The frequency of COPD exacerbations during treatment with a triple inhaler — delivering a long-acting beta-agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled glucocorticoid — ...was compared with that with a LABA–LAMA or LABA–inhaled glucocorticoid.
Background The COPD Assessment Test (CAT) is an eight-item questionnaire suitable for routine clinical use that shows reliability and validity in stable and exacerbating COPD. Methods Study 1 ...assessed CAT responsiveness to changes in health status in 67 patients during an exacerbation (days 1–14). Study 2 assessed CAT responsiveness in 64 patients undergoing pulmonary rehabilitation (days 1–42). Correlations between CAT and other outcome measures were examined. Results In study 1, mean 14-day improvement in CAT score was −1.4 ± 5.3 units ( P = .03). In patients judged to be responders (clinician defined) change in score was −2.6 ± 4.4; in nonresponders it was −0.2 ± 5.9. In study 2, the mean improvement in CAT score was −2.2 ± 5.3 ( P = .002); the effect size for the change was −0.33. Effect size for changes in the Chronic Respiratory Questionnaire—Self Administered Standardized (CRQ-SAS) form domain scores ranged from −0.02 to 0.34. Change in 6-min walk distance (6MWD) was 41 ± 55 m. CAT and CRQ-SAS domain scores correlated at baseline ( r = −0.54 to −0.69, P < .0001) and in terms of change following pulmonary rehabilitation ( r = −0.39 to −0.63, P < .01). Correlations were less strong between change in the CAT and St. George Respiratory Questionnaire for COPD in study 1 ( r < 0.24) and for 6MWD ( r < 0.11) in study 2. Conclusions These studies indicate that the CAT is sensitive to changes in health status following exacerbations and is as responsive to pulmonary rehabilitation as more complex COPD health status measures.
Breathlessness is a primary clinical feature of chronic obstructive pulmonary disease (COPD). We aimed to describe the frequency of and factors associated with breathlessness in a cohort of COPD ...patients identified from the Clinical Practice Research Datalink (CPRD), a general practice electronic medical records database.
Patients with a record of COPD diagnosis after January 1 2008 were identified in the CPRD. Breathlessness was assessed using the Medical Research Council (MRC) dyspnoea scale, with scoring ranging from 1-5, which has been routinely administered as a part of the regular assessment of patients with COPD in the general practice since April 2009. Stepwise multivariate logistic regression estimated independent associations with dyspnoea. Negative binomial regression evaluated a relationship between breathlessness and exacerbation rate during follow-up.
The total cohort comprised 49,438 patients diagnosed with COPD; 40,425 (82%) had any MRC dyspnoea grade recorded. Of those, 22,770 (46%) had moderate-to-severe dyspnoea (MRC ≥ 3). Breathlessness increased with increasing airflow limitation; however, moderate-to-severe dyspnoea was also observed in 32% of patients with mild airflow obstruction. Other factors associated with increased dyspnoea grade included female gender, older age (≥ 70 years), obesity (BMI ≥ 30), history of moderate-to-severe COPD exacerbations, and frequent visits to the general practitioner. Patients with worse breathlessness were at higher risk of COPD exacerbations during follow-up.
Moderate-to-severe dyspnoea was reported by >40% of patients diagnosed with COPD in primary care. Presence of dyspnoea, including even a perception of mild dyspnoea (MRC = 2), was associated with increased disease severity and a higher risk of COPD exacerbations during follow-up.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Combination long-acting bronchodilator therapy may be more effective than long-acting bronchodilator monotherapy in COPD. Our objectives were to compare the efficacy and safety of ...once-daily umeclidinium bromide (UMEC)/vilanterol (VI) 125/25 μg with placebo and UMEC or VI monotherapy in COPD. Methods This was a double-blind, placebo-controlled, parallel-group study. A total of 1,493 patients were randomized (3:3:3:2) to 24 weeks of treatment with UMEC/VI 125/25 μg, UMEC 125 μg, VI 25 μg, or placebo once daily via dry powder inhaler. Results Primary efficacy end point was trough FEV1 on day 169 (23-24 h postdose). Additional lung-function, symptomatic, and health-related quality-of-life end points were also assessed. Safety evaluations included adverse events, vital signs, ECG, and clinical laboratory measurements. All active treatments significantly improved trough FEV1 vs placebo (0.124-0.238 L, all P < .001). Improvements with UMEC/VI 125/25 μg were significantly greater than for UMEC 125 μg or VI 25 μg (0.079 L and 0.114 L, both P ≤ .001). Improvements for UMEC/VI 125/25 μg vs placebo were observed for the Transition Dyspnea Index (1.0 unit, P < .001), rescue albuterol use at weeks 1 to 24 (−1.5 puffs/d), and St. George's Respiratory Questionnaire (−3.60 units, P < .001). No safety signals were observed. Conclusions Once-daily UMEC/VI 125/25 μg was well tolerated and provided greater improvements in lung function, health status, and dyspnea scores compared with monotherapy components and placebo over 24 weeks. This study supports the use of UMEC/VI 125/25 μg for the maintenance treatment of COPD. Trial registry ClinicalTrials.gov ; No.: NCT01313637; URL: www.clinicaltrials.gov.
