title: Non-atopic intrinsic asthma and the 'family tree' of chronic respiratory disease syndromes.
abstract: We present a scheme below in which the most common forms of inflammatory diseases of the respiratory tract, notably atopic and non-atopic asthma and COPD, are depicted as separate offshoots from a common 'at-risk' pathway underpinned by genotypes related to aberrations in control of host defence and tissue repair mechanisms. We propose that entrance into this pathway is initially programmed by environmental experience during infancy and early childhood, in particular by severe lower respiratory tract infection, and that further progression towards expression of specific disease phenotype(s) is determined by the nature, timing and frequency of additional environmental insults subsequently encountered. At the one extreme, early sensitization of at-risk subjects to aeroallergens can potentially drive rapid progression towards expression of the atopic asthmatic phenotype under the dual onslaught of inflammatory responses to allergens/pathogens. At the opposite end of the spectrum the drip-feed effects of occasional infections on respiratory function(s) are amplified over a longer time frame by inflammation resulting from exposure to tobacco smoke and/or related chemical pollutants. Non-atopic asthma is envisaged to fit between these two extremes, being driven essentially by the downstream effects of respiratory infections alone in at-risk subjects. An important common factor in all three disease phenotypes is that acute exacerbations are typically driven by infections, the host responses to which display a characteristic T-helper type 2-like footprint, which in our view points to underlying genotype(s) which result in unbalanced host responses to respiratory pathogens.
authors.affiliation: Telethon Institute for Child Health Research, and Centre for Child Health Research, Faculty of Medicine and Dentistry, University of Western Australia, Perth, Australia. patrick@ichr.uwa.edu.au
authors.forename: P G
authors.initials: PG
authors.lastname: Holt
authors.forename: P D
authors.initials: PD
authors.lastname: Sly
mesh_terms: D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D004781:Environmental Exposure; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology*; D012307:Risk Factors; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens