Respiratory Research Unit, Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen, Denmark; Department of Respiratory & Sleep Medicine, John Hunter Hospital, Newcastle, New South Wales, Australia.
Respirology. 2013 Oct;18(7):1128-34. doi: 10.1111/resp.12142.
Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma, neutrophil airway inflammation increases airway closure during bronchoconstriction, while eosinophil airway inflammation increases airway hyperresponsiveness (AHR).
Asthmatic subjects (n = 26), aged ≥55 years (68% female), were studied, and AHR to 4.5% saline challenge was measured by the response-dose ratio (%fall in forced expiratory volume in 1 s (FEV1 )/mg saline). Airway closure was assessed during bronchoconstriction percent change in forced vital capacity (FVC)/percent change in FEV1 (i.e. Closing Index). Airway inflammation was assessed by induced sputum and exhaled nitric oxide (eNO).
Mean patient age was 67 years (confidence interval: 63-71) with a mean FEV1 of 78 % predicted (confidence interval: 70-85%). AHR correlated with sputum eosinophils (r = 0.68, P = 0.005) and eNO (r = 0.71, P < 0.001), but not with neutrophils or neutrophil mediators. The Closing Index correlated with total sputum neutrophils (r = 0.66, P = 0.005), neutrophil elastase, matrix metalloproteinase-9 and interleukin-8 (all P < 0.05). Further, FEV1 /FVC and residual volume/total lung capacity at rest correlated with neutrophil elastase (r = -0.46 and 0.66 respectively, P < 0.05) but not with eosinophils or eNO.
In older patients with asthma, airway inflammatory cells are linked to abnormal airway physiology. Eosinophilic airway inflammation is associated with AHR while neutrophilic inflammation may be an important determinant of airflow limitation at rest and airway closure during bronchoconstriction. The clinical implications of these findings remain to be determined.
与年轻哮喘患者相比，老年哮喘患者的相关发病率更高。老年哮喘患者的气道闭合程度也更高，这种观察结果可能是由于气道炎症的差异所致。我们假设，在患有哮喘的老年成年患者中，中性粒细胞气道炎症会在支气管收缩期间增加气道闭合，而嗜酸性粒细胞气道炎症会增加气道高反应性（AHR）。
研究了 26 名年龄≥55 岁（68%为女性）的哮喘患者，并通过 4.5%盐水激发试验的反应剂量比（FEV1 下降百分比/盐水毫克数）来测量 AHR。通过用力肺活量（FVC）的百分比变化/用力呼气量（FEV1）的百分比变化（即闭合指数）评估支气管收缩期间的气道闭合。通过诱导痰和呼气一氧化氮（eNO）评估气道炎症。
患者平均年龄为 67 岁（置信区间：63-71），平均 FEV1 为 78%预测值（置信区间：70-85%）。AHR 与痰中嗜酸性粒细胞（r=0.68，P=0.005）和 eNO（r=0.71，P<0.001）相关，但与中性粒细胞或中性粒细胞介质无关。闭合指数与总痰中性粒细胞（r=0.66，P=0.005）、中性粒细胞弹性蛋白酶、基质金属蛋白酶-9 和白细胞介素-8 相关（均 P<0.05）。此外，FEV1/FVC 和静息时残气量/总肺容量与中性粒细胞弹性蛋白酶相关（r=-0.46 和 0.66，分别为 P<0.05），但与嗜酸性粒细胞或 eNO 无关。
在患有哮喘的老年患者中，气道炎症细胞与异常的气道生理学有关。嗜酸性粒细胞气道炎症与 AHR 相关，而中性粒细胞炎症可能是静息时气流受限和支气管收缩时气道闭合的重要决定因素。这些发现的临床意义仍有待确定。
