Cystic Fibrosis Foundation Evidence-Based Guideline for the Management of CRMS/CFSPID.

A multidisciplinary committee developed evidence-based guidelines for the management of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID). A total of 24 patient, intervention, comparison, and outcome questions were generated based on surveys sent to people with CRMS/CFSPID and clinicians caring for these individuals, previous recommendations, and expert committee input. Four a priori working groups (genetic testing, monitoring, treatment, and psychosocial/communication issues) were used to provide structure to the committee. A systematic review of the evidence was conducted, and found numerous case series and cohort studies, but no randomized clinical trials. A total of 30 recommendations were graded using the US Preventive Services Task Force methodology. Recommendations that received ≥80% consensus among the entire committee were approved. The resulting recommendations were of moderate to low certainty for the majority of the statements because of the low quality of the evidence. Highlights of the recommendations include thorough evaluation with genetic sequencing, deletion/duplication analysis if <2 disease-causing variants were noted in newborn screening; repeat sweat testing until at least age 8 but limiting further laboratory testing, including microbiology, radiology, and pulmonary function testing; minimal use of medications, which when suggested, should lead to shared decision-making with families; and providing communication with emphasis on social determinants of health and shared decision-making to minimize barriers which may affect processing and understanding of this complex designation. Future research will be needed regarding medication use, antibiotic therapy, and the use of chest imaging for monitoring the development of lung disease.

Clinical outcomes at 9-10 years of age in children born with cystic fibrosis transmembrane conductance regulator related metabolic syndrome.

BACKGROUND AND OBJECTIVES: There are limited data on cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to analyze outcomes of infants with CRMS up to the age of 9-10 years using the CF Foundation Patient Registry (CFFPR). METHODS: We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010 and 2020. We classified all patients based on the clinical diagnosis reported by the CF care center and the diagnosis using CFF guideline definitions for CF and CRMS, classifying children into groups based on agreement between clinical report and guideline criteria. Descriptive statistics for the cohort were calculated for demographics, nutritional outcomes, and microbiology for the first year of life and lung function and growth outcomes were summarized for ages 6-10 years. RESULTS: From 2010 to 2020, there were 8765 children with diagnosis of CF or CRMS entered into the CFFPR with sufficient diagnostic data for classification, of which 7591 children had a clinical diagnosis of CF and 1174 had a clinical diagnosis of CRMS. CRMS patients exhibited normal nutritional indices and pulmonary function up to age 9-10 years. The presence of respiratory bacteria associated with CF, such as Pseudomonas aeruginosa from CRMS patients ranged from 2.1% to 9.1% after the first year of life. CONCLUSIONS: Children with CRMS demonstrate normal pulmonary and nutritional outcomes into school age. However, a small percentage of children continue to culture CF-associated respiratory pathogens after infancy.

A Cross-Sectional Study of Pediatric Feeding Disorder in Children with Cystic Fibrosis.

BACKGROUND: The exact prevalence of feeding problems in children with cystic fibrosis (CF) is unknown. Pediatric feeding disorder (PFD) encompasses poor oral intake with associated medical, nutrition, psychosocial, or feeding skill dysfunction. We hypothesized that PFD is common in CF and aimed to categorize feeding dysfunction across various domains in children with CF. METHODS: An observational cross-sectional study was conducted in children with CF. Data collected included anthropometrics, nutrition data (including need for tube feeding/enteral nutrition [EN] or high-energy beverages, dietary diversity), feeding skills (Pediatric version of the Eating Assessment tool [pEAT]), and psychosocial function (About Your Child's Eating questionnaire [AYCE] in children 2-17 years of age/Behavioral Pediatric Feeding Assessment Scale [BPFAS] in children 12-23 months of age). PFD was defined as poor oral intake with: (a) pEAT score > 5; and/or (b) AYCE or BPFAS score > 2 standard deviation of normative controls; and/or (c) nutrition dysfunction (body mass index/weight-for-length z score < -1 and/or preference of oral high energy beverages or dependence on EN and/or decreased dietary diversity). RESULTS: Of 103 children in the study, 62 (60.1%) had PFD, 7 children (6.8%) were malnourished, 10 needed EN (9.7%), and 30 (29.1%) needed oral high-energy beverages. Dietary diversity was decreased in 42 children (41.5%), 1 child had feeding skill dysfunction, and 11 (10.8%) met criteria for psychosocial dysfunction. CONCLUSION: Almost 2/3rd of children with CF have PFD and many have poor dietary diversity. A significant percentage of children rely on EN and oral supplements, but psychosocial dysfunction is less prevalent.

