Anna Ribera

Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes: results from the ASSESS study

BackgroundFew studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related. This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.MethodsThe study enrolled patients with stable COPD in clinical practice. Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.ResultsThe full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline. Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively). Symptom severity was comparable for each period assessed. Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day. Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both). Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period). In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).ConclusionsMore than half of patients experienced COPD symptoms throughout the whole 24-hour day. There was a significant relationship between night-time, early morning and daytime symptoms. In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.

Onset of Effect of Aclidinium, a Novel, Long-Acting Muscarinic Antagonist, in Patients with COPD

ABSTRACT Aclidinium bromide is a novel, long-acting, inhaled muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). The aim of this study was to assess the rate of onset of bronchodilation with aclidinium compared with placebo and tiotropium. This was a double-blind, double-dummy, multicenter, crossover study in COPD patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥30% and <60% predicted. On study days, patients received single doses of aclidinium 200 μg, tiotropium 18 μg, or placebo. Serial spirometry was conducted from 10 minutes to 3 hours post-dose. The primary variable was the percentage of patients with an increase in FEV1 of ≥10% above baseline at 30 minutes post-dose. Other assessments included change from baseline in FEV1 and dyspnea over 3 hours post-dose. A total of 115 patients entered the study. Significantly more patients had an increase in FEV1 of ≥10% above baseline at 30 minutes with aclidinium and tiotropium versus placebo (49.5% and 51.8% versus 13.8%; p < 0.0001). At 30 minutes, the relative increase from baseline in FEV1 was significantly higher for aclidinium and tiotropium versus placebo (12% and 11% versus 3%; p < 0.0001). Aclidinium and tiotropium also significantly increased FEV1 (p < 0.01) and improved the perception of dyspnea compared with placebo at all measured time points from 10 minutes to 3 hours post-dose. In conclusion, aclidinium provided effective bronchodilation, similar to that seen with tiotropium, with significant improvements compared with placebo observed from 10 minutes post-dose.

Preference, satisfaction and critical errors with Genuair and Breezhaler inhalers in patients with COPD: a randomised, cross-over, multicentre study.

Background:The specific attributes of inhaler devices can influence patient use, satisfaction and treatment compliance, and may ultimately impact on clinical outcomes in patients with chronic obstructive pulmonary disease (COPD).Aims:To assess patient preference, satisfaction and critical inhaler technique errors with Genuair (a multidose inhaler) and Breezhaler (a single-dose inhaler) after 2 weeks of daily use.Methods:Patients with COPD and moderate to severe airflow obstruction were randomised in a cross-over, open-label, multicentre study to consecutive once-daily inhalations of placebo via Genuair and Breezhaler, in addition to current COPD medication. The primary end point was the proportion of patients who preferred Genuair versus Breezhaler after 2 weeks (Patient Satisfaction and Preference Questionnaire). Other end points included overall satisfaction and correct use of the inhalers after 2 weeks, and willingness to continue with each device.Results:Of the 128 patients enrolled, 127 were included in the safety population (male n=91; mean age 67.6 years). Of the 110 of the 123 patients in the intent-to-treat population who indicated an inhaler preference, statistically significantly more patients preferred Genuair than Breezhaler (72.7 vs. 27.3%; P<0.001). Mean overall satisfaction scores were also greater for Genuair than for Breezhaler (5.9 vs. 5.3, respectively; P<0.001). After 2 weeks, there was no statistically significant difference in the number of patients who made ⩾1 critical inhaler technique error with Breezhaler than with Genuair (7.3 vs. 3.3%, respectively).Conclusions:Patient overall preference and satisfaction was significantly higher with Genuair compared with Breezhaler. The proportion of patients making critical inhaler technique errors was low with Genuair and Breezhaler.

Understanding the impact of symptoms on the burden of COPD

Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities. We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis. In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered. The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden.

A dose-ranging study of the bronchodilator effects of abediterol (LAS100977), a long-acting β2-adrenergic agonist, in asthma; a Phase II, randomized study.

