Johanna I. Lutter

Purpose: Real-world evidence on the impact of forced expiratory volume in one second (FEV₁) and exacerbations on health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD) is sparse especially with regard to GOLD ABCD groups. This study investigates how changes in FEV₁ and exacerbations affect generic and disease-specific HRQoL in COPD patients over one year. Methods: Using German claims data and survey data, we classified 3016 COPD patients and analyzed their health status by GOLD groups AB and CD. HRQoL was measured with the disease-specific COPD assessment test (CAT) and the visual analog scale (VAS) from the generic Euro-Qol 5D-5L. We applied change score models to assess associations between changes in FEV₁ (≥ 100 mL decrease/no change/≥ 100 mL increase) or the development of severe exacerbations with change in HRQoL. Results: FEV₁ decrease was associated with a significant but not minimal important difference (MID) deterioration in disease-specific HRQoL (mean change [95% CI]: CAT +0.74 [0.15 to 1.33]), while no significant change was observed in the generic VAS. Experiencing at least one severe exacerbation also had a significant impact on CAT deterioration (+1.58 [0.52 to 2.64]), but again not on VAS. Here, GOLD groups AB showed not only a statistically but also a clinically relevant MID deterioration in CAT (+2.1 [0.88 to 3.32]). These particular patient groups were further characterized by a higher probability of being male, having a higher mMRC and Charlson index, and a lower probability of having higher FEV₁ or BMI values. Conclusion: FEV₁ decline and the occurrence of ≥ 1 severe exacerbation are significantly associated with overall deterioration in disease-specific HRQoL. Preventing severe exacerbations particularly in patients without previous severe exacerbations (ABCD groups A and B) may help to stabilize the key patient-reported outcome HRQoL.

Hintergründe: Bei der Chronisch Obstruktiven Lungenerkrankung (COPD) gibt geschlechtsspezifische Unterschiede in der Prävalenz von Komorbiditäten und in Bezug auf die Symptomäusserung. Wir prüften im Rahmen der COSYCONET-Studie ob sich auch in den Beziehungen von Lungenfungenfunktion, Komorbiditäten und Symptomatik geschlechtsspezifische Unterschiede zeigen und ob sich hieraus Hinweise für die Diagnostik von kardialen Komorbiditäten ergeben. Methoden: Insgesamt wurden 2046 Patienten, (GOLD 1 – 4, 795 weiblich; 38.8%) in die Analyse eingeschlossen. Neben unterschiedlichen Komorbiditäten wurden lungenfunktionelle Parameter, einzelne CAT Items und die mMRC Scala berücksichtigt. Geschlechtsspezifische Unterschiede in Bezug auf die Symptomatik kardialer Komorbiditäten (Herzinfarkt, Herzinsuffizienz, Koronare Herzerkrankung) wurden in multivariaten Regressionsanalysen unter Berücksichtigung unterschiedlicher Kovariaten sowie separat für Männer und Frauen analysiert. Ergebnisse: Die meisten funktionellen Parameter, Komorbiditäten, sowie die CAT Items 1 (Husten), 2 (Auswurf) und 5 (häusliche Aktivitäten), unterschieden sich signifikant (p < 0.05) zwischen Männern und Frauen. Ferner zeigten sich in der Beziehung der funktionellen Parameter und Komorbiditäten gegenüber der Symptomatik, insbesondere in Bezug auf die einzelnen CAT Items relevante Geschlechtsunterschiede. Bei Männern waren CAT Item 8 (Energie), mMRC, Raucherstatus, BMI Alter und die Spirometrie mit kardialen Erkrankungen assoziiert wohingegen sich bei Frauen lediglich das Alter als prädiktive erwies. Zusammenfassung: Die vorliegenden Daten zeigen, dass Geschlechtsunterschiede bei COPD neben der Prävalenz unterschiedlicher Komorbiditäten und den Symptom Level auch qualitative Unterschiede in deren vielfältigen Beziehungen betreffen. Anamnestische Hinweise bezüglich kardialer Komorbiditäten sollten bei Männern und Frauen unterschiedlich berücksichtigt werden. Article published online: 30 April 2021 © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Background: In COPD patients of GOLD groups A and B, a high degree of treatment with inhaled corticosteroids (ICS) has been reported, which is regarded as overtreatment according to GOLD recommendations. We investigated which factors predict ICS use and which relationship it has to clinical and functional outcomes, or healthcare costs. Methods: We used pooled data from visits 1 and 3 of the COSYCONET cohort (n=2741, n=2053, interval 1.5 years) including patients categorized as GOLD grades 1– 4 and GOLD group A or B at both visits (n=1080). Comparisons were performed using ANOVA, and regression analyses using propensity matching and inverse probability weighting to adjust for differences between ICS groups. These were defined as having ICS at both visits (always) vs no ICS at both visits (never). Measures were divided into predictors of ICS treatment and outcomes. Results: Among 1080 patients, 608 patients were eligible for ICS groups (n=297 never, n=311 always). Prior to matching, patients with ICS showed significantly (p< 0.05 each) impaired lung function, symptoms and exacerbation history. After matching, the outcomes generic quality of life and CO diffusing capacity were increased in ICS patients (p< 0.05 each). Moreover, costs for respiratory medication, but not total health care costs, were significantly elevated in the ICS group by 780€ per year. Conclusion: ICS therapy in COPD GOLD A/B patients can have small positive and negative effects on clinical outcomes and health care costs, indicating that the clinical evaluation of ICS over-therapy in COPD requires a multi-dimensional approach.

