Cystic Fibrosis Foundation Pulmonary Guidelines. Use of Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy in Patients with Cystic Fibrosis.

RATIONALE: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators are a new class of medications targeting the underlying defect in CF. Ivacaftor (IVA) and IVA combined with lumacaftor (LUM; IVA/LUM) have been approved by the U.S. Food and Drug Administration (FDA) for use in patients with CF. However, the FDA label for these medications encompasses patient groups that were not studied as part of the drug approval process. CF clinicians, patients, and their families have recognized a need for recommendations to guide the use of these medications. OBJECTIVE: Develop evidence-based guidelines for CFTR modulator therapy in patients with CF. METHODS: A multidisciplinary committee of CF caregivers and patient representatives was assembled. A methodologist, an epidemiologist, a medical librarian, and a biostatistician were recruited to assist with the literature search, evidence grading, and generation of recommendations. The committee developed clinical questions using the Patient-Intervention-Comparison-Outcome format. A systematic review was conducted to find relevant publications. The evidence was then evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach, and recommendations were made based on this analysis. RESULTS: For adults and children aged 6 years and older with CF due to gating mutations other than G551D or R117H, the guideline panel made a conditional recommendation for treatment with IVA. For those with the R117H mutation, the guideline panel made a conditional recommendation for treatment with IVA for 1) adults aged 18 years or older, and 2) children aged 6-17 years with a forced expiratory volume in 1 second (FEV1) less than 90% predicted. For those with the R117H mutation, the guideline panel made a conditional recommendation against treatment with IVA for 1) children aged 12-17 years with an FEV1 greater than 90% predicted, and 2) children less than 6 years of age. Among those with two copies of F508del, the guideline panel made a strong recommendation for treatment with IVA/LUM for adults and children aged 12 years and older with an FEV1 less than 90% predicted; and made a conditional recommendation for treatment with IVA/LUM for 1) adults and children aged 12 years or older with an FEV1 greater than 90% predicted, and 2) children aged 6-11 years. CONCLUSIONS: Using the GRADE approach, we have made recommendations for the use of CFTR modulators in patients with CF. These recommendations will be of help to CF clinicians, patients, and their families in guiding decisions regarding use of these medications.

Improved screening for cystic fibrosis-related diabetes by an integrated care team using an algorithm.

OBJECTIVE: To determine whether implementation of a standardized, clinic-based algorithm improves compliance with cystic fibrosis-related diabetes (CFRD) screening guidelines. STUDY DESIGN: A CFRD screening algorithm was developed as part of a quality improvement initiative through collaboration between the pediatric pulmonary and endocrine divisions and implemented prospectively to children aged 8-17 years in our CF center for a 6-month period. The primary outcome measure was the percentage rate of CF patients who were appropriately screened with an oral glucose tolerance test (OGTT) during the quality improvement period as compared to the year prior. RESULTS: Ninety-seven percent (37/38) of OGTTs were appropriately ordered by providers, and 89% (34/38) of patients obtained the OGTT at the completion of the quality improvement period. Compared with the percentage of eligible patients completing the OGTT the year prior, the use of the algorithm significantly improved screening (P = 0.03). Data collected 1-year post-algorithm implementation revealed 97% (33/34) of OGTTs were ordered and 79% (27/34) of OGTTs were completed. The use of the algorithm 1-year post-implementation did not reveal a significant improvement in screening when compared to the reference year and implementation period (P = 0.08). CONCLUSIONS: Implementation of a clinical algorithm resulted in a statistically significant improvement in screening during the quality improvement period, but this improvement was not sustained the following year despite continued physician compliance with ordering the OGTT. Barriers to patient compliance need to be explored.

Non-physician providers as clinical providers in cystic fibrosis: survey of U.S. programs.

BACKGROUND AND METHODS: Non-physician providers (NPPs) including nurse practitioners (NPs) and physician assistants (PAs) are important members of CF care teams, but limited data exist about the extent NPPs are involved in CF care. A subcommittee was established by the CF Foundation to gather information about current involvement of NPPs. Surveys were sent to adult, pediatric and affiliate CF program directors (PDs) and NPPs working in US CF programs. RESULTS: Responses were received from 108 PDs (49% pediatric, 34% adult, 17% affiliate). Overall, 53% of the 108 programs had NPPs and 70% had or planned to hire NPPs. Reasons for NPP use included ideal clinical role (75%), expansion of services (72%), and physician shortage (40%). The survey collected 73 responses from NPPs (96% NPs, 4% PAs) who worked in pediatric (49%), adult (29%), affiliate (3%), or multiple programs (19%). Training occurred on the job in 88% and from prior CF experience in 21%. NPPs provided coverage in outpatient clinics (82%), inpatient care (64%), and weekend and/or night call (22%). In addition to clinical roles, NPPs are involved in education (95%), research (81%), and leadership (55%). The major obstacle reported by PDs and NPPs was billing with only 12% of programs reporting NPP salaries covered by billing revenue alone. Salary support included hospital support (67%), billing (39%), center grant (35%), and other grant/contract (25%). NPPs bill for outpatient and inpatient care in 65% and 28% of programs, respectively. CONCLUSIONS: NPPs are working with physicians in many centers and have the potential to help meet the increasing clinical workforce demands. Further evaluation of financial issues is indicated to continue the support of NPP jobs in CF. Roles and expectations need to be clearly defined. Initial and ongoing training standards and opportunities should be explored.

