Interpatient variability in rates of asthma progression: Can genetics provide an answer?

Asthma progression: Can we and should we measure it?

“…Drs John Holloway, Ian Yang, and Stephen Holgate discuss the interpatient variability in rates of asthma progression and whether genetics can provide some clues to unraveling the mystery. 9 They indicate that interpatient genetic variability has been shown to affect multiple facets of asthma progression from susceptibility to disease, progression to severe disease, and response to treatment. However, at present, we are not in a position to use the rapidly accumulating knowledge of genetic variants that influence progression in clinical practice.…”

Comparison of childhood wheezing phenotypes in 2 birth cohorts: ALSPAC and PIAMA

“…1,2 However, asthma symptoms are heterogeneous in early childhood. 3,4 Identification of different subtypes of asthma in early life is important to study potential pathways of asthma development. 5,6 Different asthma-related phenotypes have been categorized in early childhood by using longitudinal analyses of wheezing history.…”

Genetics of allergic disease

“…115 However, the identification of further risk factors and the development of better methods for incorporating genetic factors into risk models are likely to substantially increase the value of genotypic risk factors and may also provide a means for predicting progression to severe disease and targeting of preventative treatment in the future. 116 The potential utility of such an approach for allergic disease has been highlighted by the recent observation that in infants with eczema and sensitization to food allergens, FLG mutations predict subsequent development of childhood asthma with 100% positive predictive value. 117 Predicting asthma subtypes A simplistic view of asthma or any other allergic disorder that focuses entirely on T H 2 polarization and activation of allergy related cells, such as mast cells, basophils, and eosinophils, fails to take account of locally acting genetic and environmental factors that are required to translate the atopic phenotype in a specific organ to create disease.…”

“…117 Predicting asthma subtypes A simplistic view of asthma or any other allergic disorder that focuses entirely on T H 2 polarization and activation of allergy related cells, such as mast cells, basophils, and eosinophils, fails to take account of locally acting genetic and environmental factors that are required to translate the atopic phenotype in a specific organ to create disease. 116 In addition, the limited efficacy of biologic agents targeting individual T-cell receptors, such as CD25, 118 IL-5, 119,120 and TNF-a, 121 indicate that although individual patients might benefit from such therapies, they form only a small subgroup of the whole disease spectrum. Thus the concept is emerging of subphenotypes of asthma driven by differing gene-environment interactions.…”