James Stoller, MD: Delayed Diagnosis of Alpha-1 Antitrypsin Deficiency

Alpha-1 Antitrypsin Deficiency is often diagnosed long after it's developed, and late diagnosis leads to worse outcomes.

Not all patients with COPD will develop Alpha-1 Antitrypsin Deficiency, but for those that do, early diagnosis is paramount. James Stoller, MD, MS, professor and chairman of the Cleveland Clinic's Educational institute, sat with MD Magazine at the 2017 annual CHEST conference in Toronto, Ontario, Canada, to discuss early diagnosis, and how it could improve outcomes.


Alpha-1 Antitrypsin Deficiency is under recognized. We certainly know that from many lines of evidence. There's a long interval between when patients first have symptoms, and when they're first recognized, first diagnosed as having this condition. That interval of time, on average, may be as long as 7 to 8 years.

There are 2 reasons that matters. These patients, number 1, have a genetic condition that predisposes them and their family members, their siblings, their children, even their parents, if recognized early enough, as being at risk for lung, and in some instances, liver disease. And there are specific therapies that are available that can sow the progression of the disease. This is a progressive loss of lung function, and sometimes progressive onset of liver disease, causing cirrhosis. So those 2 lines of reasoning strongly support the rationale for detecting these patients.

A number of guidelines from the American Thoracic Society, European Respiratory Society in 2003 have endorsed testing all adult patients with symptoms who have COPD for Alpha-1 Antitrypsin Deficiency, and yet we know that compliance with those recommendations has been less than perfect, and I think that contributes to the continued under recognition of these patients.

Our interest in this study was based upon the desire to examine whether a delay in diagnosis is associated with adverse clinical impact. The goal was to identify these patients at the moment of first recognition of Alpha-1.

What period of time transpired between your first symptom related to alpha-1, and the moment of diagnosis? In this particular study, the range was anywhere from 0 to as long as 26.8 years, with a median diagnostic delay interval - that's what we call this interval of time between first symptom and first diagnosis - of 3.5 years in this study.

So the essence is, number 1: it appears from these preliminary data, that delay in diagnosis is associated with worsened clinical status. It seems logical to presume on that basis that this is yet another impetus to make the diagnosis of Alpha-1 Antitrypsin Deficiency at an earlier time in the patient's natural history so that appropriate interventions can be made.

Again, as the guidelines suggest, every patient with COPD should be tested for Alpha-1 Antitrypsin Deficiency with a serum level and a genotype in order to characterize this patient's risk.

Most of these patients - most COPD patients will not have Alpha-1 Antitrypsin Deficiency. Only 2 or 3% will be found to have it. But for those 2 or 3% that diagnosis is highly impactful. That's the essential takeaway.