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Basu, K; Palmer, C N A; Lipworth, B J; Irwin, W H; Terron-Kwiatkowski, A; Zhao, Y; Liao, H; Smith, F J D; Mitra, A; Mukhopadhyay, S (2008)
Publisher: Wiley
Languages: English
Types: Article
Subjects: RJ0047.3

Classified by OpenAIRE into

mesheuropmc: respiratory tract diseases
Background: Filaggrin (FLG) null mutations are important genetic predisposing factors for atopic asthma and have recently been shown to influence controller and reliever medication needs in asthmatic children. Our objective was to study the role of FLG null alleles in asthma exacerbations. \ud \ud Methods: FLG mutations R501X and 2282del4 were assayed in 1135 individuals ranging from 3 to 22 years old with asthma from Tayside and Dumfries, Scotland. Asthma exacerbations over the previous 6 months were also studied. \ud \ud Results: The FLG mutations were significantly associated with greater risk of exacerbations in children with asthma. Exacerbations were significant for the R501X but not the 2282del4 mutation and the combined genotype compared to the wild-type with odds ratios of 1.97 (95% CI, 1.19–3.22; P = 0.009) and 1.61 (95% CI, 1.08–2.40; P = 0.021), respectively. Individuals with FLG null alleles were more likely to require oral steroids (31.4%vs 19.5%; OR = 1.89; P = 0.021) for their exacerbations. There was also a 1.71-fold increased risk (42.6%vs 30%; P = 0.041) of school absence owing to asthma exacerbations in asthmatic individuals with FLG null mutation. On sub-group analysis, the effect of FLG mutations on asthma exacerbations is significant (P = 0.045) only for participants with relatively mild asthma controlled on inhaled steroids, with inhaled albuterol according to need. \ud \ud Conclusion: In addition to their effect on asthma medication requirements reported previously, there is an association between the presence of FLG null mutations and the risk of asthma exacerbations in asthmatic children and young adults.
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    • 1. Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 2005;6:328-340.
    • 2. Sandilands A, Terron-Kwiatkowski A, Hull PR, O Regan GM, Clayton TH, Watson RM et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet 2007;39:650-654.
    • 3. Palmer CNA, Irvine AD, TerronKwiatkowski A, Zhao Y, Liao H, Lee SP et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006;38:441-446.
    • 4. Hudson TJ. Skin barrier function and allergic risk. Nat Genet 2006;38:399- 400.
    • 5. Smith FJD, Irvine AD, TerronKwiatkowski A, Sandilands A, Campbell LE, Zhao Y et al. Lossof-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 2006;38:337-342.
    • 6. Barker JNWN, Palmer CNA, Zhao Y, Liao H, Hull PR, Lee SP et al. Null mutations in the Filaggrin Gene (FLG) determine major susceptibility to earlyonset atopic dermatitis that persists into adulthood. J Invest Dermatol 2007;127:564-567.
    • 7. Marenholz I, Nickel R, Ru¨ schendorf F, Schulz F, Esparza-Gordillo J, Kerscher T et al. Filaggrin loss-of-function mutations predispose to phenotypes involved in the atopic march. J Allergy Clin Immunol 2006;118:866-871.
    • 8. Morar N, Cookson W, Harper JI, Moffatt MF. Filaggrin mutations in children with severe atopic dermatitis. J Invest Dermatol 2007;127:1667- 1672.
    • 9. Ruether A, Stoll M, Schwarz T, Schreiber S, Fo¨ lster-Holst R. Filaggrin loss-of-function variant contributes to atopic dermatitis risk in the population of Northern Germany. Br J Dermat 2006;155:1093-1094.
    • 10. Stemmler S, Parwez Q, Petrasch-Parwez E, Epplen J, Hoffjan S. Two common loss-of-function mutations within the filaggrin gene predispose for early onset of atopic dermatitis. J Invest Dermatol 2006;127:722-724.
    • 11. Weidinger S, Illig T, Baurecht H, Irvine A, Rodriguez E, Diaz-Lacava A et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol 2006;118:214- 219.
    • 12. Nomura T, Sandilands A, Akiyama M, Liao H, Evans AT, Sakai K et al. Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol 2007;119:434-440.
    • 13. Sandilands A, Smith FJD, Irvine AD, McLean WHI. Filaggrin s fuller figure: a glimpse into the genetic architecture of atopic dermatitis. J Invest Dermatol 2007;127:1282-1284.
    • 14. Palmer CNA, Ismail T, Lee SP, TerronKwiatkowski A, Zhao Y, Liao H et al. Filaggrin null mutations are associated with increased asthma severity in children and young adults. J Allergy Clin Immunol 2007;120:64-68.