Cystic fibrosis pulmonary guidelines: airway clearance therapies.

Cystic fibrosis (CF) is a genetic disease characterized by dehydration of airway surface liquid and impaired mucociliary clearance. As a result, there is difficulty clearing pathogens from the lung, and patients experience chronic pulmonary infections and inflammation. Clearance of airway secretions has been a primary therapy for those with CF, and a variety of airway clearance therapies (ACTs) have been developed. Because ACTs are intrusive and require considerable time and effort, it is important that appropriate techniques are recommended on the basis of available evidence of efficacy and safety. Therefore, the Cystic Fibrosis Foundation established a committee to examine the clinical evidence for each therapy and provide guidance for their use. A systematic review was commissioned, which identified 7 unique reviews and 13 additional controlled trials that addressed one or more of the comparisons of interest and were deemed eligible for inclusion. Recommendations for use of the ACTs were made, balancing the quality of evidence and the potential harms and benefits. The committee determined that, although there is a paucity of controlled trials that assess the long-term effects of ACTs, the evidence quality overall for their use in CF is fair and the benefit is moderate. The committee recommends airway clearance be performed on a regular basis in all patients. There are no ACTs demonstrated to be superior to others, so the prescription of ACTs should be individualized. Aerobic exercise is recommended as an adjunctive therapy for airway clearance and for its additional benefits to overall health.

Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health.

RATIONALE: Cystic fibrosis is a recessive genetic disease characterized by dehydration of the airway surface liquid and impaired mucociliary clearance. As a result, individuals with the disease have difficulty clearing pathogens from the lung and experience chronic pulmonary infections and inflammation. Death is usually a result of respiratory failure. Newly introduced therapies and aggressive management of the lung disease have resulted in great improvements in length and quality of life, with the result that the median expected survival age has reached 36 years. However, as the number of treatments expands, the medical regimen becomes increasingly burdensome in time, money, and health resources. Hence, it is important that treatments should be recommended on the basis of available evidence of efficacy and safety. OBJECTIVES: The Cystic Fibrosis Foundation therefore established a committee to examine the clinical evidence for each therapy and to provide guidance for the prescription of these therapies. METHODS: The committee members developed and refined a series of questions related to drug therapies used in the maintenance of pulmonary function. We addressed the questions in one of three ways, based on available evidence: (1) commissioned systematic review, (2) modified systematic review, or (3) summary of existing Cochrane reviews. CONCLUSIONS: It is hoped that the guidelines provided in this article will facilitate the appropriate application of these treatments to improve and extend the lives of all individuals with cystic fibrosis.

Alterations in regional ventilation, perfusion, and shunt after smoke inhalation measured by PET.

Regional changes in ventilation and perfusion occurring in the early hours after smoke inhalation injury were evaluated through the use of positron emission tomography. Five lambs were imaged before and 1, 2, and 4 h after receiving 100 breaths of cotton smoke. Utilizing a recently developed model of (13)N tracer kinetics (3), we evaluated changes in ventilation, perfusion, shunt, and regional gas content in nondependent, middle, and dependent lung zones. The data demonstrated a progressive development of regional shunt in dependent (dorsal) regions in which perfusion remained the highest throughout the study. These findings, together with decreasing regional ventilation and fractional gas content in the dependent regions, correlated with decreasing arterial Pa(O(2)) values over the course of the study. A negative correlation between regional shunt fraction and regional gas content in dependent and middle regions suggests that shunt was caused by progressive alveolar derecruitment or flooding.

Regional VA, Q, and VA/Q during PLV: effects of nitroprusside and inhaled nitric oxide.

Partial liquid ventilation (PLV) with high-specific-weight perfluorocarbon liquids has been shown to improve oxygenation in acute lung injury, possibly by redistributing perfusion from dependent, injured regions to nondependent, less injured regions of the lung. Our hypothesis was that during PLV in normal lungs, a shift in perfusion away from dependent lung zones might, in part, be due to vasoconstriction that could be reversed by infusing sodium nitroprusside (NTP). In addition, delivering inhaled NO during PLV should improve gas exchange by further redistributing blood flow to well-ventilated lung regions. To examine this, we used a single transverse-slice positron emission tomography camera to image regional ventilation and perfusion at the level of the heart apex in six supine mechanically ventilated sheep during five conditions: control, PLV, PLV + NTP, and PLV + NO at 10 and 80 ppm. We found that PLV shifted perfusion from dependent to middle regions, and the dependent region demonstrated marked hypoventilation. The vertical distribution of perfusion changed little when high-dose intravenous NTP was added during PLV, and inhaled NO tended to shift perfusion toward better ventilated middle regions. We conclude that PLV shifts perfusion to the middle regions of the lung because of the high specific weight of perflubron rather than vasoconstriction.