Air Pollution Relates to Airway Pathology in Children with Wheezing

Bonato, Matteo; Gallo, Elisa; Bazzan, Erica; Marson, Giovanna; Zagolin, Luca; Cosio, Manuel G.; Barbato, Angelo; Saetta, Marina; Gregori, Darío; Baraldo, Simonetta

doi:10.1513/annalsats.202010-1321oc

Cited by 13 publications

(11 citation statements)

References 43 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With the deterioration in air quality, the global incidence of asthma has been increasing. 26 In that context, airway remodeling as an important common feature of asthma, especially severe refractory asthma, remains a challenge for treatment and clinical management. 7 Currently, the airway epithelium is considered to play significant roles in the progression of asthma.…”

Section: Discussionmentioning

confidence: 99%

The TL1A-DR3 Axis in Asthma: Membrane-Bound and Secreted TL1A Co-Determined the Development of Airway Remodeling

Zhang

Pan

et al. 2022

Allergy Asthma Immunol Res

View full text Add to dashboard Cite

Purpose Tumor necrosis factor-like ligand 1A (TL1A), especially its secreted form, has been shown to contribute to eosinophilic inflammation and mucus production, cardinal features of asthma, through its receptor, death receptor 3 (DR3). However, the role of the TL1A-DR3 axis in asthma, especially in terms of airway remodeling, has not yet been fully understood. Methods The present study investigated the expression and secretion of TL1A in the lung and human bronchial epithelial cells. DR3 small interfering RNA (siRNA), TL1A siRNA, and truncated plasmids were used respectively to identify the function of the TL1A-DR3 axis in vitro . To further validate the roles of the TL1A-DR3 axis in asthma, we collected airway biopsies and sputa from asthmatic patients and constructed a mouse model following rTL1A administration, DR3 knockdown, and TL1A knockout, the asthma-related inflammatory response and the pathological changes in airways were analyzed using various experimental methods. Associated signaling pathways downstream of TL1A knockout in the mouse model were analyzed using RNA sequencing. Results TL1A, especially its non-secreted form (nsTL1A) was involved in the remodeling process in asthmatics’ airways. Knockdown of TL1A or its receptor DR3 decreased the expression of fibrosis-associated protein in BEAS-2B cells. Reversely, overexpression of nsTL1A in airway epithelial cells facilitated the transforming growth factor-β-induced remodeling progress. In the asthma mouse model, activating the TL1A-DR3 axis contributes to airway inflammation, remodeling, and tissue destruction. Reciprocally, DR3 knockdown or TL1A knockout partly reverses airway remodeling in the asthma model induced by ovalbumin. Conclusions Our results confirm differential TL1A expression (including its secreted and non-secreted form) in asthma, which modulates remodeling. The shared mechanism of action by which nsTL1A and secreted TL1A exert their effects on asthma development might be mediated via the nuclear factor-κB pathway. The TL1A-DR3 axis presents a promising therapeutic target in asthma.

show abstract

Section: Discussionmentioning

confidence: 99%

The TL1A-DR3 Axis in Asthma: Membrane-Bound and Secreted TL1A Co-Determined the Development of Airway Remodeling

Zhang

Pan

et al. 2022

Allergy Asthma Immunol Res

View full text Add to dashboard Cite

show abstract

“…Of interest, we recently observed a dual effect of long-term pollutants exposure on cellular inflammation in airway tissue: while in asthmatic children air pollution enhances eosinophilic inflammation in bronchial mucosa, in non-asthmatic ones it associates with reduced numbers of both eosinophils and neutrophils ( 24 ). Altogether the results of the two studies suggest that air pollution can have a pro-inflammatory effect in susceptible subjects (asthmatics) while, at the same time, impairing innate immune responses.…”

