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.

Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in turn caused the loss of mitochondrial membrane potential (MMP). The increase of oxidative stress in lung cancer cells treated with BA6 was accompanied by a decrease in the expression of antioxidant enzymes Cu/Zn SOD, MnSOD, and catalase. In addition, OXPHOS performed in the mitochondria and glycolysis in the cytoplasm were inhibited, which subsequently reduced downstream ATP production. Pretreatment with mitochondria-targeted antioxidant MitoTEMPO reduced BA6-induced apoptosis through the mitochondria-dependent apoptotic pathway, which was accompanied by increased cell viability, decreased mtROS, enhanced MMP, and suppressed expression of cleaved caspase-3 and caspase-9 proteins. In conclusion, the results of this study clarify the mechanism of BA6-induced apoptosis in lung cancer cells via the mitochondrial apoptotic pathway, suggesting that it is a potentially innovative alternative to the treatment of human lung cancer.

Smoking, sex, air pollution, lifestyle, and diet may act independently or in concert with each other to contribute to the different outcomes of lung cancer (LC). This study aims to explore their associations with the carcinogenesis of LC, which will be useful for formulating further preventive strategies. This retrospective, longitudinal follow-up cohort study was carried out by connecting to the MJ Health Database, Taiwan Cancer Registry database, and Taiwan cause of death database from 2000 to 2015. The studied subjects were persons attending the health check-ups, distributed throughout the main island of Taiwan. Cox proportional hazards regression models were used to investigate the risk factors associated with LC development and mortality after stratifying by smoking status, with a special emphasis on ambient two-year average PM_2.5 exposure, using a satellite-based spatiotemporal model at a resolution of 1 km², and on dietary habit including consumption of fruits and vegetables. After a median follow-up of 12.3 years, 736 people developed LC, and 401 people died of LC-related causes. For never smokers, the risk of developing LC (aHR: 1.32, 95%CI: 1.12–1.56) and dying from LC-related causes (aHR: 1.28, 95%CI: 1.01–1.63) rises significantly with every 10 μg/m³ increment of PM_2.5 exposure, but not for ever smokers. Daily consumption of more than two servings of vegetables and fruits is associated with lowering LC risk in ever smokers (aHR: 0.68, 95%CI: 0.47–0.97), and preventing PM_2.5 exposure is associated with lowering LC risk for never smokers.

Weekly rifapentine and isoniazid therapy (known as 3HP) for latent tuberculosis infection (LTBI) is increasingly used, but systemic drug reactions (SDR) remain a major concern. Methods: We prospectively recruited two LTBI cohorts who received the 3HP regimen. In the single-nucleotide polymorphism (SNP) cohort, we collected clinical information of SDRs and examined the NAT2, CYP2E1, and AADAC SNPs. In the pharmacokinetic (PK) cohort, we measured plasma drug and metabolite levels at 6 and 24 h after 3HP administration. The generalised estimating equation model was used to identify the factors associated with SDRs. Candidate SNPs predicting SDRs were validated in the PK cohort. A total of 177 participants were recruited into the SNP cohort and 129 into the PK cohort, with 14 (8%) and 13 (10%) in these two cohorts developing SDRs, respectively. In the SNP cohort, NAT2 rs1041983 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 7.00 [2.03–24.1]) and CYP2E1 rs2070673 (AA vs. TT+TA, OR [95% CI]: 3.50 [1.02–12.0]) were associated with SDR development. In the PK cohort, isoniazid level 24 h after 3HP administration (OR [95% CI]: 1.61 [1.15–2.25]) was associated with SDRs. Additionally, the association between the NAT2 SNP and SDRs was validated in the PK cohort (rs1041983 TT vs. CC+CT, OR [95% CI]: 4.43 [1.30–15.1]). Conclusions: Isoniazid played a role in the development of 3HP-related SDRs. This could provide insight for further design of a more optimal regimen for latent TB infection.

As a cause of lung disease (LD), Mycobacterium kansasii is regarded as a highly virulent species among nontuberculous mycobacteria (NTM). Both the frequency of M. kansasii isolates and global prevalence of M. kansasii-LD have increased gradually over recent decades. Treatment of M. kansasii-LD is recommended because of the disease's poor prognosis and fatal outcome. The decision on the optimal time point for treatment initiation should be based on both the benefits and risks posed by multiple antimicrobial agents. For treatment-naïve patients with M. kansasii-LD, rifampin-containing multiple antimicrobial regimens for ≥12 months after culture negative conversion are effective. However, some challenges remain, such as determining the precise length of treatment duration as well as addressing intolerable adverse effects, the uncertain effectiveness of isoniazid and ethambutol in treatment, the uncertain correlation between in vitro drug susceptibility testing and clinical outcomes, and the increasing prevalence of clarithromycin-resistant M. kansasii isolates. Short-course and effective therapies must be developed. New candidate drugs, such as tedizoid and clofazimine, exhibit excellent antimycobacterial activity against M. kansasii in vitro, but in vivo studies of their clinical applications are lacking. This paper reviews the treatment, outcomes and future directions in patients with M. kansasii-LD.

The weekly rifapentine plus isoniazid for 3 months (3HP) improves completion rate of latent tuberculosis infection treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in HIV-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations. This randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites. A total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46-50.79] vs. 22.94 [14.67-31.65], p 0.018) and 6 hours (26.13 [15.80-53.06] vs. 29.83 [18.13-34.01], p 0.047) after dosing. In non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%.