哮喘联盟

    肺换气障碍不仅与气道收缩有关，还可能反映与气道炎症有关的小气道变化。为了比较5-磷酸腺苷（Adenosine 5’-monophosphate，AMP)和乙酰甲胆碱（methacholine, MCh）对V/Q失衡的影响，Manrique等对36例哮喘患者进行了一项随机、双盲研究。    
    该研究分为3个交叉研究：AMP/MCh激发前、后（研究1）；AMP激发后，沙丁胺醇/安慰剂治疗前、后30min（研究2）；MCh激发后，沙丁胺醇/安慰剂治疗前、后30min（研究3）。在激发前和激发后4h收集痰标本。研究发现，在相同的支气管收缩强度下(FEV1下降范围，28-44%)，AMP激发引起的肺内换气异常与MCh相当。当以支气管舒张剂——沙丁胺醇抑制AMP/MCh诱导的支气管收缩后，PaO2和AaPO2紊乱也有所减轻（AMP，46%和58%；MCh，42%和57%）。与MCh相比，AMP明显增加痰中性粒细胞数量（从28%±17%增至38%±16%，p<0.05），但在沙丁胺醇预处理组，这一现象并不明显。    
    研究证实，AMP不仅能够复制急性哮喘发作时肺功能的变化，而且能引起中性粒细胞增多和局部低氧血症。但这些变化都可被沙丁胺醇完全抑制，作者认为这可能是因为β激动剂能同时作用于支气管和肺循环两方面。     

  
Adenosine 5’-monophosphate (AMP) bronchoprovocation could reproduce the lung function abnormalities spontaneously occurring during acute asthma and detect peripheral airway inflammation better than direct bronchoconstrictive agents. Pulmonary gas exchange disturbances may reflect changes in small airways related to airway inflammation rather than bronchoconstriction alone.We investigated whether AMP induces more ventilation-perfusion (VA/Q) imbalance than methacholine (MCh) at equivalent degree of bronchoconstriction with and without salbutamol pre-medication. We studied 36 asthmatics in three randomised, double-blinded, cross-over studies: before and after AMP/MCh (Study-1); and before and 30 min after salbutamol/placebo, followed by AMP (Study-2)/MCh (Study-3) challenge. Sputum was collected before and 4 h post-challenge.Compared to MCh, AMP provoked similar pulmonary gas exchange abnormalities at an equivalent degree of intense bronchoconstriction (FEV1 fall, range 28-44%). While salbutamol blocked AMP/MCh-induced bronchoconstriction, PaO2 and AaPO2 disturbances were partially blocked (AMP, by 46% and 58%; MCh, by 42% and 57%, respectively). Compared to MCh, AMP increased neutrophils (from 28+/-17% to 38+/-16%, p<0.05) but not after salbutamol pre-treatment.Both AMP and MCh induce similar peripheral airway dysfunction. The fully inhibited AMP-induced neutrophilia with residual hypoxaemia observed after salbutamol is likely related to beta-agonists acting on both bronchial and pulmonary circulations.