquid culture were performed to compare the NTM positive detection rates between the two methods. The NTM strain isolated from liquid culture were identified by rDNA sequencing and the results of identification were compared with those of gene chip detection using BALF specimens. A total of 221 cases of NTM were detected in 308 BALF specimens by the gene chip method; the positive rate was 71.75% (221/308). A total of 218 cases of NTM were detected by the liquid culture method, and the positive rate was 70.78% (218/308). There was no significant difference in the positive rate of NTM detected in BALF specimens between the two methods (χ2=0.138 P=0.804>0.05); 187 cases were detected with both sequencing and gene chip detection, and the coincidence rate of strain identification with the two methods reached 96.79% (181/187). Sequencing of 218 strains of NTM was carried out; eight species were identified, and the top four species were M. intracellulare (131/218, 60.09%), M. avium (48/218, 22.02%), M. abscessus (27/218, 12.38%), and M. kansasii (5/218, 2.29%). Gene chip technology can rapidly detect NTM in BALF and accurately identify bacterial species. It has important clinical value in the early diagnosis and treatment of NMLD.

Validity of Diagnosis Code-Based Claims to Identify Pulmonary NTM Disease in Bronchiectasis Patients.

Nontuberculous mycobacteria infection is increasing in incidence and can lead to chronic, debilitating pulmonary disease. We investigated the accuracy of diagnosis code–based nontuberculous mycobacteria lung disease claims among Medicare beneficiaries in the United States. We observed that these claims have moderate validity, but given their low sensitivity, incidence might be underestimated.

1652. Diagnoses of Non- Tuberculosis Mycobacterium (NTM) in patients with granuloma on lung biopsy

BackgroundThe prevalence of non-Tuberculous mycobacteria (NTM) lung disease has increased from 8.7 to 13.9/100,000 from 2008-2013 making NTM lung disease a rising public health problem. Patterns of infection include fibrocavitary, bronchiectatic or nodular. Diagnosis of NTM may be incidental after surgical resection performed during malignancy work up. We aimed to identify the proportion of NTM in resected lung lesions (both nodules and masses) with granulomas (GL) both necrotizing (NGL) and non-necrotizing (n-NGL) on pathology and to compare differences in characteristics of patients with NTM versus those without NTM.MethodsThis was a retrospective chart review of patients who underwent resection of lung nodules and/or a lung mass during malignancy work up from January 2013 through March 2019 including only those with granulomatous inflammation on pathology. 497 patients met these criteria and their electronic medical records were reviewed. Findings of culture-confirmed NTM on tissue, bronchoalveolar lavage or sputum (at time of resection) were classified as “NTM” group; and those with no NTM diagnoses were classified as “Non-NTM” group. Patients with NTM and another diagnoses were classified within the NTM group. Study variables were compared by the dichotomous NTM group using Chi-square test for categorical variables and T-test for continuous variables.ResultsAmong all patients, the most common diagnosis was lung cancer (21.93%). There were 81 (16.3%) patients with NTM (Table 1). Within the NTM group, percentage of Asians, presence of NGL, placement on airborne precautions and prior history of tuberculosis were significantly higher. The NTM group also had a higher proportion of both COPD and lung cancer as their underlying condition (Table 2). 161 patients had non-diagnostic biopsies.Table 1 Table 2 Table 2 ConclusionMycobacterial infections made up a significant percentage of resected lung nodules and/or lung masses for malignancy evaluation. NTM were isolated with greater frequency than M. Tuberculosis even with NGL on lung pathology. This reflects the changing epidemiology of NTM. The significant proportion of Asians with NTM compared with GL found during a malignancy work up without NTM is interesting and deserves further investigation.Disclosures All Authors: No reported disclosures

PIN57 Burden of NON-Tuberculous Mycobacterial LUNG Disease (NTMLD) in France: A Claim Database Analysis

