Division of Geriatrics, Department of Medicine, Campus Bio-Medico University and Teaching Hospital, Rome, Italy.
Division of Intramural Research, National Institute of Environmental Health Sciences, 111 TW Alexander Dr, Research Triangle Park, NC, 27709, USA.
Respir Res. 2021 Feb 1;22(1):30. doi: 10.1186/s12931-020-01610-x.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) carry significant morbidity and mortality. AECOPD treatment remains limited. High molecular weight hyaluronan (HMW-HA) is a glycosaminoglycan sugar, which is a physiological constituent of the lung extracellular matrix and has notable anti-inflammatory and hydrating properties.
We hypothesized that inhaled HMW-HA will improve outcomes in AECOPD.
We conducted a single center, randomized, placebo-controlled, double-blind study to investigate the effect of inhaled HMW-HA in patients with severe AECOPD necessitating non-invasive positive-pressure ventilation (NIPPV). Primary endpoint was time until liberation from NIPPV.
Out of 44 screened patients, 41 were included in the study (21 for placebo and 20 for HMW-HA). Patients treated with HMW-HA had significantly shorter duration of NIPPV. HMW-HA treated patients also had lower measured peak airway pressures on the ventilator and lower systemic inflammation markers after liberation from NIPPV. In vitro testing showed that HMW-HA significantly improved mucociliary transport in air-liquid interface cultures of primary bronchial cells from COPD patients and healthy primary cells exposed to cigarette smoke extract.
Inhaled HMW-HA shortens the duration of respiratory failure and need for non-invasive ventilation in patients with AECOPD. Beneficial effects of HMW-HA on mucociliary clearance and inflammation may account for some of the effects (NCT02674880, www.clinicaltrials.gov ).
慢性阻塞性肺疾病（COPD）急性加重（AECOPD）会带来显著的发病率和死亡率。AECOPD 的治疗仍然有限。高分子量透明质酸（HMW-HA）是一种糖胺聚糖，是肺细胞外基质的生理成分，具有显著的抗炎和保湿特性。
我们假设吸入 HMW-HA 将改善 AECOPD 的结局。
我们进行了一项单中心、随机、安慰剂对照、双盲研究，以研究吸入 HMW-HA 对需要无创正压通气（NIPPV）的重度 AECOPD 患者的影响。主要终点是从 NIPPV 中解脱出来的时间。
在 44 名筛选的患者中，有 41 名患者纳入了研究（21 名接受安慰剂，20 名接受 HMW-HA）。接受 HMW-HA 治疗的患者 NIPPV 持续时间明显缩短。HMW-HA 治疗组患者在从 NIPPV 中解脱出来后，呼吸机上的测量峰值气道压力和全身炎症标志物也较低。体外试验表明，HMW-HA 显著改善了 COPD 患者和暴露于香烟烟雾提取物的健康原代细胞的气道上皮细胞的气液界面培养物中的黏液纤毛转运。
吸入 HMW-HA 可缩短 AECOPD 患者呼吸衰竭和需要无创通气的时间。HMW-HA 对黏液清除和炎症的有益作用可能是其部分作用的原因（NCT02674880，www.clinicaltrials.gov）。
