Nontuberculous Mycobacterial Pulmonary Disease Research Articles

Immunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection.

Nontuberculous mycobacteria (NTM) are emerging as pathogens of high consequence, as cases of NTM pulmonary disease (NTMPD) have exceeded those of Mycobacterium tuberculosis. NTMPD can be debilitating, particularly in patients over 65 years of age, as it causes chronic cough and fatigue requiring prolonged treatments with antibiotics. The underlying mechanisms of this increased disease severity with age are poorly understood, hampering the development of therapeutics and vaccines. Here, we use a rhesus macaque model to investigate the impact of age on host-NTM interactions. This work shows that aging is associated with increased disease severity and bacterial persistence in aged rhesus macaques, thus providing a preclinical model to develop and test novel therapeutics and interventions.

Comparison of the sputum microbiome between patients with stable nontuberculous mycobacterial pulmonary disease and patients requiring treatment.

We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics. We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups. In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013). Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.

Exploring the Association of Bacterial Coinfections with Clinical Characteristics of Patients with Nontuberculous Mycobacterial Pulmonary Disease.

Clinical data for bacterial coinfection of the lower respiratory tract in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) are scarce. This study aims to assess the prevalence of bacterial coinfection and clinical features in NTM-PD patients. This retrospective study screened 248 patients with NTM-PD who underwent bronchoscopy between July 2020 and July 2022, from whom newly diagnosed NTM-PD patients were analyzed. Bacterial culture using bronchial washing fluid was performed at the time of NTM-PD diagnosis. In the 180 patients (median age 65 years; 68% female), Mycobacterium avium complex (86%) was the most frequent NTM isolated. Bacterial coinfections were detected in 80 (44%) patients. Among them, the most common bacterium was Klebsiella pneumoniae (n=25/80, 31.3%), followed by Pseudomonas aeruginosa (n=20/80, 25%) and Staphylococcus aureus (n=20/80, 25%). Compared with NTM-PD patients without bacterial coinfections, patients with bacterial coinfections showed more frequent extensive lung involvement (33% vs. 1%, p<0.001). Additionally, compared with NTM-PD patients without P. aeruginosa infection, those with P. aeruginosa infection were older (74 years vs. 64 years, p=0.001), had more frequent respiratory symptoms (cough/excessive mucus production 70% vs. 38%, p=0.008; dyspnea 30% vs. 13%, p=0.047), and had extensive lung involvement (60% vs. 9%, p<0.001). Less than half of patients with newly diagnosed NTM-PD had bacterial coinfections, linked to extensive lung involvement. Specifically, P. aeruginosa coinfection was significantly associated with older age, more frequent respiratory symptoms, and extensive lung involvement.

The diagnostic impact of fractional exhaled nitric oxide for asthmatic cough in nontuberculous mycobacterial pulmonary disease.

Measurement of exhaled nitric oxide (FeNO) is a potentially useful diagnostic test for asthma. However, no study has explored the relationship between FeNO and respiratory symptoms of nontuberculous mycobacterial pulmonary disease (NTM-PD) complicated with asthma. The objective of this study was to assess the utility of measuring FeNO levels in patients with NTM-PD complicated by asthma. In this single-center retrospective cohort study, 140 NTM-PD patients with FeNO measured were enrolled. We selected NTM-PD patients who complicated with asthma as the NTM+BA group, defined using the following criteria: NTM patients with symptoms consistent with asthma, and NTM patients with symptomatic improvement after diagnostic therapy with ICS ± a long-acting beta 2-agonist (LABA). We then calculated a diagnostic cutoff point to distinguish between the NTM+BA groups and the NTM groups (all others). High-resolution computed tomography (HRCT) images were evaluated using the CT scoring system and their association with FeNO was examined. A total of 89 patients were included in the study. (31 in the NTM+BA group and 58 in the NTM group). Compared with the NTM group, the NTM+BA group had higher rates of allergic disease (51.6% vs. 22.4%; p=0.0085) and higher FeNO values (median, 23 [interquartile range {IQR}, 15.0-43.0] ppb vs. median, 17 [IQR, 11.8-23.0] ppb; p=0.015). With diagnostic asthma care using mainly ICS/LABA with reference to the FeNO, most patients (91.0%, 20/22) in the NTM-preceding subgroup in the NTM+BA group demonstrated a prompt improvement of their symptoms and AFB culture findings did not worsen (Culture positive rate (%): Pre-treatment: 59.1% vs. Post-treatment: 40.9%, p=0.3660) at 6 months after starting diagnostic therapy. The optimal diagnostic cutoff point of FeNO to distinguish between the two groups was calculated as 21.5 ppb by the ROC curve (sensitivity 75%, specificity 71.93%, p<0.0001; area under the curve: 0.7989). No significant correlation was observed between FeNO and the severity of CT images in the patients. A certain number of patients with NTM-PD showed exacerbated respiratory symptoms due to asthmatic complications. Elevated FeNO levels suggest asthma complications, even in patients with NTM.

