The new generation nebuliser PARI eFlow^® rapid allows a highly efficient aerosol delivery at reduced inhalation time. However, lung function data during long-term use of this device are not available until now. 70 clinically stable adult cystic fibrosis patients participated in this observation study. Lung function tests were performed prospectively 12 weeks after and again 9 to 12 months after switching the inhalation device from a conventional jet nebulizer to the PARI eFlow^® rapid. Lung function data were collected retrospectively from the visits 1 year as well as 12 weeks prior to the switch-over. Lung function data for all time points were only available for 59 patients. Treatment time and patient's satification were recorded for both conventional and new nebuliser in all 70 patients. After 1 year of inhalation with eFlow^® rapid, the mean change in FEV1% was -- 1.4% (n = 59 patients). The decrease in FEV1 was smaller than the change in FEV1 after 1 year of inhalation with the conventional jet nebuliser (control period, -3.1%), although this difference was not statistically significant. The same effect was seen in MEF25[%] '(-2.6% with conventional nebuliser compared to --1.6% after eFlow^® rapid). Concerning the FVC, there was a greater improvement after 1 year of inhalation with the eFlow^® rapid than with the jet nebuliser (+ 2.9% vs. +1.1%). For PEF%, there was an increase during the control period, whereas after inhalation with eFlow^® rapid there was a decrease (+1.1% vs. --2.9%). All changes were not significantly different. The eFlow^® rapid reduced total daily inhalation time by two-thirds (conventional nebuliser: 31.1 min/day; eFlow^® rapid: 10.2 min/day, n = 70 patients) Inhalation with the new nebuliser eFlow rapid does not alter FEV1, FVC or PEF significantly after 1 year of inhalation. The treatment time could be reduced significantly by the eFlow^® rapid.

Background/Objectives: Elexacaftor, tezacaftor, and ivacaftor (ETI) have significantly improved lung function in people with cystic fibrosis (pwCF). Despite exceptional improvements in most cases, treatment-related inter-subject variability and drug–drug interactions that complicate modulator therapy have been reported. Methods: This retrospective analysis presents data on the serum concentration of ETI in our pwCF with full or reduced dosage from August 2021 to December 2023 via routine therapeutic drug monitoring (TDM). The data were compared with the maximum drug concentrations (Cmax) from the pharmaceutical company’s summary of product characteristics. Results: A total of 786 blood samples from 155 pwCF (41% female, 59% male) were analyzed. The examinations were divided into four groups: full dose within the given tmax (38.5% of all measurements), full dose outside the tmax (29%), reduced dose within the tmax (19.2%), and reduced dose outside the tmax (13.2%). In pwCF receiving the full dose and blood taken within the tmax, 45.3% of serum concentrations of elexacaftor, 51.1% of serum concentrations of ivacaftor, and 8.9% of serum concentrations of tezacaftor were found to be above the Cmax, respectively. For those on reduced doses within the tmax, 24.5% had a serum concentration of elexacaftor, 23.2% had a serum concentration of ivacaftor, and 2.5% had a serum concentration of tezacaftor above the Cmax, respectively. Conclusions: Many pwCF under ETI therapy have Cmax values for elexacaftor and ivacaftor above the recommended range, even on reduced doses or before the tmax was reached. This highlights the value of a TDM program. Further pharmacokinetic studies are necessary.

Rationale: The mucoid phenotype of Staphylococcus aureus is caused by adaptation. Excessive biofilm formation associated with a protective effect for mucoid S. aureus was observed in isolates from respiratory samples of people with cystic fibrosis (pwCF). Objectives: There is little knowledge about the prevalence of mucoid S. aureus in pwCF and a potential association with CF lung disease. Methods: A prospective multicenter study was conducted (cross-sectional and longitudinal). Specimens and case report forms were sent to the central study laboratory for characterization of S. aureus and analysis of clinical parameters. Measurements and Main Results: In the cross-sectional study, in 41 (9.1%) of 451 S. aureus–positive pwCF from 13 CF centers, mucoid S. aureus was cultured. In the longitudinal study, the distribution of CFTR genotypes and the number of pwCF with highly effective modulator therapy and coinfection with Pseudomonas aeruginosa were equivalent in the mucoid group (35 pwCF) versus the control group (only nonmucoid S. aureus; 36 pwCF). Although lung function did not differ between groups as a whole, a subgroup analysis revealed significantly worse lung function for female pwCF with mucoid S. aureus as well as for pwCF if P. aeruginosa coinfection was excluded. Conclusions: In the era of highly effective modulator therapy, worse lung function was associated with female and P. aeruginosa–negative pwCF with mucoid S. aureus compared with pwCF with only nonmucoid S. aureus. Therefore, appropriate culture conditions should be established to detect mucoid S. aureus. Further investigations are needed to elucidate the relationship between mucoid S. aureus and CF lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT04171583).