Validation of epistaxis severity score for hereditary hemorrhagic telangiectasia in Japan

Hayama, Masaki; Maeda, Yohei; Shikina, Takashi; Tatehara, Shun; Inokuchi, Go; Hoag, Jeffrey B.; Sato, Tomoharu; Obata, Sho; Nakatani, Ayaka; Amano, Yuta; Hida, Eisuke; Nibu, Ken‐ichi; Inohara, Hidenori

doi:10.1016/j.anl.2021.11.005

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…Early protective effects of KLF6 may result from a compensatory increase in the expression of PAH-associated genes such as BMPR2, SOX17, KDR, ENG, CAV1, ACVRL1, SMAD1, SMAD4 and CDH5 26 as well as increased expression of eNOS, prostacyclin and suppression of glycolysis 53 . Likewise, KLF6 activation may potentially benefit patients with hereditary haemorrhagic telangiectasia (HHT) where loss-of-function mutations in KLF6-upregulated genes, such as ENG, ACVRL1, or SMAD4, plays a contributory role 54 .…”

Section: Discussionmentioning

confidence: 99%

KLF6 in Pulmonary Hypertension: The Dual Role of Friend and Foe

Alharbi,

Keles,

Fernandes

et al. 2024

Preprint

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Background: Pulmonary arterial hypertension (PAH) is a severe lung condition with an unmet clinical need. Endothelial damage is followed by excessive repair and narrowing of lung arteries, but the mechanisms are unclear. Methods: We investigated the role of Kruppel-like transcription factor 6 (KLF6), known for its involvement in tissue injury response and cancer onset, in PAH through functional and expression analyses of human pulmonary artery endothelial cells (HPAECs) and PAH lung tissues. KLF6 activation patterns and transcriptional programs were compared with those regulated by KLF2 and KLF4, previously linked to PAH. Results: KLF6 expression increased due to hypoxic and inflammatory triggers in early rodent PAH. KLF6 overexpression improved endothelial survival and induced angiogenesis in cultured HPAECs and human pulmonary arterial explants. Transcriptomic analysis of KLF6-overexpressing HPAECs revealed its role in regulating endothelial homeostasis and expression of arterial identity genes, such as SOX17, ERG, BMPR2, KDR, TEK, ENG, ACVRL1 and CDH5. DisGeNET analysis showed a significant association of KLF6-regulated genes with PAH. Spatial transcriptomic analysis of PAH lung vascular tissues (n=6/group) revealed significant enrichment of KLF6-regulated genes in angiogenesis, cell motility, VEGFR signalling, and extracellular matrix organization. KLF6+ Erg+ vWF+ cells accumulated in vascular channels of remodelled PAH lungs and. KLF6 expression was elevated in PAH blood-derived endothelial progenitor cells (n=5) and pulmonary arterial cells in PAH associated with Alveolar Capillary Dysplasia. Conclusions: KLF6 uniquely orchestrates endothelial repair but its sustained activation promotes development of the apoptosis-resistant, angio-proliferative vascular phenotype in human PAH. Dysregulation of KLF6 signalling may have broader implications for pulmonary vascular disease.

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Section: Discussionmentioning

confidence: 99%

KLF6 in Pulmonary Hypertension: The Dual Role of Friend and Foe

Alharbi,

Keles,

Fernandes

et al. 2024

Preprint

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“…8 The ESS has also been used to assess the severity of disease before and after interventions to measure response to treatment. 3,4,8,11,12,17,18 The objective of this study was to assess the IC, intercorrelation, factor analysis, and test-retest reliability of the ESS in HHT patients. To our knowledge, this is the first report evaluating these psychometric properties of the ESS for epistaxis in patients with HHT.…”

Section: Discussionmentioning

confidence: 99%

Assessing the Psychometric Validity of the Epistaxis Severity Score: Internal Consistency and Test–Retest Reliability

Gong,

Bolsegui,

Lee

et al. 2023

Am J Rhinol�Allergy

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Background The Epistaxis Severity Score (ESS) is the gold-standard patient-reported outcome measure for evaluating nosebleed severity in patients with hereditary hemorrhagic telangiectasia (HHT). To date, the ESS has been assessed only for content validity and concurrent validity. Objective We evaluate the internal consistency and test–retest reliability of the ESS. Materials and Methods After receiving institutional review board approval, we sent an online survey battery, including the ESS survey, to 305 (39% male) English-speaking HHT patients ≥18 years old at a single center. Of those, 140 (46%) patients completed the battery, and 110/140 (79%) reported epistaxis. Cronbach's alpha and correlation analyses were used to evaluate internal consistency. For the test–retest reliability evaluation, we recruited 69 HHT patients during HHT clinic to complete 2 self-administered ESS surveys 2 weeks apart. Participants also completed a modified Clinical Global Impression-Improvement scale with readministration of the ESS survey. We calculated the intraclass correlation coefficient in a 2-way mixed model with absolute agreement. Results The ESS survey demonstrated low internal consistency (Cronbach's alpha = 0.495), suggesting that it measured multiple unrelated concepts. Factor analysis revealed 3 latent factors with moderate intercorrelation, suggesting the presence of 3 related but distinct constructs underlying the ESS. However, the ESS demonstrated excellent test–retest reliability (intraclass correlation coefficient = 0.955; 95% CI, 0.91-0.98). Conclusion Although the ESS demonstrates high test–retest reliability, it may not adequately assess different dimensions of nosebleed severity. Additional correlated survey questions and sub-scores may be needed to increase internal consistency to accurately measure each component of epistaxis severity. It is necessary to acknowledge epistaxis severity from different dimensions and to consider evaluating individual ESS items separately for a comprehensive understanding.

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鼻科領域での難病疾患へのアプローチ

端山

2023

Nippon Jibiinkoka Tokeibugeka Gakkai Kaiho(Tokyo)

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Validation of epistaxis severity score for hereditary hemorrhagic telangiectasia in Japan

Cited by 3 publications

References 24 publications

KLF6 in Pulmonary Hypertension: The Dual Role of Friend and Foe

KLF6 in Pulmonary Hypertension: The Dual Role of Friend and Foe

Assessing the Psychometric Validity of the Epistaxis Severity Score: Internal Consistency and Test–Retest Reliability

鼻科領域での難病疾患へのアプローチ

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