Abstract
BackgroundAcute 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.Research questionWe hypothesized that inhaled HMW-HA will improve outcomes in AECOPD.MethodsWe 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.ResultsOut 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.InterpretationInhaled 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).
Highlights
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) carry significant morbidity and mortality
In vitro testing showed that High molecular weight hyaluronan (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
Interpretation: Inhaled HMW-HA shortens the duration of respiratory failure and need for non-invasive ventilation in patients with AECOPD
Summary
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) carry significant morbidity and mortality. 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. High molecular weight hyaluronan (HMW-HA) is a naturally occurring sugar, that is abundant in the extracellular matrix, including in the lung. HMW-HA has several properties that make it an attractive candidate as a therapeutic in AECOPD: HMW-HA is a very hydrophilic molecule [10], and has been used as an airway hydrating agent for several years [11], which may improve mucociliary transport in COPD. We hypothesized that inhaled HMW-HA may be beneficial in AECOPD, especially in patients with impeding respiratory failure. This randomized, placebo-controlled, double-blind study included patients with severe AECOPD, necessitating bi-level non-invasive positive pressure ventilation (NIPPV). We reasoned that inhaled HMWHA may assist in improving lung function and shorten the need for NIPPV in these patients
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