Digital Action Plan (Web App) for Managing Asthma Exacerbations: Randomized Controlled Trial.

BACKGROUND: A written action plan (WAP) for managing asthma exacerbations is recommended. OBJECTIVE: We aimed to compare the effect on unscheduled medical contacts (UMCs) of a digital action plan (DAP) accessed via a smartphone web app combined with a WAP on paper versus that of the same WAP alone. METHODS: This randomized, unblinded, multicenter (offline recruitment in private offices and public hospitals), and parallel-group trial included children (aged 6-12 years) or adults (aged 18-60 years) with asthma who had experienced at least 1 severe exacerbation in the previous year. They were randomized to a WAP or DAP+WAP group in a 1:1 ratio. The DAP (fully automated) provided treatment advice according to the severity and previous pharmacotherapy of the exacerbation. The DAP was an algorithm that recorded 3 to 9 clinical descriptors. In the app, the participant first assessed the severity of their current symptoms on a 10-point scale and then entered the symptom descriptors. Before the trial, the wordings and ordering of these descriptors were validated by 50 parents of children with asthma and 50 adults with asthma; the app was not modified during the trial. Participants were interviewed at 3, 6, 9, and 12 months to record exacerbations, UMCs, and WAP and DAP use, including the subjective evaluation (availability and usefulness) of the action plans, by a research nurse. RESULTS: Overall, 280 participants were randomized, of whom 33 (11.8%) were excluded because of the absence of follow-up data after randomization, leaving 247 (88.2%) participants (children: n=93, 37.7%; adults: n=154, 62.3%). The WAP group had 49.8% (123/247) of participants (children: n=45, 36.6%; mean age 8.3, SD 2.0 years; adults: n=78, 63.4%; mean age 36.3, SD 12.7 years), and the DAP+WAP group had 50.2% (124/247) of participants (children: n=48, 38.7%; mean age 9.0, SD 1.9 years; adults: n=76, 61.3%; mean age 34.5, SD 11.3 years). Overall, the annual severe exacerbation rate was 0.53 and not different between the 2 groups of participants. The mean number of UMCs per year was 0.31 (SD 0.62) in the WAP group and 0.37 (SD 0.82) in the DAP+WAP group (mean difference 0.06, 95% CI -0.12 to 0.24; P=.82). Use per patient with at least 1 moderate or severe exacerbation was higher for the WAP (33/65, 51% vs 15/63, 24% for the DAP; P=.002). Thus, participants were more likely to use the WAP than the DAP despite the nonsignificant difference between the action plans in the subjective evaluation. Median symptom severity of the self-evaluated exacerbation was 4 out of 10 and not significantly different from the symptom severity assessed by the app. CONCLUSIONS: The DAP was used less often than the WAP and did not decrease the number of UMCs compared with the WAP alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT02869958; https://clinicaltrials.gov/ct2/show/NCT02869958.

Longitudinal assessment of loss and gain of lung function in childhood asthma.

OBJECTIVE: The Childhood Asthma Management Program revealed that 25.7% of children with mild to moderate asthma exhibit loss of lung function. The objective was to assess the trajectories of function by means of serial FEV1 in asthmatic children participating in out-of-hospital follow-up. METHODS: A total of 295 children (199 boys) who had undergone at least 10 spirometry tests from the age of 8 were selected from a single-center open cohort. The annualized rate of change (slope) for prebronchodilator FEV1 (percent predicted) was estimated for each participant and three patterns were defined: significantly positive slope, significantly negative slope, and null slope (non-significant P-value; Pearson test). The standard deviation (SD) of each individual slope was recorded as a variability criterion of FEV1. RESULTS: The median (25th; 75th percentile) age at inclusion and the last visit was 8.5 (8.2; 9.3) and 15.4 (14.8, 16.0) years, respectively. Tracking of function (null slope) was observed in 68.8% of the children, while 27.8% showed a loss of function or reduced growth (negative slope) and 3.4% showed a gain in function (positive slope). The children characterized by loss of function depicted a better initial function and a lower FEV1 variability during their follow-up than children with tracking or gain of lung function. At the last visit, these children were characterized by a lower lung function than children with tracking or gain of lung function. CONCLUSION: Better initial FEV1 value and less FEV1 variability are associated with loss of lung function or reduced lung growth in asthmatic children.