BackgroundLong-acting β2-adrenergic agonists (LABAs) are recommended in combination with inhaled corticosteroids (ICSs) for asthma management. Abediterol is a novel, selective, potent, once-daily LABA in development for treatment of asthma and chronic obstructive pulmonary disease. This study aimed to determine abediterol doses with similar peak bronchodilatory effect to salbutamol 400 μg, and duration of action compatible with once-daily dosing in patients with persistent, stable asthma.MethodsThis was a Phase II, randomized, double-blind, double-dummy, crossover, placebo-controlled, dose-ranging study (ClinicalTrials.gov NCT01425801) in 62 patients with mild-to-moderate asthma who were also receiving an ICS. Patients received single doses of abediterol 0.313, 0.625, 1.25, or 2.5 μg, salbutamol 400 μg, or placebo in the morning. Spirometry was performed up to 36 h post-dose; safety and tolerability were assessed throughout the study. The primary endpoint was change from baseline in peak forced expiratory volume in 1 s (FEV1). Additional endpoints included trough FEV1, normalized area under the FEV1 curve (FEV1 AUC) up to 24 h post-dose, and peak and trough forced vital capacity (FVC).ResultsAbediterol produced dose-dependent improvements in peak FEV1 from baseline compared with placebo, from 0.274 (95% CI 0.221, 0.327) to 0.405 L (95% CI 0.353, 0.458) for abediterol 0.313 to 2.5 μg, respectively (p < 0.0001 all doses). Abediterol 0.625, 1.25, and 2.5 μg had similar magnitude of peak FEV1 effect to salbutamol. Dose-dependent changes from baseline in trough FEV1 versus placebo were 0.219 (95% CI 0.136, 0.302) to 0.400 L (95% CI 0.317, 0.483) for abediterol 0.313 to 2.5 μg, respectively (p < 0.0001). All abediterol doses achieved significant improvements versus placebo in FEV1 AUC 0–6, 0–12, and 0–24 h, and peak and trough FVC (p < 0.05). Less than 10% of patients experienced treatment-related adverse events for each dose of abediterol; most were mild to moderate in intensity and the most common were headache and nasopharyngitis. There were no clinically relevant changes in heart rate.ConclusionsAbediterol 0.625–2.5 μg provided dose-dependent, clinically and statistically significant bronchodilation versus placebo in patients with asthma, with a peak effect similar to salbutamol and duration of action compatible with once-daily dosing. All doses of abediterol were well tolerated.

The Relationship Between 24-Hour Symptoms and COPD Exacerbations and Healthcare Resource Use: Results from an Observational Study (ASSESS)

ABSTRACT This observational study assessed the relationship between nighttime, early-morning and daytime chronic obstructive pulmonary disease (COPD) symptoms and exacerbations and healthcare resource use. COPD symptoms were assessed at baseline in patients with stable COPD using a standardised questionnaire during routine clinical visits. Information was recorded on exacerbations and healthcare resource use during the year before baseline and during a 6-month follow-up period. The main objective of the analysis was to determine the predictive nature of current symptoms for future exacerbations and healthcare resource use. 727 patients were eligible (65.8% male, mean age: 67.2 years, % predicted forced expiratory volume in 1 second: 52.8%); 698 patients (96.0%) provided information after 6 months. Symptoms in any part of the day were associated with a prior history of exacerbations (all p < 0.05) and nighttime and early-morning symptoms were associated with the frequency of primary care visits in the year before baseline (both p < 0.01). During follow-up, patients with baseline symptoms during any part of the 24-hour day had more exacerbations than patients with no symptoms in each period (all p < 0.05); there was also an association between 24-hour symptoms and the frequency of primary care visits (all p ≤ 0.01). Although there was a significant association between early-morning and daytime symptoms and exacerbations during follow-up (both p < 0.01), significance was not maintained when adjusted for potential confounders. Prior exacerbations were most strongly associated with future risk of exacerbation. The results suggest 24-hour COPD symptoms do not independently predict future exacerbation risk.

