Use of CFTR modulators in special populations, part 1: Pregnancy and lactation.

Safety and efficacy data regarding cystic fibrosis transmembrane conductance regulator (CFTR) modulator use in the setting of pregnancy or breastfeeding remains lacking due to exclusion from key trials and lack of multicenter prospective and retrospective studies in the post-CFTR modulator era. A scoping review of English articles from the period of January 1, 2012, to July 31, 2023, was conducted utilizing PubMed and EmBase databases with the following terms: "special population (pregnancy, lactation, breastfeeding)" AND "ivacaftor OR lumacaftor OR tezacaftor OR elexacaftor"; "cystic fibrosis transmembrane conductance regulator" AND "off label drug use." Search results were reviewed by title and abstract for duplications and relevance. Relative to pregnancy or breastfeeding, a total of 18 publications were included for review. Majority of case reports and surveys concluded maternal and infant health were preserved throughout gestation. Likewise, breastfeeding infant case reports show possible changes in liver function and lens opacities, though risk may be increased with both in-utero and breastfeeding exposure. Ivacaftor (IVA) and lumacaftor (LUM) concentrations in fetal cord blood and maternal blood were found to be equivalent. Yet, low concentrations of IVA and LUM were detectable in breastmilk and infant plasma. Current safety data surrounding CFTR modulator use in the setting of pregnancy and lactation is relatively reassuring; however, long-term safety remains unclear, necessitating ongoing observation, and reporting by care teams. As such, treatment decisions should be individualized and coproduced.

Use of CFTR modulators in special populations, part 2: Severe lung disease.

Safety and efficacy data surrounding cystic fibrosis transmembrane regulator (CFTR) modulator administration for people with CF (pwCF) and severe lung disease elect has remained unclear as a result of exclusion from key trials. A scoping review of English language articles from the period of 1 January 2012, to 31 July 2023 was conducted utilizing PubMed and EmBase databases with the following terms: "severe lung disease" OR "advanced lung disease" AND "ivacaftor OR lumacaftor OR tezacaftor OR elexacaftor"; "cystic fibrosis transmembrane conductance regulator" AND "off label drug use." Search results were reviewed by title and abstract for relevance. Twenty articles specific to CFTR modulator use in the setting of severe lung disease were included for review, with few specific to pediatric-aged pwCF. PwCF and severe lung disease experienced significant improvement in pulmonary function, body weight, number of IV antibiotic days, and quality of life. A few studies reported a transient decline in pulmonary function among pwCF shortly after LUM/IVA initiation. However, preemptive reductions in the dose of LUM/IVA may mitigate this reaction. ELE/TEZ/IVA utilization in pwCF and severe lung disease appears to be devoid of the transient decline in pulmonary function observed with LUM/IVA while providing the same clinical benefit. Current available data regarding use of CFTR modulators in pwCF and severe lung disease is reassuring; however, there remains a lack data regarding outcomes among the pediatric population including long-term outcomes. Therefore, treatment decisions should be individualized and coproduced.

Pharmacists' perspectives on school stock inhaler access for children.

Several states in the United States (U.S.) have laws permitting stock inhalers, including short-acting beta-agonist inhalers, such as albuterol, and spacers to be prescribed to, dispensed to, and stocked in schools for use in students in respiratory distress, based on a protocol. This survey study assessed Arizona pharmacists' (1) levels of comfort for dispensing a short-acting beta-agonist inhaler to an individual child versus a stock inhaler to a school, and (2) awareness of the related Arizona state law. Researchers surveyed pharmacists licensed in Arizona who self-reported practicing in an outpatient pharmacy setting. Among 251 pharmacist participants, 62% practiced in a chain community pharmacy. About 80.8% felt comfortable filling a prescription for an albuterol inhaler in a pediatric patient case, whereas only 26.7% felt comfortable filling a prescription for albuterol inhalers to be used as stock inhalers for a given school. Among those who would not fill the stock inhaler prescription, only 5.5% reported awareness of the state law compared to 42.6% of those who would fill it (p < 0.0001). This survey identified a lack of pharmacist awareness of state laws pertaining to stock inhalers for schools.