Nonpharmacological Treatment for Nontuberculous Mycobacterial Pulmonary Disease.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) results from the exposure of susceptible hosts to a diverse group of environmental mycobacteria. The emphasis on nonpharmacological strategies is motivated by the widespread presence of NTM in various environments, and the inconsistent success rates of pharmacological treatments. Modifiable factors contributing to NTM-PD development include impaired airway clearance, low body mass index, gastroesophageal reflux disease, and exposure to NTM habitats. This suggests that lifestyle and environmental modifications could affect disease development and progression. The review highlights several modalities that can modify the risk factors. Airway clearance techniques, informed by the "gel-on-brush" model of the bronchial epithelium, aim to enhance mucociliary clearance, and have the potential to alleviate symptoms and improve lung function. The impact of nutritional status is also examined, with a lower body mass index linked to an increased risk and progression of NTM-PD, indicating the importance of targeted nutritional support. Additionally, the theoretical and epidemiological links between gastroesophageal reflux disease and NTM-PD advocate careful management of reflux episodes. Understanding the risk of NTM transmission through environmental exposure to contaminated water and soil is also crucial. Strategies to mitigate this risk, including effective water management and minimizing soil contact, are presented as vital preventive measures. The review supports the inclusion of nonpharmacological treatments within a comprehensive NTM-PD management strategy, alongside conventional pharmacological therapies. This integrated approach seeks to improve the overall understanding and handling of NTM-PD.

Is there a role for lung or bronchial biopsies for the diagnosis of mycobacterial pulmonary disease in patients with bronchiectasis?

BackgroundWorkup of bronchiectasis patients mandates microbiological characterization often being sought via Bronchoscopy. However, whether to perform bronchial or lung biopsies, is unknown, especially for the diagnosis of NTM pulmonary disease. We aimed to assess the current practice and yield of the different bronchoscopic procedures in this setting. MethodsData from an adult cohort with bronchiectasis referred for bronchoscopy for microbiologic sampling was reviewed, including demographics, etiology, imaging and results of the different bronchoscopic procedures performed. Results127 subjects were analyzed (mean age 61, 56% female). BAL culture was positive in 44%. Frequent pathogens were Hemophilus Influenza (20%), pseudomonas aeruginosa (8%) and Staphylococcus aureus (7%). NTM and tuberculosis were found in 6% and 1.5% respectively. BAL cytology was sent in 125 procedures, EBB was performed in 51 patients (40%) and TBLB in 38 patients (30%). BAL cytology and both EBB and TBB (including tissue cultures) had no benefit over BAL with respect to microbiological diagnosis, including identification of mycobacterial disease. ConclusionsIn adult subjects with Non-CF bronchiectasis requiring bronchoscopy for microbiological characterization, BAL cytology and lung tissue biopsies were frequently performed but were of minimal additional benefit over BAL culture (including for mycobacterial pulmonary disease), and are most likely futile.

Time to diagnosis of nontuberculous mycobacterial pulmonary disease and longitudinal changes on CT before diagnosis

BackgroundThe healthcare burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, but the diagnosis remains challenging and sometimes requires considerable time. This nested case-control study aims to clarify the time to diagnosis of NTM-PD, the factors that affect diagnosis and diagnostic delay, and changes in CT findings before diagnosis. Patients and methodsWe retrospectively analyzed 187 patients suspected of having NTM-PD based on computed tomography (CT) findings at our institution between January 2019 and September 2020. We investigated the time to diagnosis of NTM-PD for all suspected and diagnosed patients. Multivariate analyses identified the factors affecting diagnosis and diagnostic delay over 6 months. We also evaluated longitudinal changes in CT findings during the observation period using CT scoring system. ResultsThe median times to diagnosis of NTM-PD were 71.8 months in all suspected patients and 3.2 months in only the diagnosed patients. Multivariable analysis showed that severity of the cavity domain of the CT score and anti-glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody positivity were significantly associated with establishing the diagnosis. A low CT score in the cavity domain was a risk factor for delayed diagnosis. In patients with delayed diagnosis, the total CT score was less severe than that in the early diagnosis patients at their first visits; however, it had deteriorated prior to the diagnosis. ConclusionThe diagnosis of NTM-PD sometimes required several years, and the absence or mild cavitation predicted a diagnostic delay. Of concern, a delay in diagnosis can result in a delay in treatment.