The efficacy of aclidinium/formoterol on lung function and symptoms in patients with COPD categorized by symptom status: a pooled analysis

Background Patients with chronic obstructive pulmonary disease (COPD) experience respiratory symptoms, which impair quality of life. This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status. Methods Data were pooled from two 24-week, randomized, placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]). These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a) Evaluating Respiratory Symptoms (E-RS™) score ≥10/<10 and b) Baseline Dyspnea Index score <7/≥7. Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, E-RS total score, early-morning and nighttime symptom severity, early-morning limitation of activities, and exacerbation rate. Results Data for 3,394 patients were analyzed (mean age: 63.5 years; 60.5% male). In both definitions of less and more symptomatic patients, aclidinium/formoterol improved 1-hour morning postdose FEV1 from baseline at week 24 versus placebo (P<0.001) and both monotherapies (P<0.05). Aclidinium/formoterol improved trough FEV1 from baseline in both groups versus placebo (P<0.05) and formoterol (P<0.05); improvements were greater in more symptomatic patients. Improvements versus aclidinium were also observed in more symptomatic patients (P<0.05). Aclidinium/formoterol improved dyspnea, early-morning symptom severity, and limitation of activities versus placebo in both less and more symptomatic patients (P<0.001). In more symptomatic patients, aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies (P<0.05). The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients. Conclusion Aclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD, regardless of the definition used. Furthermore, patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV1, dyspnea, and early-morning symptoms.

The impacts of morning, daytime, and nighttime symptoms on disease burden in real-world patients with COPD

Background Respiratory symptoms are increasingly recognized as an important consideration in COPD management. Understanding the links between the time(s) of day symptoms are experienced and overall symptom burden could support personalized management strategies. This real-world study aimed to establish the association between the time of day of symptoms and the burden on patients using validated patient-reported outcomes, health care resource utilization, and physician-perceived impact of COPD on patients’ lives. Materials and methods Analyses used data from four waves (2012, 2013, 2014, and 2016) of the Respiratory Disease Specific Programme: cross-sectional surveys of patients with COPD in Germany, Italy, Spain, and the UK. Patients were classified by their physicians as having symptoms in the morning (M), daytime (D), and/or nighttime (N) in the 4 weeks before entering the Disease Specific Programme. Outcomes included health care resource utilization, work productivity and activity impairment, COPD Assessment Test, EuroQol 5-dimension 3-level questionnaire with visual analog scale, and Jenkins Sleep Evaluation Questionnaire. Results In total, 8,844 patients were included, and 8,185 had evaluable time-of-day symptom data. Physicians reported that in the previous 4 weeks, 25% of patients experienced no symptoms, 16% D only, 17% M/D only, 6% D/N only, 4% M, N, or M/N only, and 32% M/D/N. In general, patients with M/D/N symptoms utilized more health care resources in the previous 12 months, had more prior exacerbations, and reported worse activity impairment, health status, and sleep than other symptom groups, whereas patients with symptoms at any time of the day utilized more resources, experienced more exacerbations, and reported worse health status than patients with no symptoms during the 4 weeks before entering the survey. Conclusion Patients experiencing morning, daytime, and nighttime symptoms experience a greater disease burden than those in other groups. An individualized approach to COPD treatment based on the timing and persistence of symptoms may improve outcomes for these patients.

Aclidinium bromide improves symptoms and sleep quality in COPD: a pilot study

In patients with chronic obstructive pulmonary disease (COPD), nighttime and early-morning symptoms are associated with an increased rate of exacerbation, hospital admission and reduced survival [1, 2]. Furthermore, patients with COPD frequently have poor sleep quality [3] and reduced physical activity [4, 5]. We hypothesised that nighttime airflow obstruction in patients with COPD is associated with impaired sleep quality, leading to early-morning symptoms and reduced physical activity. Aclidinium statistically improved symptoms, and sleep and physical activity in moderate COPD http://ow.ly/2chV30adLbW

P215 The incremental disease burden associated with the persistence of morning, daytime and night-time symptoms in chronic obstructive pulmonary disease patients