Use of CFTR modulators in special populations, part 3: Solid organ transplant.

BACKGROUND: Solid organ transplant (SOT) recipients with cystic fibrosis (CF) may benefit from the pulmonary and extrapulmonary benefits associated with CF transmembrane conductance regulator modulators. Nevertheless, evolution of modulator safety and efficacy data prompts consideration. METHODS: The search terms "transplant" AND "ivacaftor"(IVA) OR "lumacaftor"(LUM) OR "tezacaftor" (TEZ) OR "elexacaftor" (ELX) were utilized to conduct a scoping review of English articles from the period of January 1, 2012 to December 31, 2022. Search results from PubMed and Embase databases were reviewed by title and abstract for relevance. Included studies reported efficacy and safety outcomes of modulators in SOT recipients. RESULTS: One hundred thirty-six patients from one cohort study (90 lung transplant recipients) and eight case reports and series (29 lung transplant recipients, 16 liver transplant recipients and one lung/liver transplant patient) were included. Post-modulator initiation, 33 patients did not necessitate tacrolimus dose adjustments, 10 required dose uptitration, and 43 required dose reductions. Moreover, LUM/IVA use with azole antifungals may lead to subtherapeutic levels but opposing effects sustained tacrolimus levels. Liver transplant recipients were more likely to experience elevations in transaminases requiring pharmacologic or medical interventions. Majority of patients experienced improvements in pulmonary function, fasting blood glucose, hemoglobin, body mass index, and rhinosinusitis symptoms. However, intolerance or lack of benefit prompted discontinuation of ELX/TEZ/IVA in over 40% of lung-transplant recipients in one study. CONCLUSION: Modulator therapy has been reported to produce pulmonary and extra-pulmonary benefits in the CF population with SOT. Considerations for modulator therapy initiation ought to include modulator pharmacokinetics, concomitant medications, and transplant type due to the complex nature of SOT recipients.

Adherence to hydroxyurea and clinical outcomes among children with sickle cell anemia.

OBJECTIVE: Hydroxyurea lowers the incidence of vaso-occlusive pain crises (VOC) and acute chest syndrome (ACS) among children with sickle cell anemia (SCA). Our objective was to assess the relationship between levels of adherence to hydroxyurea and clinical outcomes among children and adolescents with SCA. METHODS: This retrospective cohort study included Medicaid data (2005-2012) from Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. The study population consisted of children 1-17 years old with SCA enrolled in Medicaid for 3 years. Among children that initiated hydroxyurea, the medication possession ratio (MPR) was calculated as the proportion of days covered by hydroxyurea. Six months after initiation of hydroxyurea, clinical outcomes were assessed through the end of the study period: numbers of VOC-related inpatient admissions and emergency department visits, and encounters for ACS. Multivariable Poisson models were used to predict outcomes by MPR quartile adjusting for previous healthcare utilization, state, and age. RESULTS: Hydroxyurea was initiated by 515 children. The median MPR was 0.53 (interquartile range = 0.3-0.8). The annual median number of visits was 0.0 for ACS, 1.3 for VOC-related emergency department, and 1.4 for VOC-related inpatient admissions. For each outcome, the highest quartile of MPR had the lowest predicted count; this difference was significant for ACS visits when compared with the lowest quartile of MPR. CONCLUSION: This study demonstrated a high level of adherence (>75%) was essential to achieve a lower incidence of common negative clinical outcomes. Further, moderate and severe hydroxyurea nonadherence may be more common than previously appreciated among children, emphasizing the importance of developing and testing innovative strategies to increase adherence.

Clearing up the smoke: Physical and mental health considerations regarding cannabis use in adolescents with cystic fibrosis.

The cannabis plant is the most used federally illegal drug in the United States and is widely used by adolescents. Cannabis has complex effects on the body and mind. All health professionals who take care of adolescents with cystic fibrosis (CF) should be aware of the factors impacting cannabis use in CF. Given limited evidence regarding the benefits of cannabis and the significant risks, clinicians have the responsibility to identify risk of cannabis use early, counsel patients about the risks, provide a safe space for ongoing conversations about cannabis use in the context of CF care, and deliver evidence-based interventions.

