CHEST pulmonary最新文献_第8页

Association of Communication With Smoking Attitudes and Behaviors Among Patients Undergoing Lung Cancer Screening 肺癌筛查患者吸烟态度和行为与沟通的关系

CHEST pulmonary

Pub Date : 2025-06-01 DOI: 10.1016/j.chpulm.2025.100154

Christopher G. Slatore MD , Anne C. Melzer MD , Ian Ilea MSW , Liana Schweiger MD, MCR , Janel DeSalvo MD , Donald R. Sullivan MD, MCR , Sean P.M. Rice PhD , Renda S. Wiener MD, MPH , Santanu Datta PhD , James M. Davis MD , Christopher H. Chang MD , Kimberly A. Curlin MN, FNP-BC , Sara E. Golden PhD

Background

Many patients who undergo lung cancer screening (LCS) actively use cigarettes.

Research Question

What are the longitudinal, patient-reported smoking attitudes and behaviors across the LCS process in routine care settings, and are these smoking attitudes and behaviors associated with patient-centered communication?

Study Design and Methods

This prospective, longitudinal, repeated measures cohort study was conducted among patients undergoing LCS in 3 health care systems. Participants were surveyed by using validated measures of smoking attitudes and behaviors and patient-centered communication domains up to 1 year following low-dose CT (LDCT) imaging for LCS. For longitudinal analyses, a series of generalized estimating equations were applied to measure the adjusted associations of overall communication quality, LCS knowledge, and decision role concordance with smoking attitudes and behaviors.

Results

A total of 253 participants who currently used cigarettes or who had recently stopped were enrolled. Of these, 83 participants (36.7% of patients with nonmissing information) had moderate or high levels of nicotine dependence. Of 133 participants who were using cigarettes at baseline who contributed data, 24 (18%) were abstinent 12 months after baseline. During the screening period, no more than 33% of participants reported receiving cessation resources from their clinician at any given point. Almost 70% of participants reported high-quality communication at baseline, which was associated with a positive stage of cigarette use behavior change (adjusted OR, 2.27; 95% CI, 1.21-4.26). Longitudinal high-quality communication was associated with cigarette abstinence (adjusted OR, 3.63; 95% CI, 1.58-8.34). LCS knowledge and decision role concordance were not associated with smoking attitudes or behaviors.

Interpretation

Our results indicate that it may be challenging to substantially improve smoking behaviors through communication strategies. Additional interventions to increase smoking cessation are required.

背景：许多接受肺癌筛查（LCS）的患者积极吸烟。研究问题：在常规护理环境中，LCS过程中的纵向、患者报告的吸烟态度和行为是什么？这些吸烟态度和行为是否与以患者为中心的沟通有关？研究设计和方法本前瞻性、纵向、重复测量队列研究在3个卫生保健系统的LCS患者中进行。在LCS低剂量CT （LDCT）成像后的一年内，通过使用有效的吸烟态度和行为以及以患者为中心的交流域的测量对参与者进行调查。在纵向分析中，我们应用了一系列广义估计方程来衡量整体沟通质量、LCS知识和决策角色一致性与吸烟态度和行为的调整后的关联。结果共有253名目前吸烟或最近戒烟的参与者被纳入研究。其中，83名参与者（36.7%的未丢失信息的患者）有中度或高度的尼古丁依赖。133名在基线时吸烟的参与者提供了数据，其中24名（18%）在基线后12个月戒烟。在筛查期间，不超过33%的参与者报告在任何给定时间点从他们的临床医生那里获得戒烟资源。几乎70%的参与者在基线时报告了高质量的沟通，这与卷烟使用行为改变的积极阶段有关(调整OR， 2.27；95% ci, 1.21-4.26)。纵向高质量沟通与戒烟相关(校正OR为3.63；95% ci, 1.58-8.34)。LCS知识和决策角色一致性与吸烟态度或行为无关。我们的研究结果表明，通过沟通策略大幅改善吸烟行为可能具有挑战性。需要采取额外的干预措施来促进戒烟。

