Genetic counseling access and service delivery in New York State is variable for parents of infants with complex CFTR genotypes conferring uncertain phenotypes.

BACKGROUND: New York State (NYS) utilizes a three-tiered cystic fibrosis newborn screening (CFNBS) algorithm that includes cystic fibrosis transmembrane conductance regulator (CFTR) gene sequencing. Infants with >1 CFTR variant of potential clinical relevance, including variants of uncertain significance or varying clinical consequence are referred for diagnostic evaluation at NYS cystic fibrosis (CF) Specialty Care Centers (SCCs). AIMS: As part of ongoing quality improvement efforts, demographic, screening, diagnostic, and clinical data were evaluated for 289 CFNBS-positive infants identified in NYS between December 2017 and November 2020 who did not meet diagnostic criteria for CF and were classified as either: CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID) or CF carriers. RESULTS: Overall, 194/289 (67.1%) had CFTR phasing to confirm whether the infant's CFTR variants were in cis or in trans. Eighteen complex alleles were identified in cis; known haplotypes (p.R117H+5T, p.F508del+p.L467F, and p.R74W+p.D1270N) were the most common identified. Thirty-two infants (16.5%) with all variants in cis were reclassified as CF carriers rather than CRMS/CFSPID. Among 263 infants evaluated at an NYS SCC, 70.3% were reported as having received genetic counseling about their results by any provider, with 96/263 (36.5%) counseled by a certified genetic counselor. CONCLUSION: Given the particularly complex genetic interpretation of results generated by CFNBS algorithms including sequencing analysis, additional efforts are needed to ensure families of infants with a positive CFNBS result have CFTR phasing when needed to distinguish carriers from infants with CRMS/CFSPID, and access to genetic counseling to address implications of CFNBS results.

Changes in Body Mass Index in Children and Adolescents with Asthma during the COVID-19 Pandemic.

Background: Increased weight gain in children during the COVID-19 pandemic has been reported. Changes in weight in children with asthma during this period have not been well described. Methods: Retrospective review of children with asthma, 6-18 years of age, seen in 2019 and 2020. Mean monthly rates of change in body mass index (BMI) were compared between years. Demographic and asthma-related factors were examined. Results: Two hundred sixty-seven patients were enrolled. BMI increased by 0.128 ± 0.283 kg/m2/month during the pandemic year as compared with 0.084 ± 0.160 kg/m2/month during the previous year (P = 0.03). Patients with baseline overweight or obesity trended toward higher rates of BMI increase than those starting with normal weight, with the greatest BMI increase occurring in the severely obese. Conclusions: In this single-site study of children with asthma, there was a greater monthly rate of BMI gain during the early pandemic as compared with that observed in the previous year.

The relationship between weight and pulmonary outcomes in overweight and obese people with cystic fibrosis: A retrospective observational study.

Background: A major focus in cystic fibrosis (CF) care aims to increase weight gain. Rates of overweight and obese people with CF have gradually increased over the past decade. Obesity could be a risk for restriction of lung volumes and airway obstruction as well as increase rates of pulmonary exacerbations in people with CF. Aim: To assess the relationship between weight categories and pulmonary outcomes in children and adults with CF. Methods: Patients 6 years of age and older were categorized into weight categories based on the Centers for Disease Control and Prevention (CDC) definitions. A retrospective chart review was conducted to obtain lung function testing and other outcomes. Results: One hundred five patients with a median age of 20.6 years were included in this analysis. 8.4%, 64%, 18%, and 10% of patients were underweight, normal/healthy weight, overweight, and obese, respectively. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) (% predicted) did not differ between patients with weights in the normal range versus patients in the overweight/obese categories. Linear regression analysis showed a direct correlation between body mass index (BMI) and FEV1 that continued as BMI entered overweight and obese categories in both pediatric and adult patients. Overweight/obese patients did not have increased rates of pulmonary exacerbations compared to those in the normal/healthy weight category. Conclusion: As CF therapies continue to improve, an increasing number of people with CF are exceeding the CDC's normal-weight range. Gaining weight past the normal range does not appear to negatively impact pulmonary health of people with CF. If this trend of increased weight gain continues, it remains to be seen if it will eventually negatively affect lung health.

Counseling Tobacco Smoke Exposure Reduction Measures in Pediatrics: A Quality Improvement Project.

With over 40% of children in the USA exposed to tobacco smoke, the AAP recommends tobacco smoke exposure (TSE) assessment during clinic visits. We aimed to increase the rates of TSE screening and provider counseling regarding TSE reduction using an evidence-based approach. Methods: We conducted the project at a large pediatric pulmonology practice. Baseline caregiver surveys and medical record review of TSE documentation took place in July/August, 2019. From September 2019 to July 2021, PDSA cycles were conducted to increase TSE screening and reduce counseling. Results: Before starting the project, 18% of smoking caregivers acknowledged smoking in the home and 41% in the car. While caregivers strongly desired to decrease TSE (median 9.4/10 on Likert scale), physician counseling of TSE reduction was offered only to 44%. PDSA cycles led to refining our patient passport, a document used during patient intake, which increased screening of TSE from 46% to 85%. Creating an educational handout in our electronic record addressing TSE increased TSE reduction counseling from 44% to 80% of children with smokers in the home. Conclusions: Incorporating TSE screening into established nursing documentation of vital signs led to the sustained screening of TSE among children in a pediatric pulmonology practice. Embedding educational material in our electronic record and changes in clinic processes increased TSE reduction counseling. Similar changes could improve rates of counseling caregivers of other guidelines aimed to improve the children's health.

