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Are polymorphisms in LTC4 synthase associated with asthma phenotype?
Childhood determinants of persistent adult asthma Associations between childhood experiences and persistence of asthma in adulthood are emerging from several long-term prospective studies. Although these studies are providing invaluable insights and sometimes have remarkable retention rates, the overall number of subjects is still small. Another approach to studying the importance of childhood exposures on the prevalence of asthma in adulthood is taken in the paper by de Marco and coauthors (p 845) in this month’s issue of the Journal. They analyzed data regarding childhood exposures obtained retrospectively from subjects 20 to 44 years of age enrolled in the European Community Respiratory Health Survey. A total of 18,156 subjects from 36 centers in 16 countries contributed the data. The presence of asthma and the age of onset were determined. Asthma was considered in
remission if the subject had neither been under treatment nor experienced an attack of asthma in the past 24 months. In all, 8.6% of the subjects reported having asthma. A family history of asthma/allergy was associated with a higher risk of developing asthma and a lower chance of remission throughout life. A serious respiratory infection before 5 years of age was associated with an increased lifelong risk of asthma onset, whereas contact with older children conferred permanent protection against asthma and increased the chance of remission in childhood asthma. Pet ownership in childhood again was reported to have a protective effect. Maternal smoking, however, did not show a significant association with asthma. The sex pattern was confirmed: being female was negatively associated with onset of asthma in childhood and positively associated with onset of asthma in adulthood. The authors conclude that genetic predisposition and exposure to infectious agents are major early determinants that influence a subsequent history of asthma.
Nebulized lidocaine in mild-moderate asthma Previous uncontrolled studies have reported dramatic responses to inhaled lidocaine in a high percentage of adults and children with severe asthma. In this issue of the Journal, Hunt and coworkers (p 853) report the results of a placebo-controlled, 8-week study in 50 adult subjects with asthma. All subjects were using inhaled but not systemic corticosteroids. After randomization to either placebo or inhaled lidocaine 4 times daily, their inhaled steroids were withdrawn, stepwise, over 4 weeks. Similar numbers in each group remained in the study at 4 and 8 weeks. Reasons for withdrawal included worsening asthma (4 on lidocaine and 6 on placebo) and treatment intolerance (4 on lidocaine). Intent-to-treat analysis revealed a significant benefit for lidocaine treatment compared with placebo for FEV1 symptom scores, nighttime awakening, b-agonist use, and blood eosinophils. There were no serious adverse effects in either
Are polymorphisms in LTC4 synthase associated with asthma phenotype? Kedda et al (p 889) have used a large Australian Caucasian adult population of nonasthmatic individuals, individuals with mild/moderate/severe asthma, and aspirinintolerant asthmatic individuals to look for associations between 2 polymorphisms in the LTC4 synthase gene and different asthma phenotypes. They have identified a new polymorphism (IVS1-10c>a), which was not associated with asthma or asthma severity, and they have conducted association studies of the A–444C polymorphism, previously shown to be associated with aspirin-intolerant asthma. In
Changes in asthma severity in the lidocaine and placebo groups.
group. The authors conclude that nebulized lidocaine provided effective and safe therapy in subject with mild to moderate asthma. this population, they have shown that the A–444C polymorphism was weakly associated with asthma per se, but not with chronic asthma severity or aspirin intolerance. They also conducted a meta-analysis of all of the genetic association studies conducted to date and have shown significant between-study heterogeneity in C–444 allele frequencies within different clinical subgroups. In vitro studies revealed no significant functional differences between the A–444 and C–444 alleles. The authors have thus confirmed that independent of transcriptional activity, the C–444 allele in the LTC4 synthase gene is weakly associated with the asthma phenotype but is not related to disease severity or aspirin intolerance.
Selected articles are indicated in the Table of Contents by
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J ALLERGY CLIN IMMUNOL
remission if the subject had neither been under treatment nor experienced an attack of asthma in the past 24 months. In all, 8.6% of the subjects reported having asthma. A family history of asthma/allergy was associated with a higher risk of developing asthma and a lower chance of remission throughout life. A serious respiratory infection before 5 years of age was associated with an increased lifelong risk of asthma onset, whereas contact with older children conferred permanent protection against asthma and increased the chance of remission in childhood asthma. Pet ownership in childhood again was reported to have a protective effect. Maternal smoking, however, did not show a significant association with asthma. The sex pattern was confirmed: being female was negatively associated with onset of asthma in childhood and positively associated with onset of asthma in adulthood. The authors conclude that genetic predisposition and exposure to infectious agents are major early determinants that influence a subsequent history of asthma.
Nebulized lidocaine in mild-moderate asthma Previous uncontrolled studies have reported dramatic responses to inhaled lidocaine in a high percentage of adults and children with severe asthma. In this issue of the Journal, Hunt and coworkers (p 853) report the results of a placebo-controlled, 8-week study in 50 adult subjects with asthma. All subjects were using inhaled but not systemic corticosteroids. After randomization to either placebo or inhaled lidocaine 4 times daily, their inhaled steroids were withdrawn, stepwise, over 4 weeks. Similar numbers in each group remained in the study at 4 and 8 weeks. Reasons for withdrawal included worsening asthma (4 on lidocaine and 6 on placebo) and treatment intolerance (4 on lidocaine). Intent-to-treat analysis revealed a significant benefit for lidocaine treatment compared with placebo for FEV1 symptom scores, nighttime awakening, b-agonist use, and blood eosinophils. There were no serious adverse effects in either
Are polymorphisms in LTC4 synthase associated with asthma phenotype? Kedda et al (p 889) have used a large Australian Caucasian adult population of nonasthmatic individuals, individuals with mild/moderate/severe asthma, and aspirinintolerant asthmatic individuals to look for associations between 2 polymorphisms in the LTC4 synthase gene and different asthma phenotypes. They have identified a new polymorphism (IVS1-10c>a), which was not associated with asthma or asthma severity, and they have conducted association studies of the A–444C polymorphism, previously shown to be associated with aspirin-intolerant asthma. In
Changes in asthma severity in the lidocaine and placebo groups.
group. The authors conclude that nebulized lidocaine provided effective and safe therapy in subject with mild to moderate asthma. this population, they have shown that the A–444C polymorphism was weakly associated with asthma per se, but not with chronic asthma severity or aspirin intolerance. They also conducted a meta-analysis of all of the genetic association studies conducted to date and have shown significant between-study heterogeneity in C–444 allele frequencies within different clinical subgroups. In vitro studies revealed no significant functional differences between the A–444 and C–444 alleles. The authors have thus confirmed that independent of transcriptional activity, the C–444 allele in the LTC4 synthase gene is weakly associated with the asthma phenotype but is not related to disease severity or aspirin intolerance.
Selected articles are indicated in the Table of Contents by
Page 804 May 2004
EC d
J ALLERGY CLIN IMMUNOL