Bronchopulmonary Infectious Complications of Cystic Fibrosis

When cystic fibrosis (CF) was first described over 50 years ago, survival was measured in months rather than years. Each succeeding decade has seen an improvement in life expectancy, which increases the relevance of this topic for internists as well as pediatricians. Most patients in developed countries now survive childhood, up to 75% of affected individuals in some centers now reaching adulthood, and the mean life span is 26 years in the United States. The oldest known CF patient in the United States is 64 years of age and a previously undiagnosed 69-year-old European man with an abnormal response to a sweat test, disturbed pancreatic function, and chronic obstructive airways disease is the oldest individual at the time of diagnosis to be reported. CF patients are now at risk of developing a long list of diseases more commonly found in adults, including hypertension, neoplasms, sarcoidosis, and chronic renal failure.' Such are the demographics of the late 1980s. The 21st century will change the face of CF forever, for there is much stirring in CF research these days. The science is exciting and novel approaches are being brought to bear on this devastating disease. The two areas generating the most excitement are the description of the gene mutated in CF patients' and the search for the basic defect. Those developments holding particular promise for patient screening and serving to foster the development of novel, "curative" therapies in CF will be discussed later in this review. The growing number of adults with CF has begun to have an impact on internists, subspecialists, and other physicians caring for patients with chronic pulmonary disease. For although CF is a multisystem genetic disease with wide variability in expression, it remains a lung disease that in 1990 still determines the mortality and accounts for much of the excess morbidity. All fields of medicine are touched by this disease, and it is possible for the astute physician to find adult CF patients while evaluating chronic sinusitis, asthma, pancreatic insufficiency, sprue-like symptoms, azoospermia, or cirrhosis and portal hypertension. Similarly, there is great variability in the course of this disease and deterioration does not occur at the same rate in all patients. Nevertheless, 90% of CF patients die of respiratory failure, and in most cases this is complicated by a bacterial infection of the airway caused by the mucoid colonial variant of Pseudomonas aeruginosa. Many excellent reviews of CF lung disease exist, and we have recently reviewed the role aeruginosa plays in the pathogenesis of this lung lesion. Accordingly, after a brief review of CF lung pathology, we will emphasize in this discussion the nonPseudomonas infectious complications in CF airways. Selected aspects pertinent to the acquisition of P. aeruginosa and conversion in the CF airway from the nonmucoid to mucoid colonial variant will be discussed. Finally, because Dr. Weg has previously discussed in Seminars in Respiratory Medicine general therapeutic approaches to bronchiectasis, only therapeutic approaches most often applied to the chronically infected CF lung will be reviewed here. These therapeutic approaches have contributed materially to the increased survival already noted. Nevertheless, P. aeruginosa once acquired is seldom eradicated, the airway secretions remain infected, and the smoldering, destructive inflammatory airways disease continues its insidious downhill course. Unfortunately, despite the ferment in CF-related research, P. aeruginosa in the CF lung remains an example, par excellence, of a chronic pulmonary infection.