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引用次数: 0

Establishing the Obesity Paradox in Alpha-1 Antitrypsin Deficiency-Related COPD α -1抗胰蛋白酶缺乏相关性慢性阻塞性肺病的肥胖悖论

CHEST pulmonary

Pub Date : 2025-06-01 DOI: 10.1016/j.chpulm.2025.100153

Daniel Yee MD , Monica P. Goldklang MD

引用次数: 0

A Breath of Fresh Air 呼吸新鲜空气

CHEST pulmonary

Pub Date : 2025-06-01 DOI: 10.1016/j.chpulm.2025.100150

Berty Baskaran MD, Ryan Butzko DO

引用次数: 0

Pragmatic Comparative Effectiveness Trials in Rheumatoid Arthritis-Associated Interstitial Lung Disease 类风湿关节炎相关间质性肺疾病的实用比较疗效试验

CHEST pulmonary

Pub Date : 2025-06-01 DOI: 10.1016/j.chpulm.2025.100159

Angela Kaczorowski-Worthley BSN , Dinesh Pal Mudaranthakam PhD, MBA, MS , Janell Reichuber APRN , Chris Streiler MD , Sahil Pandya MD , Ryan Boente MD , Susan K. Mathai MD , Ayodeji Adegunsoye MD , Jeff Swigris DO, MS , Elizabeth R. Volkmann MD, MS , Joshua J. Solomon MD , Bryant R. England MD, PhD , Scott M. Matson MD

Background

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) portends a devastating prognosis for patients, with survival typically being < 5 to 8 years after diagnosis. Limited clinical trial data exist to guide treatment strategies, and the efficacy of current strategies—immunomodulation and antifibrotics—remains uncertain. Large randomized controlled trials are costly, but pragmatic trial designs could reduce expenses. Establishing equipoise and assessing feasibility from both patient and expert perspectives are essential for developing these trials.

Research Question

What are the perceptions of RA-ILD experts and patients with interstitial lung disease surrounding equipoise, feasibility, and trial design?

Study Design and Methods

A qualitative study involving a panel of 10 RA-ILD experts and 3 patient panels was conducted. Experts were recruited via snowball sampling, and patient panels included 29 individuals with interstitial lung disease or their caregivers. Discussions were transcribed and analyzed using inductive coding, creating a thematic network based on the Attride-Stirling guidelines.

Results

Expert themes included variability in treatment strategies, prioritizing patient-reported outcomes and balancing pragmatism with data collection in trial design. Patient themes highlighted outcomes of importance, participation barriers, and the need for patient-centered research.

Interpretation

Both expert and patient panels endorsed using real-world clinical outcomes and patient-reported outcomes as primary trial end points. Pragmatic trials could reduce costs and expand inclusion criteria, highlighting the potential of patient-centered approaches in RA-ILD research.

背景：类风湿关节炎相关间质性肺疾病（RA-ILD）预示着患者的灾难性预后，生存率通常为1 / 3。诊断后5 - 8年。有限的临床试验数据用于指导治疗策略，目前的策略-免疫调节和抗纤维化-的疗效仍然不确定。大型随机对照试验是昂贵的，但实用的试验设计可以减少费用。从患者和专家的角度建立平衡和评估可行性对于开展这些试验至关重要。研究问题：RA-ILD专家和间质性肺病患者对平衡、可行性和试验设计的看法是什么？研究设计和方法进行了一项定性研究，包括10名RA-ILD专家和3名患者。通过滚雪球抽样招募专家，患者小组包括29名间质性肺病患者或其护理人员。使用归纳编码对讨论进行转录和分析，创建基于Attride-Stirling指南的主题网络。专家主题包括治疗策略的可变性，优先考虑患者报告的结果，以及在试验设计中平衡实用主义与数据收集。患者主题强调了结果的重要性、参与障碍以及以患者为中心的研究的必要性。解释：专家和患者小组均赞同使用真实世界的临床结果和患者报告的结果作为主要试验终点。实用试验可以降低成本，扩大纳入标准，突出以患者为中心的方法在RA-ILD研究中的潜力。

