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

Background: Falls are frequent among people with chronic obstructive pulmonary disease (COPD) and associated with increased morbidity, mortality, and healthcare costs. Understanding modifiable medication factors that contribute to fall risk is an important step to developing fall prevention strategies for this highly susceptible group.

Methods: This is a retrospective cohort study using electronic health record data from a single health system linked to Washington State death certificates of adults ages 40 or older who died between 2014-2018 with COPD. We identified demographics, comorbidities, fall-risk increasing drug (FRID) burden, and the occurrence of injurious falls within the 2 years prior to the date of death. We defined injurious falls using published algorithms of International Classification of Disease codes.

Results: Of 8204 decedents with COPD, 2454 (30%) had an injurious fall in the two years before death, and FRID use was common among 65%. A higher percentage of patients with falls received prescriptions for anticonvulsants (35% vs 26%), antipsychotics (24% vs 13%), atypical antidepressants (28% vs 19%), tricyclic antidepressants (10% vs 5%) versus those without a fall. In multivariable logistic regression, after adjusting for confounders, FRID burden was associated with greater odds of injurious fall (odds ratio (OR) 1.07 (95% confidence interval (CI) 1.04-1.09).

Conclusion: Our findings highlight an opportunity for collaboration between pharmacists, pulmonologists, and patients to develop new processes to potentially deprescribe and optimize the use of FRIDs among patients with COPD to increase safety.

Rationale: Acute exacerbations of COPD (AECOPD) are heterogeneous. Machine learning (ML) has previously been used to dissect some of the heterogeneity in COPD. The widespread adoption of electronic health records (EHRs) has led to the rapid accumulation of large amounts of patient data as part of routine clinical care. However, it is unclear whether the implementation of ML in EHR-derived data has the potential to identify subgroups of AECOPD.

Objectives: Determine whether ML implementation using EHR data from severe AECOPD requiring hospitalization identifies relevant subgroups.

Methods: This study used two retrospective cohorts of patients with AECOPD (non-COVID-19 and COVID-19) treated at Yale-New Haven Hospital (YNHHS). K-means clustering was used to identify patient subgroups.

Measurements and main results: We identified three subgroups in the non-COVID cohort (n=1,736). Each subgroup had distinct clinical characteristics. The reference subgroup was the largest (n=904), followed by cardio-renal (n = 548) and eosinophilic (n=284). The eosinophilic subgroup had milder severity of AECOPD, including a shorter hospital stay (p<0.01). The cardio-renal subgroup had the highest mortality during (5%) and in the year after hospitalization (30%). Validation of the severe AECOPD classifier in the COVID-19 cohort recapitulated the characteristics seen in the non-COVID cohort. AECOPD subgroups in the COVID-19 cohort had different IL-1 beta, IL-2R, and IL-8 levels (FDR ≤ 0.05. These specific leukocyte and cytokine profiles resulted in inflammatory differences between the AECOPD subgroups based on C-reactive protein levels.

Conclusions: Incorporating ML with EHR-data allows the identification of specific clinical and biological subgroups for severe AECOPD.

A recent study found that the prevalence of COPD is significantly higher among adults who began smoking cigarettes before (vs after) 15 years of age, independent of current smoking, cigarette pack-years, and smoking duration. The current analysis went a step further to also account for second-hand smoke exposure, using data from U.S. adults aged 40+ years during Wave 5 (2018-2019) of the Population Assessment of Tobacco and Health (PATH) Study. Adults who had ever smoked cigarettes were asked at what age they began smoking fairly regularly. Multivariable Poisson regression assessed risk of self-reported COPD diagnosis due to childhood smoking (<15 years), adjusting for current smoking, cigarette pack-years or smoking duration, second-hand smoke exposure, and sociodemographic covariates. Overall, 13.4% reported that they had COPD. COPD prevalence was 7.5% for adults who never smoked compared to 29.0% and 21.1% for smoking onset at age <15 and 15+ years, respectively. Adults who initiated smoking at <15 (vs 15+) years had higher prevalence of current smoking (45.9% vs 33.3%), longer smoking duration (mean 34.2 vs 27.3 years), greater cigarette pack-years (mean 48.8 vs 30.8), and greater second-hand smoke exposure (p's<0.05). In multivariable analysis, the relative risk for COPD for smoking onset <15 (vs 15+) years of age was 1.27 (95% confidence interval [CI]=1.06, 1.51). The increased risk of COPD due to childhood smoking was independent of cigarette pack-years, smoking duration, second-hand smoke exposure, and current smoking. Findings give further evidence of increased COPD risk related to childhood smoking.

