Sameer Desai1, Hubert Wong1, Jenna Sykes2, Anne L Stephenson3,2, Joel Singer1, Bradley S Quon1,4. 1. 1 University of British Columbia Vancouver, British Columbia. 2. 3 St. Michael's Hospital Toronto, Ontario, Canada and. 3. 2 University of Toronto Toronto, Ontario, Canada. 4. 4 St. Paul's Hospital and University of British Columbia Vancouver, British Columbia, Canada.
From the Authors:We thank Fieuws and colleagues for raising this important point regarding the timescale applied in our study (1). Our analysis showed that age at diagnosis is a predictor of lung-transplant-free survival. However, as Fieuws and colleagues have highlighted, this is not surprising, as those individuals diagnosed late are older and inherently at a higher risk for mortality, which is a possible artifact of strong age effects.As recommended by Fieuws and colleagues, we have redone the analysis, using age as the timescale. The association with diabetes (hazard ratio [HR], 3.69, 95% confidence interval [CI], 1.21–11.26) and lung function (HR, 1.36 per 5% decrease in forced expiratory volume in 1 s percentage predicted; 95% CI, 1.24–1.50) remained unchanged, but the association between age at diagnosis and survival is now reversed (HR, 0.58 per 5-yr increase; 95% CI, 0.39–0.86). This suggests that older age at diagnosis is protective of our outcome as an indicator of less aggressive CF disease. Unfortunately, this analysis also carries a built-in selection bias, as individuals diagnosed at an older age must live to that age to be diagnosed and included in the cystic fibrosis registry, which leads to an “immortal” survival time bias.The relationship between age at diagnosis and survival is complex and must be interpreted with caution, as noted by Fieuws and colleagues. Although older age at diagnosis inherently increases the risk for death because of age effects, older age at diagnosis may also reflect milder disease and reduced risk for death. However, being diagnosed later in life also means there were additional years of untreated cystic fibrosis, which could result in a negative effect on health and, hence, result in an increased risk for death. We again thank Fieuws and colleagues for bringing attention to this important issue and for highlighting that older age at diagnosis may not necessarily be a risk factor for worse outcomes in adult-diagnosed cystic fibrosis, a message we would not want miscommunicated to patients.