Christophe Marguet

Local side‐effects of inhaled corticosteroids in asthmatic children: influence of drug, dose, age, and device

Background: The objective was to investigate the local side‐effects of inhaled corticosteroids (ICS) in daily life in asthmatic children, particularly the younger ones, by an observational prospective cross‐sectional cohort study.

In very young infants severity of acute bronchiolitis depends on carried viruses.

Background RT amplification reaction has revealed that various single viruses or viral co-infections caused acute bronchiolitis in infants, and RV appeared to have a growing involvement in early respiratory diseases. Because remaining controversial, the objective was to determine prospectively the respective role of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very young infants. Methods and Principal Findings 209 infants (median age: 2.4 months) were enrolled in a prospective study of infants <1 year old, hospitalized for a first episode of bronchiolitis during the winter epidemic season and with no high risk for severe disease. The severity was assessed by recording SaO2% at admission, a daily clinical score (scale 0–18), the duration of oxygen supplementation and the length of hospitalization. Viruses were identified in 94.7% by RT amplification reaction: RSV only (45.8%), RV only (7.2%), hMPV only (3.8%), dual RSV/RV (14.3%), and other virus only (2%) or coinfections (9%). RV compared respectively with RSV and dual RSV/RV infection caused a significant less severe disease with a lower clinical score (5[3.2–6] vs. 6[4–8], p = 0.01 and 5.5[5–7], p = 0.04), a shorter time in oxygen supplementation (0[0–1] days vs. 2[0–3] days, p = 0.02 and 2[0–3] days, p = 0.03) and a shorter hospital stay (3[3–4.7] days vs.6 [5–8] days, p = 0.001 and 5[4–6] days, p = 0.04). Conversely, RSV infants had also longer duration of hospitalization in comparison with RSV/RV (p = 0.01) and hMPV (p = 0.04). The multivariate analyses showed that the type of virus carried was independently associated with the duration of hospitalization. Conclusion This study underlined the role of RV in early respiratory diseases, as frequently carried by young infants with a first acute bronchiolitis. RSV caused the more severe disease and conversely RV the lesser severity. No additional effect of dual RSV/RV infection was observed on the severity.

Influence of Interleukin-10 on Aspergillus fumigatus Infection in Patients with Cystic Fibrosis

Recent evidence suggests that genetic polymorphisms that affect the production of interleukin (IL)-10 may play a role in the response to pathogens in cystic fibrosis (CF). The present study was designed to investigate a possible association between alleles carried at position -1082 in the promoter region of the IL-10 gene and clinical data on 378 patients with CF. After adjustment for potential confounding variables, a significant relationship was found between the -1082GG genotype and both colonization with Aspergillus fumigatus and allergic bronchopulmonary aspergillosis. In addition, higher serum levels of IL-10 were observed in patients colonized with A. fumigatus. These results suggest that polymorphisms in the promoter region of the IL-10 gene may influence the host response to A. fumigatus in the context of CF.

Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey

Omalizumab has been shown to reduce exacerbation rates in moderate to severe allergic asthma. Our aim was to evaluate omalizumab efficacy and safety in a real-life setting in severe asthmatic children. 104 children (aged 6–18 years), followed up in paediatric pulmonary tertiary care centres, were included at the beginning of omalizumab treatment. Asthma control levels, exacerbations, inhaled corticosteroid dose, lung function and adverse events were evaluated over 1 year. Children were characterised by allergic sensitisation to three or more allergens (66%), high IgE levels (mean 1125 kU·L−1), high rate of exacerbations (4.4 per year) and healthcare use during the previous year, and high inhaled corticosteroid dose (mean 703 &mgr;g equivalent fluticasone per day). Asthma control levels defined as good, partial or poor, improved from 0%, 18% and 82% at entry to 53%, 30% and 17% at week 20, and to 67%, 25% and 8% at week 52, respectively (p<0.0001). Exacerbation and hospitalisation rates dropped by 72% and 88.5%, respectively. At 12 months, forced expiratory volume in 1 s improved by 4.9% (p=0.023), and inhaled corticosteroid dose decreased by 30% (p<0.001). Six patients stopped omalizumab for related significant adverse events. Omalizumab improved asthma control in children with severe allergic asthma and was generally well tolerated. The observed benefit was greater than that reported in clinical trials. Omalizumab improves asthma control in children with severe allergic asthma and is generally well tolerated http://ow.ly/oLoBp