The objective of the study was to describe the epidemiology, management and cost of Non-tuberculous mycobacteria lung disease (NTMLD) in France. A retrospective analysis was performed using the SNIIRAM database over 2010-2017. NTMLD patients were identified based on the ICD10 codes during hospitalizations and/or specific antibiotics treatment regimens. The study population was matched (age, gender and region) to a control group (1: 3) without NTMLD. 5,628 NTMLD patients (men: 52.9%, mean age=60.9y) were identified. 1,433 patients (25.5%) were treated with antibiotics. The proportion of patients still treated at 6 and 12 months was 40% and 22%, respectively. NTMLD patients had more co-morbidities as compared to controls - the mean Charlson comorbidity index score was 1.6 (versus 0.2 for controls; p <0.0001). Risk factors comparisons between NTMPD cases and control group were statistically significant (p<0.0001): corticosteroids (57.3% vs 33.8%), Chronic lower respiratory diseases (34.4% vs 2.7%), other infectious pneumonia (24.4% vs 1.4%), malnutrition (22.0% vs 2.0%), tuberculosis (14.1% vs 0.1%), HIV (8.7% vs 0.2%), lung cancer and graft (5.7% vs 0.4%), cystic fibrosis (3.2% vs 0.0%), gastro-esophageal reflux disease (2.9% vs 0.9%) and bone marrow transplant (1.3% vs 0.0%). A higher 5-year mortality rate was observed in subjects with NTMLD: 19.7% versus 5.5% (p<0.0001, Log-Rank). Annual total expenses the year following the infection in a societal perspective were € 24,083 (SD: 29,358) in NTMLD subjects versus € 3,402 (SD: 8,575) in controls (p<0.0001). Main driver of the total expense for NTMLD patients was hospital expense (>50% of the total expense). NTMLD patients have high comorbidity burden, mortality and healthcare expenses. Only minority of patients get treated with antibiotics and many stop therapies before the infection can be successfully eradicated. These results underline the high burden associated with NTMLD and the need for appropriate management of this condition.

Macrophage Signaling Pathways in Pulmonary Nontuberculous Mycobacteria Infections.

The incidence and prevalence of nontuberculous mycobacteria (NTM) lung disease is rising worldwide and accounts for most clinical cases of NTM disease. NTM infections occur in both immunocompetent and immunocompromised hosts. Macrophages are the primary host cells that initiate an immune response to NTM. Defining the molecular events that govern the control of infection within macrophages is fundamental to understanding the pathogenesis of NTM disease. Here, we review key macrophage host signaling pathways that contribute to the host immune response to pulmonary NTM infections. In this review, we focus primarily on NTM that are known to cause lung disease, including Mycobacterium avium intracellulare, M. abscessus, and M. kansasii.

Antibiotic treatment for nontuberculous mycobacteria lung infection in people with cystic fibrosis.

Nontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous mycobacteria species (most commonly Mycobacterium avium complex and Mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 40% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is not clear which antibiotic regimen may be the most effective in the treatment of these individuals. This is an update of a previous review. The objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters, hospitalizations and use of oral antibiotics. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 24 February 2020. We also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date of last search: 21 March 2019. Any randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Data were not collected because in the one trial identified by the search, data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company. One completed trial was identified by the searches, but data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company. This review did not find any evidence for the effectiveness of different antimicrobial treatment for nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes available, it is reasonable for clinicians to follow published clinical practice guidelines for the diagnosis and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex or Mycobacterium abscessus in patients with cystic fibrosis.

Non-tuberculous mycobacterial lung disease in patients with bronchiectasis: perceived risk, severity and guideline adherence in a European physician survey

BackgroundPatients with bronchiectasis are at increased risk of developing non-tuberculous mycobacteria lung disease (NTM-LD), and published guidelines recommend regular testing for NTM infection in this patient population.ObjectiveThis study aimed to...

Real-life evaluation of clinical outcomes in patients undergoing treatment for non-tuberculous mycobacteria lung disease: A ten-year cohort study.