Patients at risk of nontuberculous mycobacterial pulmonary disease who need testing evaluated using a modified Delphi process by European experts

BackgroundIdentifying patients at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) is challenging. Delays in NTM-PD identification and management are associated with declining lung function and increased morbidity and mortality.Study design and methodsEuropean NTM-PD experts (n=12) participated in a three-round modified Delphi process to score symptoms and comorbidities potentially associated with NTM-PD as reasons to test for nontuberculous mycobacteria.ResultsExperts reached a consensus on the symptoms and comorbidities that should and should not prompt testing for nontuberculous mycobacteria. Requirements for testing were scored as high (mean ≥7), medium (mean ≥4–&lt;7) or low (mean &lt;4). Nontuberculous mycobacteria testing should be undertaken when multiple suggestive symptoms are present simultaneously in all patients except those with cancer (7.3–8.8), or when radiology is indicative of NTM-PD (≥8.9). Symptoms of persistent sputum production, recurrent respiratory infection and haemoptysis should prompt testing for nontuberculous mycobacteria, particularly in those with underlying respiratory diseases. Symptomatic patients with bronchiectasis or previous tuberculosis/NTM-PD or those being prescribed or undergoing long-term macrolide therapy for a respiratory condition should also be tested. Testing is not warranted in patients without an underlying respiratory disorder or in those without a history of respiratory disorders unless presenting with multiple symptoms.ConclusionsAssessing patients’ risk of NTM-PD is challenging. This Delphi consensus process provides insight into symptoms and clinical characteristics that should prompt NTM-PD assessment. Timely testing and diagnosis would enable initiation of appropriate management.

Epidemiological Characteristics of Nontuberculous Mycobacterial Pulmonary Disease in South Korea: A Meta-analysis of Individual Participant Data.

Despite the global increase in nontuberculous mycobacterial pulmonary disease (NTM-PD), clinical characteristics show geographical variations. We investigated the clinical characteristics of patients with NTM-PD in South Korea. We systematically reviewed articles concerning patients with NTM-PD in South Korea until February 2022. Individual participant data, regardless of treatment, were collected using a standard case report form. Data of 6,489 patients from 11 hospitals between 2002 and 2019 were analyzed. The mean age was 61.5±11.7 years, of whom 57.7% were women. Mycobacterium avium (41.4%) and Mycobacterium intracellulare (38.4%) comprised most of the causative species, followed by Mycobacterium abscessus subspecies abscessus (8.6%) and M. abscessus subspecies massiliense (7.8%). Bronchiectasis (59.4%) was the most common pulmonary comorbidity. Although reported cases of NTM-PD increased over the years, the proportions of causative species and radiologic forms remained similar. Distinct clinical characteristics were observed according to age and sex. Men were older at the time of diagnosis (median 63.8 years vs. 59.9 years, p&lt;0.001), and had more cavitary lesions than women (38.8% vs. 21.0%, p&lt;0.001). The older group (≥65 years) had higher proportions of patients with body mass index &lt;18.5 kg/m2 (27.4% vs. 18.6%, p&lt;0.001) and cavitary lesions (29.9% vs. 27.6%, p=0.009) than the younger group. We conducted a meta-analysis of the clinical characteristics of patients with NTM-PD in South Korea, and found age- and sex-related differences in disease- specific severity. Further investigation would enhance our comprehension of the nature of the disease, and inherited and acquired host factors.

