GENETIC AND IMMUNOLOGICAL ASPECTS OF CYSTIC-FIBROSIS

Learning Objectives: Reading this article will enable the readers to r einforce their knowledge of the pathophysiology of cystic fibrosis (CF ), the pathogenesis of the lung disease, the criteria for diagnosis, a nd CF genotype/phenotype relationships. The focus of this review is on the genetic and immunologic aspects of CF. Data Source: Relevant arti cles, current texts, data presented at the annual North American Cysti c Fibrosis Conferences and distributed to the Directors of CF Centers by the CF Foundation were reviewed. A MEDLINE database using subject k eywords was searched from 1987 to date. Background information derived from the author's 33 years of clinical experience at three of the CF Foundation's CF Care, Teaching and Resource Centers was also included. Study Selection: Since CF is an inherited disorder, the genetic aspec ts are emphasized. With the cloning of the CF gene, DNA analysis has a ssumed an important role in confirming the clinical diagnosis and in t he improved understanding of the pathophysiology of this disorder. Alt hough DNA testing is highly specific, it is not very sensitive. Result s: Cystic fibrosis gene structure and function are described briefly. The pathophysiology of CF, as it relates to the CF gene defect, and th e current knowledge of the pathogenesis of the lung disease are review ed. The criteria for the diagnosis proposed by the Clinical Practice G uidelines for CF are discussed. Problems of establishing the diagnosis and the importance of correlations of laboratory and clinical finding s in CF are emphasized. Conclusions: As a multisystem disorder, CF can masquerade as other disorders, including allergic respiratory disease . Primary care physicians often refer patients to allergists/immunolog ists because of recurrent respiratory problems. This review discusses the genetic heterogeneity of CF.