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引用次数: 0

Does a Patient-Centered Informational Video Impact Real-World Perception of Lung Cancer Screening Among At-Risk Veterans? 以患者为中心的信息视频是否会影响高危退伍军人对肺癌筛查的真实感知？

CHEST pulmonary

Pub Date : 2025-04-08 DOI: 10.1016/j.chpulm.2025.100169

Norah N. Zaza MD , Eduardo Lopez-Gutierrez BS , Dominic J. Vitello MD , Jessica Gardner BS , Thanh-Huyen T. Vu MD, PhD , Eleanor Riviera MSN , Sayyed Hamidi MD , Israel Rubinstein MD , Howard S. Gordon MD , David J. Bentrem MD

引用次数: 0

Prospective REALITI-A Study 前瞻性现实研究

CHEST pulmonary

Pub Date : 2025-03-01 DOI: 10.1016/j.chpulm.2024.100107

Cristiano Caruso MD, PhD , G. Walter Canonica MD , Manish Patel MBChB, PhD , Andrew Smith MBChB, PhD , Mark C. Liu MD , Rafael Alfonso-Cristancho MD, PhD , Robert G. Price MSc , Rupert W. Jakes PhD , Lydia Demetriou MSc , Antonio Valero MD , Thomas C. Köhler MD , Charles Pilette MD, PhD , Geoffrey Chupp MD , Guy Brusselle MD , Peter Howarth DM

Background

Mepolizumab, a monoclonal antibody targeting IL-5, is of proven clinical benefit in severe asthma; however, prospective, long-term, real-world data in severe asthma are required.

Research Question

What is the real-world benefit of 2 years of mepolizumab treatment in severe asthma?

Study Design and Methods

REALITI-A was a 2-year, international, prospective study enrolling adults with asthma on newly initiated mepolizumab 100 mg subcutaneously (physician decision). Outcomes in the 1-year premepolizumab vs 2-year follow-up periods included rates of clinically significant asthma exacerbations (CSEs) (deterioration requiring systemic corticosteroids and/or emergency department [ED] visit/hospitalization), exacerbations requiring ED visit/hospitalization, exacerbations requiring hospitalization, proportion of patients with no exacerbations, median daily maintenance oral corticosteroids (mOCSs) dose, proportion of patients discontinuing mOCSs completely, Asthma Control Questionnaire-5 score, FEV₁, and adverse events (AEs).

Results

After 2 years’ follow-up, 73% of patients (599 of 822) had no record of mepolizumab discontinuation. During the 2-year follow-up vs premepolizumab period (N = 822), rates of CSEs, exacerbations requiring ED visit/hospitalization, or hospitalization only were reduced by 74%, 79%, and 73%, respectively (odds ratio for no CSEs, 10.0; 95% CI, 7.55- 13.25). Median daily mOCS dose decreased from 10.0 (quartile 1, 5.0; quartile 3, 14.7) mg at week 0 (n = 297) to 0.0 (quartile 1, 0.0; quartile 3, 5.0) mg at weeks 101 to 104 (n = 168), and the proportion of patients discontinuing mOCSs increased progressively to 43% at 1 year and 57% at 2 years. There was a 1.53-point reduction in Asthma Control Questionnaire-5 scores from baseline at 2 years. At months 21 to 24, least square mean FEV₁ improved by 142 mL from baseline. Ninety (11%) and 7 (< 1%) patients experienced mepolizumab-related AEs and serious AEs during the follow-up period, respectively.

Interpretation

In patients with severe asthma, real-world mepolizumab treatment for 2 years was well tolerated and was associated with sustained reductions in exacerbations and progressive reductions in mOCS use.