Beyond Symptoms: Radiologic identification of asymptomatic Mycobacterium avium complex pulmonary infections

BackgroundAlthough international nontuberculous mycobacterial pulmonary disease (NTM-PD) guidelines highlight symptom presence at diagnosis, the clinical characteristics of asymptomatic Mycobacterium avium complex pulmonary infection (MAC-PI) patients remain understudied. We clarified the clinical characteristics and course of asymptomatic MAC-PI patients. MethodsWe retrospectively analyzed 200 consecutive patients with MAC-PIs and adequate available data who newly met the microbiological and radiological criteria for NTM-PD at Fukujuji Hospital from January 2018 to June 2020. We compared the clinical characteristics and course of asymptomatic patients with symptomatic patients and evaluated factors influencing treatment initiation through multivariate analysis. Results111 patients were symptomatic and 89 were asymptomatic at diagnosis. While the proportion was significantly lower than that in the symptomatic group (28.8 %), 15.7 % of asymptomatic group patients had cavitary lesions (P = 0.042). In the asymptomatic group, treatments were initiated in 38 (42.7 %) patients, and cavitary lesions, a positive acid-fast bacilli smear, and younger age were independent risk factors for treatment initiation. Among 22 (57.9 %) patients who experienced disease progression necessitating treatment during follow-up, 13 (34.2 %) displayed radiological progression without any worsening of symptoms. Agents used for treatment were consistent across the groups, with no significant differences in culture conversion, microbiological recurrence rates, or spontaneous culture conversion rates. ConclusionRoutine health checkups and radiological examinations can detect clinically important MAC-PIs even in the absence of symptoms. Considering that the clinical course of asymptomatic MAC-PI patients is largely similar to that of symptomatic patients, timely and appropriate management and intervention are essential for all MAC-PI patients.

Improvement in Health-Related Quality of Life Following Antibiotic Treatment in Nontuberculous Mycobacterial Pulmonary Disease: Initial Analysis of the NTM-KOREA Cohort.

Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. ClinicalTrials.gov identifier: NCT03934034.

Efficacy of SPR720 in murine models of non-tuberculous mycobacterial pulmonary infection.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide, with Mycobacterium avium complex (MAC) and Mycobacterium abscessus as the predominant pathogens. Current treatments are poorly tolerated and modestly effective, highlighting the need for new treatments. SPR719, the active moiety of the benzimidazole prodrug SPR720, inhibits the ATPase subunits of DNA gyrase B, a target not exploited by current antibiotics, and therefore, no cross-resistance is expected with standard-of-care (SOC) agents. To evaluate the in vitro activity of SPR719 against MAC and M. abscessus clinical isolates, including those resistant to SOC agents, and in vivo efficacy of SPR720 in murine non-tuberculous mycobacteria (NTM) pulmonary infection models. NTM isolates were tested for susceptibility to SPR719. Chronic C3HeB/FeJ and severe combined immunodeficient murine models of pulmonary infection were used to assess efficacy of SPR720 against MAC and M. abscessus, respectively. SPR719 was active against MAC (MIC90, 2 mg/L) and M. abscessus (MIC90, 4 mg/L) clinical isolates. Efficacy of SPR720 was demonstrated against MAC pulmonary infection, both as a monotherapy and in combination with SOC agents. SPR720 monotherapy exhibited dose-dependent reduction in bacterial burden, with the largest reduction observed when combined with clarithromycin and ethambutol. Efficacy of SPR720 was also demonstrated against M. abscessus pulmonary infection where monotherapy exhibited a dose-dependent reduction in bacterial burden with further reductions detected when combined with SOC agents. In vitro activity of SPR720 against common NTM pathogens and efficacy in murine infections warrant the continued clinical evaluation of SPR720 as a new oral option for the treatment of NTM-PD.

Adjuvant surgical resection for nontuberculous mycobacterial pulmonary disease: Effectiveness and complications.

Standard antibiotic treatment for nontuberculous mycobacteria pulmonary disease (NTMPD) has unsatisfactory success rates. Pulmonary resection is considered adjunctive therapy for patients with refractory disease or severe complications, but surgical indications and extent of resection remain unclear. We present surgical treatment outcomes for NTMPD and analyzes risk factors for unfavorable outcomes. We conducted a retrospective investigation of medical records for patients diagnosed with NTMPD who underwent surgical treatment at Asan Medical Center between 2007 and 2021. We analyzed clinical data including microbiological and surgical outcomes. A total of 71 NTMPD patients underwent thoracic surgery. Negative conversion of acid-fast bacillus (AFB) culture following pulmonary resection was observed in 51 (73.9%) patients. In terms of long-term outcomes, negative conversion was sustained in 38 cases (55.1%). Mortality occurred in 7 patients who underwent pulmonary resections for NTMPD. Statistically significant associations with factors for recurrence or non-negative conversion of AFB culture were found in older age (odds ratio [OR] =1.093, 95% confidence interval [CI]: 1.029-1.161, P = 0.004), male sex (OR = 0.251, 95% CI: 0.071-0.892, P = 0.033), and extensive NTMPD lesions involving three lobes or more (OR = 5.362, 95% CI: 1.315-21.857, P = 0.019). Interstitial lung disease (OR = 13.111, 95% CI: 1.554-110.585, P = 0.018) and pneumonectomy (OR = 19.667, 95% CI: 2.017-191.797, P = 0.018) were statistically significant risk factors for postoperative mortality. Pulmonary resection can be an effective adjuvant treatment option for NTMPD patients, with post-operative antibiotic treatment as the primary treatment. Careful patient selection is crucial, considering the associated risk factors and resectability due to complications and recurrence.

