Chronic Obstructive Pulmonary Diseases-Journal of the Copd Foundation最新文献

Background: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease associated with respiratory muscle weakness and activity-limiting symptoms such as dyspnea. Respiratory muscle strength training (RMST) is an empirically validated therapy to increase respiratory muscle strength. The theoretically-informed, technology-enhanced RESPiratory FITness (RESP-FIT) intervention for COPD is a 6-week combined inspiratory and expiratory muscle strength training program with symptom measurement in real time via ecological momentary assessment (EMA).

Objectives: In addition to hypothesis-generating purposes, the purpose of this randomized control pilot study was to explore whether observed effects (on symptoms, patient-reported outcomes, and respiratory muscle strength) support carrying out a future large-scale trial of RESP-FIT.

Methods: A total of 30 adults with COPD were randomized to intervention (n=15) or control groups, with the intervention group undergoing 6 weeks of mHealth-enhanced RMST. Daily symptom data were collected in real time over the 6-week intervention period using EMA.

Results: Compared to the control group, participants in the intervention group reported decreased dyspnea and anxiety, increased happiness, and improved respiratory muscle strength. However, reports of fatigue and sleep disturbance increased in the intervention group compared to the control group.

Conclusion: Results support the hypothesis that the 6-week RESP-FIT program will improve respiratory muscle strength, emotional state (anxiety and happiness), and breathlessness in COPD but may contribute to fatigue, at least in the short term. Future work is needed to determine the efficacy of RESP-FIT, determine mechanisms of action on dyspnea and fatigue, and conduct within-participant comparisons of EMA data to explore individual or environmental fluctuations in COPD symptoms.

Background: The interactions between fibroblasts and bronchial epithelial cells play important roles in the development of chronic obstructive pulmonary disease (COPD). Interleukin (IL)-17A triggers the activation of fibroblasts and the secretion of inflammatory mediators, which promotes epithelial-mesenchymal transition (EMT) in bronchial epithelial cells. Fibroblasts secrete C-X-C motif chemokine ligand 12 (CXCL12), which specifically binds to its receptor, C-X-C motif chemokine receptor 4 (CXCR4) to mediate inflammatory responses. This study aims to investigate IL-17A- and CXCL12-induced airway remodeling.

Methods: Primary lung fibroblasts were isolated from human and murine lung tissue for the in vitro experiments, and a mouse model of cigarette smoke (CS)-induced COPD was established for the in vivo experiments. The results were analyzed using a one-way analysis of variance and Tukey's test or Bonferroni's test for the post-hoc test. A p-value < 0.05 was considered statistically significant.

Results: Through in vitro experiments, we found that IL-17A-activated primary lung fibroblasts secreted CXCL12 and stimulated EMT in bronchial epithelial cells. However, these effects could be blocked by neutralizing IL-17A or CXCL12. In vivo, an anti-IL-17A antibody or a CXCR4 antagonist could reverse the degree of EMT in the lungs of the COPD mouse model. The IL-17A-induced EMT and increased CXCL12 expression occurred via extracellular signal-regulated kinase (ERK)/phosphorylated-ERK pathways.

Conclusion: This study showed that exposure of mice to CS and IL-17A stimulation upregulated CXCL12 expression and induced EMT by activating the ERK signaling pathway. These data offer a novel perspective regarding the molecular mechanism of CXCL12/CXCR4 signaling in IL-17A-induced EMT related to airway remodeling.

Individuals living in rural areas in the United States experienced disparities in COVID-19 incidence and mortality rates, and people with chronic obstructive pulmonary disease (COPD) are at high risk of poor outcomes. We sought to determine whether veterans with COPD living in rural areas experienced different perceptions and practices of COVID-19 mitigation strategies, access to care, and health disparities during the COVID-19 pandemic, compared to their urban-living counterparts. We performed a one-time survey of veterans with COPD, collecting COVID-19-related information including individual perceptions and practice of mitigation strategies, COVID-19 vaccination status, access to care, and respiratory symptoms stratified by rural-urban status. A total of 100 participants completed the survey with 47 living in rural areas and 53 living in urban areas. There were no significant differences in perceptions and practices related to COVID-19 mitigation strategies (including vaccination), access to care, or respiratory and mental health outcomes. This lack of disparity between rural and urban veterans with COPD might be explained by the strength of the Veterans Health Administration in telemedicine or by an increased uptake of mitigation practices in people with chronic respiratory illness.

Introduction: Bronchiectasis occurs in patients with alpha-1 antitrypsin deficiency (AATD), but it is unknown whether an association exists independently of chronic obstructive pulmonary disease (COPD). We assessed whether bronchiectasis was associated with COPD in our cohort, and whether it has clinical significance for lung function decline, exacerbation rate, or symptoms.

