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MKSAP Quiz: Follow-up of progressive dyspnea

A 42-year-old man is evaluated in the office for follow-up of progressive dyspnea of 2 years' duration. He first noted dyspnea with exercise but now has symptoms when walking up a flight of stairs. Pulmonary function tests 2 years ago showed moderate airflow obstruction. He has no significant smoking history but a family history of emphysema. After physical examination and a chest radiograph, what is the most appropriate test to perform next?


A 42-year-old man is evaluated in the office for follow-up of progressive dyspnea of 2 years' duration. He first noted dyspnea with exercise but now has symptoms when walking up a flight of stairs. He has intermittent wheezing but no coughing or nocturnal respiratory symptoms. At the time of his initial evaluation 2 years ago, pulmonary function tests demonstrated moderate airflow obstruction. He has a 1-pack-year smoking history but has not smoked in 20 years. He has no environmental exposures. His father and uncle both have emphysema without a history of smoking. He takes no medications.

On physical examination, vital signs are normal. Oxygen saturation is 94% breathing ambient air. Examination reveals no clubbing or jugular venous distention, extra cardiac sounds, edema, pulmonary crackles, or wheezing.

A chest radiograph shows hyperinflation and diaphragmatic flattening.

Which of the following is the most appropriate test to perform next?

A. α1-Antitrypsin level
B. Exhaled nitric oxide test
C. High-resolution CT scan of the chest
D. Vascular endothelial growth factor-D

Reveal the Answer

MKSAP Answer and Critique

The correct answer is A. α1-Antitrypsin level. This content is available to MKSAP 18 subscribers as Question 18 in the Pulmonology and Critical Care section. More information about MKSAP is available online.

An α1-antitrypsin level should be obtained. This patient is younger than the usual age of presentation of COPD, and he does not have a significant smoking history. In this situation it is prudent to rule out other causes of dyspnea, especially in a patient where a diagnosis of COPD is unexpected. White patients experiencing symptoms of COPD and who are younger than 45 years of age or have a strong family history of COPD should be tested for α1-antitrypsin deficiency. Several guidelines even recommend that all patients with COPD regardless of age should be tested for α1-antitrypsin deficiency after weighing the risks and benefits of testing. Patients with this disorder are often misdiagnosed with asthma for many years. They may have a modest smoking history and basilar emphysema (although they may present with any pattern of emphysema), and they may have concurrent liver disease. Patients with α1-antitrypsin deficiency who never smoke may develop symptoms later in life. If the diagnosis of α1antitrypsin deficiency is confirmed, α1-antitrypsin augmentation therapy may slow disease progression, although data on its efficacy are limited.

Nitric oxide promotes dilation of bronchial blood vessels and airways. The fractional exhaled nitric oxide (FENO) is a noninvasive test most commonly used in patients with severe airflow obstruction when other techniques are difficult to perform (for example, assessing airflow in a child or mentally impaired adult). High levels of FENO are typically associated with asthma and other inflammatory airway conditions. Measurement of FENO is not indicated as the next diagnostic test in this patient with a history strongly suspicious for α1-antitrypsin deficiency.

High-resolution CT (HRCT) is indicated if diffuse parenchymal lung disease is suspected. HRCT can help narrow the differential diagnosis based on the distribution of the lung parenchymal abnormalities and the presence or absence of associated findings. Diffuse parenchymal lung disease should be suspected in the presence of restrictive or combined obstructive/restrictive diseases. HRCT is also diagnostically definitive for bronchiectasis, but this condition is typically characterized by cough and voluminous, often purulent, sputum production, which is not present in this patient.

A vascular endothelial growth factor-D level can help in the diagnosis of lymphangioleiomyomatosis (LAM). However, LAM is a cystic lung disease that mostly affects young women, so testing would not be indicated for this patient.

Key Point

  • Measurement of α1-antitrypsin level is indicated for white patients experiencing symptoms of COPD and who are younger than 45 years of age or have a strong family history of COPD.