Nontuberculous Mycobacteria, Mucociliary Clearance, and Bronchiectasis.

Nontuberculous mycobacteria (NTM) are environmental and ubiquitous, but only a few species are associated with disease, often presented as nodular/bronchiectatic or cavitary pulmonary forms. Bronchiectasis, airways dilatations characterized by chronic productive cough, is the main presentation of NTM pulmonary disease. The current Cole's vicious circle model for bronchiectasis proposes that it progresses from a damaging insult, such as pneumonia, that affects the respiratory epithelium and compromises mucociliary clearance mechanisms, allowing microorganisms to colonize the airways. An important bronchiectasis risk factor is primary ciliary dyskinesia, but other ciliopathies, such as those associated with connective tissue diseases, also seem to facilitate bronchiectasis, as may occur in Lady Windermere syndrome, caused by M. avium infection. Inhaled NTM may become part of the lung microbiome. If the dose is too large, they may grow excessively as a biofilm and lead to disease. The incidence of NTM pulmonary disease has increased in the last two decades, which may have influenced the parallel increase in bronchiectasis incidence. We propose that ciliary dyskinesia is the main promoter of bronchiectasis, and that the bacteria most frequently involved are NTM. Restoration of ciliary function and impairment of mycobacterial biofilm formation may provide effective therapeutic alternatives to antibiotics.

The additional value of 18F-FDG PET/CT imaging in guiding the treatment strategy of non-tuberculous mycobacterial patients

ObjectivesNon-tuberculous mycobacteria (NTM) infection is an increasing health problem due to delaying an effective treatment. However, there are few data on 18F-FDG PET/CT for evaluating the status of NTM patients. The aim of this study was to investigate the potential value of 18F-FDG PET/CT in guiding the treatment strategy of NTM patients.MethodsWe retrospectively analyzed the cases of 23 NTM patients who underwent 18F-FDG PET/CT. The clinical data, including immune status and severity of NTM pulmonary disease (NTM-PD), were reviewed. The metabolic parameters of 18F-FDG included maximum standardized uptake value (SUVmax), SUVmax of the most FDG-avid lesion (SUVTop), SUVTop/SUVmax of the liver (SURLiver), SUVTop/SUVmax of the blood (SURBlood), metabolic lesion volume (MLV), and total lesion glycolysis (TLG). The optimal cut-off values of these parameters were determined using receiver operating characteristic curves.ResultsThere were 6 patients (26.09%) with localized pulmonary diseases and 17 patients (73.91%) with disseminated diseases. The NTM lesions had high or moderate 18F-FDG uptake (median SUVTop: 8.2 ± 5.7). As for immune status, the median SUVTop in immunocompromised and immunocompetent patients were 5.2 ± 2.5 and 10.0 ± 6.4, respectively, with a significant difference (P = 0.038). As for extent of lesion involvement, SURLiver and SURBlood in localized pulmonary and disseminated diseases were 1.9 ± 1.1 vs. 3.8 ± 1.6, and 2.7 ± 1.8 vs. 5.5 ± 2.6, respectively, with a significant difference (P = 0.016 and 0.026). Moreover, for disease severity, SUVmax of the lung lesion (SUVI−lung) and SUVmax of the marrow (SUVMarrow) in the severe group were 7.7 ± 4.3 and 4.4 ± 2.7, respectively, significantly higher than those in the non-severe group (4.4 ± 2.0 and 2.4 ± 0.8, respectively) (P = 0.027 and 0.036). The ROC curves showed that SUVTop, SURLiver, SURBlood, SUVI−lung, and SUVMarrow had a high sensitivity and specificity for the identification of immune status, lesion extent, and severity of disease in NTM patients.Conclusion18F-FDG PET/CT is a useful tool in the diagnosis, evaluation of disease activity, immune status, and extent of lesion involvement in NTM patients, and can contribute to planning the appropriate treatment for NTM.