Study design and methods: PiZZ, PiSZ, and PiMZ patients from the Birmingham AATD Research Database were studied. Demographics were recorded, along with the outcomes of symptoms, forced expiratory volume in 1 second (FEV₁), transfer factor of carbon monoxide (TLCO), carbon monoxide transfer coefficient (KCO), and annualized exacerbation rate. Lung function decline was calculated for those with ≥3 measurements. Multivariate regression analyses were conducted to assess for associations of bronchiectasis with each outcome. A further binomial logistic regression model assessed for predictors of bronchiectasis diagnosis, including COPD. Those with alternative bronchiectasis causes were excluded from statistical models.

Results: A total of 1290 patients were eligible. PiZZ patients with bronchiectasis were older at presentation (54 versus 49 years, p<0.001), less likely to have smoked (65% versus 76.1%, p=0.001), and had higher modified Medical Research Council scores (mMRC) (mMRC 2 versus 0 odds ratio [OR] 1.97, 95% constant interval [CI] 1.20-3.25, p=0.008; mMRC 3 versus 0 OR 2.58 95% CI 1.59-4.19, p<0.001; mMRC 4 versus 0 OR 2.2 95% CI 1.23-3.92; p=0.008) than those without. The OR of bronchiectasis diagnosis was not associated with COPD diagnosis in any phenotype. Bronchiectasis was associated with lower serum alpha-1 antitrypsin levels in PiZZ patients (p=0.012). Bronchiectasis was not associated with a difference in FEV₁ percentage predicted (pp)/year decline, KCO pp/year, TLCO pp/year decline, or exacerbation rate in multivariate analysis.

Conclusion: Bronchiectasis exists in a significant minority of AATD patients independently of COPD and is associated with more severe shortness of breath. Appropriate treatment of bronchiectasis in AATD is essential.

Background: The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition.

Objectives: Accordingly, with National Heart, Lung and Blood Institute support, we initiated the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression.

Methods/discussion: SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global initiative for chronic Obstructive Lung Disease (GOLD) groups 0-2 or with preserved ratio-impaired spirometry; and an additional n=40 never-smoker controls. Participants undergo baseline and 3-year follow-up visits, each including high-resolution computed tomography, respiratory oscillometry and spirometry (pre- and postbronchodilator administration), exhaled breath condensate (baseline only), and extensive biospecimen collection, including sputum induction. Symptoms, interim health care utilization, and exacerbations are captured every 6 months via follow-up phone calls. An embedded bronchoscopy substudy involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture.

Conclusion: SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.

Background: This present work focused on predicting prognostic outcomes of inpatients developing acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and enhancing patient monitoring and treatment by using objective clinical indicators.

Methods: The present retrospective study enrolled 322 AECOPD patients. Registry data downloaded based on the chronic obstructive pulmonary disease (COPD) Pay-for-Performance Program database from January 2012 to December 2018 were used to check whether the enrolled patients were eligible. Our primary and secondary outcomes were intensive care unit (ICU) admission and in-hospital mortality, respectively. The best feature subset was chosen by recursive feature elimination. Moreover, 7 machine learning (ML) models were trained for forecasting ICU admission among AECOPD patients, and the model with the most excellent performance was used.

Results: According to our findings, a random forest (RF) model showed superb discrimination performance, and the values of area under the receiver operating characteristic curve were 0.973 and 0.828 in training and test cohorts, separately. Additionally, according to decision curve analysis, the net benefit of the RF model was higher when differentiating patients with a high risk of ICU admission at a <0.55 threshold probability. Moreover, the ML-based prediction model was also constructed to predict in-hospital mortality, and it showed excellent calibration and discrimination capacities.

Conclusion: The ML model was highly accurate in assessing the ICU admission and in-hospital mortality risk for AECOPD cases. Maintenance of model interpretability helped effectively provide accurate and lucid risk prediction of different individuals.

Background: Patients with chronic obstructive pulmonary disease (COPD) often develop other morbidities, suggesting a systemic component to this disease. This retrospective noninterventional cohort study investigated relationships between multimorbidities in COPD and their impact on COPD exacerbations and COPD-related health care resource utilization (HCRU) using real-world evidence from Optum's de-identified Clinformatics® Data Mart Database.

Methods: Demographic and clinical characteristics were assessed. Overall comorbidity burden and proportion of individuals with gastroesophageal reflux disease (GERD), diabetes, or osteoporosis/osteopenia were compared in age-matched COPD versus non-COPD cohorts using descriptive statistics. COPD exacerbations and COPD-related HCRU (hospitalizations and emergency department visits) were compared between age-matched cohorts of COPD patients with and without specific common morbidities (GERD, diabetes, and osteoporosis/osteopenia). Additional weight-matching was performed for matched cohorts of COPD patients with and without diabetes, and with and without osteoporosis/osteopenia. The follow-up period was 5 years.

