The clinical and integrated management of COPD.

COPD is a chronic pathological condition of the respiratory system characterized by persistent and partially reversible airflow obstruction, to which variably contribute remodeling of bronchi (chronic bronchitis), bronchioles (small airway disease) and lung parenchyma (pulmonary emphysema). COPD can cause important systemic effects and be associated with complications and comorbidities. The diagnosis of COPD is based on the presence of respiratory symptoms and/or a history of exposure to risk factors, and the demonstration of airflow obstruction by spirometry. GARD of WHO has defined COPD "a preventable and treatable disease". The integration among general practitioner, chest physician as well as other specialists, whenever required, assures the best management of the COPD person, when specific targets to be achieved are well defined in a diagnostic and therapeutic route, previously designed and shared with appropriateness. The first-line pharmacologic treatment of COPD is represented by inhaled long-acting bronchodilators. In symptomatic patients, with pre-bronchodilator FEV1 < 60%predicted and ≥ 2 exacerbations/year, ICS may be added to LABA. The use of fixed-dose, single-inhaler combination may improve the adherence to treatment. Long term oxygen therapy (LTOT) is indicated in stable patients, at rest while receiving the best possible treatment, and exhibiting a PaO2 ≤ 55 mmHg (SO2<88%) or PaO2 values between 56 and 59 mmHg (SO2 < 89%) associated with pulmonary arterial hypertension, cor pulmonale, or edema of the lower limbs or hematocrit > 55%. Respiratory rehabilitation is addressed to patients with chronic respiratory disease in all stages of severity who report symptoms and limitation of their daily activity. It must be integrated in an individual patient tailored treatment as it improves dyspnea, exercise performance, and quality of life. Acute exacerbation of COPD is a sudden worsening of usual symptoms in a person with COPD, over and beyond normal daily variability that requires treatment modification. The pharmacologic therapy can be applied at home and includes the administration of drugs used during the stable phase by increasing the dose or modifying the route, and adding, whenever required, drugs as antibiotics or systemic corticosteroids. In case of patients who because of COPD severity and/or of exacerbations do not respond promptly to treatment at home hospital admission should be considered. Patients with "severe or "very severe COPD who experience exacerbations should be carried out in respiratory unit, based on the severity of acute respiratory failure. An integrated system is required in the community in order to ensure adequate treatments also outside acute care hospital settings and rehabilitation centers. This article is being simultaneusly published in Multidisciplinary Respiratory Medicine 2014; 9:25.

Beclomethasone/formoterol in the management of COPD: a randomised controlled trial.

OBJECTIVES: To evaluate the effect of beclomethasone/formoterol versus budesonide/formoterol (non-inferiority) and versus formoterol (superiority) in patients with severe stable chronic obstructive pulmonary disease (COPD). METHODS: A double-blind, double-dummy, randomised, active-controlled, parallel-group study. After 4 weeks run-in with ipratropium/salbutamol (40/200 µg, three times daily) patients were randomised to receive beclomethasone/formoterol (200/12 µg pressurised metered dose inhaler), budesonide/formoterol (400/12 µg dry powder inhaler) or formoterol (12 µg dry powder inhaler) twice daily for 48 weeks. Co-primary efficacy variables were change from baseline to 48 weeks in pre-dose morning forced expiratory volume in 1 s (FEV(1)) and mean rate of COPD exacerbations. RESULTS: Of 718 patients randomised, 703 (232 beclomethasone/formoterol, 238 budesonide/formoterol, 233 formoterol) were in the ITT analysis. Improvement in pre-dose morning FEV(1) was 0.077 L, 0.080 L and 0.026 L for beclomethasone/formoterol, budesonide/formoterol and formoterol respectively (LS mean from the ANCOVA model). Beclomethasone/formoterol was not inferior to budesonide/formoterol (95% CI of the difference -0.052, 0.048) and superior to formoterol (p = 0.046). The overall rate of COPD exacerbations/patient/year was similar and not statistically significantly different among treatments (beclomethasone/formoterol 0.414, budesonide/formoterol 0.423 and formoterol 0.431). Quality of life and COPD symptoms improved in all groups and use of rescue medication decreased. Safety profiles were as expected and treatments well-tolerated. CONCLUSIONS: Beclomethasone/formoterol (400/24 µg) treatment for 48 weeks improved pulmonary function, reduced symptoms compared to formoterol, was safe and well-tolerated in patients with severe stable COPD. Neither of the long-acting ß2-agonist/inhaled corticosteroid combinations affected the low exacerbation rate seen in this population.

