According to the findings of a cohort study conducted by a cystic fibrosis (CF) unit in London, there has been a marked improvement in the survival of patients with CF who have a low lung function, some of which may be due to the use of recombinant human DNase.

The authors note that outcomes in CF are improving overall, with increasing life expectancy; it is not known if this is also true for patients with late stage disease.  A forced expiratory volume in one second (FEV1) of <30% predicted is widely used as an appropriate trigger for consideration of lung transplantation, as the 2-year mortality of these patients is generally accepted to be >50%.  In their study they sought to determine whether the survival of patients with CF and a FEV1 of <30% has improved, and to determine factors associated with any survival change.

The study included 276 patients referred to the centre, with a FEV1 of <30% predicted recorded between January 1990 and December 2003.  The main outcome was survival – this was examined through to December 2007, with the dates of death taken from medical records (those lost to follow-up had their survival censored at the time of their last clinic attendance, as did those who had lung transplantation).  A multivariate Cox regression model was used to examine factors that may be associated with survival.

Around half of the patients (53%) were male, with a mean age of 25.9 years at entry into the cohort.  The mean FEV1 was 23.9% predicted and 92.3% were taking pancreatic supplements.  The median survival improved from 1.2 years in the 1990-1 cohort to 5.3 years in the 2002-3 cohort, with a marked improvement from 1994 to 1997 – this coincides with the introduction of nebulised recombinant DNase.  The authors found that use of recombinant DNase was significantly associated with a reduced risk of death (hazard ratio 0.59, 95% CI 0.44 to 0.79), whereas use of long term oxygen therapy (HR 3.52, 2.49 to 4.99) and nebulised antibiotics (1.84, 1.05 to 3.22), and a body mass index under 19 (hazard ratio 1.52, 1.10 to 2.10) were associated with an increased risk of death. 

The authors discuss the strengths and limitations of their study.  They comment that the threshold of FEV<30% predicted should no longer be considered in isolation as the start of end-stage disease - the survival of these patients has improved markedly over recent years, with a median predicted survival of 5.3 years.  They say that “the reasons for the improvement in survival are almost certainly multifactorial, but providing a multidisciplinary approach, with attention to details such as nutrition and airway clearance, is likely to be a key element in maintaining health even at low levels of lung function.”