Outcome recognition is a crucial step in the management of non-tuberculous mycobacteria lung disease (NTM-LD). In order to explore NTM-LD outcomes in a real-life setting, an observational, retrospective study enrolling consecutive adults who received treatment for NTM-LD in Milan, Italy, from 2007 to 2017 was conducted. Among 170 patients (68.2% females; median age: 68 years), NTM-LD was mainly due to M. avium complex (MAC) (71.2%), M. kansasii (9.4%) and M. xenopi (7.1%). Along a median follow-up of 31 months, adverse events occurred in 37.6% of the patients. Treatment outcomes of the entire study population included an unsuccessful outcome in 35.3% of the patients, including treatment halted in 13.5%, recurrence in 11.2%, re-infection in 5.3%, treatment failure in 4.1% and relapse in 1.2%. The main reason for treatment halted was drug intolerance. No differences were detected between patients with MAC-LD vs. those with other NTM-LD in terms of unsuccessful outcome in general (35.5% vs. 34.7%). A significantly higher prevalence of patients who underwent treatment halted was found in patients with NTM-LD other than MAC in comparison to patients with MAC-LD (22.4% vs. 9.9%, p=0.030). One third of adults undergoing treatment for a NTM-LD experiences an unsuccessful outcome with adverse events and treatment discontinuation being major challenges in patients' management.

Diagnosis and treatment of nontuberculous mycobacteria lung disease

Diagnosis and treatment of nontuberculous mycobacteria lung disease

Changing epidemiology of nontuberculous mycobacterial lung disease over the last two decades in a region of the Basque country.

Recent studies suggest an increasing prevalence of nontuberculous mycobacteria (NTM) lung disease. The aim of the present study was to describe incidence rates of NTM lung disease and trends therein in our area over a 20-year period.This was a retrospective study of all cases of NTM lung disease between 1997 and 2016 that met the 2007 American Thoracic Society criteria. We analysed the annual incidence rates, species of mycobacteria isolated, trends over time and annual mortality in 327 patients.Mycobacterium kansasii was the most common mycobacterium isolated (84%), followed by Mycobacterium avium complex (MAC) (13%). We compared two periods: 1997–2006 (257 cases, 79%) and 2007–2016 (70 cases, 21%). The incidence rates tended to decrease across these years, with a peak of incidence in 2000 with 10.6 cases per 100 000. There was a clearly decreasing trend in M. kansasii infection, not only in the first period (incident rate ratio (IRR) 0.915, 95% CI 0.88–0.90; p<0.0001) but also in the second (IRR 0.869, 95% CI 0.780–1.014; p=0.080), reaching 1.8 per 100 000 in 2016. In contrast, MAC infection tended to increase across the two periods (IRR 1.251, 95% CI 1.081–1.447; p=0.003).In our region, the incidence of NTM lung disease has notably decreased in recent years. M. kansasii had high incidence rates in the first decade but clearly decreased in the second decade.

NLRP3 inflammasome is attenuated in patients with Mycobacterium avium complex lung disease and correlated with decreased interleukin-1\u03b2 response and host susceptibility

The incidence of nontuberculous mycobacteria lung disease (NTM-LD) is increasing in patients without human immunodeficiency virus. Mycobacterium avium complex (MAC) is one of the most common pathogenic species. The presence of MAC has a clinical relevance of around 35~42%, indicating the possibility of host susceptibility. Previous studies have shown that interleukin (IL)-1β and IL-1-receptor knock-out mice are susceptible to mycobacterial infections; however, the role of inflammasome-driven interleukin (IL)-1β has not been studied in MAC-LD. We enrolled patients with MAC-LD and healthy controls. Peripheral blood mononuclear cells (PBMCs), monocytes, and monocyte-derived macrophages were stimulated by MAC bacilli. The responses of interleukin(IL)-1β and the expression of inflammasome and toll-like receptors (TLRs) were measured. Single nucleotide polymorphisms (SNPs) were also examined for NLRP3 and TLR2 genes. In the patients with MAC-LD, the IL-1β responses decreased in PBMCs, monocytes, and macrophages assayed by MAC bacilli in comparison to the healthy controls. In addition, the level of caspase-1 after stimulation was lower in the MAC-LD group, although the mRNA level of IL-1β was not significantly lower. In surveying the activation of IL-1β, the MAC-LD group had an attenuated mRNA level of NLRP3 but similar levels of AIM2 and ASC compared with the controls. The SNPs rs3806268 and rs34298354 in NLRP3 for females and rs3804100 in TLR2 for males were associated with MAC-LD. In conclusion, our patients with MAC-LD had attenuated IL-1β production, which may have been due to lower activation of the NLRP3-caspase-1 axis. Two SNPs of NLRP3 and one of TLR2 were correlated with MAC-LD, possibly indicating host susceptibility.