Most Short Children with Cystic Fibrosis Do Not Catch Up by Adulthood

Poor linear growth is common in children with cystic fibrosis (CF) and predicts pulmonary status and mortality. Growth impairment develops in infancy, prior to pulmonary decline and despite aggressive nutritional measures. We hypothesized that growth restriction during early childhood in CF is associated with reduced adult height. We used the Cystic Fibrosis Foundation (CFF) patient registry to identify CF adults between 2011 and 2015 (ages 18–19 y, n = 3655) and had height for age (HFA) records between ages 2 and 4 y. We found that only 26% CF adults were ≥median HFA and 25% were <10th percentile. Between 2 and 4 years, those with height < 10th percentile had increased odds of being <10th percentile in adulthood compared to children ≥ 10th percentile (OR = 7.7). Of HFA measured between the 10th and 25th percentiles at ages 2–4, 58% were <25th percentile as adults. Only 13% between the 10th and 25th percentile HFA at age 2–4 years were >50th percentile as adults. Maximum height between ages 2 and 4 highly correlated with adult height. These results demonstrate that low early childhood CF height correlates with height in adulthood. Since linear growth correlates with lung growth, identifying both risk factors and interventions for growth failure (nutritional support, confounders of clinical care, and potential endocrine involvement) could lead to improved overall health.

Environmental predictors of pulmonary nontuberculous mycobacteria (NTM) sputum positivity among persons with cystic fibrosis in the state of Florida

Nontuberculous mycobacteria (NTM) are opportunistic human pathogens that are commonly found in soil and water, and exposure to these organisms may cause pulmonary nontuberculous mycobacterial disease. Persons with cystic fibrosis (CF) are at high risk for developing pulmonary NTM infections, and studies have shown that prolonged exposure to certain environments can increase the risk of pulmonary NTM. It is therefore important to determine the risk associated with different geographic areas. Using annualized registry data obtained from the Cystic Fibrosis Foundation Patient Registry for 2010 through 2017, we conducted a geospatial analysis of NTM infections among persons with CF in Florida. A Bernoulli model in SaTScan was used to identify clustering of ZIP codes with higher than expected numbers of NTM culture positive individuals. Generalized linear mixed models with a binomial distribution were used to test the association of environmental variables and NTM culture positivity. We identified a significant cluster of M. abscessus and predictors of NTM sputum positivity, including annual precipitation and soil mineral levels.

Burden of cystic fibrosis in children <12 years of age prior to the introduction of CFTR modulator therapies

BackgroundCystic fibrosis (CF) is a genetic, multisystemic, progressive and life-shortening disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Different genotypes have been linked to variations in disease progression among people with CF. The burden of illness (BOI) in children with CF is incompletely characterised, particularly as it relates to CFTR genotypes prior to the availability of the first CFTR modulators. This retrospective, cross-sectional, descriptive study evaluated the BOI in US children with CF <12 years of age prior to the first approval of CFTR modulators.MethodsData from the US Cystic Fibrosis Foundation Patient Registry from 2011 were used to summarise key patient and disease characteristics using descriptive statistics, overall and grouped by age (0 to <2 years, 2 to <6 years and 6 to <12 years) and genotype (F508del/F508del, F508del/minimal function (MF), MF/MF, gating mutation on ≥1 allele, residual function mutation on ≥1 allele and R117H on ≥1 allele) group.ResultsThe analysis included 9185 children. Among 6-year-olds to <12-year-olds, mean (SD) per cent predicted FEV1 in 1 s was 92.6% (17.5%). Among all children <12 years of age, the mean (SD) all-cause hospitalisation and pulmonary exacerbation rates in 2011 were 0.4 (1.0) and 0.3 (0.8), respectively. Most (93.6%) had ≥1 positive lung microbiology culture. CF-related medication and nutritional supplementation use was common across all ages and genotypes. More than half (54.7%) had ≥1 CF-related complication. Evidence of disease burden was observed across the age and genotype groups studied.ConclusionsPrior to the approval of the first CFTR modulator therapies in children <12 years of age, CF was associated with substantial BOI from an early age—including respiratory infections, hospitalisations/pulmonary exacerbations, need for supplemental nutrition and pharmacological treatments—irrespective of genotype.

PREVALENCIA DE ASPERGILOSIS BRONCOPULMONAR ALÉRGICA EN NIÑOS CON FIBROSIS QUÍSTICA

La aspergilosis broncopulmonar alérgica (ABPA) es una reacción de hipersensibilidad secundaria al Aspergllus fumigatus (Af) que complica la evolución en fibrosis quística (FQ). Existen pocos estudios pediátricos de su prevalencia publicados en el mundo y en Chile se desconoce. El objetivo de este trabajo fue estimar la prevalencia de ABPA en niños con FQ en un hospital de referencia, explorar factores de riesgo y describir los criterios diagnósticos, tratamiento y evolución. Se incluyeron retrospectivamente los niños con FQ atendidos en un hospital terciario en Santiago de Chile (Hospital Roberto del Río) entre los años 2011 a 2019, se identificaron aquellos con diagnóstico de ABPA. Se registraron criterios diagnósticos según la Cystic Fibrosis Foundation, presencia de factores de riesgo, tratamientos recibidos y efectos adversos. De 65 pacientes con FQ atendidos en este período, la prevalencia de ABPA fue del 12%. El promedio de edad al diagnóstico fue ± 11 años (5-17 años), predominando la edad adolescente y el género masculino. El 50% cumplieron con los criterios clásicos, el 87,5% usaron antibióticos y el 62,5% corticoides inhalados. La respuesta favorable al tratamiento inicial con corticoides y antifúngico vía oral fue 62,5%, con una exacerbación al momento del estudio. El 25% se comportaron como refractario y el 12,5% respondieron a tratamiento con pulsos de metilprednisolona. El 37,5% presentaron eventos adversos relacionados a corticoides. La prevalencia de ABPA observada es comparable a las series publicadas. Se necesitan trabajos prospectivos para conocer la prevalencia nacional y su tendencia a lo largo de los años, identificando factores de riesgo.

Wildfire Smoke Exposure Is Associated With Severe Pulmonary Exacerbation in Adult Cystic Fibrosis Patients

PurposeBecause pulmonary exacerbations in cystic fibrosis cause a step-wise decline in FEV1 function and contribute significantly to disease progression, it is important to identify potential environmental triggers. Studies have been done on general air quality and its relationship to cystic fibrosis disease activity, but none have examined air pollution caused by wildfire smoke. Our study intends to better understand this relationship. MethodsA retrospective cohort study was conducted using data collected from people with cystic fibrosis (CF) between 2012 and 2019. Data on pulmonary exacerbations was extracted from the patient registry hosted and maintained by the Cystic Fibrosis Foundation. Exposures were determined using measurements of fine particulate matter (PM2.5) from the Environmental Protection Agency. A logistic regression model was created in order to identify both univariate and adjusted odds ratios and their associated confidence intervals.Results82.7% (n = 415) of individuals with CF experienced an exposure to wildfire smoke during the study period. The adjusted odds ratio for a pulmonary exacerbation within one month following an exposure to wildfire smoke was 1.50 (95% CI = 1.13 – 1.99, p = 0.006) for adults and 0.92 (95% CI = 0.69 – 1.23, p = 0.578) for children. ConclusionWildfire smoke exposure is associated with severe pulmonary exacerbation in adults but not in children. This suggests that wildfire smoke may be an environmental risk factor for exacerbation in adults with CF. Further study is needed to understand why and how wildfire smoke exposure affects adult with CF differently than the pediatric population.