Alpha-1 Finds a Voice
by Greg Thompson
Thanks to the Alpha-1 Foundation, many COPD patients with alpha-1 antitrypsin deficiency have been properly diagnosed and treated, but the work is far from over.
Prior to 1995, the genetic disorder known as alpha-1 antitrypsin deficiency (alpha-1 for short) was the underdog in a race for research dollars. Lumped under the COPD umbrella, the disease failed to gain the support of investigators necessary in the quest for better therapies—or even cures. Alpha-1 is characterized by a deficiency in the production of the protein alpha-1 antitrypsin, which protects lungs from enzymes of inflammatory cells, especially elastase. In its absence, elastase is free to break down elastin, which contributes to the elasticity of the lungs, resulting in respiratory complications such as emphysema or COPD.
The complexion of that race changed imperceptibly in 1989 when businessman John Walsh, who owned a technology firm at the time, was diagnosed with alpha-1. Walsh had shown symptoms for 5 years, but physicians thought he had only allergy-induced asthma. Left with only 37% lung function, Walsh learned all he could about the genetic condition, and eventually participated in a National Institutes of Health (NIH) study. Ultimately, the NIH decided that the study's conclusion would mark the end of alpha-1 research.
The NIH rationalized that they had successfully identified the alpha-1 protein in plasma, which was subsequently commercialized into a drug—with the objective to slow down the progression of the disease. "The NIH said they were not going to do any more research," says Walsh. "So we created the Alpha-1 Foundation (www.alphaone.org) to provide the leadership and resources to increase that research, improve health, promote worldwide detection, and cure alpha-1."
The Race Begins
In short, alpha-1 was now a contender. Walsh and two other "alphas" from Miami in 1995 founded the organization, and 3 years later—when they had developed the organization's infrastructure—funding began. Working with collaborators in the scientific community, Walsh and his colleagues created a research registry of individuals who had alpha-1. If researchers needed patients who could participate in clinical trials, a database stood at the ready. After that, they coordinated an investigative group made up of clinicians who understood alpha-1. That initial group has expanded to include more than 60 clinical resource centers across the country.
Expanding the network of clinicians who "understood" was not an easy task, as Bob Campbell, communications manager for the Alpha-1 Foundation, can attest. As an alpha-1 and COPD patient himself, the 64-year-old Campbell was not diagnosed until age 55. Even though Campbell had clearly defined COPD in his 20s (despite never smoking a cigarette), his physician "was not terribly curious" about the unusual situation.
In fact, none of the pulmonary specialists he encountered over many years expressed any particular surprise that a young nonsmoker could have COPD. Illumination only came after Campbell took the initiative to go to an allergist at the age of 55, a time when he was working full time in a difficult job that demanded a lot of energy. Thinking allergy shots might help what he thought was asthma, Campbell self-referred and eventually received knowledge that would change his life. "The allergist told me that he did not see any major allergens when he did all the testing," says Campbell. "The allergist noticed the severe COPD and the lung damage, and he noticed my smoking history was nonexistent. He did the logical thing and gave me an additional test, because he just wanted to rule something out. And of course, it turned out that I had alpha-1."
Why did not even one of the long line of pulmonary specialists ever once mention alpha-1? It is a good question, and Campbell believes it is not an uncommon story in today's pulmonary world. "No one showed any signs of wanting to test me for anything in particular," laments Campbell. "Many alpha-1 patients seem to get diagnosed almost accidentally, which is the way I would describe my own diagnosis. Had it not been for that one extra test, there is no reason to think that I would have been correctly diagnosed today."
For Campbell, the chance diagnosis proved invaluable because there were some treatments for alpha-1. The bottom line, says Campbell, is that doctors are not testing the prime suspects for it, and respiratory therapists do not have it on their radar. "Anybody with COPD and no smoking history, or a family history of alpha-1, ought to be tested for alpha-1," says Campbell without equivocation. "At that point, the question of genetics should be obvious. People who come down with COPD very early in life are a tiny minority of the COPD population. Even pack-a-day smokers rarely come down with COPD in their early 30s or 40s. It's much more common to have someone diagnosed with COPD in his 60s or 70s after a long period of smoking."
And alpha-1 patients who smoke tend to come down with COPD even earlier than those who do not smoke. Many of those patients are still not being tested for alpha-1, and smoking is, instead, being blamed 100%. In addition to helping patients, Campbell and Walsh hope to educate RTs and pulmonary physicians about alpha-1, how it develops, and how it can be treated.