Régis Matran

Changes in Oxidative Stress Markers and Biological Markers of Muscle Injury with Aging at Rest and in Response to an Exhaustive Exercise

Purpose The aim of this study was to evaluate whether oxidative stress markers and biomarkers of muscle injury would be affected by aging at rest and in response to an incremental exhaustive exercise. Methods Fifteen young (20.3±2.8 years) and fifteen older adults (65.1±3.5 years) performed an incremental cycle ergometer test to exhaustion. Before and after exercise, oxidative stress [superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), ascorbic acid, α-Tocopherol, malondialdehyde (MDA)] and muscle injury [creatine kinase (CK), lactate deshydrogenase (LDH)] biomarkers were assessed. Results At rest, there was no difference in oxidative stress markers and LDH level between the groups, however CK was significantly higher in the young group than the elderly group (p<0.05). During recovery, in comparison with resting values, a significant increase in SOD (1092±145.9 vs. 1243±98 U/g Hb), GPX (67.4±12.7 vs. 79.2±15.6 U/g Hb) and GR (6.5±0.9 vs. 7.7±0.5 U/g Hb) activities were observed only in the young group (p<0.05). MDA has increased only in the older group (0.54±0.2 vs. 0.79±0.2 µmol/l) (p<0.01). CK increased in both groups (young group: 122.5±22.2 vs. 161.9±18.7 UI/l; older group: 88.8±34.1 vs. 111.1±25.9 UI/l) (p<0.01), however LDH has increased only in the young group (400.5±22.2 vs. 485±18.7 UI/l) (p<0.01) without alteration in the older group (382.8±34.1 vs. 418.5±25.9 UI/l). Conclusions These findings indicate that aging is associated with a decrease in antioxidant efficiency and an increase in oxidative stress damage. Furthermore, older adults would not more susceptible to exercise-induced muscle injury than young people.

Cardiopulmonary response following surgical repair of pectus excavatum in adult patients

OBJECTIVE Severe pectus excavatum are common in adult patients, often causing psychological complaints and physiological impairments. Although lung function at rest may minimally deteriorate after surgical correction, it remains unclear if surgery improves exercise capacity. The objective of present study is to assess whether the surgical repair of pectus excavatum in adults would improve exercise tolerance. METHODS A prospective study was performed to compare pulmonary and cardiovascular function at rest and at maximal exercise, before, and at 1 year after pectus excavatum repair. RESULTS From December 2005 to May 2009, 120 adult patients underwent pectus excavatum repair. Of these patients, 70 (nine women, 61 men) underwent thorough preoperative, 6-, and 12-month postoperative assessments, and were included in the present study. Age ranged from 18 to 62 years (mean 27 years). The pectus index (Haller index) was 4.5 ± 1.1. Lung function tests at rest were within the normal range, whereas maximal oxygen uptake (peak VO₂) was only 77 ± 2% of the predicted value. At 1-year follow-up, the pectus excavatum repair was associated with minor changes in lung function tests and significant increase (p=0.0005) in VO₂ (87 ± 2% of the predicted value). Postoperative O₂ pulse increase at maximal exercise suggested that aerobic capacity improvement was the result of better cardiovascular adaptation at maximal workload. CONCLUSION These results demonstrate sustained improvement in exercise cardiopulmonary function at 1-year follow-up of pectus excavatum surgical repair in adult patients.

The effect of zafirlukast on repetitive exercise-induced bronchoconstriction: the possible role of leukotrienes in exercise-induced refractoriness.

BACKGROUND Single doses of zafirlukast attenuate exercise-induced bronchoconstriction (EIB), but previous studies have not measured zafirlukasts effects after regular dosing or its duration of effect beyond 4 hours. OBJECTIVE The purpose of this study was to assess the effects of zafirlukast 20 mg and 80 mg twice daily compared with placebo on exercise challenges performed at 2 and 8 hours after the last dose of regular administration. METHODS Twenty-four adult patients with stable asthma taking beta(2)-agonists, inhaled corticosteroids, or both received treatment with zafirlukast (20 mg and 80 mg) and placebo. The patients were treated twice daily for 14 days in a randomized, double-blind, 3-way cross-over fashion, with a 7-day washout period between each treatment. Exercise challenges were performed at 2 and 8 hours after the morning dose on day 14. FEV(1) was measured before exercise and at set intervals after exercise until it returned to within 7% of its baseline value. RESULTS Both zafirlukast treatments significantly reduced EIB, as measured by the area under the FEV(1) time curve after the 2-hour (P <.001) and 8-hour (P <.001) exercise challenges and maximum fall in FEV(1) at the 2-hour challenge (P <.001). The comparison at 8 hours between treatments was affected by the unexpected finding that EIB was less in the placebo group after the 8-hour challenge than after the 2-hour challenge, as measured by the within-group change in the maximum fall in FEV(1) (P <.001) and the area under the FEV(1) time curve (P =.0023). CONCLUSION Regular zafirlukast treatment protects against EIB for at least 8 hours after regular dosing. A refractory period, which may be caused by exercise-induced leukotriene release, may last for up to 6 hours after the initial response to exercise.