School Stock Inhaler Statutes and Regulations in the United States: A Systematic Review.

BACKGROUND: Children with asthma should have immediate access to rescue medication. Yet, <15% of children have access to this life-saving drug while at school. METHODS: A search was conducted in the all states database of Westlaw to identify which the US states, territories, and the District of Columbia have a law for K-12 schools. Terms searched included (inhaler or asthma/s medic!) and school and (prescription or order) from conception to December 2020. Demographic data from states with and without a policy were compared. All policies were examined for the following components: (1) type of law (statute or regulation); (2) type of school (charter, private/parochial or public); (3) training requirements; (4) devices; (5) prescriptive authority/safe harbor; (6) medication requirements; and (7) mandated documentation, reporting and funding. RESULTS: Our systematic search revealed 15 locations with existing laws. States with a law had a higher percentage of children under 17-years than states without a law (p = .02). Common components described were the applicability to various types of schools, training requirements for those empowered to administer, and civil liability protections for trained school personnel. CONCLUSIONS: Existing stock inhaler laws differ vastly across the United States that may impact access to stock albuterol for children at their schools.

Cystic Fibrosis Foundation otolaryngology care multidisciplinary consensus recommendations.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disease that often requires otolaryngology care. Individuals with CF commonly have chronic rhinosinusitis but also present with hearing loss and dysphonia. Given these manifestations of CF, otolaryngologists are frequently involved in the care of patients with CF; however, there is limited consensus on optimal management of sinonasal, otologic, and laryngologic symptoms. METHODS: The Cystic Fibrosis Foundation convened a multidisciplinary team of otolaryngologists, pulmonologists, audiologists, pharmacists, a social worker, a nurse coordinator, a respiratory therapist, two adults with CF, and a caregiver of a child with CF to develop consensus recommendations. Workgroups developed draft recommendation statements based on a systematic literature review, and a ≥80% consensus was required for acceptance of each recommendation statement. RESULTS: The committee voted on 25 statements. Eleven statements were adopted recommending a treatment or intervention, while five statements were formulated recommending against a specific treatment or intervention. The committee recommended eight statements as an option for select patients in certain circumstances, and one statement did not reach consensus. CONCLUSION: These multidisciplinary consensus recommendations will help providers navigate decisions related to otolaryngology consultation, medical and surgical management of CF-CRS, hearing, and voice in individuals with CF. A collaborative and multidisciplinary approach is advocated to best care for our patients with CF. Future clinical research is needed utilizing standardized, validated outcomes with comprehensive reporting of patient outcome, effects of modulator therapies, and genetic characteristics to help continue to advance care, decrease morbidity, and improve the quality of life for individuals with CF.

Ensuring Access to Albuterol in Schools: From Policy to Implementation. An Official ATS/AANMA/ALA/NASN Policy Statement.

