严重哮喘研究计划（SARP）中的骨骼肌脂肪沉积和肺功能轨迹
2022/10/17
摘要
理由：哮喘的肺外表现，包括组织中的脂肪浸润，可能反映全身炎症，并影响肺功能和疾病严重程度。
目的：确定骨骼肌脂肪浸润是否可预测哮喘患者的肺功能轨迹。
方法：采用基线CT成像和纵向支气管扩张剂后FEV1%预测值（中位随访5年[1132人/年]）对成人重症哮喘研究计划-3参与者进行评估。计算第12胸椎体左右棘突旁肌密度（PSMD）的平均值（Hounsfield单位[HU]）。PSMD较低反映肌肉脂肪浸润较高。我们从健康、非哮喘对照组中得出PSMD参考范围。线性多变量混合效应模型评估了基线PSMD与按性别分层的肺功能轨迹的相关性。
测量和主要结果：参与者包括219名哮喘患者（67%女性，平均（SD）BMI为32.3[8.8]kg/m2）；和37名对照组（51%女性，平均[SD]BMI为26.3（4.7）kg/m2）。哮喘患者的校正PSMD低于对照组（42.2对55.8 HU，p<0.001）。在调整后的模型中，PSMD预测了哮喘女性患者的肺功能轨迹，[（β=-0.47Δ-每10 HU下降一个斜率），p=0.03]，但男性患者没有预测[（β=0.11Δ-每个10 HU减少一个斜度），p=0.77]。最高PSMD三分位数预测哮喘女性5年内FEV1%下降2.9%，最低PSMD四分位数预测FEV1%降低1.8%。
结论：哮喘患者PSMD较低，反映出肌肉脂肪浸润较大。基线PSMD预测哮喘女性患者的肺功能下降，但男性患者没有。这些数据支持代谢功能障碍在肺功能下降中的重要作用。
Skeletal Muscle Adiposity and Lung Function Trajectory in the Severe Asthma Research Program (SARP)
Matthew C Tattersall, Kristine E Lee, Nanae Tsuchiya, Fauzia Osman, Claudia E Korcarz, Kristin M Hansen, Michael C Peters, John V Fahy, Colin A Longhurst, Eleanor Dunican, Sally E Wentzel, Joseph K Leader, Elliot Israel, Bruce D Levy, Mario Castro, Serpil C Erzurum, Jason Lempel, Wendy Moore, Eugene Bleecker, Brenda R Phillips, David T Mauger, Eric A Hoffman, Sean B Fain, Scott B Reeder, Ron L Sorkness, Nizar N Jarjour, Loren C Denlinger, Mark L Schiebler
Abstract
Rationale: Extra-pulmonary manifestations of asthma, including fatty infiltration in tissues, may reflect systemic inflammation and influence lung function and disease severity.
Objectives: To determine if skeletal muscle adiposity predicts lung function trajectory in asthma.
Methods: Adult Severe Asthma Research Program-3 participants with baseline computed tomography imaging and longitudinal post-bronchodilator FEV1%-predicted (median follow-up 5 years [1132 person-years]) were evaluated. The mean (Hounsfield unit [HU]) of the left and right paraspinous muscle density (PSMD) at the 12th thoracic vertebral body was calculated. A lower PSMD reflects higher muscle adiposity. We derived PSMD reference ranges from healthy, non-asthma controls. A linear multivariable mixed-effects model evaluated associations of baseline PSMD, and lung function trajectory stratified by sex.
Measurements and main results: Participants included 219 with asthma (67% female, mean (SD) BMI of 32.3 [8.8] kg/m2); and 37 controls (51% female, mean [SD] BMI of 26.3 (4.7) kg/m2). Asthmatic participants had lower adjusted PSMD than controls (42.2 vs. 55.8 HU, p<0.001). In adjusted models, PSMD predicted lung function trajectory in asthmatic females, [(β= -0.47 Δ-slope per 10 HU decrease), p= 0.03], but not males [(β= 0.11 Δ-slope per 10 HU decrease), p= 0.77]. The highest PSMD tertile predicted a 2.9% improvement while the lowest tertile predicted a 1.8% decline in FEV1%-predicted among asthmatic females over 5 years.
Conclusions: Asthmatic participants have lower PSMD, reflecting greater muscle fat infiltration. Baseline PSMD predicted lung function decline among females with asthma, but not males. These data support an important role of metabolic dysfunction in lung function decline.