Rationale: Evidence-based guidelines recommend screening all individuals with chronic obstructive pulmonary disease (COPD) for the genetic disorder alpha-1 antitrypsin deficiency (AATD). However, it is estimated that only 5% of people with COPD have been tested for AATD, and a large fraction of the estimated 70,000 to 100,000 Americans with AATD have not yet been diagnosed. Low familiarity with AATD and limited knowledge about diagnostic tests and available treatments contribute to suboptimal screening rates.

Objectives: To address barriers to and improve rates of guideline-based AATD diagnostic testing among racially and ethnically diverse patients with COPD at a large community health center.

Methods: A quality improvement initiative consisting of educational sessions and electronic health record (EHR) system interventions was implemented to improve the adoption of guideline-based screening for AATD in patients with COPD.

Results: An analysis of EHR data demonstrated that of patients with a COPD diagnosis (N = 1,030), 22.2% (n = 229) were screened for AATD in the 12 months following the start of the quality improvement initiative compared with 1.3% (n = 13) of patients with a COPD diagnosis (N = 972) seen in the 12 months prior to the start of the quality improvement initiative (P < 0.001).

Conclusions: A quality improvement initiative consisting of educational sessions and EHR system modifications was successful in increasing clinicians' knowledge and diagnostic screening rates for AATD in patients with COPD at a large community health center.

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 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: Thirty adults with COPD were randomized to intervention (n=15) or control, with 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 (PIMax). 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 efficacy of RESP-FIT, determine mechanisms of action on dyspnea and fatigue, and conduct within-subject comparisons of EMA data to explore individual or environmental fluctuations in COPD symptoms.

Background: Continuous respiratory monitoring can support integrated care for chronic obstructive pulmonary disease (COPD) patients, by coupling them with remote clinical personnel who triage patients in coordination with their health care providers. When deploying such services, there remains uncertainty surrounding outcomes when at-risk patients are proactively identified and escalated for provider evaluation. This study presents findings from a service deployed in a real-world COPD cohort by analyzing the clinical interventions made during in-person and telehealth pulmonary outpatient visits following remote escalations.

Methods: A single-center, retrospective, observational study of real-world COPD patients at a multi-site pulmonary practice was conducted. Patients who were enrolled in a continuous respiratory monitoring service for at least one year and were seen by a provider within seven days of an escalation by the service (N=168) were included. To evaluate the potential impact of these escalations on provider and patient burden, medical charts from outpatient visits were manually reviewed and grouped into six categories based on the clinical action(s) taken by the provider.

Results: A total of 245 outpatient visits occurred from 168 patients within seven days of escalation. Of the 245 visits, 206 (84.1%) resulted in clinical intervention and 163 (66.5%) resulted in treatment consistent with acute exacerbations of COPD (AECOPDs). 1.6% of the outpatient visits resulted in referral to the emergency room.

Conclusion: Provider encounters occurring following the escalation of a patient from a continuous respiratory monitoring service consistently resulted in that provider administering a treatment to the escalated patient.

Alpha-1 antitrypsin deficiency is an autosomal codominant disorder caused by SERPINA1 gene mutations. PI*Z and PI*S mutations commonly underlie this deficiency, but rarer homozygous PI*null (Q0) mutations may result in a complete loss of alpha-1 antitrypsin (AAT). Such rare mutations lead to severe AAT deficiency and early onset of lung disease. We present a case of 35-year-old female never-smoker born to consanguineous parents who developed severe panlobular emphysema and end-stage respiratory insufficiency requiring lung transplantation. Subsequent genetic testing identified her as homozygous for a novel c.82del mutation - here named Q0_Bani-Yas based on the region of the primary carrier's origin - which resulted in undetectable levels of alpha-1 antitrypsin protein.

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.