ABSTRACT
INTRODUCTION: Periodic breathing (PB) is considered physiological in the neonatal period and usually disappears in the first months of life. There are few data available on persistent PB after the neonatal period. The objective of this study was to characterize infants born at term with persistent PB after the age of 1 month through polysomnography (PSG) performed during symptoms. METHODS: This retrospective case series included infants born at term between 2012 and 2021, without an underlying disease, who presented with symptoms of persistent PB during a PSG. Persistent PB was defined as more than 1 % of total sleep time (TST) of PB after 1 month of life, and PB was defined as a succession of at least three episodes of central apnea lasting more than 3 s and separated by less than 20 s of normal breathing. RESULTS: A total of 10 infants born at term were included. They underwent PSG for brief resolved unexplained events, desaturation, pauses in breathing, cyanosis, and/or signs of respiratory distress. The percentage of TST spent with PB was 18.1 % before 3 months of age (n = 7), and 4.7 % between 3 and 6 months of age (n = 10). During the first PSG, ≥3 % of desaturation events were observed in 77-100 % of the PB episodes. At the first PSG, nine of the 10 infants had an obstructive apnea-hypopnea index of >10/h and five of 10 infants had a central apnea index of >5/h. Gastroesophageal reflux (GER) was suspected in eight infants. All infants showed improvement in the initial symptoms during the first year of life. CONCLUSION: This study presents cases of persistent and symptomatic PB after 1 month of life in infants born at term. The interesting finding was the presence of obstructive sleep apnea syndrome and/or central apnea syndrome in the majority of children, along with GER.
Subject(s)
Polysomnography , Humans , Retrospective Studies , Male , Female , Infant , Infant, Newborn , Sleep Apnea Syndromes/diagnosis , Sleep Apnea, Central/diagnosis , Sleep Apnea, Central/therapyABSTRACT
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.
Subject(s)
Allergens , Asthma , Child , Child, Preschool , Animals , Humans , Immunoglobulin E , Asthma/diagnosis , Asthma/epidemiology , Pyroglyphidae , Dermatophagoides pteronyssinus , Respiratory SoundsABSTRACT
Background: Cardiac involvement is central in MIS-C and represents the main cause of morbidity. In this study, we aimed to assess myocardial damage in patients with MIS-C using cardiac magnetic resonance (CMR) during the acute phase, as well as left ventricular and atrial longitudinal strain on admission, at discharge, and after 3 months. Methods: We performed a single-center prospective cohort study and case-control study. Between September 2020 and February 2022, we enrolled 39 patients hospitalized for MIS-C at our center. We performed left ventricular and atrial longitudinal 2D strain analysis on admission and during follow-up; echocardiographic data were compared to a matched control population. Patients above 4 years old with increased troponin underwent CMR. Results: Of 24 patients (mean age: 8.2 ± 4.9 years) who underwent CMR, 14 (58%) presented myocardial edema and 6 (25%) late gadolinium enhancement (LGE). LGE was associated with older age (p < 0.01), increased BMI (p = 0.03), increased ferritin levels (p < 0.001), lower left ventricular (LV) ejection fraction (p < 0.001), LV longitudinal strain (p = 0.004), left atrial (LA) strain (p = 0.05), and prolonged hospital stay (p = 0.02). On admission, LV ejection fraction, LV longitudinal strain, and LA strain were impaired, but each improved gradually over time; LVEF was the fastest to recover, while global LV longitudinal strain was still impaired as compared to controls after 3 months (p = 0.01). Conclusion: Our study demonstrates that myocardial injury is present in a quarter of MIS-C patients, and impaired LA and LV myocardial deformation persist for at least several weeks after the acute phase. CMR and LV/LA strain could help us to individualize follow-up of MIS-C patients.
ABSTRACT
BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).
Subject(s)
Anaphylaxis , Desensitization, Immunologic , Peanut Hypersensitivity , Child, Preschool , Humans , Infant , Allergens/adverse effects , Anaphylaxis/etiology , Arachis/adverse effects , Desensitization, Immunologic/adverse effects , Desensitization, Immunologic/methods , Peanut Hypersensitivity/complications , Peanut Hypersensitivity/therapy , Administration, CutaneousABSTRACT
BACKGROUND: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. OBJECTIVE: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. METHODS: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. RESULTS: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4-CD8-) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. CONCLUSION: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.