Refinement of newborn screening for cystic fibrosis with next generation sequencing.

BACKGROUND: Newborn screening for cystic fibrosis (CF) has been underway universally in the United States for more than a decade, as well in most European countries, and algorithms have been evolving throughout this period with quality improvement projects as immunoreactive trypsinogen (IRT) determinations alone have been transformed to a 2-tier strategy with DNA analyses. OBJECTIVE: To apply next generation sequencing (NGS) as a screening method to expand the DNA tier and identify substantially more variants in the CF transmembrane conductance regulator (CFTR) gene to enhance sensitivity and equity while minimizing incidental findings. DESIGN: Sequential evaluation and improvement plan in three phases using algorithm modifications coupled to statewide follow up and analysis of screening outcomes. RESULTS: After demonstrating feasibility in the first phase, we studied an IRT/NGS algorithm that included CFTR Variants with Varying Clinical Consequences (VVCCs). This revealed a high identification of CF patients with 2-variants detected through screening, but for every CF case there were 1.4 with CF metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID). This led us to a third phase of improvement in which the VVCCs were eliminated except for R117H, resulting in 94% 2-variant detection of patients and 0.44:1 ratio of CRMS/CFSPID to CF. CONCLUSION: NGS can be used with IRT as an effective method of identifying infants at risk for CF without an appreciable increase in detection of carriers. Its potential added value includes facilitating equity, enhancing sensitivity and detecting more CF patients with 2-variants during the screening process.

Factors associated with HIV testing and treatment among young Black MSM and trans women in three jail systems.

Black men who have sex with men (BMSM) and transgender women (BTW) are disproportionately affected by incarceration and HIV. We assessed factors associated with HIV testing and viral suppression among 176 incarcerated BMSM and BTW in Chicago, IL; Los Angeles, CA; and Houston, TX. In multivariable logistic regression, having a sexual orientation of bisexual, heterosexual, or other vs. gay or same-gender loving was associated with higher odds of testing in custody (aOR 8.97; 95% CI 1.95 - 41.24). Binge drinking (aOR 0.19; 95% CI 0.04 - 0.92) and being unemployed prior to incarceration (aOR 0.03; 95% CI 0.00 - 0.23) were associated with lower odds of testing; participants in Los Angeles were also more likely to be tested than those in Chicago. Being housed in protective custody (aOR 3.12; 95% CI 1.09-9.59) and having a prescription for ART prior to incarceration (aOR 2.58; 95% CI 1.01-6.73) were associated with higher odds of viral suppression when adjusted for site and duration of incarceration, though the associations were not statistically significant in the full multivariable model. Future research should examine structural and process level factors that impact engagement in HIV testing and treatment among detained BMSM and BTW.

Defining and identifying early-onset lung disease in cystic fibrosis with cumulative clinical characteristics.

BACKGROUND: Because of the heterogeneity in cystic fibrosis (CF) lung disease among young children, a clinical method to identify early-onset lung disease is needed. OBJECTIVE: To develop a CF early-onset lung disease (CFELD) scoring system by utilizing prospectively collected longitudinal data on manifestations in the first 3 years of life. DESIGN: We studied 145 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and followed to 36 months of age. Cough severity, pulmonary exacerbations (PEx), respiratory cultures, and hospitalizations were collected at each CF center visit (every 1-2 months in infancy and quarterly thereafter). These data were used to construct the CFELD system and to classify lung disease into five categories: asymptomatic, minimal, mild, moderate, and severe. RESULTS: The most frequent manifestation of CF early lung disease was MD-reported PEx episodes, PEx hospitalizations, and positive Pseudomonas aeruginosa cultures. Parent-reported cough severity was correlated with the number of respiratory hospitalizations (r = 0.48, p < 0.0001). The distribution of CFELD categories was 10% asymptomatic, 17% minimal, 29% mild, 33% moderate, and 12% severe. The moderate and severe categories occurred threefold higher in pancreatic insufficient (PI, 49%) versus sufficient subjects (16%), p < 0.0001. In addition to PI, gastrointestinal and nutrition-related hospitalizations, plasma cytokines interleukin (IL)-6 and IL-10, duration of CFTR modulator therapy, and type of health insurance were significant predictors of CFELD scores. CONCLUSION: The CFELD scoring system is novel, allows systematic evaluation of lung disease prognosis early, and may aid in therapeutic decision-making particularly in the initiation of CFTR modulator therapy.

Cystic fibrosis year in review 2020: Section 2 pulmonary disease, infections, and inflammation.

