Pulmonary Q&A: More Treatment Choices for Patients With COPD

Q:What are the newer optionsfor patients with chronicobstructive pulmonary disease(COPD)?

A: Several new drugs are being introduced--and more are on thehorizon.

Tiotropium. This long-acting anticholinergicbronchodilator, introducedearlier in Europe and elsewhere,is now approved for long-term,once-daily maintenance treatment ofCOPD in the United States. Tiotropiumis delivered as a dry powder via adevice known as the HandiHaler. It offersseveral advantages over the establishedanticholinergic, ipratropium,which is used extensively as a firstlineshort-acting bronchodilator forsymptomatic relief. Tiotropium binds to M₃ muscarinic receptors responsiblefor bronchodilatation more firmly and for a longer time than ipratropium.^1,2 Theduration of action of tiotropium is 24 hours or more, which makes it suitable foronce-daily dosing.³ By comparison, ipratropium is usually administered 4 to 6times per day. Recent controlled clinical trials show that tiotropium is superiorto ipratropium for long-term bronchodilation and symptomatic improvement.^3,4

Ipratropium and albuterol have also been available for some time in acombination aerosol bronchodilator that is used 3 or 4 times a day for symptomaticrelief.

Tiotropium offers sustained bronchodilation that exceeds that producedby the 2 long-acting β-agonists salmeterol and formoterol. When tested againstsalmeterol, tiotropium was more potent and longer-lasting.^5,6 No studies havethus far evaluated the effectiveness of tiotropium combined with a long-actingβ-agonist.

Tiotropium may well become a “cornerstone drug” in the maintenancemanagement of symptomatic stages of COPD. Unlike other widely used bronchodilators,tiotropium appears to elevate baseline lung function, as measuredby forced expiratory volume in 1 second (FEV₁) over time.⁷ It may thus be useful in early stages of COPD, although it has not yet been evaluated in thisclinical setting.

Fluticasone/salmeterol. The combination of fluticasone and salmeterol,which is delivered in a dry-powder inhaler (Diskus), was approved by the FDAas maintenance therapy for patients with COPD.^8,9 Although the role of inhaledcorticosteroids remains controversial in moderate to severe COPD, their useis increasing.¹⁰ The Global Initiative for Chronic Obstructive Lung Disease(GOLD) recommendations specify that long-term use of inhaled and oral corticosteroidsbe reserved for patients who have a documented spirometric responseto corticosteroids and those who have an FEV₁ of less than 50% of predictedand repeated exacerbations that require treatment with antibiotics andoral corticosteroids.¹¹

Future options. Drugs on the horizon include the phosphodiesterase-4inhibitors, 2 of which--cilomilast and roflumilast--are in phase 3 clinical trials.Roflumilast is currently awaiting regulatory approval in Europe for the managementof asthma and COPD. Results of early clinical trials appear to showthat this agent, taken once daily, improves FEV₁ significantly more than placeboand reduces the number of COPD exacerbations in a dose-dependent manner.¹² Other drugs, such as mucotropic agents, are being investigated.¹³