Health-related quality of life in patients with alpha-1 antitrypsin deficiency: the French experience.

The French registry of patients with alpha-1 antitrypsin deficiency (AATD)-associated emphysema was launched in 2006. Here, we aimed to report on the baseline characteristics of these patients, their health-related quality of life (HRQoL) and factors associated with HRQoL. Another goal was to survey the practices of French physicians regarding augmentation therapy. We included 273 patients with AATD, emphysema, obstructive-pattern [forced expiratory volume in 1 sec/forced volume capacity (FEV1/FVC) < 0.7], FEV1 ≤ 80% predicted. Mean (SD) age was 51.8 (11.1) years, 240 (87.9%) of patients were smokers or ex-smokers, mean (SD) FEV1 was 40.5% (15.7) predicted. Mean (SD) SGRQ score was 49.0 (20.0) and was higher for females than males (52.7 [20.7] vs 46.8 [18.2]; p = 0.01). Dyspnea showed the strongest association with SGRQ score (r = 0.65; p < 0.0001), followed by chronic bronchitis (r = 0.33; p < 0.0001) and wheezing (r = 0.32; p < 0.0001). Number of exacerbations in the year before inclusion was also significantly associated with SGRQ score (r = 0.36; p < 0.0001). The SGRQ score was associated with the 6-min walking distance (r = -0.53, p < 0.0001), FEV1 (% predicted, r = -0.53, p < 0.0001) and DLCO (% predicted, r = -0.52, p < 0.0001). It was also associated with the GOLD 2006 (r = 0.53; p < 0.0001) and GOLD 2011 (r = 0.63; p< 0.0001) classifications and with the BODE index (r = 0.37; p < 0.0001). Age, history of tobacco smoking or current smoking did not show any association with SGRQ total scores. On multivariate analysis, a model including age, chronic bronchitis, dyspnea (MRC scale), diffusing lung capacity and 6-min walking distance explained 57% of the variation in the score. The French registry provides important insights into the clinical characteristics of French patients with AATD-related emphysema.

Performance of the BODE index in patients with α1-antitrypsin deficiency-related COPD.

The BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) index is used to decide on referral and transplantation of patients with chronic obstructive pulmonary disease (COPD). The BODE index has not been validated in patients with α1-antitrypsin deficiency, who account for 15% of COPD patients undergoing lung transplantation. We sought to validate the BODE index in α1-antitrypsin deficiency-related COPD. We assessed the prognostic value of the BODE index in 191 patients followed from 2006 to 2012 in a French prospective cohort of patients with α1-antitrypsin deficiency. 20 patients died during follow-up and 22 underwent lung transplantation. Survival (95% CI) was 93.0% (91.7-94.3%) at 3 years and 76.0% (72.9-79.1%) at 5 years. The 3-year survival was 97.4% (96.6-98.2%), 98.0% (96.7-99.3%), 87.7% (84.5-90.9%) and 75.3% (66.0-84.6%) for patients with BODE index 0-2, 3-4, 5-6 and 7-10, respectively. Survival discrimination of the BODE index was better than with both forced expiratory volume in 1 s and Global Initiative for Chronic Obstructive Lung Disease classification. Regarding calibration, expected survival by BODE index was noticeably lower than observed survival. The BODE index showed very good survival discrimination in patients with α1-antitrypsin deficiency-related COPD. Larger studies are needed to support its use to drive patient referral for lung transplantation.

Levocetirizine in children: evidenced efficacy and safety in a 6-week randomized seasonal allergic rhinitis trial.

Studies evaluating newer antihistamines in children are few. Levocetirizine is a potent and highly selective H1-antihistamine with a proven efficacy in adults. Primary objective was to assess the efficacy of levocetirizine 5 mg once-daily in reducing seasonal allergic rhinitis (SAR) symptoms, as measured by Total Four Symptom Score (T4SS = sum of sneezing, rhinorrhea, nasal and ocular pruritus), over the first 2 wk of treatment. Efficacy over 4 and 6 wk of treatment, effect on nasal congestion and on health-related quality of life as measured by PRQLQ (Paediatric Rhinoconjunctivitis Quality of Life Questionnaire) were among the major secondary objectives. A double-blind, randomized, placebo-controlled study including 177 children with a documented SAR (to grass and/or weed) for at least a year and having a mean baseline T4SS > or = 6 (out of 12). Children evaluated daily the severity of T4SS and nasal congestion on a scale from 0 (absent) to 3 (severe). PRQLQ responses were assessed on a scale from 0 (not bothered) to 6 (extremely bothered) and analysed descriptively. Global evaluation of disease evolution judged by investigators, parents and children was made on a scale from 1 (marked worsening) to 7 (marked improvement). For the primary objective, levocetirizine was statistically highly superior to placebo with a difference in adjusted means of 1.29 (95% CI: 0.66-1.92) in favour of levocetirizine (p < 0.001). The effect of levocetirizine was almost twice that of placebo (94.1% relative improvement over placebo). Nasal congestion was improved with levocetirizine reaching maximum difference to placebo of 0.31 (p < 0.05), a relative improvement over placebo of 77.5%. PRQLQ scores at week 2 improved with levocetirizine more than with placebo (0.85 vs. 0.51, respectively) remaining larger after 4 and 6 wk of treatment. In the study, 84.3%, 80.9%, 80.9% of children had their disease evolution rated as slightly-to-markedly improved by, respectively, the investigators, the parents and children themselves. Incidence of treatment-emergent adverse events was similar in both groups (33.7% with levocetirizine; 30.7% with placebo). No child in the levocetirizine group discontinued treatment because of adverse events. The 6-wk duration of this study was longer than the usual 2-4-wk duration for similar studies and shows that levocetirizine controls SAR symptoms in children over the entire pollen season.

Diffuse infiltrative lung disease associated with flecainide. Report of two cases.

We present two patients who developed subacute diffuse infiltrative lung disease while receiving flecainide for supraventricular arrhythmia. They had bilateral subpleural lung opacities on computed tomography. Bronchoalveolar lavage revealed increased numbers of lymphocytes and eosinophils, and a low CD4/CD8 ratio. Nonspecific interstitial pneumonia was documented by open lung biopsy in patient 1. The outcome was favorable after flecainide withdrawal and prednisone treatment. Drug-induced pneumonitis should be suspected in patients treated with flecainide presenting with subacute diffuse infiltrative lung disease.