A 38-year-old man comes to the office due to progressive shortness of breath and cough with mucoid sputum over the past 6 months. His shortness of breath is worse with exertion. The patient has no chest pain, weight loss, or night sweats. Past medical history is otherwise unremarkable, and he takes no medications. He smoked cigarettes for 5 years but quit 13 years ago. The patient does not use alcohol or illicit drugs. Temperature is 36.7 C (98 F), blood pressure is 128/78 mm Hg, pulse is 78/min, and respirations are 16/min. His pulse oximetry is 96% on room air. BMI is 32 kg/m2. Breath sounds are decreased at the bases, and there are no crackles or wheezes. Heart sounds are normal. There is no jugular venous distension or peripheral edema. Chest imaging reveals bilateral basilar hyperlucency. Complete blood count and basic metabolic panel are normal. Which of the following is the most appropriate next step in management?
This patient with chronic shortness of breath, productive cough, and evidence of destruction of the lower lung lobes likely has alpha-1 antitrypsin (AAT) deficiency. AAT deficiency-related lung disease presents similarly to other forms of chronic obstructive pulmonary disease (COPD) but results in panacinar (panlobular) emphysema. Smoking-induced centriacinar (centrilobular) emphysema most commonly causes disease in the upper lobes of the lungs, whereas the panacinar emphysema of AAT deficiency classically results in greater destruction of the lower lobes. On average, smokers present in their 30s, whereas nonsmokers present in their 40s. AAT deficiency is frequently associated with liver disease, most commonly resulting in neonatal hepatitis, cirrhosis, or hepatocellular carcinoma.
AAT deficiency should be considered in a number of situations, including in patients with:
Diagnosis is confirmed by measuring serum AAT levels, and pulmonary function testing should also be performed. Treatment includes intravenous supplementation with pooled human AAT.
(Choice A) Sleep disordered breathing due to obesity such as obstructive sleep apnea (confirmed by polysomnography) more commonly presents with daytime sleepiness, impaired concentration, and morning headaches.
(Choice B) Bronchoprovocation testing with methacholine can be used to confirm asthma diagnosis in selected groups of patients such as those with typical asthma symptoms but normal spirometry. Hyperinflation may be seen on chest x-ray, but basilar hyperlucency is unlikely.
(Choice C) An echocardiogram is very useful to evaluate cardiac sources of dyspnea. However, this patient's pulmonary findings along with the lack of jugular venous pressure elevation and peripheral edema make a cardiac cause less likely.
(Choice E) Sweat chloride testing is used to confirm the diagnosis of cystic fibrosis (CF); however, adult presentations of CF are more commonly characterized by gastrointestinal, endocrine, and fertility problems. The absence of bronchiectasis on lung imaging also makes CF less likely.
(Choice F) Lung biopsy is an invasive procedure with associated morbidity. Measurement of the serum AAT level is less invasive, and low values are highly diagnostic for AAT deficiency.
Educational objective:
Alpha-1 antitrypsin (AAT) deficiency should be considered in patients who lack typical risk factors for chronic obstructive pulmonary disease (eg, age <45) or those with atypical features (eg, basilar-predominant disease). Diagnosis is confirmed by measuring serum AAT levels.