研究设计与方法REALITI-A是一项为期2年的国际前瞻性研究，研究对象为新开始皮下注射甲泼尼单抗100毫克（由医生决定）的成人哮喘患者。使用前 1 年与随访 2 年的结果包括临床上严重的哮喘加重（CSEs）率（病情恶化需要使用全身皮质类固醇和/或去急诊科就诊/住院）、需要去急诊科就诊/住院的加重率、需要住院的加重率、需要去急诊科就诊/住院的加重率、需要去急诊科就诊/住院的加重率、需要去急诊科就诊/住院的加重率、需要去急诊科就诊/住院的加重率、结果经过 2 年的随访后，该研究发现了哮喘控制问卷-5 评分、FEV1 和不良事件 (AEs)。结果随访2年后，73%的患者（822人中有599人）没有停用美泊利珠单抗的记录。在2年随访期间与使用美泊珠单抗前相比（N = 822），CSE、需要急诊室就诊/住院治疗的病情加重或仅住院治疗的比率分别降低了74%、79%和73%（无CSE的几率比为10.0；95% CI为7.55-13.25）。mOCS 每日中位剂量从第 0 周的 10.0（四分位 1，5.0；四分位 3，14.7）毫克（n = 297）降至第 101-104 周的 0.0（四分位 1，0.0；四分位 3，5.0）毫克（n = 168），停用 mOCS 的患者比例逐渐增加，1 年时达到 43%，2 年时达到 57%。2 年时，哮喘控制问卷-5 评分比基线降低了 1.53 分。在第 21 至 24 个月，最小平方平均 FEV1 比基线提高了 142 毫升。在随访期间，分别有90例（11%）和7例（< 1%）患者出现甲泼尼单抗相关不良反应和严重不良反应。

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引用次数: 0

Racialized Economic Segregation and Disparities in Non-Small Cell Lung Cancer Care and Outcomes 非小细胞肺癌治疗和预后的种族经济隔离和差异

CHEST pulmonary

Pub Date : 2025-03-01 DOI: 10.1016/j.chpulm.2024.100101

Pratibha Shrestha MPH, PhD , Min Lian MD, PhD , James Struthers BA , Oumarou Nabi PhD , Bayu B. Bekele MPH, PhD , Benjamin Kozower MD , Maria Baggstrom MD , Ying Liu MD, PhD

Background

Little is known about the impact of residential segregation on early detection, treatment, and prognosis of non-small cell lung cancer (NSCLC), a predominant type of lung cancers.

Research Question

Does racialized economic segregation play a role in NSCLC treatment and outcomes and contribute to racial disparities?

Study Design and Methods

This study included non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients with NSCLC diagnosed between 2007 and 2015 and identified from the Surveillance, Epidemiology, and End Results data set. County-level racialized economic segregation was estimated by using the Index of Concentration at the Extremes (ICE). Multilevel logistic regression and multilevel Cox regression accounting for county-level clustering were used to estimate ORs for late-stage diagnosis and treatment underutilization, and hazard ratios (HRs) were used for mortality.

Results

Of 203,441 patients, 85.8% were NHW, and 14.2% were NHB. Compared with patients living in the counties with the highest concentration of high-income NHW households (lowest ICE quintile), patients living in the counties with the highest concentration of low-income NHB households (highest ICE quintile) had higher risks of late-stage diagnosis (OR, 1.09; 95% CI, 1.02-1.16; P_trend < .001), underutilization of guideline-recommended treatment (OR, 1.28; 95% CI, 1.16-1.41; P_trend < .0001), lung cancer-specific mortality (HR, 1.10; 95% CI, 1.07-1.14; P_trend < .0001), and overall mortality (HR, 1.12; 95% CI, 1.09-1.16; P_trend < .0001). The association between segregation and treatment underutilization was stronger in NHW patients than in NHB patients (P_interaction = .02). There was no significant difference in the segregation-related risk of late-stage diagnosis, lung cancer-specific mortality, or overall mortality between NHW and NHB patients.

Interpretation

Living in segregated, low-income counties with predominately NHB residents has adverse impacts on early detection, treatment, and outcomes of NSCLC. However, residential segregation did not explain the excess risks of NSCLC care underutilization and mortality in NHB patients compared with NHW patients.

