Asthma Clinical Research Network (ACRN)
Smoking Modulates Outcomes of Glucocorticoid Therapy in Asthma (SMOG)
In subjects with persistent asthma who smoke, the effect of continuous daily treatment with an ICS on FEV1 does not differ from the effect observed in subjects with persistent asthma who do not smoke.
All patients were required to be between the ages of 18 and 50, have pre-bronchodilator FEV1 70-90% of predicted, and have ≥12% reversibility after albuterol inhalation or methacholine PC20 < 8mg/ml. Non-smokers were required to have a total lifetime smoking history of < 2 pack-years, and no smoking for at least 1 year. This was a randomized, double-dummy, crossover trial of treatment with an ICS (beclomethasone, QVAR™, 160 µg bid) or an LTRA (montelukast, Singulair™, 10 mg once daily). After a 2-week run-in period, patients entered an 8-week single-blind placebo treatment period. Patients were randomly assigned to receive either QVAR™ or Singulair™ for an 8-week double-blind period. At randomization, smokers and non-smokers were matched according to gender, age, and FEV1. After the first 8-week treatment period, patients entered a 6-week placebo wash-out period, and then crossed over to the alternate treatment during a second 8-week treatment period. Spirometry, methacholine reactivity, and asthma-specific quality of life were measured, and sputum induction was performed. The primary outcome was the change in pre-bronchodilator FEV1 over the 8-week treatment period in smokers compared to non-smokers.
Enrollment for SMOG began in January 2002 and the last patient visits occurred in February 2004. There were 83 randomized patients (44 smokers, 39 non-smokers). Non-smokers on QVAR™ displayed significant increases in FEV1 (170ml), FEV1% predicted (5%), spirometry PEF (28 L/m), daily AM and PM PEF (12L/m, 7L/m), and PC20 (0.63), and a reduction in sputum eosinophils (-2.6%). In contrast, smokers on QVAR™ displayed no such effects except for daily AM PEF. Non-smokers and smokers did not differ significantly (p > 0.05). Smokers on Singulair™ displayed a significant increase in daily AM PEF and their increase was better than non-smokers (p = 0.02). Singulair™ also decreased daily PEF variability in smokers and improved Asthma Quality of Life in non-smokers. Neither smokers nor non-smokers increased their FEV1 significantly after 8 weeks of Singulair™. The major publication was submitted to the Annals of Internal Medicine:
Lazarus SC, Chinchilli VM, Rollings NJ, Boushey HA, Cherniack R, Craig TJ, Deykin A, DiMango EA, Fish JE, Ford JG, Israel E, Kiley J, Kraft M, Lemanske RF, Jr, Leone FT, Martin RJ, Pesola GR, Peters SP, Sorkness CA, Szefler SJ, Wechsler ME, Fahy JV. The effects of cigarette response to treatment with inhaled steroids or leukotriene receptor antagonists in asthma: A randomized trial. Annals of Internal Medicine (submitted).
