The ontogeny of airway macrophages (AMs) in human lung and their contribution to disease are poorly mapped out. In mice, aging is associated with an increasing proportion of peripherally, as opposed to perinatally derived AMs. We sought to understand AM ontogeny in human lung during healthy aging and after transplant. We characterized monocyte/macrophage populations from the peripheral blood and airways of healthy volunteers across infancy/childhood (2–12 yr), maturity (20–50 yr), and older adulthood (>50 yr). Single-cell RNA sequencing (scRNA-seq) was performed on airway inflammatory cells isolated from sex-mismatched lung transplant recipients. During healthy aging, the proportions of blood and bronchoalveolar lavage (BAL) classical monocytes peak in adulthood and decline in older adults. scRNA-seq of BAL cells from lung transplant recipients indicates that after transplant, the majority of AMs are recipient derived. These data show that during aging, the peripheral monocyte phenotype is consistent with that found in the airways and, furthermore, that the majority of human AMs after transplant are derived from circulating monocytes.

Children are less likely than adults to suffer severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while influenza A H1N1 severity is comparable across ages except for the very young or elderly. Airway epithelial cells play a vital role in the early defence against viruses via their barrier and immune functions. We investigated viral replication and immune responses in SARS-CoV-2-infected bronchial epithelial cells from healthy paediatric (n = 6; 2.5–5.6 years old) and adult (n = 4; 47–63 years old) subjects and compared cellular responses following infection with SARS-CoV-2 or Influenza A H1N1. While infection with either virus triggered robust transcriptional interferon responses, including induction of type I (IFNB1) and type III (IFNL1) interferons, markedly lower levels of interferons and inflammatory proteins (IL-6, IL-8) were released following SARS-CoV-2 compared to H1N1 infection. Only H1N1 infection caused disruption of the epithelial layer. Interestingly, H1N1 infection resulted in sustained upregulation of SARS-CoV-2 entry factors FURIN and NRP1. We did not find any differences in the epithelial response to SARS-CoV-2 infection between paediatric and adult cells. Overall, SARS-CoV-2 had diminished potential to replicate, affect morphology and evoke immune responses in bronchial epithelial cells compared to H1N1.

Introduction: Half of all children will experience an episode of wheezing by their sixth birthday and acute episodes of wheezing in preschool children account for the majority of all childhood hospital admissions for wheeze. Recurrent preschool wheezing associates with early loss of lung function and a life-long impact on lung health. Areas covered: We reviewed the literature on PubMed from August 2010-2020 focussing on factors associated with wheeze inception and persistence, paying specific attention to mechanistic studies that have investigated the impact of early life exposures in shaping immune responses in children with underlying susceptibility to wheezing. In particular, the role of early allergen sensitization, respiratory infections, and the impact of the environment on shaping the airway microbiome and resulting immune responses are discussed. Expert opinion: There is an abundance of associative data showing the role of in utero and postnatal factors influencing wheeze onset and persistence. However, mechanistic and stratified, biomarkerbased interventional studies that confirm these associations are now needed if we are to impact the significant healthcare burden resulting from preschool wheezing disorders.

Asthma is a common disease in childhood with a minority of affected children having severe therapy-resistant asthma (STRA). Children with STRA can be differentiated from those with mild-moderate disease by greater allergic sensitization, increased eosinophilic airway inflammation, increased airway remodelling and reduced corticosteroid responsiveness. The aetiology of STRA in children is multifactorial but allergy seems to play a key role. Many children with asthma have coexisting allergic disease, and severe rhinitis seems to be an important driver of STRA in children. Allergies to foods, moulds, pollen and pets have also been associated with severe asthma exacerbations. Identifying allergens that are driving asthma symptoms in children with STRA may provide additional strategies for improving their disease control. Avoidance strategies may be possible. Additional monoclonal antibody therapy with Omalizumab or Mepolizumab may be helpful in children with clinically important polysensitization.

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Primary Subject area Social Paediatrics Background The novel coronavirus (COVID-19) pandemic is a major global threat that emerged in 2020. Many countries have enacted policies such as mandatory school closures, business closures, and self-quarantining to keep people at home and prevent further spread of the virus. Previous research has shown that pandemics and subsequent disease containment measures negatively affect children and families, both psychosocially and economically. Objectives The current study explores the potential psychosocial impacts of the COVID-19 pandemic and subsequent disease containment measures on a number of domains (employment/business, education, finances, medical care, access to medication, technology, children/family, access to community services) through an online survey. The current abstract focuses on the emotional well-being of children and how families have been affected by the restrictions and changes related to the COVID-19 pandemic. Design/Methods Participants were asked to complete an online survey through a secure portal. The survey consisted of questions about household demographics and socio-economic status (SES), as well as five psychometric scales measuring satisfaction with life, psychological well-being, anxiety, depression, and substance use, and specific questions about how the COVID-19 pandemic has impacted respondents’ daily lives in the previously identified domains. This is the first of four longitudinal surveys that will be conducted throughout this study. Results A total of 571 participants completed the survey. Of these participants, 41.3% identified as being a parent or guardian with children under 18. The focus of this abstract is the subset of respondents with children. Roughly three quarters of participants identified that their children were emotionally impacted by COVID-19, the school closures, or missing friends or family (Yes = 46.6%; Somewhat = 30.5%). Parents also reported loss of access to childcare, disruptions to their visits with their children living outside the home, and feeling like they could not access timely medical care for their children. Demographic information and other relevant responses and information can be found in Tables 1 and 2, respectively. Conclusion The impacts of the COVID-19 pandemic will be felt for years to come and will shape an entire generation of children. Even in the current sample, which consisted largely of individuals from medium-high SES households, most reported that children had been impacted emotionally. Understanding and mitigating the impact on children and adapting resources in the short term and the long-term to meet the growing needs of our communities must be top priorities for pediatricians and community service providers.

Allergic asthma generally starts during early life and is linked to significant tissue remodelling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLS), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas. Central to the blood vessel structure, the loss of pericyte coverage was driven by mast cell (MCs) proteases, such as tryptase, that can induce pericyte retraction and loss of the critical adhesion molecule N-Cadherin. Furthermore, spatial transcriptomics of paediatric asthmatic endobronchial biopsies revealed intense remodelling associated with increased expression of MC proteases in regions enriched in blood vessels. These data provide previously unappreciated insights into the pathophysiology of allergic asthma with potential long-term vascular defects.