Arformoterol and salmeterol in the treatment of chronic obstructive pulmonary disease: A one year evaluation of safety and tolerance

Introduction: Concerns have been raised regarding the safety of extended use of long-acting β 2-agonists (LABAs). The safety of arformoterol (50 µg QD), and salmeterol (42 µg BID), was assessed over 12 months in subjects with COPD. The study also examined the occurrence of tolerance with these agents, i.e. whether improvement in airway function diminished or frequency of exacerbations increased with 12-months of use. Methods: Subjects with COPD (mean FEV1 1.2 L, ~41% predicted) were enrolled in the study and randomized to receive nebulized arformoterol 50 µg QD ( n = 528) or salmeterol 42 µg BID (MDI; n = 265) in a prospective, multicenter, open-label, 12-month trial. The frequency of adverse events, COPD exacerbations, and use of short-acting bronchodilator agents were assessed throughout the study period. Pulmonary function was also examined. Results: Among treated subjects, the frequency of adverse events was similar for those taking arformoterol (90.5%) and salmeterol (88.3%). Tremor was more frequent among subjects treated with arformoterol (13.4%) than those treated with salmeterol (1.1%). The frequency of COPD exacerbations did not increase over 12 months for arformoterol and salmeterol (weeks 0—13: 15.7% and 11.7%, respectively; weeks 39—52: 10.0% and 9.4%, respectively). Supplemental ipratropium bromide and rescue racemic albuterol use decreased for both groups by 0.8 to 1.5 actuations/day, decreases that remained stable throughout the 52-week study. Mean predose (trough) FEV1 improved for arformoterol and salmeterol at week 13 (7.1% ± 17.0 and 7.6% ± 17.8, respectively) and the improvement continued at week 52 (5.9% and 6.2%, respectively). Mean peak percent predicted postdose FEV1 over the course of the 52-week study declined by about 2% for both treatments, but throughout was higher for arformoterol than for salmeterol. Conclusion: In this trial, both arformoterol 50 µg QD and salmeterol 42 µg BID were well tolerated in patients with COPD. Both LABAs produced effective bronchodilation and their use was not associated with the development of clinically meaningful tolerance over a 1-year treatment period

Determinants of depression in the ECLIPSE chronic obstructive pulmonary disease cohort

RATIONALE: Depression is prevalent in patients with chronic obstructive pulmonary disease (COPD); however, its etiology and relationship to the clinical features of COPD are not well understood. OBJECTIVES: Using data from a large cohort, we explored prevalence and determinants of depression in subjects with COPD. METHODS: The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study is an observational 3-year multicenter study that enrolled smokers with and without COPD and nonsmoker controls. At baseline, several patient-reported outcomes were measured including the Center for Epidemiologic Studies of Depression Scale. For the purposes of this analysis, depression was defined as a score of 16 and higher on this scale, which reflects a high load of depressive symptoms and has a good correspondence with a clinical diagnosis of major depression. MEASUREMENTS AND MAIN RESULTS: The study cohort consisted of 2,118 subjects with COPD; 335 smokers without COPD (smokers); and 243 nonsmokers without COPD (nonsmokers). A total of 26%, 12%, and 7% of COPD, smokers, and nonsmokers, respectively, suffered from depression. In subjects with COPD, higher depression prevalence was seen in females, current smokers, and those with severe disease (Global Initiative for Obstructive Lung Disease [GOLD]-defined). Multivariate modeling of depression determinants in subjects with COPD revealed that increased fatigue, higher St. George's Respiratory Questionnaire for COPD patients score, younger age, female sex, history of cardiovascular disease, and current smoking status were all significantly associated with depression; physiologic and biologic measures were weak or nonsignificant descriptors. CONCLUSIONS: Depression is more prevalent in subjects with COPD compared with smokers and nonsmokers without COPD. Clinical and biologic measures were less important determinants of depression in COPD than disease symptoms and quality-of-life. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552)

Examining fatigue in COPD: development, validity and reliability of a modified version of FACIT-F scale

ABSTRACT: INTRODUCTION: Fatigue is a disruptive symptom that inhibits normal functional performance of COPD patients in daily activities. The availability of a short, simple, reliable and valid scale would improve assessment of the characteristics and influence of fatigue in COPD. METHODS: At baseline, 2107 COPD patients from the ECLIPSE cohort completed the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale. We used well-structured classic method, the principal components analysis (PCA) and Rasch analysis for structurally examining the 13-item FACIT-F. RESULTS: Four items were less able to capture fatigue characteristics in COPD and were deleted. PCA was applied to the remaining 9 items of the modified FACIT-F and resulted in three interpretable dimensions: i) general (5 items); ii) functional ability (2 items); and iii) psychosocial fatigue (2 items). The modified FACIT-F had high internal consistency (Cronbach's alpha = 0.91) and it did not fit a uni-dimensional Rasch model, confirming the prior output from the PCA. The correlations between total score and each dimension were [GREATER-THAN OR EQUAL TO] 0.64 and within dimensions [GREATER-THAN OR EQUAL TO]0.43 (p < 0.001 for all).The original and modified FACIT-F had significant convergent validity; its scores were associated with SGRQ total score (0.69 and 0.7) and mMRC dyspnoea scores (0.48 and 0.47), (p = <0.001 for all). The scale had meaningful discriminating ability in identifying patients with poor exercise performance and more depressive symptoms. CONCLUSION: The original and modified FACIT-F are valid and reliable scales in COPD. The modified version is shorter and measures not only total fatigue but also its sub-components in COPD

Reducing the hidden burden of severe asthma: recognition and referrals from primary practice

Since their introduction many decades ago, systemic corticosteroids have become a mainstay treatment for asthma. Despite being a highly effective therapy, corticosteroids can cause significant adverse effects in patients. This results in a “double hit” for some patients as they suffer the burden of disease as well as the burden of treatment-induced morbidity. This article aims to raise awareness of the potential, harmful side effects of prolonged or repeated exposure to systemic corticosteroids in asthma. It also highlights the importance of referral of the appropriate patients with asthma from primary care for specialist assessment once other considerations such as adherence, inhaler technique and co-morbidity have been evaluated. We propose a simple decision step that may help busy primary care physicians and general practitioners to identify patients who could benefit from specialist assessment. Our decision step suggests that a patient with asthma should be reviewed at least once by an asthma specialist if he/she (i) has received ≥2 courses of oral corticosteroids in the previous year; asthma remains uncontrolled despite good adherence and inhaler technique; or (ii) has attended an emergency department or was hospitalized for asthma care. Such referral could facilitate wider access to diagnostic tools, in-depth assessment of confounding comorbidities, and non-corticosteroid-based therapies as needed, which may be unavailable in primary practice. © 2020 Taylor &amp; Francis Group, LLC