Rates and Risk Factors of Progression in Patients With Nontuberculous Mycobacterial Pulmonary Disease: Secondary Analysis of a Prospective Cohort Study

BackgroundThe clinical course of nontuberculous mycobacterial pulmonary disease (NTM-PD) is varied, and a watchful waiting management strategy is appropriate for a subset of patients. Understanding disease progression and risk factors for progression is essential for deciding on an appropriate follow-up strategy. Research QuestionWhat is the rate of NTM-PD progression, and what are the predictors of progression? Study Design and MethodsPatients with NTM-PD who were enrolled in a prospective observational cohort study between July 1, 2011, and December 31, 2022 were included in this analysis. Clinical, bacterial, laboratory, and radiographic data were collected at enrollment and then regularly during follow-up. NTM-PD progression was defined as either the initiation of treatment or the clinician’s intention to treat. The rate of progression was calculated and the predictors for progression were analyzed. ResultsOf the 477 patients enrolled, NTM-PD progressed in 192 patients over a median follow-up of 5.4 years. The incidence of NTM-PD progression was 11.0 cases per 100 person-years (95% confidence interval [CI] 9.5–12.7). The proportion of patients experiencing disease progression was 21.4% at 1 year, 33.8% at 3 years, and 43.3% at 5 years. The final multivariable analysis model identified female sex (adjusted hazard ratio [aHR] 1.69, 95% CI 1.19–2.39), elevated erythrocyte sedimentation rate (aHR 1.79, 95% CI 1.31–2.43), percent predicted forced expiratory volume in 1 second (aHR 0.89, 95% CI 0.82–0.96), and the presence of a cavity (aHR 2.78, 95% CI 2.03–3.80) as predictors of progression. InterpretationAbout half of patients with NTM-PD experienced progression during an observation period of more than 5 years. Patients with risk factors for progression should be observed closely. Trial registrationClinicalTrials.gov; No.: NCT01616745; URL: www.clinicaltrials.gov

Nationwide Increasing Incidence of Nontuberculous Mycobacterial Diseases Among Adults in Denmark: Eighteen Years of Follow-Up

BackgroundThe epidemiology of nontuberculous mycobacteria (NTM) infections is not well described. In this study, we determined the incidence and prevalence of NTM infections and focused on social risk factors. Additionally, we described persons suffering from pulmonary and extrapulmonary NTM. Research questionWhat is the incidence and prevalence of NTM and what are the characteristics of the affected patients? MethodsThis is a nationwide retrospective register-based cohort study in Denmark. Adult patients with NTM diagnosis in the Danish national registers from 2000-2017 were classified as having either pulmonary or extrapulmonary NTM disease. ResultsWe identified 1,146 adults with an NTM diagnosis. 661 patients had pulmonary NTM of which 50.4% were male, while 485 had extrapulmonary NTM of which 59.6% were male. The median age (Interquartile range), was 66 years (18) and 57 years (32), respectively. The yearly incidence rate per 100,000 increased between 2000 and 2017 for both pulmonary (0.4 to 1.3) and extrapulmonary NTM (0.3 to 0.6). The annual prevalence per 100,000 increased from 0.4 to 3.5 for pulmonary and 0.3 to 1.0 for extrapulmonary NTM. The incidence rate increased with age. The incidence of pulmonary NTM was highest in 70+ year-olds (19.3 per 100,000). Compared to pulmonary NTM patients, extrapulmonary NTM patients were more likely to be employed and had a higher educational level. InterpretationThe prevalence of NTM disease in Denmark increased between 2000 and 2017. Pulmonary and extrapulmonary NTM patients are two distinct groups that differ in age, gender, education, and employment status. Increased suspicion of pulmonary NTM disease is warranted in the elderly after exclusion of more common lung infections.