背景非小细胞肺癌（NSCLC）是一种主要的肺癌类型，关于居住隔离对其早期发现、治疗和预后的影响知之甚少。种族经济隔离是否在非小细胞肺癌的治疗和结果中起作用，并导致种族差异？研究设计和方法本研究纳入2007年至2015年间诊断为NSCLC的非西班牙裔白人（NHW）和非西班牙裔黑人（NHB）患者，并从监测、流行病学和最终结果数据集中确定。采用极端集中度指数（ICE）估算县域种族化经济隔离。采用县级聚类的多水平logistic回归和多水平Cox回归来估计晚期诊断和治疗利用不足的or，并使用风险比（hr）来估计死亡率。结果203441例患者中，NHW占85.8%，NHB占14.2%。与生活在高收入NHW家庭最集中县（最低ICE五分位数）的患者相比，生活在低收入NHB家庭最集中县（最高ICE五分位数）的患者晚期诊断风险更高(OR, 1.09；95% ci, 1.02-1.16；Ptrend & lt;.001)，指南推荐治疗的未充分利用(OR, 1.28；95% ci, 1.16-1.41；Ptrend & lt;0.0001)，肺癌特异性死亡率(HR, 1.10；95% ci, 1.07-1.14；Ptrend & lt;0.0001)，总死亡率(HR, 1.12；95% ci, 1.09-1.16；Ptrend & lt;。)。隔离与治疗未充分利用之间的相关性在NHW患者中比在NHB患者中更强（p相互作用= 0.02）。在分离相关的晚期诊断风险、肺癌特异性死亡率或总体死亡率方面，NHW和NHB患者之间没有显著差异。生活在以NHB居民为主的隔离的低收入县，对NSCLC的早期发现、治疗和预后有不利影响。然而，与非小细胞肺癌患者相比，居住隔离并不能解释非小细胞肺癌患者护理利用不足和死亡率的风险。

{"title":"Racialized Economic Segregation and Disparities in Non-Small Cell Lung Cancer Care and Outcomes","authors":"Pratibha Shrestha MPH, PhD , Min Lian MD, PhD , James Struthers BA , Oumarou Nabi PhD , Bayu B. Bekele MPH, PhD , Benjamin Kozower MD , Maria Baggstrom MD , Ying Liu MD, PhD","doi":"10.1016/j.chpulm.2024.100101","DOIUrl":"10.1016/j.chpulm.2024.100101","url":null,"abstract":"<div><h3>Background</h3><div>Little is known about the impact of residential segregation on early detection, treatment, and prognosis of non-small cell lung cancer (NSCLC), a predominant type of lung cancers.</div></div><div><h3>Research Question</h3><div>Does racialized economic segregation play a role in NSCLC treatment and outcomes and contribute to racial disparities?</div></div><div><h3>Study Design and Methods</h3><div>This study included non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients with NSCLC diagnosed between 2007 and 2015 and identified from the Surveillance, Epidemiology, and End Results data set. County-level racialized economic segregation was estimated by using the Index of Concentration at the Extremes (ICE). Multilevel logistic regression and multilevel Cox regression accounting for county-level clustering were used to estimate ORs for late-stage diagnosis and treatment underutilization, and hazard ratios (HRs) were used for mortality.</div></div><div><h3>Results</h3><div>Of 203,441 patients, 85.8% were NHW, and 14.2% were NHB. Compared with patients living in the counties with the highest concentration of high-income NHW households (lowest ICE quintile), patients living in the counties with the highest concentration of low-income NHB households (highest ICE quintile) had higher risks of late-stage diagnosis (OR, 1.09; 95% CI, 1.02-1.16; <em>P</em><sub>trend</sub> < .001), underutilization of guideline-recommended treatment (OR, 1.28; 95% CI, 1.16-1.41; <em>P</em><sub>trend</sub> < .0001), lung cancer-specific mortality (HR, 1.10; 95% CI, 1.07-1.14; <em>P</em><sub>trend</sub> < .0001), and overall mortality (HR, 1.12; 95% CI, 1.09-1.16; <em>P</em><sub>trend</sub> < .0001). The association between segregation and treatment underutilization was stronger in NHW patients than in NHB patients (<em>P</em><sub>interaction</sub> = .02). There was no significant difference in the segregation-related risk of late-stage diagnosis, lung cancer-specific mortality, or overall mortality between NHW and NHB patients.</div></div><div><h3>Interpretation</h3><div>Living in segregated, low-income counties with predominately NHB residents has adverse impacts on early detection, treatment, and outcomes of NSCLC. However, residential segregation did not explain the excess risks of NSCLC care underutilization and mortality in NHB patients compared with NHW patients.</div></div>","PeriodicalId":94286,"journal":{"name":"CHEST pulmonary","volume":"3 1","pages":"Article 100101"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Occurrence of Emphysema in Individuals With Williams-Beuren Syndrome 威廉姆斯-伯恩综合征患者的肺气肿发生率：叙述性综述

