The simple act of inhaling and exhaling is one that many of us take for granted. It is a basic function that sustains life. But try to imagine taking medication by simply inhaling. Thanks to the impressive research being done in Norman Chigier's mechanical engineering lab, transplant patients and others may soon be able to gently inhale their daily medication rather than endure needles or swallow pills.

Inhaled medication is administered through a nebulizer, which is similar to an inhaler. "Nebulizers are typically used when inhalers do not supply sufficient medication." says Chigier. Inhalers are small fluorocarbon-driven devices, whereas nebulizers rely on a compressed air source to atomize a liquid supply of medicine and solution. This creates a spray that is inhaled by the patient. The use of nebulizers is commonplace for administrating medication for respiratory conditions such as asthma.

However, inhalation holds a wide scope of possibilities for taking your medicine and liking it too. Inhalable drugs present an easier and more pleasant form of dosage than shots or pills. Children and adults alike suffer from needle anxiety and difficulty swallowing. The benefits of inhalables have tremendous potential and the scope is endless. They reach the bloodstream faster than most methods and there is lesser chance of side effects, such as nausea, which often occurs with oral dosage.

Many medical conditions could benefit from such fast-acting therapy. Current research into inhaled forms of insulin may soon provide a brighter future for many diabetics. Other drugs in this form are being developed for vaccinations and to treat influenza and cystic fibrosis. It is also being used to reduce nausea and vomiting following chemotherapy. Inhaled forms of medication are already standard in rescue medications and for treating bronchial ailments such as emphysema, pneumonia, and chronic bronchitis.

Chigier had the foresight to realize the importance of sprays to the medical industry when he discovered the wide scope of their use in other areas of research. While doing work with liquid fuel in combustion for furnaces and rockets, he realized the small droplets and atomization he worked with could be used for many other things. He utilized his knowledge and experience in spray technology to address the special problems of atomization for inhalation therapy.

When he arrived at CMU in 1981, he quickly established the Combustion and Spray Laboratory, which is recognized as one of the best in the world. With a combination of vision and persistence, he has always managed to stay one step ahead of the competition. In 1984, he founded a special short course on sprays that still draws participants from all over the world. His impressive presentation of the variable application of sprays convinced one of his attendees to sponsor a Ph.D biomedical engineering student in 1997.

This had a profound effect on Chigier's line of research, which expanded to include the medical application of sprays that aroused his early curiosity. The sponsor providing funding for this very successful quest is DeVilbiss-Sunrise Medical, which provides inhalation systems to facilitate breathing and speed recovery. One of the world's largest manufactuers of medical products, they faced an immediate need for better dispensation of medication to lung transplant patients. In Chigier they found a valuable asset who shared their vision for diminishing suffering and provided a hopeful avenue for improvement in treating this disease.

Chigier now had the task of choosing the right graduate student from hundreds of applicants. He chose Timothy Corcoran, who not only had two engineering degrees from Lehigh but had also written two novels and a screenplay. "I snagged him up immediately." says Chigier who finds that Tim can do the work of several graduate students. Corcoran shares Chigier's drive and determination. He holds a B.S. and M.S. in mechanical engineering from Lehigh University and shares Chigier's compassion and concern for human suffering. Corcoran is also a rock climber and has volunteered with the CMU/EMS (emergency medical service) since 1997. He is a dedicated supervisor with EMS and "quote" from fellow volunteer.

Corcoran does his research in the basement of Hammerschlag Hall, where his lab is located. He immediately went to work on improving the performance of a nebulizer currently being used for lung transplant patients. "A fairly large percentage of these patients die within one year due to rejection." says Corcoran. The body is continuously attempting to reject the transplanted lung so the immune system is put into overdrive. To prevent the transplant from being rejected, the immune system must be weakened." Cyclosporine is a drug that reduces the level of the immune system, and the best way for it to reach the lung by inhalation. It can be taken orally but side effects occur.

Corcoran had the task at hand to improve the failure rate for this application. He started by examining what happens to the medication once it is inhaled. To do this he had to make a throat model from a cadaver. He modeled the throat in plastic but formed the trachea with glass. This allowed him to study the progress of the inhaled aerosols as they travel through the throat. "A lot of medication gets lost here," Corcoran explains because it gets deposited in this region and does not make it to the lungs." "Our aim is to design nebulizers to minimize the amount of medication that gets caught in the mouth and the throat." "By using florescent dyes we can tell how much medication actually deposits on the lungs."

Before the medication can be successfully deposited on the lungs, it first has to reach this destination. "This is a big part of the failure rate we are working against." says Chigier. He stresses the importance of the droplet size of the liquid inhaled through the nebulizer. "If it is too large it hits the surfaces fo the mouth and throat and goes to the stomach where it is useless. If it is too small it can be inhaled and exhaled and is useless." Corcoran adds, "The optimal size for the droplets to actually deposit in the lungs is right around 3 microns, which is three thousandths of a millimeter."

