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.

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).

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.

Clinical Efficacy of Mobile App-Based, Self-Directed Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-Analysis.

Background: Pulmonary rehabilitation is well known to improve clinical symptoms (including dyspnea), quality of life, and exercise capacity in patients with chronic obstructive pulmonary disease (COPD). However, researchers have reported difficulties in practicing center-based pulmonary rehabilitation. Recently, mobile app-based pulmonary rehabilitation has become available in clinical practice. We investigated the clinical outcomes of mobile app-based pulmonary rehabilitation in patients with COPD. Objective: The objective of our study was to evaluate the clinical efficacy of mobile app-based pulmonary rehabilitation versus conventional center-based pulmonary rehabilitation for patients with COPD, using a systematic review and meta-analysis. Methods: A systematic search of the literature published between January 2007 and June 2023 was performed, using the PubMed, Embase, Cochrane, and CINAHL databases to identify relevant randomized controlled trials involving patients with COPD. Pulmonary rehabilitation programs needed to provide an exercise program on a smartphone app. Study outcomes, including exercise capacity, symptom scores, quality of life, and hospitalization, were evaluated. The meta-analysis evaluated mean differences in 6-minute walk test distances (6MWDs), COPD Assessment Test (CAT) scores, modified Medical Research Council (mMRC) dyspnea scale scores, St. George Respiratory Questionnaire (SGRQ) scores, and risk ratios for hospitalization resulting from disease exacerbation. Results: Of the 1173 screened studies, 10 were included in the systematic review and 9 were included in the meta-analysis. Further, 6 studies were multicenter studies. There were a total of 1050 participants, and most were aged ≥65 years. There were discrepancies in the baseline participant characteristics, smartphone apps, interventions, and study outcomes among the included studies. In the meta-analysis, 5 studies assessed 6MWDs (mean difference 9.52, 95% CI -3.05 to 22.08 m), 6 studies assessed CAT scores (mean difference -1.29, 95% CI -2.39 to -0.20), 3 studies assessed mMRC dyspnea scale scores (mean difference -0.08, 95% CI -0.29 to 0.13), 2 studies assessed SGRQ scores (mean difference -3.62, 95% CI -9.62 to 2.38), and 3 studies assessed hospitalization resulting from disease exacerbation (risk ratio 0.65, 95% CI 0.27-1.53). These clinical parameters generally favored mobile app-based pulmonary rehabilitation; however, a statistically significant difference was noted only for the CAT scores (P=.02). Conclusions: Despite some discrepancies in the baseline participant characteristics and interventions among studies, mobile app-based pulmonary rehabilitation resulted in favorable exercise capacity, symptom score, quality of life, and hospitalization outcomes when compared with conventional pulmonary rehabilitation. In the meta-analysis, the CAT scores of the mobile app-based pulmonary rehabilitation group were significantly lower than those of the control group (P=.02). In real-world practice, mobile app-based pulmonary rehabilitation can be a useful treatment option when conventional center-based pulmonary rehabilitation is not feasible.

Smartphone application-based rehabilitation in patients with chronic respiratory and cardiovascular diseases: a randomised controlled trial study protocol.

INTRODUCTION: Rehabilitation is well known to improve clinical symptoms and decrease the risk of mortality in patients with chronic respiratory or cardiovascular diseases. We will evaluate the efficacy of smartphone application-based rehabilitation programmes in patients with chronic respiratory or cardiovascular diseases. METHODS AND ANALYSIS: This single-centre single-blind randomised controlled trial will recruit a total of 162 participants from Asan Medical Center (81 patients each for pulmonary and cardiac rehabilitation, respectively). Participants will be assigned to the pulmonary or cardiac rehabilitation groups based on their underlying disease. Participants will be allocated randomly into the intervention or control groups at the ratio of 2:1 (54 and 27 patients). The intervention group will be provided with a smartphone application and undergo smartphone application-based rehabilitation for 12 weeks. The control group will receive the usual outpatient medical treatment without rehabilitation. Participants will be evaluated at baseline and at the end of the rehabilitation. The primary outcomes will be exercise capacity, such as maximal oxygen consumption on cardiopulmonary exercise test for both groups, chronic obstructive pulmonary disease assessment test for the pulmonary rehabilitation group, and Health-related Quality of Life Instrument with 8 Items questionnaires for the cardiac rehabilitation group. The secondary outcomes will include quality of life questionnaires, symptom scores, pulmonary function test and limb muscle test. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of Asan Medical Center. Written informed consent will be obtained from all participants prior to inclusion. The findings from this study will be disseminated through peer-reviewed scientific journals and conferences. TRIAL REGISTRATION NUMBER: NCT05610358.

