Mosquito Respiratory Research Group

Mosquito, France

Mosquito Respiratory Research Group

Mosquito, France
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Beydon N.,AP HP | Beydon N.,Mosquito Respiratory Research Group | Mahut B.,Mosquito Respiratory Research Group | Maingot L.,AP HP | And 9 more authors.
Pediatric Pulmonology | Year: 2012

In children unable to perform reliable spirometry, the interrupter resistance (Rint) technique for assessing respiratory resistance is easy to perform. However, few data are available on the possibility to use Rint as a surrogate for spirometry. We aimed at comparing R int and spirometry at baseline and after bronchodilator administration in a large population of asthmatic children. We collected retrospectively Rint and spirometry results measured in 695 children [median age 7.8 (range 4.8-13.9) years] referred to our lab for routine assessment of asthma disease. Correlations between Rint and spirometry were studied using data expressed as z-scores. Receiver operator characteristic curves for the baseline Rint value (z-score) and the bronchodilator effect (percentage predicted value and z-score) were generated to assess diagnostic performance. At baseline, the relationship between raw values of Rint and FEV1 was not linear. Despite a highly significant inverse correlation between Rint and all of the spirometry indices (FEV1, FVC, FEV1/FVC, FEF 25-75%; P < 0.0001), Rint could detect baseline obstruction (FEV1 z-score ≤ -2) with only 42% sensitivity and 95% specificity. Post-bronchodilator changes in R∫ and FEV 1 were inversely correlated (rhô = -0.50, P < 0.0001), and R∫ (a;circyen < 35% predicted value decrease) detected FEV1 reversibility (> 12% baseline increase) with 70% sensitivity and 69% specificity (AUC = 0.79). R∫ measurements fitted a one-compartment model that explained the relationship between flows and airway resistance. We found that R∫ had poor sensitivity to detect baseline obstruction, but fairly good sensitivity and specificity to detect reversibility. However, in order to implement asthma guidelines for children unable to produce reliable spirometry, bronchodilator response measured by R∫ should be systematically studied and further assessed in conjunction with clinical outcomes. Pediatr Pulmonol. 2012. 47:987-993. © 2012 Wiley Periodicals, Inc.


Mahut B.,Cabinet La Berma | Mahut B.,Mosquito Respiratory Research Group | Trinquart L.,Unite de Recherche Clinique et dEpidemiologie | Trinquart L.,Mosquito Respiratory Research Group | And 4 more authors.
Journal of Asthma | Year: 2011

Background. Asthma is a heterogeneous disease but it is a common observation that children tend to "grow out of their asthma." Objective. The aim was to specifically assess the influence of age on the occurrence of a severe exacerbation (at least 3 days use of systemic corticosteroid - international 2009 definition) and of the achievement of control (GINA guidelines) in children treated for asthma. Our study was controlled for amount of therapy and for season. Methods. Children under inhaled corticosteroid (ICS) were enrolled over two 2-month periods (autumn, spring). Duration of oral steroid treatment and of symptoms, dose of ICS and long-acting beta-agonist were recorded for the past 3 months. Results. Three hundred and fifty-nine children (110 girls) were included (48 [<2 years], 116 [2-6 years], 107 [6-10 years], 88 [>10 years]) during autumn (n = 175) and spring (n = 184), all treated by ICS (mean daily dose ± SD = 378 ± 250 μg). Among the 359 children, 133 (37%) experienced at least one severe exacerbation, and control was observed in 111 (31%) children. A multivariate logistic regression model demonstrated that age, season, and ICS dose are independent risk factors for exacerbation, whereas age is the only predictor of control. The odds ratio of exacerbation and control are 0.85 (95% CI, 0.78-0.92, p < .0001) and 0.85 (95% CI, 0.79-0.91, p < .0001) per year of increase in age, respectively. Conclusions. From infancy to adolescence, each year of life reduces per se the risk of a severe exacerbation by 15% and similarly increases the achievement of control in children treated for asthma. © 2011 Informa Healthcare USA, Inc.