Revisited role for mucus hypersecretion in the pathogenesis of COPD.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex disease of which the basic pathophysiological mechanisms remain largely unknown. On the basis of recent results from pathological studies and large clinical trials, the presence of airway inflammation does not seem to be sufficient to explain the complexity of the disease and the relatively poor response to treatment. It is probably time to abandon the concept of COPD as a unique disease and define, identify and treat the various aspects, which may differ between individuals. Among the different phenotypic distinctions, the classical distinction "chronic bronchitis" has mucus hypersecretion as the key presenting symptom. Its role in COPD has been the subject of an ongoing debate; however, it now appears to be being re-evaluated due to findings from recent epidemiological and pathological studies. In this context, the view that chronic mucus hypersecretion plays a secondary role in the pathogenesis of COPD should be abandoned and instead, drugs targeting mucus hypersecretion should be considered as a treatment option.

How to interpret reduced forced expiratory volume in 1 s (FEV1)/vital capacity ratio with normal FEV1.

The aim of the present study was to determine whether the combination of low forced expiratory volume in 1 s (FEV(1))/vital capacity (VC) ratio with normal FEV(1) represents a physiological variant or a sign of early airflow obstruction. We studied 40 subjects presenting with low FEV(1)/VC, but FEV(1) within the range of normality predicted by European Respiratory Society reference equations, and 10 healthy controls. All subjects completed two questionnaires and underwent comprehensive pulmonary function testing, which included methacholine challenge and single-breath nitrogen wash-out. According to the questionnaires, the subjects were assigned to three groups, i.e. rhinitis (n = 8), bronchial asthma (n = 13) and chronic obstructive pulmonary disease (COPD; n = 12). Subjects with negative responses to questionnaires were assigned to an asymptomatic group (n = 7). Airway hyperresponsiveness was found in four subjects of the rhinitis group, all of the asthma group, and 10 of the COPD group; in the last two groups, it was associated with signs of increased airway closure and gas trapping. Bronchodilator response to salbutamol was positive in only a few individuals across groups. In the asymptomatic group, no significant functional changes were observed, possibly suggesting dysanaptic lung growth. In subjects with low FEV(1)/VC and normal FEV(1), questionnaires on respiratory symptoms together with additional pulmonary function tests may help to clarify the nature of this pattern of lung function.

Changes in lung volumes and airway responsiveness following haematopoietic stem cell transplantation.

Changes in lung volume occur following haematopoietic stem cell transplantation (HSCT); airway hyperresponsiveness was occasionally reported, without mechanistic explanation. The present authors studied 17 patients by standard methacholine (MCh) challenge before and then 3 and 12 months after HSCT (n = 16 and n = 13, respectively). Another 6 patients were challenged before and 3 months after HSCT using a modified challenge to investigate the effect of deep inhalations. No patient developed bronchiolitis obliterans or bronchiolitis obliterans organising pneumonia. At 3 months, forced vital capacity (FVC) was significantly reduced by 0.33+/-0.55 L, forced expiratory volume in one second (FEV(1)) by 0.31+/-0.50 L, total lung capacity (TLC) by 0.39+/-0.37 L and single-breath diffusing capacity of the lung for carbon monoxide (D(L,CO)) by 15+/-12%. At 12 months, TLC decreased by 0.43+/-0.36 L and D(L,CO )by 8+/-8%. With standard challenge, no significant changes in FEV(1) response to MCh were observed after HSCT but FVC decreased significantly less after HSCT compared with prior to HSCT, suggesting less air trapping. With modified challenge, deep inhalations reversed the MCh-induced decrease in partial expiratory flow more after HSCT compared with before HSCT and this correlated with TLC decrements. In conclusion, an increase in airway responsiveness is unlikely after haematopoietic stem cell transplantation, at least in patients without pulmonary complications, and mechanisms opposing airway narrowing may blunt the bronchoconstrictor response.

