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Multicenter, longitudinal studies on nontuberculous mycobacteria (NTM) pulmonary infection (PI) are lacking. This study provides a 5-year epidemiological overview of NTM-PI in Taiwan and investigated its predictors. The clinical relevance of each respiratory NTM isolate in six hospitals between 2008 and 2014 was determined according to current guidelines. Recurrent episodes were judged by serial bacteriological results. New episodes of NTM-PI and pulmonary colonization (PC) occurring since 2010 were analyzed. Logistic regression analysis was performed to identify the predictors of NTM-PI. Between 2010 and 2014, the incidence rate of NTM-PI was 46.0 episodes per 100,000 hospital-based patient-years. Mycobacterium avium intracellulare complex (MAC) was predominant in Northern Taiwan, whereas MAC and M. abscessus were copredominant in Southern Taiwan. Multiple episodes occurred in 9.5% of NTM-PI patients. No female predominance was observed, except for MAC-PI. Previous pulmonary tuberculosis and chronic obstructive pulmonary disease (COPD) were the most common pulmonary comorbidities and independent risk factors for NTM-PI. Other risk factors included M. kansasii , M. abscessus , and southern Taiwan. Geographical variation of NTM-PI exists in Taiwan. Clinicians should keep a high suspicion on NTM-PI in the risk population. In endemic area of tuberculosis and COPD, there may be no female predominance in NTM-PI.

Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. It has been suggested as an important risk factor of chronic obstructive pulmonary disease (COPD), which is also a major cause of morbidity and mortality. This study investigated the impact of pulmonary TB and anti-TB treatment on the risk of developing COPD. This cohort study used the National Health Insurance Database of Taiwan, particularly the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB cases and 15,880 control subjects matched in age, sex, and timing of entering the database. Hazard ratios of potential risk factors of COPD, especially pulmonary TB and anti-TB treatment. The mean age of pulmonary TB cases was 51.9±19.2. The interval between the initial study date and commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8±65.4 days. Independent risk factors for developing COPD were age, male, low income, and history of pulmonary TB (hazard ratio 2.054 [1.768-2.387]), while diabetes mellitus was protective. The impact of TB persisted for six years after TB diagnosis and was significant in women and subjects aged >70 years. Among TB patients, delay in anti-TB treatment had a dose-response relationship with the risk of developing COPD. Some cases of COPD may be preventable by controlling the TB epidemic, early TB diagnosis, and prompt initiation of appropriate anti-TB treatment. Follow-up care and early intervention for COPD may be necessary for treated TB patients.

Background and objective Studies focusing on pulmonary tuberculosis in advanced age (≥80 years) are lacking. This study aimed to explore treatment delay, outcomes and their predictors in this group. Methods Adult (≥20 years) patients with pulmonary tuberculosis were identified from the National Health Insurance Research Database of Taiwan from 2004 to 2009. Treatment completion and mortality rates were noted at one year after treatment. Results Among the 81,081 patients with pulmonary tuberculosis identified, 13,923 (17.2%) were aged ≥80 years, and 26,897 (33.2%) were aged 65–79 years. The treatment completion, mortality rates and treatment delay were 54.8%, 34.7% and 61 (12–128) [median, (1st-3rd quartiles)] days in patients aged ≥80 years, 68.3%, 18.5% and 53 (8–122) days in patients aged 65–79 years, and 78.9%, 6.5% and 21 (1–84) days in patients aged <65 years, respectively. The elder patients were more likely to receive second-line anti-tuberculosis agents. The treatment completion rate decreased with older age, female sex, comorbidities, low income, requiring second-line anti-tuberculosis agents, severity of pulmonary tuberculosis and longer treatment delay. Older age, female sex, comorbidities, low income, and not undergoing rapid molecular diagnostic tests were independently associated with longer treatment delays. Conclusions Pulmonary tuberculosis in advanced age has a longer treatment delay and a higher mortality rate. Applying rapid molecular diagnostic tools may reduce treatment delay and should be integrated into the diagnostic algorithm for pulmonary tuberculosis, particularly in elderly patients.