CHEST pulmonary

Pub Date : 2025-03-01 DOI: 10.1016/j.chpulm.2024.100063

Uddalak Majumdar MD , Theresa M. Kline MLIS, AHIP , James K. Stoller MD

Background

Williams-Beuren syndrome (WBS) is a multisystem genetic condition characterized by a submicroscopic deletion on the seventh chromosome (7q11.23), which usually includes the elastin gene.

Research Question

Although the elastin deficiency in WBS can predispose individuals to emphysema, the prevalence of emphysema in WBS is unknown. This narrative review aims to address this gap by estimating the frequency of emphysema (or suggestive features thereof) in patients with WBS, with a special focus on concomitant alpha-1 antitrypsin deficiency.

Study Design and Methods

Literature was reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results

Of 419 studies identified by the search strategy, 19 eligible studies reported 393 adult patients with WBS. The criteria by which emphysema was assessed varied greatly among the relatively few reports addressing this issue. Chest CT evidence of emphysema was reported in three of 26 patients (11.5%). Physiologic evidence of airflow obstruction, although not definitive for emphysema (ie, with asthma not excluded), was present in as many as 38.6% of patients. Considering studies that reported multiorgan clinical manifestations of WBS, irrespective of whether chest CT imaging and/or pulmonary function testing was reported, the frequency of spirometric and imaging signs suggestive of emphysema was 4.3%. Emphysema was not reported in any of the 11 patients with concomitant PI∗MZ heterozygous alpha-1 antitrypsin deficiency.

Interpretation

In the context that only few adults with WBS have been fully characterized regarding the occurrence of emphysema, confidently estimating the prevalence of emphysema is difficult. This review shows that the frequency of imaging and pulmonary function test abnormalities suggestive of emphysema seems relatively low in the context that the elastin deficiency of WBS clearly can predispose to emphysema, and that other manifestations of elastin deficiency are present early in life. Acknowledging the challenges of studying uncommon diseases or syndromes, further systematic study of adults with WBS is needed.

williams - beuren综合征（WBS）是一种多系统遗传疾病，其特征是第七染色体（7q11.23）上的亚微观缺失，通常包括弹性蛋白基因。研究问题：虽然WBS患者弹性蛋白缺乏可使个体易患肺气肿，但WBS患者的肺气肿患病率尚不清楚。这篇叙述性综述旨在通过估计WBS患者的肺气肿（或其暗示性特征）的频率来解决这一差距，特别关注α -1抗胰蛋白酶缺乏症。研究设计和方法根据系统评价和荟萃分析指南的首选报告项目对文献进行综述。在检索策略确定的419项研究中，19项符合条件的研究报告了393例成年WBS患者。评估肺气肿的标准在相对较少的报道中差异很大。26例患者中有3例（11.5%）有胸部CT表现为肺气肿。在38.6%的患者中存在气流阻塞的生理证据，尽管对肺气肿（即不排除哮喘）没有明确的诊断。考虑到报道WBS多器官临床表现的研究，无论是否报道胸部CT成像和/或肺功能检查，肺气肿的肺活量测量和影像学征象的频率为4.3%。在11例伴有PI * MZ杂合α -1抗胰蛋白酶缺乏症的患者中没有一例出现肺气肿。在只有少数成年WBS患者有肺气肿发生的完全特征的背景下，自信地估计肺气肿的患病率是困难的。本综述显示，在WBS的弹性蛋白缺乏明显易导致肺气肿的背景下，提示肺气肿的影像学和肺功能检查异常的频率似乎相对较低，而且弹性蛋白缺乏的其他表现在生命早期就存在。认识到研究罕见疾病或综合征的挑战，需要对成人WBS进行进一步的系统研究。

