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PURPOSE Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is more prevalent in some founder populations, but relatively unexplored in Canada. This study aimed at investigating the French-Canadian patients through phenotypic and genotypic characterization. METHOD Phenotype and demographic characterization were done for 12 affected individuals belonging to eight unrelated families. Samples from 11 cases were analyzed in a molecular clinical laboratory, and muscle biopsies were reviewed for two individuals with a limb-girdle muscle dystrophy. RESULTS The clinical phenotype was similar to that observed in European Caucasian populations but differed in the non-endocrine spectrum from the American-reported series of cases. Two cases exhibited a limb-girdle muscle dystrophy, and we found preliminary evidence of a mitochondrial dysfunction, since all three biopsies examined showed COX-deficient fibers in excess of what would be expected for age. Electron microscopy showed mitochondrial accumulation without abnormal cristea or inclusions. The c.1616C > T variant in the AIRE gene was responsible for 100% of APECED cases in the French-Canadian population of Saguenay-Lac-Saint-Jean in Quebec, Canada. CONCLUSIONS We report the first series of French-Canadian cases affected with APECED. The Saguenay-Lac-Saint-Jean region was uncovered as a new founder population for this condition. Muscle biopsy findings expanded the range of previously described APECED-related myopathology. Long term follow-up of our genetically homogeneous French-Canadian cases may help determine if the c.1616C > T variant increases the risk of muscle involvement. A neonatal screening program is under consideration to prevent undesired life-threatening endocrine manifestations.

A "frequent exacerbator phenotype" has been described, mostly in the population of patients with severe asthma. Further data are needed on such exacerbation-prone patients in milder asthma.To compare the characteristics of frequent and nonfrequent exacerbators in asthma of different severities and to assess the stability of the exacerbator status.This was an observational study comparing baseline data from frequent (≥2 exacerbations in the past year) and nonfrequent (2 exacerbations in the past year) exacerbators. Patients were also followed up for one year. Information regarding clinical, physiologic, and inflammatory characteristics was collected at baseline and one-year follow-up.Forty-seven frequent and 53 nonfrequent exacerbators were recruited. No specific clinical, physiologic, or inflammatory characteristic was observed in the frequent as compared to the nonfrequent exacerbators at baseline. Fifty-eight percent of patients reporting frequent exacerbations at baseline remained in this group after one year of follow-up. Forty-two and 62% of patients with, respectively, mild-to-moderate asthma and severe asthma had frequent exacerbations. In a post hoc analysis according to asthma severity, frequent exacerbators with severe asthma had a higher body mass index and poorer asthma control, although they reported higher adherence to medication, in comparison to frequent exacerbators with mild-to-moderate asthma. No specific characteristics could discriminate between frequent and nonfrequent exacerbators of the same asthma severity.Frequent exacerbators with severe asthma present some specific characteristics not observed in frequent exacerbators with mild-to-moderate disease. However, the latter group should be identified to reassess treatment needs and potential contributing factors.

Background Asthma seems to present in the elderly as a specific phenotype that remains to be further described. In this prospective observational study, we aimed to assess the multidimensional aspects of asthma in the elderly. Methods In young (18 to 35 years old) subjects with mild to moderate asthma and elderly subjects (aged ≥60 years) either with or without mild to moderate asthma, we compared asthma control, health care and medication use, lung function, markers of airway and systemic inflammation, and adherence to therapy. Results Fifty subjects were recruited in each group. Elderly people with asthma showed more marked airway obstruction compared with young people with asthma and elderly people without asthma. They also had poorer asthma control, mainly associated with a lower FEV 1 , compared with young people with asthma, although airway responsiveness, health care use, prescribed doses of inhaled corticosteroids, and adherence to treatment were similar in both groups. Elderly subjects had an increase in some markers of systemic inflammation and bronchial epithelial dysfunction compared with young people with asthma. Blood eosinophils were higher in both asthma groups, particularly in elderly people with asthma. Sputum neutrophils were increased in both groups of elderly subjects and sputum eosinophils were increased in elderly people with asthma compared with the other two groups. Conclusions Asthma in the elderly presents as a specific phenotype associated with increased airway obstruction and mixed airway inflammation in addition to signs of systemic inflammation.

