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

Background: Triple therapy with inhaled corticosteroids and dual bronchodilator therapy is recommended for chronic obstructive pulmonary disease (COPD) patients who have exacerbations and eosinophilia. It can be administered by single inhaler triple therapy (SITT) or by multiple inhaler triple therapy (MITT). There is a lack of evidence of the benefits of SITT over MITT in the Chinese population, especially on switching from existing MITT to SITT.

Methods: A total of 70 Chinese patients with COPD were recruited in this open-label, double-arm clinical trial to investigate the number of critical inhaler errors, the modified Medical Research Council (mMRC) dyspnea scale, the Medication Adherence Report Scale for Asthma (MARS-A) score, and a satisfaction score upon switching from MITT to SITT.

Results: The mean number of critical inhaler errors was 0.4±1.0 in the SITT group and 1.1±1.8 in the MITT group( p=0.038) at the first visit; and 0.2±0.6 in the SITT group and 0.8±1.1 in the MITT group (p=0.007) at the second visit. The mean change in MARS-A from baseline to first visit was +3.76±7.48 in the SITT group and -1.27±7.76 in the MITT group (p-value 0.008). A total of 22 (59.5%) and 8 (24.2%) of the patients in the SITT and the MITT group respectively, had an increase in MARS-A score from baseline to first visit, with an adjusted odds ratio of 6.23 (95% confidence interval=1.63-23.77, p=0.007), favoring SITT. There was no significant difference in the change in the mMRC dyspnea scale and the satisfaction score between the 2 groups.

Conclusion: Switching from MITT to SITT in Chinese COPD patients may have the benefits of having fewer critical inhaler errors and a higher MARS-A score.

Background: Cigarette smoke contributes to skeletal muscle wasting. While exercise and nutritional therapies are effective in improving skeletal muscle quantity and quality, the effect of medications on longitudinal muscle loss is unclear. We investigated whether long-term use of common medications affects longitudinal skeletal muscle changes in current and former smokers.

Methods: Using quantitative computed tomography imaging, we measured the 5-year changes in pectoralis muscle area (delta-PMA) and pectoralis muscle density (delta-PMD) of 4191 participants in the COPD Genetic Epidemiology (COPDGene^®) study. We tested whether specific medications were associated with delta-PMA and/or delta-PMD using regression analyses. Propensity score matching (PSM) analysis was performed to determine the effect of the medications on longitudinal changes on delta-PMA.

Results: Over the study period, the median delta-PMA for the entire population showed a decrease of 2.23cm² (interquartile range: -6.52, 1.54). Regression analyses demonstrated statin use was associated with less loss of PMA, whereas, aspirin use was associated with a greater loss of PMA. Specifically, in the PSM-adjusted analysis, statin use was associated with attenuated loss of PMA (median; -1.5 versus -2.5cm², p=0.017), while aspirin use was associated with increased loss of PMA (median; -2.5 versus -1.9cm², p=0.040).

Conclusion: In current and former smokers, statin use was associated with reduced pectoralis muscle wasting, while aspirin use was associated with increased muscle loss. Additional research is needed to verify these findings. (Clinicaltrials.gov identifier NCT00608764).

Chronic obstructive pulmonary disease (COPD) is a highly prevalent inflammatory lung condition characterized by chronic respiratory symptoms and airflow obstruction that often leads to diminished quality of life. Nonpharmacologic management for patients with COPD involves smoking cessation and healthy lifestyle changes. Pharmacologic treatments include inhaled bronchodilators with or without the use of inhaled corticosteroids, which can be administered through inhalation or nebulization. In addition, oral medications including macrolide antibiotics and phosphodiesterase (PDE) 4 inhibitors can help reduce exacerbation risk. However, many of these medications provide suboptimal disease control, owing to limited efficacy, increased risk of adverse events with long-term use, or difficulty in administration technique. PDE3 plays an important role in maintaining smooth muscle function, and PDE4 plays a crucial role in the inflammatory response in airway smooth muscle. Direct molecular inhibition of PDE3 or PDE4 has been shown to provide benefit in COPD. Dual PDE3 and PDE4 inhibition may, therefore, have synergistic anti-inflammatory and bronchodilator effects. These results have been observed in clinical trials of nebulized ensifentrine, a novel, dual-action PDE3 and PDE4 inhibitor that is the first in its class to be approved by the U.S. Food and Drug Administration for maintenance treatment of COPD in adult patients. In this review, we explore the pathophysiologic mechanisms of COPD, describe current paradigms and methods of drug delivery for the treatment of the disease, and illustrate how dual inhibition of PDE3 and PDE4 may provide additional benefit to current standard-of-care regimens.

Objective: Chronic obstructive pulmonary disease (COPD) is closely associated with arthritis. This study aims to evaluate the correlation between COPD and mortality among participants with arthritis.

Methods: The study included 11,298 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, who self-reported having arthritis. Cox proportional hazard models were used to assess the association between COPD and mortality among participants with arthritis. Kaplan-Meier survival curves were plotted to compare survival probabilities between groups. Subgroup and sensitivity analyses were conducted to assess the robustness of the results.

