Phenomenology of COPD: interpreting phenotypes with the ECLIPSE study.

The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study was a large 3-year observational multicentre international study aimed at defining COPD phenotypes and identifying biomarkers and/or genetic parameters that help to predict disease progression. The study has contributed to a better understanding of COPD heterogeneity, with the characterization of clinically important subtypes/phenotypes of patients, such as the frequent exacerbators or patient with persistent systemic inflammation, who may have different prognosis or treatment requirements. Because of the big amount of information that is starting to be produced from metabolomic, proteomic and genomic approaches, one of the biggest challenges is the integration of data in a biological prospective such as clinical prognosis and response to medicinal products. In this article we highlight some of the progress in phenotyping the heterogeneity of the disease that have been made thanks to the analyses of this longitudinal study.

Asthma under/misdiagnosis in primary care setting: an observational community-based study in Italy.

BACKGROUND: Published data suggest that asthma is significantly under/misdiagnosed. The present community-based study performed in Italy aims at investigating the level of asthma under/misdiagnosis among patients referring to the General Practitioner (GP) for respiratory symptoms and undergoing Inhaled corticosteroids. METHODS: A sub-analysis of a previously published observational cross-sectional study has been provided. It included subjects registered in the GP databases with at least three prescriptions of inhaled or nebulised corticosteroids during the 12 months preceding the start of the study. All subjects, independently of the diagnosis, were invited to visit their GP's office for a standardised interview and to fill the European Community Respiratory Health Survey (ECRHS) questionnaire. RESULTS: The studies involved 540 GPs in most of the Italian regions and 2090 subjects (mean age 54.9 years, 54.1 % females) were enrolled. Among them 991 cases of physician-diagnosed asthma were observed while 1099 subjects received a diagnosis other than asthma (chronic obstructive pulmonary disease, chronic upper respiratory tract infections etc.). Among the lasts, the ECRHS questionnaire was suggestive for asthma diagnosis in 365 subjects (33.2 %). CONCLUSIONS: The data suggest that there is still a large under/misdiagnosis of asthma in the Italian primary care setting, despite the spread of GINA guidelines nearly 20 years before this study. A validated tool like the ECRHS questionnaire has detected a considerable proportion of potentially asthmatic patients who should be addressed to lung function assessment to confirm the diagnosis. Further educational efforts directed to the GPs are needed to improve their diagnosis of asthma (SAM104964).

The level of control of mild asthma in general practice: an observational community-based study.

OBJECTIVE: The aim of the present community-based study was to evaluate the level of asthma control in patients with mild asthma, regularly treated with inhaled steroids (ICS). METHOD: This observational cross-sectional study included patients registered in the general practitioner (GP) database and with at least three prescriptions of ICS in the last 12 months. Patients were asked to refer to the doctor's office for a standardised interview. The level of asthma control was self-measured by the patients using the Asthma Control Test (ACT)™ (Quality Metric, Inc.). RESULTS: The study included 950 asthmatic patients, referred by 540 GPs: 54.5% were females, mean age was 51 (±19.1) years; 59.5% were non-smokers, 22.5% were current smokers and 18.0% were former smokers; 81.1% of the patients were on ICS in the last 4 weeks. Only 38.6% of patients had a spirometry in the last 12 months. According to the ACT, 13.7% of the asthmatic patients were totally controlled, 51.0% well controlled, and 35.3% poorly controlled. Smoking habit, older age (>60) and living in Central or Southern Italy were associated with poorer control. In the last 12 months 4.5% of patients had an asthma-related hospitalisation, 5.3% an emergency visit and 18.9% a specialist visit. CONCLUSIONS: More than one of three patients had poor asthma control, despite being considered by their GPs as mild asthmatics and treated with ICS. Asthmatic patients need to be regularly re-evaluated. Treatment is often inadequate and should be targeted to improve control and reduce asthma morbidity (SAM104964).

[Risk of diabetes mellitus during regular long-term inhaled glucocorticoid treatment in COPD patients: narrative review of the literature.] / Rischio di diabete mellito durante il trattamento regolare a lungo termine con glucocorticoidi per via inalatoria nei pazienti con BPCO: revisione narrativa della letteratura.

Glucocorticoids are anti-inflammatory drugs used in combination with inhaled bronchodilators, such as ß2-agonists and antimuscarinics, for the treatment of stable chronic obstructive pulmonary disease (COPD), to improve respiratory symptoms, such as exertional dyspnoea, and to decrease the risk of future COPD exacerbations. However, it remains controversial whether their regular long-term use increases the risk of developing diabetes mellitus. The objective of this narrative review is therefore to analyse all the randomized controlled trials performed in patients with stable COPD to identify the risk of new onset diabetes mellitus during a long-term (at least 52 weeks) regular treatment with inhaled glucocorticoids alone compared to placebo. From a literature search on PubMed, 19 studies fulfilling these criteria have been identified. The inhaled glucocorticoids administered were: fluticasone propionate (7 studies), budesonide (6 studies), mometasone furoate (3 studies), beclomethasone dipropionate (1 study), triamcinolone acetonide (1 study), and fluticasone furoate (1 study) respectively. Only 3 out of the 19 trials identified in our narrative review reported data on diabetes mellitus, and in these the incidence of diabetes mellitus was not significantly different in both treatment arms (inhaled glucocorticoids and placebo), regardless of the type of glucocorticoid used.

