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

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: Our objective was 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 among patients with a COPD diagnosis (n=1030), 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: Falls are frequent among people with chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity, mortality, and health care 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 the International Classification of Diseases codes.

Results: Of 8204 decedents with COPD, 2454 (30%) had an injurious fall in the 2 years before death, and FRID use was common among 65%. A higher percentage of patients with falls received prescriptions for anticonvulsants (35% versus 26%), antipsychotics (24% versus 13%), atypical antidepressants (28% versus 19%), and tricyclic antidepressants (10% versus 5%) versus those without a fall. In multivariable logistic regression, after adjusting for confounders, FRID burden was associated with greater odds of an injurious fall (odds ratio 1.07 [95% confidence interval 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.

Alpha-1 antitrypsin (AAT) 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 AAT. Such rare mutations lead to severe AAT deficiency and early onset of lung disease. We present a case of a 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 the AAT protein.

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.