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For years, corticosteriods have beenconsidered the “gold standard”’ ofmedicines for the treatment of asthma,and for good reason. They are veryeffective. Given this, corticosteriods willlikely maintain an important place inasthma treatment in the future. At thesame time, new and innovativeapproaches are being developed—someof which may result in better control ofasthma with fewer side effects.

Better UnderstandingEquals Better Drugs

The development of new treat-ments is fueled, in large part, by sci-entists’ improved understanding ofhow asthma works. Asthma is allabout inflammation—inflammationof the respiratory tract that results inwheezing, coughing, shortness ofbreath—the classic asthma symptoms.

The Cellular DanceInflammation of the airways is

caused by the interaction of variouscells in the body when a trigger isintroduced, typically an allergen, irri-tant, or respiratory infection.Understanding the details of howinflammation occurs is very compli-

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cated, which is why we’ll leave it upto the scientists! In general terms,one needs only to know that the air-way inflammation of asthma iscaused by chemical reactions involv-ing various cells, proteins, andenzymes within the body. Each per-forms specific steps in complex reac-tions that can be likened to a dance.To prevent asthma, scientists mustlearn how to prevent or alter a stepin that orchestrated dance—to inter-rupt the essential steps that lead toinflammation.

The Future Is TodayFor years, one of the most

promising new drug treatments forasthma has been a new class ofdrugs called anti-IgE. Last year, thefirst drug of this class, omalizumab,was approved by the FDA and issold under the trade name Xolair. Itis so radically different from anyprevious treatment approach that ittook many years of research andclinical trials before this approvalwas granted. (Even now, theapproval is narrow, so it is onlyavailable to a small portion of theasthma patients who may eventuallybenefit from it.)

Anti-IgE treatment is designed toprevent an allergic reaction fromoccurring. When an allergic personcomes in contact with an allergen, acascade of events occurs in the

body. During this process, a sub-stance called immunoglobulin E(IgE) attaches itself to certain cells(called mast cells). This triggersthem to release chemicals, includinghistamine and leukotrienes, whichcause the person to experience aller-gy or asthma symptoms. The anti-IgE treatment, when present in thebody, binds with the IgE in the per-son’s circulatory system so the IgEcannot attach to the mast calls. Insimple terms, it interrupts the aller-gic process, preventing allergicsymptoms. This has been found tobe very effective in preventing orreducing the severity of allergicasthma.

More anti-IgE drugs are currentlyunder investigation. In addition,approval of Xolair will likely beexpanded in the future to make itmore widely available for people withallergic asthma. Similar drugs mayalso become available for other aller-gic diseases, such as severe food aller-gies and allergic rhinitis.

In the PipelineDrug companies around the world

are working to develop other drugs totreat asthma. There are manyresearchers pursuing a variety of dif-ferent approaches, each with the samegoal: to devise new, better, and saferdrugs for controlling, and perhaps oneday curing, asthma. Here is a sam-

pling of some promising drugs thatuse different approaches to treatment.

Protecting the Lungs FromEnvironmental Triggers

Pumactant (Britannia Pharma-ceuticals) is a drug that is showingpromise and has its researchers quiteexcited. While still in early stages ofclinical trials with only a small num-ber of subjects studied, the resultshave been quite dramatic. This drypowder, when inhaled, works as asurfactant, coating the lining of thelungs and mimicking the body’s ownnatural lining. It seems to increasethe lungs’ ability to protect them-selves from allergens and irritants.

In one study, participants wererandomly selected to receive eitherPumactant or an inactive placebosubstance. The study included 7 sub-jects who received the full dose ofPumactant. They were given 2 sepa-rate doses, one 8 hours before andanother 30 minutes before exposureto an allergen. Their lung function(FEV1) was then measured at regularintervals over a 10-hour period tolook at the immediate asthmaticresponse (which occurs within 15minutes of exposure to an allergen)and the late asthmatic response(which occurs 3 to 10 hours later).They found that the immediateasthmatic response was completelyabolished! Pumactant’s ability toprevent the late asthmatic responsewas less dramatic but still promising.(EurRespir Jour 2003; 21:1046-9)

Interupting the Inflammation ProcessScientists in Japan have received

approval to market 2 drugs, Baynas(Bayer Yakuhin Ltd.) and seratrodast,to treat allergic asthma. These drugsare similar in that they target (eachin a different way) the proteinThromboxan A2 (TXA2), which isinvolved in the allergic response.

