The Role of Interferons in Driving Susceptibility to Asthma Following Bronchiolitis: Controversies and Research Gaps

Bronchiolitis is the most common cause of hospitalization in infancy and is associated with a higher risk for the development of childhood asthma. However, not all children hospitalized with bronchiolitis will develop asthma. The mechanisms underlying asthma development following bronchiolitis hospitalization are complex. Immune responses to respiratory viruses may underlie both bronchiolitis severity and long-term sequela (such as asthma). Interferons (IFNs) are important components of innate immune responses to respiratory viruses and could influence both asthma development and asthma exacerbations. However, the nature of the relationship between interferon production and wheezing illnesses is controversial. For example, low peripheral blood IFN responses at birth have been linked with recurrent wheeze and asthma development. In contrast, there is evidence that severe illnesses (e.g., hospitalization for bronchiolitis) are associated with increased IFN responses during acute infection (bronchiolitis hospitalization) and a higher risk for subsequent asthma diagnosis. Furthermore, mechanistic studies suggest that bronchial epithelial cells from asthmatic children have impaired IFN responses to respiratory viruses, which may enable increased viral replication followed by exaggerated secondary IFN responses. This review aims to discuss controversies around the role of IFNs as drivers of susceptibility to asthma development following bronchiolitis hospitalization. Past evidence from both mechanistic and cohort studies are discussed. We will highlight knowledge gaps that can inform future research study design.</p

European Respiratory Society Statement on preschool wheezing disorders: updated definitions, knowledge gaps, and proposed future research directions.

Since the publication of the European Respiratory Society (ERS) Task Force reports on the management of preschool wheezing in 2008 and 2014, a large body of evidence has accumulated suggesting the clinical phenotypes that were proposed, episodic (viral) wheezing and multiple-trigger wheezing, do not relate to underlying airway pathology and may not help determine response to treatment. Specifically, using clinical phenotypes alone may no longer be appropriate, and new approaches that can be used to inform clinical care are needed for future research. This ERS Task Force reviewed the literature published after 2008 related to preschool wheezing and has suggested the criteria used to define wheezing disorders in preschool children should include age of diagnosis (0 to &lt;6 years), confirmation of wheezing on at least one occasion, and more than one episode of wheezing ever.Furthermore, diagnosis and management may be improved by identifying treatable traits, including inflammatory biomarkers (blood eosinophils, aeroallergen sensitisation) associated with type-2 immunity and differential response to inhaled corticosteroids, lung function parameters, and airway infection. However, more comprehensive use of biomarkers/treatable traits in predicting the response to treatment requires prospective validation. There is evidence that specific genetic traits may help guide management, but these must be adequately tested. In addition, the Task Force identified an absence of caregiver-reported outcomes, caregiver/self-management options, and features that should prompt specialist referral for this age group. Priorities for future research include a focus on identifying i) mechanisms driving preschool wheezing, ii) biomarkers of treatable traits and efficacy of interventions in those without allergic sensitisation/eosinophilia, iii) the need to include both objective outcomes and caregiver-reported outcomes in clinical trials, iv) the need for a suitable action plan for children with preschool wheezing and v) a definition of severe/difficult-to-treat preschool wheezing

Respiratory virus type to guide predictive enrichment approaches in the management of the first episode of bronchiolitis: A systematic review

It has become clear that severe bronchiolitis is a heterogeneous disease; even so, current bronchiolitis management guidelines rely on the one-size-fits-all approach regarding achieving both short-term and chronic outcomes. It has been speculated that the use of molecular markers could guide more effective pharmacological management and achieve the prevention of chronic respiratory sequelae. Existing data suggest that asthma-like treatment (systemic corticosteroids and beta2-agonists) in infants with rhinovirus-induced bronchiolitis is associated with improved short-term and chronic outcomes, but robust data is still lacking. We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane’s Library to identify eligible randomized controlled trials to determine the efficacy of a personalized, virus-dependent application of systemic corticosteroids in children with severe bronchiolitis. Twelve studies with heterogeneous methodology were included. The analysis of the available results comparing the respiratory syncytial virus (RSV)-positive and RSV-negative children did not reveal significant differences in the associatons between systemic corticosteroid use in acute episode and duration of hospitalization (short-term outcome). However, this systematic review identified a trend of the positive association between the use of systematic corticosteroids and duration of hospitalization in RSV-negative infants hospitalized with the first episode of bronchiolitis (two studies). This evidence is not conclusive. Taken together, we suggest the design for future studies to assess the respiratory virus type in guiding predictive enrichment approaches in infants presenting with the first episode of bronchiolitis. </p