Background: Beyond smoking, several risk factors for the development of chronic obstructive pulmonary disease (COPD) have been described, among which socioeconomic status including education is of particular interest. We studied the contribution of education to lung function and symptoms relative to smoking in a group of never-smokers with COPD compared to a group of long-time ex-smokers with COPD. Methods: We used baseline data of the COSYCONET cohort, including patients of GOLD grades 1– 4 who were either never-smokers (n=150, age 68.5y, 53.3% female) or ex-smokers (≥ 10 packyears) for at least 10 years (n=616, 68.3y, 29.9% female). Socioeconomic status was analyzed using education level and mortality was assessed over a follow-up period of 4.5 years. Analyses were performed using ANOVA and regression models. Results: Spirometric lung function did not differ between groups, whereas CO diffusing capacity and indicators of lung hyperinflation/air-trapping showed better values in the never-smoker group. In both groups, spirometric lung function depended on the education level, with better values for higher education. Quality of life and 6-MWD were significantly different in never-smokers as well as patients with higher education. Asthma, alpha-1-antitrypsin deficiency, and bronchiectasis were more often reported in never-smokers, and asthma was more often reported in patients with higher education. Higher education was also associated with reduced mortality (hazard ratio 0.46; 95% CI 0.22– 0.98). Conclusion: Overall, in the COSYCONET COPD cohort, differences in functional status between never-smokers and long-time ex-smokers were not large. Compared to that, the dependence on education level was more prominent, with higher education associated with better outcomes, including mortality. These data indicate that non-smoking COPD patients’ socioeconomic factors are relevant and should be taken into account by clinicians.

Background: Forced expiratory volume in one second (FEV₁) characterizes the pathophysiology of COPD and different trajectories of FEV₁decline have been observed in patients with COPD (e.g. gradual or episodic). There is limited information about the development of patient-reported health-related quality of life (HRQL) over the full range of the natural history of COPD. We examined the longitudinal association between change in FEV₁and change in disease-specific and generic HRQL.Methods: We analysed data of 1734 patients with COPD participating in the COSYCONET cohort with up to 3 years of follow-up. Patients completed the Saint George’s Respiratory Questionnaire (SGRQ) and the EQ-5D Visual Analog Scale (EQ VAS). Change score models were used to investigate the relationship between HRQL and FEV₁and to calculate mean changes in HRQL per FEV₁change categories [decrease (≤ − 100 ml), no change, increase (≥ 100 ml)] after 3 years. Applying hierarchical linear models (HLM), we estimated the cross-sectional between-subject difference and the longitudinal within-subject change of HRQL as related to a FEV₁difference or change.Results: We observed a statistically significant deterioration in SGRQ (total score + 1.3 units) after 3 years, which was completely driven by the activity component (+ 4 units). No significant change was found for the generic EQ VAS. Over the same period, 58% of patients experienced a decrease in FEV₁, 28% were recorded as no change in FEV₁, and 13% experienced an increase. The relationship between HRQL and FEV₁was found to be approximately linear with decrease in FEV₁being statistically significantly associated with a deterioration in SGRQ (+ 3.20 units). Increase in FEV₁was associated with improvements in SGRQ (− 3.81 units). The associations between change in FEV₁and the EQ VAS were similar. Results of the HLMs were consistent and highly statistically significant, indicating cross-sectional and longitudinal associations. The largest estimates were found for the association between FEV₁and the SGRQ activity domain.Conclusions: Difference and change in FEV₁over time correlate with difference and change in disease-specific and generic HRQL. We conclude, that deterioration of HRQL should induce timely re-examination of physical status and lung function and possibly reassessment of therapeutic regimes.Trial registration: NCT01245933. Date of registration: 18 November 2010.

Background: Peripheral neuropathy is a common comorbidity in COPD, for which various associations with COPD characteristics have been reported. We aimed to identify effects of changes associated with COPD on neuropathy, distinguishing between direct and indirect associations. Methods: We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork, monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-minute walk distance (6-MWD), the timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters. Results: 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI depended on neuropathy and 6-MWD, exacerbations depended on FEV1, 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on BE and ABI. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same. Conclusion: We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu associated with COPD, in particular vascular status and the degree of metabolic compensation.

Background: Adherence to COPD medication is often considered to be lower than in other chronic diseases. In view of the frequent comorbidities of COPD, the economic impact of nonadherence and the potential for adverse effects, a direct comparison between the adherence to respiratory and nonrespiratory medication in the same patients seems of particular interest. Objectives: We aimed to investigate the intake of respiratory and nonrespiratory medication in the same patients with COPD and frequent comorbidities. Method: Within the COPD cohort COSYCONET, we contacted 1042 patients, mailing them a list with all medication regarding all their diseases, asking for regular, irregular and non-intake. Results: Valid responses were obtained in 707 patients covering a wide spectrum of drugs. Intake of LABA, LAMA or ICS was regular in 91.9% of patients, even higher for cardiovascular and antidiabetes medication but lower for hyperlipidemia and depression/anxiety medication. Regular intake of respiratory medication did not depend on GOLD groups A-D or grades 1–4, was highest in patients with concomitant cardiovascular disorders and was lowest for concomitant asthma. It was slightly larger for LAMA and LABA administered via combined compared to single inhalers, and lower when similar compounds were prescribed twice. Most differences did not reach statistical significance owing to the overall high adherence. Conclusion: Our results indicate a high adherence to respiratory medication in participants of a COPD cohort, especially in those with cardiovascular comorbidities. Compared to the lower adherence reported in the literature for COPD patients, our observations still suggest some room for improvement, possibly through disease management programs.