Molecular and cellular characteristics of ABCA3 mutations associated with diffuse parenchymal lung diseases in children

ABCA3 (ATP-binding cassette subfamily A, member 3) is expressed in the lamellar bodies of alveolar type II cells and is crucial to pulmonary surfactant storage and homeostasis. ABCA3 gene mutations have been associated with neonatal respiratory distress (NRD) and pediatric interstitial lung disease (ILD). The objective of this study was to look for ABCA3 gene mutations in patients with severe NRD and/or ILD. The 30 ABCA3 coding exons were screened in 47 patients with severe NRD and/or ILD. ABCA3 mutations were identified in 10 out of 47 patients, including 2 homozygous, 5 compound heterozygous and 3 heterozygous patients. SP-B and SP-C expression patterns varied across patients. Among patients with ABCA3 mutations, five died shortly after birth and five developed ILD (including one without NRD). Functional studies of p.D253H and p.T1173R mutations revealed that p.D253H and p.T1173R induced abnormal lamellar bodies. Additionally, p.T1173R increased IL-8 secretion in vitro. In conclusion, we identified new ABCA3 mutations in patients with life-threatening NRD and/or ILD. Two mutations associated with ILD acted via different pathophysiological mechanisms despite similar clinical phenotypes.

Inhalation treatment: errors in application and difficulties in acceptance of the devices are frequent in wheezy infants and young children.

The recent availability of small‐volume spacers has facilitated the general use of inhaled treatment in infants. The purpose of this study was to evaluate any errors made by parents when using this new inhalation technique and the childs behavior during the inhalation. Ninety‐four young children (61% boys) under 5 years of age were enrolled in the study. Inhalation treatment was recommended either by a general practitioner or by a pediatrician. Data concerning treatment regimens, the ability of parents to use the spacer and metered‐dose inhalers (MDIs), and the acceptance of the devices, were collected by means of a demonstration and questionnaire. Unexpectedly, the doses, administration times, and duration of the treatments varied from one child to the next. No explanation or training in administering the treatment via the spacers was given to 12% and 47% of the parents, respectively. Fourteen per cent of parents did not shake the MDIs, 12% did not monitor the valves, and 22% allowed too short a time for inhalation. The lack of explanation increased the occurence of errors in manipulation of the devices. The procedure was judged to be easy to follow by 78% of the parents, but the face mask was accepted with difficulty by 22% of the children. Repeated crying during administration of the treatment was observed in 38% of the patients, particularly the youngest. Crying influenced the acceptance of the face mask, reduced parental compliance, and made the use of the devices more difficult. Errors altering the efficiency of inhalation treatment in infants are frequent. Most of these errors could be avoided by spending more time to inform the parents about correct usage. Furthermore, repeated crying during inhalation is common in young children and this problem should to be taken into consideration in the evaluation of treatment.

Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations

This review is the synthesis of a working group on mild asthma. Mild asthma includes intermittent and persistent mild asthma according to the Global Initiative for Asthma (GINA) classification, and affects between 50% and 75% of asthmatic patients. Mild asthma is more frequent, more symptomatic, and less well controlled in children than in adults. Cohort studies from childhood to adulthood show that asthma severity usually remains stable over time. Nevertheless, mild asthma can lead to severe exacerbations, with a frequency ranging from 0.12 to 0.77 per patient‐year. Severe exacerbations in mild asthma represent 30–40% of asthma exacerbations requiring emergency consultation. In mild asthma, inflammation and structural remodelling are constant, of varying intensity, but nonspecific. Therapy with inhaled corticosteroids (ICS) decreases bronchial inflammation, but has only a slight effect on structural remodelling, and, when stopped, inflammation immediately recurs. Permanent low‐dose ICS therapy is the reference treatment for persistent mild asthma. Effectiveness is to be reassessed at 3 months, and if it is insufficient the patient is no longer considered mildly asthmatic, and treatment has to be stepped up. As mild asthma is the most frequent form of the disease, diagnosis and management require physicians’ particular attention.

