KEYSTONE, COLO. — Quadrupling the dose of inhaled corticosteroid was an effective strategy for prevention of asthma exacerbations, and low-dose theophylline enhanced steroids' anti-inflammatory benefits, Dr. Harold S. Nelson noted in a review of new asthma studies.
In the 403-patient study of inhaled corticosteroid dosages (Am. J. Respir. Crit. Care Med. 2009;180:598–602), patients who quadrupled their inhaled corticosteroid dose in response to early evidence of an exacerbation based upon morning pulmonary function testing had a 57% reduction in the relative risk of requiring oral steroids, compared with patients who made no change in their low-dose inhaled steroid regimen, Dr. Nelson said at a meeting on allergy and respiratory disease sponsored by National Jewish Health, Denver.
Although the results didn't achieve significance, he rated this trial as among the past year's highlights in the asthma literature becausetit answers an important, previously unresolved clinical question.
“The long-time teaching has been to double the dose of inhaled corticosteroid when a patient notices the onset of an asthma exacerbation. That strategy has been shown to be totally ineffective in two large, well-done studies,” noted Dr. Nelson of National Jewish Health and professor of medicine at the University of Colorado, Denver.
Among the other highlights he identified in the recent asthma literature are:
▸ Low-dose theophylline enhances the anti-inflammatory benefits of steroids: In a study of 68 asthmatic smokers, 4 weeks of theophylline at 400 mg/day plus beclomethasone at 200 mcg/day resulted in significantly greater improvements both in lung function and in asthma symptoms than either drug alone (Eur. Respir. J. 2009;33:1010-17).
The rationale for using low-dose theophylline in this setting is that cigarette smoke inhibits histone deacetylase, an enzyme that mediates the therapeutic response to corticosteroids. Low-dose theophylline increases histone deacetylase activity.
The notion that low-dose theophylline has a place in the treatment of smokers with chronic respiratory disease was reinforced in another recent study, which involved 35 patients hospitalized for acute exacerbations of COPD.
They were randomized to standard therapy—bronchodilators and systemic steroids while hospitalized, long-acting beta-agonists and inhaled corticosteroids after discharge—or to standard therapy plus 100 mg of theophylline twice daily.
At follow-up 3 months later, the theophylline group had significantly greater improvement in forced expiratory volume in 1 second than those on standard therapy. They also had more than a threefold greater increase in macrophage histone deacetylase activity, compared with baseline, and much greater reductions in inflammatory cytokine levels in their sputum (Thorax 2009;64:424-9).
▸ Tumor necrosis factor–alpha inhibition for treatment of severe persistent asthma: This double-blind trial randomized 309 patients to one of three doses of golimumab (Simponi) or placebo. The study was scheduled to run for a year but stopped early after eight golimumab-treated patients developed cancers, including five patients in the highest-dose arm. No cancers occurred in the placebo group.
There were no significant differences between the golimumab and placebo groups in the number of severe asthma exacerbations or forced expiratory volume in 1 second at 24 weeks, the two coprimary end points (Am. J. Respir. Crit. Care Med. 2009;179:549-58).
▸ Esomeprazole for poorly controlled asthma: In a study carried out by the American Lung Association Asthma Clinical Research Centers, 412 patients were randomized to 40 mg of esomeprazole twice daily or placebo for 24 weeks. There were no differences in outcomes between the two study arms in terms of number of episodes of poor asthma control, nocturnal awakening, quality of life, airway reactivity, or pulmonary function. Nor did the 40% of participants with silent gastroesophageal reflux disease benefit from esomeprazole in terms of the study end points (N. Engl. J. Med. 2009;360:1487-99). It is clear that silent or minimally symptomatic GERD is not a likely cause of poorly controlled asthma, Dr. Nelson said.
▸ Monitoring adherence to inhaled corticosteroid therapy in asthmatic children and teens: Four methods of monitoring treatment adherence were evaluated in a 1-year study of 102 asthmatic 3- to 14-year-olds. Adherence deteriorated progressively over the course of the year. Parent and self-reports gave a wildly inflated picture of adherence. So did pharmacy dispensing records. Tracking canister weight proved to be the most practical and accurate method (Allergy 2009;64:1458-62).
▸ Thermoplasty for severe asthma: Thermoplasty reduces airway smooth muscle mass. The regimen entails three treatment sessions at 2-week intervals.
In Dr. Nelson's view, the verdict remains out regarding this procedure, despite a 288-patient multicenter, randomized, double-blind, sham-controlled trial. The primary study end point was clinically meaningful improvement in the Asthma Quality of Life Questionnaire score at 52 weeks. This occurred in 79% of patients who underwent thermoplasty and 64% in the sham-procedure arm.