低T2重症哮喘人群的病情加重情况和危险因素
2022/06/17
摘要
尽管低T2哮喘仅存在于少数重症哮喘患者中，但对其潜在机制知之甚少，这使其成为哮喘研究的迫切需求。
方法：急性加重评估是对随机对照试验数据的预先规定的二次分析，比较低T2重症哮喘强化队列中使用生物标记物和症状来调整激素治疗的情况。参与者研究登记和每次急性加重时表现为低T2型[呼出一氧化氮分数（FeNO）≤20 ppb和血嗜酸细胞计数（PBE）≤150个细胞/µL]或高T2型（FeNO>20或PBE>150个细胞/µL）。我们报告了急性加重者与非急性加重者的比较、低T2和高T2加重时的生理变化以及炎症表型的稳定性。
结果：60.8%（183/301）≥1次自我报告的急性加重（共390例）。加重者更可能是女性，BMI更高，需要口服皮质类固醇（OCS）和非计划的初级保健就诊。入组时，23.6%（71/301）低T2型，76.4%（230/301）高T2型。低T2组哮喘初级保健就诊人数较多，更有可能先前进入HDU/ICU并接受维持性OCS。在加重期，低T2型在肺功能和症状增重方面与高T2型加重期无法区分，低T2加重期的T2生物标志物从稳定状态到加重状态没有增加。
结论：表现为低T2表型的哮喘急性发作在生理和症状上与高T2表型急性发作相似。临床上显著的低T2急性加重突出了未满足和迫切需要进一步了解非T2型哮喘的作用机制。
Exacerbation Profile and Risk Factors in a T2-Low Severe Asthma Population
P Jane McDowell, John Busby, Catherine E Hanratty, Ratko Djukanovic, Ashley Woodcock, Samantha Walker, Timothy Colin Hardman, Joseph R Arron, David F Choy, Peter Bradding, Chris E Brightling, Rekha Chaudhuri, Douglas Cowan, Adel H Mansur, Stephen J Fowler, Sarah E Dive, Peter Howarth, James Lordan, Andrew Menzies-Gow, Timothy Harrison, Douglas S Robinson, Cecile T J Holweg, John G Matthews, Ian D Pavord, Liam G Heaney, investigators for the MRC Refractory Asthma Stratification Program
Abstract
Although present in a minority of severe asthmatics, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research.
Methods: Exacerbation assessment was a pre-specified secondary analysis of data from a RCT comparing the use of biomarkers & symptoms to adjust steroid treatment in a T2-low severe asthma-enriched cohort. Participants were phenotyped as T2LOW(fractional exhaled nitric oxide [FeNO] ≤20 ppb & blood eosinophil count [PBE] ≤150 cells/µL) or T2HIGH ( FeNO>20 or PBE>150) at study enrolment & at each exacerbation. We report comparison of exacerbators & non-exacerbators, physiological changes at exacerbation in T2LOW & T2HIGH ,& stability of inflammatory phenotypes.
Results: 60.8% (183/301) ≥1 self-reported exacerbations (total of 390). Exacerbators were more likely to be female, have a higher BMI & more exacerbations requiring oral corticosteroid (OCS) & unscheduled primary care attendances for exacerbations. At enrolment, 23.6% (71/301) were T2LOW, & 76.4% (230/301) T2HIGH. The T2LOW group had more asthma primary care attendances, were more likely to have a previous admission to HDU/ICU & to be receiving maintenance OCS. At exacerbation the T2LOW events were indistinguishable from T2HIGH exacerbations in terms of lung function & symptom increase, with no increase in T2 biomarkers from stable to exacerbation state in the T2LOW exacerbations.
Conclusion: Asthma exacerbations demonstrating a T2LOW phenotype were physiologically & symptomatically similar to T2HIGHexacerbations. The clinically significant T2LOW exacerbations highlights the unmet & pressing need to further understand the mechanisms at play in non-T2 asthma.