The outlook for those with cystic fibrosis (CF) has never been brighter with ever increasing life expectancy and the approval of the highly effective CFTR modulators, such as elexacaftor/tezacaftor/ivacaftor. With that being said, the progressive pulmonary decline and importance of lung health, infection, and inflammation in CF remains. This review is the second part in a three-part CF Year in Review 2020. Part one focused on the literature related to CFTR modulators while part three will feature the multisystem effects related to CF. This review focuses on articles from Pediatric Pulmonology, including articles from other journals that are of particular interest to clinicians. Herein, we highlight studies published during 2020 related to CF pulmonary disease, infection, treatment, and diagnostics.

Quality Improvement Approach to Reducing Admission Hypothermia Among Preterm and Term Infants.

BACKGROUND: Newborns, particularly premature newborns, are susceptible to hypothermia when transitioning from birth to admission to the NICU, potentially leading to increased mortality and morbidity. Despite attention to this issue, our rate of admission hypothermia was 39.8%. METHODS: We aimed to reduce the rate of admission hypothermia for all inborn infants admitted to our institution to <10%. We undertook a quality improvement effort that spanned from 2013 through 2019 in our level IV NICU. Current state analysis involved investigating patient risk factors for hypothermia and staff understanding of hypothermia prevention. Improvement cycles included auditing processes, an in-hospital relocation of our NICU, expanded use of chemical heat mattresses and polyethylene bags, and staff education. Improvement was evaluated by using Shewhart control charts. RESULTS: We demonstrated a reduction in admission hypothermia from 39.8% to 9.9%, which was temporally related to educational efforts and expanded use of chemical heat mattresses and polyethylene bags. There was not an increase in admission hyperthermia over this time period. We found that our group at highest risk of admission hypothermia was not our most premature cohort but those infants born between 33 and 36 6/7 weeks' gestation and those infants prenatally diagnosed with congenital anomalies. CONCLUSIONS: Expanded use of polyethylene bags and chemical heat mattresses can improve thermoregulation particularly when combined with staff education. Although premature infants have been the focus of many hypothermia prevention efforts, our data suggest that older infants, and those infants born with congenital anomalies, require additional attention.

Lumacaftor/ivacaftor therapy fails to increase insulin secretion in F508del/F508del CF patients.

BACKGROUND: Glucose tolerance abnormalities including cystic fibrosis related diabetes (CFRD) are common in patients with cystic fibrosis (CF). The underlying pathophysiology is not fully understood. Emerging evidence suggests that CFTR dysfunction may directly or indirectly impact ß-cell function, offering the potential for improvement with CFTR modulator therapy. In small pilot studies, treatment with ivacaftor improved insulin secretion in patients with the G551D CFTR mutation. In the current study, we examined the impact of lumacaftor/ivacaftor therapy on glucose tolerance and insulin secretion in patients with CF who were homozygous for the F508del mutation. METHODS: 39 subjects from the PROSPECT Part B study who had been prescribed lumacaftor/ivacaftor by their CF care team at a CF Foundation's Therapeutic Development Network center were recruited. Subjects underwent 2-hour oral glucose tolerance tests (OGTTs) at baseline prior to first dose of lumacaftor/ivacaftor, and at 3, 6 and 12 months on therapy. OGTT glucose, insulin and c-peptide parameters were compared. RESULTS: Compared to baseline, OGTT fasting and 2 hour glucose levels, glucose area under the curve, insulin area under the curve and time to peak insulin level were not significantly different at 3, 6 and 12 months on lumacaftor/ivacaftor therapy. Similarly, C-peptide levels were no different. CONCLUSIONS: Lumacaftor/ivacaftor therapy did not improve insulin secretion or glucose tolerance in patients with CF who were homozygous for the F508del mutation.

Lactation Consultation Sustains Breast Milk Intake in Infants With Cystic Fibrosis.

Guidelines recommend breastfeeding in cystic fibrosis (CF) but breastfeeding rates decline rapidly in CF. We initiated a quality improvement project to improve breastfeeding in CF by incorporating International Board-Certified Lactation Consultants (IBCLC) into the initial CF-diagnosis visit to support mothers who were breastfeeding at diagnosis. In the preintervention group, only 8/14 (57%) continued to provide breast milk after the first visit, whereas postintervention, 16/17 (94%) mothers continued to do so (P = 0.03). The duration of any (or partial) breastfeeding increased to an average of 7.7 months from an average of 6.4 months preintervention (P = 0.45). The weight z score and weight-for-length z score at diagnosis showed no change at 6 or 12 months (all comparisons P value >0.05). We conclude that mothers who met with the IBCLC were less likely to quit breastfeeding and hypothesize that lactation support to mothers can prolong the duration of breastfeeding in infants with CF.