[Risk of pneumonia during long term regular treatment of stable COPD with inhaled glucocorticoids: a systematic review.] / Rischio di polmonite durante trattamenti regolari a lungo termine con glucocorticoidi inalatori nei pazienti con BPCO stabile: revisione sistematica della letteratura.

Inhaled glucocorticoids are anti-inflammatory drugs used in combination with long acting bronchodilators beta2-agonists for the treatment of stable chronic obstructive pulmonary disease (COPD), to improve lung function and symptoms and to reduce the future risk COPD exacerbations. However, has been also associated to an increased risk of pneumonia. The objective of this systematic review was therefore to analyze all randomized controlled trials to identify the risk of pneumonia during the regular treatment with long-term inhaled glucocorticosteroids compared to treatment with placebo in patients with stable COPD. From a literature search on PubMed, 19 randomized, placebo-controlled, long term (at least 52-week) studies have been identified. The inhaled glucocorticoids administered were: budesonide (6 studies), mometasone furoate (3 studies), beclomethasone dipropionate (1 study), triamcinolone acetonide (1 study), fluticasone propionate (7 studies) and fluticasone furoate (1 study). Only 7 of the 19 trials identified in our systematic review reported data on pneumonia and only one study required radiological evidence for diagnosis. The incidence of pneumonia was slightly increased in patients treated with glucocorticoid inhaled compared to placebo in most studies, regardless of the type of glucocorticoid inhalation used, suggesting a class effect. Older age, low body mass index, low FEV1, being a smoker are all factors variously associated with increased risk of pneumonia.

Asthma control in primary care: the results of an observational cross-sectional study in Italy and Spain.

BACKGROUND: Poor asthma control observed in several surveys may be related to a lack of systematic assessment by physicians and/or to patient underestimation of symptoms. Along this line, the purpose of this study was to investigate the level of asthma control in patients attending the GP office for different reasons, either for renewal of drug prescription or for worsening of asthma symptoms. METHODS: Each of the 145 General Practitioners (GP) in Italy and Spain selected at least eight asthmatic patients attending their office for a renewal of drug prescription (Group A) or for worsening of asthma symptoms (Group B), between May and December 2009. Asthma Control Test (ACT) and other clinical information (including SF-12 questionnaire) were collected. RESULTS: Data from 1375 patients with moderate-severe asthma were analysed (mean age: 47.2 years; female: 59%; smokers or ex-smokers: 35.4%); 57% were on treatment with ICS-LABA combination. ACT score < 20 (uncontrolled asthma) was observed in 77.8% Group B patients, as expected, but also in 28.6% Group A patients. Uncontrolled patients reported their asthma being well or fairly well controlled in 68.4% of cases. Risk factors for uncontrolled asthma were older age, asthma severity, and smoking habit. In uncontrolled patients, GPs changed or increased the level of therapy in 75.8% and initiated asthma treatment in 61.3% of cases, in association with educational intervention, closer monitoring or pulmonologist consultations. DISCUSSION: The systematic use of ACT in asthmatics attending GP's clinic may detect high rates of uncontrolled patients who underestimate their clinical conditions, particularly those asking solely for asthma medication renewal. Poor adherence to daily drug therapy was reported in more than 40% of patients and could be an important contributor of uncontrolled asthma. CONCLUSIONS: The results highlight the importance of routine longitudinal assessment of asthma patients in primary care and point to the need for an increased attention to asthma management by GPs.

Pharmacological basis and scientific rationale underlying the targeted use of inhaled corticosteroid/long-acting ß2-adrenergic agonist combinations in chronic obstructive pulmonary disease treatment.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a complex respiratory disorder, whose medical and socioeconomic burden as one of the main causes of morbidity and mortality is increasing worldwide. COPD pathophysiology includes chronic airway/lung inflammation and progressive airflow limitation. Therefore, anti-inflammatory and bronchodilator agents are key players in COPD treatment. AREAS COVERED: This review article discusses the complementary molecular interactions connecting the respective mechanisms of action of inhaled corticosteroids (ICS) and long-acting ß2-adrenergic agonists (LABAs). Moreover, attention is also focused on clinical trials, which have shown that ICS/LABA combinations are very effective in improving COPD symptoms and lung function, being also able to significantly reduce disease exacerbations. EXPERT OPINION: In selected subgroups of COPD patients, ICS/LABA combinations represent a very useful therapeutic approach for this widespread chronic respiratory disease. In addition to the well-known fixed-dose drug associations such as fluticasone propionate/salmeterol xinafoate and budesonide/formoterol fumarate, other newly developed ICS/LABA combinations are currently emerging as very interesting pharmacological options for COPD treatment.