Wheezing recognition algorithm using recordings of respiratory sounds at the mouth in a pediatric population.

BACKGROUND: Respiratory diseases in children are a common reason for physician visits. A diagnostic difficulty arises when parents hear wheezing that is no longer present during the medical consultation. Thus, an outpatient objective tool for recognition of wheezing is of clinical value. METHOD: We developed a wheezing recognition algorithm from recorded respiratory sounds with a Smartphone placed near the mouth. A total of 186 recordings were obtained in a pediatric emergency department, mostly in toddlers (mean age 20 months). After exclusion of recordings with artefacts and those with a single clinical operator auscultation, 95 recordings with the agreement of two operators on auscultation diagnosis (27 with wheezing and 68 without) were subjected to a two phase algorithm (signal analysis and pattern classifier using machine learning algorithms) to classify records. RESULTS: The best performance (71.4% sensitivity and 88.9% specificity) was observed with a Support Vector Machine-based algorithm. We further tested the algorithm over a set of 39 recordings having a single operator and found a fair agreement (kappa=0.28, CI95% [0.12, 0.45]) between the algorithm and the operator. CONCLUSIONS: The main advantage of such an algorithm is its use in contact-free sound recording, thus valuable in the pediatric population.

Avoidable Emergency Visits for Acute Asthma in Children: Prevalence and Risk Factors.

Emergency department (ED) visits for asthma exacerbation have not become less frequent, essentially because the self-management of mild-to-moderate asthma exacerbations by children and their families remains sub-optimal. The objective of our study was to assess the proportion of visits to EDs for asthma exacerbation that were potentially avoidable and their risk factors [such as no Written Asthma Action Plan (WAAP)]. We conducted an 8-month multicenter study in 6 French pediatric EDs. Parents, nurses, and physicians filled out a questionnaire, recording information on the history of asthma and education (peak flow, WAAP), the self-management of the present exacerbation, the reasons for coming to the ED, the severity of the exacerbation, and the clinical outcome. An ED visit was deemed as potentially avoidable when a child who had not received adequate prehospital treatment left the ED after a maximum of 3 nebulizations with a bronchodilator with no relapse within 48 h. We included 107 children [mean (standard deviation) age 9.8 (2.4) years, 40% were girls]. At arrival, 76 children [71%, 95% confidence interval (CI): 62-80] had not received adequate treatment for the current exacerbation. Forty-one children (38%, 95% CI: 29-48) had an avoidable ED visit. Feelings of fear/anxiety were the only independent risk factor for avoidable visits, whereas the existence of a WAAP at home did not independently influence avoidable visits. Inadequate prehospital treatment and avoidable visits are frequent in children with known asthma visiting EDs for an asthma exacerbation. Strategies to reduce avoidable visits should seek to improve the WAAP, to develop and validate new electronic tools for self-managed interventions, and to provide reassurance.

Airway Remodeling in Preschool Children with Severe Recurrent Wheeze.

RATIONALE: Airway wall structure in preschoolers with severe recurrent wheeze is poorly described. OBJECTIVES: To describe airway wall structure and inflammation in preschoolers with severe recurrent wheeze. METHODS: Flexible bronchoscopy was performed in two groups of preschoolers with severe recurrent wheeze: group 1, less than or equal to 36 months (n = 20); group 2, 36-59 months (n = 29). We assessed airway inflammation, reticular basement membrane (RBM) thickness, airway smooth muscle (ASM), mucus gland area, vascularity, and epithelial integrity. Comparisons were then made with biopsies from 21 previously described schoolchildren with severe asthma (group 3, 5-11.2 yr). MEASUREMENTS AND MAIN RESULTS: RBM thickness was lower in group 1 than in group 2 (3.3 vs. 3.9 µm; P = 0.02), was correlated with age (P < 0.01; ρ = 0.62), and was higher in schoolchildren than in preschoolers (6.8 vs. 3.8 µm; P < 0.01). ASM area was lower in preschoolers than in schoolchildren (9.8% vs. 16.5%; P < 0.01). Vascularity was higher in group 1 than in group 2 (P = 0.02) and group 3 (P < 0.05). Mucus gland area was higher in preschoolers than in schoolchildren (16.4% vs. 4.6%; P < 0.01). Inflammatory cell counts in biopsies were not correlated with airway wall structure. ASM area was higher in preschoolers with atopy than without atopy (13.1% vs. 7.7%; P = 0.01). Airway morphometrics and inflammation were similar in viral and multiple-trigger wheezers. CONCLUSIONS: In preschoolers with severe recurrent wheeze, markers of remodeling and inflammation are unrelated, and atopy is associated with ASM. In the absence of control subjects, we cannot determine whether differences observed in RBM thickness and vascularity result from disease or normal age-related development.