Mahut B.,Service de Physiologie | Mahut B.,Mosquito Respiratory Research Group | Beydon N.,Mosquito Respiratory Research Group | Delclaux C.,Service de Physiologie | And 3 more authors.
European Respiratory Journal | Year: 2012

While being overweight is a risk factor for subsequent asthma in children, the importance of body mass index (BMI) as a comorbidity factor remains debated. The aim of this study was to assess the relationships between being overweight and the characteristics of childhood asthma. The BMI, BMI z-scores and International Obesity Task Force (IOTF) grades were evaluated in asthmatic children according to atopic status, symptoms during the past 3 months, exercise breathlessness, treatment and lung function in 6-15-yr-old children with confirmed asthma. 491 asthmatic children (mean±SD age 10.8±2.6 yrs; 179 females) were prospectively enrolled. There were 78 (15.5%) overweight (IOTF grade 1) and eight (1.6%) obese (grade 2) children. The children's BMI z-scores did not differ according to atopy, exacerbation, symptom-free days or treatment. The BMI z-score correlated positively with forced vital capacity and forced expiratory volume in 1 s in females, which could be related to earlier puberty in overweight females (growth spurt with increased volumes). Compared with normal weight children, overweight and obese children had reduced lung volume ratios (functional residual capacity/total lung capacity (TLC) and residual volume/TLC), no evidence of airflow limitation and similar symptoms. In conclusion, the observed functional relationships with BMI are not specific to asthma and being overweight is not associated with significant clinical impacts on asthma during childhood. Copyright©ERS 2012.


Mahut B.,Cabinet La Berma | Mahut B.,Mosquito Respiratory Research Group | Peiffer C.,Assistance Publique Hopitaux de Paris | Peiffer C.,Mosquito Respiratory Research Group | And 7 more authors.
Respiratory Medicine | Year: 2010

Background: Gas trapping suggesting small airway disease is observed in adult asthmatic suffering from severe asthma. The aim of the study was to assess whether gas trapping could be evidenced in asthmatic children with/without severe exacerbation and with/without symptoms during the past three months. Methods and patients: Forced expiratory flows (FEV1, FVC, MEF25-75%, MEF50%), plethysmographic lung volumes (TLC, FRC, RV) before and after bronchodilation (BD) were recorded in asthmatic children with documented airflow reversibility. Three groups were defined according to the presence during the last three months of 1) severe exacerbation (oral steroid: 3 consecutive days) 2) asthma symptoms without severe exacerbation and 3) without any symptom (GINA guidelines). Results: 180 children (median 11.3 years, range 6.3-17.6, 57 girls) were included, 24 (13%) had at least one severe exacerbation, 58 (33%) had respiratory symptoms without severe exacerbation and 98 (54%) had no symptom during the past 3 months. Forced expiratory flows did not significantly differ in these three groups, while RV/TLC was significantly higher in the first group before and even after bronchodilation: before BD, 0.27 ± 0.07, 0.24 ± 0.05 and 0.23 ± 0.05, respectively (p = 0.016) and after BD, 0.25 ± 0.07, 0.21 ± 0.05, 0.21 ± 0.05, respectively (p = 0.003). Conclusion: In asthmatic children, gas trapping is associated with occurrence of a severe exacerbation during the last three months, suggesting a small airway disease that is not evidenced by forced expiratory flows. © 2010 Elsevier Ltd. All rights reserved.


Mahut B.,Cabinet La Berma | Mahut B.,Mosquito respiratory research group | Peyrard S.,CIC 9201 Plurithematique | Delclaux C.,Assistance Publique Hopitaux de Paris | And 2 more authors.
Respiratory Research | Year: 2011

Whether exhaled NO helps to identify a specific phenotype of asthmatic patients remains debated. Our aims were to evaluate whether exhaled NO (FENO0.05) is independently associated (1) with underlying pathophysiological characteristics of asthma such as airway tone (bronchodilator response) and airway inflammation (inhaled corticosteroid [ICS]-dependant inflammation), and (2) with clinical phenotypes of asthma. We performed multivariate (exhaled NO as dependent variable) and k-means cluster analyses in a population of 169 asthmatic children (age ± SD: 10.5 ± 2.6 years) recruited in a monocenter cohort that was characterized in a cross-sectional design using 28 parameters describing potentially different asthma domains: atopy, environment (tobacco), control, exacerbations, treatment (inhaled corticosteroid and long-acting bronchodilator agonist), and lung function (airway architecture and tone). Two subject-related characteristics (height and atopy) and two disease-related characteristics (bronchodilator response and ICS dose > 200 μg/d) explained 36% of exhaled NO variance. Nine domains were isolated using principal component analysis. Four clusters were further identified: cluster 1 (47%): boys, unexposed to tobacco, with well-controlled asthma; cluster 2 (26%): girls, unexposed to tobacco, with well-controlled asthma; cluster 3 (6%): girls or boys, unexposed to tobacco, with uncontrolled asthma associated with increased airway tone, and cluster 4 (21%): girls or boys, exposed to parental smoking, with small airway to lung size ratio and uncontrolled asthma. FENO0.05 was not different in these four clusters. In conclusion, FENO0.05 is independently linked to two pathophysiological characteristics of asthma (ICS-dependant inflammation and bronchomotor tone) but does not help to identify a clinically relevant phenotype of asthmatic children. © 2011 Mahut et al; licensee BioMed Central Ltd.