尽管低T2哮喘仅存在于少数重症哮喘患者中，但对其潜在机制知之甚少，这使其成为哮喘研究的迫切需求。
方法：急性加重评估是对随机对照试验数据的预先规定的二次分析，比较低T2重症哮喘强化队列中使用生物标记物和症状来调整激素治疗的情况。参与者研究登记和每次急性加重时表现为低T2型[呼出一氧化氮分数（FeNO）≤20 ppb和血嗜酸细胞计数（PBE）≤150个细胞/µL]或高T2型（FeNO>20或PBE>150个细胞/µL）。我们报告了急性加重者与非急性加重者的比较、低T2和高T2加重时的生理变化以及炎症表型的稳定性。
结果：60.8%（183/301）≥1次自我报告的急性加重（共390例）。加重者更可能是女性，BMI更高，需要口服皮质类固醇（OCS）和非计划的初级保健就诊。入组时，23.6%（71/301）低T2型，76.4%（230/301）高T2型。低T2组哮喘初级保健就诊人数较多，更有可能先前进入HDU/ICU并接受维持性OCS。在加重期，低T2型在肺功能和症状增重方面与高T2型加重期无法区分，低T2加重期的T2生物标志物从稳定状态到加重状态没有增加。
结论：表现为低T2表型的哮喘急性发作在生理和症状上与高T2表型急性发作相似。临床上显著的低T2急性加重突出了未满足和迫切需要进一步了解非T2型哮喘的作用机制。
(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 May 12. doi: 10.1164/rccm.202201-0129OC.)
(Am J Respir Crit Care Med. 2022 May 12. doi: 10.1164/rccm.202201-0129OC.)
Exacerbation Profile and Risk Factors in a T2-Low Severe Asthma Population
P Jane McDowell, John Busby, Catherine E Hanratty, Ratko Djukanovic, Ashley Woodcock, Samantha Walker, Timothy Colin Hardman, Joseph R Arron, David F Choy, Peter Bradding, Chris E Brightling, Rekha Chaudhuri, Douglas Cowan, Adel H Mansur, Stephen J Fowler, Sarah E Dive, Peter Howarth, James Lordan, Andrew Menzies-Gow, Timothy Harrison, Douglas S Robinson, Cecile T J Holweg, John G Matthews, Ian D Pavord, Liam G Heaney, investigators for the MRC Refractory Asthma Stratification Program
Abstract
Although present in a minority of severe asthmatics, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research.
Methods: Exacerbation assessment was a pre-specified secondary analysis of data from a RCT comparing the use of biomarkers & symptoms to adjust steroid treatment in a T2-low severe asthma-enriched cohort. Participants were phenotyped as T2LOW(fractional exhaled nitric oxide [FeNO] ≤20 ppb & blood eosinophil count [PBE] ≤150 cells/µL) or T2HIGH ( FeNO>20 or PBE>150) at study enrolment & at each exacerbation. We report comparison of exacerbators & non-exacerbators, physiological changes at exacerbation in T2LOW & T2HIGH ,& stability of inflammatory phenotypes.
Results: 60.8% (183/301) ≥1 self-reported exacerbations (total of 390). Exacerbators were more likely to be female, have a higher BMI & more exacerbations requiring oral corticosteroid (OCS) & unscheduled primary care attendances for exacerbations. At enrolment, 23.6% (71/301) were T2LOW, & 76.4% (230/301) T2HIGH. The T2LOW group had more asthma primary care attendances, were more likely to have a previous admission to HDU/ICU & to be receiving maintenance OCS. At exacerbation the T2LOW events were indistinguishable from T2HIGH exacerbations in terms of lung function & symptom increase, with no increase in T2 biomarkers from stable to exacerbation state in the T2LOW exacerbations.
Conclusion: Asthma exacerbations demonstrating a T2LOW phenotype were physiologically & symptomatically similar to T2HIGHexacerbations. The clinically significant T2LOW exacerbations highlights the unmet & pressing need to further understand the mechanisms at play in non-T2 asthma.
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哮喘和 COPD 重叠综合症新模型中的气道和实质组织的转录组学
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乌本苷可调节高Th2型哮喘小鼠的气道重塑