Rationale: For children with asthma, access to quick-relief medications is critical to minimizing morbidity and mortality. An innovative and practical approach to ensure access at school is to maintain a supply of stock albuterol that can be used by any student who experiences respiratory distress. To make this possible, state laws allowing for stock albuterol are needed to improve medication access.Objectives: To provide policy recommendations and outline steps for passing and implementing stock albuterol laws.Methods: We assembled a diverse stakeholder group and reviewed guidelines, literature, statutes, regulations, and implementation documents related to school-based medication access. Stakeholders were divided into two groups-legislation and implementation-on the basis of expertise. Each group met virtually to review documents and draft recommendations. Recommendations were compiled and revised in iterative remote meetings with all stakeholders.Main Results: We offer several recommendations for crafting state legislation and facilitating program implementation. 1) Create a coalition of stakeholders to champion legislation and implement stock albuterol programs. The coalition should include school administrators, school nurses and health personnel, parents, or caregivers of children with asthma, pediatric primary care and subspecialty providers (e.g., pulmonologists/allergists), pharmacists, health department staff, and local/regional/national advocacy organizations. 2) Legislative components critical for effective implementation of stock albuterol programs include specifying that medication can be administered in good faith to any child in respiratory distress, establishing training requirements for school staff, providing immunity from civil liability for staff and prescribers, ensuring pharmacy laws allow prescriptions to be dispensed to schools, and suggesting inhalers with valved holding chambers/spacers for administration. 3) Select an experienced and committed legislator to sponsor legislation and guide revisions as needed during passage and implementation. This person should be from the majority party and serve on the legislature's health or education committee. 4) Develop plans to disseminate legislation and regulations/policies to affected groups, including school administrators, school nurses, pharmacists, emergency responders, and primary/subspecialty clinicians. Periodically evaluate implementation effectiveness and need for adjustments.Conclusions: Stock albuterol in schools is a safe, practical, and potentially life-saving option for children with asthma, whether asthma is diagnosed or undiagnosed, who lack access to their personal quick-relief medication. Legislation is imperative for aiding in the adoption and implementation of school stock albuterol policies, and key policy inclusions can lay the groundwork for success. Future work should focus on passing legislation in all states, implementing policy in schools, and evaluating the impact of such programs on academic and health outcomes.

A clinician survey of use assessment, documentation, and education about cannabis in persons with cystic fibrosis.

INTRODUCTION: To help open the clinician dialogue regarding cannabis use in persons with cystic fibrosis (CF) in the United States, we aimed to describe current practices of use assessment and documentation processes related to cannabis. METHODS: A cross-sectional, anonymous survey study was distributed via email to CF directors and coordinators and to the Cystic Fibrosis Foundation (CFF) listservs of nurse, pharmacist, dietitian, social worker, and psychology care team members. The survey tool included multiple choice, scaled, and open-ended items, which assessed participants' awareness of current cannabis laws in their state, prescribing practices for medical marijuana, screening and documentation practices, knowledge of and what indications participants believe cannabis and cannabidiol (CBD) could be beneficial. Data were analyzed using descriptive statistics. RESULTS: There were 282 survey participants, with majority as providers (28%) and social workers (29%), representing all US regions. Participants varied in terms of frequency of evaluating cannabis use, with 15.4% "always," 48.4% "sometimes," and 41% "rarely," or "never" asking about it. Regarding recreational versus medical cannabis use, 55.4% and 62.5% reported documentation of each type in the medical record, respectively. Participants reported appetite, pain, and nausea as the top three advocated indications for use. About 35% and 72% of participants felt "slightly" or "not at all" prepared to answer patient/family questions about cannabis and CBD, respectively. CONCLUSIONS: The approach to cannabis use assessment, documentation, and education across CF care centers is variable. There is a need for care team and patient/caregiver education materials about cannabis/CBD and CF.

Development of an Interdisciplinary Telehealth Care Model in a Pediatric Cystic Fibrosis Center.

Background: People with cystic fibrosis (PCF) have unique physical and emotional needs, which are best met through interdisciplinary care (IDC). In the midst of the pandemic, our center aimed to begin a telehealth care model with an objective to increase successful care visits from baseline of 0-95% by June 26, 2020, including meeting cystic fibrosis (CF) care standards of IDC visits that are coproduced through agenda setting with PCF. Methods: Shifting IDC for pediatric CF patients to telehealth was part of a quality improvement initiative. Our team used asynchronous virtual visits (VVs), with the IDC team members' VVs done on different days than the physician's. Multiple plan-do-study-act cycles were completed to address evolving telehealth needs, including IDC team member flow logistics, communication with PCF, and surveying PCF for the patient perspective. Rates of IDC and agenda setting were measured from March 16, 2020 to June 26, 2020. Results: IDC VVs were at 86% in March 2020 with fluctuations until mid-May when we reached 100% and achieved sustainability. Agenda setting was reached at 100% and maintained. With continued effort, an additional 46.3% of PCF registered for the patient portal, totaling 90.6% with access. Our survey revealed 100% of PCF were able to see IDC team members that they needed to, with 87% "extremely satisfied" and 13% "somewhat satisfied" with their telehealth experience. Conclusions: Successful telehealth in pediatric CF IDC can be achieved through continuous communication, optimal utilization of available technologies, and may help foster unique opportunities to help improve health outcomes.