Results: During an average follow-up of 8.8 years, 3061 all-cause deaths were observed, including 1024 related to cardiovascular disease (CVD). After weighted multivariable adjustment, COPD was found to be significantly associated with both all-cause and CVD mortality among these arthritis participants. The hazard ratio (HR) for all-cause mortality among arthritis patients with COPD was 1.41 (95% confidence interval [CI]: 1.25-1.60, p < 0.001), and the HR for CVD mortality was 1.29 (95% CI: 1.08-1.53, p < 0.001). Kaplan-Meier survival curves attributed higher rates of both all-cause and CVD mortality among participants with COPD compared to those without (log-rank test, p < 0.001). Additionally, COPD increased the risk of both chronic lower respiratory disease (CLRD) mortality (HR 5.46, 95% CI: 3.48-8.56, p < 0.001) and non-CLRD mortality (HR 1.24, 95% CI: 1.07-1.44, p=0.004).

Conclusion: In the American population, arthritis patients with COPD have higher risks of all-cause and CVD mortality compared to those without COPD.

Background: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is one of the 6 conditions in the Hospital Readmissions Reduction Program for which institutions are penalized for high 30-day readmission rates. This institution's transitions of care (TOC) pharmacists have prescribing authority to optimize guideline-directed medical therapy (GDMT), defined as discharging on rescue plus triple therapy inhalers under an approved protocol. While several studies evaluate the impact of pharmacist-led interventions on COPD readmission rates, there is a lack of literature with respect to pharmacists prescribing inhalers under an approved protocol. This study aims to evaluate all-cause 30-day COPD readmission rates.

Methods: This was an institutional review board-approved, single-center, retrospective evaluation conducted between May 2021 and August 2023. Patients were included if they met criteria under the Centers for Medicare and Medicaid Services Hospital Readmissions Reduction Program COPD model. Patients in the pre-implementation group received usual care, with postdischarge nurse follow-up while patients in the postimplementation group received TOC pharmacy services. The primary outcome was all-cause 30-day readmission rates. Secondary outcomes included readmission reason and proportion of patients discharged on GDMT.

Results: A total of 279 patients were included, with 187 patients in the pre-implementation group and 92 patients in the postimplementation group. All-cause 30-day readmission rates in the pre- and postimplementation groups were 26% and 14%, respectively (p=0.02). The proportion of patients discharged on GDMT was 26% in the pre-implementation group and 100% in the postimplementation group (p<0.001).

Conclusion: Utilizing a TOC pharmacy service may be associated with a reduction in all-cause 30-day readmission rates for patients with COPD.

Background: The impact of iron deficiency on COPD morbidity independent of anemia status is unknown. Understanding the association between iron deficiency, anemia status, and risk of hospitalization in COPD may inform an approach to these comorbidities.

Study design and methods: Adults ≥40 years from the Johns Hopkins COPD Precision Medicine Center of Excellence data repository with an outpatient iron profile and 1 year of subsequent follow-up time were included in the study. Baseline characteristics were compared across iron status, defined by transferrin saturation (TSAT), using t-tests and Chi-squared tests. The association between continuous TSAT and all-cause hospitalization over the 1-year follow-up period was assessed by logistic regression. Models were adjusted by covariates with an interaction term for anemia and stratified by sex.

Results: There were 6532 individuals included with an average age of 65±12 years, 59% were female, and 56% White. Fifty-two percent of the cohort were iron deficient (TSAT≤20%), among whom 27% were non-anemic. Iron-deficient individuals had lower lung function and a higher prevalence of heart failure and diabetes. Iron deficiency was more prevalent among females (57%) compared to males (44%). In adjusted models, a decrease in TSAT by 10% was associated with 14.3% higher odds of all-cause hospitalization for females (95%CI:1.0-1.3), but not among males (OR:1.08, 95%CI:0.9-1.3). There was effect modification by anemia such that the association between TSAT and all-cause hospitalization was greater in non-anemic women (p-value interaction=0.08).

Interpretation: Iron deficiency may be associated with adverse outcomes in the absence of anemia, with non-anemic women being a COPD sub-population particularly sensitive to iron deficiency.

Background: Despite guideline recommendations, most patients with chronic obstructive pulmonary disease (COPD) do not undergo alpha-1 antitrypsin deficiency (AATD) testing and approximately 90% of people with AATD in the United States remain undiagnosed. This study sought to develop a predictive model using real-world data to improve detection of AATD-positive patients in the general COPD population.

Methods: A predictive model using extreme gradient boosting was developed using the EVERSANA database, including longitudinal, patient-level medical claims, prescription claims, AATD-specific testing data, and electronic health records (EHR). The model was trained and then validated to predict AATD-positive status. Patients were coded as AATD positive based on the presence of any of the following criteria: (1) ≥2 AATD diagnosis codes in claims; (2) an AATD diagnosis code in the EHR; (3) a positive laboratory test for AATD; or (4) use of AATD-related medication. Over 500 variables were used to train the predictive model and >20 models were run to optimize the predictive power.

