The effect of smoking on nontuberculous mycobacterial pulmonary disease and tuberculosis: a nationwide retrospective cohort study.

Although smoking is an established risk factor for Mycobacterial infection, the association between smoking and nontuberculous mycobacterial pulmonary disease (NTM-PD) remains unclear. We evaluated the association between smoking and NTM-PD and tuberculosis (TB) using a population-based South Korean nationwide cohort. Using the Korean National Health Insurance Database, we screened individuals over 20 years of age who underwent the national health screening program in 2009. Out of 3,774,308 eligible populations, we identified 2,964 and 26,112 cases of newly developed NTM-PD and TB, respectively. We used multivariate Cox proportional hazards models to estimate the adjusted hazard ratios (aHRs) of risk factors for NTM-PD and TB. The incidence rates for developing NTM-PD and TB were 0.08 and 0.68 per 1,000 person-years, respectively. Current smokers (aHR 0.63, 95% confidence interval [CI] 0.56-0.71) and current heavy smokers (≥ 20 pack-years, aHR 0.74, 95% CI 0.63-0.86) were at lower risk for NTM-PD development than never smokers. On the contrary, current smokers (aHR 1.19, 95% CI 1.15-1.23) and current heavy smokers (aHR 1.27, 95% CI 1.22-1.33) had a higher risk for TB development than never smokers. These trends were augmented if individuals started smoking before age 20 years. In subgroup analyses stratified by age, these trends were prominent in the 40-64 years age range. Current smoking was associated with a decreased risk of NTM-PD and increased risk of TB. These risks were augmented by early smoking initiation and in the middle age population.

The association between cumulative exposure to PM2.5 and DNA methylation measured using methyl-capture sequencing among COPD patients.

BACKGROUND: Particulate matter with a diameter of < 2.5 µm (PM2.5) influences gene regulation via DNA methylation; however, its precise mechanism of action remains unclear. Thus, this study aimed to examine the connection between personal PM2.5 exposure and DNA methylation in CpG islands as well as explore the associated gene pathways. METHODS: A total of 95 male patients with chronic obstructive pulmonary disease (COPD) were enrolled in this study. PM2.5 concentrations were measured for 12 months, with individual exposure recorded for 24 h every 3 months. Mean indoor and estimated individual PM2.5 exposure levels were calculated for short-term (7 days), mid-term (35 days), and long-term (90 days). DNA methylation analysis was performed on the blood samples, which, after PCR amplification and hybridization, were finally sequenced using an Illumina NovaSeq 6000 system. Correlation between PM2.5 exposure and CpG methylation sites was confirmed via a mixed-effects model. Functional enrichment analysis was performed on unique CpG methylation sites associated with PM2.5 exposure to identify the relevant biological functions or pathways. RESULTS: The number of CpG sites showing differential methylation was 36, 381, and 182 for the short-, mid-, and long-term indoor models, respectively, and 3, 98, and 28 for the short-, mid-, and long-term estimated exposure models, respectively. The representative genes were TMTC2 (p = 1.63 × 10-3, R2 = 0.656), GLRX3 (p = 1.46 × 10-3, R2 = 0.623), DCAF15 (p = 2.43 × 10-4, R2 = 0.623), CNOT6L (p = 1.46 × 10-4, R2 = 0.609), BSN (p = 2.21 × 10-5, R2 = 0.606), and SENP6 (p = 1.59 × 10-4, R2 = 0.604). Functional enrichment analysis demonstrated that the related genes were mostly associated with pathways related to synaptic transmission in neurodegenerative diseases and cancer. CONCLUSION: A significant association was observed between PM2.5 exposure and DNA methylation upon short-term exposure, and the extent of DNA methylation was the highest upon mid-term exposure. Additionally, various pathways related to neurodegenerative diseases and cancer were associated with patients with COPD. GOV IDENTIFIER: NCT04878367.

Low household income increases risks for chronic obstructive pulmonary disease in young population: a nationwide retrospective cohort study in South Korea.

BACKGROUND: Low socioeconomic status is a risk factor for chronic obstructive pulmonary disease (COPD); however, the association between low household income and COPD in young populations remains unclear. METHODS: We screened individuals aged 20-39 years who underwent the national health examination between 2009 and 2012 using the Korean National Health Information Database, which was searched until December 2019. We identified 5 965 366 eligible individuals, and 13 296 had newly developed COPD based on health insurance claims. We evaluated household income levels based on the health insurance premiums, categorised them into quartiles and 'Medical aid' (the lowest 3% income group), and assessed the annual income status from the preceding 4 years. Multivariate Cox proportional hazard models were used to estimate the adjusted HR (aHR) of risk factors for COPD. RESULTS: In the Medical aid group, the incidence rate for developing COPD was 0.56/1000 person-years, with an aHR of 2.45 (95% CI 1.91 to 3.13) compared with that of the highest income quartile group. This association was prominent in consecutive recipients of Medical aid (aHR 2.37, 95% CI 1.80 to 3.11) compared with those who had never been Medical aid beneficiaries. Those who experienced a decline in household income between the previous (preceding 4 years) and baseline time points had an increased risk of developing COPD, regardless of previous income status. CONCLUSION: Low household income was associated with an increased risk of developing COPD in the young population. This risk was augmented by sustained low income and declining income status.

