Pro‐inflammatory mediator responses from neonatal airway epithelial cells and early childhood wheeze

Turner, Steven; Miller, David; Walsh, Garry Michael; Scaife, Alison; Power, Ultan F.; Shields, Michael; Devereux, Graham

doi:10.1002/ppul.23915

Cited by 7 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are limited data on airway epithelial cell function at birth and later wheeze outcomes. In one study, nasal epithelial cells were harvested in newborns as a surrogate for the lower airway (47). They were followed up by parental questionnaire to determine wheeze outcomes.…”

Section: The First Steps: Episodic Viral Wheezementioning

confidence: 99%

Cytokines and Chemokines as Biomarkers of Future Asthma

Bush

2019

Front. Pediatr.

View full text Add to dashboard Cite

Antenatal and preschool factors are key in determining the progression to pre-school wheeze and eosinophilic school age asthma. The conventional view of eosinophilic asthma is that airway inflammation is the fundamental underlying abnormality, and airway inflammation and hyper-responsiveness are secondary; in fact, these three are parallel processes. Very early structural changes, independent of inflammation and infection, are associated with early airway hyper-responsiveness and later adverse respiratory outcomes. There is a bidirectional relationship between structural airway wall changes and airway inflammation, with airway contraction per se leading to the release of growth factors, and inflammatory pathways promoting airway remodeling. Early viral infection (and increasingly being appreciated, bacterial infection) is important in wheeze outcomes. There is evidence of abnormal immune function including cytokine release before the onset of viral infections. However, viral infections may also have prolonged effects on the host immune system, and the evidence for beneficial and adverse effects of viral infection is conflicting. In older children and adults, asthmatic epithelial cells show impaired interferon responses to viral infection, but only in the presence of uncontrolled type 2 inflammation, implying these are secondary phenomena. There are also compelling data relating the innate immune system to later asthma and atopy, and animal studies suggest that the effects of a high endotoxin, microbiologically diverse environment may be modulated via the epithelial alarmin IL-33. Whereas, previously only viral infection was thought to be important, early bacterial colonization of the upper airway is coming to the fore, associated with a mixed pattern of TH1/TH2/TH17 cytokine secretion, and adverse long term outcomes. Bacterial colonization is probably a marker of a subtle immune deficiency, rather than directly causal. The airway and gut microbiome critically impacts the development of Type 2 inflammatory responses. However, Type 2 inflammatory cytokines, which are critical both to progression from pre-school wheeze to eosinophilic asthma, and sustaining the eosinophilic asthmatic state, are not implicated in the very early development of the disease. Taken together, the evidence is that the earliest cytokine and chemokine signals will come from the study of bronchial epithelial cell function and their interactions with viruses and the microbiome.

show abstract

Section: The First Steps: Episodic Viral Wheezementioning

confidence: 99%

Cytokines and Chemokines as Biomarkers of Future Asthma

Bush

2019

Front. Pediatr.

View full text Add to dashboard Cite

show abstract

“…Impaired epithelial antiviral responses, with reduced interferon-β production and increased viral replication in response to human rhinovirus (HRV) [52] and respiratory syncytial virus (RSV) [53] infection has also been shown in children with wheeze/asthma in vitro. Similar responses in airway epithelial cells sampled from neonates in the first 48 hours of life prior to wheeze onset [54] suggest a potentially important role of altered airway epithelial cell function in the development of wheezing. One of the characteristic pathological features of established asthma, apparent in school-age children, is airway remodeling.…”

Section: The Airway Epithelium and Structural Cells In Preschool Wheezementioning

confidence: 81%

Factors and mechanisms contributing to the development of preschool wheezing disorders

Bonner

Scotney

Saglani

2021

Expert Review of Respiratory Medicine

View full text Add to dashboard Cite

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.

show abstract

“…Airway epithelial cells. Neonatal cells will be cultured at air liquid interface to achieve a differentiated epithelial cell layer and, as previously 12 , responses to common environmental exposures will be compared between those who have asthma symptoms and those who have no asthma symptoms by three years of age. RNA will also be extracted from cells and a particular focus will be genes involved in tissue proliferation, repair and remodelling.…”

Section: Methodsmentioning

confidence: 99%

“…Two systematic reviews have described many differences between the characteristics of AEC from children with and without asthma 10 , 11 . One proof-of-concept study described differences in neonatal nasal AEC function for individuals who went on to have asthma symptoms at age four years compared to those who did not 12 . This study 12 also observed that not all individuals with abnormal neonatal AEC function went on to have asthma symptoms, suggesting that asthma requires both abnormal neonatal AEC function and at least one other factor.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma? A description of the protocol for the Breathing Together study

Turner¹,

Čustović²,

Ghazal³

et al. 2018

Wellcome Open Res

Self Cite

View full text Add to dashboard Cite

Background. Childhood asthma is a common complex condition whose aetiology is thought to involve gene-environment interactions in early life occurring at the airway epithelium, associated with immune dysmaturation. It is not clear if abnormal airway epithelium cell (AEC) and cellular immune system functions associated with asthma are primary or secondary. To explore this, we will (i) recruit a birth cohort and observe the evolution of respiratory symptoms; (ii) recruit children with and without asthma symptoms; and (iii) use existing data from children in established STELAR birth cohorts. Novel pathways identified in the birth cohort will be sought in the children with established disease. Our over-arching hypothesis is that epithelium function is abnormal at birth in babies who subsequently develop asthma and progression is driven by abnormal interactions between the epithelium, genetic factors, the developing immune system, and the microbiome in the first years of life. Methods. One thousand babies will be recruited and nasal AEC collected at 5-10 days after birth for culture. Transcriptomes in AEC and blood leukocytes and the upper airway microbiome will be determined in babies and again at one and three years of age. In a subset of 100 individuals, AEC transcriptomes and microbiomes will also be assessed at three and six months. Individuals will be assigned a wheeze category at age three years. In a cross sectional study, 300 asthmatic and healthy children aged 1 to 16 years will have nasal and bronchial AEC collected for culture and transcriptome analysis, leukocyte transcriptome analysis, and upper and lower airway microbiomes ascertained. Genetic variants associated with asthma symptoms will be confirmed in the STELAR cohorts. Conclusions. This study is the first to comprehensively study the temporal relationship between aberrant AEC and immune cell function and asthma symptoms in the context of early gene-microbiome interactions.

show abstract

Pro‐inflammatory mediator responses from neonatal airway epithelial cells and early childhood wheeze

Abstract: Background: Airway epithelial cell (AEC) function differs between children with and

Cited by 7 publications

References 27 publications

Cytokines and Chemokines as Biomarkers of Future Asthma

Cytokines and Chemokines as Biomarkers of Future Asthma

Factors and mechanisms contributing to the development of preschool wheezing disorders

Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma? A description of the protocol for the Breathing Together study

Contact Info

Product

Resources

About