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      Morning and night symptoms in primary care COPD patients: a cross-sectional and longitudinal study. An UNLOCK study from the IPCRG

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          Abstract

          COPD symptoms show a diurnal variability. However, morning and night variability has generally not been taken into consideration in disease management plans. The aims of this study were to cross-sectionally assess morning and night symptom prevalence and correlation with health status and disease severity in COPD, and to determine to what extent they could predict longitudinal outcomes, exacerbations and health status. A further aim is to explore whether the CCQ is able to depict this morning/night symptomatology. We included 2,269 primary care COPD patients (58% male, 49% current smokers, with a mean age of 65±11 years) from a Dutch Asthma/COPD service. Spirometry, patient history, the Clinical COPD Questionnaire(CCQ) and the Asthma Control Questionnaire(ACQ) were assessed; we used the latter to evaluate morning (question 2) and night symptoms (question 1). A total of 1159 (51.9%) patients reported morning symptoms (ACQ question 2>0) and 879 (39.4%) had night complaints (ACQ question 1>0). Patients with morning/night symptoms were mostly smokers and had on average poorer lung function, higher CCQ scores and used more rescue inhalers ( P<0.0001). Patients using long-acting muscarinic antagonists (LAMAs) had less night symptoms, showing a possible favourable effect. Only a small proportion of stable or slightly unstable patients (CCQ total scores <2) had severe morning symptoms (ACQ 2⩾4: n=19, 1.1%) or severe night symptoms (ACQ 1⩾4: n=11, 0.7%). Night symptoms seemed to predict future exacerbations; however, baseline exacerbations were the strongest predictors ( n=346, OR:4.13, CI: 2.45−6.95, P<0.000). Morning symptoms increased the odds of poor health status at follow-up ( n=346, OR:12.22, CI:4.76−31.39, P<0.000). Morning and night symptoms in COPD patients are common, and they are associated with poor health status and predicted future exacerbations. Our study showed that patients with morning/night symptoms have higher scores in CCQ, and therefore we do not really miss patients with high morning/night symptomatology when we only measure CCQ. Severe morning symptoms predicted worsening of COPD health status.

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          Susceptibility to exacerbation in chronic obstructive pulmonary disease.

          Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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            Development and validation of a questionnaire to measure asthma control.

            International guidelines on asthma management indicate that the primary goal of treatment should be optimum asthma control. The aim of this study was to develop and validate the Asthma Control Questionnaire (ACQ). The authors generated a list of all symptoms used to assess control and sent it to 100 asthma clinicians who were members of guidelines committees (18 countries). They scored each symptom for its importance in evaluating asthma control. From the 91 responses, the five highest scoring symptoms were selected for the ACQ. In addition, there is one question on beta2-agonist use and another on airway calibre (total questions=7). The ACQ was tested in a 9-week observational study of 50 adults with symptomatic asthma. The ACQ and other measures of asthma health status were assessed at baseline, 1, 5 and 9 weeks. In patients whose asthma was stable between clinic visits, reliability of the ACQ was high (intraclass correlation coefficient (ICC)=0.90). The questionnaire was very responsive to change in asthma control (p<0.0001). Cross-sectional and longitudinal validity were supported by correlations between the ACQ and other measures of asthma health status being close to a priori predictions. In conclusion, the Asthma Control Questionnaire has strong evaluative and discriminative properties and can be used with confidence to measure asthma control.
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              Night-time symptoms: a forgotten dimension of COPD.

              Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD), but these night-time symptoms are frequently unnoticed by physicians and/or not reported by patients themselves. Therefore, the prevalence and clinical impact of sleep disturbances and night-time symptoms in COPD is not well understood and has not been a clinical focus to date. To address this gap, an expert panel meeting was convened in Barcelona, Spain, in March 2011 to discuss the aetiology, evolution, burden, long-term clinical consequences and optimal management of night-time symptoms in COPD. The term "night-time symptoms" in COPD has not been distinctly defined in an objective sense but epidemiological data suggests that the prevalence of nocturnal symptoms and symptomatic sleep disturbance may exceed 75% in patients with COPD. The panel concluded that night-time symptoms in COPD are prevalent and bothersome; that their cause(s) are multiple and include demographic factors, such as age and obesity, pharmacotherapy, disease-specific symptoms and the presence of comorbid sleep disorders, and other medical conditions; and that potential long-term consequences can include lung function changes, increased exacerbation frequency, emergence or worsening of cardiovascular disease, cognitive effects, depression, impaired quality of life and increased mortality. To date, few interventional studies have investigated them, but emerging data suggest that bronchodilator therapy can improve them if deployed appropriately. In summary, night-time symptoms in COPD warrant further clinical investigation with validated tools.
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                Author and article information

                Journal
                NPJ Prim Care Respir Med
                NPJ Prim Care Respir Med
                NPJ Primary Care Respiratory Medicine
                Nature Publishing Group
                2055-1010
                21 July 2016
                2016
                : 26
                : 16040
                Affiliations
                [1 ] Department of General Practice, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands
                [2 ] Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands
                [3 ] Department of Public Health and Primary Care LUMC , Leiden, The Netherlands
                Author notes
                []

                All authors participated in the concept of the research idea, in developing the protocol and in writing this draft. E.M. extracted the data from the AC service and performed the statistical analysis. I.T. wrote the first draft consequently commented and improved by all authors. T.v.d.M. manages the AC service. J.W.K. and I.T. are the guarantors of the study.

                Author information
                http://orcid.org/0000-0002-8607-9199
                http://orcid.org/0000-0002-2760-0693
                Article
                npjpcrm201640
                10.1038/npjpcrm.2016.40
                4956029
                27442618
                049ce282-b43c-4ac6-aad5-5c15f395dba9
                Copyright © 2016 Published in partnership with Primary Care Respiratory Society UK

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 12 August 2015
                : 25 March 2016
                : 27 April 2016
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