Subject(s)
Immune System Diseases , Immunologic Deficiency Syndromes , Child , Humans , Autoimmunity/genetics , Cohort Studies , Gain of Function Mutation , Immunologic Deficiency Syndromes/genetics , Mutation , STAT3 Transcription Factor/genetics , Cell Proliferation , LymphocytesABSTRACT
BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1â s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
Subject(s)
Anti-Asthmatic Agents , Asthma , Child , Humans , Adult , Quality of Life , Reproducibility of Results , Disease Progression , Asthma/drug therapy , Outcome Assessment, Health Care , Anti-Asthmatic Agents/therapeutic useABSTRACT
The aim of the study was to describe the characteristics of children with neuromuscular diseases treated with long term noninvasive ventilation or continuous positive airway pressure in France. On June 1st 2019, 387 patients (63% boys, mean age 11.2 ± 5.5 years) were treated with long term noninvasive ventilation/continuous positive airway pressure. Thirty three percent of patients had spinal muscular atrophy, 30% congenital myopathy/dystrophy, 20% Duchenne muscular dystrophy, 7% Steinert myotonic dystrophy, and 9% other neuromuscular diseases. Ninety-four percent of patients were treated with long term noninvasive ventilation and 6% with continuous positive airway pressure. Treatment was initiated electively for 85% of patients, mainly on an abnormal overnight gas exchange recording (38% of patients). Noninvasive ventilation/continuous positive airway pressure was initiated during a respiratory exacerbation in 15% of patients. Mean duration of noninvasive ventilation/continuous positive airway pressure was 3.3 ± 3.1 years. Mean objective long term noninvasive ventilation/continuous positive airway pressure use was 8.0 ± 3.1 h/24. Spinal muscular atrophy, congenital myopathy/dystrophy, and Duchenne muscular dystrophy represented 83% of children with neuromuscular diseases treated with long term noninvasive ventilation in France. Screening for nocturnal hypoventilation was satisfactory as noninvasive ventilation /continuous positive airway pressure was predominantly initiated electively.
Subject(s)
Muscular Atrophy, Spinal , Muscular Dystrophy, Duchenne , Neuromuscular Diseases , Noninvasive Ventilation , Male , Child , Humans , Child, Preschool , Adolescent , Female , Continuous Positive Airway Pressure , Muscular Dystrophy, Duchenne/complications , Muscular Dystrophy, Duchenne/therapy , Neuromuscular Diseases/complications , Neuromuscular Diseases/therapyABSTRACT
Background: ROHHAD syndrome (Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation) is rare. Rapid-onset morbid obesity is usually the first recognizable sign of this syndrome, however a subset of patients develop ROHHAD syndrome without obesity. The prevalence of this entity is currently unknown. Alteration of respiratory control as well as dysautonomic disorders often have a fatal outcome, thus early recognition of this syndrome is essential. Material and methods: A retrospective, observational, multicenter study including all cases of ROHHAD without rapid-onset obesity diagnosed in France from 2000 to 2020. Results: Four patients were identified. Median age at diagnosis was 8 years 10 months. Median body mass index was 17.4 kg/m2. Signs of autonomic dysfunction presented first, followed by hypothalamic disorders. All four patients had sleep apnea syndrome. Hypoventilation led to the diagnosis. Three of the four children received ventilatory support, all four received hormone replacement therapy, and two received psychotropic treatment. One child in our cohort died at 2 years 10 months old. For the three surviving patients, median duration of follow-up was 7.4 years. Conclusion: ROHHAD syndrome without rapid-onset obesity is a particular entity, appearing later than ROHHAD with obesity. This entity should be considered in the presence of dysautonomia disorders without brain damage. Likewise, the occurrence of a hypothalamic syndrome with no identified etiology requires a sleep study to search for apnea and hypoventilation. The identification of ROHHAD syndrome without rapid-onset obesity is a clinical challenge, with major implications for patient prognosis.
