A 7-year-old girl is brought to the emergency department due to 2 days of fever, productive cough, and shortness of breath. Medical history is significant for recurrent lung infections and cystic fibrosis. Weight is at the 5th percentile. Temperature is 38.1 C (100.6 F), pulse is 104/min, and respirations are 30/min. Pulse oximetry is 86% on room air. Examination shows a thin girl with digital clubbing and a hyperexpanded chest. Diffuse wheezes and crackles are present bilaterally. The rest of the examination is unremarkable. Chest x-ray reveals hyperinflation, chronic interstitial changes, and an infiltrate in the right lower lobe. Gram stain of sputum shows gram-negative rods. Which of the following is the most likely cause of this patient's recurrent infections?

Question

A 7-year-old girl is brought to the emergency department due to 2 days of fever, productive cough, and shortness of breath.  Medical history is significant for recurrent lung infections and cystic fibrosis.  Weight is at the 5th percentile.  Temperature is 38.1 C (100.6 F), pulse is 104/min, and respirations are 30/min.  Pulse oximetry is 86% on room air.  Examination shows a thin girl with digital clubbing and a hyperexpanded chest.  Diffuse wheezes and crackles are present bilaterally.  The rest of the examination is unremarkable.  Chest x-ray reveals hyperinflation, chronic interstitial changes, and an infiltrate in the right lower lobe.  Gram stain of sputum shows gram-negative rods.  Which of the following is the most likely cause of this patient's recurrent infections?

Quizplus · Accepted Answer

11ec160b_3b36_f01c_9249_79bbe58b33f7_MD0001_00 Cystic fibrosis (CF) is a multisystem disorder in which a defective chloride channel (CF transmembrane conductance regulator) prevents the normal hydration of mucus. Accumulation of thick, viscous secretions in the lungs leads to mucus plugging and progressive bronchiectasis, which manifest as obstructive lung disease (eg, hyperinflated lungs, barrel chest) and chronic hypoxia (eg, digital clubbing). Gastrointestinal involvement can also lead to malabsorption with decreased body weight. The abnormal airway secretions in patients with CF impair mucociliary clearance and allow colonization of bacteria such as Haemophilus influenzae, Staphylococcus aureus, and, over time, gram-negative rods such as Pseudomonas aeruginosa and Burkholderia cepacia complex. The microenvironment is particularly suitable to mucoid P aeruginosa because localized hypoxia within the airway mucus causes the bacterium to lose motility and produce alginate, a polysaccharide involved in biofilm formation. The biofilm acts as a protective matrix for the development of Pseudomonas macrocolonies, which are difficult to eradicate and cause recurrent and persistent infection. (Choice A) Natural killer cell deficiency is associated with severe, disseminated viral infections (eg, herpes simplex virus, cytomegalovirus). This patient's infiltrate in the right lower lobe and Gram stain findings are consistent with bacterial pneumonia, and she has no history of severe or recurrent viral infection. (Choice C) Neutrophil free radical formation is impaired in chronic granulomatous disease, which is characterized by recurrent multiorgan (eg, lungs, liver, lymph nodes, skin) infections by catalase-positive organisms (eg, Aspergillus, S aureus). In contrast, this patient has isolated, chronic pulmonary findings. Moreover, CF results in excessive neutrophil free radical formation due to persistent pulmonary infection, which contributes to the progressive lung damage seen in these patients. (Choice D) Inability to form the membrane attack complex occurs with terminal complement deficiency. These patients have recurrent Neisseria meningitis, not lung infections. (Choice E) Bacterial colonization in the lungs of patients with CF induces a massive infiltration of neutrophils, which results in the release of elastase, a protease that promotes bronchiectasis. Therefore, chronic lung disease in CF is characterized by excessive, not reduced, endobronchial protease activity. Educational objective: Patients with cystic fibrosis have thick, viscous mucus that accumulates in the airways and promotes colonization of bacteria, particularly Pseudomonas. This gram-negative rod can produce biofilms, which act as a protective matrix that allows bacterial macrocolonies to develop, causing persistent infection.

A 7-Year-Old Girl Is Brought to the Emergency Department Due