An Interview with Dr. Robert Sandhaus: the Latest Alpha-1 Clinical Practice Guidelines

Dr. Robert Sandhaus, thank you for talking with us about the most recently published (2016) Alpha-1 Antitrypsin Deficiency Clinical Practice Guidelines. As our readers likely know, the first Alpha-1 Antitrypsin Deficiency (AATD) diagnosis and management standards were published in 2003. What prompted this new update?

Dr. Sandhaus: The writing of the 2003 Standards document was a massive undertaking and was the first evidence-based recommendations regarding AATD. Unfortunately, it was dense with detailed information and references and very long (87 pages). Very few clinicians had the time or energy to wade through it and find the detailed answers questions they might have. In 2001, the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) approached the Alpha-1 Foundation and asked if they could provide a treatment outline for AATD to be published on the NHLBI website. It was clear from the guidance they provided to us that they were looking for a clinical practice guideline, so the Alpha-1 Foundation, in conjunction with the American Thoracic Society, decide to create a concise guideline which reviewed the literature from 2003 onwards (to update the Standards document) but also was accessible to the average clinician treating patients with AATD.

How much has our knowledge base changed in that time?

Dr. Sandhaus: Several major publications regarding the diagnosis and treatment of AATD have appeared in the medical literature since the 2003 Standards document. Therefore, the writing committee saw this as an opportunity to update some of the recommendations contained in the original Standards document and include some new approaches.

What are the most major differences between the 2003 and 2016 guidelines?

Dr. Sandhaus: The major differences between the two guidelines include a recommendation that augmentation therapy be considered in any patient with severe AATD and evidence of emphysema, independent of their spirometry results. The 2003 document had limited the recommendation to treat to those with moderate airflow obstruction. In addition, the 2016 guideline recommends against treating individuals who are carriers of a single abnormal gene for AATD. This recommendation is based on the lack of evidence to support such therapy and recent studies that have shown that while carriers have a dramatically increased risk of developing COPD if they smoke, compared with those whose alpha-1 antitrypsin genes are normal, smoking cessation or prevention eliminates that extra risk. The 2016 document also delves more broadly into the medical follow-up and monitoring that should be done on all individuals with AATD.

How important is this information for those working in primary care settings?

Dr. Sandhaus: It is important to emphasize that the majority of COPD patients are followed in the primary care setting and that approximately 1% of COPD patients have undetected severe AATD as the underlying cause of their lung disease. Healthcare providers in both primary care and specialty settings should head the strong recommendation of these guidelines that ALL patients with COPD should be tested for AATD, regardless of smoking history, age, race, or severity of disease. There is specific therapy available for those with COPD due to AATD.

As with many rare disease states, there are still gaps in our collective knowledge about the diagnosis, treatment and management of AATD. Is research improving in these areas?

Dr. Sandhaus: As the question implies, AATD is a rare disease and this means that large clinical trials of novel therapies can be very difficult or impossible to enroll. There are a broad range of new therapies that are currently under investigation including those designed to treat AATD-associated lung disease and liver disease. Gene therapy trials have already been started for this genetic condition and many exciting potential therapies are being explored. The great news is that his research may well lead to novel treatments for COPD, in general.

What do you think is the most promising research or clinical practice on the horizon that will provide the most benefit to individuals affected by this disease?

Dr. Sandhaus: The Alpha-1 Foundation has its eyes focused on curing AATD. It’s important to realize that there may be a number of very different paths to a cure. One exciting program has designed a type of gene therapy that both turns off production of the abnormal protein in the liver and begins production of normal alpha-1 antitrypsin protein in those same cells. Many patients with COPD due to AATD are looking forward to therapies that don’t require weekly intravenous infusions of plasma-derived alpha-1 antitrypsin protein the way current treatment does. They look forward to being able to inhale their treatment via a nebulizer or even take a pill each day to provide the same protection. There is research progressing right now to evaluate these different forms of therapy.

To read Dr. Sandhaus and colleagues' full article on the newest guidelines, visit the Journal of the COPD Foundation.

This page was reviewed on March 3, 2020 by the COPD Foundation Content Review and Evaluation Committee