Heinrich Worth

Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study

We evaluated the effect of QVA149, a dual bronchodilator combining indacaterol and glycopyrronium, on direct patient-reported dyspnoea in patients with moderate-to-severe chronic obstructive pulmonary disease. In this multicentre, blinded, double-dummy, three-period crossover study, 247 patients were randomised to once-daily QVA149 110/50 μg, placebo or tiotropium 18 μg. Superiority of QVA149 versus placebo (primary objective) and tiotropium (secondary objective) was assessed for improvement in dyspnoea via the self-administered computerised (SAC) version of the Baseline and Transition Dyspnoea Index after 6 weeks. Secondary end-points included lung function, rescue medication use and safety. After 6 weeks, the SAC Transition Dyspnoea Index total score was significantly higher with QVA149 versus placebo (least squares mean (LSM) treatment difference 1.37, p<0.001) and tiotropium (LSM treatment difference 0.49, p=0.021). QVA149 provided significant improvements in lung function, with higher forced expiratory volume in 1 s area under the curve from 0–4 h post-dose versus placebo and tiotropium at day 1 and week 6 (all p<0.001). Rescue medication use was significantly lower with QVA149 versus placebo (p<0.001) and tiotropium (p=0.002). All treatments were well tolerated. Once-daily QVA149 provided superior improvements in patient-reported dyspnoea and lung function versus placebo and tiotropium. These benefits were associated with improvements in other symptoms and reduced use of rescue medication. Two different bronchodilators in a single inhaler were effective in relieving patient-reported dyspnoea in COPD http://ow.ly/qjIpe

Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: A placebo-controlled double-blind trial

BackgroundThe clinical effects of mucolytics in patients with chronic obstructive pulmonary disease (COPD) are discussed controversially. Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent. We hypothesised that its known mucolytic, bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD.MethodsIn this double-blind, placebo-controlled multi-center-study we randomly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time. The frequency, duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria. Secondary outcome measures included changes of lung function, respiratory symptoms and quality of life as well as the single parameters of the exacerbations.ResultsBaseline demographics, lung function and standard medication of both groups were comparable. During the treatment period of 6 months the multiple criteria frequency, severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo. Secondary outcome measures validated these findings. Improvement of lung function, dyspnea and quality of life as multiple criteria were statistically significant relative to placebo. Adverse events were comparable in both groups.ConclusionConcomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status. This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane.Trial registrationISRCTN07600011

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.

Mechanisms, assessment and therapeutic implications of lung hyperinflation in COPD

The main complaint of patients with chronic obstructive pulmonary disease (COPD) is shortness of breath with exercise, that is usually progressive. The principal mechanism that explains this symptom is the development of lung hyperinflation (LH) which is defined by an increase of functional residual capacity (FRC) above predicted values. Patients with COPD may develop static LH (sLH) because of destruction of pulmonary parenchyma and loss of elastic recoil. In addition, dynamic LH (dLH) develops when patients with COPD breathe in before achieving a full exhalation and, as a consequence, air is trapped within the lungs with each further breath. Dynamic LH may also occur at rest but it becomes clinically relevant during exercise and exacerbation. Lung hyperinflation may have an impact beyond the lungs and the effects of LH on cardiovascular function have been extensively analysed. The importance of LH makes its identification and measurement crucial. The demonstration of LH in COPD leads to the adoption of strategies to minimise its impact on the daily activities of patients. Several strategies reduce the impact of LH; the use of long-acting bronchodilators has been shown to reduce LH and improve exercise capacity. Non pharmacologic interventions have also been demonstrated to be useful. This article describes the pathophysiology of LH, its impact on the lungs and beyond and reviews the strategies that improve LH in COPD.

Asthmatherapie bei Kindern und Erwachsenen

Zie le 9 Vermeidung von Asthmaanf~llen, 9 Wiederherstellung und Erhaltung einer normalen oder bestm6glichen Lungenfunktion, o Verhinderung einer krankheitsbedingten BeeintrSchtigung der k6rperlichen Aktivit~iten und der physischen und geistigen Entwicklung. ~1 Meidung von Anfallsausl6sem 9 Rauchen aktiv und passiv, 9 Umweltallergene sowie Allergene und inhalative Noxen am Arbeitsplatz, 9 Betarezeptorenblocker in jeder Darreichungsform, bei bekannter • empfindlichkeit: 0 Acetylsalicyls2iure, 0 weitere nichtsteroidale Antiphlogistika.

Budesonide added to formoterol contributes to improved exercise tolerance in patients with COPD

BACKGROUND Breathlessness and exercise intolerance frequently impact the daily life of patients with COPD. METHODS This double-blind, multicentre, three-period crossover study randomised 111 patients with COPD (mean age 64 years, mean FEV(1) 38% of predicted normal) to budesonide/formoterol 320/9 microg, formoterol 9 microg or placebo, twice daily for 1 week, following a 1-week run-in period with 1-week wash-out between treatments. Terbutaline (0.5 mg/dose) was used as needed. The primary efficacy variable was exercise endurance time (EET) at 75% peak work capacity with cycle ergometry assessed 1 h post-morning dose. RESULTS Budesonide/formoterol prolonged EET 1 h post-morning dose versus formoterol by 69 s (P < 0.005) and placebo by 105 s (P < 0.0001) and improved inspiratory capacity (IC) at isotime during exercise versus formoterol by 8% (P = 0.011) and placebo by 16% (P < 0.0001). Borg score at isotime was reduced by 0.48 (P = 0.12) and 0.78 (P = 0.014) compared with formoterol and placebo, respectively. At the repeated cycle test 6 h after morning dose, the effect on EET still favoured budesonide/formoterol over formoterol and placebo, while the isotime IC and Borg score were similar but better than placebo for the active study drugs. Budesonide/formoterol and formoterol improved health status (St Georges Respiratory Questionnaire total score: mean difference versus placebo -2.4 and -2.2, respectively). All treatments were well tolerated. CONCLUSIONS Budesonide/formoterol resulted in a significant improvement in endurance time 1 h after the last morning dose in a 1-week treatment period versus formoterol and placebo. This study demonstrates, for the first time, the benefit of inhaled corticosteroids in addition to long-acting beta(2)-agonists on exercise tolerance in COPD patients. www.clinicaltrials.gov registration number: NCT00489853.

