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.

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.

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.

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.

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.

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.

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.

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.

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.

Influence of age on the risk of severe exacerbation and asthma control in childhood.

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.

Influenza-like illness responsible for severe exacerbations in asthmatic children during H1N1 pandemic: a survey before vaccination.

BACKGROUND: Asthma seems to be the more prevalent underlying condition in patients hospitalized for H1N1-related flu. METHODS: A prospective survey was conducted during the early phase of H1N1 pandemic in France in asthmatic children before vaccination to assess whether severe exacerbations in childhood asthma are associated with influenza-like illness (ILI, the definition of H1N1-related flu in a pandemic). Eight pediatricians in primary care distributed in three localities (Paris, south suburb, and west suburb) conducted the survey (4 weeks/locality from week 36 to 47). At each visit, the pediatrician filled a questionnaire entering the information regarding asthma treatment, severe exacerbation (at least 3 days' use of systemic corticosteroids), and ILI (temperature ≥37.8°C, cough, and/or sore throat, in the absence of a known cause other than influenza) during the past 3 weeks. RESULTS: The survey included 1155 asthmatic children (mean age [SD]: 7.5 years [4.1]); almost all visits were scheduled (99%). A severe exacerbation was recorded in 121 children [10.5%; 95% confidence interval (CI): 8.7-12.2%], which was concomitant with ILI in 20 children (16.5%; 95% CI: 9.9-23.2%), whereas 1034 children did not exhibit any exacerbation. In these latter children, 40 ILI were observed (3.9%; 95% CI: 2.7-5.0%), which constituted a significantly lesser percentage as compared with children with both exacerbation and ILI (p < .0001). This result remained significant in each locality. Overall, 60/1155 (5.2%; 95% CI: 3.9-6.5%) asthmatic children had an ILI. CONCLUSIONS: Our survey shows that severe exacerbation and ILI are strongly associated during the H1N1 pandemic in 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.

Lung function impairment evidenced by sequential specific airway resistance in childhood persistent asthma: a longitudinal study.

BACKGROUND: Specific airway resistance (sRaw) is virtually independent of lung growth, height, and gender, thus facilitating longitudinal follow-up. OBJECTIVE: To assess whether a specific phenotype of asthmatic children with a decline in lung function can be evidenced using sRaw. METHODS: The authors hypothesized that sequential sRaw measurements over a long period would detect subtle trends. Clinical and functional data of children with persistent asthma under inhaled corticosteroids, evaluated at least three times per year for at least 4 years, were retrieved from a database. RESULTS: One hundred fourteen children (30 girls) were followed for (median [interquartile range]) 6.9 years [5.6-7.9]. Data from 1699 measurements of sRaw (median 14/child) allowed the calculation of individual slopes of sRaw plotted against time demonstrating stable values in the group as a whole between 4 and 18 years. A positive correlation between individual slopes and the degree of intraindividual variation of sRaw was observed (R(2) = .16; p < .0001). Children with more than one positive skin test showed larger intrasubject variation of sRaw (p = .011). In 19/114 children (17%), a significant increase in sRaw of 12.3% per year (median) was observed. As compared to children without, those with a significant increase in sRaw were boys (p < .0001), had a lower initial (p = .008) and a higher final resistance (p = .025) but did not differ in terms of inhaled corticosteroid dose. CONCLUSION: This retrospective study identifies a specific phenotype of asthmatic children that develops an impairment of lung function, confirming the results of a post hoc analysis of the Childhood Asthma Management Program study.

What does a single exhaled nitric oxide measurement tell us in asthmatic children?