Mahut B.,Cabinet La Berma | Mahut B.,Mosquito Respiratory Research Group | Trinquart L.,Assistance Publique Hopitaux de Paris | Trinquart L.,Mosquito Respiratory Research Group | And 8 more authors.
Respiratory Medicine | Year: 2010

Background: Exhaled NO (FENO) is a steroid dose dependent eosinophilic inflammometer, but also a mediator of bronchomotor tone, but statistically significant relationships have infrequently been obtained with pulmonary function tests (PFT). The aim was to test the hypothesis that the relationships between FENO and PFT could be uncovered by inhaled corticosteroid (ICS) treatment, namely that a link between FENO and bronchodilator response (an index of bronchomotor tone) would appear under ICS. Methods: Exhaled NO, forced expiratory flows and lung volumes were measured in atopic asthmatic children without recent (one month) respiratory symptoms. Results: Two hundred and thirty children (mean ± SD, age: 11.2 ± 2.5 years, 69 girls) were included (% predicted, FEV1: 100 ± 14; FEF50%: 76 ± 23; RV: 107 ± 29). The relationship between ICS dose (GINA classification) and FENO plateaued in children with an ICS dose higher than 200 μg beclomethasone equipotent daily dose: FENO (median [25th-75th percentiles]), 43 ppb [15-105] (no treatment, n = 65), 33 ppb [15-77] (low dose, n = 70), 23 ppb [12-57] (medium dose, n = 57) and 26 ppb [9-49] (high dose, n = 38). Statistically significant relationships between FENO and PFT were only observed in children receiving more than 200 μg/day ICS: with FEV1 (medium ICS dose: ρ = 0.43, p = 0.001; high dose: ρ = 0.32, p = 0.052) and bronchodilator (400 μg salbutamol) response (medium dose: ρ = 0.54, p = 0.001; high dose: ρ = 0.65, p = 0.002). Conclusions: A positive correlation between FENO and bronchomotor tone appears with increasing ICS doses in atopic children with clinically controlled asthma, which further suggests that children depicting the highest FENO values may have lesser steroid sensitivity. © 2010 Elsevier Ltd. All rights reserved.


Bokov P.,Assistance Publique Hopitaux de Paris | Bokov P.,University Paris Diderot | Bokov P.,Mosquito Respiratory Research Group | Mauroy B.,University Paris Diderot | And 12 more authors.
Respiratory Physiology and Neurobiology | Year: 2010

The remodelling process of COPD may affect both airway calibre and the homothety factor, which is a constant parameter describing the reduction of airway lumen (hd: diameter of child/parent bronchus) that might be critical because its reduction would induce a frank increase in airway resistance. Airway dimensions were obtained from CT scan images of smokers with (n=22) and without COPD (n=9), and airway resistance from plethysmography. Inspiratory airway resistance correlated to lumen area of the sixth bronchial generation of right lung, while peak expiratory flow correlated to the area of the third right generation (p=0.0009, R=0.57). A significant relationship was observed between hd and resistance (p=0.036; R2=0.14). A modelling approach of central airways (5 generations) further described the latter relationship. In conclusion, a constant homothety factor can be described by CT scan analysis, which partially explains inspiratory resistance, as predicted by theoretical arguments. Airway resistance is related to lumen areas of less proximal airways than commonly admitted. © 2010 Elsevier B.V.