Aims Second-generation everolimus-eluting stents (EES) are safer and more efficient than first-generation paclitaxel-eluting stents (PES). Third-generation biolimus-eluting stents (BES) have been found to be non-inferior to PES. To date, there is no available comparative study between EES and BES. We aimed to investigate the safety and efficacy of BES with biodegradable polymer compared to EES with durable polymer at a follow-up of two years in an unselected population of consecutively enrolled patients. Methods and results A group of 814 consecutive patients undergoing percutaneous coronary intervention (PCI) was enrolled between 2007 and 2010, of which 527 were treated with EES and 287 with BES implantation. Clinical outcome was compared in 200 pairs using propensity score matching. The primary endpoint was a composite of death, myocardial infarction (MI) and target vessel revascularisation (TVR) at two-year follow-up. Median follow-up was 22 months. The primary outcome occurred in 11.5% of EES and 10.5% of BES patients (HR 1.11, 95% CI: 0.61-2.00, p=0.74). At two years, there was no significant difference with regard to death (HR 0.49, 95% CI: 0.18-1.34, p=0.17), cardiac death (HR 0.14, 95% CI: 0.02-1.14, p=0.66) or MI (HR 6.10, 95% CI: 0.73-50.9, p=0.10). Stent thrombosis (ST) incidence was evenly distributed between EES (n=2) and BES (n=2) (p-value=1.0). Conclusions This first clinical study failed to demonstrate any significant difference regarding safety or efficacy between these two types and generations of drug-eluting stents (DES).

Background: Endurance athletes have a high prevalence of airway diseases, some possibly representing adaptive mechanisms to the need of conditioning large volumes of inspired air during high ventilation in specific environments. Aim: To assess the ability of athletes to condition inspired air by measuring the difference between inhaled and exhaled air temperature (ΔT) during and after Eucapnic Voluntary Hyperpnea test (EVH). Methods: Twenty-three endurance athletes (12 with airway hyperresponsiveness (AHR) and/or exercise-induced bronchoconstriction (EIB) (A+), 11 withoutAHR and/or EIB (A-)) and 23 non-athletes (12 with AHR and/or EIB (C+) and 11 without AHR and/or EIB (C-)) were recruited. All subjects attended the laboratory on three occasions, twice for baseline characterization and once to perform a modified EVH for ΔT assessment. Inspired and expired air temperatures were measured with a high-precision probe during EVH and at regular intervals until 30 minutes after the end of the test. Results: The global ΔT during the EVH was +5.80±1.48°C and +4.73±1.51°C during the 30 minutes following the EVH. No difference was found between groups either for the ΔT or the slope of ΔT, during and after the EVH. Conclusion: This study shows no evidence of improved capacity to condition inspired air in endurance athletes, which could have suggested an increased bronchial blood flow or another adaptive mechanism. The absence of an adaptive mechanism could therefore contribute to airway damage observed in athletes in allowing colder but mainly dryer air to penetrate deeper in the lung.

Endurance athletes have a high prevalence of airway diseases, some possibly representing adaptive mechanisms to the need of conditioning large volumes of inspired air during high ventilation in specific environments. The aim of this study is to assess the ability to condition (warm and humidify) inspired air in athletes by measuring the difference between inhaled and exhaled air temperature (ΔT) during and after eucapnic voluntary hyperpnea (EVH) test. Methods: Twenty-three endurance athletes from various sports, 12 with airway hyperresponsiveness (AHR) and/or exercise-induced bronchoconstriction (EIB) (A+), 11 without AHR and/or EIB (A−), 12 nonathletes with AHR and/or EIB (C+), and 11 nonathletes without AHR and/or EIB (C−) were recruited. All subjects attended the laboratory on three occasions, twice for baseline characterization, including questionnaires, pulmonary function, methacholine bronchoprovocation, allergy skin prick tests, exhaled nitric oxide measurement, and a standard EVH, and once to perform a modified EVH to assess ΔT. Inspired and expired air temperatures were measured with a high-precision probe during EVH and at regular intervals until 30 min after the end of the test. Results: The global ΔT during the EVH was +5.8°C ± 1.5°C and +4.7°C ± 1.5°C during the 30 min after the EVH. No difference was found between groups for either the ΔT or the slope of ΔT, during and after the EVH. Conclusion: This study shows no evidence of improved capacity to condition inspired air in endurance athletes, which could have suggested an increased bronchial blood flow or another adaptive mechanism. The absence of an adaptive mechanism could therefore contribute to airway damage observed in athletes in allowing colder but mainly dryer air to penetrate deeper in the lung.