Idiopathic pulmonary fibrosis (IPF) has been associated with mitochondrial dysfunction. We investigated whether mitochondrial DNA variants in peripheral blood leukocytes (PBLs), which affect proteins of the respiratory chain and mitochondrial function, could be associated with an increased risk and poor prognosis of IPF. From 2020 to 2022, we recruited 36 patients (age: 75.3 ± 8.5; female: 19%) with IPF, and 80 control subjects (age: 72.3 ± 9.0; female: 27%). The mitochondrial genome of peripheral blood leukocytes was determined using next-generation sequencing. During a 45-month follow-up, 10 (28%) patients with IPF remained stable and the other 26 (72%) progressed, with 12 (33%) mortalities. IPF patients had more non-synonymous (NS) variants (substitution/deletion/insertion) in mitochondrial COX3 gene (coding for subunit 3 of complex IV of the respiratory chain), and more mitochondrial tRNA variants located in the anticodon (AC) stem, AC loop, variable loop, T-arm, and T-loop of the tRNA clover-leaf structure in PBLs than the control group. The succumbed IPF patients were older, had lower initial diffusion capacity, and higher initial fibrosis score on high-resolution computerized tomography (HRCT) than the alive group. NS variants in mitochondrial COX3 gene and tRNA variants in PBLs were associated with shorter survival. Our study shows that (1) leukocyte mitochondrial COX3 NS variants are associated with risk and prognosis of IPF; (2) leukocyte mitochondrial tRNA variants located in the AC stem, AC loop, variable loop, T-arm, and T-loop of the tRNA clover-leaf structure are associated with risk, and the presence of tRNA variants is associated with poor prognosis of IPF.

Non-pharmacological treatment with high-flow nasal cannula (HFNC) may play a vital role in treatment of patients with chronic obstructive pulmonary disease (COPD). To evaluate the efficacy of HFNC, impulse oscillation system (IOS) is a new noninvasive technique in measuring the impedance of different portions of lungs. It shows higher sensitivity in contrast to conventional pulmonary function tests (PFT). However, whether IOS is an appropriate technique to evaluate the efficacy of HFNC in improving the impedance of small airways or peripheral lung in patients with COPD is still unclear. We enrolled 26 stable COPD participants randomised into two groups receiving HFNC or nasal cannula (NC) for 10 min followed by a 4-week washout period and crossover alternatively. IOS was used to detect the difference of respiratory impedance after HFNC or NC interventions. IOS parameters, PFT results, transcutaneous partial pressure of carbon dioxide, peripheral oxygen saturation, body temperature, respiratory rate, pulse rate, and blood pressure at the time of pre-HFNC, post-HFNC, pre-NC, and post-NC, were collected and analysed using SPSS (version 25.0, IBM, Armonk, NY, USA). The IOS measurement indicated that HFNC significantly improved R5, R5% predicted, R5–R20, X5-predicted, and Fres compared with NC, whereas no significant difference was observed through the PFT measurement. The beneficial effect of HFNC in improving small airway resistance and peripheral lung reactance compared with that of NC in patients with stable COPD was confirmed through IOS measurement. Trial registration: ClinicalTrials.gov NCT05130112 22/11/2021.

Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing prevalence. Attenuated cellular immunity associated with programmed cell death (PD)–1 may play a pathophysiological role in MAC-LD but lacks of investigation. We enrolled 80 participants in this prospective study, including 50 with MAC-LD and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs), lymphocytes and monocyte-derived macrophages were used for MAC antigen stimulation. Patients with MAC-LD had lower tumor necrosis factor-α and interferon-γ responses compared to the healthy controls in PBMC stimulation assays with MAC bacilli. These responses improved after MAC treatment. The PD-1 and PD ligand expressions and apoptosis were higher in the lymphocytes of the patients with MAC-LD compared to the controls. Both PD-1 and apoptosis on T lymphocytes were significantly increased in the patients with MAC-LD, either by direct MAC stimulation or by MAC-primed macrophage activation. Partially blocking PD-1 and the PD ligand with antagonizing antibodies in the stimulation assay significantly increased the cytokine production of IFN-γ and decreased the apoptosis on T lymphocytes. In conclusion, the patients with MAC-LD have attenuated lymphocyte immunity, which might be associated with increasing activation of PD-1 and PD-1 ligand. Regulating such activation might improve the lymphocytic secretion of IFN-γ and reduce apoptosis.

Background Tuberculosis (TB) is one of the most common infectious diseases worldwide. During active tuberculosis, T helper (Th) 17 cells are decreased, however the association with inhibitory immune regulation is unclear. Methods We enrolled 27 patients with TB and 20 age- and sex-matched controls and studies their lymphocyte status. Peripheral blood lymphocytes were isolated and programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) were measured on Th17 cells by using flow cytometry after the cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin for 6 h. In addition, Th2 and regulatory T cells were measured and analyzed. Results The TB group had lower levels of Th17 cells but higher levels of Th2 and Treg cells than the controls. In Th17 cells, the percentage of PD-L1 was higher in the TB group than that in the controls. In Th2 and Treg cells, the percentage of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) was lower in the TB group and PD-1 was higher in Treg cells in the TB group. In the patients with extra-pulmonary TB, levels of Th1, Th2 and T17 cells were lower than those with pulmonary TB. The percentage of PD-1 on Th1 lymphocytes positively correlated with radiographic score. Conclusions Lower level of Th17 in TB patients may be associated with increased percentage of PD-L1 and increasing levels of Th2 and Treg cells which influenced by CTLA-4.