AIMAR survey on COPD phenotypes.

BACKGROUND: COPD is characterized by considerable diversity in terms of clinical signs and symptoms, physiopathological mechanisms, response to treatment and disease progression. For this reason, the identification of different patient subgroups (or possible phenotypes) is important both for prognosis and for therapeutic objectives. Based on the foregoing, AIMAR has decided to conduct a survey on the perception of the prevalence of the different clinical COPD phenotypes/subtypes in the clinical practice of physicians who treat patients with chronic obstructive pulmonary disease, and on their therapeutic objectives. METHODS: The survey consisted of 19 multiple-choice questions, compiled through a form published online. All the data and answers entered into the system were checked for consistency and completeness directly online at the time they were entered, and each respondent could only complete the questionnaire once. RESULTS: The survey took place from May through October 2012. A total of 1,434 questionnaires (60% of the sample approached) were eligible for analysis, broken down as follows: 537 pulmonologists, 666 general practitioners (GPs), 72 internal medicine specialists, 36 allergists, 30 geriatricians, 93 other specialists. The results show that a significant proportion of GPs (33%) identified more than 50 patients in their practices with a diagnosis of COPD. Although most patients are or have been in treatment with a long-acting bronchodilator, the most common reasons for seeing a GP or a specialist were exacerbations and worsening of the symptoms, suggesting the importance of an appropriate background therapy in order to reduce the risk of disease instability. The frequent exacerbator phenotype was the most commonly found phenotype in clinical practice (by 75% of specialists and 66% of GPs); patients with a prevalent phenotype of chronic bronchitis were reported more often by GPs, while specialists reported a higher number of patients with a prevalent phenotype of emphysema.A medical history of exacerbations and the extent of deterioration of the spirometry parameters were considered to be the major indicators for COPD severity and clinical risk. In managing the frequent exacerbator phenotype, the therapeutic objectives - both for GPs and for specialists - included reducing airway inflammation, improving bronchial dilation, and reducing pulmonary hyperinflation. For this type of patients at high clinical risk, specialists selected a first-line therapeutic option based on a predetermined combination of an inhaled corticosteroid (ICS) and a long-acting ß2-agonist bronchodilator (LABA) and a second-line three-drug therapy (combination of ICS and two long-acting bronchodilators), while GPs' choices are more diversified, without a clear-cut prevalence of one type of treatment. In patients with COPD and concomitant cardiovascular diseases, frequently observed in clinical practice by all physicians, the combination of ICS and LABA was considered the first-choice option by the highest proportion of GPs (43%) and specialists (37%), while a smaller number of specialists (35%) opted for the long acting muscarinic antagonists (LAMA). Both GPs and specialists believe that therapeutic continuity is of primary importance for the achievement of clinical outcomes with all classes of drugs. CONCLUSIONS: A good knowledge of COPD has been observed in a high percentage of GPs, indicating an increased awareness of this disease in Primary Health Care. The frequent exacerbator phenotype is viewed by all physicians as the most prevalent in clinical practice, bearing a high risk of hospitalization. For specialists, therapeutic measures aimed at reducing the number and severity of exacerbations are primarily based on the combination of inhaled corticosteroid and bronchodilator, presumably because of the complementary pharmacological action of its components, whereas while GPs' choices tend to be more diversified. Adherence to medication regimens is of the essence for the achievement of clinical outcomes.

A review of the use of fluticasone furoate since its launch.

INTRODUCTION: Fluticasone furoate (FF) is the latest glucocorticoid officially approved for the treatment of allergic rhinitis. FF has shown the highest affinity and selectivity for the glucocorticoid receptors as well the longest tissue retention compared with other available intranasal steroids; these new pharmacologic characteristics provide the basis for its potent and prolonged anti-inflammatory activity at the target site. AREAS COVERED: A literature review achieved through PubMed and Medline research methods supports the clinical efficacy of FF versus placebo in reducing ocular and nasal symptoms related to allergic rhinitis (at the recommended starting doses of 110 µg once daily for adults and adolescents and 55 µg once daily for children), with a good safety profile. Moreover, the present review also compares FF with other intranasal steroids: FF represents a molecular evolution of fluticasone propionate (FP), and there is scientific evidence of therapeutic advantages over FP. EXPERT OPINION: Fluticasone furoate is a promising molecule in the treatment of allergic rhinitis as it fits fully all the official guidelines' criteria. It is now being considered as a topical steroid that is quite close to the ideal pharmacological model for glucocorticoids due to its satisfying safety/tolerability profile, both in adults and children, leads FF to be considered as a topical steroid that is quite close to the ideal pharmacologic model for glucocorticoids. More studies should be directed to assess the improvement of quality of life in subjects with allergic rhinitis treated with FF, in comparison with other intranasal steroids and even H1-antihistamines; in addition, it could be also interesting to analyze eventual, additional effects of FF in patients with bronchial asthma, which is frequently associated with allergic rhinitis.