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 compare the sensitization patterns between children with SRW/SA and NSRW/NSA from the French COBRAPed cohort. Methods: IgE to 112 components (c-sIgE) (ImmunoCAP® ISAC) were analyzed in 125 preschool (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<0.01). Sensitization to non-specific lipid transfer protein (nsLTP) components was more frequent among SA than NSA (16% vs 4%, p<0.01) and associated with a 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, the sensitization patterns did not clearly 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.

Introduction: Preschool wheeze is a public health issue, due to its high frequency and morbidity. When the disease is severe and uncontrolled, despite optimal treatment, explorations are needed. Patients and methods: We conducted a retrospective study at our tertiary asthma center in Rouen University Hospital, France. Each child under 3 years with severe uncontrolled preschool wheeze was admitted to a pediatric day hospital for a bronchoscopy. We collected the results of clinical, biological and radiological exams, and followed-up data at 1, 2 and 3 years (Y +1, Y +2, Y +3 respectively), to study the evolution of the disease, and identify factors of uncontrolled disease. Results: We included 135 patients; 63 (47%) were still followed-up in our center at Y +3. Median age at inclusion was 12 months. Thirty percent of patients still had severe uncontrolled wheeze at Y +3. Treatments were significantly decreased at Y +3 (p<0.001). A total IgE level higher than 7 kU/L was a factor in uncontrolled wheeze at Y +1, tobacco exposure (p<0.001) and female gender (p=0.05) were factors associated to the persistence of uncontrolled wheeze at Y +2, and a first case of bronchiolitis before 2 months old was a factor in uncontrolled disease at Y +3 (p=0.007). Discussion: Our study is unique in terms of its very young population, with very severe wheeze (80% of children included with a history of hospitalization, 8% in intensive care). Our therapeutic approach is original, enabling us to study the evolution of “therapeutic pressure” in the early years of this frequent disease, the pathophysiology of which is still poorly understood.

Background: Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasian population. Allergic bronchopulmonary aspergillosis (ABPA) is one of the severe complications of CF, on which diagnosis is based on symptoms and blood IgE levels. Many techniques of specific IgG levels measures are used, which signification is still unclear. We evaluated evolution of patients who presented a first aspergillosis IgG seroconversion. Methods: Monocentric pediatric case-control study led in Rouen, France. Every patient with a first aspergillosis IgG seroconversion was paired with a seronegative patient. Clinical data, functional respiratory investigations, CT-scan and biologic data were collected a year before (Y -1), a year after (Y +1) and at the moment of the first aspergillosis seroconversion. Results: 36 cases, paired with 36 controls. Median age was 8. Forced expiratory volume in 1 second was significantly lower at Y +1 (p=0,025) and Vital Capacity was significantly lower at Y 0 (p= 0.027) in the case-population. More respiratory exacerbations were observed in the case-population (p=0,047). Higher specific IgE against A. fumigatus levels were observed at Y 0 (p=0,014), Y -1 (p=0,001) and Y +1 (p=0,04) in the case-population. Total IgG were significantly higher at Y 0 in the case-population. On the CT-scan, bronchiectasis and pulmonary infiltrates were more important in the case-population (p=0,01 and p=0,003 respectively). Conclusion: Aspergillosis seroconversion is associated with changes of clinical, respiratory functional, biologic and radiologic parameters in CF population. Aspergillosis seroconversion is a milestone in the evolution of CF. A systematic research is needed, to evaluate actions to be taken.