Background: Traditional regression explains only part of the variation in forced expiratory volume in one second (FEV1). Machine learning (ML) methods may capture nonlinear patterns beyond linear assumptions. Methods: We analyzed 23,943 non-smoking Taiwanese men aged 45–55 years from the MJ Health Screening Cohort. Random Forest (RF), Stochastic Gradient Boosting (SGB), and XGBoost were compared with multiple linear regression (MLR) using repeated train–test splits. Model performance was evaluated with RMSE, RAE, RRSE, and SMAPE. Shapley additive explanations (SHAP) were used to interpret variable effects. Results: ML models achieved slightly lower prediction errors than MLR. The most influential predictors across models were lactate dehydrogenase (LDH), body weight (BW), education level, leukocyte count, total bilirubin, and sport area. SHAP indicated negative effects of LDH and leukocyte count and positive associations for BW, bilirubin, education, and physical activity. Conclusions: ML approaches provided modest accuracy gains and clearer interpretability compared with MLR. Biochemical and lifestyle factors—including LDH, BW, education, inflammation markers, and physical activity—contribute meaningfully to FEV1 among healthy middle-aged men.

Human immunodeficiency virus (HIV)-infected patients are at an increased risk of tuberculosis (TB) and its recurrence following completion of anti-TB treatment. We investigated whether extending anti-TB treatment to 9 months or longer reduces TB recurrence. HIV-infected patients who were diagnosed with pulmonary TB between 1997 and 2009 and who received anti-TB treatment for a duration between 5.5 and 12.5 months were identified from the National Health Insurance Research Database in Taiwan. Those who received any non-fluoroquinolone second-line anti-TB drug for >28 days were excluded. Factors associated with TB recurrence within 2 years after completion of anti-TB treatment were explored using Cox regression analysis. Sensitivity analysis was performed for a subpopulation fulfilling strict diagnostic criteria for HIV infection. TB recurrence was observed in 18 (3.5%) of 508 HIV-infected patients. The recurrence rate declined from 5.4% to 1.0% after the implementation of directly observed therapy, short course (DOTS) in 2006 (p = 0.014). The recurrence rate was 5.9%, 5.2%, and 1.6% in patients who received anti-TB treatment for <195, 195-270, and >270 days, respectively (p = 0.066). Cox regression analysis revealed that TB diagnosed in the DOTS era (hazard ratio [HR]: 0.18 [0.04-0.77]) and anti-TB treatment for >270 days (HR: 0.24 [0.06-0.89]) were associated with a reduced risk of TB recurrence. Sensitivity analysis of 449 selected patients revealed that anti-TB treatment for >270 days was a significant factor. In Taiwan, the 2-year TB recurrence rate in HIV-infected patients declined after implementation of DOTS. The risk of TB recurrence in HIV-infected patients can be further reduced by extending anti-TB treatment to 9-12.5 months.

Patients with renal failure are vulnerable to tuberculosis, a common worldwide infectious disease. In the growing dialysis population, the risk for tuberculosis among the associated sub-groups is important but unclear. This study investigated latent tuberculosis infection (LTBI) in patients with severe chronic kidney disease (CKD) and among dialysis-unit staff caring for patients on dialysis. From January 2012 to June 2013, patients undergoing dialysis, those with severe CKD (estimated glomerular filtration rate <30 ml/min/1.73 m2), and the dialysis-unit staff (nursing staff and doctors in hemodialysis units) in several Taiwan hospitals were prospectively enrolled. Interferon-gamma release assay (IGRA) through QuantiFERON-TB Gold In-tube was used to determine LTBI. Predictors for LTBI were analyzed. Of the 599 participants enrolled, 106 (25%) in the dialysis group were IGRA positive. This was higher than the seven (11%) among severe CKD patients and 12 (11%) in the dialysis-unit staff. Independent predictors of LTBI in patient with renal dysfunction were old age (odds ratio [OR]: 1.03 [1.01-1.04] per year increment), prior TB lesion on chest radiograph (OR: 2.90 [1.45-5.83]), serum albumin (OR: 2.59 [1.63-4.11] per 1 g/dl increment), and need for dialysis (OR: 2.47, [1.02-5.95]). The QFT-GIT response was similar among the three groups. Malignancy (OR: 4.91 [1.84-13.10]) and low serum albumin level (OR: 0.22 [0.10-0.51], per 1 g/dl decrease) were associated with indeterminate IGRA results. More patients on dialysis have LTBI compared to those with severe CKD and the dialysis-unit staff. Old age, prior radiographic TB lesion, high serum albumin, and need for dialysis are predictors of LTBI in patients with renal failure. Patients with severe CKD are a lower priority for LTBI screening. The hemodialysis environment is not a risk for LTBI and dialysis-unit staff may be treated as general healthcare workers.