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Background: It is unclear whether sensitization patterns differentiate children with severe recurrent wheeze (SRW)/severe asthma (SA) from those with non-severe recurrent wheeze (NSRW)/non-severe asthma (NSA). Our objective was to determine whether sensitization patterns can discriminate between children from the French COBRAPed cohort with NSRW/NSA and those with SRW/SA., Methods: IgE to 112 components (c-sIgE) (ImmunoCAP® ISAC) were analyzed in 125 preschools (3-6 years) and 170 school-age children (7-12 years). Supervised analyses and clustering methods were applied to identify patterns of sensitization among children with positive c-sIgE., Results: We observed c-sIgE sensitization in 51% of preschool and 75% of school-age children. Sensitization to house dust mite (HDM) components was more frequent among NSRW than SRW (53% vs. 24%, p < .01). Sensitization to non-specific lipid transfer protein (nsLTP) components was more frequent among SA than NSA (16% vs. 4%, p < .01) and associated with an FEV1/FVC < -1.64 z-score. Among sensitized children, seven clusters with varying patterns were identified. The two broader clusters identified in each age group were characterized by "few sensitizations, mainly to HDM." One cluster (n = 4) with "multiple sensitizations, mainly to grass pollen, HDM, PR-10, and nsLTP" was associated with SA in school-age children., Conclusions: Although children with wheeze/asthma display frequent occurrences and high levels of sensitization, sensitization patterns did not provide strong signals to discriminate children with severe disease from those with milder disease. These results suggest that the severity of wheeze/asthma may depend on both IgE- and non-IgE-mediated mechanisms., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Rationale: Children with preschool wheezing represent a very heterogeneous population with wide variability regarding their clinical, inflammatory, obstructive, and/or remodeling patterns. We hypothesized that assessing bronchial remodeling would help clinicians to better characterize severe preschool wheezers. Objectives: The main objective was to identify bronchial remodeling-based latent classes of severe preschool wheezers. Secondary objectives were to compare cross-sectional and longitudinal clinical and biological data between classes and to assess the safety of bronchoscopy. Methods: This double-center prospective study (NCT02806466) included severe preschool wheezers (1-5 yr old) requiring fiberoptic bronchoscopy. Bronchial remodeling parameters (i.e., epithelial integrity, reticular basement membrane [RBM] thickness, mucus gland, fibrosis and bronchial smooth muscle [BSM] areas, the density of blood vessels, and RBM-BSM distance) were assessed and evaluated by latent class analysis. An independent cohort of severe preschool wheezers (NCT04558671) was used to validate our results. Measurements and Main Results: Fiberoptic bronchoscopy procedures were well tolerated. A two-class model was identified: Class BR1 was characterized by increased RBM thickness, normalized BSM area, the density of blood vessels, decreased mucus gland area, fibrosis, and RBM-BSM distance compared with Class BR2. No significant differences were found between classes in the year before fiberoptic bronchoscopy. By contrast, Class BR1 was associated with a shorter time to first exacerbation and an increased risk of both frequent (3 or more) and severe exacerbations during the year after bronchoscopy in the two cohorts. Conclusions: Assessing bronchial remodeling identified severe preschool wheezers at risk of frequent and severe subsequent exacerbations with a favorable benefit to risk ratio.

