Anderson Wayne H, Coakley Raymond D, Button Brian, Henderson Ashley G, Zeman Kirby L, Alexis Neil E, Peden David B, Lazarowski Eduardo R, Davis C William, Bailey Summer, Fuller Fred, Almond Martha, Qaqish Bahjat, Bordonali Elena, Rubinstein Michael, Bennett William D, Kesimer Mehmet, Boucher Richard C
1 Pulmonary and Critical Care Medicine, Department of Medicine.
2 Marsico Lung Institute/Cystic Fibrosis Research Center.
Am J Respir Crit Care Med. 2015 Jul 15;192(2):182-90. doi: 10.1164/rccm.201412-2230OC.
Chronic bronchitis (CB) is characterized by persistent cough and sputum production. Studies were performed to test whether mucus hyperconcentration and increased partial osmotic pressure, in part caused by abnormal purine nucleotide regulation of ion transport, contribute to the pathogenesis of CB.
We tested the hypothesis that CB is characterized by mucus hyperconcentration, increased mucus partial osmotic pressures, and reduced mucus clearance.
We measured in subjects with CB as compared with normal and asymptomatic smoking control subjects indices of mucus concentration (hydration; i.e., percentage solids) and sputum adenine nucleotide/nucleoside concentrations. In addition, sputum partial osmotic pressures and mucus transport rates were measured in subjects with CB.
CB secretions were hyperconcentrated as indexed by an increase in percentage solids and total mucins, in part reflecting decreased extracellular nucleotide/nucleoside concentrations. CB mucus generated concentration-dependent increases in partial osmotic pressures into ranges predicted to reduce mucus transport. Mucociliary clearance (MCC) in subjects with CB was negatively correlated with mucus concentration (percentage solids). As a test of relationships between mucus concentration and disease, mucus concentrations and MCC were compared with FEV1, and both were significantly correlated.
Abnormal regulation of airway surface hydration may slow MCC in CB and contribute to disease pathogenesis.
慢性支气管炎（CB）的特征为持续性咳嗽和咳痰。开展了多项研究以检验黏液高渗及部分由离子转运的嘌呤核苷酸调节异常所致的渗透压升高是否参与了CB的发病机制。
我们检验了以下假设，即CB的特征为黏液高渗、黏液渗透压升高及黏液清除率降低。
我们测定了CB患者以及正常和无症状吸烟对照者的黏液浓度指标（水合作用；即固体百分比）和痰液腺嘌呤核苷酸/核苷浓度。此外，还测定了CB患者的痰液渗透压和黏液转运速率。
CB分泌物呈高渗状态，表现为固体百分比和总黏蛋白增加，部分反映了细胞外核苷酸/核苷浓度降低。CB黏液产生了浓度依赖性的渗透压升高，升至预计会降低黏液转运的范围。CB患者的黏液纤毛清除率（MCC）与黏液浓度（固体百分比）呈负相关。作为对黏液浓度与疾病之间关系的检验，将黏液浓度和MCC与第1秒用力呼气容积（FEV1）进行比较，二者均显著相关。
气道表面水合作用的异常调节可能会减慢CB患者的MCC，并导致疾病的发病机制。