Results: A total of 13,585 AATD-positive patients and 7796 AATD-negative patients were included in the model. The inclusion of non-AATD laboratory test results was critical for defining cohorts and optimizing model prediction (e.g., respiratory comorbidities, and calcium, glucose, hemoglobin, and bilirubin levels). The final model yielded high predictive power, with an area under the receiver operating characteristic curve of 0.9.

Conclusion: Predictive modeling using real-world data is a sound approach for assessing AATD risk and useful for identifying COPD patients who should be confirmed by genetic testing. External validation is warranted to further assess the generalizability of these results.

Background: Most studies on mental health among individuals with chronic obstructive pulmonary disease (COPD) utilize screening questionnaires, which detect psychiatric symptoms, but cannot be used to diagnose depression/anxiety disorders. We utilized the Mini-International Neuropsychiatric Interview (MINI) to identify depression/anxiety disorders meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnostic criteria and described associated disease burden in people with COPD.

Methods: This is a cross-sectional, secondary analysis of a multicenter study designed to evaluate anxiety questionnaires in COPD patients. Research coordinators administered both the MINI and screening questionnaires to determine participants who met diagnostic criteria for depression/anxiety disorders and to capture symptom burden, respectively. Bivariate analyses were conducted to assess differences in COPD and patient-reported outcomes between those with and without depression/anxiety disorders.

Results: Of 220 participants, 18 (8%) met the MINI criteria for depression and 17 (8%) for anxiety. Depression was associated with more breathlessness (modified Medical Research Council Dyspnea Scale 4 versus 3, p=0.045), higher COPD disease burden (COPD Assessment Test [CAT] 27 versus 17, p<0.001), worse sleep quality (Pittsburgh Sleep Quality Index 11 versus 7, p=0.001) and health-related quality of life (5-Level EQ-5D 0.31 versus 0.59, p<0.001). Anxiety was associated with lower CAT scores and worse health-related quality of life and function. Most with depression/anxiety disorders were not using antidepressants/anxiolytics, or receiving mental health counseling.

Conclusion: Depression and anxiety disorders meeting diagnostic criteria are relatively common comorbidities that substantially impair quality of life and are undertreated, highlighting a need to prioritize mental health as an integral part of comprehensive COPD care.

This study aimed to evaluate the performance of machine learning models for predicting readmission of patients with Chronic Obstructive Pulmonary Disease (COPD) based on administrative data and chart review data. The study analyzed 4,327 patient encounters from the University of Chicago Medicine to assess the risk of readmission within 90 days after an acute exacerbation of COPD. Two random forest prediction models were compared. One was derived from chart review data, while the other was derived using administrative data. The data were randomly partitioned into training and internal validation sets using a 70%/30% split. The two models had comparable accuracy (administrative data AUC = 0.67, chart review AUC = 0.64). These results suggest that despite its limitations in precisely identifying COPD admissions, administrative data may be useful for developing effective predictive tools and offer a less labor-intensive alternative to chart reviews.

Introduction: Lung physiology and chronic obstructive pulmonary disease (COPD) pathophysiology differ between sexes. This post hoc analysis investigated the InforMing the Pathway of COPD Treatment (IMPACT) trial outcomes by patient sex.

Methods: IMPACT was a double-blind, 52-week trial. Patients ≥40 years with symptomatic COPD and a history of exacerbations were randomized 2:2:1 to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25μg, FF/VI 100/25μg, or UMEC/VI 62.5/25μg. Annual rate and risk of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 second (FEV₁) and St George's Respiratory Questionnaire (SGRQ) score, and safety were assessed.

Results: Of 10,355 patients, 66.3% were male. More females reported ≥2 moderate/severe prior exacerbations (58% versus 53%) at screening versus males. Additionally, females had worse mean (standard deviation) SGRQ scores (52.4[15.97] versus 49.8[17.24]) at baseline. FF/UMEC/VI improved annual exacerbation rate, lung function, and health status for both sexes versus dual therapy. The difference in trough FEV₁ across time points with FF/UMEC/VI versus FF/VI was 103mL-110mL in males and 70mL-84mL in females. On-treatment moderate/severe exacerbation rates remained higher for females (FF/UMEC/VI: 0.99; FF/VI: 1.19; UMEC/VI: 1.35) than males (0.87; 1.01; 1.14). Fewer exacerbations were experienced by females with eosinophil counts <150 cells/µL (0.81[0.68, 0.97], p=0.024) or <2 exacerbations in the past year (0.73[0.57, 0.94], p=0.013) with FF/UMEC/VI versus UMEC/VI.

Conclusion: More females with COPD reported exacerbations in the prior year at screening, as well as during the study, versus males, across all treatments. FF/UMEC/VI improved exacerbation rates versus UMEC/VI in females with eosinophil counts <150 cells/µL or <2 exacerbations in the prior year, suggesting inhaled corticosteroids may play an important role in exacerbation reduction for females in this patient population. Clinical Trial Registration: GSK (CTT116855/NCT021645B).