Background: Severe asthma (SA) in children is a complex, heterogeneous disease, associated with a considerable burden. However, factors influencing asthma severity are poorly described and may differ according to age., Objective: To determine whether factors associated with asthma severity differ between preschoolers with severe recurrent wheeze (SRW) and school-age children with SA., Methods: Data from the French multicenter prospective observational cohort of preschool (3-6 years) children with SRW and nonsevere recurrent wheeze (NSRW) and school-age (7-11 years) children with SA and nonsevere asthma (NSA) (Pediatric Cohort of Bronchial Obstruction and Asthma) were analyzed., Results: A total of 131 preschool children (92 SRW and 49 NSRW) and 207 school-age children (92 SA and 115 NSA) were included. In both univariable and multivariable analysis, SRW was associated with second-hand smoke exposure (multivariable analysis: odds ratio [95% CI], 29.8 [3.57-3910]) and exposure to mold/dampness at home (multivariable analysis: odds ratio [95% CI], 4.22 [1.25-18.2]) compared with NSRW. At school-age, history of atopic dermatitis and food allergy was more frequent in children with SA than in those with NSA. Multivariable analysis confirmed that SA was associated with a history of food allergy (odds ratio [95% CI], 5.01 [2.23-11.9])., Conclusions: Our data suggest that factors influencing asthma severity may differ according to age. In preschool children with SRW, second-hand smoke and exposure to mold are predominant, whereas associated allergic disorders are mainly involved in SA at school-age., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The influence of airway remodelling and inflammation in preschoolers with severe recurrent wheeze on asthma outcomes is poorly understood., Objective: To assess their association with asthma symptoms and lung function at school age., Methods: Preschoolers (38.4 months) initially investigated with bronchial biopsies were re-assessed for asthma symptoms and lung function at school age., Results: Thirty-six of 49 preschoolers (73.5%) were assessed at 10.9 years. Twenty-six (72.2%) had persistent asthma. Submucosal eosinophil counts were higher in children with severe exacerbations at school age than in those without (16/0.1 mm 2 [11.2-30.4] vs 8/0.1 mm 2 [2.4-17.6], P = .02), and correlated with the number of severe exacerbations (P = .04, r = .35). Submucosal neutrophil counts correlated with FEV1/FVC (P < .01, r = .47) and FEF 25-75% predicted (P = .02, r = .43). Airway smooth muscle (ASM) area correlated with FEV1/FVC (P < .01, r = .51). Vessel numbers negatively correlated with FEV1% predicted and FEV1/FVC (P = .03, r = -.42; P = .04, r = -.41; respectively) and FEF 25-75% predicted (P = .02, r = -.46)., Conclusion: Eosinophilic inflammation in preschoolers with severe recurrent wheeze might be predictive of future severe exacerbations, neutrophilia might be associated with better lung function. Changes in ASM and vascularity might affect lung function at school age., (© 2018 John Wiley & Sons Ltd.)

Asthma is characterized by airway hyperresponsiveness (AHR) and inflammation leading to airway remodeling (AR). In children, AR may occur very early prior to the age of 6 years. Treatments to prevent or reverse AR are unknown., Aim: We sought to determine (i) whether short allergenic sensitization at a young age in a mouse model may induce enhanced AR and inflammation compared to adults; (ii) the effect of Montelukast on such AR., Methods: Immature and adult Balb/c mice were sensitized and challenged with ovalbumin. AHR and AR were measured using cultured precision-cut lung slices and inflammation by bronchoalveolar lavage. Experiments were repeated after administration of Montelukast., Results: OVA-challenged mice developed AHR to methacholine regardless of age of first exposure to OVA. Young mice developed greater thickened basement membrane, increased smooth muscle mass, and increased area of bronchovascular fibrosis compared with adult mice. Cellular infiltrates in BAL differed depending upon animal age at first exposure with higher eosinophilia measured in younger animals. Montelukast decreased ASM mass, BAL cellularity., Conclusion: We provide thus evidence for a greater degree of AR after allergenic sensitization and challenge in younger mice versus adults. This study provides proof of concept that airway remodeling can be prevented and reversed in this case by anti-asthmatic drug Montelukast in this model., (© 2018 Wiley Periodicals, Inc.)