    • 15. Milton B, Whitehead M, Holland P, Hamilton V. The social and economic consequences of childhood asthma across the lifecourse: a systematic review. Child Care Health Dev 2004;30:711-728.
    • 16. Baraldi E, Carraro S, Alinovi R, Pesci A, Ghiro L, Bodini A et al. Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations. Thorax 2003;58:505-509.
    • 17. Flores G, Abreu M, Tomany-Korman S, Meurer J. Keeping children with asthma out of hospitals: parents and physicians perspectives on how pediatric asthma hospitalizations can be prevented. Pediatrics 2005;116:957-965.
    • 18. Palmer CNA, Doney AS, Ismail T, Lee SP, Murrie I, Macgregor DF et al. PPARG locus haplotype variation and exacerbations in asthma. Clin Pharmacol Ther 2007;81:13-18.
    • 19. Palmer CNA, Doney AS, Lee SP, Murrie I, Ismail T, Macgregor DF et al. Glutathione-S-transferase M1 and P1 genotype, passive smoking and peak expiratory flow in asthma. Pediatrics 2006;118:710-716.
    • 20. BTS, SIGN. British guidelines on the management of asthma. Thorax 2003;58:1-94.
    • 21. Timonen KL, Pekkanen J, Korppi M, Vahteristo M, Salonen RO. Prevalence and characteristics of children with chronic respiratory symptoms in eastern Finland. Eur Respir J 1995;8: 1155-1160.
    • 22. Lerbaek A, Bisgaard H, Agner T, Ohm Kyvik K, Palmer CN, Menne´ T. Filaggrin null alleles are not associated with hand eczema or contact allergy. Br J Dermatol 2007;157:1199-1204.
    • 23. Arshad SH. Primary prevention of asthma and allergy. J Allergy Clin Immunol 2005;116:3-14.
    • 24. Holgate ST. Exacerbations - the asthma paradox. Am J Respir Crit Care Med 2005;172:941-942.
    • 25. Andersson F, Borg S, Stahl E. The impact of exacerbations on the asthmatic patient s preference scores. J Asthma 2003;5:615-623.
    • 26. Lane S, Molina J, Plusa T. An international observational prospective study to determine the cost of asthma exacerbations (COAX). Respir Med 2006;100: 434-450.
    • 27. Skrepnek GH, Skrepnek SV. Epidemiology, clinical and economic burden, and natural history of chronic obstructive pulmonary disease and asthma. Am J Manag Care 2004;10:S129-S138.
    • 28. Johnston NW, Sears MR. Asthma exacerbations: epidemiology. Thorax 2006;1:61.
    • 29. Johnston N, Johnston SL, Duncan JM, Greene JM, Kebadze T, Keith PK et al. The September epidemic of asthma exacerbation in children: a search for etiology. J Allergy Clin 2005;115:230- 232.
    • 30. Johnston SL, Pattemore PK, Sanderson G, Smith S, Campbell MJ, Josephs LK et al. The relationship between upper respiratory infections and hospital admissions for asthma: a time trend analysis. Am J Respir Crit Care Med 1996;154:654-660.
    • 31. Johnston SL, Pattemore PK, Sanderson G, Smith S, Lampe F, Josephs L et al. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. Br Med J 1995;310:1225-1228.
    • 32. Doull IJ, Lampe FC, Smith S, Schreiber J, Freezer NJ, Holgate ST. Effect of inhaled corticosteroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial. BMJ 1997;31:858-862.
    • 33. Wilson NM, Silverman M. Treatment of acute, episodic asthma in preEditorials 943 school children using intermittent high dose inhaled steroids at home. Arch Dis Child 1990;65:407-410.
    • 34. Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, Debenedetto A et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol 2007;120:150- 155.
    • 35. Hunninghake GM, Soto-Quiro´ s ME, Avila L, Su J, Murphy A, Demeo DL et al. Polymorphisms in IL13, total IgE, eosinophilia, and asthma exacerbations in childhood. J All Clin Immunol 2007;120:84-90.
    • 36. Elbahlawan L, Binaei S, Christensen ML, Zhang Q, Quasney MW, Dahmer MK. Beta2-adrenergic receptor polymorphisms in African American children with status asthmaticus. Pediatr Crit Care Med 2006;7:15-18.
    • 37. Palmer CNA, Lipworth BJ, Lee S, Ismail T, Macgregor DF, Mukhopadhyay S. Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol. Thorax 2006;61:940-944.
    • 38. Weir TD, Mallek N, Sandford AJ, Bai TR, Awadh N, Fitzgerald JM et al. Beta2-Adrenergic receptor haplotypes in mild, moderate and fatal/near fatal asthma. Am J Respir Crit Care Med 1998;158:787-791.
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