However, this assessment is likely to be underestimated based on the calculation that if there are 13 million subjects with chronic obstructive pulmonary disease (COPD) in the U.S. — and that AAT deficiency (mostly PiZZ) is a well-established risk factor for COPD and PiZZ comprises 1–3% of all COPD cases [42] with both lower and higher prevalence reported based on the cohort defined [43] — then 130 000–390 000 with known COPD are predicted to be AAT deficient (PiZZ). The gene discussed is SERPINA1; the disease is alpha 1-antitrypsin deficiency.