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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

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. Source

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

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. Source

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

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. Source

Mahut B.,La Berma Clinic | Mahut B.,Mosquito Respiratory Research Group | Peiffer C.,Assistance Publique Hopitaux de Paris | Peiffer C.,Mosquito Respiratory Research Group | And 8 more authors.

Background and objective: Changes in specific airway resistance (ΔsRaw) after bronchodilation, as measured by plethysmography and FEV 1, are frequently considered to be interchangeable indices of airway obstruction. However, the baseline relationship between these two indices is weak, and the value of ΔsRaw that best predicts FEV1 reversibility in children has yet to be determined. The aim of this study was (i) to establish the sRaw cut-off value that best distinguishes between positive and negative bronchodilator responses, as measured by FEV1 reversibility; (ii) to determine whether the discrepancy between ΔsRaw and ΔFEV1 might be explained by independent correlations between ΔFEV1 and both ΔsRaw (mainly airway obstruction) and ΔFVC (airway closure); and (iii) to assess the effect of height and age on the relationship between ΔsRaw and ΔFEV1. Methods: A retrospective study was performed in 481 children (median age 10.5 years, range 6.1-17.6) with actual or suspected asthma, for whom sRaw and spirometry data were obtained at baseline and after administration of a bronchodilator. Results: The sRaw cut-off value that best predicted FEV1 reversibility was a 42% decrease from baseline (P = 0.0001, area under the curve 0.70, sensitivity 55%, specificity 77%) and was independent of height and age. Changes in FEV 1 were significantly but independently related to ΔsRaw and ΔFVC (index of air trapping) (r = 0.40, P < 0.0001 and r = 0.39, P < 0.0001, respectively). Conclusions: A 42% decrease in sRaw predicted FEV 1 reversibility reasonably well, whereas a smaller decrease in sRaw failed to detect approximately one out of two positive responses detected by FEV1, with no influence of height or age. FEV1 and specific airway resistance (sRaw) are used interchangeably as markers of bronchodilator response. A 42% decrease in sRaw showed good specificity but poor sensitivity for predicting FEV1 reversibility, partly because FEV1 and sRaw have different physiological components. © 2011 Asian Pacific Society of Respirology. Source

Tadie J.-M.,Assistance Publique Hopitaux de Paris | Tadie J.-M.,University of Paris Descartes | Trinquart L.,University of Paris Descartes | Trinquart L.,Mosquito Respiratory Research Group | And 11 more authors.

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. Source

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