Prevalence of overestimation or underestimation of the functional capacity using MRC score as compared to 6-minute walk test in patients with cardio-respiratory disorders.

OBJECTIVES: The first objective of our study was to assess whether patients diagnosed with cardio-respiratory disorders report overestimation or underestimation on recall (Medical Research Council (MRC) dyspnea scale) of their true functional capacity (walked distance during a 6-minute walk test (6MWT)). The second objective was to assess whether the measurement of breathlessness at the end of a 6MWT (Borg score) may help to identify dyspneic patients on recall. METHODS: The 6MWTs of 746 patients aged from 40 to 80 years who were diagnosed with either chronic obstructive pulmonary disease (COPD, n = 355), diffuse parenchymal lung disease (n = 140), pulmonary vascular diseases (n = 188) or congestive heart failure (n = 63) were selected from a prospective Clinical Database Warehouse. RESULTS: The percentage of patients who overestimated (MRC ≤ 2 with distance < lower limit of normal (LLN), 61/746, 8%; 95% confidence interval (CI): 6 to 10%) or underestimated (MRC > 2 with distance ≥LLN, 121/746, 16%; 95%CI: 14 to 19%) on recall their capacity was elevated. The overestimation seemed related to self-limitation, while the underestimation seemed related to patients who "work through" their breathing discomfort. These two latter groups of patients were mainly diagnosed with COPD. A Borg dyspnea score >3 (upper limit of normal) at the end of the 6MWT had 84% specificity for the prediction of a MRC score >1. CONCLUSION: Almost one fourth of patients suffering from cardio-pulmonary disorders overestimate or underestimate on recall their true functional capacity. An elevated Borg dyspnea score at the end of the 6MWT has a good specificity to predict dyspnea on recall.

Homothety ratio of airway diameters and site of airway resistance in healthy and COPD subjects.

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.

Cross-sectional assessment of exertional dyspnea in otherwise healthy children.

OBJECTIVES: Exertional dyspnea during sport at school in children with asthma or in otherwise healthy children is commonly attributed to exercise-induced asthma (EIA), but when a short-acting beta agonist (SABA) trial fails to improve symptoms the physician is often at a loose end. DESIGN: The aims were to prospectively assess the causes of exertional dyspnea in children/adolescents with or without asthma using a cardiopulmonary exercise test while receiving a SABA and to assess the effects of standardized breathing/reassurance therapy. RESULTS: Seventy-nine patients (12.2 ± 2.3 years, 41 girls, 49 with previously diagnosed asthma) with dyspnea unresponsive to SABA were prospectively included. Exercise test outcomes depicted normal or subnormal performance with normal ventilatory demand and capacity in 53/79 children (67%) defining a physiological response. The remaining 26 children had altered capacity (resistant EIA [n = 17, 9 with previous asthma diagnosis], vocal cord dysfunction [n = 2]) and/or increased demand (alveolar hyperventilation [n = 3], poor conditioning [n = 7]). Forty-two children who had similar characteristics than the remaining 37 children underwent the two sessions of standardized reassurance therapy. They all demonstrated an improvement that was rated "large." The degree of improvement correlated with % predicted peak V'O2 (r = -0.37, P = 0.015) and peak oxygen pulse (r = -0.45, P = 0.003), whatever the underlying dyspnea cause. It suggested a higher benefit in those with poorer conditioning condition. CONCLUSIONS: The most frequent finding in children/adolescents with mild exertional dyspnea unresponsive to preventive SABA is a physiological response to exercise, and standardized reassurance afforded early clinical improvement, irrespective of the dyspnea cause.

Cross-sectional assessment of the relationships between dyspnea domains and lung function in diffuse parenchymal lung disease.

