What is the most appropriate next step in diagnosis for a 19-year-old man with recurrent pneumonias and poor response to antibiotic therapy, presenting with chronic lung disease symptoms?

From the Guidelines

The most appropriate next step in diagnosis for this 19-year-old man with recurrent pneumonias and poor antibiotic response is a sweat chloride test to evaluate for cystic fibrosis (CF). This non-invasive test measures the concentration of chloride in sweat and is the gold standard for CF diagnosis. The test involves stimulating sweat production on a small area of skin (usually forearm) using pilocarpine iontophoresis, collecting the sweat, and analyzing its chloride content. A chloride concentration ≥60 mmol/L strongly supports a CF diagnosis, while values between 30-59 mmol/L are considered borderline and require additional testing. The clinical presentation of recurrent pneumonias with poor antibiotic response in a young adult strongly suggests CF, which is an autosomal recessive genetic disorder affecting the CFTR protein that regulates chloride transport across cell membranes. This leads to thick, sticky secretions in the lungs that promote recurrent infections. If the sweat test is positive or borderline, genetic testing for CFTR mutations should follow to confirm the diagnosis and determine the specific genetic variants, which may have implications for treatment options including CFTR modulator therapies 1.

Some key points to consider in this diagnosis include:

• The patient's history of recurrent pneumonias and poor response to antibiotic therapy, which suggests an underlying condition such as CF.
• The patient's age and lack of other risk factors for chronic obstructive pulmonary disease (COPD), making CF a more likely diagnosis.
• The importance of early diagnosis and treatment of CF to improve morbidity, mortality, and quality of life.
• The need for genetic testing to confirm the diagnosis and determine the specific genetic variants, which can inform treatment decisions.

In terms of the patient's symptoms and physical examination findings, the increased anteroposterior diameter of the chest and wider than normal lateral chest diameter are consistent with hyperinflation of the lungs, which is a common feature of CF. The patient's low body mass index (BMI) of 17 kg/m² is also consistent with CF, as patients with this condition often experience malnutrition and growth failure due to malabsorption of nutrients.

Overall, the clinical presentation and physical examination findings in this patient strongly suggest CF, and a sweat chloride test is the most appropriate next step in diagnosis.

From the Research

Patient Presentation and History

The patient is a 19-year-old man with a history of recurrent pneumonias and poor response to antibiotic therapy, presenting with chronic lung disease symptoms. He has had eight admissions to the hospital during the past 3 years for management of pneumonia and eight ear infections that have not responded well to antibiotic therapy.

Clinical Findings

The patient is 180 cm (5 ft 11 in) tall and weighs 54 kg (120 lb), with a BMI of 17 kg/m². The anteroposterior diameter of the chest is increased and wider than the lateral chest diameter, suggesting possible chest deformity or lung hyperinflation.

Diagnostic Considerations

Given the patient's history of recurrent infections and poor response to antibiotic therapy, along with the physical findings, there is a need to consider underlying conditions that may predispose him to these infections and chronic lung disease. One such condition is alpha-1 antitrypsin deficiency, a genetic disorder that can lead to chronic obstructive pulmonary disease (COPD) and increased susceptibility to lung infections.

Appropriate Next Step in Diagnosis

Considering the patient's presentation and the need to investigate for alpha-1 antitrypsin deficiency, the most appropriate next step in diagnosis would be:

• Measurement of serum alpha-1 antitrypsin activity, as this is a direct test for the deficiency that can cause the patient's symptoms 2, 3, 4, 5.

Rationale

The studies referenced provide evidence for the importance of diagnosing alpha-1 antitrypsin deficiency in patients with recurrent lung infections and chronic lung disease. They discuss the role of alpha-1 antitrypsin augmentation therapy in managing the condition and the need for early diagnosis to initiate appropriate treatment 2, 3, 4, 5. Additionally, recent developments in gene therapy offer potential future treatment options for alpha-1 antitrypsin deficiency-associated lung disease, highlighting the importance of accurate diagnosis 6.

Diagnostic Options

The options provided include:

• A) Measurement of FEV1: This is a test of lung function but does not directly diagnose alpha-1 antitrypsin deficiency.
• B) Measurement of serum alpha-1 antitrypsin activity: This is the correct answer as it directly tests for the deficiency.
• C) Methacholine challenge test: This test is used to diagnose asthma and is not relevant to diagnosing alpha-1 antitrypsin deficiency.
• D) Smear and culture of sputum for acid-fast bacilli: This test is used to diagnose tuberculosis and is not relevant to the current clinical scenario.
• E) Sweat chloride test: This test is used to diagnose cystic fibrosis, another condition that can cause chronic lung disease, but it is not the most appropriate next step given the suspicion of alpha-1 antitrypsin deficiency.