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

Background: Alpha-1 antitrypsin deficiency (AATD) is characterized by low alpha-1 antitrypsin (AAT) levels, predisposing individuals to lung disease. The standard of care, plasma-derived AAT (pdAAT), is delivered as weekly infusions to maintain serum AAT concentrations ≥11µM (≈50% of those in healthy individuals). INBRX-101, a recombinant human AAT-Fc fusion protein, was designed to have a longer half-life and achieve higher AAT levels than pdAAT.

Methods: In this phase 1 dose-escalation study (N=31), adults with AATD received 1 dose (part 1) or 3 doses (part 2) of 10 (part 1), 40, 80, or 120mg/kg INBRX-101 every 3 weeks (Q3W) via intravenous infusion. The primary endpoint was safety and tolerability. Secondary endpoints were pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of INBRX-101.

Results: INBRX-101 was well tolerated. Most treatment-emergent adverse events were grade ≤2. In part 2 (n=18; each dose, n=6), dose-related increases in serum functional AAT (fAAT) were observed; mean fAAT levels remained above the 21 µM target for up to 4 weeks after the final dose in the 120-mg/kg cohort. Antidrug antibodies had no meaningful impact on PK or PD. INBRX-101 was detected in pulmonary epithelial lining fluid (PELF) from all patients assessed (n=11), and PELF fAAT increased after dosing. PK/PD modeling projected steady-state serum fAAT ≥21µM at 120 mg/kg Q3W (average concentration ≈43µM; trough concentration ≈28µM) and Q4W (≈34µM; ≈21µM).

Conclusion: The favorable safety profile and ability to maintain serum fAAT levels >21µM with extended-interval dosing, support a phase 2 trial evaluating Q3W and Q4W dosing of INBRX-101.

Background: Daily physical activity is part of the self-management of patients with chronic obstructive pulmonary disease (COPD), and didactic information sessions may be insufficient for the provision of these skills. Prior activation can determine sensitivity to these sessions. We evaluated whether the activation in patients with COPD, as measured by the Patient Activation Measure (PAM)-13 questionnaire, determined their responses to an educational group session on physical activity (PA), which were measured with actigraphy by the number of steps/day.

Methods: We conducted an uncontrolled clinical trial in an outpatient clinic with 75 patients with nonexacerbating COPD (forced expiratory volume in 1 second 30%-80%) who were selected consecutively. Patients were provided with an actigraph that they used for 15 days and completed the PAM-13 questionnaire. On the eighth day, they attended a group educational session where they were given PA information. We compared the changes in activity after the session by pooled PAM levels and the correlation between the change in the number of steps/day and the PAM-13 questionnaire.

Results: A total of 26 patients had activation levels of 1-2, while 49 patients had levels of 3-4. After the session, patients in Levels 1-2 decreased their number of steps (-596±42), while those in Levels 3-4 increased them (680±253, p<0.01). The level of activation was positively correlated with change in the number of steps/day (p<0.05).

Conclusion: COPD patients with greater activation showed greater improvements in daily PA after a group educational session.

Background: Patient perception of medication onset of effect is important for adherence. Although the Onset of Effect Questionnaire (OEQ) has been validated in patients with asthma, it has not been evaluated in patients with chronic obstructive pulmonary disease (COPD). This study evaluated the COPD-OEQ in patients with COPD.

Methods: Two analyses (qualitative and quantitative) were conducted to assess the content validity and psychometric properties of the COPD-OEQ in participants with COPD. In the qualitative analysis, interviews assessed content validity by concept elicitation (CE) and cognitive interviewing (CI). CE included questions to understand patient experience related to onset of medication effect. CI included completion of the COPD-OEQ and assessment of the COPD-OEQ items, response options, and instructions. During the 2-week quantitative analysis, 2 versions of the COPD-OEQ (Weekly and Daily) were administered to assess test-retest reliability, construct validity, and known-groups validity.

Results: The qualitative analysis demonstrated that 3 of the 5 COPD-OEQ items were relevant and understood as intended. Qualitative findings demonstrated inconsistent evidence that the COPD-OEQ Weekly and Daily were reliable and valid measures in participants with COPD. Test-retest reliability was observed for the COPD-OEQ Weekly and Daily; however, construct validitywas weak and demonstrated inconsistent correlations among COPD-OEQ items. Overall, known-groups validity was not demonstrated.