Effect of smoking on the development of chronic obstructive pulmonary disease in young individuals: a nationwide cohort study.

Background: Cigarette smoking is an important risk factor for developing chronic obstructive pulmonary disease (COPD). However, the effect of smoking on the development of COPD in young individuals remains unclear. We aimed to evaluate the effect of smoking on COPD development in young individuals. Methods: Using the Korean National Health Information Database, we screened individuals aged 20-39 years who participated in the national health check-up between 2009 and 2012. We defined physician-diagnosed COPD based on health insurance claims and searched the database until December 2019. We identified 6,307,576 eligible individuals, and 13,789 had newly developed COPD. We used multivariate Cox proportional hazards models to estimate the adjusted hazard ratio (aHR) of risk factors for COPD. Results: The incidence rate for developing COPD was 0.26/1000 person-year. The risk of developing COPD was significantly higher in current smokers [aHR 1.46, 95% confidence interval (CI) 1.39-1.53] and former smokers (aHR 1.21, 95% CI 1.14-1.29) than in non-smokers. Furthermore, the risk increased with increasing smoking amounts (≥20 pack-years, aHR 2.24; 10-20 pack-years, aHR 1.55; <10 pack-years, aHR 1.27). Female participants had a higher relative risk of developing COPD due to smoking, compared with their male counterparts. Conclusion: Cigarette smoking increased the risk of developing COPD in young individuals. Current and heavy smokers had higher risks of developing COPD than non-smokers. Female smokers were more likely to develop COPD than male smokers.

Clinical impact of weight loss on mortality in patients with idiopathic pulmonary fibrosis: a retrospective cohort study.

Patients with idiopathic pulmonary fibrosis (IPF) often experience weight loss during the follow-up period. However, the prevalence and clinical impact of weight loss in these patients still need to be elucidated. This retrospective single-center study reviewed 134 consecutive patients diagnosed with IPF. Weight loss of 5% or more over 1 year was defined as significant weight loss. Clinical data of patients were compared according to the significant weight loss. We analyzed whether the clinical impact of significant weight loss differed regarding the pirfenidone dose. The median follow-up period was 22.1 months. The mean age of patients was 67.3 years, and 92.5% were men. Of the 134 patients, 42 (31.3%) showed significant weight loss. Multivariate cox regression analysis revealed that significant weight loss was independently associated with mortality (hazard ratio [HR]; 2.670; 95% confidence interval [CI] 1.099-6.484; p = 0.030) after adjusting for lung function and other significant risk factors (6-min walk test distance: HR, 0.993; 95% CI 0.987-0.998; p = 0.005). The median survival of patients with significant weight loss (n = 22) was relevantly shorter than that of those without significant weight loss (n = 43) in the reduced dose pirfenidone group (28.2 ± 3.3 vs. 43.3 ± 3.2 months, p = 0.013). Compared with patients without significant weight loss (n = 38), patients with significant weight loss (n = 15) also showed a marginally-significant shorter survival in the full-dose pirfenidone group (28.9 ± 3.1 vs. 39.8 ± 2.6 months, p = 0.085). Significant weight loss is a prognostic factor in patients with IPF regardless of pirfenidone dose. Vigilant monitoring might be necessary to detect weight loss during the clinical course in these patients.

Factors associated with dose reduction of pirfenidone in patients with idiopathic pulmonary fibrosis: A study based on real-world clinical data.

INTRODUCTION: Although pirfenidone slows disease progression in patients with idiopathic pulmonary fibrosis (IPF), in clinical practice, patients often cannot tolerate the recommended dose because of several adverse events. This study aimed to investigate adverse events associated with pirfenidone and factors associated with dose reduction. METHODS: This single-center retrospective cohort study included 156 consecutive patients with IPF who received pirfenidone. Demographic characteristics, pulmonary function, and pirfenidone-related adverse events were investigated. We compared patients who received standard and reduced doses of pirfenidone. RESULTS: The mean patient age was 69.7 years. The median follow-up duration was 243 days. The low-dose group (n = 73) included older patients (71.0 years vs. 67.4 years, p = 0.016), fewer smokers (80.8% vs. 96.4%, p = 0.008), and patients with a lower body mass index (BMI; 24.1 kg/m2 vs. 25.7 kg/m2, p = 0.027) than the standard dose group (n = 57). Multivariate logistic regression analysis revealed that older age (odds ratio = 1.066, p = 0.016) was significantly associated with dose reduction of pirfenidone after adjusting for sex, smoking history, emphysema, and BMI. No significant difference was found in the rates of a reduced forced vital capacity and diffusing capacity for carbon monoxide between the two groups. CONCLUSIONS: Although older patients are more likely to undergo dose reduction of pirfenidone, low-dose pirfenidone might be effective for treating patients with IPF. Low-dose pirfenidone could be considered an effective treatment option for older patients with IPF.