BACKGROUND: Activity-related dyspnea is the main contributor to the altered quality of life in diffuse parenchymal lung diseases (DPLD). Instruments pertaining to dyspnea are classified as pertaining to domains of sensory-perceptual experience, affective distress or symptom/disease impact; whether these domains are equally related to lung function impairments remains to be established. OBJECTIVES: They were to assess the relationships between two domains of dyspnea (sensory-perceptual experience and symptom impact) and pulmonary function tests according to their evaluation of ventilatory demand, capacity and drive in patients suffering from DPLD. METHODS: Fifty patients were prospectively enrolled (median age, 58 years; 25 women) and underwent spirometry, body plethysmography, measurements of lung diffusion for carbon monoxide (DLCO) and nitric oxide, maximal airway pressures (capacity and demand assessments), mouth occlusion pressure at 0.1 s (P0.1: respiratory drive assessment) and a 6-min walk test with Borg score assessment (dyspnea: sensory domain). The impact domain of dyspnea was evaluated using the baseline dyspnea index. RESULTS: The sensory domain of dyspnea was linked to demand (CO transfer coefficient, kCO) only, while the impact domain was independently linked to demand and capacity (kCO and forced vital capacity, respectively). Among resting pulmonary function tests, both P0.1 and DLCO allowed the assessment of these two domains of dyspnea. CONCLUSIONS: In DPLD, the sensory-perceptual domain of dyspnea is mainly linked to alterations in ventilatory demand while the impact domain is related to both demand and capacity. DLCO that assesses both demand and capacity and P0.1 were the strongest correlates of dyspnea.

Cross-sectional assessment of the roles of comorbidities in resting and activity-related dyspnea in severely obese women.

OBJECTIVES: Obesity has been associated with a lesser degree of asthma control that may be biased by other comorbidities. The objectives of this cross-sectional study were to describe resting and activity-related dyspnea complaints according to the presence of obesity-related comorbidities (asymptomatic airway hyperresponsiveness (AHR), asthma, gastroesophageal reflux disease (GERD) and sleep-disordered breathing (SDB)). We hypothesized that obese women can exhibit both resting and activity-related dyspnea, independently of the presence of asthma. METHODS: Severely obese (body mass index (BMI) > 35 kg m(-2)) women prospectively underwent description of resting and activity-related dyspnea (verbal descriptors and Medical Research Council (MRC) scale), pulmonary function testing (spirometry, absolute lung volumes, and methacholine challenge test), oesogastro-duodenal fibroscopy, and overnight polygraphy. Thirty healthy lean women without airway hyperresponsiveness were enrolled. RESULTS: Resting dyspnea complaints were significantly more prevalent in obesity (prevalence 41%) than in healthy lean women (prevalence 3%). Chest tightness and the need for deep inspirations were independently associated with both asthma and GERD while wheezing and cough were related to asthma only in obese women. Activity-related dyspnea was very prevalent (MRC score > 1, 75%), associated with obesity, with the exception of wheezing on exertion due to asthma. Asymptomatic AHR and SDB did not affect dyspneic complaints. CONCLUSIONS: In severely obese women referred for bariatric surgery, resting dyspnea complaints are observed in association with asthma or GERD, while activity-related dyspnea was mainly related to obesity only. Consequently, asthma does not explain all respiratory complaints of obese women.

Risk factors for airway hyperresponsiveness in severely obese women.

Obesity affects airway diameter and tidal ventilation pattern, which could perturb smooth muscle function. The objective was to assess the pathophysiology of airway hyperresponsiveness in obesity while controlling for gastro-oesophageal reflux disease. Obese women (n=118, mean±SD BMI 46.1±6.8kg/m(-2)) underwent pulmonary function testing (including tidal ventilation monitoring and methacholine challenge) and oesogastro-duodenal fibroscopy. Fifty-seven women (48%, 95% CI: 39-57%) exhibited hyperresponsiveness (dose-response slope ≥2.39% decrease/µmol) that was independently and positively correlated with predicted % FRC, Raw0.5 and negatively correlated with sigh frequency during tidal ventilation. Obese women had an increased breathing frequency but a similar sigh frequency than healthy lean women (n=30). Twenty-two obese women (19%, 95% CI: 12-26%) were classified as asthmatics (hyperresponsiveness and suggestive symptoms) without confounding effect of gastro-oesophageal reflux disease. In conclusion, in women referred for bariatric surgery, unloading of bronchial smooth muscle (reduced airway calibre and sigh frequency) is associated with hyperresponsiveness.

