Filaggrin null mutations are associated with increased asthma severity in children and young adults

Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults

“…A significantly greater proportion of FLG null allele carriers with asthma were on higher BTS treatment steps 3 and 4 (14). Together, the two papers, thus, reinforce the position that epithelial barrier defects resulting from FLG mutations have a major influence on day-to-day aspects of asthma management and control, including overall risk of asthma exacerbations, use of oral steroids, together with Ôas requiredÕ doses of inhaled bronchodilators (14) and regular asthma medication needs (14). Thus, FLG gene status appears to influence the overall burden of disease in asthmatic children and young adults.…”

“…Since the completion of our data collection for our initial study (3), we have continued recruiting patients with asthma for the Scottish cohort primarily ascertained with asthma to generate statistical power to investigate further the possible roles of filaggrin gene defects on asthma medication use (14) and, subsequently, risk of asthma exacerbations. Our data demonstrate that individuals with FLG null alleles have a significantly increased risk of exacerbations requiring hospital admissions, courses of oral steroids, or experiencing school absences.…”

“…The mechanisms of viralinduced asthma exacerbations are different from those with allergen exposure, possibly explaining the degree of refractoriness to inhaled or oral corticosteroids (32,33). We have discussed the possible up-regulation of epithelia T H 2-type immunity with preferential activation of the immunological cascade as a likely mechanism for the role of epidermal permeability on asthma medication needs (14). Similar mechanisms could explain the associations between FLG gene defects and the increased risk of asthma exacerbations in children and young adults reported in this paper.…”

“…As similar penetrance differences may occur in asthma, we compared the relative effects of the null mutations as well as the combined genotype on the asthma severity outcomes and symptomatic control measures of the BREATHE study. The previous data demonstrated that individuals with FLG null alleles have a significantly increased disease burden, both in terms of lung function, the null mutation carriers having greater airway obstruction, and in the intensity of medication required for disease control (14). The individual contribution to the overall signal of the 2282del4 allele was lower than that observed for the R501X mutation (14).…”

“…The previous data demonstrated that individuals with FLG null alleles have a significantly increased disease burden, both in terms of lung function, the null mutation carriers having greater airway obstruction, and in the intensity of medication required for disease control (14). The individual contribution to the overall signal of the 2282del4 allele was lower than that observed for the R501X mutation (14). However, the association of these mutations with the risk of asthma exacerbations has never been assessed.…”