The most appropriate diagnostic test to perform next is sweat chloride testing. Although traditionally considered a pediatric disease, an increasing number of cases of cystic fibrosis (CF) are diagnosed in adult patients. Conditions suggesting the diagnosis of CF in adults include chronic asthma-like symptoms, chronic sinusitis, nasal polyposis, recurrent pancreatitis, male infertility, nontuberculous mycobacterial infection, allergic bronchopulmonary aspergillosis, bronchiectasis, and positive sputum culture for Burkholderia cepacia and/or Pseudomonas aeruginosa. This young patient has a history of pulmonary disease since childhood with a chronic productive cough, chronic sinus disease, nasal polyps on physical examination, findings suggestive of CF (such as hyperinflation) on chest radiograph, and pulmonary function tests showing obstruction; therefore, based on this history, he should be evaluated for CF. Diagnosis of CF is based on a combination of CF-compatible clinical findings in conjunction with either biochemical (sweat chloride testing, nasal potential difference) or genetic (CFTR mutations) techniques. Sweat chloride testing and CFTR analysis are the definitive diagnostic tests.

α₁-Antitrypsin (AAT) is an inhibitor of proteolytic enzymes, with deficiency leading to accelerated emphysema and liver disease. A characteristic radiographic finding of the emphysema associated with AAT is bullous changes most prominent at the bases, which are not present in this patient. Additionally, liver disease is more common in younger patients, which is also not present in this patient; lung disease usually occurs beyond the second and third decades of life. Therefore, AAT testing would not be the most appropriate next diagnostic test in this patient with a clinical history suggestive of possible CF.

Antineutrophil cytoplasmic antibody assays are useful in diagnosing granulomatosis with polyangiitis (GPA), which may present with both upper and lower airway disease as well as kidney involvement. Although this patient has evidence of both upper and lower airway disease, he has no apparent kidney involvement, and his lung imaging is more consistent with bronchiectasis, compared with the common findings in GPA of nodules, diffuse opacities, transient pulmonary infiltrates, and hilar lymphadenopathy. Additionally, GPA tends to affect an older patient population and also has a more acute onset than the symptoms present in this patient, making this a less likely diagnostic consideration. ANCA antibodies are also associated with eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome). There is no eosinophilia in this patient, and the chronicity since childhood makes this an unlikely diagnosis.

Although imaging of the sinuses may be helpful in defining the extent of polyposis noted on examination, it would not be useful in determining the cause of the polyps or underlying lung disease. Additionally, CT is the preferred imaging modality for sinus disease because of inadequate sensitivity and specificity of plain radiography, making this an inappropriate next diagnostic intervention.