Conclusion: The weak evidence from the quantitative analysis of the COPD-OEQ Weekly and Daily tools does not support use of the OEQ in general COPD. The study supports the content validity for the assessment of perceived onset of effect in patients with COPD.

Background: Chronic obstructive pulmonary disease (COPD) is a significant public health concern and intercepting the development of emphysema is vital for COPD prevention. Smokers are a high-risk population for emphysema with limited prevention strategies. We aimed to determine if adherence to a nutritionally rich, plant-centered diet among young ever-smokers is associated with reduced risk of future radiographic emphysema.

Methods: We studied participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Lung Prospective Cohort Study who were 18-30 years old at enrollment and followed for 30 years. We analyzed 1706 adults who reported current or former smoking by year 20. Repeated measures of diet history were used to calculate A Priori Diet Quality Scores (APDQSs), and categorized into quintiles, with higher quintiles representing higher nutritionally rich plant-centered food intake. Emphysema was assessed at year 25 (n=1351) by computed tomography (CT). Critical covariates were selected, acknowledging potential residual confounding.

Results: Emphysema was observed in 13.0% of the cohort, with a mean age of 50.4 ± 3.5 years. The prevalence of emphysema was 4.5% in the highest APDQS quintile (nutritionally rich), compared with 25.4% in the lowest quintile. After adjustment for multiple covariates, including smoking, greater adherence to a plant-centered diet was inversely associated with emphysema (highest versus lowest quintile odds ratio: 0.44, 95% CI 0.19-0.99, p_trend=0.008).

Conclusion: Longitudinal adherence to a nutritionally rich, plant-centered diet was associated with a decreased risk of emphysema development in middle adulthood, warranting further examination of diet as a strategy for emphysema prevention in a high-risk smoking population.

Background: Revefenacin, a once-daily, nebulized, long-acting muscarinic antagonist approved in the United States for the maintenance of chronic obstructive pulmonary disease (COPD), significantly improves lung function and quality of life versus placebo in patients with moderate-to-very severe COPD. Comorbid anxiety and/or depression may alter patients' symptom perception and response to bronchodilators. The impact of revefenacin in patients with COPD with comorbid anxiety and/or depression has not been previously investigated.

Methods: This post hoc subgroup analysis examined data from two 12-week, randomized, phase 3 trials in patients with moderate-to-very severe COPD with the following self-reported subgroups: anxiety only (A), depression only (D), anxiety and depression (+A/+D), and neither anxiety nor depression (-A/-D). We assessed change from baseline in trough forced expiratory volume in 1 second (FEV₁) at Day 85 and health status by the St George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT).

Results: Of 812 patients, 90 (11%), 110 (14%), 141 (17%), and 471 (58%) had A, D, +A/+D, and -A/-D respectively. In revefenacin versus placebo, trough FEV₁ significantly improved from baseline at Day 85 across all subgroups as well as the SGRQ and CAT scores in patients with A, +A/+D, and -A/-D. Revefenacin was well tolerated regardless of A/D status, with a minimal incidence of treatment-emergent antimuscarinic adverse events across subgroups.

Conclusion: In this analysis, revefenacin versus placebo significantly improved health outcomes in patients with moderate-to-very severe COPD with A, +A/+D, and -A/-D, but not in patients with D. The safety profile of revefenacin was not affected by comorbid anxiety/depression status.

Background: We examined the effect of physical position on peak inspiratory flow (PIF) in patients with chronic obstructive pulmonary disease (COPD) using dry-powder inhalers (DPIs) with low‑medium internal resistance (R2) and/or high internal resistance (R5).

Methods: This prospective study in stable, ambulatory patients with spirometry-confirmed COPD evaluated the effect of 3 physical positions on maximal PIF achieved. Participants had PIFs of 30-90L/min (R5) or 60-90L/min (R2 DPIs) using the In-Check™ DIAL. PIF was measured in triplicate randomly in 3 positions that patients might be in while using their inhaler (standing, sitting, and semi-upright [supine position with the head of the bed at 45°, neck flexed forward]) against prescribed DPI resistance (R2/R5/both). Correlations between PIF and percentage decline in PIF between positions and differences in participant characteristics with >10% versus ≤10% PIF decline standing to semi-upright were calculated.

