New perspectives of biological therapy for severe asthma in adults and adolescents.

Severe asthma is associated with increased morbidity, mortality, healthcare costs and impaired quality of life. Asthma is no longer considered as a single entity but as a heterogeneous disease with different clinical presentations (phenotypes) and variable underlying mechanistic biological pathways (endotypes). Two different endotypes are based on the inflammatory Type 2 T-helper response: T2-high and T2-low. The understanding of these endotypes has revolutionised the management of severe asthma. Recent guidelines from the 2019 European Respiratory Society/American Thoracic Society (ERS/ATS) and Global Initiative for Asthma (GINA) 2021 specifically address the diagnosis and the management of severe asthma in adults, but less evidence exists for the paediatric population. Presently, five biologics for the treatment of severe asthma are approved, i.e., omalizumab (anti-IgE antibody), mepolizumab and reslizumab (anti-IL-5 antibody), benralizumab (anti-IL-5 receptor antibody) and dupilumab (anti-IL-4 receptor alpha antibody). This article reviews the pathological mechanisms of severe asthma, clinical biomarkers related to the T2-high endotype, and their use for the prediction of the severity of the disease and response to biological therapy. Furthermore, future developments of biologics for severe asthma are presented.

Successful home respiratory polygraphy to investigate sleep-disordered breathing in children.

OBJECTIVE: Sleep-disordered breathing (SDB) in children is common. Interest in sleep tests, such as polygraphy (PG), which can be performed in a non-attended setting, are gaining is increasing. PG has, however, been little studied in children with co-morbidities other than obstructive sleep apnea (OSA), and in particular, if performed in a non-attended setting. We report on the feasibility and interpretability of implementing PGs at home versus in hospital. METHODS: PGs were analyzed according to the setting (hospital or home) and sequence (initial or subsequent) in which they were performed. Non-interpretability was defined as absent or unreliable oxygen saturation by pulse oximetry (SpO2), or airflow and respiratory inductance plethysmography flow trace signals during the time analyzed. RESULTS: We retrospectively analyzed 400 PGs; 332/400 were initial PGs. Indications were: suspected OSA (65%), obesity (13%), craniofacial malformations (5%), neuromuscular disease (4%), and other (13%) which included prematurity. 16% were recorded in hospitals and 84% at home. The mean age was 5.7 ± 5.8 years and 7.3 ± 4.5 years for the hospital and home groups, respectively. Interpretability was similar in both settings (87%). In the 68 subsequent PGs, interpretability was 84% when performed for follow-up and 96% when repeated for non-interpretability. Non-interpretability was predominantly due to a failure of the SpO2 channel. CONCLUSIONS: PG performed at home is both feasible and interpretable for a variety of indications. Non-interpretability was not predictable in association with the setting, anthropometric data, or indication, independently of the sequence (initial or subsequent PG) in which the parameters were analyzed.

A disease model for wheezing disorders in preschool children based on clinicians' perceptions.

BACKGROUND: Wheezing disorders in childhood vary widely in clinical presentation and disease course. During the last years, several ways to classify wheezing children into different disease phenotypes have been proposed and are increasingly used for clinical guidance, but validation of these hypothetical entities is difficult. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to develop a testable disease model which reflects the full spectrum of wheezing illness in preschool children. We performed a qualitative study among a panel of 7 experienced clinicians from 4 European countries working in primary, secondary and tertiary paediatric care. In a series of questionnaire surveys and structured discussions, we found a general consensus that preschool wheezing disorders consist of several phenotypes, with a great heterogeneity of specific disease concepts between clinicians. Initially, 24 disease entities were described among the 7 physicians. In structured discussions, these could be narrowed down to three entities which were linked to proposed mechanisms: a) allergic wheeze, b) non-allergic wheeze due to structural airway narrowing and c) non-allergic wheeze due to increased immune response to viral infections. This disease model will serve to create an artificial dataset that allows the validation of data-driven multidimensional methods, such as cluster analysis, which have been proposed for identification of wheezing phenotypes in children. CONCLUSIONS/SIGNIFICANCE: While there appears to be wide agreement among clinicians that wheezing disorders consist of several diseases, there is less agreement regarding their number and nature. A great diversity of disease concepts exist but a unified phenotype classification reflecting underlying disease mechanisms is lacking. We propose a disease model which may help guide future research so that proposed mechanisms are measured at the right time and their role in disease heterogeneity can be studied.

Bird breeder's disease: a rare diagnosis in young children.

UNLABELLED: Bird breeder's lung disease is the most common form of hypersensitivity pneumonitis and is a rare entity in young children. We report three cases of children under 7 years of age in whom this diagnosis was confirmed early in the course of the disease. Three children aged 4.4 to 6.5 years presented with dry cough lasting for more than 1 month, dyspnoea, variable loss of appetite, weight loss, fatigue, fever and mild signs of respiratory distress. Chest X-ray films and CT scans showed a bilateral micronodular infiltrate. All three patients had strongly suggestive bronchoalveolar lavage fluid findings with lymphocytosis; two had elevated cell counts and decreased CD4/CD8 ratios. Lung biopsy confirmed the diagnosis in all children. Contact with allergens was identified in all children: two had spent holidays close to a farm in the previous month and one was living next to a pigeon house. In all children, avian precipitins were positive. The symptoms rapidly resolved after allergen avoidance and treatment with oral prednisone. Corticoid treatment was given between 11 and 15 weeks. One child relapsed and required long-term low-dose corticotherapy for 1 year. Lung function tests were normal in all three patients, 3.9 to 5.7 years after diagnosis. CONCLUSION: Bird breeder's lung disease is a rare entity but should be considered in young children presenting long lasting cough. While rapid allergen exclusion and start of treatment can avoid the evolution into irreversible lung fibrosis, clinical and biological evolution should be monitored carefully even after stopping corticoid treatment because of the possibility of relapse.