BACKGROUND: Second-generation everolimus-eluting stents (EES) and third generation biolimus-eluting stents (BES) have been shown to be superior to first-generation paclitaxel-eluting stents (PES) and second-generation sirolimus-eluting stents (SES). However, neointimal proliferation and very late stent thrombosis is still an unresolved issue of drug-eluting stent (DES) implantation overall. The Absorb™ (Abbott Vascular, Abbott Park, IL, USA) is the first CE approved DES with a bioresorbable vascular scaffold (BVS) thought to reduce long-term complication rates. The EVERBIO II trial was set up to compare the BVS safety and efficacy with both EES and BES in all patients viable for inclusion. METHODS/DESIGN: The EVERBIO II trial is a single-center, assessor-blinded, randomized trial. The study population consists of all patients aged≥18 years old undergoing percutaneous coronary intervention. Exclusion criterion is where the lesion cannot be treated with BVS (reference vessel diameter>4.0 mm). A total of 240 patients will be enrolled and randomly assigned into 3 groups of 80 with either BVS, EES or BES implantation. All patients will undergo a follow-up angiography study at 9 months. Clinical follow-up for up to 5 years will be conducted by telephone. The primary endpoint is in-segment late lumen loss at 9 months measured by quantitative coronary angiography. Secondary endpoints are patient-oriented major adverse cardiac event (MACE) (death, myocardial infarction and target-vessel revascularization), device-oriented MACE (cardiac death, myocardial infarction and target-lesion revascularization), stent thrombosis according to ARC and binary restenosis at follow-up 12 months angiography. DISCUSSION: EVERBIO II is an independent, randomized study, aiming to compare the clinical efficacy, angiographic outcomes and safety of BVS, EES and BES in all comer patients. TRIAL REGISTRATION: The trial listed in clinicaltrials.gov as NCT01711931.

Background Although work-exacerbated asthma (WEA) is a prevalent condition likely to have an important societal burden, there are limited data on this condition. Objectives The aims of this study were (1) to compare the clinical, functional, and inflammatory characteristics of workers with WEA and occupational asthma (OA) and (2) compare health care use and related costs between workers with WEA and OA, as well as between workers with work-related asthma (WRA; ie, WEA plus OA) and those with non–work-related asthma (NWRA) in a prospective study. Methods We performed a prospective observational study of workers with and without WRA with a 2-year follow-up. The diagnosis of OA and WEA was based on the positivity and negativity of results on specific inhalation challenges, respectively. Results One hundred fifty-four subjects were enrolled: 53 with WEA, 68 with OA, and 33 control asthmatic subjects (NWRA). WEA was associated with more frequent prescriptions of inhaled corticosteroids (odds ratio [OR], 4.4; 95% CI, 1.4-13.6; P = .009), a noneosinophilic phenotype (OR, 0.3; 95% CI, 0.1-0.9; P = .04), a trend toward a lower FEV 1 (OR, 0.9; 95% CI, 0.9-1.0; P = .06), and a higher proportion of smokers (OR, 2.5; 95% CI, 0.96-9.7; P = .06) than the diagnosis of OA. The health care use of WRA and related costs were 10-fold higher than those of NWRA. Conclusion Workers with WEA appeared to have features of greater asthma severity than workers with OA. In contrast with OA, WEA was associated with a noneosinophilic phenotype. Both OA and WEA were associated with greater health care use and 10-fold higher direct costs than NWRA.

Le rapport à l’automobile de 70 résidents de secteurs périphériques de l’agglomération de Québec, non desservis par le transport en commun, est analysé à travers leurs comportements de mobilité, ainsi que leurs discours sur l’environnement et l’automobile. Leurs déplacements quotidiens varient beaucoup et tous les actifs ne se déplacent pas quotidiennement vers le centre-ville. Des différences selon l’âge et le sexe caractérisent non tant les comportements en tant que tels, mais plutôt le rapport affectif ou fonctionnel entretenu envers la voiture. Si les femmes aiment conduire leur voiture dans la même proportion que les hommes, ce n’est pas pour les mêmes raisons. Diminuer le recours à la voiture individuelle, ce serait transformer en profondeur tout un mode de vie ; comprendre ce mode de vie et ce pour quoi plusieurs personnes l’apprécient est essentiel dans l’atteinte de cet objectif., In terms of their relationship to the automobile, 70 residents of outlying districts of the Québec City area that are not served by public transit are analysed according to their mobility behaviours, and through their discourse on the environment and on the automobile. Their daily trips vary greatly, and not all employed individuals travel downtown on a daily basis. Differences according to age and gender come to light not so much in terms of their actual behaviours, but rather in terms of their emotional or functional relationships toward cars. While the same proportion of women enjoy driving their cars as men, it is not for the same reasons. Reducing the use of personal cars would deeply transform an entire way of life; an understanding of this way of life and why many appreciate it is essential to the achievement of this objective.