Corcoran points out that it's difficult to get medication onto the surface of the lungs so that it can penetrate and get into the bloodstream. The nebulizer allows patients to inhale the cyclosporine, making it easier to reach the surface of the lung so that it can be absorbed. "The advantage of working with the lung," Corcoran points out, "is that we are able to put the nebulized medication right onto the area where the rejection will occur." "It is a topical application like when you have a rash and are able to put hydrocortisone right on it."

The critical importance of this droplet size is a key feature in the success of Chigier's research. His early vision provided a unique measuring tool called a phase Doppler particle analyzer (PDPA) which features lasers that measure droplet size, velocity and temperature simulataneously in one microsecond. Recognizing the importance of such an instrument, Chigier bought the first one produced and this is the only instrument of it's kind in the world.

It was an insight that is changing the future of the medical treatment and the success rate. Chigier and Corcoran have broken time barriers in perfecting the nebulizer to quickly and efficiently dispense medication. In just a little over three years they have designed a nebulizer that has reduced the deposition in the nebulizer by almost half.

"The trick with the nebulizer we produced is that about 80 to 90 percent of the droplets it produces are less than five microns, so they are respirable whereas most of the nebulizers currently on the market can only produce about 50 percent of the droplets in the respirable range." says Corcoran.

"We also study the physiology behind why those numbers are what they are. I've studied the throat to try to determine whether we can combine our design and our physiology experiments and see if what we are producing is actually the best."

The incentive has been strong for Chigier and Corcoran. They are driven by the need of patients who can't wait. "When working with an immunosuppressant like cyclosporine," Corcoran says, "there is no way to know whether it is working or not until it stops working and the patient dies." It is important that a significantly improved product for dispensing this medication reaches the market soon.

Patent applications for the nebulizer were filed in January 1999 in the U.S., Canada and a few European countries. Corcoran says they are in the final stages of negotiation with the Food and Drug Administration. He expects DeVilbiss-Sunrise to start production in a few months. "They'll produce it with the patent still pending. The patent itself may not go through for a year or more. It can take a while but as long as the patent is pending the actual design is protected."

The process has gone quickly in pushing this through to the point of production. But Chigier is a determined man who is used to breaking records in getting things done. A man of action and purpose, Chigier has spent a lifetime being a step ahead of everyone else. Born and raised in South Africa, he entered Witwatersand University at the age of 14 and received an undergraduate degree in mechanical engineering. He then entered Cambridge and was one of youngest students to receive an M.A. in mechanical engineering in 1960 and a Ph.d in 1961. He also holds an Sc.D. On first applying for the revered doctorate of science, he was told he was too young and had not written enough books. A few years later he applied again and received this special distinguished degree based upon international recognition and many publications in 1977.

Chigier has an enthusiastic presence coupled with an engaging smile and a playful demeanor. His office in Scaife Hall is an expanse of concentrated energy where a constant stream of ideas seem to be bouncing off the walls. Stacked on the floor are copies of the two journals he publishes, books line one wall, and comfortable post modern furniture create a stylish atmosphere. The eye is drawn to color photographs on a horizontal file cabinet of a younger Chigier posed on a ski slope in Switzerland. More recent photos reflect the same interest and ability. These photos portray a man always poised for action who is constantly on the brink of a new discovery or challenge. Talking to him is like opening a book that you don't want to put down.

A twist of fate brought him to CMU, which he had no intention of doing originally. He was in Sheffield, England, when the mechanical engineering department head, William Sirignano called and invited him here to give a seminar. "I told him I never heard of CMU and had no idea where Pittsburgh was." says Chigier. "I was in no way interested." Not one to give up, Sirignano invited his wife, to come to Pittsburgh with the intention of convincing Chigier to join the faculty here. It worked. His wife loved it here and after three days she decided to stay. This convinced Chigier to move here in 1981.

CMU benefited from the decision Chigier made. Wherever he puts down roots, he thrives. He founded the international journal "Progress in Energy & Combustion Science" in 1974 and he is founder of the archival research journal, "Atomization and Sprays" He is also editor of the "Hemisphere International Book Series on Combustion." Chigier jokes that his hobby is founding things. He was also one of the founding members of the International Institute of Liquid Atomization & Spray Systems and is President of the organization's international council. He is also president of a small business, Combustion Research, which he uses for consulting and publishing.

A man with many missions, his energy level and curiosity seem to be boundless. Perhaps his ingenuity, zeal for life, and progressive research are based on his personal discipline. He has walked to work everyday for almost 20 years from his home nearby. "I have braved howling snow storms and torrential downpours." Says Chigier, who enjoys the commute on foot. "I also never use the elevator." His discipline also carries over to the diet that keeps him trim. "I always have the same thing for lunch." Says Chigier. "Every day I eat three raw carrots, four radishes, one tomato, half a green pepper, and whole grain bread with hummus. Oh, and an apple for dessert."

Chigier uses his stamina to always look beyond his current project. One of his most recent ventures involves an agreement that has recently been reached with UPMC for collaborative research to establish a deposition laboratory in Presbyterian-University Hospital. Radioactive traces will be used in clinical FDA trials to to determine the quanitity of medication that is deposited in particular locations of the respiratory tract and lung surfaces.

Kathy Brown Sutton