Combination long-acting bronchodilator treatment might be more effective than long-acting bronchodilator monotherapy for the treatment of chronic obstructive pulmonary disease (COPD). We aimed to ...compare the efficacy and safety of umeclidinium (UMEC) plus vilanterol (VI) with tiotropium (TIO) monotherapy, UMEC monotherapy, or VI monotherapy in patients with moderate to very severe COPD.
In two multicentre, randomised, blinded, double-dummy, parallel-group, active-controlled trials, eligible patients (current or former smokers aged 40 years or older with an established clinical history of COPD) were randomly assigned in 1:1:1:1 ratio to UMEC 125 μg plus VI 25 μg, UMEC 62·5 μg plus VI 25 μg, TIO 18 μg, and either VI 25 μg (study 1) or UMEC 125 μg (study 2). All study drugs were used once daily for 24 weeks. TIO was delivered via the HandiHaler inhaler and all other active treatments were delivered via the ELLIPTA dry powder inhaler. Random assignment (by a validated computer-based system) was done by centre and was not stratified. All patients and physicians were masked to assigned treatment during the studies. The primary efficacy endpoint of both studies was trough forced expiratory volume in 1 s (FEV1) on day 169, which was analysed in the intention-to-treat population. Both studies are registered with ClinicalTrials.gov, numbers NCT01316900 (study 1) and NCT01316913 (study 2).
1141 participants were recruited in study 1, and 1191 in study 2. For study 1, after exclusions, 208, 209, 214, and 212 patients were included in the intention-to-treat analyses for TIO monotherapy, VI monotherapy, UMEC 125 μg plus VI 25 μg, and UMEC 62·5 μg plus VI 25 μg, respectively. For study 2, 215, 222, 215, and 217 patients were included in the intention-to-treat analyses for TIO monotherapy, UMEC monotherapy, UMEC 125 μg plus VI 25 μg, and UMEC 62·5 μg plus VI 25 μg, respectively. In both studies, we noted improvements in trough FEV1 on day 169 for both doses of UMEC plus VI compared with TIO monotherapy (study 1, UMEC 125 μg plus VI 25 μg: 0·088 L 95% CI 0·036 to 0·140; p=0·0010; study 1, UMEC 62·5 μg plus VI 25 μg: 0·090 L 0·039 to 0·141; p=0·0006; study 2, UMEC 125 μg plus VI 25 μg: 0·074 L 0·025 to 0·123; p=0·0031; study 2, UMEC 62·5 μg plus VI 25 μg: 0·060 L 0·010 to 0·109; nominal p=0·0182). Both doses of UMEC plus VI also improved trough FEV1 compared with VI monotherapy (UMEC 125 μg plus VI 25 μg: 0·088 L 0·036 to 0·140; p=0·0010; UMEC 62·5 μg plus VI 25 μg: 0·090 L 0·039 to 0·142; p=0·0006, but not compared with UMEC 125 μg monotherapy (UMEC 125 μg plus VI 25 μg: 0·037 L -0·012 to 0·087; p=0·14; UMEC 62·5 μg plus VI 25 μg: 0·022 L -0·027 to 0·072; p=0·38). All treatments produced improvements in dyspnoea and health-related quality of life; we noted no significant differences in symptoms, health status, or risk of exacerbation between UMEC plus VI and TIO. The most common on-treatment, severe-intensity adverse event in both studies was acute exacerbation of COPD (1-4 <1-2% patients across treatment groups in study 1 and 1-6 <1-3% patients in study 2). We recorded five to 15 (2-7%) on-treatment serious adverse events across treatment groups in study 1, and nine to 22 (4-10%) in study 2. We noted no substantial changes from baseline in vital signs, clinical laboratory findings, or electrocardiography findings in any of the treatment groups.