ERS International Congress 2023:highlights from the Paediatrics Assembly

Respiratory health in children is essential for general wellbeing and healthy development in the short and long term. It is well known that many respiratory diseases in adulthood have their origins in early life, and therefore research on prevention of respiratory diseases and management of children with respiratory diseases will benefit patients during the full life course. Scientific and clinical advances in the field of respiratory health are moving at a fast pace. This article summarises some of the highlights in paediatric respiratory medicine presented at the hybrid European Respiratory Society (ERS) International Congress 2023 which took place in Milan (Italy). Selected sessions are summarised by Early Career Members of the Paediatrics Assembly (Assembly 7) under the supervision of senior ERS officers, and cover a wide range of research areas in children, including respiratory physiology and sleep, asthma and allergy, cystic fibrosis, respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology and bronchology.</p

ERS International Congress 2021: highlights from the Paediatric Assembly

In this review, Early Career Members of the European Respiratory Society (ERS) and the Chairs of the ERS Assembly 7: Paediatrics present the highlights in paediatric respiratory medicine from the ERS International Congress 2021. The eight scientific Groups of this Assembly cover respiratory physiology and sleep, asthma and allergy, cystic fibrosis (CF), respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology, bronchology, and lung and airway development. We here describe new developments in lung function testing and sleep-disordered breathing diagnosis, early life exposures affecting pulmonary function in children and effect of COVID-19 on sleep and lung function. In paediatric asthma, we present the important role of the exposome in asthma development, and how biologics can provide better outcomes. We discuss new methods to assess distal airways in children with CF, as some details remain blind when using the lung clearance index. Moreover, we summarise the new ERS guidelines for bronchiectasis management in children and adolescents. We present interventions to reduce morbidity and monitor pulmonary function in newborns at risk of bronchopulmonary dysplasia and long-term chronic respiratory morbidity of this disease. In respiratory epidemiology, we characterise primary ciliary dyskinesia, identify early life determinants of respiratory health and describe the effect of COVID-19 preventive measures on respiratory symptoms. Also, we describe the epidemiology of interstitial lung diseases, possible consequences of tracheomalacia and a classification of diffuse alveolar haemorrhage in children. Finally, we highlight that the characterisation of genes and pathways involved in the development of a disease is essential to identify new biomarkers and therapeutic targets

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Current data indicate that the “bronchiolitis” diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)-induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV-specific monoclonal antibody is available; (b) rhinovirus-induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2-year-old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor.</p

Research needs in allergy: an EAACI position paper, in collaboration with EFA

Abstract In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21 st century. The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients&apos; Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients&apos; organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels. Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein

The genomic signature of human rhinoviruses A, B and C.

Human rhinoviruses are single stranded positive sense RNA viruses that are presented in more than 50% of acute upper respiratory tract infections. Despite extensive studies on the genetic diversity of the virus, little is known about the forces driving it. In order to explain this diversity, many research groups have focused on protein sequence requirements for viable, functional and transmissible virus but have missed out an important aspect of viral evolution such as the genomic ontology of the virus. This study presents for the first time the genomic signature of 111 fully sequenced HRV strains from all three groups HRV-A, HRV-B and HRV-C. We observed an HRV genome tendency to eliminate CpG and UpA dinucleotides, coupling with over-representation of UpG and CpA. We propose a specific mechanism which describes how rapid changes in the HRV genomic sequence can take place under the strict control of conservation of the polypeptide backbone. Moreover, the distribution of the observed under- and over-represented dinucleotides along the HRV genome is presented. Distance matrice tables based on CpG and UpA odds ratios were constructed and viewed as heatmaps and distance trees. None of the suppressions can be attributed to codon usage or in RNA secondary structure requirements. Since viral recognition is dependent on RNA motifs rich in CpG and UpA, it is possible that the overall described genome evolution mechanism acts in order to protect the virus from host recognition