ABSTRACT
Introduction: Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome is an underreported pediatric vascular disorder from the group of acrosyndromes. In children, these include paroxysmal acrosyndromes (Raynaud's phenomenon and chilblain-like lesions), permanent acrosyndromes (acrocyanosis), and transient acrosyndromes, in which their pathogeneses are associated with virus infections, Epstein-Barr virus, and, more recently, SARS-CoV-2, respectively. Methods: We reported a case of BASCULE syndrome associated with postural orthostatic tachycardia syndrome (POTS) and provided a narrative review of case reports describing the BASCULE syndrome in children. Moreover, we presented the results of a prospective practice survey that we performed in the French medical community. Results: A 14-years-old boy reported pruritic erythrocyanic lesions on the lower limbs, which occurred whenever he was in a standing position and fully resolved when he laid down. He reported asthenia and cramps. He presented a typical BASCULE syndrome associated with POTS confirmed by a tilt-test. Physical and vascular examinations were within the normal range. We identified 12 case reports, describing 21 pediatric cases since 2016. Most patients were adolescents between 12 and 19 years of age or were newborns. Furthermore, 20% of cases in the literature have presented POTS or orthostatic intolerance. Our survey among 95 French physicians confirmed that BASCULE syndrome is an underdiagnosed and under recognized disease in the general pediatric practice, at least in France. Among these physicians, 65% had already encountered patients with similar symptoms, but only 30% declared that they had knowledge of the BASCULE syndrome. Conclusion: The under-recognition of the clinical manifestations leads the patients to consult emergency rooms, with multiple unnecessary investigations performed. Therefore, we suggest that the diagnosis of BASCULE syndrome is based on clinical observations, without the need for laboratory tests, to avoid unnecessary health costs. We suggest physicians to perform a tilt-test when POTS is suspected.
ABSTRACT
BACKGROUND: Food allergy is a potentially life-threatening disease, affecting up to 10% of the pediatric population. OBJECTIVE: The aim of our study was to assess the health-related quality of life (HRQL) of food-allergic patients compared with the general population and patients with other chronic diseases with dietary or allergic burden, in a cross-sectional study. METHODS: We recruited patients aged 8-17 years diagnosed with food allergy and matched healthy controls recruited in schools. We also included patients with asthma, inflammatory bowel disease, celiac disease, diabetes, obesity, and eating disorders. We used the CHQ-CF87 questionnaire for generic HRQL assessment. Food allergy HRQL was also assessed using specific questionnaires: Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM). RESULTS: One hundred and thirty-five food-allergic children, 255 children with chronic diseases, and 463 healthy controls were included in the analyses. Food-allergic patients had a better HRQL than healthy controls in the Behavior (BE), Bodily Pain (BP), Family Activities (FA), and Mental Health (MH) domains and a worse HRQL in the General Health Perception (GH) domain (p = .048). Food-allergic patients exhibited a better HRQL than patients affected by other chronic diseases, notably diabetes. Although an epinephrine autoinjector had been prescribed to 87.4% of the food-allergic children, only 54.2% of them carried it at all times. CONCLUSION: Food-allergic patients display overall good HRQL compared with the general population and those with other diseases with daily symptoms and treatments, in line with recent improvements in food allergy management.