理由：哮喘的肺外表现，包括组织中的脂肪浸润，可能反映全身炎症，并影响肺功能和疾病严重程度。
目的：确定骨骼肌脂肪浸润是否可预测哮喘患者的肺功能轨迹。
方法：采用基线CT成像和纵向支气管扩张剂后FEV1%预测值（中位随访5年[1132人/年]）对成人重症哮喘研究计划-3参与者进行评估。计算第12胸椎体左右棘突旁肌密度（PSMD）的平均值（Hounsfield单位[HU]）。PSMD较低反映肌肉脂肪浸润较高。我们从健康、非哮喘对照组中得出PSMD参考范围。线性多变量混合效应模型评估了基线PSMD与按性别分层的肺功能轨迹的相关性。
测量和主要结果：参与者包括219名哮喘患者（67%女性，平均（SD）BMI为32.3[8.8]kg/m2）；和37名对照组（51%女性，平均[SD]BMI为26.3（4.7）kg/m2）。哮喘患者的校正PSMD低于对照组（42.2对55.8 HU，p<0.001）。在调整后的模型中，PSMD预测了哮喘女性患者的肺功能轨迹，[（β=-0.47Δ-每10 HU下降一个斜率），p=0.03]，但男性患者没有预测[（β=0.11Δ-每个10 HU减少一个斜度），p=0.77]。最高PSMD三分位数预测哮喘女性5年内FEV1%下降2.9%，最低PSMD四分位数预测FEV1%降低1.8%。
结论：哮喘患者PSMD较低，反映出肌肉脂肪浸润较大。基线PSMD预测哮喘女性患者的肺功能下降，但男性患者没有。这些数据支持代谢功能障碍在肺功能下降中的重要作用。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Am J Respir Crit Care Med. 2022 Oct 4. doi: 10.1164/rccm.202203-0597OC.)
(Am J Respir Crit Care Med. 2022 Oct 4. doi: 10.1164/rccm.202203-0597OC.)
Skeletal Muscle Adiposity and Lung Function Trajectory in the Severe Asthma Research Program (SARP)
Matthew C Tattersall, Kristine E Lee, Nanae Tsuchiya, Fauzia Osman, Claudia E Korcarz, Kristin M Hansen, Michael C Peters, John V Fahy, Colin A Longhurst, Eleanor Dunican, Sally E Wentzel, Joseph K Leader, Elliot Israel, Bruce D Levy, Mario Castro, Serpil C Erzurum, Jason Lempel, Wendy Moore, Eugene Bleecker, Brenda R Phillips, David T Mauger, Eric A Hoffman, Sean B Fain, Scott B Reeder, Ron L Sorkness, Nizar N Jarjour, Loren C Denlinger, Mark L Schiebler
Abstract
Rationale: Extra-pulmonary manifestations of asthma, including fatty infiltration in tissues, may reflect systemic inflammation and influence lung function and disease severity.
Objectives: To determine if skeletal muscle adiposity predicts lung function trajectory in asthma.
Methods: Adult Severe Asthma Research Program-3 participants with baseline computed tomography imaging and longitudinal post-bronchodilator FEV1%-predicted (median follow-up 5 years [1132 person-years]) were evaluated. The mean (Hounsfield unit [HU]) of the left and right paraspinous muscle density (PSMD) at the 12th thoracic vertebral body was calculated. A lower PSMD reflects higher muscle adiposity. We derived PSMD reference ranges from healthy, non-asthma controls. A linear multivariable mixed-effects model evaluated associations of baseline PSMD, and lung function trajectory stratified by sex.
Measurements and main results: Participants included 219 with asthma (67% female, mean (SD) BMI of 32.3 [8.8] kg/m2); and 37 controls (51% female, mean [SD] BMI of 26.3 (4.7) kg/m2). Asthmatic participants had lower adjusted PSMD than controls (42.2 vs. 55.8 HU, p<0.001). In adjusted models, PSMD predicted lung function trajectory in asthmatic females, [(β= -0.47 Δ-slope per 10 HU decrease), p= 0.03], but not males [(β= 0.11 Δ-slope per 10 HU decrease), p= 0.77]. The highest PSMD tertile predicted a 2.9% improvement while the lowest tertile predicted a 1.8% decline in FEV1%-predicted among asthmatic females over 5 years.
Conclusions: Asthmatic participants have lower PSMD, reflecting greater muscle fat infiltration. Baseline PSMD predicted lung function decline among females with asthma, but not males. These data support an important role of metabolic dysfunction in lung function decline.
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呼吸道变应原的累积IgE水平作为预测以抗IgE为基础的重症哮喘治疗疗效的生物标志物
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利用表位特异性IgE抗体谱预测过敏儿童对离散量花生蛋白的耐受概率
