ABSTRACT
Since 1938, key scientic advances-including the identi- cation of hypertonic sweat in the 1950s and the discovery of the CF gene (cystic brosis transmembrane conductance regulator gene, CFTR) in 1989-have been instrumental in improving our understanding of CF pathophysiology.7-9 However, even before these, important improvements in care had been implemented as a result of careful clinical observation and a systematic approach to the disease complications (e.g., infection and nutritional deciency) resulting in a signicant decline in mortality. Key treatment milestones included the introduction of penicillin and eective nutritional management (crude pancreatic extract and a high fat/protein diet) in the 1940s; routine physiotherapy for airway clearance and eective surgical management of meconium ileus in the 1950s; the opening of specialized CF centers and founding of many national CF organizations in the 1960s; inhaled antibiotics; lung transplant programs commencing in the 1980s; eective mucus treatment with drugs such as nebulized recombinant human deoxyribonuclease (DNase),10 from the early 1990s; azithromycin from the 2000s11; and more recently, the introduction of mutation-specic, protein modulating, drugs.12 In the United States and other developed countries, median survival rose from 14 years in 1968 to 20 years in the mid1970s.13 Since then median survival has improved almost by a year every year and is now approximately 40 years in most developed countries (e.g., 41.4 years; UK Registry 2010 Annual Report).2,14 CF is no longer a disease that primarily aects children-in the United Kingdom, 55.7% of the total CF population are ≥16 years and 7.6% are aged >40 years (Figure 30.2); in the United States, 48.3% are aged ≥18 years.2,14 Successive cohorts are living progressively longer, with children born at the turn of the twenty-rst century predicted to live beyond 50 years of age.15