Introduction The current Global Initiative for Chronic Obstructive Lung Disease Strategy makes limited references to the variability of chronic obstructive pulmonary disease (COPD) symptoms according to the time of day patients experience symptoms, on awakening/morning, in the daytime and at night-time; therefore it’s unclear whether specific treatment approaches are needed. Aims To establish the association between time of day of symptoms and the burden experienced by patients; as measured by validated patient-reported outcomes (PROs), healthcare resource utilisation (HRU) and physician-perceived impact of COPD on patients’ lives. Methods Data were taken from four waves (2012–2016) of the Respiratory Disease Specific Programme (DSP); cross-sectional surveys of COPD patients in France, Germany, Italy, Spain, and the UK. Patients were defined as suffering from symptoms on awakening/morning (M), in the daytime (D), at night-time (N) or combinations of these according to physician-reported time of day of symptoms within the last 4 weeks. Kruskal-Wallis tests assessed statistical significance of outcomes across patient groups. Outcomes included HRU in the last 12 months, EQ-5D-3L with visual analogue scale, Jenkins Sleep Evaluation Questionnaire, COPD Assessment Test, activity impairment (measured by the work productivity and activity impairment questionnaire), and physician-reported impact COPD has on the patient’s sleep. Results In total, 8185 patients receiving treatment were analysed; 25% suffered no symptoms, 16% D only, 17% M/D only, 6% D/N only, 4% M, N or M/N only and 32% M/D/N. Across the four DSP waves, patients suffering any M, D or N symptoms ranged from 46%−64%, 67%–77% and 38%–47%, respectively. All outcomes differed significantly across patient groups (Table 1). In general, M/D/N patients utilised the most healthcare resources, suffered more exacerbations requiring emergency room visits or hospital admissions, had higher activity impairment and reported worse quality of life and sleep, whilst asymptomatic patients utilised the least resources and reported the best quality of life and sleep. The remaining groups suffered similar levels of burden. Conclusions In this analysis, patients experiencing morning, daytime and night-time symptoms have the worst PROs and more disease burden. Clearer recognition of symptom burden and an individualised treatment approach may be warranted for these patients. Abstract P215 Table 1 Outcomes (Mean, S.D.) None(n = 2060) D only(n = 1274) M/D only(n = 1378) D/N only(n = 477) M, N or M/N only(n = 345) M/D/N(n = 2651) PCP consultations 2.8 (2.9) 3.1 (3.0) 3.0 (3.0) 3.8 (3.2) 3.1 (3.1) 4.4 (4.5) Specialist consultations 1.7 (1.8) 2.3 (2.2) 2.4 (2.2) 2.1 (2.0) 1.7 (1.9) 2.8 (2.8) ER visits 0.0 (0.3) 0.1 (0.4) 0.1 (0.4) 0.2 (0.5) 0.1 (0.4) 0.3 (0.6) Hospital admissions 0.0 (0.2) 0.1 (0.5) 0.2 (0.6) 0.2 (0.5) 0.1 (0.5) 0.5 (1.0) % activity impairment 24.6 (20.0) 36.8 (20.1) 41.0 (22.0) 45.0 (19.4) 33.7 (22.2) 56.4 (23.2) EQ-5D-3L 0.89 (0.18) 0.85 (0.19) 0.81 (0.22) 0.80 (0.19) 0.86 (0.17) 0.69 (0.28) EQ-VAS 72.7 (15.0) 66.7 (14.8) 63.7 (15.0) 62.9 (16.1) 68.6 (13.9) 56.3 (17.6) CAT 14.2 (7.4) 18.4 (7.1) 20.2 (6.9) 21.5 (6.1) 18.9 (7.1) 25.7 (6.6) JSEQ 2.4 (2.9) 3.6 (3.3) 4.3 (3.9) 5.6 (3.4) 4.4 (3.5) 8.3 (4.8) Impact on Sleep, n (%) None 485 (42.1) 212 (32.9) 189 (26.2) 11 (4.5) 42 (20.1) 60 (4.2) Low 512 (44.5) 295 (45.7) 347 (48.1) 90 (37.0) 86 (41.1) 364 (25.2) Medium 121 (10.5) 103 (16.0) 142 (19.7) 105 (43.2) 50 (23.9) 557 (38.6) High 30 (2.6) 33 (5.1) 39 (5.4) 36 (14.8) 22 (10.5) 367 (25.5) Constant 3 (0.3) 2 (0.3) 4 (0.6) 1 (0.4) 9 (4.3) 94 (6.5) PCP – Primary care physician; ER – Emergency Room; M – Morning; D – Daytime; N – Night time; CAT – COPD Assessment Test; JSEQ – Jenkins Sleep Evaluation Questionnaire