[Changing patterns of medication prescription for COPD patients in France. Impact of long-acting muscarinic antagonists' availability]. / Évolution des traitements de fond entre 2001 et 2012 chez les patients atteints de BPCO en France. Impact de la mise à disposition des anticholinergiques de longue durée d'action.

INTRODUCTION: We studied the pattern changes over time of medication prescriptions for COPD and their conformity with French and international recommendations using data from patients in the prospective French cohort "Initiatives BPCO". METHOD: Eight hundred and forty-six patients have been included during a first period from August, 2001 till May 2006 (n=425) and a second period from June, 2006 till June, 2012 (n=421). The pivotal date was based on the tiotropium availability in France. RESULTS: During period 1, we recruited older patients (average 65 vs 64 years), less often women (19 vs 26 %) and having less severe airflow obstruction (mean FEV1 48 vs 54 %). The ICS prescriptions decreased in mild COPD, but there was no change for inhaled long-acting beta-2 agonist (LABA) (68 %). The use of LABA+LAMA association without ICS increased from 0.9 to 7 %, but remained lower than the fixed LABA+ICS association (26 %), less often prescribed than the triple association LABA+ICS+LAMA (32.5 % in period 2). The use of long-acting bronchodilators increased from 68 to 80 % between both periods. Vaccinations and rehabilitation remained insufficiently prescribed. LAMA had been added but did not appear to replace other drugs.

Asthma-COPD overlap syndrome (ACOS) vs 'pure' COPD: a distinct phenotype?

BACKGROUND: Some studies suggest that asthma-COPD overlap syndrome (ACOS) is associated with worse outcomes than chronic obstructive pulmonary disease (COPD). The goal of this study was to further explore the clinical characteristics and survival of patients with ACOS identified in a real-life cohort of patients with COPD. METHODS: Data from the French COPD cohort 'INITIATIVES BronchoPneumopathie Chronique Obstructive' (n = 998 patients) were analyzed to assess the frequency of ACOS defined as a physician diagnosis of asthma before the age of 40 years and to analyze its impact. Univariate analyses were performed to assess the relationship between ACOS and sociodemographic characteristics, risk factors (smoking, occupational exposure, atopic diseases), symptoms (chronic bronchitis, dyspnea-modified Medical Research Council scale and baseline dyspnea index), quality of life (QoL), mood disorders, exacerbations, comorbidities, lung function, prescribed treatment, and survival. RESULTS: ACOS was diagnosed in 129 patients (13%). In multivariate analyses, ACOS was associated negatively with cumulative smoking (odds ratio [OR]: 0.992; 95% CI 0.984-1.000 per pack-year) and positively with obesity: OR: 1.97 [1.22-3.16], history of atopic disease (hay fever: OR: 5.50 [3.42-9.00] and atopic dermatitis: OR 3.76 [2.14-6.61]), and drug use (LABA + ICS: 1.86 [1.27-2.74], antileukotrienes 4.83 [1.63-14.34], theophylline: 2.46 [1.23-4.91], and oral corticosteroids: [2.99;.1.26-7.08]). No independent association was found with dyspnea, QoL, exacerbations, and mortality. CONCLUSIONS: Compared to 'pure' COPD patients, patients with ACOS exhibit lower cumulative smoking, suffer more from obesity and atopic diseases, and use more asthma treatments. Disease severity (dyspnea, QoL, exacerbations, comorbidities) and prognosis (mortality) are not different from 'pure' COPD patients.

[Early detection of COPD in occupational medicine in the Alpes-Maritimes]. / Détection précoce de la BPCO en milieu professionnel dans les Alpes-Maritimes.

INTRODUCTION: This study evaluated a standardized procedure aiming at early detection of COPD in a consecutive population of employees visiting occupational medicine. METHODS: A total of 2818 employees were included by 22 occupational physicians in 5 centers. Respiratory symptoms, smoking status, occupational exposures and socioprofessional categories were collected. Subjects with at least one symptom and/or risk factor underwent spirometry. RESULTS: In this population aged 39±12 years, 2603 patients were free of known asthma or COPD. The presence of at least one symptom was observed in 23.6 % of employees and was significantly associated with smoking status, occupational exposure to organic dust, gas fumes and vapors, and agriculture (P<0.0001). Airflow obstruction (FEV1/FVC < 0.70) was detected in 1.7 % of 1605 employees who underwent spirometry. With the inclusion of known COPD subjects (n=22), the prevalence reached 2.38 %. COPD was significantly associated with smoking intensity. Information on subsequent diagnosis was obtained in only two cases. The quality of spirometry was inadequate in 30 % of cases. Thirty-three percent of detected COPD subjects did not report any respiratory symptoms. CONCLUSION: The strategy used in this study (specific questionnaire plus spirometry) allowed detection of a few cases of previously undiagnosed COPD. Occupational physicians need specific training in spirometry and a better follow-up of care pathways is required to obtain diagnostic confirmation.

