Janwillem Kocks

Factors that influence disease-specific quality of life or health status in patients with COPD: a systematic review and meta-analysis of Pearson correlations

BACKGROUND A major goal in the management of chronic obstructive pulmonary disease (COPD) is to ensure that the burden of the disease for patients with COPD is limited and that patients will have the best possible quality of life. AIMS To explore all the possible factors that could influence disease-specific quality of life and health status in patients with COPD. METHODS A systematic review of the literature and a meta-analysis were performed to explore the factors that could have a positive or negative effect on quality of life and/or health status in patients with COPD. RESULTS Quality of life and health status are determined by certain factors included gender, disease severity indices, lung function parameters, body mass index, smoking, symptoms, co-morbidity, depression, anxiety, and exacerbations. Factors such as dyspnoea, depression, anxiety and exercise tolerance were found to be more correlated with health status than the widely used spirometric values. Forced expiratory volume in one second had a weak to modest Pearson weighted correlation coefficient which ranged from -0.110 to -0.510 depending on the questionnaire used. CONCLUSIONS The broad range of determining factors suggests that, in order to reach the management goals, health status should be measured in addition to lung function in patients with COPD.

Assessing health status in COPD. A head-to-head comparison between the COPD assessment test (CAT) and the clinical COPD questionnaire (CCQ)

BackgroundHealth status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management. We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St. George Respiratory Questionnaire (SGRQ).MethodsWe administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits. Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits. Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.ResultsWe enrolled 90 COPD patients. Cronbachs alpha for both CAT and CCQ was high (0.86 and 0.89, respectively). Patients with severe COPD reported worse health status compared to milder subgroups. CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01). Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01). Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98). The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ. Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations. More than half of patients preferred CCQ instead of CAT.ConclusionsThe CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients.

Moving from the Oslerian paradigm to the post-genomic era: are asthma and COPD outdated terms?

In the majority of cases, asthma and chronic obstructive pulmonary disease (COPD) are two clearly distinct disease entities. However, in some patients there may be significant overlap between the two conditions. This constitutes an important area of concern because these patients are generally excluded from randomised controlled trials (mostly because of smoking history in the case of asthma or because of significant bronchodilator reversibility in the case of COPD). As a result, their pathobiology, prognosis and response to therapy are largely unknown. This may lead to suboptimal management and can limit the development of more personalised therapeutic options. Emerging genetic and molecular information coupled with new bioinformatics capabilities provide novel information that can pave the way towards a new taxonomy of airway diseases. In this paper we question the current value of the terms ‘asthma’ and ‘COPD’ as still useful diagnostic labels; discuss the scientific and clinical progress made over the past few years towards unravelling the complexity of airway diseases, from the definition of clinical phenotypes and endotypes to a better understanding of cellular and molecular networks as key pathogenic elements of human diseases (so-called systems medicine); and summarise a number of ongoing studies with the potential to move the field towards a new taxonomy of airways diseases and, hopefully, a more personalised approach to medicine, in which the focus will shift from the current goal of treating diseases as best as possible to the so-called P4 medicine, a new type of medicine that is predictive, preventive, personalised and participatory.

Primary Care COPD Patients Compared with Large Pharmaceutically-Sponsored COPD Studies : An UNLOCK Validation Study

Background Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS). There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care. Objective We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials. Methods Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS. In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria. Results Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01). There were large differences in GOLD stage distribution compared to primary care patients. Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant. Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year. The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT). Conclusion Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations. More research is needed to determine the effect of pharmacological treatment in mild to moderate patients. We encourage future guideline makers to involve primary care populations in their recommendations.

Reliability and validity of the clinical COPD questionniare and chronic respiratory questionnaire

BACKGROUND Questionnaires are often used in assessing health-related quality of life in patients with chronic obstructive pulmonary disease (COPD). It is important that these questionnaires have good reliability, validity, and responsiveness. The aim of this study was to investigate and compare these properties in the disease specific Clinical COPD Questionnaire (CCQ) and the Chronic Respiratory Questionnaire self-reported (CRQ-SR). METHODS Two hundred ninety six participants with spirometry confirmed mild to moderate COPD were included in a smoking cessation trial. It was assumed that health-related quality of life would improve in participants who stopped smoking. The questionnaires were administered at baseline and at weeks 5, 26, and 52 after the target quit date. RESULTS At baseline, 292 (97%) participants returned the CCQ and 296 (100%) the CRQ-SR questionnaire. For both instruments, the internal consistency was good (Cronbachs alpha >70%) as was the convergent validity with each other but not with spirometry. The CCQ was responsive to improvements in respiratory symptoms at both week 26 (-1.02, SD = 0.81) and 52 (-1.04, SD = 0.91) and in the total score at week 26 (-0.54, SD = 0.50) and 52 (-0.43, SD = 0.44). The mastery domain and the total score of the CRQ-SR were responsive at week 26 (1.14, SD = 0.82; 0.67, SD = 0.97 respectively) but not at week 52 (0.04, SD = 0.93; 0.38, SD = 0.57 respectively). CONCLUSION Both the CCQ and CRQ-SR are equally reliable and valid. The long-term responsiveness of the CCQ is better. Both questionnaires can be used in future studies involving patients with mild to moderate COPD. However, when the follow-up exceeds 26 weeks, the CCQ is the recommended alternative. Netherlands Trial Register: ISRCTN 64481813.

COPD management: role of symptom assessment in routine clinical practice.

Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life. Despite this, COPD treatment and its management are mainly based on lung function assessments. There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives. Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD. Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice. In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed.

