COPD: Providing the right treatment for the right patient at the right time.

Chronic Obstructive Pulmonary Disease (COPD) is a common disease associated with significant morbidity and mortality that is both preventable and treatable. However, a major challenge in recognizing, preventing, and treating COPD is understanding its complexity. While COPD has historically been characterized as a disease defined by airflow limitation, we now understand it as a multi-component disease with many clinical phenotypes, systemic manifestations, and associated co-morbidities. Evidence is rapidly emerging in our understanding of the many factors that contribute to the pathogenesis of COPD and the identification of "early" or "pre-COPD" which should provide exciting opportunities for early treatment and disease modification. In addition to breakthroughs in our understanding of the origins of COPD, we are optimizing treatment strategies and delivery of care that are showing impressive benefits in patient-centered outcomes and healthcare utilization. This special issue of Respiratory Medicine, "COPD: Providing the Right Treatment for the Right Patient at the Right Time" is a summary of the proceedings of a conference held in Stresa, Italy in April 2022 that brought together international experts to discuss emerging evidence in COPD and Pulmonary Rehabilitation in honor of a distinguished friend and colleague, Claudio Ferdinando Donor (1948-2021). Claudio was a true pioneer in the field of pulmonary rehabilitation and the comprehensive care of individuals with COPD. He held numerous leadership roles in in the field, provide editorial stewardship of several respiratory journals, authored numerous papers, statement and guidelines in COPD and Pulmonary Rehabilitation, and provided mentorship to many in our field. Claudio's most impressive talent was his ability to organize spectacular conferences and symposia that highlighted cutting edge science and clinical medicine. It is in this spirit that this conference was conceived and planned. These proceedings are divided into 4 sections which highlight crucial areas in the field of COPD: (1) New concepts in COPD pathogenesis; (2) Enhancing outcomes in COPD; (3) Non-pharmacologic management of COPD; and (4) Optimizing delivery of care for COPD. These presentations summarize the newest evidence in the field and capture lively discussion on the exciting future of treating this prevalent and impactful disease. We thank each of the authors for their participation and applaud their efforts toward pushing the envelope in our understanding of COPD and optimizing care for these patients. We believe that this edition is a most fitting tribute to a dear colleague and friend and will prove useful to students, clinicians, and researchers as they continually strive to provide the right treatment for the right patient at the right time. It has been our pleasure and a distinct honor to serve as editors and oversee such wonderful scholarly work.

Patient and Clinical Demographics of New Users to Single-Inhaler Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy was approved by the United States Food and Drug Administration in 2017 as a maintenance therapy for chronic obstructive pulmonary disease (COPD). Patient characteristics and treatment patterns prior to initiating FF/UMEC/VI are currently unknown. This study assessed patient characteristics, exacerbation, and medication history in patients with COPD before the initiation of FF/UMEC/VI or multiple-inhaler triple therapy (MITT). METHODS: This was a retrospective study using the Optum Clinformatics® Data Mart. Patients who initiated FF/UMEC/VI triple therapy or MITT (consisting of a long-acting muscarinic antagonist [LAMA], long-acting ß2-agonist [LABA], and inhaled corticosteroid [ICS]) between October 2017 and September 2018, were enrolled in commercial or Medicare Advantage Prescription Drug plans, were aged > 40 years, and had a COPD diagnosis were eligible. Patient characteristics, comorbidities, COPD medication use, exacerbations, and eosinophil counts were assessed in the 12-month baseline period prior to initiation of FF/UMEC/VI triple therapy or MITT. RESULTS: The study population included 3933 FF/UMEC/VI users and 18,244 MITT users. Mean (standard deviation) patient age was 72.2 (8.6) years in FF/UMEC/VI users and 70.7 (9.7) years in MITT users. Prior to initiating triple therapy, the majority of FF/UMEC/VI (89.1%) and MITT (93.8%) users experienced a moderate or severe exacerbation or used a COPD maintenance therapy during the baseline period. In addition, 41.2% of FF/UMEC/VI users received overlapping ICS/LAMA/LABA, 20.3% received ICS/LABA, and 9.7% received LAMA/LABA. CONCLUSION: In this population of COPD patients, triple therapy was frequently initiated after previous maintenance medication use or an exacerbation, in line with treatment guideline recommendations.