Background: Many asthmatic patients exhibit uncontrolled asthma despite high-dose inhaled corticosteroids (ICS). Airway epithelial cells (AEC) have distinct activation profiles that can influence ICS response., Objectives: A pilot study to identify gene expression markers of AEC dysfunction and markers of corticosteroid sensitivity in asthmatic and non-asthmatic control children, for comparison with published reports in adults., Methods: AEC were obtained by nasal brushings and primary submerged cultures, and incubated in control conditions or in the presence of 10 ng/ml TNFalpha, 10-8M dexamethasone, or both. RT-PCR-based expression of FKBP51 (a steroid hormone receptor signalling regulator), NF-kB, IL-6, LIF (an IL-6 family neurotrophic cytokine), serpinB2 (which inhibits plasminogen activation and promotes fibrin deposition) and porin (a marker of mitochondrial mass) were determined., Results: 6 patients without asthma (median age 11yr; min-max: 7-13), 8 with controlled asthma (11yr, 7-13; median daily fluticasone dose = 100 μg), and 4 with uncontrolled asthma (12yr, 7-14; 1000 μg fluticasone daily) were included. Baseline expression of LIF mRNA was significantly increased in uncontrolled vs controlled asthmatic children. TNFalpha significantly increased LIF expression in uncontrolled asthma. A similar trend was observed regarding IL-6. Dexamethasone significantly upregulated FKBP51 expression in all groups but the response was blunted in asthmatic children. No significant upregulation was identified regarding NF-kB, serpinB2 and porin., Conclusion: LIF and FKBP51 expression in epithelial cells were the most interesting markers of AEC dysfunction/response to corticosteroid treatment.

Introduction: Although guidelines recommend the prescription of written asthma action plans (WAAP), their use remains limited., Methods: A prospective survey was performed from 2013 to 2014. We interviewed respiratory physicians, paediatric respiratory physicians and allergologists taking care of asthmatic patients and practicing in the Aquitaine region of France, using computerized questionnaires, regarding their everyday practice in the use of WAAP., Results: A total of 59/143 (41%) clinicians, with a mean age of 47 years, participated in the study. A total of 41/59 (69.5%) were using a WAAP (12 different models with very inhomogeneous contents, mostly targeting symptoms only). WAAP prescribers were younger than non-prescribers, were more often female, working mostly in the Gironde area, with mixed hospital and private-based activity, and were paediatric-respiratory physicians or respiratory physicians. The severity of asthma had little influence on WAAP prescriptions., Conclusion: In the Aquitaine region, prescription of WAAPs remains inadequate and shows large disparities. WAAP users are mostly younger female specialists., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Mycoplasma pneumoniae has been implicated in asthma exacerbations and chronic asthma. A 2-year longitudinal study has been conducted to investigate the role of M. pneumoniae infections in 168 and 20 hospitalized children and adults, respectively, with asthma exacerbation compared with outpatients (88 children and 48 adults) with chronic asthma (without an exacerbation). The prevalence of Chlamydia pneumoniae and respiratory viruses was also assessed in these 2 populations., Methods: Lung function testing, blood sampling and microbiological testing (polymerase chain reaction, culture and serology) were performed for 256 children and 68 adults followed by a 7-week, follow-up visit with repeated blood sampling for serological testing and phone interviews at 6 and 12 months later., Results: M. pneumoniae infection was more prevalent in children with chronic asthma (13.6%) compared with children with exacerbation (7.1%), while the reverse was true in adults (6.3 vs. 10.0%, respectively). However, these differences were not statistically significant. Acute C. pneumoniae infection was identified in 3.9% of children and 7.4% adults. Children seen for chronic asthma were significantly more likely to be infected with C. pneumoniae than children hospitalized for an asthma exacerbation. Viruses were the most prevalent microorganisms detected in children with an asthma exacerbation. No differences in the outcome parameters were identified between M. pneumoniae-infected and noninfected patients., Conclusions: The present study suggests that M. pneumoniae does not play a direct role in the pathogenicity of acute or chronic asthma in most children.

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 μg 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.

