Pharmacokinetic variability of CFTR modulators from standard and alternative regimens.

Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance.

Mobile-based asthma action plans for adolescents.

PURPOSE: To examine feasibility and utilization of a mobile asthma action plan (AAP) among adolescents. METHODS: Adolescents (aged 12-17 years) with persistent asthma had their personalized AAP downloaded to a smartphone application. Teens were prompted by the mobile application to record either daily symptoms or peak flow measurements and to record medications. Once data were entered, the application provided immediate feedback based on the teen's AAP instructions. Asthma Control Test (ACT(®)) and child asthma self-efficacy scores were examined pre- and post-intervention. RESULTS: Adolescents utilized the mobile AAP a median 4.3 days/week. Participant satisfaction was high with 93% stating that they were better able to control asthma by utilizing the mobile AAP. For participants with uncontrolled asthma at baseline, median (interquartile range) ACT scores improved significantly from 16 (5) to 18 (8) [p = 0.03]. Median asthma attack prevention self-efficacy scores improved from 34 (3.5) to 36 (5.3) [p = 0.04]. CONCLUSIONS: Results suggest that personalized mobile-based AAPs are a feasible method to communicate AAP instructions to teens.

Improving knowledge, technical skills, and confidence among pediatric health care providers in the management of chronic tracheostomy using a simulation model.

OBJECTIVE: The results from a recent national survey about catastrophic complications following tracheostomy revealed that the majority of events involved a loss of airway. Most of the events due to airway loss involved potentially correctable deficits in caregiver education. Training in a simulated environment allows skill acquisition without compromising patient safety. We assessed the knowledge and confidence level of pediatric health care providers at a large tertiary care children's hospital in routine and emergency tracheostomy care and evaluated the efficacy of a comprehensive simulation-based tracheostomy educational program. METHODS: The prospective observational study was comprised of 33 subjects including pediatric residents, internal medicine-pediatric residents, pediatric hospitalist faculty physicians, and advanced practice registered nurses who are involved in the care of patients with tracheostomies within a tertiary-care children's hospital. The subjects completed self-assessment questionnaires and objective multiple-choice tests before and after attending a comprehensive educational course that employed patient simulation. The outcome measurements included pre- and post-course questionnaires, pre- and post-course test scores, and observational data from the simulation sessions. RESULTS: Before the education and simulation, the subjects' comfort and confidence levels on a five-point Likert scale in performing routine tracheostomy tube care, routine tracheostomy tube change, and an emergency tracheostomy tube change were as follows (median (Q1, Q3)): 1 (1, 2), 1 (1, 2), and 1 (1, 2), respectively (n = 28). The levels of comfort and confidence after completing the course improved significantly to 4 (4, 5), 4 (4, 5), 4 (4, 5), respectively (P < 0.001) (n = 20). For the knowledge assessment, the pre-course test mean score was 0.53 ± 0.50, and the scores on the post-course test improved significantly with a mean score of 0.82 ± 0.39 (P < 0.001). During the educational intervention, specific deficiencies observed included a lack of understanding or familiarity with different types of tracheostomy tubes (e.g., cuffed versus uncuffed), physiological significance of the cuff, mechanism of action and physiological significance of the speaking valve, and the importance of the obturator in changing the tracheostomy tube. CONCLUSION: There is a need for improved tracheostomy education among pediatric health care providers. Incorporation of patient-simulation into a tracheostomy educational program was effective in improving knowledge, confidence, and skills. Pediatr Pulmonol. 2016;51:696-704. © 2015 Wiley Periodicals, Inc.

Pediatric flexible airway endoscopy.

Flexible airway endoscopy has been used in clinical and research investigations of pediatric airway and pulmonary disorders for nearly 25 years. Not only has clinical use of the flexible bronchoscope improved our evaluation and management of a variety of airway and pulmonary diseases in children, but also research investigations using lavage and biopsy specimens obtained with the flexible bronchoscope have contributed extensively to our understanding of lung inflammation and infection. Improvements and new developments in fiberoptic endoscope technology, training of airway endoscopists, preoperative and sedative medications, patient monitoring, and airway endoscopic techniques, as well as adjunctive minimally invasive and noninvasive diagnostic modalities, continue to refine and enhance the pediatric clinical and research applications of flexible airway endoscopy.

Limited reliability of lipid-laden macrophage index restricts its use as a test for pulmonary aspiration: comparison with a simple semiquantitative assay.

The lipid-laden macrophage index (LLMI) is a semiquantitative evaluation of alveolar macrophage lipid content used in diagnosis of pulmonary aspiration. To date, there are no published reports regarding the reliability of LLMI. We sought to evaluate the interobserver and intraobserver variability and validity of LLMI and to compare it to a simpler macrophage lipid content index (LCI). To evaluate reliability we compared both the LLMI and LCI of 26 bronchoalveolar lavage (BAL) specimens from 14 aspirators and 12 non-aspirators on 10 separate occasions by two observers. The ranges of means and standard deviations (SD) of LLMI for observer 1 (Obs 1) were 19-160 (5-31) for aspirators, and 0-48 (0-15) for non-aspirators; and those of observer 2 (Obs 2) were 77-249 (13-33) for aspirators and 47-170 (8-37) for non-aspirators. The ranges of means and SD of LCI for Obs 1 were 2-8 (0-2) for aspirators and 0-4 (0-1) for non-aspirators, compared with 2-9 (0-2) for aspirators and 1-6 (0-2) for non-aspirators for Obs 2. No statistical significance was found between LLMI and LCI by comparing coefficients of variation (CV) in either groups or observers. Poor agreement between the two observers was found using a Bland Altman analysis, with the difference of the two observations mostly exceeding zero and becoming larger as the average of the two observations became bigger. The combined sensitivity, specificity, and positive and negative predictive value (PPV and NPV) for both observers of the LLMI were 57%, 75%, 84%, and 69% and those of LCI were 58%, 92%, 93%, and 69%. We conclude that there is poor reliability for both methods. The LCI is simpler and appears to be at least as good as the LLMI.