WS19.1 Disease-causing CFTR mutation and carriage of airway infections

Abstract

Objectives Quantify the association of CFTR mutations of different classes and specific identities with carriage of eight clinically relevant airway infections. Methods After obtaining IRB approval, we analyzed data from the CFFPR from 2003–2011. We examined carriage of Pseudomonas aeruginosa, methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA), Burkholderia sp., Alcaligenes xylosoxidans, Stenotrophomonas maltophilia, Aspergillus sp. and Candida sp. We used logistic regression (glm function in R), corrected by patient age, to compare carriage by F508del homozygotes and heterozygotes, classifying heterozygotes both by mutation class (I–V) and specific non-F508del mutation. Results Focusing on 18564 patients with genetic and microbiological data in 2010, we found that a mutation of class IV or V. decreases carriage of all infections: P. aeruginosa (OR 0.54, p MSSA (OR 0.92, p=0.0002), MRSA (OR 0.57, p Burkholderia (OR 0.57, p A. xylosoxidans (OR 0.63, p S. maltophilia (OR 0.70, p Aspergillus (OR 0.70, p Candida (OR 0.85, p Five specific mutations were associated with reduced carriage of P. aeruginosa at the p S. maltophilia and Aspergillus was lower in patients with the R117H mutation. Conclusion CF patients with milder mutations (class IV and V) have better survivorship. We show lower carriage of eight important airway pathogens is associated with milder mutation class and with specific disease-causing CFTR mutations.