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      Symptom variability in COPD: a narrative review

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          Chronic obstructive pulmonary disease (COPD) has traditionally been considered an inexorably progressive disease, associated with a constant increase of symptoms that occur as the forced expiratory volume in 1 second (FEV 1) worsens, only intermittently interrupted by exacerbations. However, this paradigm has been challenged in recent decades by the available evidence. Recent studies have pointed out that COPD-related symptoms are not consistently perceived by patients in the same way, showing not only seasonal variation, but also changes in symptom perception during a week or even within a single day. According to the available data, patients experience the biggest increase in respiratory symptoms during the first hours of the early morning, followed by the nighttime. This variation over time is of considerable importance, since it impacts on daily life activities and health-related quality of life, as measured by a recently developed ad hoc questionnaire. Additionally, recent clinical trials have suggested that the use of rapid-onset long-acting bronchodilators may have an impact on morning symptoms, despite their current use as maintenance treatment for a determined period. Although this hypothesis is to be validated in future long-term clinical trials comparing fast-onset versus slow-onset inhaled drugs in COPD, it may bring forward a new concept of long-term bronchodilator therapy. At the present time, the two available long-acting, fast-onset bronchodilators used in the treatment of COPD are formoterol and the recently marketed indacaterol. Newer drugs have also been shown to have a rapid onset of action in preclinical studies. Health care professionals caring for COPD patients should consider this variation in the perception of symptoms during their clinical interview as a potential new target in the long-term treatment plan.

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          Most cited references 30

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          The natural history of chronic airflow obstruction.

          A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).
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            Patient insight into the impact of chronic obstructive pulmonary disease in the morning: an internet survey.

            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. 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 > or =3) and one or more COPD exacerbations in the preceding 12 months. 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. 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.
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              Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: the GLOW2 study

              NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD). The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks. Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks. Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks. 1,066 patients were randomised, 810 completed the study. At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6–130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6–121.4; p<0.001). Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001). NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo. NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes. Safety profiles were similar across groups. NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium. NVA237 can potentially be an alternative choice of LAMA for COPD patients.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                07 May 2013
                : 8
                : 231-238
                [1 ]Unidad Medico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio, Seville, Spain
                [2 ]CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
                Author notes
                Correspondence: Jose Luis Lopez-Campos, Hospital Universitario Virgen del Rocio, Avda Manuel Siurot, s/n, 41013, Seville, Spain, Tel +34 95 501 3167, Fax +34 95 501 3167, Email lcampos@
                © 2013 Lopez-Campos et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.



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