Experiences of cystic fibrosis newborn screening and genetic counseling.

The South Carolina cystic fibrosis (CF) newborn screening (NBS) program changed in 2019 to include CFTR genotyping for babies with top 4% immunoreactive trypsinogen, which improves sensitivity and timeliness but increases carrier detection. Carrier identification has genetic implications for the family and parents of NBS+ babies have increased emotional distress. Genetic counseling (GC) may increase parent understanding and reduce anxiety yet is not uniformly offered at CF centers. We report our early results after implementing GC for NBS+ families at the time of sweat chloride testing based on GC availability, which resulted in an unselected GC- control arm. Sixteen mothers (GC+ = 9, GC- = 7) participated in an online survey about their experience. Responses were analyzed in aggregate and for differences between GC+ and GC- groups. All-respondent sadness and anxiety increased with notification of the NBS+ result and decreased after sweat test results. Anxiety and sadness were greater in GC- compared to GC+ until after the diagnosis was resolved, though emotional differences between the groups were not statistically significant. On a scale of 0 = not at all to 10 = extremely, GC was rated very helpful (mean 9.0, range 5-10), informative (mean 8.9, range 4-10), comforting (mean 9.1, range 6-10), and minimally distracting (mean 1.8, range 0-9). All participants correctly identified that a risk for a child to have CF exists when both parents are (at least) carriers. Delivery of NBS results to respondents varied by timing, informant, and information given. The child's pediatrician notified 10 (62.5%) of the NBS+ result. Parents felt they were notified in a timely manner (68.8%), by someone knowledgeable about NBS (62.5%), the sweat test (62.5%), CF (43.8%), and genetics (43.8%) and who cared about them (81.3%). Parents felt worried (81.3%), confused (81.3%), empowered (25%), and other (sad, shocked, scared, overwhelmed, devastated, defeated). Data from this single-center study suggest benefit of GC, that families would value earlier contact with an expert, and that prompt diagnostic resolution may reduce duration of parental distress.

Evolving nutritional needs, obesity, and overweight status in cystic fibrosis.

PURPOSE OF REVIEW: The nutritional landscape in cystic fibrosis has shifted dramatically in the era of CFTR modulator therapy. In this review, we will critically examine the literature on overweight and obesity in CF, current nutritional care unknowns and opportunities for further investigation or adaptation in clinical care. RECENT FINDINGS: Results of clinical trial and real-world data reflect marked improvement in nutritional status and quality of life. Clinical outcomes including CF related diabetes and CF related liver disease appear positively impacted. Secondary impacts on cardiometabolic disease have been noted, especially in association with excessive weight gain. SUMMARY: The prior approaches to optimizing nutrition in cystic fibrosis with caloric excess can likely be safely retired for many. As modulator access expands across the lifespan, a longitudinal focus on health maintenance should be considered.

Obesity in Cystic fibrosis: prevalence, trends and associated factors data from the US cystic fibrosis foundation patient registry.

Strong emphasis has been placed historically on increasing weight and improving nutritional status in cystic fibrosis patients. Due to correlation between nutritional indices (e.g. BMI) and lung function, CF Nutrition Guidelines have recommended BMI percentile goals at the 50th percentile or higher. Trends in increasing BMI across CF programs suggest significantly increasing proportions of overweight and obese status in recent years. We identify that between 2000 and 2019 there has been a relative decrease in underweight status by ∼40%, simultaneously with a > 300% increase in overweight status, and >400% increase in obesity. Patient specific factors associated with higher prevalence of obesity included age ≥46, living in a zip code where the median income was < $20,000, having at least one allele with a class IV or V mutation, a ppFEV1 >90 prescribed ivacaftor, and not prescribed pancreatic enzymes. Program specific factors were not identified.

A case report of CFTR modulator administration via carrier mother to treat meconium ileus in a F508del homozygous fetus.

We report elexacaftor-tezacaftor-ivacaftor (ETI) treatment of a F508del carrier who was pregnant with a F508del homozygous fetus. At 23-weeks gestation meconium ileus (MI) was evident on ultrasound including dilated, hyperechoic bowel, which persisted on subsequent imaging. Through shared decision-making, the mother began ETI at 32 weeks with intent to treat fetal MI. The ultrasound findings persisted at treatment day 13, but bowel dilation had resolved by imaging on treatment day 27. A female infant was delivered vaginally at 36 weeks with no complications. The mother continued ETI while breastfeeding. Stool elastase at age 2 weeks was 240 mcg/g. Sweat chloride measurement was 64 and 62 mEq/L. Maternal and infant liver function testing have been normal. Maternal ETI treatment likely led to resolution of the MI and there is evidence supporting continued infant benefit through breastmilk. Logistical and ethical considerations regarding treatment of a carrier mother for infant benefit are discussed.

