Respiratory Viral and Bacterial Factors That Influence Early Childhood Asthma

Abstract

Asthma is a chronic respiratory condition characterised by episodes of shortness of breath due to reduced airway flow. The disease is triggered by a hyperreactive immune response to innocuous allergens, leading to hyper inflammation, mucus production, changes in structural cells lining the airways, and airway hyperresponsiveness. Asthma, although present in adults, is considered as a childhood condition, with a total of about 6.2 million children aged 18 and below affected globally. There has been progress in understanding asthma heterogeneity in adults, which has led to better patient stratification and characterisation of multiple asthma endotypes with distinct, but overlapping inflammatory features. The asthma inflammatory profile in children is not well-defined and heterogeneity of the disease is less described. Although many factors such as genetics, food allergies, antibiotic usage, type of birth, and cigarette smoke exposure can influence asthma development particularly in children, respiratory infections are thought to be the major contributing factor in poor lung function and onset of the disease. In this review, we focus on viral and bacterial respiratory infections in the first 10 years of life that could influence development of asthma in children. We also review literature on inflammatory immune heterogeneity in asthmatic children and how this overlaps with early lung development, poor lung function and respiratory infections. Finally, we review animal studies that model early development of asthma and how these studies could inform future therapies and better understanding of this complex disease.

Poly(I:C) Exacerbates Airway Goblet Cell Hyperplasia and Lung Inflammation in HDM-Exposed Balb/C Mice by YAP/FOXM1 Pathway

“…The HDM promotes airway goblet epithelial cell metaplasia and airway inflammation via the IL-13/STAT6/FOXM1/SPDEF pathway [11]. Respiratory virus infection is the primary pathogenic factor for acute asthma exacerbations in children [31,32]. Approximately 80-85% of asthma exacerbations in children and adolescents are associated with respiratory virus infection.…”

Advances and Highlights of miRNAs in Asthma: Biomarkers for Diagnosis and Treatment

“…Asthma exacerbations are episodes in which there is worsening of asthma symptoms and lung function (Global Initiative for Asthma (GINA)) [ 55 ]. Many viral acute respiratory infections (ARIs) are thought to be the major triggers of exacerbation of symptoms in chronic respiratory diseases, especially in asthma; as a result, these ARIs are responsible for a substantial proportion of asthma-related morbidity and all asthma-related mortality [ 56 ]. It is well-documented in other reviews on the subject that miRNAs simultaneously carry out a regulatory function in controlling the immune response against respiratory viruses and those that cause viral ARIs, such as human rhinovirus (hRV), influenza virus (IV), human metapneumovirus (hMPV), human coronavirus (hCoV), and respiratory syncytial virus (RSV) and at the same time are modulated by these viral ARIs [ 57 ].…”

The role of the CBM complex in allergic inflammation and disease

“…These observations indicate that other CARD9-mediated functionssuch as the recruitment of and fungal killing by neutrophilsare required for IFD susceptibility. 53 Although CARD9 is also activated by bacteria (via nucleotide-binding oligomerization domain-containing protein 2) and viruses (via Rad50 doublestranded break repair protein, RIG1, and melanoma differentiation-associated protein 5)-including species associated with asthma exacerbations 41,[54][55][56] -it is worth noting that CARD9-deficient patients are not susceptible to bacterial and viral infections, and thus it seems unlikely that CARD9 plays a crucial role in protecting against bacterial-and viral-associated sequelae of asthma and other allergic diseases. In addition to T H 17 polarization, CARD9 appears to promote T H 1 over proallergic T H 2 polarization.…”