Browsing by Author "Howenstine, Michelle"

Now showing 1 - 5 of 5
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    Defining and identifying early-onset lung disease in cystic fibrosis with cumulative clinical characteristics
    (Wiley, 2022) Huang, Leslie; Lai, HuiChuan J.; Antos, Nicholas; Rock, Michael J.; Asfour, Fadi; Howenstine, Michelle; Gaffin, Jonathan M.; Farrell, Philip M.; Pediatrics, School of Medicine
    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.
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    Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation
    (Elsevier, 2017-02) Farrell, Philip M.; White, Terry B.; Ren, Clement L.; Hempstead, Sarah E.; Accurso, Frank; Derichs, Nico; Howenstine, Michelle; McColley, Susanna A.; Rock, Michael; Rosenfeld, Margaret; Sermet-Gaudelus, Isabelle; Southern, Kevin W.; Marshall, Bruce C.; Sosnay, Patrick R.; Department of Pediatrics, School of Medicine
    Objective Cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, continues to present diagnostic challenges. Newborn screening and an evolving understanding of CF genetics have prompted a reconsideration of the diagnosis criteria. Study design To improve diagnosis and achieve standardized definitions worldwide, the CF Foundation convened a committee of 32 experts in CF diagnosis from 9 countries to develop clear and actionable consensus guidelines on the diagnosis of CF and to clarify diagnostic criteria and terminology for other disorders associated with CFTR mutations. An a priori threshold of ≥80% affirmative votes was required for acceptance of each recommendation statement. Results After reviewing relevant literature, the committee convened to review evidence and cases. Following the conference, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 27 of 28 statements, 7 of which needed revisions and a second round of voting. Conclusions It is recommended that diagnoses associated with CFTR mutations in all individuals, from newborn to adult, be established by evaluation of CFTR function with a sweat chloride test. The latest mutation classifications annotated in the Clinical and Functional Translation of CFTR project (http://www.cftr2.org/index.php) should be used to aid in diagnosis. Newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may be designated CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis; these terms are now merged and equivalent, and CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis may be used. International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for use in diagnoses associated with CFTR mutations are included.
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    GME Expansion to Community Hospitals: Residency Training Beyond the Academic Health Center
    (2020-03-06) Cico, Stephen John; Bratcher, Linda; Leveque, Emilie; Howenstine, Michelle
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    Impact of acid blocker therapy on growth, gut microbiome, and lung disease in young children with cystic fibrosis
    (Wiley, 2024) Liu, Cathy; Bach, Taiya R.; Farrell, Philip M.; Pavelec, Derek; Antos, Nicholas J.; Rock, Michael J.; Asfour, Fadi; Howenstine, Michelle; Gaffin, Jonathan M.; Lai, HuiChuan J.; Pediatrics, School of Medicine
    Objective: Acid blocker therapy (ABT) has become common in cystic fibrosis (CF), despite insufficient evidence for benefits and studies showing potentially negative effects. We examined associations between ABT usage and growth, gut microbiome (GM), and early-onset lung disease in young children with CF. Methods: One hundred and forty-five infants with CF born during 2012-2017, diagnosed through newborn screening by age 3 months and followed to 36 months of age at six CF centers were evaluated. Longitudinal data on growth, pancreatic functional status, pulmonary symptoms, and acid blocker medications were prospectively collected. Early-onset lung disease severity was evaluated by a clinical scoring system. GM composition was assessed by 16S rRNA methodology. Results: ABT use before age 3 years was frequent, with 81 (56%) of patients on H2 receptor antagonist (H2RA) or proton pump inhibitor (PPI), and higher among pancreatic insufficient (60%) versus pancreatic sufficient (26%) children. H2RA was commonly prescribed in infancy before transitioning to PPI. Growth improvements were not significantly greater, while GM α-diversity at 3 years of age was significantly lower and early-onset lung disease more severe, in persistent ABT users compared to nonusers of ABT. Conclusion: In our cohort of young children with CF, early and persistent ABT use was not associated with significant growth benefits and instead showed associations with reduced GM diversity and negative effects on early-onset lung disease. Consequentially, there is a critical need for systematic evaluation and comprehensive risk-benefit analysis of ABT to ensure proper guidelines for children with CF.
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    The Frequency and Potential Implications of HFE Genetic Variants in Children With Cystic Fibrosis
    (Wiley, 2025) Huang, Leslie; Lai, HuiChuan J.; Furuya, Katryn N.; Antos, Nicholas J.; Asfour, Fadi; Boyne, Kathleen L.; Howenstine, Michelle; Rock, Michael J.; Sawicki, Gregory S.; Gaffin, Jonathan M.; Worthey, Elizabeth A.; Farrell, Philip M.; Pediatrics, School of Medicine
    Background: Genetic modifiers have been identified that increase the risks of lung disease and other complications, such as diabetes in people with cystic fibrosis (CF). Variants in the hemochromatosis gene (HFE) were reported in a study of adults to be associated with worse lung disease. Objectives: To ascertain the frequency of HFE variants, particularly C282Y (c.845G > A) and H63D (c.187C > G) and to determine if they are associated with variations in the onset and early severity of CF lung disease as well as abnormalities in iron status. Design: We studied with whole genome sequencing and clinical outcome measures in a cohort of 104 children with CF at 5-6 years old who were previously found to show an association between aggregated genetic modifiers and an earlier onset and a more severe lung disease phenotype. Results: In our cohort, 23% have H63D and 11% have C282Y. Lung function at age 6 years and Pseudomonas aeruginosa infections did not differ by HFE variants, but having C282Y was associated with more pulmonary exacerbations in the first 6 years of life. Three patients have H63D/C282Y genotype, and all showed phenotypic expression of hemochromatosis with abnormal iron indices. Conclusion: Our study revealed that the presence of HFE variant C282Y in people with CF may lead to more severe lung disease manifestations beginning in early childhood. There is a risk of hemochromatosis in CF patients with two HFE variants, and thus they should be followed for evidence of iron overload.