Year in Review 2020: Multisystemic impact of cystic fibrosis

Sharma, Preeti; Sathe, Meghana; Savant, Adrienne P.

doi:10.1002/ppul.25584

Cited by 5 publications

(1 citation statement)

References 53 publications

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“…1 Globally, the presence of endocrine disruption is associated with a negative impact on the clinical outcomes and mortality of those affected. 2 There is still not enough data to show the frequency of endocrinopathies in the pediatric population. Therefore, the present study was aimed at evaluating the frequency of vitamin D insufficiency/ deficiency, bone disease involving densitometry, thyroid and adrenal axis disorders, short stature, and pubertal delay in a population of children with CF in Medellín, Colombia.…”

Section: Introductionmentioning

confidence: 99%

High Frequency of Cystic Fibrosis-Related Endocrinopathies in a Population of Colombian Children: A Cross-Sectional Study

Rojas,

Pereira Gómez,

Espinosa

et al. 2024

respiramj

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Objective: The median length of survival for cystic fibrosis (CF) has significantly increased in recent years; however, this means that endocrine complications are more frequently observed in affected patients. This research was aimed at evaluating the frequency, clinical and paraclinical features, and the treatment of linear growth and pubertal disturbances, vitamin D insufficiency/deficiency, CF-related bone disease, and adrenal and thyroid function disturbances in patients with CF, as well as to explore their association with lung function and colonization. Method: A cross-sectional study with a retrospective collection of information from patients under 18 years of age with a confirmed diagnosis of CF, evaluated on an outpatient or in-hospital basis by a pediatric pulmonologist or endocrinologist, or in a multidisciplinary CF consultation, between January 2011–December 2020. Results: A total of 87 patients were included. A high frequency of endocrinopathies was found. Vitamin D insufficiency/deficiency was persistent despite cholecalciferol supplementation in 72%, short stature in 38%, pubertal delay in 26%, and thyroid axis disorders in 8% of cases. Bone disease involving densitometry and adrenal insufficiency secondary to chronic corticosteroid use were also frequent among the screened subjects (44% [n=16] and 12% [n=51], respectively). No significant differences were found for pulmonary function or bacterial lung colonization in the context of any endocrinopathies. Conclusion: Endocrine comorbidities are frequent in patients with CF, and early recognition improves the prognosis and quality of life in these patients. The findings for this cohort ratify the importance of multidisciplinary management of patients with CF.

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Section: Introductionmentioning

confidence: 99%

High Frequency of Cystic Fibrosis-Related Endocrinopathies in a Population of Colombian Children: A Cross-Sectional Study

Rojas,

Pereira Gómez,

Espinosa

et al. 2024

respiramj

View full text Add to dashboard Cite

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DNA-PKcs inhibition improves sequential gene insertion of the full-length CFTR cDNA in airway stem cells

Stack,

Rayner,

Nouri

et al. 2024

Molecular Therapy - Nucleic Acids

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DNA-PKcs Inhibition Improves Sequential Gene Insertion of the Full-LengthCFTRcDNA in Airway Stem Cells

Stack,

Rayner,

Nouri

et al. 2024

Preprint

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Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although many people with CF (pwCF) are treated using CFTR modulators, some are non-responsive due to their genotype or other uncharacterized reasons. Autologous airway stem cell therapies, in which theCFTRcDNA has been replaced, may enable a durable therapy for all pwCF. Previously, CRISPR-Cas9 with two AAVs was used to sequentially insert two halves of theCFTRcDNA and an enrichment cassette into theCFTRlocus. However, the editing efficiency was <10% and required enrichment to restore CFTR function. Further improvement in gene insertion may enhance cell therapy production. To improveCFTRcDNA insertion in human airway basal stem cells (ABCs), we evaluated the use of the small molecules AZD7648 and ART558 which inhibit non-homologous end joining (NHEJ) and micro-homology mediated end joining (MMEJ). Adding AZD7648 alone improved gene insertion by 2-3-fold. Adding both ART558 and AZD7648 improved gene insertion but induced toxicity. ABCs edited in the presence of AZD7648 produced differentiated airway epithelial sheets with restored CFTR function after enrichment. Adding AZD7648 did not increase off-target editing. Further studies are necessary to validate if AZD7648 treatment enriches cells with oncogenic mutations.

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Year in Review 2020: Multisystemic impact of cystic fibrosis

Cited by 5 publications

References 53 publications

High Frequency of Cystic Fibrosis-Related Endocrinopathies in a Population of Colombian Children: A Cross-Sectional Study

High Frequency of Cystic Fibrosis-Related Endocrinopathies in a Population of Colombian Children: A Cross-Sectional Study

DNA-PKcs inhibition improves sequential gene insertion of the full-length CFTR cDNA in airway stem cells

DNA-PKcs Inhibition Improves Sequential Gene Insertion of the Full-LengthCFTRcDNA in Airway Stem Cells

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