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引用次数: 0

Accurate Indentification of Pathogenic Mutations Conferring α1-Antitrypsin Deficiency by a Novel Multiplexed Molecular Assay 新型多重分子测定法可准确识别α-1 抗胰蛋白酶缺乏症的致病突变

CHEST pulmonary

Pub Date : 2025-03-01 DOI: 10.1016/j.chpulm.2024.100076

Emily K. DeCurtis BSc , Sharon K. Kuss-Duerkop PhD , Iara M.P. Machado PhD , Zoe P. Stewart BSc , Matt Jackson MS , Ellie Hasenohr BSc , Jessica L. Crumby BSc , Steve D. Groshong MD, PhD , Claire M. Coeshott PhD , Ronald J. Harbeck PhD , James P. Woodrow MD , Robert A. Sandhaus MD, PhD , Yongbao Wang PhD

Background

α₁-Antitrypsin deficiency (AATD) is a common, underdiagnosed disease caused by mutations in the polymorphic SERPINA1 gene. AATD often causes COPD, other respiratory ailments, and severe liver disease. AATD underdiagnosis is associated with the lack of a quick, high-precision test for SERPINA1 variants.

Research Question

Can a rapid and more accurate molecular diagnostic assay be developed that identifies AATD-associated mutations and outperforms current limited methodology?

Study Design and Methods

We developed a multiplexed polymerase chain reaction (PCR) assay that that uses mass spectrometry to detect 20 pathogenic SERPINA1 mutations, two normal M allele variants, and an additional variant of unknown significance as an accessible frontline genetic test for AATD. Blood or buffy coat samples from 177 patients with AATD indication, 176 blood samples from people with presumed normal genotypes in addition to 10 buccal swabs and 10 blood spots (total of 373) were tested to validate the assay. Additionally, 760 whole blood samples from patients with AATD indications were evaluated to identify AATD-associated mutations.

Results

The novel genotyping assay described here accurately detected 23 SERPINA1 single nucleotide polymorphisms (23-SNP AAT assay). Of 177 AATD samples, 96% showed abnormal single nucleotide polymorphisms (SNPs), whereas 9.1% of the 176 presumed normal samples showed abnormal SNPs. The 23-SNP AAT genotypes correlated well with known serum α₁-antitrypsin levels. This genotyping assay was more accurate and streamlined than a phenotyping isoelectric focusing assay used to identify AATD variants. For clinical testing, serum α₁-antitrypsin protein level determination and the 23-SNP AAT genotyping assay were performed. The 23-SNP AAT assay was successfully implemented using AATD indication patient samples to evaluate the most common SERPINA1 mutations indicative of AATD. The 23-SNP AAT assay has allowed for quick and accurate α₁-antitrypsin genotyping of patients.

Interpretation

These findings indicate that we developed a novel, multiplexed genotyping assay that rapidly and accurately identified multiple AATD-associated SERPINA1 SNPs. This assay may be useful to diagnose AATD quickly in patients with pulmonary or hepatic diseases or both of unknown origin.