Treatment of exercise-induced asthma, respiratory and allergic disorders in sports and the relationship to doping: Part II of the report from the Joint Task Force of European Respiratory Society (ERS) and European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA(2)LEN.

AIM: The aims of part II is to review the current recommended treatment of exercise-induced asthma (EIA), respiratory and allergic disorders in sports, to review the evidence on possible improvement of performance in sports by asthma drugs and to make recommendations for their treatment. METHODS: The literature cited with respect to the treatment of exercise induced asthma in athletes (and in asthma patients) is mainly based upon the systematic review given by Larsson et al. (Larsson K, Carlsen KH, Bonini S. Anti-asthmatic drugs: treatment of athletes and exercise-induced bronchoconstriction. In: Carlsen KH, Delgado L, Del Giacco S, editors. Diagnosis, prevention and treatment of exercise-related asthma, respiratory and allergic disorders in sports. Sheffield, UK: European Respiratory Journals Ltd, 2005:73-88) during the work of the Task Force. To assess the evidence of the literature regarding use of beta(2)-agonists related to athletic performance, the Task Force searched Medline for relevant papers up to November 2006 using the present search words: asthma, bronchial responsiveness, exercise-induced bronchoconstriction, athletes, sports, performance and beta(2)-agonists. Evidence level and grades of recommendation were assessed according to Sign criteria. RESULTS: Treatment recommendations for EIA and bronchial hyper-responsiveness in athletes are set forth with special reference to controller and reliever medications. Evidence for lack of improvement of exercise performance by inhaled beta(2)-agonists in healthy athletes serves as a basis for permitting their use. There is a lack of evidence of treatment effects of asthma drugs on EIA and bronchial hyper-responsiveness in athletes whereas extensive documentation exists in treatment of EIA in patients with asthma. The documentation on lack of improvement on performance by common asthma drugs as inhaled beta(2)-agonists with relationship to sports in healthy individuals is of high evidence, level (1+). CONCLUSIONS: Exercise induced asthma should be treated in athletes along same principles as in ordinary asthma patients with relevance to controller and reliever treatment after careful diagnosis. There is very high level of evidence for the lack of improvement in athletic performance by inhaled beta2-agonists.

Exercise-induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA2LEN.

AIMS: To analyze the changes in the prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergies in elite athletes over the past years, to review the specific pathogenetic features of these conditions and to make recommendations for their diagnosis. METHODS: The Task Force reviewed present literature by searching Medline up to November 2006 for relevant papers by the search words: asthma, bronchial responsiveness, EIB, athletes and sports. Sign criteria were used to assess level of evidence and grades of recommendation. RESULTS: The problems of sports-related asthma and allergy are outlined. Epidemiological evidence for an increased prevalence of asthma and BHR among competitive athletes, especially in endurance sports, is provided. The mechanisms for development of asthma and bronchial hyperresponsiveness in athletes are outlined. Criteria are given for the diagnosis of asthma and exercise induced asthma in the athlete. CONCLUSIONS: The prevalence of asthma and bronchial hyperresponsiveness is markedly increased in athletes, especially within endurance sports. Environmental factors often contribute. Recommendations for the diagnosis of asthma in athletes are outlined.

Outcomes for COPD pharmacological trials: from lung function to biomarkers.

The American Thoracic Society/European Respiratory Society jointly created a Task Force on "Outcomes for COPD pharmacological trials: from lung function to biomarkers" to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

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