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      Basic & Clinical Pharmacology & Toxicology
      Blackwell Publishing Ltd

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          Abstract

          The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD). The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD. This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD. It is intended to be used mainly in primary health care but not forgetting respiratory specialists and other healthcare workers. The new recommendations and statements are based on the best evidence available from the medical literature, other published national guidelines and the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report. This guideline introduces the diagnostic approach, differential diagnostics towards asthma, assessment and treatment strategy to control symptoms and to prevent exacerbations. The pharmacotherapy is based on the symptoms and a clinical phenotype of the individual patient. The guideline defines three clinically relevant phenotypes including the low and high exacerbation risk phenotypes and the neglected asthma–COPD overlap syndrome (ACOS). These clinical phenotypes can help clinicians to identify patients that respond to specific pharmacological interventions. For the low exacerbation risk phenotype, pharmacotherapy with short-acting β2-agonists (salbutamol, terbutaline) or anticholinergics (ipratropium) or their combination (fenoterol–ipratropium) is recommended in patients with less symptoms. If short-acting bronchodilators are not enough to control symptoms, a long-acting β2-agonist (formoterol, indacaterol, olodaterol or salmeterol) or a long-acting anticholinergic (muscarinic receptor antagonists; aclidinium, glycopyrronium, tiotropium, umeclidinium) or their combination is recommended. For the high exacerbation risk phenotype, pharmacotherapy with a long-acting anticholinergic or a fixed combination of an inhaled glucocorticoid and a long-acting β2-agonist (budesonide–formoterol, beclomethasone dipropionate–formoterol, fluticasone propionate–salmeterol or fluticasone furoate–vilanterol) is recommended as a first choice. Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium–indacaterol or umeclidinium–vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting β2-agonist and a long-acting anticholinergic. If the patient has severe-to-very severe COPD (FEV1 < 50% predicted), chronic bronchitis and frequent exacerbations despite long-acting bronchodilators, the pharmacotherapy may include also roflumilast. ACOS is a phenotype of COPD in which there are features that comply with both asthma and COPD. Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD. Thus, evidence-based recommendation of treatment cannot be given. The treatment should cover both diseases. Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2-agonist or anticholinergic or both).

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          Most cited references128

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          Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study.

          Information about the influence of regular physical activity on the course of chronic obstructive pulmonary disease (COPD) is scarce. A study was undertaken to examine the association between regular physical activity and both hospital admissions for COPD and all-cause and specific mortality in COPD subjects. From a population-based sample recruited in Copenhagen in 1981-3 and 1991-4, 2386 individuals with COPD (according to lung function tests) were identified and followed until 2000. Self-reported regular physical activity at baseline was classified into four categories (very low, low, moderate, and high). Dates and causes of hospital admissions and mortality were obtained from Danish registers. Adjusted associations between physical activity and hospital admissions for COPD and mortality were obtained using negative binomial and Cox regression models, respectively. After adjustment for relevant confounders, subjects reporting low, moderate or high physical activity had a lower risk of hospital admission for COPD during the follow up period than those who reported very low physical activity (incidence rate ratio 0.72, 95% confidence interval (CI) 0.53 to 0.97). Low, moderate and high levels of regular physical activity were associated with an adjusted lower risk of all-cause mortality (hazard ratio (HR) 0.76, 95% CI 0.65 to 0.90) and respiratory mortality (HR 0.70, 95% CI 0.48 to 1.02). No effect modification was found for sex, age group, COPD severity, or a background of ischaemic heart disease. Subjects with COPD who perform some level of regular physical activity have a lower risk of both COPD admissions and mortality. The recommendation that COPD patients be encouraged to maintain or increase their levels of regular physical activity should be considered in future COPD guidelines, since it is likely to result in a relevant public health benefit.
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            Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.