Home telemonitoring (forced expiratory volume in 1 s) in children with severe asthma does not reduce exacerbations

Some children with severe asthma develop frequent exacerbations despite intensive treatment. We sought to assess the outcome (severe exacerbations and healthcare use, lung function, quality of life and maintenance treatment) of a strategy based on daily home spirometry with teletransmission to an expert medical centre and whether it differs from that of a conventional strategy. 50 children with severe uncontrolled asthma were enrolled in a 12-month prospective study and were randomised into two groups: 1) treatment managed with daily home spirometry and medical feedback (HM) and 2) conventional treatment (CT). The children’s mean age was 10.9 yrs (95% confidence interval 10.2–11.6). 44 children completed the study (21 in the HM group and 23 in the CT group). The median number of severe exacerbations per patient was 2.0 (interquartile range 1.0–4.0) in the HM group and 3.0 (1.0–4.0) in the CT group (p=0.38 with adjustment for age). There were no significant differences between the two groups for unscheduled visits (HM 5.0 (3.0–7.0), CT 3.0 (2.0–7.0); p=0.30), lung function (pre-&bgr;2-agonist forced expiratory volume in 1 s (FEV1) p=0.13), Paediatric Asthma Quality of Life Questionnaire scores (p=0.61) and median daily dose of inhaled corticosteroids (p=0.86). A treatment strategy based on daily FEV1 monitoring with medical feedback did not reduce severe asthma exacerbations.

Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma

In the sample of 295 French EGEA families with at least one asthmatic subject, a genome screen was conducted to identify potential linkage regions specific either to allergic rhinitis (AR) or to asthma as well as those shared by the two diseases. Two binary rhinitis phenotypes based on (1) diagnosis (ARbin1) and (2) symptoms (ARbin2) and a categorical ordered trait (ARcat) were considered. Asthma phenotype was based on answers to a standardized questionnaire plus the presence of bronchial hyper-responsiveness. Linkage analyses were conducted using the maximum likelihood binomial (MLB) method. These analyses provided potential evidence for linkage to three regions in the whole sample: 1p31 for the phenotype defined by ARbin2 plus asthma (P=0.00016), 2q32 for ARbin2 (P=0.00016) and 3p24–p14 for ARcat (P=0.001). Two other regions were detected in the subset of 185 families with at most one asthmatic sib: 9p22 and 9q22–q34 for ARbin1 (P=0.001 and 0.0007, respectively). No region showed evidence for linkage to asthma without being also linked to AR. While 1p31 may contain a genetic determinant common to asthma and AR, 2q32, 3p24–p14, 9p22 and 9q22–q34 are more likely to harbor genetic factors specific to AR.

The Borg dyspnoea score: a relevant clinical marker of inspiratory muscle weakness in amyotrophic lateral sclerosis

The aim of the study was to determine whether the Borg dyspnoea scale could be a useful and simple marker to predict respiratory muscle weakness in amyotrophic lateral sclerosis (ALS). From April 1997 to 2001, respiratory function was perfomed in 72 patients together with the Borg score in both the upright (uBorg) and supine (sBorg) positions. Mean upright vital capacity (VC) was 81±24% predicted, sniff nasal inspiratory pressure (SNIP) was 55±26% pred, maximal inspiratory pressure (PI,max) was 57±26% pred and arterial carbon dioxide tension (Pa,CO2) was 41±6 mmHg. The mean Borg scores in the upright and supine positions were 1.7±1.5 and 2.2±2, respectively. A significant relationship between SNIP and uBorg (r = 0.4; p = 0.0007) and SNIP and sBorg (r = 0.58; p<0.0001) was observed. Upright VC, ΔVC (measured as the supine fall in VC as a percentage of seated VC), PI,max and Pa,CO2 were significantly correlated with SNIP. A cut-off value of 3 on the sBorg scale provided the best sensitivity (80%) and specificity (78%) (area under the curve 0.8) to predict a SNIP ≤40 cmH2O, indicating severe inspiratory muscle weakness. Patients with a sBorg score ≥3 also exhibited significantly lower VC, PI,max and twitch mouth pressure during cervical magnetic stimulation, and slightly higher Pa,CO2 (43.7±7 versus 39.2±5 mmHg; p = 0.05). The Borg dyspnoea scale is a valuable noninvasive test for the prediction of inspiratory muscle weakness in ALS patients.