Relationships between respiratory and airway resistances and activity-related dyspnea in patients with chronic obstructive pulmonary disease.

BACKGROUND: The aims of the study were: (1) to compare numerical parameters of specific airway resistance (total, sRaw(tot), effective, sRaw(eff) and at 0.5 L · s(-1), sRaw(0.5)) and indices obtained from the forced oscillation technique (FOT: resistance extrapolated at 0 Hz [Rrs(0 Hz)], mean resistance [Rrs(mean)], and resistance/frequency slope [Rrs(slope)]) and (2) to assess their relationships with dyspnea in chronic obstructive pulmonary disease (COPD). METHODS: A specific statistical approach, principal component analysis that also allows graphic representation of all correlations between functional parameters was used. A total of 108 patients (mean ± SD age: 65 ± 9 years, 31 women; GOLD stages: I, 14; II, 47; III, 39 and IV, 8) underwent spirometry, body plethysmography, FOT, and Medical Research Council (MRC) scale assessments. RESULTS: Principal component analysis determined that the functional parameters were described by three independent dimensions (airway caliber, lung volumes and their combination, specific resistance) and that resistance parameters of the two techniques were not equivalent, obviously. Correlative analyses further showed that Raw(tot) and Raw(eff) (and their specific resistances) can be considered as equivalent and correlated with indices that are considered to explore peripheral airways (residual volume (RV), RV/ total lung capacity (TLC), Rrs(slope)), while Rrs(mean) and Raw(0.5) explored more central airways. Only specific resistances taking into account the specific resistance loop area (sRaw(tot) and sRaw(eff)) and Rrs(slope) were statistically linked to dyspnea. CONCLUSION: Parameters obtained from both body plethysmography and FOT can explore peripheral airways, and some of these parameters (sRaw(tot), sRaw(eff,) and Rrs(slope)) are linked to activity-related dyspnea in moderate to severe COPD patients.

Activity-related dyspnea is not modified by psychological status in people with COPD, interstitial lung disease or obesity.

Sensory (physiological) and affective (psychological) dimensions of dyspnea have been described but the usefulness of measuring psychological status in addition to ventilatory capacity (spirometry, lung volumes) in the assessment of exertional dyspnea remains controversial. We hypothesized that activity-related dyspnea would not be modified by psychological status. Principal component analysis (PCA) was used to reduce the number of parameters (psychological or functional) to fewer independent dimensions in 328 patients with altered ventilatory capacity: severe obesity (BMI ≥ 35, n = 122), COPD (n = 128) or interstitial lung disease (n = 78). PCA demonstrated that psychological status (Hospital Anxiety-Depression, Fatigue Impact scales) and dyspnea (Medical Research Council [MRC] scale) were independent dimensions. Ventilatory capacity was described by three main dimensions by PCA related to airways, volumes, and their combination (specific airway resistance, FEV(1)/FVC), which were weakly correlated with dyspnea. In conclusion, in patients with COPD, interstitial lung disease or severe obesity, psychological status does not modify activity-related dyspnea rating as evaluated by the MRC scale.

Diffusing capacity for carbon monoxide is linked to ventilatory demand in patients with chronic obstructive pulmonary disease.

Dyspnea is deemed to result from an imbalance between ventilatory demand and capacity. The single-breath diffusing capacity for carbon monoxide (DLCO) is often the best correlate to dyspnea in COPD. We hypothesized that DLCO contributes to the assessment of ventilatory demand, which is linked to physiological dead space /tidal volume (V(D)/V(T)) ratio. An additional objective was to assess the validity of non-invasive measurement of transcutaneous P(CO2) allowing the calculation of this ratio. Forty-two subjects (median [range] age: 66 [43-80] years; 12 females) suffering mainly from moderate-to-severe COPD (GOLD stage 2 or 3: n = 36) underwent pulmonary function and incremental exercise tests while taking their regular COPD treatment. DLCO% predicted correlated with both resting and peak physiological V(D)/V(T) ratios (r = -0.55, p = 0.0015 and r = -0.40, p = 0.032; respectively). The peak physiological V(D)/V(T) ratio contributed to increase ventilation (increased ventilatory demand), to increase dynamic hyperinflation and to impair oxygenation on exercise. Indirect (MRC score) and direct (peak Borg score/% predicted VO(2)) exertional dyspnea assessments were correlated and demonstrated significant relationships with DLCO% predicted and physiological V(D)/V(T) at peak exercise, respectively. The non-invasive measurement of transcutaneous P(CO2) both at rest and on exercise was validated by Bland-Altman analyses. In conclusion, DLCO constitutes and indirect assessment of ventilatory demand, which is linked to exertional dyspnea in COPD patients. The assessment of this demand can also be non invasively obtained on exercise using transcutaneous PCO(2) measurement.