Tadie J.-M.,Georges Pompidou Hospital | Tadie J.-M.,University of Paris Descartes | Trinquart L.,University of Paris Descartes | Trinquart L.,Georges Pompidou Hospital | And 13 more authors.
Shock | Year: 2010

The development of biomarkers able to predict the occurrence of nosocomial infection could help manage preventive strategies, especially in medical patients whose degree of acquired immunosuppression may be variable. We hypothesized that the NO fraction present in the airways (upper and lower) of critically ill patients under mechanical ventilation could constitute such a biomarker. We conducted an observational proof-of-concept study in a medical intensive care unit of a teaching hospital. Forty-five patients (26 men; 72 [25th-75th percentiles] years [56-82]; Simplified Acute Physiology Score II, 63 [50-81], 14 infected) under mechanical ventilation (>3 days) underwent on day 1 and day 3 of their stay: nasal and exhaled (partitioned in bronchial and alveolar sources) bedside NO measurements, determination of urine NO end products and plasma cytokine (IL-6, IL-10) concentrations, and Sequential Organ Failure Assessment score calculation. Nosocomial infection incidence was recorded during the 15 subsequent days. Fifteen patients (33%) acquired a nosocomial infection (16 infections, 15 ventilator-associated pneumonia and 1 bacteremia). Nasal NO was the only marker significantly different between patients with and without subsequent infection (day 1, 52 ppb [20-142] vs. 134 [84-203], P = 0.038; day 3, 98 ppb [22-140] vs. 225 [89-288], P = 0.006, respectively). Nasal NO fraction 148 ppb or less at day 3 had an 80% sensitivity, a 70% specificity, and an odds ratio of 2.7 (95% confidence interval, 1.9-3.8) to predict acquisition of nosocomial infection. Nonsurvivors had a higher IL-6 concentration on day 3 (P = 0.014), whereas their nasal NO fractions were not significantly different. Nasal NO seems to be a relatively sensitive and specific biomarker of subsequent nosocomial infection acquisition (at least for ventilator-associated pneumonia), which warrants confirmation in a multicenter trial. © 2010 by the Shock Society.


Bokov P.,Assistance Publique HOpitaux de Paris | Bokov P.,University Paris Diderot | Bokov P.,Mosquito Respiratory Research Group | Mauroy B.,University of Nice Sophia Antipolis | And 6 more authors.
Respiratory Physiology and Neurobiology | Year: 2014

Our objective was to evaluate whether a decrease in the homothety ratio (h: diameter of child/parent bronchus, constant over generations) explains the shift in airway resistance toward periphery in chronic obstructive pulmonary disease (COPD). Using a validated computational model of fluid motion, we determined that reduced values of h (<0.76) were associated with a shift in resistance toward periphery. The calculated luminal diameters of terminal bronchioles using normal h (0.80-0.85) or reduced h (0.70-0.75) fitted well with measured micro-CT values obtained by McDonough et al. (N. Engl. J. Med., 2011; 365:1567-75) in control and COPD patients, respectively. A semi-analytic formula of resistance using tracheal dimensions and h was developed, and using experimental data (tracheal area and h from patients [Bokov et al., Respir. Physiol. Neurobiol., 2010; 173:1-10]), we verified the agreement between measured and calculated resistance (r= 0.42). In conclusion, the remodeling process of COPD may reduce h and explain the shift in resistance toward lung periphery. © 2013 Elsevier B.V.


PubMed | University of Nice Sophia Antipolis, Mosquito Respiratory Research Group, University of Paris Descartes and University Paris Diderot
Type: | Journal: Respiratory physiology & neurobiology | Year: 2013

Our objective was to evaluate whether a decrease in the homothety ratio (h: diameter of child/parent bronchus, constant over generations) explains the shift in airway resistance toward periphery in chronic obstructive pulmonary disease (COPD). Using a validated computational model of fluid motion, we determined that reduced values of h (<0.76) were associated with a shift in resistance toward periphery. The calculated luminal diameters of terminal bronchioles using normal h (0.80-0.85) or reduced h (0.70-0.75) fitted well with measured micro-CT values obtained by McDonough et al. (N. Engl. J. Med., 2011; 365:1567-75) in control and COPD patients, respectively. A semi-analytic formula of resistance using tracheal dimensions and h was developed, and using experimental data (tracheal area and h from patients [Bokov et al., Respir. Physiol. Neurobiol., 2010; 173:1-10]), we verified the agreement between measured and calculated resistance (r=0.42). In conclusion, the remodeling process of COPD may reduce h and explain the shift in resistance toward lung periphery.

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