Seratrodast has shown promisingresults in early clinical trials in theUnited States, with a small group oftreated patients experiencing signifi-cant improvements, including fewer

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asthma symptoms and decreased useof a rescue inhaler, compared to acontrol group (CHEST 2000;118:73-9). According to the researchers,seratrodast “elicits a decrease in theamount of daily production of spu-tum and improves breathlessness,wheezing, and cough, with minimalside effects, in patients with mild tomoderate asthma.”

New Look at OlderTreatments

Improving on an Older DrugTwo drugs, roflumilast and Ariflo

(SmithKline Beecham), are in PhaseIII clinical trials. Both of thesedrugs are PDE inhibitors. You mayhave heard of one commonly pre-scribed PDE inhibitor, theophylline.Unlike today’s theophylline, these 2new drugs are much more specificin the enzymes they target, whichmay mean fewer side effects for thepatient.

It’s All in the DeliveryResearch is focusing on another

aspect of asthma treatment: drugdelivery. One of the reasons inhaledcorticosteroids are so widely used isthat the inhalers transmit the drugdirectly to the airways, reducing theamount of drug absorbed into therest of the body and, therefore, thepotential for side-effects. Look formore inhaled medicines in thefuture, especially in powdered form.

Making Allergy Shots SaferLikewise, systems of delivery for

other treatments are being investi-gated. Scientists are looking at theage-old treatment, immunotherapy(allergy shots). Immunotherapy hasbeen shown over the years to beextremely effective in reducingsymptoms of allergic rhinitis, andrecent studies have shown that itcan also be very effective in control-ling allergic asthma. However, it isnot widely used because it requiresregular, frequent injections andposes the risk of the patient having a

severe allergic response to the treat-ment. Researchers are looking toalter the vaccines using geneticallymodified versions of the allergens—versions in which the protein thatcan cause an allergic reaction isremoved or made impotent. Thisnew type of immunotherapy isdesigned so that the body will devel-op the protective response to theallergen without the risk of a seriousallergic reaction.

Combination DrugsAnother approach in the develop-

ment of new treatments to helppatients better manage their asthmais the creation of “combination”drugs—the proper dosage of 2 dif-ferent medications contained in asingle inhaler. For the patient, itmeans fewer inhalers to keep trackof, fewer to get refilled in a timelymanner, and fewer to remember touse. So much of successful asthmamanagement relies on patients actu-ally taking their medications asinstructed. Combination drugs facil-itate this process, and it is likely thatcombination drugs will becomemore common in the future.

Almost Science FictionYou have probably heard of the

investigation into “gene therapy”for other diseases. This is beingstudied for the treatment of asthmaas well. One possible therapyinvolves modifying the segment ofhuman gene involved in the pro-duction of cytokines. Cytokines areproteins in the body that areinvolved in regulating the immuneresponse and are believed to play animportant roll in asthma. Througha process of gene therapy, scientistsbelieve it may be possible to “turnoff ” cytokine production, whichmay prevent asthma symptoms.Scientists are using mice to investi-gate this angle that may somedaylead to gene therapy in humans.

Other approaches to manipulatingcytokines to prevent asthma are alsobeing studied. Some cytokines actu-

ally counter inflammation. IL-10 isone “anti-inflammatory” cytokinethat the body produces naturally.Scientists believe that by learninghow to increase the body’s produc-tion of IL-10, it may be possible toinduce the body to create its ownantidote to asthma.

How Advances WillAffect Patients

There is a great deal of excitingresearch going on in the field ofallergy and asthma. While some newmedications will become available inthe near future, there are teams ofscientists working on research thatmay not result in a marketable drugor treatment for many years. Whilelooking forward to future advancesin treatment, it is important now tolearn about and properly use the veryeffective treatments that are alreadyavailable.

“The goal of therapy is control ofasthma symptoms, whatever medi-cines might be required,” explainsWilliam Storms, MD, of ColoradoSprings, Colo. Individuals with asth-ma should make a point to checkwith their specialists every couple ofyears to see if new treatments offer aviable alternative to their current reg-imen. “Guidelines and medicationrecommendations change,” explainsDr. Storms, “and the patient shouldhave the benefit of the most up-to-date therapy.”

Gretchen W. Cook is a freelance writerin Jackson, Miss., who specializes infamily and health topics. She wasdiagnosed with asthma at age 6.

Reprint orders: Elsevier Inc., 11830 WestlineIndustrial Dr., St. Louis, MO 63146-3318;phone (314)453-4350.doi: 1016/j.asthmamag.2004.01.004