Combination treatment with once-daily UMEC plus VI improved lung function compared with VI monotherapy and TIO monotherapy in patients with COPD. Overall our results suggest that the combination of UMEC plus VI could be beneficial for the treatment of moderate to very severe COPD.
GlaxoSmithKline.
Physical activity (PA) is a relevant outcome measure in chronic obstructive pulmonary disease (COPD). Low PA is prevalent and drives prognosis 1. Unfortunately, the determinants of PA and its change ...over time are poorly understood 1. The fact that the PA progressively declines over time along with worsening of lung function and health status 2 suggests that the PA decline could be due to the progression of the disease and specifically to acute exacerbations 3. An acute reduction in PA at the onset has been reported both in severe exacerbations requiring a hospitalisation 4 and in ambulatory treated exacerbations 5, 6. A sustained PA reduction has been shown 1 month after hospital discharge 4 whereas PA almost returns to stable levels after community-treated exacerbations 6. One study found faster PA decline in patients with a history of two or more exacerbations in the 12 months prior to the study 5. This analysis did not adjust for confounders of the association (e.g. airflow obstruction, symptom burden) or external variables influencing PA (e.g. climate). It could also be argued that the greater decline in PA was due to lower health status at baseline. Although PA is an important outcome for COPD patients, little is known about the role of exacerbations in patients' experience of PA. Importantly, both the amount of activity and difficulties experienced during activity are integral to the concept of PA limitation 7. The aim of the present analysis was to assess the association between the number and severity of exacerbations and changes in PA and PA experience.
Background
Symptom constructs included in the Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS®: COPD) tool may be relevant to patients with asthma. The purpose of this ...study was to evaluate content validity and psychometric performance of the E-RS: COPD in moderate/severe asthma patients.
Methods
Content validity of the E-RS: COPD was evaluated in patients with moderate/severe asthma using concept elicitation and cognitive debriefing interviews. Secondary analyses using data from two clinical trials in patients with moderate/severe asthma evaluated the factor structure of the E-RS: COPD plus two supplementary items (wheeze; shortness of breath with strenuous physical activity) and assessed psychometric properties of the tool, which will be referred to as E-RS®: Asthma when used in asthma populations.
Results
Qualitative interviews (
N
= 25) achieved concept saturation for asthma respiratory symptoms. Concepts in the E-RS: COPD were relevant to patients and instructions were understood. Most patients (19/25; 76%) reported experiencing all concepts in the E-RS: COPD; no patients indicated missing symptoms. Secondary analyses of clinical trial data supported the original factor structure (RS-Total and three symptom-specific subscales). The two supplemental items did not fit with this factor structure and were not retained. RS-Total and subscale score reliability was high (internal consistency α > 0.70). Validity was demonstrated through significant (
P
< 0.0001) relationships with the St George’s Respiratory Questionnaire (SGRQ) and Asthma Symptom Severity scale. E-RS: Asthma was responsive to change when evaluated using SGRQ, Patient Global Impression of Change and Asthma Quality of Life Questionnaire as anchors (
P
< 0.0001). Clinically meaningful change thresholds were also identified (RS-Total: − 2.0 units).
Conclusions
The E-RS: Asthma is reliable and responsive for evaluating respiratory symptoms in patients with moderate/severe asthma.
Background
Chronic obstructive pulmonary disease (COPD) and muscle weakness can cause impaired physical function, significantly impacting patients’ health-related quality of life (HRQoL). Loss of ...muscle strength is usually assessed through clinical and performance outcome (PerfO) assessments, which consists of tasks performed in a standardized manner, providing evidence of a patient’s functional ability. However, evidence documenting the patient experience of COPD and muscle weakness is limited.
Methods
This two-stage qualitative study used semi-structured interviews in patients aged 45–80 years with COPD (post-bronchodilator forced expiratory volume in 1s FEV
1
/forced vital capacity ratio < 0.70, and FEV
1
% predicted of 30–80%) and muscle weakness. In Stage 1, 30-minute concept elicitation interviews were conducted with participants recruited across three US sites to explore impacts on physical functioning and activities of daily living. In Stage 2, interviews were performed with participants exiting a Phase IIa trial investigating the efficacy of a selective androgen receptor modulator (GSK2881078) on leg strength, whereby PerfOs were used to evaluate strength and physical functioning endpoints. These participants completed either 60-minute in-depth (
n
= 32) or 15-minute confirmatory (
n
= 35) interviews exploring trial experience, completion of outcome measures, disease experience and treatment satisfaction.
