Nocturnal asthma uncontrolled by inhaled corticosteroids - Theophylline orlong-acting beta(2) agonists?

Asthma is an inflammatory disease of the airways that is frequently charact erised by marked circadian rhythm. Nocturnal and early morning symptoms are quite common among patients with asthma. Increased mortality and decreased quality of life are associated with nocturnal asthma. Although numerous me chanisms contribute to the pathophysiology of nocturnal asthma, increasing evidence suggests the most important mechanisms relate to airway inflammati on. According to international guidelines, patients with persistent asthma should receive long term daily anti-inflammatory therapy. A therapeutic tri al with anti-inflammatory therapy alone (without a long-acting bronchodilat or) should be assessed to determine if this therapy will eliminate nocturna l and early morning symptoms. If environmental control and low to moderate doses of inhaled corticosteroids do not eliminate nocturnal symptoms, the a ddition of a long-acting bronchodilator is warranted. Long-acting inhaled beta (2) agonists (e.g. salmeterol, formoterol) are eff ective in managing nocturnal asthma that is inadequately controlled by anti -inflammatory agents. In addition, sustained release theophylline and contr olled release oral beta (2) agonists are effective. In patients with noctur nal symptoms despite low to high doses of inhaled corticosteroids, the addi tion of salmeterol has been demonstrated to be superior to doubling the inh aled corticosteroid dose. In trials comparing salmeterol with theophylline. 3 studies revealed salmeterol was superior to theophylline (as measured by e.g. morning peak expiratory flow, percent decrease in awakenings, and nee d for rescue salbutamol), whereas 2 studies found the therapies of equal ef ficacy. Studies comparing salmeterol to oral long-acting beta (2) agonists reveal salmeterol to be superior to terbutaline and equivalent in efficacy to other oral agents. Microarousals unrelated to asthma are consistently in creased when theophylline is compared to salmeterol in laboratory sleep stu dies. In addition to efficacy data, clinicians must weigh benefits and risks in c hoosing therapy for nocturnal asthma. Long-acting inhaled beta (2) agonists are generally well tolerated, if theophylline therapy is to be used safely , clinicians must be quite familiar with numerous factors that alter cleara nce of this drug, and they must be prepared to use appropriate doses and mo nitor serum concentrations. Comparative studies using validated, disease sp ecific quality of life instruments (e.g. Asthma Quality of Life Questionnai re) have shown long-acting inhaled beta (2) agonists are preferred to other long-acting bronchodilators. Examination of costs for these therapeutic op tions reveals that evening only doses of long-acting oral bronchodilators a re less expensive than multiple inhaled doses. However, costs of monitoring serum concentrations, risks, quality of life and other outcome measures mu st also be considered. Long-acting inhaled beta (2) agonists are the agents of choice for managing nocturnal asthma in patients who are symptomatic despite anti-inflammatory agents and other standard management (e.g. environmental control). These a gents offer a high degree of efficacy along with a good margin of safety an d improved quality of life.