Baseline and post-bronchodilator interrupter resistance and spirometry in asthmatic children.

In children unable to perform reliable spirometry, the interrupter resistance (R(int) ) technique for assessing respiratory resistance is easy to perform. However, few data are available on the possibility to use R(int) 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 R(int) 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 R(int) and spirometry were studied using data expressed as z-scores. Receiver operator characteristic curves for the baseline R(int) 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 R(int) and FEV(1) was not linear. Despite a highly significant inverse correlation between R(int) and all of the spirometry indices (FEV(1) , FVC, FEV(1) /FVC, FEF(25-75%) ; P < 0.0001), R(int) could detect baseline obstruction (FEV(1) z-score ≤ -2) with only 42% sensitivity and 95% specificity. Post-bronchodilator changes in R(int) and FEV(1) were inversely correlated (rhô = -0.50, P < 0.0001), and R(int) (≥35% predicted value decrease) detected FEV(1) reversibility (>12% baseline increase) with 70% sensitivity and 69% specificity (AUC = 0.79). R(int) measurements fitted a one-compartment model that explained the relationship between flows and airway resistance. We found that R(int) 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(int) should be systematically studied and further assessed in conjunction with clinical outcomes.

Overweight is not a comorbidity factor during childhood asthma: the GrowthOb study.

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.

Pathophysiology of airway hyperresponsiveness in patients with nasal polyposis.

BACKGROUND: It has been hypothesized that airway hyperresponsiveness (AHR) is characterized by sensitivity (strength of stimulus) and reactivity (responsiveness to stimulus); the latter could be the intrinsic characteristic of AHR. The underlying mechanisms leading to AHR could be 1) airway inflammation, 2) reduction of forces opposing bronchoconstriction, and 3) structural airway changes/geometric factors. OBJECTIVE: Our main objective was to assess the relationships between reactivity in patients with nasal polyposis and these three mechanisms using measurements of 1) bronchial and bronchiolar/alveolar NO, 2) bronchomotor response to deep inspiration, and 3) forced expiratory flows and an index of airway to lung size, i.e. FEF(25-75%)/FVC. METHODS: Patients underwent spirometry, multiple flow measurement of exhaled NO (corrected for axial diffusion), assessment of bronchomotor response to deep inspiration by forced oscillation technique and methacholine challenge allowing the calculation of reactivity (slope of the dose-response curve) and sensitivity (PD(10)). RESULTS: One hundred and thirty-two patients were prospectively enrolled of whom 71 exhibited AHR. Airway reactivity was correlated with alveolar NO concentration (rho = 0.35; p = 0.017), with airflow limitation (FEF(25-75%): rho = -0.40; p = 0.003) and with an index of airway size to lung size (FEF(25-75%)/FVC: rho = -0.38; p = 0.005), of which only alveolar NO remained the only independent factor in a stepwise multiple regression analysis (variance 25%). Airway sensitivity was not correlated with any pulmonary function or exhaled NO parameter. CONCLUSION: In patients with nasal polyposis, alveolar NO is associated with airway reactivity, suggesting that bronchiolar/alveolar lung inflammation may constitute one intrinsic characteristic of increased responsiveness.

Exhaled nitric oxide and clinical phenotypes of childhood asthma.

Whether exhaled NO helps to identify a specific phenotype of asthmatic patients remains debated. Our aims were to evaluate whether exhaled NO (FENO(0.05)) 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. FENO(0.05) was not different in these four clusters.In conclusion, FENO(0.05) 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.

Use of specific airway resistance to assess bronchodilator response in children.

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 FEV(1) 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 FEV(1) reversibility; (ii) to determine whether the discrepancy between ΔsRaw and ΔFEV(1) might be explained by independent correlations between ΔFEV(1) 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 ΔFEV(1) . METHODS: A retrospective study was performed in 481 children (median age 10.5years, 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 FEV(1) 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 FEV(1) , with no influence of height or age.