Medication Use in Schools.

This article serves as a Position Statement of the Pediatric Pharmacy Association (PPA), which supports safe and effective medication use in schools. PPA recommends that schools develop comprehensive medication use policies to support safe and appropriate administration of both chronic and emergency medication in schools. These policies must address issues specific to pediatric patients, including off-label and over-the-counter medication use, various pediatric dosage forms, as well as appropriate medication storage, administration, and disposal practices. PPA also advocates for continued staff development and education regarding laws, regulations, and policies surrounding medication use in school to ensure safe and effective care of children and adolescents in the school setting.

Medication Use in Schools: Current Trends, Challenges, and Best Practices.

There are a significant number of students on maintenance medications for chronic diseases or with diagnoses that may result in medical emergencies requiring administration of medications in school. With passing of legislation in all 50 states allowing self-administration of emergency medications for allergic reactions and asthma, the landscape of medication use in schools is changing. These changes have raised questions about the need for legislation or policy development relating to self-carrying and self-administration of medications for other disease states, undesignated stock of emergency medications, and administration of medications by non-medical personnel. Medication administration in the school setting has become a complex issue, and this review will discuss current legislation related to medication use in schools and provide best practices for administering medications to children and adolescents while at school.

Advanced design and development of nanoparticle/microparticle dual-drug combination lactose carrier-free dry powder inhalation aerosols.

Rationale: lactose is the only FDA-approved carrier for dry powder inhaler (DPI) formulations in the US. Lactose carrier-based DPI products are contraindicated in patients with a known lactose allergy. Hence, inhaler formulations without lactose will benefit lactose allergic asthmatics. Objectives: to rationally design and develop lactose carrier-free dry powder inhaler formulations of fluticasone propionate and salmeterol xinafoate that will benefit people with known lactose allergy. The study also aims at improving the aerosol deposition of the dry powder formulation through advanced particle engineering design technologies to create inhalable powders consisting of nanoparticles/microparticles. Methods: advanced DPI nanoparticle/microparticle formulations were designed, developed and optimized using organic solution advanced closed-mode spray drying. The co-spray dried (co-SD) powders were comprehensively characterized in solid-state and in vitro comparative analysis of the aerodynamic performance of these molecularly mixed formulations was conducted with the marketed formulation of Advair® Diskus® interactive physical mixture. Measurements and main results: comprehensive solid-state physicochemical characterization of the powders showed that the engineered co-SD particles were small and spherical within the size range of 450 nm to 7.25 µm. Improved fine particle fraction and lower mass median aerodynamic diameter were achieved by these DPI nanoparticles/microparticles. Conclusions: this study has successfully produced a lactose-free dry powder formulation containing fluticasone propionate and salmeterol xinafoate with mannitol as excipient engineered as inhalable DPI nanoparticles/microparticles by advanced spray drying. Further, co-spray drying with mannitol and using Handihaler® device can generate higher fine particle mass of fluticasone/salmeterol. Mannitol, a mucolytic agent and aerosol performance enhancer, is a suitable excipient that can enhance aerosol dispersion of DPIs.

Developing Future Clinical Pharmacy Leaders in the Interprofessional Care of Children with Special Health Care Needs and Medical Complexity (CSHCN-CMC) in a Pediatric Pulmonary Center.

