Parental Smoking Modifies the Relation between Genetic Variation in Tumor Necrosis Factor-α (TNF) and Childhood Asthma

BACKGROUND: Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-α (TNF) and lymphotoxin-α (LTA, also called TNF-β) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand smoke and ozone both stimulate TNF production. OBJECTIVES: Our goal was to investigate whether genetic variation in TNF and LTA is associated with asthma and atopy and whether the association is modified by parental smoking in a Mexican population with high ozone exposure. METHODS: We genotyped six tagging single nucleotide polymorphisms (SNPs) in TNF and LTA, including functional variants, in 596 nuclear families consisting of asthmatics 4–17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests. RESULTS: The A allele of the TNF-308 SNP was associated with increased risk of asthma [relative risk (RR) = 1.54; 95% confidence interval (CI), 1.04–2.28], especially among children of non-smoking parents (RR = 2.06; 95% CI, 1.19–3.55; p for interaction = 0.09). Similarly, the A allele of the TNF-238 SNP was associated with increased asthma risk among children of nonsmoking parents (RR = 2.21; 95% CI, 1.14–4.30; p for interaction = 0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the single SNP findings in magnitude and direction. TNF and LTA SNPs were not associated with the degree of atopy. CONCLUSIONS: Our results suggest that genetic variation in TNF may contribute to childhood asthma and that associations may be modified by parental smoking

Proof of concept study to evaluate step-down therapy with inhaled corticosteroid alone or additive therapy on surrogate inflammatory markers in asthma

AIM: The aim of the study was to evaluate the usefulness of inflammatory surrogates in determining step-down therapy in asthma. METHODS: AMP challenge, serum eosinophil cationic protein (ECP), exhaled nitric oxide (eNO) and pulmonary function tests were recorded. Subjects were divided into two groups following high dose inhaled corticosteroids (ICS): Group A fixed dose ICS vs. Group B ICS alone and in combination with add on therapies. RESULTS: No differences were seen in inflammatory measures between fixed dose ICS and reduced dose ICS alone or with combination therapies. CONCLUSIONS: AMP challenge conferred no additional benefit in guiding step-down therapy. The role of inflammatory surrogates may still play a role in predicting failed step-down on an individual basis