Progression of Lung Disease in Preschool Patients with Cystic Fibrosis.

RATIONALE: Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. OBJECTIVES: To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progression in preschool children with CF. METHODS: Children with CF between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy control subjects were enrolled at three North American CF centers. Multiple breath washout tests were performed at baseline, 1, 3, 6, and 12 months to mimic time points chosen in clinical care and interventional trials; spirometry was also conducted. A generalized linear mixed-effects model was used to distinguish LCI changes associated with normal growth and development (i.e., healthy children) from the progression of CF lung disease. MEASUREMENTS AND MAIN RESULTS: Data were collected on 156 participants with 800 LCI measurements. Although both LCI and spirometry discriminated health from disease, only the LCI identified significant deterioration of lung function in CF over time. The LCI worsened during cough episodes and pulmonary exacerbations, whereas similar symptoms in healthy children were not associated with increased LCI values. CONCLUSIONS: LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF.

Attributes and Actions Required to Advance Quality and Safety in Hospitals: Insights from Nurse Executives.

To lead effectively within their organizations, nurse executives must possess quality and safety literacy and be able to engage and motivate clinicians to participate in safety and quality initiatives. Given the paucity of research in Canada, a study was undertaken to explore nurse executives' understanding of the key concepts and strategies associated with patient safety and quality improvement, and their engagement with patient safety and quality improvement in their hospitals and healthcare systems. This study used an exploratory qualitative design with a content analysis approach on 20 nurse executives working in hospitals in Ontario. Three key themes emerged from the narrative data set including: (1) being a strategic and system thinker while possessing the emotional intelligence to influence staff; (2) building credibility and relationships with point-of-care staff, board of directors, and leadership team and (3) creating a culture of safety and high reliability. Study findings can be useful in informing future learning opportunities for nurse executives and nurses leaders at all levels to enhance their quality and safety literacy.

A randomized controlled trial to evaluate the lung clearance index as an outcome measure for early phase studies in patients with cystic fibrosis.

BACKGROUND: Outcome measures that can evaluate treatment efficacy are important to enhance development of new therapeutic agents for Cystic Fibrosis (CF). We investigated whether the lung clearance index (LCI) measured by multiple breath washout (MBW) can detect a treatment effect of hypertonic saline (HS) inhalation after single dosing within a 24 h period. METHODS: In this randomized controlled cross-over trial, CF patients received inhalation of HS and isotonic saline (IS). MBW and spirometry were performed at 5 time points over 24 h. LCI was measured using both a nitrogen washout technique (LCIN2) and sulfur hexafluoride as a tracer gas (LCISF6). The primary endpoint was the change in the LCIN2 between baseline and 24 h. Secondary endpoints included change in LCISF6 and spirometry outcomes. RESULTS: Twenty-one patients were randomized. Sixteen completed all study visits and all time point measurements. Eighteen patients contributed to the intention to treat analysis. Significant changes were not detected for either LCI or the spirometry outcomes. However, the primary outcome parameter (change in LCI between the baseline visits and 24 h after inhalation) demonstrated a trend towards improved LCI, in the HS treatment arm compared with the IS treatment arm, -0.60 LCIN2 (SE 0.32), p = 0.08); similar trends were not observed for spirometric measures. The overall effect size of HS was smaller than in previous studies of longer duration. CONCLUSIONS: These data suggest that LCI may potentially be used as an outcome measure in early phase trials with therapeutic agents that have a larger treatment effects than a single inhalation of HS.

A Systematic Approach to Multiple Breath Nitrogen Washout Test Quality.

BACKGROUND: Accurate estimates of multiple breath washout (MBW) outcomes require correct operation of the device, appropriate distraction of the subject to ensure they breathe in a manner representative of their relaxed tidal breathing pattern, and appropriate interpretation of the acquired data. Based on available recommendations for an acceptable MBW test, we aimed to develop a protocol to systematically evaluate MBW measurements based on these criteria. METHODS: 50 MBW test occasions were systematically reviewed for technical elements and whether the breathing pattern was representative of relaxed tidal breathing by an experienced MBW operator. The impact of qualitative and quantitative criteria on inter-observer agreement was assessed across eight MBW operators (n = 20 test occasions, compared using a Kappa statistic). RESULTS: Using qualitative criteria, 46/168 trials were rejected: 16.6% were technically unacceptable and 10.7% were excluded due to inappropriate breathing pattern. Reviewer agreement was good using qualitative criteria and further improved with quantitative criteria from (κ = 0.53-0.83%) to (κ 0.73-0.97%), but at the cost of exclusion of further test occasions in this retrospective data analysis. CONCLUSIONS: The application of the systematic review improved inter-observer agreement but did not affect reported MBW outcomes.