The health care needs of children with special health care needs and medical complexity (CSHCN-CMC) are multifaceted and often require the expertise of various disciplines. The medication-related needs of this population can be further complicated with off-label medication use, polypharmacy, and vulnerability to medication errors. Although clinical pharmacists are increasingly becoming a common part of inpatient, pediatric interprofessional patient care teams, their presence remains lacking in the outpatient or ambulatory care realm. Pediatric clinical pharmacists in the ambulatory care setting have the potential to help optimize medication use and safety through collaborative efforts as part of the interprofessional team. Since the late 1960s, Pediatric Pulmonary Centers (PPCs) provide training programs designed to develop interprofessional leaders who will improve the health status of CSHCN-CMC, specifically those with chronic respiratory and sleep-related conditions. The addition of pharmacists not only provides a more comprehensive care model for CSHCN-CMC, it creates an avenue to encourage the career paths of pediatric pharmacists in the ambulatory care setting. Here, we describe the addition of clinical pharmacy as part of an interprofessional patient care team and the development and implementation of a maternal child health (MCH) pharmacy discipline training model designed to mentor future pharmacist leaders in the care of CSHCN-CMC.

Pediatric-to-adult healthcare transitions: Current challenges and recommended practices.

PURPOSE: An overview of the pediatric-to-adult healthcare transition (HCT) process, including stakeholders, challenges, and fundamental components that present opportunities for pharmacists and pharmacy technicians, is provided. SUMMARY: Pediatric-to-adult HCT programs should be longitudinal in nature, be patient focused, and be coproduced by patients, caregivers, and care team members. Educational components of HCT programs should include knowledge and skills in disease state management and self-care; safe and effective use of medications, as well as other treatment modalities; and healthcare system navigation, including insurance issues. Interprofessional involvement in HCT is encouraged; however, roles for each discipline involved are not clearly delineated in current guidelines or literature. Possible influencing elements in achieving successful pediatric-to-adult HCT outcomes include those that are related to patient and/or caregiver factors, clinician awareness, availability of resources, and ability to achieve financial sustainability. CONCLUSION: The use of structured pediatric-to-adult HCT programs is currently recommended to optimize patient and health-system outcomes. Given the importance of medication-related knowledge and healthcare system navigation skills to successful care transitions, there are opportunities for pharmacists and pharmacy technicians to contribute to HCT programs.

Influence of the Vibralung Acoustical Percussor on pulmonary function and sputum expectoration in individuals with cystic fibrosis.

BACKGROUND: The Vibralung Acoustical Percussor is a new airway clearance therapy (ACT) utilizing intrapulmonary sound waves in addition to positive expiratory pressure (PEP). We evaluated the safety of the Vibralung and collected preliminary data on its ability to mediate sputum expectoration in individuals with cystic fibrosis (CF). METHODS: Over two separate studies, 10 and 11 mild to moderate CF patients were recruited for study I and II, respectively. Study I: Vibralung was used for 20 min with either no sound (NS: PEP only) or sound (S: PEP and sound) on randomized visits. Pulmonary function, diffusion capacity of the lungs for carbon monoxide and nitric oxide (DLCO/DLNO), symptoms, and peripheral oxygen saturation (SpO2) were measured at baseline and at 1 and 4 h post treatment. Expectorated sputum was collected over 4 h post treatment. Study II: over 5 days of in-hospital therapy, the Vibralung or vibratory vest therapy (Vest) were used for two therapy sessions per day, with sputum collected for 20 min following each therapy and pulmonary function accessed pre and post each 5-day period (days 1-5 or 7-11) in a randomized crossover design. RESULTS: Vibralung usage resulted in no change from baseline to 4 h post in pulmonary function, SpO2 or symptoms ( p > 0.05). At 4 h post therapy, the DLCO- and DLNO-derived measure of alveolar-capillary unit function (DM/ VC) showed improvement (DM/ VC = 12.5 ± 5.5 versus 7.3 ± 18.8% change, S versus NS) with no difference between S and NS ( p = 0.74). Sputum expectoration was similar between S and NS conditions (wet sputum = 10.5 ± 4.6 versus 9.9 ± 3.2 g, S versus NS, p = 0.25). There were no differences in the improvement in pulmonary function between Vibralung and Vest during either 5-day period during the hospital stay. CONCLUSIONS: Vibralung was well tolerated and caused no detrimental changes in pulmonary function metrics. The Vibralung appears to be a safe ACT in individuals with CF.