Results: Age-matched cohorts with and without COPD each comprised 158,106 patients. Morbidities were more common in the COPD cohort than the cohort without COPD (GERD: 44.9% versus 27.8%; diabetes: 40.8% versus 31.1%; osteoporosis/osteopenia: 18.8% versus 14.1%, respectively). Compared with matched cohorts with COPD only, cohorts of COPD patients with either GERD, diabetes, or osteoporosis/osteopenia experienced increased risk of severe exacerbations (odds ratio [OR]=1.819, OR=1.119, and OR=1.373, respectively), moderate exacerbations (OR=1.699, OR=1.102, and OR=1.322, respectively), or any exacerbations (OR=1.848, OR=1.099, and OR=1.384, respectively, p<0.001 for all comparisons) and increased risk of COPD-related HCRU (emergency department visits: OR=1.983, OR=1.098, and OR=1.343, respectively; hospitalization visits: OR=2.222, OR=1.26, and OR=1.368, respectively; p<0.001 for all comparisons).

Conclusion: These real-world data confirm that GERD, diabetes, and osteoporosis are common morbidities in patients with COPD and, moreover, that they affect frequency of exacerbation and HCRU. Determining and addressing the mechanisms behind the systemic effects of COPD may be beneficial for COPD patients and may also help reduce COPD exacerbations.

Background: Social distancing early in the COVID-19 pandemic helped mitigate viral spread and protect vulnerable populations. Broad availability of vaccines allowed social re-integration, but effects on mental health, social determinants of health, and attitudes among individuals with chronic obstructive pulmonary disease (COPD), who are high risk for adverse outcomes following COVID-19 infection, are unknown.

Methods: Participants in the Losartan Effects on Emphysema Progression trial were recruited into an ancillary study from May to November 2020. Study coordinators administered telephone questionnaires to evaluate respiratory symptoms (COPD Assessment Test [CAT]), anxiety (Generalized Anxiety Disorder-7 [GAD-7]) and depressive (Patient Health Questionnaire [PHQ-8]) symptoms, social isolation, instrumental support, and attitudes and actions related to the COVID-19 pandemic. Generalized estimating equation models evaluated changes in patient-reported scores from the period before vaccine availability (prevaccine, May to December 2020) to the postvaccine period (May 2021 to September 2022).

Results: Of 157 enrolled participants, 138 were interviewed during both periods. Compared with the prevaccine period, severe respiratory symptoms (CAT>20) were higher in the postvaccine period (odds ratio [OR] 1.36, 95% confidence interval [CI] 95%: 1.00-1.85), as were moderate anxiety symptoms (GAD-7≥10; OR 1.65, 95%CI: 1.11-2.46) and moderate depressive symptoms (PHQ-8≥10; OR 1.77, 95%CI: 1.22-2.55). Social isolation improved, though not significantly, and instrumental support was unchanged. In the postvaccine period compliance with COVID-19 mitigation strategies remained high and governmental health care entities were viewed as trustworthy by fewer respondents.

Conclusion: Despite a trend towards less social isolation following broad availability of COVID-19 vaccines, individuals with COPD reported worse symptoms, and greater anxiety and depressive symptoms compared to the prevaccine period.

Objective: The objective of this review is to synthesize current evidence of the association between body mass index (BMI) categories and the risk of exacerbation in patients with chronic obstructive pulmonary disease (COPD).

Methods: A systematic search was conducted across 3 electronic databases: PubMed, Embase, and Scopus. Eligible studies must have reported on the association between BMI (either as continuous or categorical) and risk of COPD exacerbation, as defined according to recognized clinical criteria. Observational studies (cohort, case-control, cross-sectional) were eligible for inclusion. The Newcastle Ottawa Scale (NOS) was used to evaluate the methodological quality. Combined effect sizes were reported as relative risk (RR) and corresponding 95% confidence intervals (CI).

Results: A total of 11 studies were included. Of them, 4 studies were prospective, 4 were retrospective cohorts in design, 2 were cross-sectional studies, and one study was a secondary data analysis from a randomized trial. Compared to patients with a normal BMI, underweight patients had an increased risk of COPD exacerbation (RR 1.90, 95% CI: 1.03, 3.48; N=7, I²=94.2%). Overweight and obese BMI status was associated with a similar risk of exacerbation.

Conclusion: Our findings report that underweight, but not overweight or obese patients, have an increased risk of COPD exacerbation, compared to individuals with a normal BMI. This differential association emphasizes the need for nuanced investigations into the underlying mechanisms of the impact of BMI on the course of COPD. Further research is needed to inform personalized interventions and improve COPD management strategies.