Glutathione-S-transferase M1, M3, P1 and T1 polymorphisms and severity of lung disease in children with cystic fibrosis

OBJECTIVES Progression and severity of lung disease differs markedly and early between patients with cystic fibrosis (CF). We investigated the hypothesis that polymorphisms in the detoxifying enzymes glutathione-S-transferase (GST) could influence phenotypic presentation of lung disease in CF. METHODS Genotypes for GSTM1, GSTM3, GSTP1 and GSTT1 were determined in a cohort of 146 children with CF by PCR-based methods. Pulmonary function, assessed by spirometric measures of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), was analysed in children at the age of 9. RESULTS No association between spirometric measurements, and GSTM1, GSTP1 or GSTT1 genotypes was found. As compared with patients homozygous for GSTM3*A allele, CF children carrying the GSTM3*B allele displayed a significant better lung function, assessed by both mean values of FEV1 and of FVC (respectively P = 0.01 and P = 0.002). These correlations remained significant after adjustment for potential confounding factors (respectively adjusted P = 0.008 and P = 0.002) and also in subgroups of CF patients who carry the deltaF508 CFTR mutation. Haplotype analysis of GSTM3 in combination with GSTM1 indicated that the positive impact of GSTM3*B allele on pulmonary performances was barely influenced by the GSTM1 genotypes of CF children. CONCLUSIONS These data provide the first evidence suggesting that polymorphism of the GSTM3 gene contributes to clinical severity in CF, which may have prognostic significance and could prompt to start a more targeted therapy in young patients with CF.

Real-life long-term omalizumab therapy in children with severe allergic asthma

We previously reported the French real-life experience of 1 year of add-on treatment with omalizumab in 101 severe allergic asthmatic children (6–18 years), 92 of whom were still receiving the treatment at the end of the first year [1]. The study provided complementary data to the previous randomised trials [2–6]. We showed a marked drop of 72% in the mean rate of severe exacerbations (from 4.4 per patient during the preceding year to 1.25 during the year of treatment) and of 88.5% for hospitalisations (44% of the patients during the preceding year to 6.7% during the year of treatment); a large improvement in asthma control (from 0% at initiation to 67% of well-controlled patients after 1 year); a decrease of 30% of the mean inhaled corticosteroid (ICS) dose (from 703 at initiation to 488 µg fluticasone equivalent per day after 1 year); and a forced expiratory volume in 1 s (FEV1) increase, from a mean of 88% to 92.1% of the predicted value. Treatment was discontinued in six patients due to serious adverse events attributed to omalizumab by the practitioner. Here we report the outcome of this cohort after 2 years of omalizumab treatment. Beneficial effects at 2 years of omalizumab on severe exacerbations and control in severe allergic asthmatic children http://ow.ly/LGgnw

Hospitalizations for Asthma in Children Are Linked to Undertreatment and Insufficient Asthma Education

Background. Most hospital admissions for asthma exacerbation are avoidable with adequate disease management. Objectives. The objective of this study was to describe the characteristics of children hospitalized with an asthma exacerbation to identify modifiable factors leading to hospitalization. Methods. The study was conducted in 14 pediatric units and included children 3–17 years of age who were hospitalized for an asthma exacerbation. The present analysis covers 498 children with known asthma. Staff physicians used a standardized questionnaire to collect data. Asthma history came from a parental interview and included usual asthma care, frequency of symptoms and quick-relief medication use in the previous month, frequency of exacerbations and number of unscheduled healthcare visits during the past year, and prior asthma-related hospitalizations. Results. More than half the children had previously been hospitalized for an exacerbation, 42% used continuous inhaled corticosteroids, and 57% had a regular follow-up for asthma. Asthma had been well controlled over the past year for 11%, 12% had experienced exacerbations during the past year but that had been optimally controlled during the previous month, and 11% had recently become poorly controlled (infrequent exacerbations in the previous year and non-optimal control in the previous month). The remaining 327 children (66%) were consistently poorly controlled (non-optimal asthma control in the previous month and frequent exacerbations over the previous year). Among this group, 69% had at least one of the following preventable risk factors for hospitalization: no regular controller therapy (49%), no asthma action plan (40%), or no follow-up for asthma (35%). Conclusions. Two-thirds of the children with asthma hospitalized for an exacerbation had been consistently poorly controlled during the previous year. They were frequently undertreated and insufficiently educated about asthma. Further efforts are needed to improve asthma treatment and education in France.