Section: Discussionmentioning

confidence: 99%

Air Pollution Exposure Impairs Airway Epithelium IFN-β Expression in Pre-School Children

et al. 2021

Self Cite

View full text Add to dashboard Cite

IntroductionAir pollution is a risk factor for respiratory infections and asthma exacerbations. We previously reported impaired Type-I and Type-III interferons (IFN-β/λ) from airway epithelial cells of preschool children with asthma and/or atopy. In this study we analyzed the association between rhinovirus-induced IFN-β/λ epithelial expression and acute exposure to the principal outdoor air pollutants in the same cohort.MethodsWe studied 34 children (17asthmatics/17non-asthmatics) undergoing fiberoptic bronchoscopy for clinical indications. Bronchial epithelial cells were harvested by brushing, cultured and experimentally infected with Rhinovirus Type 16 (RV16). RV16-induced IFN-β and λ expression was measured by quantitative real time PCR, as was RV16vRNA. The association between IFNs and the mean exposure to PM10, SO2 and NO2 in the day preceding bronchoscopy was evaluated using a Generalized Linear Model (GLM) with Gamma distribution.ResultsAcute exposure to PM10 and NO2 was negatively associated to RV16-induced IFNβ mRNA. For each increase of 1ug/m3 of NO2 we found a significative decrease of 2.3x103 IFN-β mRNA copies and for each increase of 1ug/m3 of PM10 a significative decrease of 1x103 IFN-β mRNA copies. No significant associations were detected between IFN-λ mRNA and NO2 nor PM10. Increasing levels of NO2 (but not PM10) were found to be associated to increased RV16 replication.ConclusionsShort-term exposure to high levels of NO2 and PM10 is associated to a reduced IFN-β expression by the airway epithelium, which may lead to increased viral replication. These findings suggest a potential mechanism underlying the link between air pollution, viral infections and asthma exacerbations.

show abstract

“…Furthermore, the nerve density and airway reactivity in adult age was linked to IL-5 exposure during embryogenesis [21,22]. Today, it is widely assumed that poor indoor air quality and exposure to allergens are the main reasons for developing childhood asthma [23][24][25][26][27][28]. Rhinovirus infection at a young age presents another risk factor to develop asthma later in life [29].…”

Section: Early Events Leading To Asthma and Airway Wall Remodeling In...mentioning

confidence: 99%

“…The authors concluded that the current asthma therapies do not affect airway wall remodeling in children with asthma. In another study, structural changes of the airways were investigated in biopsies obtained from 53 children with wheezing and compared to 45 children without wheezing [26]. Prolonged exposure to PM10 (10 microns) resulted in increased thickness of the basement membrane and eosinophilic inflammation in wheezing children.…”

Section: Early Events Leading To Asthma and Airway Wall Remodeling In...mentioning

confidence: 99%

Airway Wall Remodeling in Childhood Asthma—A Personalized Perspective from Cell Type-Specific Biology

Fang

Roth

2021

JPM

View full text Add to dashboard Cite

Airway wall remodeling is a pathology occurring in chronic inflammatory lung diseases including asthma, chronic obstructive pulmonary disease, and fibrosis. In 2017, the American Thoracic Society released a research statement highlighting the gaps in knowledge and understanding of airway wall remodeling. The four major challenges addressed in this statement were: (i) the lack of consensus to define “airway wall remodeling” in different diseases, (ii) methodologic limitations and inappropriate models, (iii) the lack of anti-remodeling therapies, and (iv) the difficulty to define endpoints and outcomes in relevant studies. This review focuses on the importance of cell-cell interaction, especially the bronchial epithelium, in asthma-associated airway wall remodeling. The pathology of “airway wall remodeling” summarizes all structural changes of the airway wall without differentiating between different pheno- or endo-types of asthma. Indicators of airway wall remodeling have been reported in childhood asthma in the absence of any sign of inflammation; thus, the initiation event remains unknown. Recent studies have implied that the interaction between the epithelium with immune cells and sub-epithelial mesenchymal cells is modified in asthma by a yet unknown epigenetic mechanism during early childhood.

show abstract

Air Pollution Relates to Airway Pathology in Children with Wheezing

Cited by 13 publications

References 43 publications

The TL1A-DR3 Axis in Asthma: Membrane-Bound and Secreted TL1A Co-Determined the Development of Airway Remodeling

The TL1A-DR3 Axis in Asthma: Membrane-Bound and Secreted TL1A Co-Determined the Development of Airway Remodeling

Air Pollution Exposure Impairs Airway Epithelium IFN-β Expression in Pre-School Children

Airway Wall Remodeling in Childhood Asthma—A Personalized Perspective from Cell Type-Specific Biology

Contact Info

Product

Resources

About