Oral antibiotic prescribing patterns for treatment of pulmonary exacerbations in two large pediatric CF centers

Introduction: Oral antibiotics are frequently prescribed for outpatient pulmonary exacerbations (PEx) in children with cystic fibrosis (CF). This study aimed to characterize oral antibiotic use for PEx and treatment outcomes at two large US CF centers. Methods: Retrospective, descriptive study of oral antibiotic prescribing practices among children with CF ages 6–17 years over 1 year. The care setting for antibiotic initiation (clinic or phone encounter) was determined and outcomes were compared. Results: A total of 763 oral antibiotic courses were prescribed to 312 patients aged 6–17 years (77% of 403 eligible patients) with a median of two courses per year (range: 1–10). Fifty‐eight percent of prescriptions were provided over the phone. Penicillin was the most commonly prescribed antibiotic class (36% of prescriptions) but differences in antibiotic class prescriptions were noted between the two centers. Hospitalizations occurred within 3 months following 19% of oral antibiotic courses. Forced expiratory volume in 1 s (FEV1) recovered to within 90% of prior baseline within 6 months in 87% of encounters; the mean (SD) % recovery was 99.6% (12.1%) of baseline. Outcomes did not differ between phone and clinic prescriptions. Conclusions: Phone prescriptions, commonly excluded in studies of PEx, made up more than half of all oral antibiotic courses. Heterogeneity in prescribing patterns was observed between the two centers. Most patients had improvement in FEV1 returning to near their prior baseline, but hospitalizations occurred in one‐fifth following oral antibiotic treatment. Efforts to optimize PEx treatment must consider care that occurs over the phone; this is particularly important as the use of telemedicine increases.This work was supported by the Cystic Fibrosis Foundation (SANDERS18A1, HOPPE16A0)

Case report: Cystic fibrosis with kwashiorkor: A rare presentation in the era of universal newborn screening

BackgroundUniversal newborn screening changed the way medical providers think about the presentation of cystic fibrosis (CF). Before implementation of universal screening, it was common for children with CF to present with failure to thrive, nutritional deficiencies, and recurrent infections. Now, nearly all cases of CF are diagnosed by newborn screening shortly after birth before significant symptoms develop. Therefore, providers often do not consider this illness in the setting of a normal newborn screen. Newborn screening significantly decreases the risk of complications in early childhood, yet definitive testing should be pursued if a patient with negative newborn screening presents with symptoms consistent with CF, including severe failure to thrive, metabolic alkalosis due to significant salt losses, or recurrent respiratory infections.Case presentationWe present a case of a 6-month-old infant male with kwashiorkor, severe edema, multiple vitamin deficiencies, hematemesis secondary to coagulopathy, and diffuse erythematous rash, all secondary to severe pancreatic insufficiency. His first newborn screen had an immunoreactive trypsinogen (IRT) value below the state cut-off value, so additional testing was not performed, and his growth trajectory appeared reassuring. He was ultimately diagnosed with CF by genetic testing and confirmatory sweat chloride testing, in the setting of his parents being known CF carriers and his severe presentation being clinically consistent with CF. Acutely, management with supplemental albumin, furosemide, potassium, and vitamin K was initiated to correct the presenting hypoalbuminemia, edema, and coagulopathy. Later, pancreatic enzyme supplementation and additional vitamins and minerals were added to manage ongoing deficiencies from pancreatic insufficiency. With appropriate treatment, his vitamin deficiencies and edema resolved, and his growth improved.ConclusionDue to universal newborn screening, symptomatic presentation of CF is rare and presentation with kwashiorkor is extremely rare in resource-rich communities. The diagnosis of CF was delayed in our patient because of a normal newborn screen and falsely reassuring growth, which after diagnosis was determined to be secondary to severe edematous malnutrition. This case highlights that newborn screening is a useful but imperfect tool. Clinicians should continue to have suspicion for CF in the right clinical context, even in the setting of normal newborn screen results

Pulmonary exacerbations and clinical outcomes in a longitudinal cohort of infants and preschool children with cystic fibrosis

Abstract Background Pulmonary exacerbations (PEx) in school aged children and adults with cystic fibrosis (CF) lead to increased morbidity and lung function decline. However, the effect of exacerbations in young children with CF is not fully understood. We sought to characterize the frequency and clinical impact of PEx in a pilot study of infants and pre-school aged children with CF. Methods Thirty young children with CF [median (range) 1.5 years (0.2–4.9)] were prospectively followed for 2 years. Exacerbation frequency (hospitalizations and outpatient antibiotic use) was determined. Chest radiographs were performed at enrollment and study completion and assigned a Brasfield score. Lung function at age 7 years was assessed in a subset of children. The association between PEx frequency, chest radiograph score, and lung function was determined using Spearman correlation coefficients and corresponding 95% confidence intervals. Correlations with an absolute magnitude of 0.3 or greater were considered clinically significant. Results Over 2 years, participants experienced a median of two PEx (range 0–13). Chest radiograph scores at enrollment and study completion were inversely associated with PEx frequency (R = −0.48 and R = −0.44, respectively). The association between frequency of PEx and lung function [forced expiratory volume in 1 s (FEV1)] at age 7 years was small (R = 0.20). Higher forced vital capacity (FVC) at 7 years was associated with more frequent PEx during the study (R = 0.44). Conclusions Children with worse chest radiograph scores had more frequent PEx over the subsequent 2 years, suggesting a group of patients at higher risk for PEx. Frequent PEx in infants and young children with CF were not associated with lower FEV1 and FVC at 7 years, although spirometry in this age group may not be a sensitive marker of mild lung disease and disease progression