Influence of three nasal continuous positive airway pressure devices on breathing pattern in preterm infants.

The pattern of breathing was studied in 13 premature newborns treated by variable-flow Nasal Continuous Positive Airway Pressure (NCPAP), conventional NCPAP, and nasal cannulae. Compared to constant-flow NCPAP and nasal cannulae, the variable-flow NCPAP increases tidal volume and improves thoraco-abdominal synchrony, suggesting that variable-flow NCPAP provides more effective ventilatory support than conventional NCPAP or nasal cannulae.

Nutritional Status at 2 Years in Former Infants with Bronchopulmonary Dysplasia Influences Nutrition and Pulmonary Outcomes During Childhood

Improved survival rates for extreme prematurity have been accompanied by an increase in the incidence of bronchopulmonary dysplasia (BPD). The objective of this study was to assess factors associated with long-term nutritional and pulmonary function outcomes. The study was a cross-sectional study of 52 children who had been born prematurely, had experienced BPD, and were 4–8 y old at the time of the study. Undernutrition was defined as a Z score for weight-for-height of <–2 SD. Body composition and lung function were evaluated. Resting energy expenditure (REE) was measured using indirect calorimetry. Stepwise logistic regression was used to test for factors associated with undernutrition and pulmonary function. Eighteen children (35%) with BPD, predominantly girls, were undernourished. Undernutrition occurred within the first months of life and was associated with high REE. Multivariate analysis showed that factors significantly associated with undernutrition were female sex and undernutrition at age 2 y. Thirty-one children (60%) had abnormal lung function tests. Multivariate analysis showed that undernutrition at age 2 y was the only factor associated with the risk of developing distension of the airways. Nutritional status at age 2 y in children who had BPD in infancy influences nutritional and pulmonary outcomes in childhood.

Associations between Nitric Oxide Synthase Genes and Exhaled NO-Related Phenotypes according to Asthma Status

Background The nitric oxide (NO) pathway is involved in asthma, and eosinophils participate in the regulation of the NO pool in pulmonary tissues. We investigated associations between single nucleotide polymorphisms (SNPs) of NO synthase genes (NOS) and biological NO-related phenotypes measured in two compartments (exhaled breath condensate and plasma) and blood eosinophil counts. Methodology SNPs (N = 121) belonging to NOS1, NOS2 and NOS3 genes were genotyped in 1277 adults from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA). Association analyses were conducted on four quantitative phenotypes: the exhaled fraction of NO (Fe NO), plasma and exhaled breath condensate (EBC) nitrite-nitrate levels (NO2–NO3) and blood eosinophils in asthmatics and non-asthmatics separately. Genetic heterogeneity of these phenotypes between asthmatics and non-asthmatics was also investigated. Principal Findings In non-asthmatics, after correction for multiple comparisons, we found significant associations of FeNO levels with three SNPs in NOS3 and NOS2 (P≤0.002), and of EBC NO2–NO3 level with NOS2 (P = 0.002). In asthmatics, a single significant association was detected between Fe NO levels and one SNP in NOS3 (P = 0.004). Moreover, there was significant heterogeneity of NOS3 SNP effect on FeNO between asthmatics and non-asthmatics (P = 0.0002 to 0.005). No significant association was found between any SNP and NO2–NO3 plasma levels or blood eosinophil counts. Conclusions Variants in NO synthase genes influence FeNO and EBC NO2–NO3 levels in adults. These genetic determinants differ according to asthma status. Significant associations were only detected for exhaled phenotypes, highlighting the critical relevance to have access to specific phenotypes measured in relevant biological fluid.

Evidence for linkage of a new region (11p14) to eczema and allergic diseases

Asthma, allergic rhinitis (AR) and atopic dermatitis also called eczema are allergic co-morbidites, which are likely to depend on pleiotropic genetic effects as well as on specific genetic factors. After a previous genome-wide linkage screen conducted for asthma and AR in a sample of 295 French EGEA families ascertained through asthmatic subjects, the aim here was to search for genetic factors involved in eczema and more particularly the ones shared by the three allergic diseases using the same EGEA data. In this sake, eczema and phenotypes of “allergic disease” accounting for the joint information on the presence/absence of the three diseases were examined by linkage analyses using the maximum likelihood binomial method. A fine mapping was carried out in regions detected for potential linkage, followed by association studies using the family-based association test (FBAT). Evidence for linkage to 11p14 region was shown for “allergic disease” and eczema. Linkage was also indicated between eczema and 5q13 and between “allergic disease” and both 5p15 and 17q21 regions. Fine mapping supported the evidence of linkage to 11p14 and FBAT analyses showed the association between “allergic disease” and a marker located at the linkage peak on 11p14. Further investigations in this region will allow identifying genetic factor(s) which could have pleiotropic effect in the three allergic diseases.