The Winter 2015 issue of Alpha-1-To-One magazine is in the mail to some 27,000 people with free subscriptions and is now available online.
Q: How close are we to an inhaled augmentation therapy for Alpha-1? Will I be able to carry a little inhaler in my pocket, the way I carry my albuterol now? That would be so great.
A: For sure, a convenient, effective, inhaled form of augmentation therapy has great appeal. Some published studies do suggest that alpha-1 antitrypsin from pooled human plasma can be administered to the lungs of people safely and, at least in the short-term, can preserve lung function. Of course, before any therapy can be approved, rigorous studies of safety and effectiveness are required.
James Stoller, MD
One way to help evaluate inhaled therapy is to participate in a study being performed at two sites in the U.S. This is a double blind, placebo controlled trial sponsored by Kamada. Patients already receiving intravenous augmentation therapy will have to stop this treatment for 8 weeks before the study and during the entire time of participation in the study. If you join this study, you will receive a bronchoscopy at the beginning and again after 12 weeks on either placebo inhalations, or one of two different doses of inhaled augmentation therapy. At the end of the blinded portion of the study, participants may elect to continue in a 12-week open label portion during which everyone will receive the highest dose of inhaled alpha-1 antitrypsin. To learn more about this study, contact Joanna Nolte in Gainesville, FL at (352) 273-7225 or email@example.com; or contact James Stocks, MD, in Tyler, TX at firstname.lastname@example.org.
Please understand that this study uses a nebulizer for inhalation – not a little metered dose inhaler (MDI) of the kind that many people now carry in their pocket or purse. There are currently no trials of inhaled Alpha-1 augmentation therapy using devices like the one you mentioned, the pocket-sized inhalers that many Alphas are familiar with.
Like you, others are enthusiastic about the possibility of inhaled augmentation therapy. But for now, we will all need to stay tuned.
Q: I am very interested in an Alpha-1 research study that I read about. My doctor said it’s OK for me to be in the study, but he pointed out that two bronchoscopies are required. Bronchoscopies scare me. What is your opinion?
A: Bronchoscopy is a routine test performed by lung doctors, usually for diagnosis and occasionally for treatment of lung conditions. While every invasive test carries some risk, the procedure is usually very well tolerated.
The generally low risks of bronchoscopy can be broken down into three aspects: 1. Sedation or anesthesia 2. Placing the bronchoscope into the lung and examining the airways and 3. Performing any biopsies. If biopsies are done, the risk depends on whether the biopsies are of the airways or bronchial tubes themselves or of other structures in the lung, like lymph nodes or even the lung tissue itself. Most of this very low risk relates to biopsies, which can cause bleeding, or if the lung tissue is sampled, a collapsed lung (called a pneumothorax).
Usually, bronchoscopy is done using calming medicines called “conscious sedation,” in which short-acting sedatives like midazolam, trade name Versed, are used along with a short- acting narcotic like fentanyl or morphine. These medicines provide excellent sedation and amnesia, so that patients rarely remember having had the procedure. The procedure is done with close monitoring of oxygen levels, vital signs, etc.
Another aspect of your question is the importance of research in Alpha-1 Antitrypsin Deficiency. The amazing progress that has been made in Alpha-1 over the 52 years since it was first described by Carl-Bertil Laurell and Sten Eriksson in 1963 has been due to the partnership between patients and the clinical/scientific community. We need patient participation to achieve better treatments and diagnosis.
In the end, participation in a research study is a highly personal matter and requires a candid consent discussion between researchers and patients. You must fully understand the study procedures, timeline, risks, and potential benefits without any sense of pressure. With that information and awareness of how important research is, I know you will make the right, informed decision for you.
Q: I’m a ZZ Alpha. I have cirrhosis, and some emphysema, too. If I have a liver transplant eventually, will that also cure my emphysema?
A: Severe deficiency of the PI*ZZ type is primarily a liver disease in which the alpha-1 protein is trapped in the liver and cannot escape into the bloodstream to bathe and protect the lung against enzymes that break down the walls of the air sacs called alveoli. Liver transplantation is offered to Alphas with advanced liver damage, most commonly scarring, called cirrhosis.
When an Alpha receives a liver from a normal donor, the transplanted liver makes a normal amount of alpha-1 antitrypsin and secretes it into the bloodstream, so the transplant patient now has a normal amount and type of alpha-1 antitrypsin in the blood.
While there is some variation from patient to patient, the best evidence suggests that the emphysema will no longer progress at a rate faster than normal. Still, just as augmentation therapy cannot restore lung function that is lost, so too would a liver transplant be expected to stabilize – but not restore - lost lung function or existing emphysema damage.