Human cellular differences in cAMP - CREB signaling correlate with light-dependent melatonin suppression and bipolar disorder

Various lines of evidence suggest a mechanistic role for altered cAMP‐CREB (cAMP response element ‐ binding protein) signaling in depressive and affective disorders. However, the establishment and validation of human inter‐individual differences in this and other major signaling pathways has proven difficult. Here, we describe a novel lentiviral methodology to investigate signaling variation over long periods of time directly in human primary fibroblasts. On a cellular level, this method showed surprisingly large inter‐individual differences in three major signaling pathways in human subjects that nevertheless correlated with cellular measures of genome‐wide transcription and drug toxicity. We next validated this method by establishing a likely role for cAMP‐mediated signaling in a human neuroendocrine response to light – the light‐dependent suppression of the circadian hormone melatonin – that shows wide inter‐individual differences of unknown origin in vivo. Finally, we show an overall greater magnitude of cellular CREB signaling in individuals with bipolar disorder, suggesting a possible role for this signaling pathway in susceptibility to mental disease. Overall, our results suggest that genetic differences in major signaling pathways can be reliably detected with sensitive viral‐based reporter profiling, and that these differences can be conserved across tissues and be predictive of physiology and disease susceptibility.

Day-to-day measurement of patient-reported outcomes in exacerbations of chronic obstructive pulmonary disease

Background Exacerbations of chronic obstructive pulmonary disease (COPD) are a major burden to patients and to society. Little is known about the possible role of day-to-day patient-reported outcomes during an exacerbation. This study aims to describe the day-to-day course of patient-reported health status during exacerbations of COPD and to assess its value in predicting clinical outcomes. Methods Data from two randomized controlled COPD exacerbation trials (n = 210 and n = 45 patients) were used to describe both the feasibility of daily collection of and the day-to-day course of patient-reported outcomes during outpatient treatment or admission to hospital. In addition to clinical parameters, the BORG dyspnea score, the Clinical COPD Questionnaire (CCQ), and the St George’s Respiratory Questionnaire were used in Cox regression models to predict treatment failure, time to next exacerbation, and mortality in the hospital study. Results All patient-reported outcomes showed a distinct pattern of improvement. In the multivariate models, absence of improvement in CCQ symptom score and impaired lung function were independent predictors of treatment failure. Health status and gender predicted time to next exacerbation. Five-year mortality was predicted by age, forced expiratory flow in one second % predicted, smoking status, and CCQ score. In outpatient management of exacerbations, health status was found to be less impaired than in hospitalized patients, while the rate and pattern of recovery was remarkably similar. Conclusion Daily health status measurements were found to predict treatment failure, which could help decision-making for patients hospitalized due to an exacerbation of COPD.

The minimal clinically important difference of the control of allergic rhinitis and asthma test (CARAT): Cross-cultural validation and relation with pollen counts

Background:The Control of Allergic Rhinitis and Asthma Test (CARAT) monitors control of asthma and allergic rhinitis.Aims:To determine the CARAT’s minimal clinically important difference (MCID) and to evaluate the psychometric properties of the Dutch CARAT.Methods:CARAT was applied in three measurements at 1-month intervals. Patients diagnosed with asthma and/or rhinitis were approached. MCID was evaluated using Global Rating of Change (GRC) and standard error of measurement (s.e.m.). Cronbach’s alpha was used to evaluate internal consistency. Spearman’s correlation coefficients were calculated between CARAT, the Asthma Control Questionnaire (ACQ5) and the Visual Analog Scale (VAS) on airway symptoms to determine construct and longitudinal validity. Test–retest reliability was evaluated with intra-class correlation coefficient (ICC). Changes in pollen counts were compared with delta CARAT and ACQ5 scores.Results:A total of 92 patients were included. The MCID of the CARAT was 3.50 based on GRC scores; the s.e.m. was 2.83. Cronbach’s alpha was 0.82. Correlation coefficients between CARAT and ACQ5 and VAS questions ranged from 0.64 to 0.76 (P<0.01). Longitudinally, correlation coefficients between delta CARAT scores and delta ACQ5 and VAS scores ranged from 0.41 to 0.67 (P<0.01). Test–retest reliability showed an ICC of 0.81 (P<0.01) and 0.80 (P<0.01). Correlations with pollen counts were higher for CARAT than for ACQ5.Conclusions:This is the first investigation of the MCID of the CARAT. The CARAT uses a whole-point scale, which suggests that the MCID is 4 points. The CARAT is a valid and reliable tool that is also applicable in the Dutch population.

Associations between chronic comorbidity and exacerbation risk in primary care patients with COPD

BackgroundCOPD often coexists with chronic conditions that may influence disease prognosis. We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.MethodRetrospective cohort study based on 2012–2013 electronic health records from 179 Dutch general practices. Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes. Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.ResultsFourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years. At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5. The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%). Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38–2.14), blindness & low vision (OR 1.46; 1.21–1.75), pulmonary cancer (OR 1.85; 1.28–2.67), depression 1.48; 1.14–1.91), prostate disorders (OR 1.50; 1.13–1.98), asthma (OR 1.36; 1.11–1.70), osteoporosis (OR 1.41; 1.11–1.80), diabetes (OR 0.80; 0.66–0.97), dyspepsia (OR 1.25; 1.03–1.50), and peripheral vascular disease (OR 1.20; 1.00–1.45). From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17–1.36).ConclusionChronic comorbidities are highly prevalent in primary care COPD patients. Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk.