Niklas Karlsson

Patient insight into the impact of chronic obstructive pulmonary disease in the morning: an internet survey

ABSTRACT Objective: To determine diurnal variability of symptoms in chronic obstructive pulmonary disease (COPD) and to assess the impact of COPD upon patients’ morning activities and routines. Research design and methods: Quantitative internet interviews with 803 COPD patients from Europe and the USA, including 289 patients with severe COPD. Severe COPD was defined according to regular use of COPD medication, third level of breathlessness or above using the modified Medical Research Council (MRC) dyspnoea scale (MRC dyspnoea score ≥3) and one or more COPD exacerbations in the preceding 12 months. Results: Morning was the worst time of day for COPD symptoms, particularly in patients with severe COPD (reported by 46% of severe patients). In these patients, shortness of breath was the most frequently reported symptom, correlating strongly with problems experienced with morning activities. Morning activities most affected by COPD were walking up and down stairs, putting on shoes and socks, making the bed, dressing, showering or bathing and drying. The majority of patients were not taking their medication in time for it to exert its optimal effect. Conclusions: Many patients consider the impact of COPD on morning activities to be substantial. Physicians should question patients about morning activities to assess disease impact and to advise regarding the optimal time to use therapy. This was an internet-based questionnaire survey and possible bias in patient selection and self-reported diagnosis of COPD and its severity should be taken into account.

Determinants and outcomes of physical activity in patients with COPD: a systematic review

Background The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed. Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD. Methods We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012. Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence. Results 86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both. Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence. Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low. As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence. Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence. Conclusions Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment.

The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD. Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts. 236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”. After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbachs α>0.8), test–retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity. Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients. Both PROactive hybrid tools are simple, valid, and reliable measures of physical activity in COPD patients http://ow.ly/LJqP8

The PROactive innovative conceptual framework on physical activity.

Although physical activity is considered an important therapeutic target in chronic obstructive pulmonary disease (COPD), what “physical activity” means to COPD patients and how their perspective is best measured is poorly understood. We designed a conceptual framework, guiding the development and content validation of two patient reported outcome (PRO) instruments on physical activity (PROactive PRO instruments). 116 patients from four European countries with diverse demographics and COPD phenotypes participated in three consecutive qualitative studies (63% male, age mean±sd 66±9 years, 35% Global Initiative for Chronic Obstructive Lung Disease stage III–IV). 23 interviews and eight focus groups (n = 54) identified the main themes and candidate items of the framework. 39 cognitive debriefings allowed the clarity of the items and instructions to be optimised. Three themes emerged, i.e. impact of COPD on amount of physical activity, symptoms experienced during physical activity, and adaptations made to facilitate physical activity. The themes were similar irrespective of country, demographic or disease characteristics. Iterative rounds of appraisal and refinement of candidate items resulted in 30 items with a daily recall period and 34 items with a 7-day recall period. For the first time, our approach provides comprehensive insight on physical activity from the COPD patients’ perspective. The PROactive PRO instruments’ content validity represents the pivotal basis for empirically based item reduction and validation. Conceptual framework as basis of PROactive PRO instruments to assess physical activity from COPD patient perspective http://ow.ly/ytJoS

Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used.

Background The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient’s distribution in relation to the questionnaire used. Methods 136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis. Results GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants. Conclusions Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion. Clinical Trial Registration ClinicalTrials.gov NCT01388218

Asthma-chronic obstructive pulmonary disease overlap syndrome in the urban Chinese population: prevalence and disease burden using the 2010, 2012, and 2013 China National Health and Wellness Surveys