            To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease. Double blind, placebo controlled study. Eighteen UK hospitals. 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV(1)) 50% of predicted normal. Inhaled fluticasone propionate 500 microgram twice daily from a metered dose inhaler or identical placebo. Efficacy measures: rate of decline in FEV(1) after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events. There was no significant difference in the annual rate of decline in FEV(1 )(P=0.16). Mean FEV(1) after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P<0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P=0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P=0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P=0.034). Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV(1) but did produce a small increase in FEV(1). Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.
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              Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study.

              To determine whether a program incorporating smoking intervention and use of an inhaled bronchodilator can slow the rate of decline in forced expiratory volume in 1 second (FEV1) in smokers aged 35 to 60 years who have mild obstructive pulmonary disease. Randomized clinical trial. Participants randomized with equal probability to one of the following groups: (1) smoking intervention plus bronchodilator, (2) smoking intervention plus placebo, or (3) no intervention. Ten clinical centers in the United States and Canada. A total of 5887 male and female smokers, aged 35 to 60 years, with spirometric signs of early chronic obstructive pulmonary disease. Smoking intervention: intensive 12-session smoking cessation program combining behavior modification and use of nicotine gum, with continuing 5-year maintenance program to minimize relapse. Bronchodilator: ipratropium bromide prescribed three times daily (two puffs per time) from a metered-dose inhaler. Rate of change and cumulative change in FEV1 over a 5-year period. Participants in the two smoking intervention groups showed significantly smaller declines in FEV1 than did those in the control group. Most of this difference occurred during the first year following entry into the study and was attributable to smoking cessation, with those who achieved sustained smoking cessation experiencing the largest benefit. The small noncumulative benefit associated with use of the active bronchodilator vanished after the bronchodilator was discontinued at the end of the study. An aggressive smoking intervention program significantly reduces the age-related decline in FEV1 in middle-aged smokers with mild airways obstruction. Use of an inhaled anticholinergic bronchodilator results in a relatively small improvement in FEV1 that appears to be reversed after the drug is discontinued. Use of the bronchodilator did not influence the long-term decline of FEV1.
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                Author and article information

                Journal
                Basic Clin Pharmacol Toxicol
                Basic Clin. Pharmacol. Toxicol
                bcpt
                Basic & Clinical Pharmacology & Toxicology
                BlackWell Publishing Ltd (Oxford, UK )
                1742-7835
                1742-7843
                April 2015
                22 January 2015
                : 116
                : 4
                : 291-307
                Affiliations
                [1 ]Department of Respiratory Medicine, Seinäjoki Central Hospital Seinäjoki, Finland
                [2 ]Department of Respiratory Medicine, University of Tampere Tampere, Finland
                [3 ]Department of Internal Medicine, Unit of Respiratory Medicine, Medical Research Center, Oulu University Hospital Oulu, Finland
                [4 ]Department of Respiratory Medicine, University of Turku Turku, Finland
                [5 ]Heart and Lung Center, University of Helsinki and Helsinki University Central Hospital Helsinki, Finland
                [6 ]Department of Palliative Medicine, University of Tampere Tampere, Finland
                [7 ]Department of Oncology, Tampere University Hospital Tampere, Finland
                [8 ]Ranua Health Care Center Ranua, Finland
                [9 ]Finnish Medical Society Duodecim Helsinki, Finland
                [10 ]Department of Internal Medicine, Tampere University Hospital Tampere, Finland
                [11 ]Allergy Centre, Tampere University Hospital Tampere, Finland
                Author notes
                Author for correspondence: Hannu Kankaanranta, Department of Respiratory Medicine, Seinäjoki Central Hospital, 60220 Seinäjoki, Finland (fax +358 6 415 4989, e-mail hannu.kankaanranta@ 123456epshp.fi ).
                Article
                10.1111/bcpt.12366
                4409821
                25515181
                c54c17bf-614e-4a2f-ba44-a5e0fe701167
                © 2014 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 29 September 2014
                : 07 December 2014
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                Toxicology
                Toxicology

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