Incidence and prevalence of common respiratory pathogens before and after implementation of the Cystic Fibrosis Foundation Infection Prevention and Control Guideline.

BACKGROUND: The 2013 Cystic Fibrosis Foundation's Infection Prevention and Control Guideline (CFF IP&C) was developed to reduce the risk of acquisition and transmission of respiratory pathogens in patients with cystic fibrosis (CF). OBJECTIVE: We hypothesised that the incidence of common CF respiratory pathogens would decrease at our centre after implementation of the guideline. METHODS: All patients with CF seen at our centre from August 2012 through August 2017 who had respiratory cultures were included. Patients were excluded from incidence analysis if they did not have at least one culture per year. Quarterly data were collected for one year before and three years after implementation of the guidelines to determine the incidence and prevalence of seven organisms commonly found in respiratory cultures of patients with CF. RESULTS: Quarterly and annual incidence and prevalence rates of common organisms did not change during the study period. DISCUSSION: There were no significant differences in the incidence or prevalence of common respiratory organisms in the first three years after implementation of the CF IP&C guideline. Long-term follow-up is needed to determine if changes occur over time.

Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators correct the basic defect caused by CFTR mutations. Improvements in health outcomes have been achieved with the combination of a CFTR corrector and potentiator in people with cystic fibrosis homozygous for the F508del mutation. The addition of elexacaftor (VX-445), a next-generation CFTR corrector, to tezacaftor plus ivacaftor further improved F508del-CFTR function and clinical outcomes in a phase 2 study in people with cystic fibrosis homozygous for the F508del mutation. METHODS: This phase 3, multicentre, randomised, double-blind, active-controlled trial of elexacaftor in combination with tezacaftor plus ivacaftor was done at 44 sites in four countries. Eligible participants were those with cystic fibrosis homozygous for the F508del mutation, aged 12 years or older with stable disease, and with a percentage predicted forced expiratory volume in 1 s (ppFEV1) of 40-90%, inclusive. After a 4-week tezacaftor plus ivacaftor run-in period, participants were randomly assigned (1:1) to 4 weeks of elexacaftor 200 mg orally once daily plus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h versus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h alone. The primary outcome was the absolute change from baseline (measured at the end of the tezacaftor plus ivacaftor run-in) in ppFEV1 at week 4. Key secondary outcomes were absolute change in sweat chloride and Cystic Fibrosis Questionnaire-Revised respiratory domain (CFQ-R RD) score. This study is registered with ClinicalTrials.gov, NCT03525548. FINDINGS: Between Aug 3 and Dec 28, 2018, 113 participants were enrolled. Following the run-in, 107 participants were randomly assigned (55 in the elexacaftor plus tezacaftor plus ivacaftor group and 52 in the tezacaftor plus ivacaftor group) and completed the 4-week treatment period. The elexacaftor plus tezacaftor plus ivacaftor group had improvements in the primary outcome of ppFEV1 (least squares mean [LSM] treatment difference of 10·0 percentage points [95% CI 7·4 to 12·6], p<0·0001) and the key secondary outcomes of sweat chloride concentration (LSM treatment difference -45·1 mmol/L [95% CI -50·1 to -40·1], p<0·0001), and CFQ-R RD score (LSM treatment difference 17·4 points [95% CI 11·8 to 23·0], p<0·0001) compared with the tezacaftor plus ivacaftor group. The triple combination regimen was well tolerated, with no discontinuations. Most adverse events were mild or moderate; serious adverse events occurred in two (4%) participants receiving elexacaftor plus tezacaftor plus ivacaftor and in one (2%) receiving tezacaftor plus ivacaftor. INTERPRETATION: Elexacaftor plus tezacaftor plus ivacaftor provided clinically robust benefit compared with tezacaftor plus ivacaftor alone, with a favourable safety profile, and shows the potential to lead to transformative improvements in the lives of people with cystic fibrosis who are homozygous for the F508del mutation. FUNDING: Vertex Pharmaceuticals.

Staphylococcus aureus nasal colonization among pediatric cystic fibrosis patients and their household contacts.

BACKGROUND: Little is known about the prevalence of Staphylococcus aureus nasal colonization and the epidemiology of methicillin-susceptible and methicillin-resistant S. aureus (MRSA) among cystic fibrosis (CF) patients and their household members. OBJECTIVES: We sought to determine the epidemiology of S. aureus among children and adolescents with CF and their household members. METHODS: Three CF centers enrolled case subjects with at least 1 MRSA-positive respiratory tract culture from 2001 to 2006 and control subjects with MRSA-negative cultures. S. aureus isolates from the anterior nares of CF subjects and their household members were assessed for staphylococcal chromosomal cassette (SCC) mec type. Strain similarity was determined by pulsed-field gel electrophoresis. RESULTS: S. aureus nasal colonization occurred in 52.4% (22/42), 27.0% (17/63), and 25.0% (72/288) of case, control, and household participants, respectively. Case subjects and their contacts were more likely to harbor MRSA in their nares and be from a multipatient CF family. Of 31 MRSA strains, 10 (32.3%) were SCCmec type IVa, associated with community-acquisition. Overall, 27.6% of 98 households had > or =2 members colonized with closely related isolates. Household members were equally likely to be colonized with closely related strains of MRSA (20/31, 65%) versus MSSA (38/80, 48%). CONCLUSIONS: This study demonstrated that household members of CF children harbor both MSSA and MRSA, including CA-MRSA, and that S. aureus is transmitted within CF households. Carriage of S. aureus by household members of CF children may have implications for infection control and treatment strategies. Future studies should monitor the distribution and virulence of SCCmecA types in patients with CF.