α1-Antitrypsin deficiency in patients with COPD

Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 38-year-old man is evaluated for a 1-year history of cough with mucoid sputum and a 6-month history of mildly progressive dyspnea. He has a 12-pack-year history of smoking. He has no history of asthma, allergies, skin disease, or liver disease.

On physical examination, vital signs are normal. Pulmonary examination discloses decreased breath sounds bilaterally with no wheezing.

Laboratory studies, including a complete blood count and complete metabolic panel, are normal. Oxygen saturation is 97% breathing ambient air. The electrocardiogram is normal. CT scan of the chest shows basilar lucency without bronchiectasis. Spirometry reveals an FEV1 of 53% of predicted and an FEV1/FVC ratio of 64%. The DLCO is 67% of predicted. There is no significant improvement in airflow after bronchodilator administration.

Which of the following is the most appropriate next step in management?

A: α1-Antitrypsin level measurement
B: Initiation of an inhaled corticosteroid
C: Sweat chloride testing
D: Z and S genotyping for α1-antitrypsin alleles

MKSAP Answer and Critique

The correct answer is A: α1-Antitrypsin level measurement.

The most appropriate next step in management is measurement of the α1-antitrypsin (AAT) level. This patient’s symptoms and spirometry findings are consistent with COPD. In this young patient with COPD, AAT deficiency is a likely cause. AAT is an antiproteolytic enzyme that neutralizes neutrophil elastase. AAT deficiency results in excessive amounts of neutrophil elastase in the lung, which destroys elastin and causes early-onset obstructive pulmonary disease, typically panacinar emphysema with basilar predominance. Some patients with AAT deficiency may develop liver and skin disorders. AAT deficiency should be evaluated in selected patients with COPD because of the availability of specific therapy. AAT deficiency should be considered in patients with persistent airflow obstruction (particularly those diagnosed with COPD at age 45 years or younger), nonsmokers with emphysema, patients with predominantly basilar lung disease, and patients with chronic liver disease.

Inhaled corticosteroids may be indicated in patients with severe COPD in addition to a long-acting bronchodilator, but they should not be used as monotherapy in any stage of COPD.

Sweat chloride testing is the diagnostic test for cystic fibrosis. Bronchiectasis and purulent sputum are hallmarks of this disease. However, this patient has no evidence of bronchiectasis on CT scan. Patients with this degree of airflow obstruction and no purulent sputum would not have cystic fibrosis.

Genotyping for the most common AAT alleles is usually performed in patients who have documented deficiency of AAT, but it is premature to perform genotyping before documenting AAT deficiency.

Key Point