Risk factors for lung function decline in a large cohort of young cystic fibrosis patients

Abstract

Objective To identify novel risk factors and corroborate previously identified risk factors for mean annual decline in FEV1 percent predicted in a large, contemporary, U.S. cohort of young cystic fibrosis patients. Methods Retrospective observational study of participants in the EPIC Observational Study, who were Pseudomonas–negative and ≤12 years of age at enrollment in 2004-2006. The associations between potential demographic, clinical and environmental risk factors evaluated during the baseline year and subsequent mean annual decline in FEV1 percent predicted were evaluated using generalized estimating equations. Results The 946 participants in the current analysis were followed for a mean of 6.2 (SD 1.3) years. Mean annual decline in FEV1 % predicted was 1.01% (95% CI 0.85-1.17%). Children with 1 or no F508del mutations had a significantly smaller annual decline in FEV1 compared to F508del homozygotes. In a multivariable model, risk factors during the baseline year associated with a larger subsequent mean annual lung function decline included female gender, frequent or productive cough, low BMI (<66th percentile, median in the cohort), ≥1 pulmonary exacerbation, high FEV1 (≥115% predicted, in the top quartile), and respiratory culture positive for methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus or Stenotrophomonas maltophilia. Conclusions We have identified a range of risk factors for FEV1 decline in a large cohort of young, CF patients who were Pa negative at enrollment, including novel as well as previously identified characteristics. These results could inform the design of a clinical trial in which rate of FEV1 decline is the primary endpoint and identify high-risk groups that may benefit from closer monitoring.

Factors Associated with Worse Lung Function in Cystic Fibrosis Patients with Persistent Staphylococcus aureus

“…First, our inclusion and exclusion criteria selected a sub-group of CF patients, which do not reflect the entire CF population. However, lung function data of our patients were comparable to other studies [27,41]. Our data should thus provide meaningful results for the general CF population.…”

Incident Stenotrophomonas maltophilia infection and lung function decline in cystic fibrosis

“…This increased annual decline of 0.63 exceeds our finding of 0.35 in our overall model and 0.47 in our sensitivity analysis. However, it is difficult to compare magnitude given that Cogen et al conducted a between subject analysis in contrast to our within subject analysis.…”

“…The effect of S. maltophilia infection on lung function decline and other respiratory outcomes in CF is unclear . While older studies have not shown an effect on respiratory outcomes, there is emerging evidence that S. maltophilia is associated with increased risk of pulmonary exacerbations and possibly even acceleration of lung function decline …”

Cystic Fibrosis

“…In addition to the high prevalence of S. aureus among children, pediatric CF studies have provided further reason to worry: S. aureus has been associated with higher airway inflammation 25,26 , lower lung function 27,28 , and even higher subsequent mortality when detected together with P. aeruginosa 29 . Further, these associations were for all S. aureus ; as described below, specific subtypes of S. aureus (such as MRSA and small-colony variants of S. aureus (SCVs)) may be associated with even worse outcomes than other S. aureus .…”