Clinical course of nontuberculous mycobacterial pulmonary disease in patients with rheumatoid arthritis

ObjectivesThe impact of rheumatoid arthritis (RA) on nontuberculous mycobacterial pulmonary disease (NTM-PD) has not been well established. In this study, we investigated the clinical course of NTM-PD in patients with RA and the impact of RA on the prognosis of NTM-PD.MethodsWe analyzed patients who developed NTM-PD after being diagnosed with RA from January 2004 to August 2023 at a tertiary referral hospital in South Korea. The patient’s baseline characteristics, clinical course, and prognosis were evaluated. An optimal matching analysis was performed to measure the impact of RA on the risk of mortality.ResultsDuring the study period, 18 patients with RA [median age, 68 years; interquartile range (IQR) 59–73; female, 88.9%] developed NTM-PD. The median interval between RA diagnosis and subsequent NTM-PD development was 14.8 years (IQR, 8.6–19.5). At a median of 30 months (IQR, 27–105) after NTM-PD diagnosis, 10 of 18 (55.6%) patients received anti-mycobacterial treatment for NTM-PD and 5 (50.0%) patients achieved microbiological cure. When matched to patients with NTM-PD but without RA, patients with both RA and NTM-PD had a higher risk of mortality (adjusted hazard ratio, 8.14; 95% confidence interval, 2.43–27.2).ConclusionNTM-PD occurring after RA is associated with a higher risk of mortality than NTM-PD in the absence of RA.

Nontuberculous mycobacterial pulmonary disease added burden to COPD and bronchiectasis in Japan.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) prevalence in Japan is among the highest worldwide. COPD and bronchiectasis are common comorbidities among patients with NTM-PD, and it is challenging to treat NTM-PD in patients with these conditions. There are limited data on the incremental burden that NTM-PD adds to underlying COPD or bronchiectasis in Japan. Therefore, the objective of this study was to assess the incremental burden associated with NTM-PD in patients with pre-existing COPD and/or bronchiectasis. This nested case-control study was based on JMDC, Inc. claims data (2015-2020). Patients with COPD and/or bronchiectasis with NTM-PD (cases) were age and sex matched 1:3 to patients with COPD and/or bronchiectasis without NTM-PD (controls), resulting in three mutually exclusive patient groups (COPD, bronchiectasis or both; with or without NTM-PD). Incremental burden of NTM-PD was assessed within each group by comparing hospitalisations during the 1-year period after NTM-PD diagnosis (index) between cases and controls with both univariate analysis and multivariate analysis adjusting for pre-index comorbidities. Univariate analyses in the three patient groups consistently demonstrated incremental hospitalisation burden in cases versus controls (e.g. COPD group: 20% of 492 cases versus 13% of 1476 controls had all-cause hospitalisations; 11% versus 5% had respiratory-related hospitalisations; and 6% versus 2% had COPD-related hospitalisations). Subsequent multivariate analysis further confirmed the findings. The substantial incremental burden of hospitalisation associated with NTM-PD in patients with COPD and/or bronchiectasis highlights the urgent need for appropriate management of NTM-PD in Japan.

Integrating Paper-Based Microfluidics and Lateral Flow Strip into Nucleic Acid Amplification Device toward Rapid, Low-Cost, and Visual Diagnosis of Multiple Mycobacteria.

Efficient diagnosis of mycobacterial infections can effectively manage and prevent the transmission of infectiousdiseases. Unfortunately, existing diagnostic strategies are challenged by long assay times, high costs, and highly specialized expertise to distinguish between pulmonary tuberculosis (PTB) and nontuberculous mycobacterial pulmonary diseases (NTM-PDs). Herein, in this study, an optimized 3D paper-based analytical device (µPAD) is incorporated with a closed lateral flow (LF) strip into a loop-mediated isothermal amplification (LAMP)device (3D-µPAD-LF-LAMP) for rapid, low-cost, and visual detection of pathogenic mycobacteria. The platform's microfluidic featureenhanced the nucleic acid amplification, thereby reducing the costs and time as compared to boiling, easyMAG, and QIAGEN techniques. Moreover, the LF unitis specifically designed to minimize aerosol contamination for a user-friendly and visual readout. 3D-µPAD-LF-LAMP is optimized and assessed using standard strains, demonstrating a limit of detection (LOD) down to 10 fgreaction-1 . In a cohort of 815 patients, 3D-µPAD-LF-LAMP displays significantly better sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy than conventional bacterial culture and Xpert techniques. Collectively, 3D-µPAD-LF-LAMP demonstrates enhanced accessibility, efficiency, and practicality for the diagnosis of multiple pathogenic mycobacteria, which can be applied across diverse clinical settings, thereby ultimately improving public health outcomes.