LP contributed to study design, data collection, data analysis, data interpretation, figures, and wrote the manuscript. SS contributed to conceptualization and design of the study, funding acquisition, data analysis, data interpretation, figures and manuscript review and editing. MS contributed to data curation, data analysis, data interpretation, figures and manuscript review and editing. RJ, NMD, SI, CC, JG, LF and SJ contributed to data collection, data analysis, and manuscript review and editing. SDD contributed to funding acquisition, study design, data interpretation and manuscript review and editing. MS HG VW NS and DBS contributed to study design, data interpretation and manuscript review and editing.FR conceptualized, designed and supervised the study and contributed to funding acquisition, data analysis, data interpretation, figures, manuscript review and editing.

BackgroundThe lung clearance index (LCI) measured by the multiple breath washout (MBW) test is sensitive to early lung disease in children with cystic fibrosis (CF). While LCI worsens during the preschool years in CF, there is limited evidence to clarify whether this continues during the early school age years, and whether the trajectory of disease progression as measured by LCI is modifiable.MethodsA cohort of children (healthy (HC) and CF) previously studied for 12 months as preschoolers were followed during school age (5–10 years). LCI was measured every 3 months for a period of 24 months using the Exhalyzer® D MBW nitrogen washout device. Linear mixed effects regression was used to model changes in LCI over time.ResultsA total of 582 MBW measurements in 48 healthy subjects and 845 measurements in 64 CF subjects were available. The majority of children with CF had elevated LCI at the first preschool and first school age visits (57.8% (37/64)), whereas all but six had normal forced expiratory volume in 1 s (FEV1) values at the first school age visit. During school age years, the course of disease was stable (−0.02 units·year−1 (95% CI −0.14; 0.10). LCI measured during preschool years, as well as the rate of LCI change during this time period, were important determinants of LCI and FEV1, at school age.ConclusionPreschool LCI was a major determinant of school age LCI; these findings further support that the preschool years are critical for early intervention strategies.

Elderly normal volunteers (N = 12, mean age 70.4 years) were administered placebo or diazepam 2.5, 5, 10 mg in four consecutive sessions separated by at least a 1-week interval. Memory and psychomotor performance and plasma diazepam concentrations were assessed at baseline and at 1 and 3 h following drug administration. Significant impairments were found in response to all doses of diazepam. The maximum impairment occurred at 1 h, which coincided with the highest plasma concentration of the drug.

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