Background Research has suggested a significant burden for patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). However, few studies have studied this population in the People’s Republic of China, a region in the midst of rapid epidemiological change with respect to respiratory disease. The aim of this study was to assess the prevalence of ACOS and its association with patient outcomes in urban China. Methods Data from the 2010, 2012, and 2013 China National Health and Wellness Survey, an Internet-based survey of adults in urban China, were used (N=59,935). Respondents were categorized into one of four groups based on self-reported physician diagnoses: ACOS, asthma only, COPD only, or control (ie, no asthma or COPD). A propensity score matching procedure was conducted to cull the control group into a subgroup (ie, matched controls) who resembled patients with ACOS, asthma only, and COPD only. These four groups (ACOS, asthma only, COPD only, matched controls) were then compared with respect to health status (Short Form-12 version 2/Short Form-36 version 2), work productivity, and health care resource use using generalized linear models. Results Patients with ACOS (N=366) comprised 0.61% of the adult population, 30.73% of the asthma population, and 18.60% of the COPD population in the People’s Republic of China. Patients with ACOS reported significantly worse health status (eg, health utilities =0.63, 0.66, 0.63, and 0.69 for ACOS, COPD only, asthma only, and matched controls, respectively) and significantly greater work impairment (eg, overall work impairment =43.65%, 35.19%, 48.55%, and 29.80%, respectively) and health care resource use (eg, physician visits in the past 6 months =5.13, 3.84, 4.65, and 2.39, respectively) compared with matched controls and patients with COPD only. Few significant differences were observed between patients with ACOS and asthma only. Conclusion Patients with ACOS have a greater comorbidity burden and significantly worse health outcomes compared with COPD only patients and matched controls. Better management of these patients may help to improve their outcomes.

Depression symptoms reduce physical activity in COPD patients: a prospective multicenter study

Background The role of anxiety and depression in the physical activity (PA) of patients with COPD is controversial. We prospectively assessed the effect of symptoms of anxiety and depression on PA in COPD patients. Methods We evaluated anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), PA (Dynaport® accelerometer), and other relevant characteristics in 220 COPD patients from five European countries at baseline and at 6 and 12 months of follow-up. HADS score was categorized as: no symptoms (score 0–7), suggested (8–10), and probable (>11) anxiety or depression. We estimated the association between anxiety and depression at t (baseline and 6 months) and PA at t+1 (6 and 12 months) using regression models with a repeated measures approach. Results Patients had a mean (standard deviation) age of 67 (8) years, forced expiratory volume in 1 second 57 (20)% predicted. At baseline, the prevalence of probable anxiety and depression was 10% and 5%, respectively. In multivariable models adjusted by confounders and previous PA, patients performed 81 fewer steps/day (95% confidence interval, −149 to −12, P=0.02) per extra point in HADS-depression score. HADS-anxiety symptoms were not associated with PA. Conclusion In COPD patients, symptoms of depression are prospectively associated with a measurable reduction in PA 6 months later.

A cross-sectional assessment of the prevalence and burden of mild asthma in urban China using the 2010, 2012, and 2013 China National Health and Wellness Surveys

ABSTRACT Objective: To estimate the prevalence of mild asthma in urban China and to measure the association between asthma severity and quality of life (QOL), work productivity, and healthcare resource use. Methods: Data were from the China National Health and Wellness Surveys (NHWS) conducted between 2010 and 2013 (N = 59,935), Internet-based surveys of adults in urban China. Patients were categorized by asthma severity according to self-report and Global Initiative for Asthma (GINA2014) guidelines via self-reported medication use (mild [GINA 1-2] vs moderate/severe [GINA 3-4]). Propensity scores were used to identify matched controls without asthma. These three groups (mild vs. moderate/severe vs. matched control) were compared with respect to QOL (revised Short Form-12/36), work productivity (WPAI questionnaire), and healthcare use using generalized linear models. Results: 1,191 respondents reported an asthma diagnosis (1.99%). Then 455 (0.77% and 76.86% of the total sample and asthma sample which could be categorized based on GINA2014 guidelines, respectively) and 897 (1.50% and 75.31% of the total and asthma sample, respectively) had mild asthma based on GINA2014 guidelines and self-report, respectively. Compared with matched controls, mild patients based on GINA2014 guidelines reported worse QOL (Physical Component Summary = 44.67 vs. 48.97), more overall work impairment (54.51% vs. 34.35%), and more all-cause emergency room visits in the past 6 months (1.95 vs. 0.63 visits) (all p <.05). Similar results were observed using self-reported severity. Conclusions: Most patients with asthma in the China NHWS are mild according to either definition. Asthma patients experience significant burden to QOL, work productivity, activity impairment, and healthcare resource use.