BACKGROUND: Due to the multiple factors affecting exhaled nitric oxide (NO) value, physicians are often puzzled by the result of a single measurement in asthmatic patients. OBJECTIVE: The aim of this prospective transversal study was to evaluate the relative contributions to exhaled NO fraction (FE(NO)) of the commonly considered major NO determinants, i.e., recent symptoms (upper and lower respiratory tract), atopy (prick skin tests and degree of allergic exposure), and treatment (dose of inhaled corticosteroid [ICS]) to know what information gives a single measure. METHODS: FE(NO) at 50 mL/s expiratory flow was measured in 199 asthmatic children (141 boys, age: 11.2 years +/- 2.5 years). The allergic risk due to pollen exposure (ARPE index) was independently evaluated by the "Réseau National de Surveillance Aérobiologique." RESULTS: A multivariate analysis of FE(NO) as dependent variable showed that explanatory variables explained 23% of total FE(NO) variance (symptoms > atopy > ICS). In the children without recent symptoms (n = 118), a FE(NO) > 23 ppb predicted atopy (sensitivity 47%, specificity 85%, p = 0.0006). Multiple regression only showed a trend to significance between FE(NO) and the dose of ICS (p = 0.057, r = - 0.19). Incidentally, despite similar dose of ICS, children under fluticasone (mean +/- SD, 259 +/- 149 microg/day) had lower FE(NO) than those under budesonide (299 +/- 195 microg/day) (median [interquartile], 21 ppb [14-42], n = 55 versus 35 ppb [19-47], n = 104; p = 0.007), which may be due to a higher potency of fluticasone. A relationship between FE(NO) and ARPE index was significant in children with exclusive seasonal sensitisation (n = 31, r = 0.48, p = 0.008). CONCLUSION: Common exhaled NO determinants weakly explain a single value of FE(NO), which only can confidently predict atopy.

Impairment of nitric oxide output of conducting airways in primary ciliary dyskinesia.

Nasal nitric oxide (NO) concentration is dramatically reduced in primary ciliary dyskinesia (PCD). The aims of this study were to apply a multiple-flow NO analysis to investigate whether NO output from the bronchial tree was affected in a similar way to nasal NO output, and to search for a relationship between flow-independent exchange parameters and airflow limitation. Multiple flow rate analysis of exhaled NO, allowing the calculation of maximum airway wall flux and alveolar NO concentration, was performed in 17 PCD patients (median age, 25-75th percentiles: 13.5, 12.1-17.6) with documented ultrastructural cilia abnormalities and 28 healthy subjects (16.0, 11.0-21.0). Median maximum airway wall flux and median alveolar NO concentration were significantly reduced in PCD patients compared to healthy subjects: 16.0, 7.5-29.5, vs. 25.0, 15.0-32.5 nl/min (P<0.05) and 2.5, 1.6-3.3, vs. 5.0, 3.6-6.5 ppb (P<0.01), respectively. Significant correlations between maximum airway wall flux and airflow limitation were found, i.e., resistance of respiratory system (rho=0.74, P<0.005), forced expiratory volume in one second (FEV(1))/VC (rho= -0.61, P<0.05), FEV(1) (rho=-0.52, P< 0.05), mid expiratory flow between 25 and 75% of forced vital capacity (MEF(25-75)) (rho=-0.54, P<0.05), and maximal instantaneous expiratory flow at 50% of the vital capacity (MEF(50)) (rho=-0.55, P<0.05). In conclusion, the impairment of NO output is less pronounced in the lower than in the upper (nasal) respiratory tract in PCD. A decrease in maximal NO output from conducting airways is associated with limited airflow impairment.

Validity criteria and comparison of analytical methods of flow-independent exhaled NO parameters.

The objective was to assess both validity and comparability of multiple constant (MCF, mainly performed) and dynamically changing (DCF, new method) flow analyses calculating alveolar concentration (Calv(NO)), maximum conducting airway flux (J'aw(NO)) and airway diffusing capacity (Daw(NO)) of exhaled NO (FE(NO)). (Calv(NO), J'aw(NO))(R) where R is the correlation coefficient of the linear regression between NO output and expiratory flow rate (MCF) and (Calv(NO), J'aw(NO), Daw(NO))(Delta100) where Delta100 is the ratio ([observed-predicted FE(NO)]/observed FE(NO)) at 100 ml/s (DCF) were assessed in 18 healthy subjects (10 atopic). MCF demonstrated a linear relationship (R > or = 0.80) between NO output and expiratory flow in 15/18 subjects. DCF was valid (Delta100 < or = 30%) in 12/18 subjects. A good agreement between MCF and DCF was evidenced in the nine subjects with R > or = 0.80 and Delta100 < or = 30%. Failure of validity criteria was mainly observed in atopic subjects. In conclusion, when validity criteria are satisfied, the new DCF method similarly characterizes NO exchange parameters than MCF approach.

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.