Diagnostic delay and clinical modifiers in alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency (AATD) is one of the most prevalent inherited diseases in Whites, but identification of affected patients and establishment of the diagnosis is still unsatisfactory. This study assessed the latencies and numbers of physicians involved in identifying AATD patients, and the importance of smoking, vaccination status, and specific augmentation therapy on the course of the disease.

Patients from Germany and Austria underwent a single written interview with 28 items. Five hundred and ninety-six patients were addressed and 44.9% replied.

The age at symptom onset was 39.1±10.1 years, and the diagnosis was established at the age of 45.1±10.9 years. From the 6-year delay in establishing the diagnosis, 1.4±1.7 (range 0.5-10.5) years were due to patients' reluctance to seek medical attention. There were 3.2±2.4 (range 1-13) physicians involved in establishing the diagnosis. Smoking was associated with an earlier onset of respiratory symptoms and lower exercise capacity. Vaccination against pneumococci and/or influenza, and augmentation therapy resulted in significantly fewer exacerbations and fewer emergency room visits. Airway infections and passive smoking during childhood were not found to influence the onset of respiratory symptoms.

In conclusion, there is still a large delay between symptom onset and AATD diagnosis. Smoking history, vaccination status, and augmentation therapy have an important impact on the course of the disease.