Randomized trial of allergen-induced asthmatic response in smokers and non-smokers: effects of inhaled corticosteroids.

BACKGROUND: It is thought that asthmatics who smoke cigarettes respond less well to inhaled corticosteroid (ICS) therapy than asthmatics who do not smoke. OBJECTIVE: To evaluate the effects of smoking on allergen-induced airway responses in asthmatics treated with ICS. METHODS: Randomized, double-blind, crossover study evaluating twice daily fluticasone propionate (FP) 100 µg, FP 500 µg and placebo, for 7 days, on allergen-induced asthmatic responses in 18 non-smoking and 17 smoking atopic asthmatics (NCT01400906). At 1 h post-morning dose on Day 6, forced expiratory volume in 1 sec (FEV1 ) was measured up to 10 h post-challenge. Exhaled nitric oxide (eNO), induced sputum cell counts, and responsiveness to methacholine were assessed the following day. RESULTS: The late asthmatic response (LAR) was suppressed by FP in smokers and non-smokers; with placebo, the LAR was also attenuated in smokers versus non-smokers (adjusted mean minimum change in FEV1 (L) over 4-10 h [95% CI] in non-smokers: placebo -1.01 [1.31, 0.70], FP 100 µg -0.38 [0.54, 0.22], FP 500 µg -0.35 [0.54-0.22]; and in smokers: placebo -0.63 [0.84, 0.43]; FP 100 µg -0.44 [0.65, 0.23]; FP 500 µg -0.46 [0.59-0.32]). The Early AR was suppressed by FP treatment in non-smokers, but was not impacted in smokers. The reduction in methacholine hyperresponsiveness after FP was greater in non-smokers (1.5- and twofold doubling dose difference from placebo after FP 100 µg and FP 500 µg) than smokers (1.0 and 1.3 difference, respectively). Allergen-induced increases in eNO and sputum eosinophils were lower in smokers than non-smokers and were suppressed in both groups by FP. CONCLUSION AND CLINICAL RELEVANCE: Allergen-induced LARs were of a similar amplitude in both smoking and non-smoking atopic asthmatics at the end of ICS treatment, but attenuation of the LAR in smokers was only partly associated with ICS treatment. The marked attenuation of the LAR observed in smokers in the absence of ICS treatment is a novel observation.

Homocysteine, migration and early vascular impairment in people of African descent.

OBJECTIVES: A gradient of increased vascular risk with migration exists across the African diaspora. We investigated the hypothesis that differences in homocysteine/folic acid status contribute to this increased risk. DESIGN: Community cohort study of 73 Afro-Caribbeans in the United Kingdom and 151 matched Afro-Caribbeans in Jamaica with no conventional vascular risk factors. METHODS: Subjects were compared for baseline characteristics, vascular risk profile, homocysteine (tHcy), folate and B(12) concentrations. Endothelium-dependent vasodilatation was assessed by measuring the absolute change from baseline in the reflection index (RI) of the digital volume pulse during intravenous infusion of albuterol (5 microg/min, Delta RI(ALB)) and glyceryltrinitrate (GTN) (5 microg/min, Delta RI(GTN)). Carotid intima media thickness (CIMT) was measured ultrasonographically in the distal 1 cm of the common carotid artery. RESULTS: UK Afro-Caribbeans had higher tHcy (mean difference 2.3 (95% confidence interval 1.3 to 3.4) micromol/l) and lower folate (mean difference 3.2 (95% CI 1.8 to 4.7) microg/l) levels. Delta RI(ALB) was 5.1 (95% CI 2.5 to 7.6) percentage points lower and CIMT 0.124 (95% CI 0.075 to 0.173) mm greater in UK Afro-Caribbeans. Higher tHcy and lower folate concentrations correlated with impaired Delta RI(ALB) and increased CIMT. A 1 microg/l increase in folate concentration was associated with 0.3 (95% CI 0.1 to 0.5) percentage point increase in Delta RI(ALB) and 0.002 (95% CI 0.001 to 0.006) mm decrease in CIMT, independent of blood pressure, smoking and vascular risk profile. CONCLUSIONS: Lower folate concentrations in UK compared with West Indian African-Caribbeans may contribute to the higher stroke risk seen in UK African-Caribbean people.