Rate of Lung Function Decline in People with Cystic Fibrosis Having a Residual Function Gene Mutation.

IF 2.3 Q2 RESPIRATORY SYSTEM

Pulmonary Therapy Pub Date : 2022-12-01 DOI:10.1007/s41030-022-00202-y

Gregory S Sawicki, Michael W Konstan, Edward F McKone, Richard B Moss, Barry Lubarsky, Ellison Suthoff, Stefanie J Millar, David J Pasta, Nicole Mayer-Hamblett, Christopher H Goss, Wayne J Morgan, Margaret E Duncan, Yoojung Yang

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引用次数: 0

Abstract

Introduction: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Approximately 5% of people with CF have residual function (RF) CFTR mutations that result in partially retained CFTR activity. Published literature on disease trajectory among those with RF mutations is limited. In this retrospective study, we characterized lung function decline across different age groups in CFTR modulator-untreated people with CF heterozygous for F508del and an RF mutation (F/RF).

Methods: Rate of decline in percent predicted forced expiratory volume in 1 s (ppFEV₁) was analyzed using data from the US CF Foundation Patient Registry (2006-2014) in F/RF (all), F/RF (excluding R117H), and F508del homozygous (F/F) cohorts. Annual rates of ppFEV₁ decline were estimated over 2-year periods based on calendar year. Subgroup analyses by age [6-12 (children), 13-17 (adolescents), 18-24 (young adults), and ≥ 25 years (adults)] were performed.

Results: The estimated annualized rate of ppFEV₁ decline was - 0.70 percentage points per year (95% CI -1.09, -0.30) in the F/RF (all) cohort (N = 1242) versus -1.91 percentage points per year (95% CI -2.01, -1.80) in the F/F cohort (N = 11,916) [difference, 1.29 percentage points per year (95% CI 0.88, 1.70); P < 0.001]. In the F/RF (all) cohort, all age groups demonstrated lung function decline ranging from -0.30 to -1.38. In the F/RF (excluding R117H) cohort, the rate of decline was -1.05 percentage points per year (95% CI -1.51, -0.60) [difference versus F/F cohort, 0.95 percentage points per year (95% CI 0.48, 1.41; P < 0.001); not statistically significant in children and young adults].

Conclusion: Progressive lung function decline was observed in people with F/RF genotypes across all assessed age groups, reinforcing the importance of early intervention and clinical monitoring to preserve lung function in all people with CF.

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残留功能基因突变的囊性纤维化患者肺功能下降率

简介:囊性纤维化(CF)是一种常染色体隐性遗传病，由CF跨膜传导调节因子(CFTR)基因突变引起。大约5%的CF患者有残留功能(RF) CFTR突变，导致CFTR活性部分保留。已发表的关于RF突变患者疾病轨迹的文献是有限的。在这项回顾性研究中，我们研究了CFTR调节剂未经治疗的CF杂合F508del和RF突变(F/RF)的不同年龄组肺功能下降。方法:使用美国CF基金会患者登记处(2006-2014)F/RF(全部)、F/RF(不包括R117H)和F508del纯合子(F/F)队列的数据，分析1 s内预测用力呼气量百分比下降率(ppFEV1)。ppFEV1的年递减率是基于日历年估算的2年期间。按年龄进行亚组分析[6-12岁(儿童)、13-17岁(青少年)、18-24岁(青年)和≥25岁(成人)]。结果:F/RF(所有)队列(N = 1242)中ppFEV1的估计年化下降率为- 0.70个百分点/年(95% CI -1.09， -0.30)，而F/F队列(N = 11,916)中ppFEV1的估计年化下降率为-1.91个百分点/年(95% CI -2.01， -1.80)[差异为1.29个百分点/年(95% CI 0.88, 1.70);结论:在所有被评估的年龄组中，F/RF基因型患者的肺功能均出现进行性下降，这加强了早期干预和临床监测对所有CF患者肺功能保护的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pulmonary Therapy Medicine-Pulmonary and Respiratory Medicine

CiteScore

5.20

自引率

3.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Pulmonary Therapy is an international, open access, peer-reviewed (single-blind), and rapid publication journal. The scope of the journal is broad and will consider all scientifically sound research from pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the use of pulmonary therapies, devices, and surgical techniques. Areas of focus include, but are not limited to: asthma; chronic obstructive pulmonary disease; idiopathic pulmonary fibrosis; pulmonary hypertension; cystic fibrosis; lung cancer; respiratory tract disorders; allergic rhinitis and other respiratory allergies; influenza, pneumococcal infection, respiratory syncytial virus and other respiratory infections; and inhalers and other device therapies. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/series, trial protocols and short communications such as commentaries and editorials. Pulmonary Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. Rapid Publication The journal’s publication timelines aim for a rapid peer review of 2 weeks. If an article is accepted it will be published 3–4 weeks from acceptance. The rapid timelines are achieved through the combination of a dedicated in-house editorial team, who manage article workflow, and an extensive Editorial and Advisory Board who assist with peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid, efficient communication of the latest research and reviews, fostering the advancement of pulmonary therapies. Open Access All articles published by Pulmonary Therapy are open access. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning authors will always have an editorial contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. 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