Pathogenesis of Early Lung Disease in Cystic Fibrosis: A Window of Opportunity To Eradicate Bacteria

Pathogenesis of Early Lung Disease in Cystic Fibrosis: A Window of Opportunity To Eradicate Bacteria

Timothy D. Starner, MD; and
Paul B. McCray, Jr., MD

From University of Iowa, Iowa City, Iowa.

PHYSIOLOGY IN MEDICINE: A SERIES OF ARTICLES LINKING MEDICINE WITH SCIENCE

Co-sponsored by the American College of Physicians and the American Physiological Society

Physiology in Medicine: Dennis A. Ausiello, MD, Editor; Dale J. Benos, PhD, Deputy Editor; Francois Abboud, MD, Associate Editor; William J. Koopman, MD, Associate Editor

Annals of Internal Medicine: Paul Epstein, MD, Series Editor

Clinical Principles

Early lung disease in patients with cystic fibrosis may be clinically silent.

Bacterial colonization, inflammation, or both can be detected before other signs or symptoms of lung disease develop.

Pathophysiologic Principles

The early pathophysiology of lung disease in patients with cystic fibrosis has several interconnected deleterious cycles leading to impaired innate immunity.

Patients with cystic fibrosis typically experience transition from sterile lower airways, to transient infections (with organisms including nontypeable Haemophilius influenzae, Staphylococcus aureus, and Pseudomonas aeruginosa), to chronic nonmucoid P. aeruginosa infection, to mucoid biofilm P. aeruginosa infection.

The time before chronic colonization with P. aeruginosa represents a window of opportunity to eradicate bacteria and delay persistent infection. Increasing evidence suggests that early eradication can slow progression of lung disease.

For definition of terms used, see Glossary.

The patient, a previously asymptomatic 18-year-old man with cystic fibrosis, presented with a chronic, nonproductive cough. His medical history was significant for pancreatic insufficiency and homozygosity for the ΔF508 CFTR mutation. Pancreatic insufficiency was well controlled by enzyme supplementation, and the patient achieved a normal height and weight. He had Pseudomonas aeruginosa detected by bronchoscopy at the age of 5 years and by throat culture at the age of 16 years, both of which were successfully eradicated by prolonged courses of antibiotics. Chest radiographs were normal, and he did not have chronic respiratory symptoms until cough 2 months earlier. Bronchoscopy was done to evaluate the patient for respiratory infections and inflammation. The culture of …

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