Optimizing outcomes of pulmonary exacerbations in cystic fibrosis.

PURPOSE OF REVIEW: Pulmonary exacerbations are described as worsening of the daily symptoms of cystic fibrosis airways disease, typically with increased cough and sputum production. There are often associated signs such as weight loss and reduced lung function. These events occur frequently and are associated with considerable cost and morbidity. Although approved maintenance therapies are shown to reduce exacerbations, they still occur and are associated with poor outcomes despite treatment. Guidelines to define best practices found a paucity of evidence upon which to base recommendations. RECENT FINDINGS: There are ongoing studies that are trying to build the evidence upon which to improve our practice. Antibiotics remain a core aspect of treatment, but there is high variance in practice patterns including selection of antibiotics and duration of therapy. In addition, there is a discordance between antibiotic susceptibility test results and clinical outcomes, suggesting we need better approaches to guide antibiotic selection. SUMMARY: Treatment durations are highly variable but recent evidence has demonstrated worse outcomes with shorter durations; longer durations may be associated with complications of treatment, suggesting an optimal duration could be identified. New studies aim to define best practices to improve outcomes with treatment of pulmonary exacerbations.

Combined effects of multiple risk factors on asthma in school-aged children.

BACKGROUND: Little is known about synergistic effects of several risk factors on asthma. We developed a risk score in Puerto Rican children, and then used this score to estimate the combined effects of multiple risk factors on asthma at school age in Puerto Rican and Swedish children. METHODS: Case-control study in 609 Puerto Rican children (aged 6-14 years) and longitudinal birth cohort study of 2290 Swedish children followed up to age 12 years (The Children, Allergy, Milieu, Stockholm, Epidemiological Survey [BAMSE] Study). In both cohorts, there was data on parental asthma, sex, obesity, allergic rhinitis, and early-life second-hand smoke (SHS); data on diet and (in children ≥9 years) lifetime exposure to gun violence were also available in the Puerto Rico study. Asthma was defined as physician-diagnosed asthma and ≥1 episode of wheeze in the previous year. RESULTS: In a multivariable analysis in Puerto Rican children, male sex, parental asthma, allergic rhinitis, early-life SHS, an unhealthy diet and (in children ≥9 years) gun violence were each significantly associated with asthma. We next created a risk score using these variables (range, 0 to 5-6 in Puerto Rico and 0 to 4 in BAMSE). Compared with Puerto Rican children without any risk factors (i.e. a score of 0), Puerto Rican children with 2, 3, and at least 4 risk factors had 3.6 times (95% CI = 1.4-9.2), 10.4 times (95% CI = 4.0-27.0), and 21.6 times (95% CI = 7.2-64.9) significantly higher odds of asthma, respectively. In BAMSE, the presence of 2, 3, and at least 4 risk factors was significantly associated with 4.1 times (95% CI = 2.3-7.4), 6.3 times (95% CI = 3.0-13.3), and 17.2 times (95% CI = 4.1-73.2) increased odds of asthma at age 12 years. CONCLUSIONS: Our findings emphasize the multifactorial etiology of asthma, and suggest that concurrent eradication or reduction of several modifiable risk factors may better prevent or reduce the burden of childhood asthma.

Clinical correlates of lung ventilation defects in asthmatic children.

BACKGROUND: Lung ventilation defects identified by using hyperpolarized 3-helium gas ((3)He) lung magnetic resonance imaging (MRI) are prevalent in asthmatic patients, but the clinical importance of ventilation defects is poorly understood. OBJECTIVES: We sought to correlate the lung defect volume quantified by using (3)He MRI with clinical features in children with mild and severe asthma. METHODS: Thirty-one children with asthma (median age, 10 years; age range, 3-17 years) underwent detailed characterization and (3)He lung MRI. Quantification of the (3)He signal defined ventilation defect and hypoventilated, ventilated, and well-ventilated volumes. RESULTS: The ventilation defect to total lung volume fraction ranged from 0.1% to 11.6%. Children with ventilation defect percentages in the upper tercile were more likely to have severe asthma than children in the lower terciles (P = .005). The ventilation defect percentage correlated (P < .05 for all) positively with the inhaled corticosteroid dose, total number of controller medications, and total blood eosinophil counts and negatively with the Asthma Control Test score, FEV1 (percent predicted), FEV1/forced vital capacity ratio (percent predicted), and forced expiratory flow rate from 25% to 75% of expired volume (percent predicted). CONCLUSION: The lung defect volume percentage measured by using (3)He MRI correlates with several clinical features of asthma, including severity, symptom score, medication requirement, airway physiology, and atopic markers.