Results
In Stage 1 (
n
= 20), most participants described their muscles as weak (83.3%). Difficulties with walking (100%) and lifting heavy objects (90%) were reported. In Stage 2, 60-minute interviews, all participants (
n
= 32) reported a positive trial experience. Most participants reported that the home exercise program was easy to fit into daily life (77.8%), the PROactive daily diary was easy to complete (100%) and wearable sensors were easy to use (65.6%). However, technical issues were reported (71%), and few participants (19.4%) found physical assessments easy to complete. Improvements in muscle strength and functional limitations were reported by most participants. The shorter 15-minute confirmatory interviews (
n
= 35) supported the in-depth interview results.
Conclusion
The qualitative interviews generated in-depth evidence of key concepts relevant to patients with COPD and muscle weakness and support the assessments of patient strength and physical function as outcome measures in this population in future studies.
Trial number
GSK Stage 1: 206869; Stage 2: 200182, NCT03359473; Registered December 2, 2017,
https://clinicaltrials.gov/ct2/show/NCT03359473
.
Real-world trial data comparing single- with multiple-inhaler triple therapy (MITT) in COPD patients are currently lacking. The effectiveness of once-daily single-inhaler fluticasone furoate ...(FF)/umeclidinium (UMEC)/vilanterol (VI) and MITT were compared in usual clinical care.
INTREPID was a multicentre, randomised, open-label, phase IV effectiveness study comparing FF/UMEC/VI 100/62.5/25 µg
the ELLIPTA inhaler with a clinician's choice of any approved non-ELLIPTA MITT in usual COPD clinical practice in five European countries. Primary end-point was proportion of COPD Assessment Test (CAT) responders (≥2-unit decrease in CAT score from baseline) at week 24. Secondary end-points in a subpopulation included change from baseline in forced expiratory volume in 1 s (FEV
) and percentage of patients making at least one critical error in inhalation technique at week 24. Safety was also assessed.
3092 patients were included (FF/UMEC/VI n=1545; MITT n=1547). The proportion of CAT responders at week 24 was significantly greater with FF/UMEC/VI
non-ELLIPTA MITT (OR 1.31, 95% CI 1.13-1.51; p<0.001) and mean change from baseline in FEV
was significantly greater with FF/UMEC/VI (77 mL
28 mL; treatment difference 50 mL, 95% CI 26-73 mL; p<0.001). The percentage of patients with at least one critical error in inhalation technique was low in both groups (FF/UMEC/VI 6%; non-ELLIPTA MITT 3%). Safety profiles, including incidence of pneumonia serious adverse events, were similar between treatments.
In a usual clinical care setting, treatment with once-daily single-inhaler FF/UMEC/VI resulted in significantly more patients gaining health status improvement and greater lung function improvement
non-ELLIPTA MITT.
Background
There is limited information available on the impact of moderate asthma exacerbations, often called “asthma attacks” (i.e., those not requiring hospitalisation or treatment with systemic ...corticosteroids) on patients’ lives. This multi-country qualitative study explored the patient experience of these events.
Methods
Semi-structured concept elicitation interviews were conducted in the USA and Germany with adult patients with asthma who had experienced a moderate asthma exacerbation in the prior 30 days. Physicians with experience in managing patients with asthma were also interviewed. Interviews explored patients’ experience of symptoms and impact of moderate exacerbations and associated exacerbation triggers and treatment patterns. Physicians were also asked about their interpretation of a clinical definition and treatment of a moderate exacerbation.
Results
Twenty-eight patient (n = 20 in the USA, n = 8 in Germany) and six physician (n = 3 in the USA, n = 3 in Germany) interviews were conducted. During their moderate exacerbation, all patients reported experiencing shortness of breath, which many considered to be severe and the most bothersome symptom. Wheezing was also reported by all patients and considered severe by two thirds of patients. Most patients also reported coughing and chest tightness. All or almost all patients reported that moderate exacerbation caused fatigue/tiredness and impacted their physical functioning, emotional functioning, activities of daily living and work/school life. Most patients reported using rescue or maintenance inhalers to alleviate symptoms of the exacerbation. Conceptual saturation (i.e., the point at which no new concepts are likely to emerge with continued data collection) was achieved. Findings were used to develop a patient-focused conceptual model of the experience of moderate asthma exacerbations, outlining concepts related to triggers, symptoms, impact, and treatment from the patient perspective. Physician data was consistent with patient reports and complemented the conceptual model.
Conclusions
Findings from concept elicitation interviews highlight the increased frequency, duration and severity of asthma symptoms and increased rescue medication use during moderate asthma exacerbations compared with the typical daily asthma experience, which have a substantial impact on patients’ lives.
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