Clinical COPD phenotypes: a novel approach using principal component and cluster analyses.

Classification of chronic obstructive pulmonary disease (COPD) is usually based on the severity of airflow limitation, which may not reflect phenotypic heterogeneity. Here, we sought to identify COPD phenotypes using multiple clinical variables. COPD subjects recruited in a French multicentre cohort were characterised using a standardised process. Principal component analysis (PCA) was performed using eight variables selected for their relevance to COPD: age, cumulative smoking, forced expiratory volume in 1 s (FEV(1)) (% predicted), body mass index, exacerbations, dyspnoea (modified Medical Research Council scale), health status (St George's Respiratory Questionnaire) and depressive symptoms (hospital anxiety and depression scale). Patient classification was performed using cluster analysis based on PCA-transformed data. 322 COPD subjects were analysed: 77% were male; median (interquartile range) age was 65.0 (58.0-73.0) yrs; FEV(1) was 48.9 (34.1-66.3)% pred; and 21, 135, 107 and 59 subjects were classified in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1, 2, 3 and 4, respectively. PCA showed that three independent components accounted for 61% of variance. PCA-based cluster analysis resulted in the classification of subjects into four clinical phenotypes that could not be identified using GOLD classification. Importantly, subjects with comparable airflow limitation (FEV(1)) belonged to different phenotypes and had marked differences in age, symptoms, comorbidities and predicted mortality. These analyses underscore the need for novel multidimensional COPD classification for improving patient care and quality of clinical trials.

[Antihypertensive effectiveness and tolerance of cicletanine. Results obtained with monotherapy in a large population]. / Efficacité antihypertensive et tolérance du ciclétanine. Résultats obtenus en monothérapie sur une large population.

A multicentre open study to which 229 investigators participated was carried out to demonstrate the safety of cicletanine, a new therapeutic agent, in routine clinical use. Cicletanine was administered alone for three months and normalized blood pressure (less than 160/95 mmHg) in 63 p. 100 of the 1,238 hypertensive patients who entered the study. There was a significant fall of systolic arterial pressure from 178.4 +/- 14.8 to 151.8 +/- 14.2 mmHg and a similar fall of diastolic arterial pressure from 104.0 +/- 6.7 to 86.3 +/- 6.2 mmHg. The reduction of BP values was accompanied by a significant decrease of differential BP (SBP-DBP) from 72.5 to 65.8 mmHg. The initial dosage (50 mg/day) was doubled in only one-third of the patients. The mean daily dose was 66 mg. This antihypertensive effect was paralleled by a significant and major improvement of signs (dyspnoea, oedema of the lower limbs) and symptoms (mainly dizziness, headache, visual and auditory disorders, asthenia) which existed at inclusion. A modest, but significant, reduction of heart rate from 76.7 to 73.9 beats/mn was also noted. Cicletanine produced no toxic or severe adverse events. Clinical side-effects consisted of pruritus, fatigue, headache, vertigo, lower limb oedema and gastrointestinal disorders. These effects were mild and non-specific (doubtful drug imputability); each of them occurred with an incidence ranging from 4.0 to 1.0 p. 100. They were responsible for the withdrawal of about 30 patients (2.4 p. 100). No significant alteration of biochemical or haematological values was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

[Antihypertensive effectiveness and tolerance of cicletanine. Results obtained with bitherapy]. / Efficacité antihypertensive et tolérance du ciclétanine. Résultats obtenus en bithérapie.

In a multicentre open trial involving 229 investigators, cicletanine, a new antihypertensive agent, was administered orally in doses of 50 to 100 mg/day either alone (1,238 patients) or combined with another drug (430 patients). In this second group of patients with essential hypertension whose BP had not been normalized by a beta-blocker (n = 157), a calcium inhibitor (n = 67), an angiotensin-converting enzyme inhibitor (n = 134) or an alpha-blocker (n = 7), cicletanine normalized BP (less than 160/95 mmHg) in 48.8% of the patients and significantly lowered BP values which fell from 177.7 +/- 15.9/103.3 +/- 6.3 mmHg to 157.2 +/- 17.6/88.8 +/- 8.7 mmHg. The addition of cicletanine to treatments with beta-blockers, calcium inhibitors and angiotensin-converting enzyme inhibitors normalized BP in 48%, 52% and 47% of patients respectively. A significant reduction of symptoms was noted, notably as regards headache, dizziness, palpitations, lower limb oedema, asthenia, auditory disorders and dyspnoea. The side-effects reported (headache, dizziness, gastralgia, nausea, pruritus) were minor and non-specific; they accounted for the withdrawal of only 8 patients. The only significant, though moderate, biochemical variations observed were decreases in natremia and cholesterolaemia unconfirmed by qualitative analysis. Altogether, cicletanine proved to be effective and well tolerated when administered in combination with other antihypertensive drugs belonging to three main therapeutic classes.