Association between exposure to specific PM2.5 constituents and environment, lifestyle, and clinical parameters in patients with COPD.

This study investigated the correlation between the individual chemical constituents of particulate matter 2.5 µm (PM2.5) and respiratory parameters as well as the living environment and daily behaviors in patients with chronic obstructive pulmonary disease (COPD). Data were obtained from prospective COPD panel conducted in South Korea. Following collection via a microPEM, 18 metallic elements were determined using energy-dispersive X-ray fluorescence spectroscopy. All participants completed detailed questionnaires on living environments and lifestyle practices. Eighty-nine stable COPD patients (mean age 68.1 years; 94.4% male) were analyzed. Several constituents (titanium, aluminum, bromine, and silicone) were significantly associated with respiratory outcomes. Copper and manganese concentrations were significantly associated with the living environment. Increased ventilation time and air purifier operation were associated with lower concentrations of copper, silicone, barium, and titanium. These findings suggest varying relationships between PM2.5 constituents and clinical parameters in COPD patients, providing a basis for personalized interventions and future research.

Application of Microbiome-Based Therapies in Chronic Respiratory Diseases.

The application of microbiome-based therapies in various areas of human disease has recently increased. In chronic respiratory disease, microbiome-based clinical applications are considered compelling options due to the limitations of current treatments. The lung microbiome is ecologically dynamic and affected by various conditions, and dysbiosis is associated with disease severity, exacerbation, and phenotype as well as with chronic respiratory disease endotype. However, it is not easy to directly modulate the lung microbiome. Additionally, studies have shown that chronic respiratory diseases can be improved by modulating gut microbiome and administrating metabolites. Although the composition, diversity, and abundance of the microbiome between the gut and lung are considerably different, modulation of the gut microbiome could improve lung dysbiosis. The gut microbiome influences that of the lung via bacterial-derived components and metabolic degradation products, including short-chain fatty acids. This phenomenon might be associated with the cross-talk between the gut microbiome and lung, called gut-lung axis. There are multiple alternatives to modulate the gut microbiome, such as prebiotics, probiotics, and postbiotics ingestion and fecal material transplantation. Several studies have shown that high-fiber diets, for example, present beneficial effects through the production of short-chain fatty acids. Additionally, genetically modified probiotics to secrete some beneficial molecules might also be utilized to treat chronic respiratory diseases. Further studies on microbial modulation to regulate immunity and potentiate conventional pharmacotherapy will improve microbiome modulation techniques, which will develop as a new therapeutic area in chronic respiratory diseases.

Fine particulate matter aggravates smoking induced lung injury via NLRP3/caspase-1 pathway in COPD.

BACKGROUND: Exposure to noxious particles, including cigarette smoke and fine particulate matter (PM2.5), is a risk factor for chronic obstructive pulmonary disease (COPD) and promotes inflammation and cell death in the lungs. We investigated the combined effects of cigarette smoking and PM2.5 exposure in patients with COPD, mice, and human bronchial epithelial cells. METHODS: The relationship between PM2.5 exposure and clinical parameters was investigated in patients with COPD based on smoking status. Alveolar destruction, inflammatory cell infiltration, and pro-inflammatory cytokines were monitored in the smoking-exposed emphysema mouse model. To investigate the mechanisms, cell viability and death and pyroptosis-related changes in BEAS-2B cells were assessed following the exposure to cigarette smoke extract (CSE) and PM2.5. RESULTS: High levels of ambient PM2.5 were more strongly associated with high Saint George's respiratory questionnaire specific for COPD (SGRQ-C) scores in currently smoking patients with COPD. Combined exposure to cigarette smoke and PM2.5 increased mean linear intercept and TUNEL-positive cells in lung tissue, which was associated with increased inflammatory cell infiltration and inflammatory cytokine release in mice. Exposure to a combination of CSE and PM2.5 reduced cell viability and upregulated NLRP3, caspase-1, IL-1ß, and IL-18 transcription in BEAS-2B cells. NLRP3 silencing with siRNA reduced pyroptosis and restored cell viability. CONCLUSIONS: PM2.5 aggravates smoking-induced airway inflammation and cell death via pyroptosis. Clinically, PM2.5 deteriorates quality of life and may worsen prognosis in currently smoking patients with COPD.

Endobronchial valves for emphysema and persistent air-leak: 10-year experience in an Asian country.