Airway Inflammation in Children with Primary Ciliary Dyskinesia

Rationale: The role of airway inflammation in disease pathogenesis in children with primary ciliary dyskinesia (PCD) is poorly understood. Objectives: We investigated relationships between sputum inflammation measurements, age, lung function, bronchiectasis, airway infection, and ultrastructural defects in children with PCD. Methods: Spontaneously expectorated sputum was collected from clinically stable children and adolescents with PCD ages 6 years and older participating in a multicenter, observational study. Sputum protease and inflammatory cytokine concentrations were correlated with age, lung function, and chest computed tomography measures of structural lung disease, whereas differences in concentrations were compared between ultrastructural defect categories and between those with and without detectable bacterial infection. Results: Sputum from 77 children with PCD (39 females [51%]; mean [standard deviation] age, 13.9 [4.9] yr; mean [standard deviation] forced expiratory volume in 1 second [FEV1]% predicted, 80.8 [20.5]) was analyzed. Sputum inflammatory marker measurements, including neutrophil elastase activity, IL-1β (interleukin-1β), IL-8, and TNF-α (tumor necrosis factor α) concentrations, correlated positively with age, percentage of bronchiectasis, and percentage of total structural lung disease on computed tomography, and negatively with lung function. Correlations between neutrophil elastase concentrations and FEV1% predicted and percentage of bronchiectasis were -0.32 (95% confidence interval, -0.51 to -0.10) and 0.46 (0.14 to 0.69), respectively. Sputum neutrophil elastase, IL-1β, and TNF-α concentrations were higher in those with detectable bacterial pathogens. Participants with absent inner dynein arm and microtubular disorganization had similar inflammatory profiles compared with participants with outer dynein arm defects. Conclusions: In this multicenter pediatric PCD cohort, elevated concentrations of sputum proteases and cytokines were associated with impaired lung function and structural damage as determined by chest computed tomography, suggesting that sputum inflammatory measurements could serve as biomarkers in PCD.</p

Airway Inflammation in Children with Primary Ciliary Dyskinesia

Rationale: The role of airway inflammation in disease pathogenesis in children with primary ciliary dyskinesia (PCD) is poorly understood. Objectives: We investigated relationships between sputum inflammation measurements, age, lung function, bronchiectasis, airway infection, and ultrastructural defects in children with PCD. Methods: Spontaneously expectorated sputum was collected from clinically stable children and adolescents with PCD ages 6 years and older participating in a multicenter, observational study. Sputum protease and inflammatory cytokine concentrations were correlated with age, lung function, and chest computed tomography measures of structural lung disease, whereas differences in concentrations were compared between ultrastructural defect categories and between those with and without detectable bacterial infection. Results: Sputum from 77 children with PCD (39 females [51%]; mean [standard deviation] age, 13.9 [4.9] yr; mean [standard deviation] forced expiratory volume in 1 second [FEV1]% predicted, 80.8 [20.5]) was analyzed. Sputum inflammatory marker measurements, including neutrophil elastase activity, IL-1β (interleukin-1β), IL-8, and TNF-α (tumor necrosis factor α) concentrations, correlated positively with age, percentage of bronchiectasis, and percentage of total structural lung disease on computed tomography, and negatively with lung function. Correlations between neutrophil elastase concentrations and FEV1% predicted and percentage of bronchiectasis were -0.32 (95% confidence interval, -0.51 to -0.10) and 0.46 (0.14 to 0.69), respectively. Sputum neutrophil elastase, IL-1β, and TNF-α concentrations were higher in those with detectable bacterial pathogens. Participants with absent inner dynein arm and microtubular disorganization had similar inflammatory profiles compared with participants with outer dynein arm defects. Conclusions: In this multicenter pediatric PCD cohort, elevated concentrations of sputum proteases and cytokines were associated with impaired lung function and structural damage as determined by chest computed tomography, suggesting that sputum inflammatory measurements could serve as biomarkers in PCD.</p

Reconstructing molar growth from enamel histology in extant and extinct Equus

The way teeth grow is recorded in dental enamel as incremental marks. Detailed analysis of tooth growth is known to provide valuable insights into the growth and the pace of life of vertebrates. Here, we study the growth pattern of the frst lower molar in several extant and extinct species of Equus and explore its relationship with life history events. Our histological analysis shows that enamel extends beyond the molar's cervix in these mammals. We identifed three diferent crown developmental stages (CDS) in the frst lower molars of equids characterised by diferent growth rates and likely to be related to structural and ontogenetic modifcations of the tooth. Enamel extension rate, which ranges from ≈400 μm/d at the beginning of crown development to rates of ≈30 μm/d near the root, and daily secretion rate (≈17 μm/d) have been shown to be very conservative within the genus. From our results, we also inferred data of molar wear rate for these equids that suggest higher wear rates at early ontogenetic stages (13mm/y) than commonly assumed. The results obtained here provide a basis for future studies of equid dentition in diferent scientifc areas, involving isotope, demographic and dietary studies