Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study

Abstract

Background 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. Research question We hypothesized that inhaled HMW-HA will improve outcomes in AECOPD. Methods 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. Results 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. Interpretation 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).

Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission

“…One strategy is to counteract changes in the extracellular matrix by giving glycosaminoglycans such as hyaluronic acid or heparan sulfate. A placebo-controlled randomised trial 250 showed that high-molecular-weight hyaluronan ameliorated respiratory failure in patients with severe COPD exacerbations. Several antivirals are also in the pipeline, including a dry-powder formulation of ribavirin.…”

Effectiveness of Noninvasive Positive Pressure Ventilation Combined with Enteral Nutrition in the Treatment of Patients with Combined Respiratory Failure after Lung Cancer Surgery and Its Effect on Blood Gas Indexes

“…The efficacy of NIPPV in the treatment of severe respiratory failure has been clinically recognized [ 12 , 13 ]. Its mechanism of action is mainly to re-expand atrophied alveoli through effective ventilation, to improve respiratory muscle function, and reduce oxygen consumption, thereby correcting hypercapnia.…”

The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan

“…Our findings support a novel proposed model of S-protein-induced cell injury ( Figure 7 ): beyond the well-described interaction of the S-protein with host alveolar epithelia via the receptor human angiotensin-converting enzyme 2 (hACE2) (25; 47; 51), the S-protein also exerts pathological effects (changes in Proteome, E2F1, CREB, p65 activation) independent of ACE2. Furthermore, HMW-HA, which is naturally found in mammalian airways (1; 17), and can also be given pharmacologically (18), attenuates the deleterious effects of S-protein ( Figure 7 ). Thus, our findings suggest a novel injury pathway and a novel treatment agent for COVID-19 associated lung injury.…”