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BACKGROUND Tracheomalacia (TM) occurs in approximately 1 in 2,100 children. Because the trachea develops abnormally in animal models of cystic fibrosis (CF), we hypothesized this may also occur in children with CF, increasing their risk of TM. PURPOSE To examine the prevalence and clinical consequences of TM in children with CF. METHODS We studied children with CF born between 1995 and 2012. TM was defined as dynamic collapse of the trachea, and the severity was recorded as described in the chart. The effect of TM on patient outcomes, including FEV1, CT changes, and acquisition of CF pathogens, was assessed using a longitudinal patient dataset. RESULTS 89% of children with CF had at least one bronchoscopy (n = 97/109). 15% of these children had TM described in any bronchoscopy report (n= 15/97). Of the patients with TM, 8 had meconium ileus (p = 0.003) and all were pancreatic insufficient. Pseudomonas aeruginosa infection occurred 1.3 years earlier among children with TM (p = 0.01). Starting FEV1 values by age 8 were diminished by over 18% of predicted for patients with TM. Life-threatening episodes of airway obstruction occurred in 3 of 15 patients with CF and TM, including one leading to death. Gender, prematurity, and hepatic disease were not associated with TM. No difference was observed in the frequency of bronchiectasis. CONCLUSIONS TM is significantly more common in infants and children with CF than in the general population and is associated with airway obstruction and earlier Pseudomonas acquisition.

SUMMARY Staphylococcus aureus is a bacterial pathogen responsible for a wide range of diseases and is also a human commensal colonizing the upper respiratory tract. Strains belonging to the clonal complex group CC30 are associated with colonization, although the colonization state itself is not clearly defined. In this work, we developed a co-culture model with S. aureus colonizing the apical surface of polarized human airway epithelial cells. The S. aureus are grown at the air-liquid interface to allow an in-depth evaluation of a simulated colonization state. Exposure to wild-type S. aureus bacteria or conditioned media killed airway epithelial cells within one day, while mutant S. aureus strains lacking alpha-toxin (hla) persisted on viable cells for at least two days. Recent S. aureus CC30 isolates are natural hla mutants, and we observed that these strains displayed reduced toxicity toward airway epithelial cells. Quantitative real-time PCR of known virulence factors showed the expression profile of S. aureus grown in co-culture correlates with results from previous human colonization studies. Microarray analysis indicated significant shifts in S. aureus physiology in the co-culture model toward lipid and amino acid metabolism. The development of the in vitro colonization model will enable further study of specific S. aureus interactions with the host epithelia.

Background The cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor and lumacaftor/ivacaftor improve the status of existing infections in patients with cystic fibrosis (CF). It is unknown how well these drugs protect patients against incident infections. We hypothesized that CFTR modulator treatment would decrease new infections with Pseudomonas aeruginosa or Staphylococcus aureus. Methods We retrospectively studied a single‐center cohort of patients with CF during two time periods (2008‐2011, Era 1) and (2012‐2015, Era 2) based on the January 2012 approval of ivacaftor. Using Kaplan–Meier analysis, we compared the time to any new infection with P. aeruginosa, methicillin‐resistant S. aureus (MRSA), or methicillin‐sensitive S. aureus (MSSA) that was absent during a 2‐year baseline. We stratified the analysis based on whether patients received ivacaftor or lumacaftor/ivacaftor during Era 2. We used the log‐rank test and considered P < 0.05 statistically significant. Results For patients receiving ivacaftor or lumacaftor/ivacaftor in Era 2, there was a statistically significant delay in the time to new bacterial acquisition in Era 2 vs. Era 1 ( P = 0.008). For patients who did not receive CFTR modulators, there was a trend toward slower acquisition of new bacterial infections in Era 2 compared to Era 1, but this was not statistically significant ( P = 0.10). Conclusions Patients receiving ivacaftor or lumacaftor/ivacaftor for CF had significantly delayed acquisition of P. aeruginosa and S. aureus after these drugs were released. This method for analyzing incident infections may be useful for future studies of CFTR modulators and bacterial acquisition in CF registry cohorts.