A 38-year-old man comes to the office due to progressive shortness of breath for the past several months. The patient gets winded when carrying groceries up a flight of stairs and when walking 2-3 city blocks. He also has a frequent cough productive of thick yellow sputum, especially in the morning. The patient has no other medical conditions. He says he smoked cigarettes occasionally during college, but recently he has been smoking 3 or 4 cigarettes daily after he began work at a new company 2 years ago. The patient does not use alcohol or illicit drugs.
Blood pressure is 124/72 mm Hg and pulse is 84/min. Oxygen saturation is 96% on room air. Lung auscultation reveals occasional expiratory wheezes and rhonchi. There are no heart murmurs. Chest x-ray reveals hyperinflated lungs. Spirometry shows the following:
Which of the following additional testing is most appropriate for this patient?

Question

A 38-year-old man comes to the office due to progressive shortness of breath for the past several months.  The patient gets winded when carrying groceries up a flight of stairs and when walking 2-3 city blocks.  He also has a frequent cough productive of thick yellow sputum, especially in the morning.  The patient has no other medical conditions.  He says he smoked cigarettes occasionally during college, but recently he has been smoking 3 or 4 cigarettes daily after he began work at a new company 2 years ago.  The patient does not use alcohol or illicit drugs.
Blood pressure is 124/72 mm Hg and pulse is 84/min.  Oxygen saturation is 96% on room air.  Lung auscultation reveals occasional expiratory wheezes and rhonchi.  There are no heart murmurs.  Chest x-ray reveals hyperinflated lungs.  Spirometry shows the following:
 Which of the following additional testing is most appropriate for this patient?

Quizplus · Accepted Answer

This patient's presentation is concerning for alpha-1 antitrypsin (AAT) deficiency, a common genetic disorder that affects the lungs, liver, and occasionally the skin (eg, panniculitis). AAT is a protease inhibitor that protects the lungs from the neutrophil elastases that can lead to emphysematous lung destruction when unchecked. Cigarette smoking and infections can accelerate the decline in pulmonary function in affected patients. In most patients, liver disease (eg, hepatitis, cirrhosis) predominates in the first 4 decades of life, whereas pulmonary manifestations (eg, emphysema, pneumothorax, bronchiectasis) become more significant at older ages. Chest x-ray reveals basilar emphysema rather than in the apices, as seen with typical smoking-induced emphysema. It is generally recommended that AAT levels should be tested in all patients with new-onset obstructive pulmonary disease, but early-onset emphysema (age ≤45 years), emphysema with minimal smoking history, or unexplained liver disease are particularly suggestive of reduced levels. Identification of the deficiency allows for early management (eg, smoking cessation, inhaled bronchodilators, corticosteroids, supplemental oxygen) for affected patients. In addition, intravenous augmentation therapy with pooled human plasma AAT effectively increases levels and can slow emphysema progression and decline of lung function. (Choice A) Allergen skin testing is an important part of the evaluation of adult-onset asthma in order to identify key risk factors and triggers; however, this patient's presentation is more consistent with emphysema. Specifically, the lack of reversibility of airflow obstruction with bronchodilators is much more suggestive of AAT deficiency than new-onset asthma. (Choice B) Lung biopsy can be helpful in evaluating the underlying cause of interstitial lung disease, which can also present with dyspnea and reductions in lung volumes on spirometry. However, physical examination and chest x-ray more commonly reveal crackles and interstitial infiltrates, respectively. Moreover, the reductions in lung volumes are proportional and the FEV1/FVC ratio is normal. (Choice C) This patient's presentation is not typical for either asthma or chronic obstructive pulmonary disease (COPD) and consequently requires further investigation for other underlying causes such as AAT deficiency. COPD usually presents in patients age 50-60, and adult-onset asthma is associated with bronchodilator reversibility. (Choice D) Right heart catheterization is important in the evaluation of pulmonary hypertension, which is characterized by progressive dyspnea, fatigue, and evidence of right heart failure (eg, peripheral edema). Productive cough and wheezes are not typical unless pulmonary hypertension is secondary to underlying obstructive lung disease. Educational objective: Alpha-1 antitrypsin levels should be tested in all patients with new-onset obstructive pulmonary disease, but early-onset emphysema (age ≤45 years), emphysema with minimal smoking history, or unexplained liver disease are particularly suggestive. Deficiency typically results in early-onset, basilar emphysema, liver disease, and, occasionally, panniculitis. __________ References: Alpha1-antitrypsin deficiency: forgotten etiology. (http://www.ncbi.nlm.nih.gov/pubmed/20090075) Diagnosing a1-antitrypsin deficiency: how to improve the current algorithm. (http://www.ncbi.nlm.nih.gov/pubmed/25726555)

A 38-Year-Old Man Comes to the Office Due to Progressive