Prognostic implication of bronchoalveolar lavage fluid analysis in patients with Pneumocystis jirovecii pneumonia without human immunodeficiency virus infection.

BACKGROUND: The prognostic value of bronchoalveolar lavage (BAL) fluid analysis in non-human immunodeficiency virus (HIV)-infected patients with Pneumocystis jirovecii pneumonia (PJP) has not been well elucidated. We aimed to investigate the prognostic implication of BAL fluid analysis in non-HIV patients with PJP. METHODS: The data of 178 non-HIV patients diagnosed with PJP based on the results of the polymerase chain reaction assay of BAL fluid specimens between April 2018 and December 2020 were retrospectively reviewed. The clinical characteristics, laboratory findings, and BAL fluid analysis results of patients who died within 90 days after hospital admission were compared. RESULTS: Twenty patients (11.2%) died within 90 days from admission. The neutrophil count in BAL fluid was significantly higher (median 22.0%, interquartile range [IQR] 2.0-46.0% vs. median 6.0%, IQR 2.0-18.0%, P = 0.044), while the lymphocyte count was significantly lower (median 24.0%, IQR 7.0-37.0% vs. median 41.0%, IQR 22.5-60.5%, P = 0.001) in the non-survivor group compared with that in the survivor group. In the multivariate analysis, the C-reactive protein level (odds ratio [OR] 1.093, 95% confidence interval [CI] 1.020-1.170, P = 0.011) and a BAL fluid lymphocyte count of ≤ 30% (OR 3.353, 95% CI 1.101-10.216, P = 0.033) were independently associated with mortality after adjusting for albumin and lactate dehydrogenase levels. CONCLUSION: A low lymphocyte count in BAL fluid may be a predictor of mortality in non-HIV patients with PJP.

Baseline serum Krebs von den Lungen-6 as a biomarker for the disease progression in idiopathic pulmonary fibrosis.

Disease progression (DP) is an important parameter for the prognosis of idiopathic pulmonary fibrosis (IPF). This study aimed to evaluate the baseline serum biomarkers for predicting the DP in IPF. Seventy-four patients who were diagnosed with IPF and had their serum Krebs von den Lungen-6 (KL-6) and monocyte count, which might be associated with prognosis of IPF, checked more than twice were included. KL-6 ≥ 1000 U/mL and monocyte ≥ 600/µL were arbitrarily set as the cut-off values for DP. The DP was defined as a 10% reduction in forced vital capacity, a 15% reduction in diffusing capacity of the lung for carbon monoxide relative to the baseline, or disease-related mortality. Of the 74 patients, 18 (24.3%) were defined as having DP. The baseline KL-6 level was significantly increased in the DP group compared to the stable disease group (median, 1228.0 U/mL vs. 605.5 U/mL, P = 0.019). Multivariate Cox analyses demonstrated that a high KL-6 level (KL-6 ≥ 1000 U/mL; hazard ratio, 2.761 or 2.845; P = 0.040 or 0.045) was independently associated with DP in each model. The baseline serum KL-6 level might be a useful biomarker for DP in IPF.

Safety of latent tuberculosis infection treatment in older patients with immune-mediated inflammatory diseases.

INTRODUCTION: Screening and treatment of latent tuberculosis infections (LTBI) are required before starting biologics in patients with immune-mediated inflammatory diseases (IMIDs). This study aimed to assess the safety of LTBI treatment in older patients with IMIDs. METHODS: The medical records of 916 patients treated for LTBI before the start of biologics for IMIDs between January 2004 and December 2018 were reviewed. The safety profiles of LTBI treatment were retrospectively compared according to age. RESULTS: Among the 916 patients, 201 were aged > 60 years (older age group). The older age group showed female predominance, more frequent history of previous tuberculosis, and more comorbidities, and received biologics mainly for rheumatoid arthritis. Most patients (74.0%) took isoniazid and rifampicin daily for 3 months. The treatment completion rate was 90.4% in the overall population and was lower in the older age group (91.9% vs. 85.1%, P = 0.005). Adverse drug events were more frequent in the older age group (22.9% vs. 9.8%, P < 0.001); however, differences were mainly observed for nausea (5.5% vs. 2.1%, P = 0.016) and flu-like syndrome (6.5% vs. 1.7%, P = 0.001), but not hepatotoxicity. CONCLUSION: LTBI treatment is generally safe in older patients with IMIDs, especially with respect to hepatotoxicity. Key points • The older age group had significantly more nausea and flu-like syndrome but not hepatotoxicity, compared to the younger age group. • LTBI treatment was acceptable and generally safe in the older age group.