Subject(s)
Food Hypersensitivity , Quality of Life , Adolescent , Child , Cross-Sectional Studies , Humans , Mental Health , Surveys and QuestionnairesABSTRACT
OBJECTIVES: To understand how children perceive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in relation to public representations and to evaluate their interpretations. METHODS: Children's perceptions of SARS-CoV-2 were evaluated by asking 103 French children, aged 5 to 17 years old, first to draw a coronavirus and then to identify SARS-CoV-2 in a series of 16 images during summer 2020. RESULTS: One hundred three children were included in the study, either during outpatient visits at the hospital (in Marseille and Paris) or through the authors' social network, and were grouped in terms of age, parents' occupation, mode of recruitment, and recollection of having previously seen a representation of a coronavirus. Half of the children drew the coronavirus as circular in shape, and almost all included a crownlike feature. One-third of the drawings had anthropomorphic features. Although the pictorial representations of the virus were fairly accurate overall, the children's interpretations of the crownlike structure were imaginative. The explanations the children gave for their drawings were in some cases surprising. Among the 16 pictures they were shown, the children correctly identified those of SARS-CoV-2, other than the electron micrograph, in more than two-thirds of cases. CONCLUSIONS: Children of all ages, even the youngest, and both sexes had a relatively accurate perception of SARS-CoV-2, as evaluated through their drawings and their ability to recognize it among other pictures. The children's drawings of the coronavirus were colorful and had a less frightening tone than expected in the light of media coverage, suggesting that they had developed coping mechanisms.
Subject(s)
Art , Attitude to Health , SARS-CoV-2 , Adolescent , Child , Child, Preschool , Female , France , Humans , MaleABSTRACT
Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vß21.3 T cell receptor ß chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vß21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vß21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19/pathology , Receptors, Antigen, T-Cell, alpha-beta/immunology , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/pathology , Adult , Child , Child, Preschool , Cytokines/blood , HLA-DR Antigens/immunology , Humans , Lymphocyte Activation/immunology , SARS-CoV-2/immunologyABSTRACT
OBJECTIVE: To describe the characteristics of children treated with long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in France. DESIGN: Cross-sectional national survey. SETTING: Paediatric CPAP/NIV teams of 28 tertiary university hospitals in France. PATIENTS: Children aged <20 years treated with CPAP/NIV since at least 3 months on June 1st, 2019. INTERVENTION: An anonymous questionnaire was filled in for every patient. RESULTS: The data of 1447 patients (60% boys), mean age 9.8 ± 5.8 years were analysed. The most frequent underlying disorders were: upper airway obstruction (46%), neuromuscular disease (28%), disorder of the central nervous system (13%), cardiorespiratory disorder (7%), and congenital bone disease (4%). Forty-five percent of the patients were treated with CPAP and 55% with NIV. Treatment was initiated electively for 92% of children, while 8% started during an acute illness. A poly(somno)graphy (P(S)G) was performed prior to treatment initiation in 26%, 36% had a P(S)G with transcutaneous carbon dioxide monitoring (PtcCO2), while 23% had only a pulse oximetry (SpO2) with PtcCO2 recording. The decision of CPAP/NIV initiation during an elective setting was based on the apnea-hypopnea index (AHI) in 41% of patients, SpO2 and PtcCO2 in 25% of patients, and AHI with PtcCO2 in 25% of patients. Objective adherence was excellent with a mean use of 7.6 ± 3.2 h/night. Duration of CPAP/NIV was 2.7 ± 2.9 years at the time of the survey. CONCLUSION: This survey shows the large number of children treated with long term CPAP/NIV in France with numerous children having disorders other than neuromuscular diseases.
Subject(s)
Continuous Positive Airway Pressure , Noninvasive Ventilation , Adolescent , Age Factors , Airway Obstruction/therapy , Child , Child, Preschool , Continuous Positive Airway Pressure/statistics & numerical data , Cross-Sectional Studies , Female , France/epidemiology , Humans , Infant , Male , Noninvasive Ventilation/statistics & numerical data , Patient Compliance/statistics & numerical data , Sleep Apnea Syndromes/therapy , Surveys and Questionnaires , Time Factors , Young AdultABSTRACT
This is a Brighton Collaboration Case Definition of the term "Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A)" to be utilized in the evaluation of adverse events following immunization. The case definition was developed by topic experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2. The format of the Brighton Collaboration was followed, including an exhaustive review of the literature, to develop a consensus definition and defined levels of certainty. The document underwent peer review by the Brighton Collaboration Network and by selected expert external reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated into this final manuscript.
Subject(s)
COVID-19 , Adult , COVID-19 Vaccines , Child , Data Collection , Humans , Immunization/adverse effects , SARS-CoV-2 , Systemic Inflammatory Response SyndromeABSTRACT
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.