Results: A total of 76 participants (mean age, 65.2 years) had positional measurements; 59% reported seated DPI use at home. The mean (standard deviation) PIF standing, sitting, and semi-upright was 80.7 (13.4), 77.8 (14.3), and 74.0 (14.5) L/min, respectively, for R2 and 51.1 (9.52), 48.6 (9.84), and 45.8 (7.69) L/min, respectively, for R5 DPIs. PIF semi-upright was significantly lower than sitting and standing (R2; P < 0.0001) and standing (R5; P= 0.002). Approximately half of the participants had >10% decline in PIF from standing to semi-upright. Patient characteristics exceeding the 0.10 absolute standardized difference threshold with the decline in PIF for both the R2 and R5 DPIs were waist-to-hip ratio, modified Medical Research Council dyspnea score, and postbronchodilator percentage predicted forced vital capacity and PIF by spirometry.

Conclusions: PIF was significantly affected by physical position regardless of DPI resistance. PIF was highest when standing and lowest when semi-upright. We recommend that patients with COPD stand while using an R2 or R5 DPI. Where unfeasible, the position should be sitting rather than semi-upright. ClinicalTrials.gov identifier NCT04168775.

Background: Health inequities among individuals with chronic obstructive pulmonary disease (COPD) are often associated with differential access to health care and health outcomes. A greater understanding of the literature concerning such variation is necessary to determine where gaps or inequities exist along the continuum of COPD care.

Methods: A rapid review of the published and grey literature reporting variations in health care access and/or health outcomes for individuals with COPD was completed. Variation was defined as differential patterns in access indicators or outcome measures within sociodemographic categories, including age, ethnicity, geography, race, sex, and socioeconomic status. Emergent themes were identified from the included literature and synthesized narratively.

Results: Thirty-five articles were included for final review; the majority were retrospective cohort studies. Twenty-five studies assessed variation in access to health care. Key indicators included: access to spirometry testing, medication adherence, participation in pulmonary rehabilitation, and contact with general practitioners and/or respiratory specialists. Twenty-one studies assessed variation in health outcomes in COPD and key metrics included: hospital-based resource utilization (length of stay and admissions/readmissions), COPD exacerbations, and mortality. Patients who live in rural environments and those of lower socioeconomic status had both poorer access to care and outcomes at the system and patient level. Other sociodemographic variables, including ethnicity, race, age, and sex were associated with variation in health care access and outcomes, although these findings were less consistent.

Conclusion: The results of this rapid review suggest that substantial variation in access and outcomes exists for individuals with COPD, highlighting opportunities for targeted interventions and policies.

Study objectives: Observational studies link untreated obstructive sleep apnea (OSA) with adverse outcomes in chronic obstructive pulmonary disease (COPD). The first step in addressing OSA is a clinical assessment. However, given competing demands and a lack of high-quality evidence, it is unclear how often such assessments occur. We explored the documentation of OSA assessment among patients with COPD in primary care, and the patient and provider characteristics associated with these assessments.

Methods: We conducted a cross-sectional study of patients with clinically diagnosed COPD at 2 primary care practices. We abstracted charts to determine whether providers assessed OSA, defined as documentation of symptoms, treatment, or a referral to sleep medicine. We performed multivariable mixed-effects logistic regression to assess the associations of patient and provider characteristics with OSA assessment.

Results: Among 641 patients with clinically diagnosed COPD, 146 (23%) had OSA assessed over a 1-year period. Positive associations with OSA assessment included body mass index ≥ 30 (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-7.0), pulmonary subspecialist visits (OR 3.9, 95%CI 2.4-6.3), and a prior sleep study demonstrating OSA documented within the electronic medical record (OR 18.0, 95%CI 9.0-35.8). Notably, patients identifying as Black were less likely to have OSA assessed than those identifying as White (OR 0.5, 95%CI 0.2-0.9).

Conclusions: Providers document an assessment of OSA among a quarter of patients with COPD. Our findings highlight the importance of future work to rigorously test the impact of assessment on important health outcomes. Our findings also reinforce that additional strategies are needed to improve the equitable delivery of care.