In France, an annual seasonal influenza vaccination has been recommended since 2000 for patients suffering from chronic respiratory diseases, including asthma. Each year, a free influenza vaccination voucher is sent by the French Public Health Insurance authorities to patients with chronic respiratory disease, including severe asthma. In November 2006, this measure was extended to all asthmatic patients, irrespective of asthma severity. The present paper examines the 2006-2007 influenza vaccination coverage rate in 433 asthmatic children aged six to 17 years (mean age: 9.5 years; male: 61%) who consulted a pediatric pulmonologist between March and September 2007 in eight hospitals throughout France. The influenza vaccination coverage rate was 15.7% for the 2006-2007 season (13.9% for the 2005-2006 season and 10.9% for the 2004-2005 season). General practitioners vaccinated 72.1% of the children. Lack of information (42%) was the most frequently reported reason for non-vaccination. Free vouchers (received by 39.6% of the children) significantly increased the vaccination coverage rate (31% versus 5.9%; p < 0.001). In France, in 2006-2007, the influenza vaccination coverage rate in asthmatic children was far below the national public health objective to achieve for the year 2008 (at least 75%). Concerted action is needed to improve the influenza vaccination coverage rate in asthmatic children.

In France, annual seasonal influenza vaccination has been recommended since 2000 for patients suffering from chronic respiratory diseases, including asthma. Since 1988, each year from September to December, a free influenza vaccination voucher is sent by the French Public Health Insurance authorities to patients with chronic respiratory disease, including severe asthma. In November 2006, this measure was extended to all asthmatic patients, irrespective of asthma severity. The present paper examines the 2006-7 influenza vaccination coverage rate (VCR) in 433 asthmatic children aged 6 to 17 years (mean age: 9.5 years; male: 61%) who consulted a paediatric pulmonologist between March and September 2007 in eight hospitals throughout France. The influenza VCR was 15.7% for the 2006-7 season (13.9% for the 2005-6 season and 10.9% for the 2004-5 season). General practitioners vaccinated 72.1% of the children. "Lack of information" (42%) was the most frequently reported reason for non-vaccination. Vouchers (received by 39.6% of the children) significantly increased the VCR (31% versus 5.9%; p<0.001). In France, in 2006-7, the influenza VCR in asthmatic children was far below the national public health objective (at least 75% for the year 2008). Concerted action is needed to improve the influenza VCR in asthmatic children.

Unlabelled: The correct use of inhaler devices is important for the efficacy of the treatment of childhood asthma. Few studies have compared the use of inhaler devices in real life, in particular in children., Aim: To determine whether such devices were correctly used in asthmatic children within a primary care setting., Population and Methods: Three hundred and sixty-four children aged 5 to 18 years (mean+/-SD: 14.1+/-3.3) treated for at least 1 month by an inhaler device were included. During a routine visit to the doctor, the primary care physician assessed the childrens' handling of their current device, using a checklist established for each device from the package leaflet., Results: At least half of the patients made at least 1 error, regardless of the inhaler used. The best result was obtained with the Diskus (46% error-rate) and the worst with the pressurized metered-dose inhaler (pMDI) (78% error-rate). The rank order of increasing critical-error rate (at least 1 error) was as follows: Diskus (6%)

Human airway smooth muscle cells (HASMC) secrete fractalkine (FKN), a chemokine the concentration of which is increased in asthmatic patients. HASMC also induce mast cell chemotaxis, as a component of asthma inflammation. We therefore evaluated the role of smooth muscle-derived FKN in mast cell migration. We assessed the capacity of recombinant FKN to induce human mast cell chemotaxis. This effect implicates a calcium-independent pathway involving actin reorganization and protein kinase C-delta. We found that HASMC constitutively produce FKN, the synthesis of which is reinforced upon proinflammatory stimulation. Under basal experimental conditions, FKN production by HASMC is not sufficient to induce mast cell chemotaxis. However, pretreatment of mast cells with the neuropeptide vasoactive intestinal peptide (VIP) increases FKN potency to attract mast cells. Since we observed, in asthmatic patients, an increase in both FKN and VIP expression by airway smooth muscle and a positive correlation between VIP staining and mast cell infiltration of the smooth muscle layer, we conclude that HASMC-derived FKN may contribute to mast cell recruitment in asthma.

