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“Nitric oxide is the chemical mediatorfor signaling in the brain - this ishow our brain does much of its neurotransmission,”says Dr. Erzurum,who is the principal investigator of afive-year National Institutes of Healthstudy to determine the factors leadingto asthma. “Nitric oxide also isproduced by the cells lining the bloodvessels of our body, and it is the primaryvasodilator of our system. Bycausing the muscle walls of the bloodvessels to dilate, it prevents hypertension.Overall, nitric oxide is essentialfor our body to function normally.”By the mid-1990s, new, highly sensitivetools were developed to detectnitric oxide in the much more preciseparts-per-billion range. Usingthese tools, researchers found thatnitric oxide was present in the exhaledbreath of all humans and elevated inthe lungs of patients with asthma.According to Raed Dweik, M.D.,staff physician with the Department ofPulmonary, Allergy and Critical CareMedicine, there are several theoriesabout the role of this excessive amountof nitric oxide. One theory is thatthe nitric oxide found in the lungs ofasthmatics is produced by a differentkind of cellular enzyme than the onesthat produce the “good” nitric oxide,and that this nitric oxide acts as a freeradical, causing damage to the cells inthe airways. A second theory holds thatthe high level of nitric oxide in thelungs of those with asthma is merely aharmless by-product of the inflammatoryprocess and plays no significantrole, either good or bad. “The thirdtheory, suggested by some researchhere and elsewhere, is that this nitricoxide is protective,” Dr. Dweik says.“There is some evidence that it bindswith more toxic oxidants in the lungsand neutralizes them.”While the exact role of nitric oxidein asthma remains a clinical question,the Food and Drug Administrationhas approved a machine - called aNIOX system - for clinical measurementsof nitric oxide in thelungs. Patients take a deep breath,blow into the NIOX machine, andthe level of nitric oxide is registeredinstantly on a screen. Whenthe patients undergo anti-inflammatorytherapy, the machine showsthat their nitric oxide levels drop.While the machine has been usedmostly in laboratories thus far, itsmanufacturer is developing a smallhand-held model that can be usedby asthma patients at home. Withthis device, patients can monitor thelevel of inflammation in their lungsonce a day or even more frequently,just as diabetics monitor their bloodsugar at home, and modify theirtherapy accordingly. The ClevelandClinic and three other research centersbegan clinical trials to test thehand-held device earlier this year.An even newer tool for identifyingasthma inflammation involves a test fordetecting a by-product of inflammationin the airways, called bromotyrosine,in an asthmatic’s blood or urine.Bromotyrosine is formed within thelungs and airways when a group of whiteblood cells known as eosinophils areactivated and release an enzyme calledeosinophil peroxidase (EPO).“Eosinophils are the professional hitmen in the body,” says Stanley Hazen,M.D., Ph.D., Section Head, PreventiveCardiology and Director of the Centerfor Cardiovascular Diagnostics andPrevention. “Their job is to kill invadingparasites and bacteria.”“‘Why, bless my lifeand soul!’ said Mr.Omer, ‘how do youfi nd yourself? Takea seat. Smoke notdisagreeable, I hope?’‘By no means,’ said I.‘I like it - in somebodyelse’s pipe.’‘What, not in your own,eh?’ Mr. Omer returned,laughing. ‘All the better,sir. Bad habit for ayoung man. Take aseat. I smoke, myself,for the asthma.’”DAVID COPPERFIELDBY CHARLES DICKENSwww.clevelandclinic.org 13