BACKGROUND: Endobronchial valve (EBV) therapy, a validated method for bronchoscopic lung volume reduction (BLVR) in severe emphysema, has been explored for persistent air-leak (PAL) management. However, its effectiveness and safety in the Asian population require further real-world evaluation. In this study, we assessed the outcomes of treatment with EBV within this demographic. METHODS: We conducted a retrospective analysis of medical records from 11 Korean centers. For the emphysema cohort, inclusion criteria were patients diagnosed with emphysema who underwent bronchoscopy intended for BLVR. We assessed these patients for clinical outcomes of chronic obstructive pulmonary disease. All patients with PAL who underwent treatment with EBV were included. We identified the underlying causes of PAL and evaluated clinical outcomes after the procedure. RESULTS: The severe emphysema cohort comprised 192 patients with an average age of 70.3 years, and 95.8% of them were men. Ultimately, 137 underwent treatment with EBV. Three months after the procedure, the BLVR group demonstrated a significant improvement in forced expiratory volume in 1 s (+160 mL vs. +30 mL; P = 0.009). Radiographic evidence of lung volume reduction 6 months after BLVR was significantly associated with improved survival (adjusted hazard ratio 0.020; 95% confidence interval 0.038-0.650; P = 0.010). Although pneumothorax was more common in the BLVR group (18.9% vs. 3.8%; P = 0.018), death was higher in the no-BLVR group (38.5% vs. 54.5%, P = 0.001), whereas other adverse events were comparable between the groups. Within the subset of 18 patients with PAL, the predominant causes of air-leak included spontaneous secondary pneumothorax (44.0%), parapneumonic effusion/empyema (22.2%), and post-lung resection surgery (16.7%). Following the treatment, the majority (77.8%) successfully had their chest tubes removed. Post-procedural complications were minimal, with two incidences of hemoptysis and one of empyema, all of which were effectively managed. CONCLUSIONS: Treatment with EBV provides substantial clinical benefits in the management of emphysema and PAL in the Asian population, suggesting a favorable outcome for this therapeutic approach.

Does Rheumatoid Arthritis Increase the Risk of COPD?: A Nationwide Retrospective Cohort Study.

BACKGROUND: Most reports of pulmonary manifestations in rheumatoid arthritis (RA) have been related to interstitial lung diseases. RA and COPD are both chronic inflammatory systemic diseases. RESEARCH QUESTION: Does RA increase the risk of developing COPD? Is there a difference between seropositive and seronegative RA in the risk of COPD? STUDY DESIGN AND METHODS: Using the Korean National Health Insurance Database, we screened individuals diagnosed with RA between 2010 and 2017. We identified 46,030 patients with RA (32,608 with seropositive RA and 13,422 with seronegative RA) and 230,150 matched control individuals; we monitored them until December 2019. We used multivariate Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) of risk factors for the development of COPD. RESULTS: The incidence of COPD among patients with RA was 5.04 per 1,000 person-years; it was 2.23 per 1,000 person-years in the control group. Patients with RA showed a higher risk of developing COPD (aHR, 2.11; 95% CI, 1.96-2.28) compared with the control group. Although both seropositive RA and seronegative RA were associated with an increased risk of COPD, patients with seropositive RA had a higher risk for the development of COPD (aHR, 1.26; 95% CI, 1.09-1.46) than patients with seronegative RA. In the subgroup analyses, smoking history did not demonstrate significant interactions between RA and COPD development. INTERPRETATION: RA was shown to be associated with an increased risk of COPD development, augmented by seropositivity. Physicians should monitor respiratory symptoms and pulmonary function carefully in patients with RA.

Smartphone application-based rehabilitation in patients with chronic respiratory and cardiovascular diseases.

Rehabilitation improves symptoms, quality of life, and survival in patients with chronic respiratory or cardiovascular disease. We evaluated smartphone application-based rehabilitation programs for patients with chronic respiratory or cardiovascular diseases. This was a single-center prospective single arm study. Participants underwent smartphone application-based pulmonary or cardiac rehabilitation for 12 weeks. A total of 93 participants were recruited, and 75 visited after rehabilitation. Their median age was 67.0 (interquartile range, 60.0-70.8) years, and 60 (80.0%) were men. For patients with chronic respiratory disease (n = 41), VO2peak (median 13.7 to 15.4 ml/kg/min, P = 0.049), chronic obstructive pulmonary disease assessment test (median 14 to 6, P < 0.001), Euro-QoL 5-Dimension 5-Level (EQ-5D-5L) index (median 0.795 to 0.862, P = 0.001), and Health-related Quality of Life Instrument with 8 Items (HINT-8) index (median 0.784 to 0.855, P < 0.001) were significantly improved. For patients with chronic cardiovascular disease (n = 34), VO2peak (median 21.8 to 23.3, P = 0.007), EQ-5D-5L index (median 0.871 to 1.000, P = 0.037), and HINT-8 index (median 0.890 to 0.903, P < 0.001) were significantly improved. The smartphone application-based rehabilitation program improved exercise capacity and quality of life in patients with chronic respiratory or cardiovascular disease.Trial registration: https://clinicaltrials.gov/ct2/show/NCT05383950 (20/05/2022).