A 24-year-old man comes to the office due to worsening productive cough with tenacious sputum, fever, and shortness of breath for a week. Today, he noticed blood streaks in the sputum. The patient had several similar episodes in the past, and the symptoms usually improved somewhat with antibiotics but never went away completely. He also has decreased exercise tolerance, fatigue, and weight loss. The patient does not use tobacco, alcohol, or illicit drugs. There is no family history of similar problems. Temperature is 38.9 C (102 F), blood pressure is 130/80 mm Hg, pulse is 102/min, and respirations are 20/min. Examination reveals crackles in both upper lung fields, and heart sounds are normal without murmurs. The patient's abdomen is soft, nontender, and without organomegaly. Digital clubbing is present. Leukocyte count is 15,000/mm³. Chest x-ray reveals a right upper lobe infiltrate, and a sputum culture grew Pseudomonas aeruginosa. Which of the following is the most likely underlying cause of this patient's current symptoms?

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11ec25c8_d4a9_d6fe_bc81_fd5464efa809_MD0003_00 This patient's presentation - recurrent episodes of dyspnea, fever, tenacious sputum production, and hemoptysis along with the physical examination findings of crackles and digital clubbing - is consistent with an exacerbation of bronchiectasis, a disease of bronchial thickening and dilation due to a recurrent cycle of bacterial infection, inflammation, and tissue damage. Bronchiectasis is associated with a number of underlying etiologies, and its development requires an infectious insult in combination with impaired bacterial clearance (eg, immunodeficiency, structural airway defect). recurrent cycle In this young patient, the underlying etiology of bronchiectasis is most likely undiagnosed cystic fibrosis (CF). Approximately 7% of patients with CF are diagnosed at age >18, and testing for CF is recommended in the evaluation of bronchiectasis. A mutation of the CF transmembrane conductance regulator gene results in defective chloride and sodium transport and leads to thick secretions and impaired mucociliary clearance. Chronic bacterial infection ensues, leading to enhanced neutrophil recruitment and excessive release of elastase, which contributes to bronchial airway damage. Pseudomonas aeruginosa is a characteristic finding in the sputum. In addition, upper lung lobe involvement (evidenced by upper lung field crackles and right upper lobe infiltrate in this patient) is characteristic of bronchiectasis due to CF and helps differentiate it from bronchiectasis due to other causes. > (Choice A) As in CF, excessive elastase activity also causes lung damage in alpha-1-antitrypsin deficiency. Bronchiectasis can occur, but emphysema that is predominant in the lower lobes is the typical disease manifestation. (Choice B) Complement deficiency causes susceptibility to encapsulated bacteria and likely creates a predisposition for bronchiectasis. However, a childhood history of recurrent infection (eg, meningitis, pneumonia) would be expected. (Choice D) Disorders of cell-mediated immunity (eg, DiGeorge syndrome, HIV) likely cause a predisposition for bronchiectasis. However, a history of opportunistic infections (eg, Candida, Pneumocystis jirovecii) would be expected. (Choice E) Disorders of impaired neutrophil migration (eg, leukocyte adhesion deficiency) are not associated with bronchiectasis as enhanced tissue infiltration by neutrophils likely plays an important role in the development of bronchiectasis. (Choice F) Splenic dysfunction occurs in sickle-cell anemia and results in increased susceptibility to encapsulated bacteria, which likely creates a predisposition for bronchiectasis. There is no suggestion of splenic dysfunction (eg, history of pain crises, splenectomy) in this patient. Educational objective: Impaired immune defense contributes to the development of bronchiectasis. Impaired mucociliary clearance in cystic fibrosis typically leads to bronchiectasis located predominantly in the upper lobe. References: Classic respiratory disease but atypical diagnostic testing distinguishes adult presentation of cystic fibrosis. (http://www.ncbi.nlm.nih.gov/pubmed/19965956) Bronchiectasis. (http://www.ncbi.nlm.nih.gov/pubmed/18842914)

A 24-Year-Old Man Comes to the Office Due to Worsening