In order to understand the epidemiological aspects of chronic cough, we analysed 100 patients' files referred for chronic cough in five pediatric-pulmonology consultations. The patients had a chronic cough for more than 3 weeks. The distribution of causes was: asthma, 56%; upper airway disorders, 16%; psychogenic, 4%; whooping cough, 4%; Mycoplasma pneumoniae pulmonary infection, 3%; Chlamydia pneumoniae pulmonary infection, 1%; bronchiectasis, 1%. In 15% of cases two or more causes were associated; In most cases, the clinical characteristics of the cough are evident enough to establish a diagnosis with few secondary explorations. The prognosis is on the whole favourable.

The aims of this retrospective study were to (i) determine the risk of contamination of lower respiratory tract samples obtained during fiberoscopy in children; (ii) determine the incidence and profile of the bacterial flora of the lower respiratory tract in a selected group of asthmatic children at high risk for bacterial infection; and (iii) identify risk markers for such findings. In 29 asthmatic children, comparison of bacterial cultures of specimens obtained from the upper and, lower respiratory tracts showed that contamination was a possibility in only 3.4% (1/29) of cases. The results from bacterial samples obtained via flexible bronchoscopy in a further 273 consecutively investigated physician-diagnosed asthmatic children were analysed. Patients were selected for bronchoscopy if they had severe chronic asthma or in order to exclude other diseases able to provoke wheezing. Their mean (SD) and median ages were 32.2 (38.3) and 17.5 mo, respectively. The incidence of positive bacterial cultures was 12.1% (33/273 patients). Bacterial flora included H. influenzae (39.5%, 15/38), B. catarrhalis (23.7%, 9/38), Neisseria species (7.9%, 3/38), M. pneumoniae (7.9%, 3/38), P. non-aeruginosa (5.3%, 2/38) and P. aeruginosa (2.6%, 1/38). No clinical or radiological markers were significantly associated with lower respiratory tract bacterial infection. Large quantities of bacteria were present in the lower respiratory tracts of a substantial number of children (1/8) in this selected group of asthmatics. For the moment, however, the clinical implications of this finding remain unclear.

Therapy for asthma is being prescribed more frequently. However, asthma mortality remains high in many countries. Fatal outcome is not always related to inadequate follow-up. In this article we report that children with mild to moderate symptoms may present a fatal attack. Many factors are responsible for such an outcome: asphyxia +3 due to ventilation/perfusion mismatch and/or bronchospasm, cardiac failure, cardiac arrhythmia, intrinsic positive expiratory pressure, or metabolic disturbances (hypokalemia, for example). Such problems can occur in predisposed patients: it has been shown that the chemosensitivity to hypoxia and the perception of dyspnoea are altered in certain patients with near-fatal asthma. It is very important to identify children at risk of severe asthma and to organize care so as to optimize the management of such children.

Résumé: Bien que les corticostéroïdes inhalés (CSI) jouent un rôle central (traitement de première intention) dans le traitement de l’asthme de l’enfant, ils ne permettent pas d’obtenir un contrôle satisfaisant chez tous les asthmatiques. Selon les situations cliniques, le clinicien a la possibilité de prescrire les anti-récepteurs de leucotriènes (ARLT) en monothérapie, ou en association avec des CSI (± des bronchodilatateurs de longue durée d’action). Le choix du schéma thérapeutique dépend de plusieurs facteurs, dont l’âge et le sexe du patient, la réponse aux CSI, les co-morbidités, le phénotype d’asthme et le terrain, l’environnement, et le profil génotypique du patient. Les ARLT sont particulièrement intéressants chez le sujet asthmatique jeune, dans l’asthme à l’effort, s’accompagnant d’une rhinite allergique, à type de toux chronique, chez l’obèse, induit par l’aspirine, et/ou dans un contexte de tabagisme important. [ABSTRACT FROM AUTHOR]

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