Adherence and persistence to once-daily single-inhaler versus multiple-inhaler triple therapy among patients with chronic obstructive pulmonary disease in the USA: A real-world study.

BACKGROUND: Triple therapy comprising an inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting ß2 agonist (ICS/LAMA/LABA) is recommended for chronic obstructive pulmonary disease (COPD) patients at risk of exacerbation. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence; however, these outcomes have not been evaluated for single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI). METHODS: This retrospective analysis of the IQVIA PharMetrics Plus claims database identified patients with COPD initiating triple therapy between 18 September 2017 and 30 June 2019. The first date of single-inhaler FF/UMEC/VI dispensing, or first day of overlapping ICS, LAMA, and LABA medications for MITT users, defined the index date. Patients were ≥40 years, had ≥12 months of continuous insurance coverage pre-index (baseline) and ≥6 months' coverage post-index; those with MITT during baseline were excluded. Inverse probability weighting was used to balance baseline characteristics. Adherence was assessed using proportion of days covered (PDC) and was evaluated using linear and log-binomial models. Persistence (non-persistence identified as >30-day gap between fills) was evaluated using Cox models. RESULTS: 9942 patients (FF/UMEC/VI: 2782; MITT: 7160) were included. Adherence was significantly higher for FF/UMEC/VI versus MITT users (mean PDC, 0.66 vs. 0.48; p < 0.001), and FF/UMEC/VI users were twice as likely to be adherent (PDC ≥0.8) than MITT users (46.5% vs. 22.3%; risk ratio [95% CI]: 2.08 [1.85-2.30]; p < 0.001). After 12 months, significantly more FF/UMEC/VI users persisted on therapy than MITT users (35.7% vs. 13.9%; hazard ratio [95% CI]: 1.91 [1.81-2.01]; p < 0.001). CONCLUSIONS: COPD patients initiating single-inhaler FF/UMEC/VI had significantly improved adherence and persistence compared with MITT.

Meeting the challenge of COPD care delivery in the USA: a multiprovider perspective.

The burden of chronic obstructive pulmonary disease (COPD) in the USA continues to grow. Although progress has been made in the the development of diagnostics, therapeutics, and care guidelines, whether patients' quality of life is improved will ultimately depend on the actual implementation of care and an individual patient's access to that care. In this Commission, we summarise expert opinion from key stakeholders-patients, caregivers, and medical professionals, as well as representatives from health systems, insurance companies, and industry-to understand barriers to care delivery and propose potential solutions. Health care in the USA is delivered through a patchwork of provider networks, with a wide variation in access to care depending on a patient's insurance, geographical location, and socioeconomic status. Furthermore, Medicare's complicated coverage and reimbursement structure pose unique challenges for patients with chronic respiratory disease who might need access to several types of services. Throughout this Commission, recurring themes include poor guideline implementation among health-care providers and poor patient access to key treatments such as affordable maintenance drugs and pulmonary rehabilitation. Although much attention has recently been focused on the reduction of hospital readmissions for COPD exacerbations, health systems in the USA struggle to meet these goals, and methods to reduce readmissions have not been proven. There are no easy solutions, but engaging patients and innovative thinkers in the development of solutions is crucial. Financial incentives might be important in raising engagement of providers and health systems. Lowering co-pays for maintenance drugs could result in improved adherence and, ultimately, decreased overall health-care spending. Given the substantial geographical diversity, health systems will need to find their own solutions to improve care coordination and integration, until better data for interventions that are universally effective become available.

The natural history of chronic obstructive pulmonary disease.

This paper explores the natural history of chronic obstructive pulmonary disease (COPD), including our present understanding of COPD risk factors, phenotypes, and burden, along with COPD progression, including the traditional 'accelerated lung function decline' paradigm, to newer paradigms that include other factors. Questions remain unanswered, and there is considerable room for improvement. One of those questions is how the disease should best be defined. While this question has generated lively debate in the literature, it may not be the most important area with regard to advancing our understanding of the disease. The different phenotypes of COPD, particularly with regard to differential interventions and outcomes, is an area that should receive much more attention. Finally, a more holistic view of what comprises COPD progression, looking well beyond the traditional lung function decline paradigm, may also provide additional insights in how to better care for our patients.

