重症哮喘研究计划（SARP）中的骨骼肌脂肪沉积和肺功能轨迹
2022/10/17
摘要
背景：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的严重程度。
目的：确定骨骼肌脂肪沉积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吸入后FEV1占预计值的百分比（中位随访时间5年[1132人·年]）对成人重症哮喘研究计划-3中的参与者进行评估。计算第12胸椎体左右棘突旁肌肉密度（PSMD）的平均值（Hounsfield单位[HU]）。PSMD较低反映肌肉肥胖症较高。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。
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 vs. 55.8 HU，p<0.001）。在校正模型中，PSMD预测了女性哮喘患者的肺功能轨迹，[（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]。在女性哮喘患者中，最高PSDM三分位数预测出患者5年内FEV1%pred降低2.9%，最低PSDM三分位数预测出患者5年内FEV1%pred降低1.8%。
结论：对哮喘患者而言，PSMD低反映肌肉脂肪沉积多。基线PSMD预测女性哮喘患者的肺功能下降，但男性患者没有。上述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)
Tattersall MC, Lee KE, Tsuchiya N, Osman F, Korcarz CE, Hansen KM, Peters MC, Fahy JV, Longhurst CA, Dunican E, Wentzel SE, Leader JK, Israel E, Levy BD, Castro M, Erzurum SC, Lempel J, Moore W, Bleecker E, Phillips BR, Mauger DT, Hoffman EA, Fain SB, Reeder SB, Sorkness RL, Jarjour NN, Denlinger LC, Schiebler ML.
Abstract
BACKGROUND: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.
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.
背景：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的严重程度。
目的：确定骨骼肌脂肪沉积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吸入后FEV1占预计值的百分比（中位随访时间5年[1132人·年]）对成人重症哮喘研究计划-3中的参与者进行评估。计算第12胸椎体左右棘突旁肌肉密度（PSMD）的平均值（Hounsfield单位[HU]）。PSMD较低反映肌肉肥胖症较高。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。
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 vs. 55.8 HU，p<0.001）。在校正模型中，PSMD预测了女性哮喘患者的肺功能轨迹，[（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]。在女性哮喘患者中，最高PSDM三分位数预测出患者5年内FEV1%pred降低2.9%，最低PSDM三分位数预测出患者5年内FEV1%pred降低1.8%。
结论：对哮喘患者而言，PSMD低反映肌肉脂肪沉积多。基线PSMD预测女性哮喘患者的肺功能下降，但男性患者没有。上述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 张婧媛 摘译 林江涛 审校)
(Am J Respir Crit Care Med. 2022 Oct 4. Epub ahead of print. doi: 10.1164/rccm.202203-0597OC. PMID: 36194556..)
(Am J Respir Crit Care Med. 2022 Oct 4. Epub ahead of print. doi: 10.1164/rccm.202203-0597OC. PMID: 36194556..)
Skeletal Muscle Adiposity and Lung Function Trajectory in the Severe Asthma Research Program (SARP)
Tattersall MC, Lee KE, Tsuchiya N, Osman F, Korcarz CE, Hansen KM, Peters MC, Fahy JV, Longhurst CA, Dunican E, Wentzel SE, Leader JK, Israel E, Levy BD, Castro M, Erzurum SC, Lempel J, Moore W, Bleecker E, Phillips BR, Mauger DT, Hoffman EA, Fain SB, Reeder SB, Sorkness RL, Jarjour NN, Denlinger LC, Schiebler ML.
Abstract
BACKGROUND: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.
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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环境温度引起的哮喘死亡率：中国的一项病例交叉研究
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孟德尔随机分析揭示了特应性皮炎、哮喘和GERD之间复杂的遗传相互作用