Oral health of cystic fibrosis patients at a north american center: A pilot study

Background: The objective of this study was to describe the oral health status of Cystic Fibrosis (CF) children in a US facility. Material and Methods: Twenty CF children ages 6-18 were recruited from Children's Hospital of Wisconsin Pulmonary Clinic. Parents completed a health questionnaire. Clinical examinations checked dental caries using the dmft/DMFT index, dental hygiene using the Simplified Greene-Vermillion Index (DI-S), gingival inflammation using the Community Periodontal Index of Treatment Needs, and enamel defects using the modified Developmental Defects of Enamel Index. Results: The majority (90%) brush twice a day, 65% consume sugary snacks, and 70% visit the dentist every 6 months. Clinically, they presented DMFT 0.25 and dmft 0.90, fair oral hygiene with DI-S 1.02, 75% had mild gingivitis and 50% had enamel defects. The more antibiotics they took, significantly more frequent (p = 0.007) and more severe (p = 0.017) enamel defects were noted. Similar trend was found between the number of surgeries and the presence of enamel defects (p=0.076) and dental caries (p = 0.028). Conclusions: Within the limitations of this study, CF patients were found to be at oral health risk due to the high prevalence of dental enamel defects. Oral health for CF children should be part of the multidisciplinary care

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Building school health partnerships to improve pediatric asthma care: the School-based Asthma Management Program.

PURPOSE OF REVIEW: Children with asthma require care that is seamlessly coordinated so that asthma symptoms are recognized and managed at home and at school. The purpose of this review is to discuss recent consensus recommendations in school-based asthma care. RECENT FINDINGS: The School-based Asthma Management Program (SAMPRO) provides a widely endorsed framework to coordinate care with schools and consists of four components: establishing a circle of support around the child with asthma; facilitating bidirectional communication between clinicians and schools; comprehensive asthma education for schools; and assessment and remediation of environmental asthma triggers at school. SAMPRO standardizes recommendations for school-based asthma care coordination and provides a toolkit with websites and resources useful for the care of children with asthma in the school setting. SUMMARY: The review will discuss the need for coordinated school asthma partnerships, the inception and development of SAMPRO, and its vision to improve pediatric asthma care coordination within the circle of support, comprising clinicians, school nurses, families, and communities.

Creation and implementation of SAMPRO™: A school-based asthma management program.

Clinicians who care for children with asthma have an obligation to coordinate asthma care with the schools. Aside from routine clinical care of asthmatic children, providers must educate the family and child about the need for an asthma treatment plan in school and support the school nurse meeting the needs of the student requiring school-based asthma care. The following article was developed by multiple stakeholders to address this need. It describes the 4 components of the School-based Asthma Management Program (SAMPRO™). SAMPRO™ details elements necessary for the education of children, families, clinicians, and school-based personnel based on a "circle of support" that would enhance multidirectional communication and promote better care for children with asthma within the school setting.

Improving inpatient cystic fibrosis pulmonary exacerbation care: two success stories.

BACKGROUND: Pulmonary exacerbations (PEx) in cystic fibrosis (CF) are a frequent cause of hospitalisations and lead to long-term decline in pulmonary function. Successful CF inpatient care requires the coordination of multiple providers and complex therapies. Children's Hospital of Wisconsin (CHW) and Children's Healthcare of Atlanta (CHoA) independently identified PEx inpatient care for focused improvements, with emphasis on improving care coordination and patient outcomes. METHODS: Both centres began by forming multidisciplinary workgroups, including patient and family representatives. CHW's specific aim was to eliminate delays in the time to initial intravenous antibiotics. A written handoff tool was developed to allow more efficient ordering. Efforts at CHoA focused on coordination and consistent care delivery. A written schedule and patient incentive programme were devised to ensure proper administration of treatments and promote patient adherence. RESULTS: At CHW, interventions decreased the mean antibiotic order time by 59% with resultant decrease in administration time by 25%. At CHoA, improvements led to a 42% decrease in the proportion of hospitalisations unsuccessful in returning lung function back to within 90% of baseline. CONCLUSIONS: Inpatient CF PEx care is complex and requires multiple competing activities and treatments. Consistent and timely delivery of these treatments is challenging. Our improvements used the skills and insights of providers and patients to improve, standardise and synchronise care, and to develop tools to coordinate hand offs. With these improvements, applicable to hospital treatment of many other conditions, both centres were successfully able to deliver treatments in a more consistent and timely manner with improved outcomes.