α - 1抗胰蛋白酶缺乏症（AATD）是一种常见的未被诊断的疾病，由多态SERPINA1基因突变引起。AATD通常会导致慢性阻塞性肺病、其他呼吸系统疾病和严重的肝脏疾病。AATD诊断不足与缺乏快速、高精度的SERPINA1变异检测方法有关。研究问题：能否开发出一种快速、更准确的分子诊断方法来识别aatd相关突变，并超越目前有限的方法？研究设计和方法我们开发了一种多重聚合酶链反应（PCR）检测方法，该方法使用质谱法检测20个致病性SERPINA1突变，两个正常的M等位基因变异和一个未知意义的额外变异，作为AATD的一线基因检测方法。对177例AATD适应症患者的血液或黄皮毛样本、176例假定基因型正常的人的血液样本以及10个口腔拭子和10个血点（共373个）进行了测试，以验证该测定方法。此外，对760例AATD适应症患者的全血样本进行评估，以确定AATD相关突变。结果本文描述的新型基因分型方法准确检测了23个SERPINA1单核苷酸多态性（23- snp AAT法）。在177份AATD样本中，96%的样本显示单核苷酸多态性异常，而在176份正常样本中，9.1%的样本显示单核苷酸多态性异常。23-SNP AAT基因型与已知血清α1-抗胰蛋白酶水平密切相关。这种基因分型分析比用于识别AATD变体的表型分型等电聚焦分析更准确和简化。临床检测采用血清α1-抗胰蛋白酶蛋白水平测定和23-SNP AAT基因分型。使用AATD指征患者样本成功实施了23-SNP AAT测定，以评估最常见的指示AATD的SERPINA1突变。23-SNP AAT检测可以快速准确地对患者进行α1-抗胰蛋白酶基因分型。这些发现表明，我们开发了一种新的多重基因分型分析方法，可以快速准确地识别多个与aatd相关的SERPINA1 snp。该方法可用于快速诊断病因不明的肺部或肝脏疾病患者的AATD。

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引用次数: 0

An Unusual Case of Giant Bullous Disease 巨大大疱病的罕见病例

CHEST pulmonary

Pub Date : 2025-03-01 DOI: 10.1016/j.chpulm.2024.100121

Kenji Yoshino MD , Jonathan Ioanitescu MD , Haiying Zhang MD , Tiana Endicott-Yazdani MD, PhD , Susan K. Mathai MD

Case Presentation

A 50-year-old African American woman presented to the lung transplant clinic for evaluation after experiencing gradually worsening dyspnea over the preceding 5 years. She had been diagnosed with COPD by another pulmonologist. Since her diagnosis 10 years before presentation, the patient had been on continuous supplemental oxygen therapy at 2 L/min. Her treatment regimen included a once daily combination inhaler (a corticosteroid and an ultra-long-acting ß-adrenoceptor agonist) along with an albuterol inhaler used as needed. The patient’s dyspnea limited her ability to walk half a block, and she often required a few minutes to recover after these efforts. Her symptoms were partially alleviated by use of her albuterol inhaler. In addition to dyspnea, the patient reported a nonproductive cough that was exacerbated by activity and relieved by rest. The patient’s medical history included OSA requiring positive airway pressure therapy and a hospitalization for respiratory distress due to a COVID-19 infection 12 months before presentation. She had a < 10-pack-year smoking history and childhood exposure to secondhand smoke. She had no known exposure to organic dusts or asbestos.

病例介绍一名50岁的非裔美国妇女，在经历了5年逐渐加重的呼吸困难后，来到肺移植诊所进行评估。她被另一位肺病专家诊断为慢性阻塞性肺病。自发病前10年确诊以来，患者一直以2l /min的速度持续补充供氧。她的治疗方案包括每日一次的联合吸入器（皮质类固醇和超长效肾上腺素受体激动剂）和沙丁胺醇吸入器。患者的呼吸困难限制了她行走半个街区的能力，在这些努力之后，她通常需要几分钟才能恢复。她的症状通过使用沙丁胺醇吸入器得到部分缓解。除呼吸困难外，患者报告有非生产性咳嗽，活动加重，休息缓解。患者的病史包括阻塞性睡眠呼吸暂停，需要气道正压治疗，并在就诊前12个月因COVID-19感染导致呼吸窘迫住院。她有一个<；10年的吸烟史和童年接触二手烟。她没有接触过有机粉尘或石棉。

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引用次数: 0