A cross-sectional assessment of the burden of COPD symptoms in the US and Europe using the National Health and Wellness Survey

Introduction Past research has suggested significant relationships between symptoms and health outcomes among patients with COPD. However, these studies have generally focused on a broad COPD sample and may have included those not receiving proper treatment. As a result, the aim of this study was to document the burden of COPD symptoms among those who are currently treated with the standard-of-care (SOC) medications in both the US and Western Europe. Methods Data from the 2013 US (N=75,000) and 2011 (N=57,512)/2013 (N=62,000) European (France, Germany, Italy, Spain, and UK; 5EU) National Health and Wellness Survey (NHWS) were used. The NHWS is a health survey administered to a demographically representative sample of the adult population in each country. A total of 1,666 and 2,006 patients with self-reported physician diagnosis of COPD in the 5EU and US, respectively, were being treated with the appropriate SOC (based on self-reported medication use) and were included in the analyses. Symptoms (eg, dyspnea, coughing, wheezing) were reported descriptively and summed to create a symptom score (with higher score indicating more frequent symptoms). The relationships between the symptom score and patient outcomes (eg, health status using the Short Form-36 version 2 [SF-36v2], work productivity and activity impairment [WPAI], and self-reported health care resource use) were explored using regression modeling. Results Nearly all patients (99.7% and 99.8% in the 5EU and US, respectively) reported experiencing symptoms and >80% reported experiencing at least one symptom “often”. Increasing symptom scores were associated with poorer health status (unstandardized beta [b] =−0.87 and −0.78 for mental component summary and physical component summary, respectively, in the US and b =−0.67 and −0.79 in the 5EU, respectively; all P<0.05). Increasing symptom scores were also associated with greater work impairment (b =0.09 and 0.06 for the US and 5EU, respectively), activity impairment (b =0.05 and 0.06, respectively), and health care resource utilization (eg, hospitalizations: b =0.05 and 0.06, respectively) (all P<0.05). Approximately 70% of patients reported some level of non-adherence. Greater non-adherence was significantly associated with more frequent symptoms, poorer health status, and greater work impairment and health care resource use (all P<0.05). Conclusion Patients with COPD who are using the appropriate SOC still experience symptoms, which have a significant effect on both humanistic and economic outcomes.

Responder Analyses for Treatment Effects in COPD Using the St George’s Respiratory Questionnaire

Background: Patient-reported outcomes data in clinical trials are usually reported as mean values, interpreted in comparison to a minimum clinically important difference (MCID) and ignoring the possibility of a sizable proportion of patients experiencing a worthwhile benefit when the majority did not. This analysis tested the reliability of calculated responder rates (from chronic obstructive pulmonary disease [COPD] patients) with the St Georges Respiratory Questionnaire (SGRQ) using a range of responder cut-points above and below the MCID (4 units). Methods: Individual patient data (i.e., data from long-acting bronchodilator [LAB] and inhaled corticosteroids [ICS]/long-acting beta2-agonist [LABA] randomized clinical studies) in the COPD Biomarker Qualification Consortium database were used: short-term (≤1-year duration; 14,814 patients,) and medium-term (2-4 years; 12,043 patients). Responder rates versus placebo across SGRQ score change thresholds ranging from -1.5 to -8.0 were tested; differences were expressed as the odds ratio (OR) of a patient exceeding the threshold versus no change or deterioration. Results: The ORs measuring benefit of active treatment were similar across thresholds in short-term studies (LAB, ORs 1.40-1.42; LABA/ICS, 1.50-1.56) and medium-term LAB studies (ORs 1.34-1.43), whereas ORs in medium-term studies with LABA/ICS intervention showed a trend for higher response rates at higher values of threshold cut-points (1.64-1.79). In short-term studies, different thresholds had little effect on the OR between active drugs versus a trend for lower ORs with lower thresholds in medium-term studies. Conclusions: The OR for a treatment effect compared with placebo appears consistent across a range of responder cut-points. In medium-term trials, the treatment difference between active drugs suggests that use of a lower threshold would not increase the odds of observing a measured treatment difference.