title: Childhood asthma: causes, risks, and protective factors; a role of innate immunity.
abstract: Childhood asthma is an umbrella of multifactorial diseases with similar clinical features such as mast cell and eosinophil infiltration causing airway hyper responsiveness, inflammation, and airway obstruction. There are various factors that are implicated in childhood asthma pathogenesis. A combined contribution of genetic predisposition, environmental insults, and epigenetic changes account for polarisation of the immune system towards T helper (Th) type 2 cell responses that include production of pro-inflammatory cytokines, IgE, and eosinophil infiltrates, shown to associate with asthma. Environmental cues in prenatal, perinatal, and early childhood seem to determine development of asthma incidence or protection against it. Mode of birth delivery, use of antibiotics, oxidative stress, exposure to tobacco smoke and an industrialised lifestyle are significant contributors to childhood asthma exacerbation. Environmental stimuli such as exposure to maternal antibodies through breast milk, and certain early infections favour Th1 cell responses, leading to the production of anti-inflammatory cytokines that protect from asthma. Aside from the Th cell responses the role of innate immunity in the context of alveolar macrophages, dendritic cells, and surfactant protein A (SP-A) and SP-D is discussed. SP-A and SP-D enhance pathogen phagocytosis and cytokine production by alveolar macrophages, bind and clear pathogens, and interact with dendritic cells to mediate adaptive immunity responses. Further study of the interactions between genetic variants of genes of interest (SP-A and SP-D) and the environment may provide valuable knowledge about the underlying mechanisms of various interactions that differentially affect asthma susceptibility, disease severity, and reveal potential points for therapeutic interventions.
authors.affiliation: Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research Department of Pediatrics, College of Medicine The Pennsylvania State University, Hershey, Pennsylvania, USA.
authors.forename: Georgios T
authors.initials: GT
authors.lastname: Noutsios
authors.affiliation: a Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research Department of Pediatrics, College of Medicine The Pennsylvania State University, Hershey, Pennsylvania, USA; Department of Obstetrics and Gynecology, College of Medicine The Pennsy.
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
mesh_terms: D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology*; D001942:Breast Feeding; D004032:Diet; D004777:Environment; D057890:Epigenomics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007234:Infant, Premature; D008019:Life Style; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology; D065840:Protective Factors; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D012307:Risk Factors; D017678:Sex Distribution; D012959:Socioeconomic Factors
chemical_list: D018927:Anti-Asthmatic Agents; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D