Cardiac autonomic changes associated with fish oil vs soy oil supplementation in the elderly.

INTRODUCTION: Omega-3 fatty acid levels are associated with decreased risk for sudden death; however, the protective cardiovascular mechanisms of omega-3 are poorly understood. This study addresses the heart rate variability (HRV) changes in a cohort of elderly subjects randomized to receive either a daily high dose of marine-derived omega-3 fatty acids (fish oil) or a lower daily dose of a plant-derived omega-3 fatty acid (alpha-linolenic acid) in soy oil. METHODS: A total of 58 elderly nursing home residents were randomized to receive 2 g/d of fish oil capsules vs 2 g/d of soy oil capsules, and were subsequently followed up every other day for a period of 6 months with 6-min measurements of HRV while resting supine. An initial control period of 2 months without supplementation was allowed to establish an HRV baseline for each participant. RESULTS: The average time- and frequency-domain parameters of HRV increased significantly during the supplementation period in both the fish oil and soy oil groups. In the regression model after adjusting for age and mean heart rate, supplementation with fish oil was associated with a significant increase in the high- and low-frequency components, and SD of normal RR intervals (SDNN), whereas only SDNN increased significantly in the soy oil group. CONCLUSIONS: Supplementation with 2 g/d of fish oil was well tolerated and was associated with a significant increase in HRV. Supplementation with 2 g/d of soy oil was associated with a lesser but significant increase in HRV.

Dietary intake, physical activity, body mass index, and childhood asthma in the Third National Health And Nutrition Survey (NHANES III).

Childhood asthma may be affected by dietary changes and increased body mass related to a sedentary lifestyle, although the mechanisms are poorly understood. To test this hypothesis, we used data from the National Health and Nutrition Survey (NHANES III) from 1988-1994, including 7,904 children. We analyzed cross-sectional information on body mass index (BMI = weight/height2), physical activity (hr/day viewing television), dietary intake (24-hr recall), and vitamin C intake (60 mg/day). The probability of self-reported asthma or wheezing relating to risk factors was calculated by logistic regression. After controlling for dietary intake, physical activity, and sociodemographic variables, asthma risk was three times higher for children aged 6-16 years in the highest percentiles of BMI (>95th percentile) when compared to children in percentiles 25-49 (OR = 3.44; 95% CI, 1.49-7.96). No increase was observed in children aged 2-5 years. Low vitamin C intake was marginally related to self-reported current wheezing in children aged 6-16 years. Our results show that increased BMI may influence asthma prevalence in children, but further investigation is needed.

Serum antioxidant concentrations among U.S. adults with self-reported asthma.

Antioxidants may protect the lungs of people with asthma against oxidative stress. Among participants aged > or = 20 years from the Third National Health and Nutrition Examination Survey (1988-1994), we examined serum antioxidant concentrations of 771 persons with current asthma, 352 persons with former asthma, and 15,418 persons without asthma. After adjustment for age, participants with current asthma had similar mean concentrations of vitamin A, retinyl esters, vitamin C, vitamin E, vitamin E/cholesterol ratio, vitamin E/triglyceride ratio, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, lycopene, and selenium as participants without asthma. We repeated these analyses among participants who did not use vitamin or mineral supplements. After age adjustment, participants with current asthma had lower vitamin C and beta-cryptoxanthin concentrations and a lower mean vitamin E/triglyceride ratio than participants without asthma. In multiple linear regression models that included age, sex, race or ethnicity, education, smoking status, nonhigh-density lipoprotein cholesterol concentration, high-density lipoprotein cholesterol concentration, body mass index, physical activity, and alcohol use, asthma status was not significantly associated with any of the antioxidant concentrations. However, lower vitamin C concentrations were observed among people with current or former asthma than among people who never had asthma (p = 0.014). In the United States, people with asthma do not have manifest antioxidant deficiencies.