Patients with Asthma Benefit from Concomitant Therapy with Cineole: A Placebo-Controlled, Double-Blind Trial

Background and Aims. Cineole is the main constituent of eucalyptus oil, and it is mainly used as a mucolytic agent in inflammatory airway diseases. With its known mucolytic, bronchodilating, and anti-inflammatory effects, cineole reduces the exacerbation rate in patients suffering from chronic obstructive pulmonary disease. Based on these pharmacodynamic effects, we arrived at the hypothesis that asthma patients would benefit from concomitant therapy with cineole. Methods. As part of a double-blind, placebo-controlled, multicenter study, 247 patients with confirmed asthma were randomly selected according to the guidelines for this study. All patients were administered 200 mg of cineole, or a placebo, three times per day as a concomitant therapy over a period of 6 months. The combined primary outcome measures, which were implemented as a multiple criteria testing process, were improvement of lung function, asthma symptoms, and quality of life. Results. Following the completion of the 6-month treatment period, it was noted that the patient group treated with cineole showed significantly more improvements to the multiple testing criteria than the patients in the placebo group (p = .0027). The statistical significance of the individual outcome measures could also be proven in accordance with the Wei–Lachin procedure (i.e., for Forced expiratory Volume 1 Second, p = .0398; for asthma symptoms, p = .0325; and for Asthma Quality of Life Questionnaire (AQLQ), p = .0475). Conclusion. Concomitant therapy using cineole can lead to notable improvement in lung function and health condition as well as to reduce dyspnea in asthma patients.

InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in European adult patients - the LIAISON study protocol

BackgroundAccording to international guidelines, the goal of asthma management is to achieve and maintain control of the disease, which can be assessed using composite measures. Prospective studies are required to determine how these measures are associated with asthma outcomes and/or future risk. The ‘InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol (LIAISON)’ observational study has been designed to evaluate asthma control and its determinants, including components of asthma management.Methods/designThe LIAISON study will be conducted in 12 European countries and comprises a cross-sectional phase and a 12-month prospective phase. Both phases will aim at assessing asthma control (six-item Asthma Control Questionnaire, ACQ), asthma-related quality of life (Mini Asthma Quality of Life Questionnaire, Mini-AQLQ), risk of non-adherence to treatment (four-item Morisky Medication Adherence Scale, MMAS-4), potential reasons for poor control, treatment strategies and associated healthcare costs.The cross-sectional phase will recruit > 8,000 adult patients diagnosed with asthma for at least 6 months and receiving the same asthma treatment in the 4 weeks before enrolment.The prospective phase will include all patients with uncontrolled/poorly controlled asthma at the initial visit to assess the proportion reaching control during follow-up and to examine predictors of future risk. Visits will take place after 3, 6 and 12 months.DiscussionThe LIAISON study will provide important information on the prevalence of asthma control and on the quality of life in a broad spectrum of real-life patient populations from different European countries and will also contribute to evaluate differences in management strategies and their impact on healthcare costs over 12 months of observation.Trial registrationClinicalTrials.gov identifier, NCT01567280.

A year in the life of German patients with COPD: the DACCORD observational study.

Introduction Randomized interventional trials generally recruit highly selected patients. In contrast, long-term, noninterventional studies can reflect standard of care of real-life populations. DACCORD (Die ambulante Versorgung mit langwirksamen Bronchodilatatoren: COPD-Register in Deutschland [Outpatient Care With Long-Acting Bronchodilators: COPD Registry in Germany]) is an ongoing observational study, conducted in primary and secondary care in Germany, aiming to describe the impact of disease and treatments on real-life patients with chronic obstructive pulmonary disease (COPD). Methods Patients had a clinical and spirometry diagnosis of COPD, were aged ≥40 years, and were initiating or changing COPD maintenance medication. The only exclusion criteria were asthma and participation in a randomized clinical trial. Exacerbation data were collected every 3 months. COPD medication, COPD Assessment Test, and forced expiratory volume in 1 second (FEV1) were recorded at the end of the 1 year period. Results In the 6 months prior to baseline, 26.5% of the 3,974 patients experienced ≥1 exacerbation, compared with 26.1% over the 1-year follow-up (annualized rate 0.384). Importantly, only previous exacerbations and not poor lung function alone predicted an increased exacerbation risk. There was a general shift to lower disease severity from baseline to 1 year, predominantly as a consequence of a lower proportion of patients considered at high risk due to exacerbations. COPD Assessment Test mean change from baseline was −1.9, with 48.9% of patients reporting a clinically relevant improvement. Overall persistence to medication was high, with 77.2% of patients still receiving the same class of medication at 1 year. Conclusion DACCORD suggests that in clinical practice, the large majority of COPD patients are symptomatic but seldom exacerbate and that widely used tools and treatment recommendations do not reflect this fully.

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.