Inhaled Sugar Formulation May Reduce Ventilation Duration, Improve Lung Function in AECOPD

Inhaled high molecular weight hyaluronan ameliorates (HMW-HA) can improve lung function and shorten the need for ventilation in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), according to a pilot study published in Respiratory Research.

“Our study shows for the first time the therapeutic potential of an extracellular matrix molecule in acute exacerbation of human lung disease,” wrote the investigators.

Investigators said that COPD-associated morbidity and mortality are increasing worldwide. AECOPD is estimated to occur in over 90% of patients with COPD, who often require hospitalization, a major cost driver in COPD. There is a lack of bronchodilators, nonspecific anti-inflammatory corticosteroids, antibiotics, and anti-inflammatory agents to treat AECOPD.

HMW-HA, a naturally occurring sugar that is abundant in the lungs, is routinely used as an airway-hydrating agent in patients with cystic fibrosis; however, its use in patients with AECOPD, is limited. Investigators hypothesized that HMW-HA may improve mucociliary transport in COPD.

The study was a randomized, placebo-controlled, double-blind, single-center study of adult patients admitted to the Internediate Care Section, Geriatric Unit, of Campus Bio-Medico at the University of Rome between March 2016 and July 2019. All had a diagnosis of AECOPD and required noninvasive positive pressure ventilation (NIPPV).

Of 44 patients screened for eligibility, 41 were included in the study. Twenty received HMW-HA and 21 received a placebo. Both groups received treatment twice daily until they were taken off NIPPV or until NIPPV failure. HMW-HA was administered in a breathing apparatus similar to a continuous positive airway pressure machine.

“Inhaled hyaluronan qualifies as a stimulating aid for patients with exacerbated COPD, as it is safe and easy to administer….Furthermore, it acts locally, only in the bronchial tree, and, thus, cannot interfere with any systemic drug,” said Raffaele Incalz, MD, Department of Medicine, Campus Bio-Medico, co-senior author of the study, in a statement.

Investigators found that patients treated with HMW-HA were taken off of NIPPV an average of 1 day sooner than patients treated with placebo; they spent a mean (SD) 5.2 (0.4) vs 6.4 (0.5) days on NIPPV, respectively (P = .037). Overall total length of hospital stay in days was also shortened for patients treated with HMW-HA compared with placebo-treated patients: 7.2 (0.3) vs 10.2 (1.3) (P = .039).

Peak pressures reported by the ventilator software were significantly lower among patients treated with HMW-HA vs those treated with placebo. However, arterial blood gas values significantly improved only in patients treated with HMW-HA.

The investigators also evaluated serum markers of inflammation on admission and on the day of NIPPV liberation. However, because some samples were destroyed while in transit from Italy to a US lab, only 13 samples per group could be analyzed.

Although markers for acute phase inflammation decreased over time in both groups, the patients receiving HMW-HA had a more noticeable response in inflammation markers than patients receiving the placebo, suggesting that HMW-HA may be beneficial in reducing the effects of systemic inflammation associated with AECOPD.

The researchers noted that the hydrating effect often associated with HMW-HA did not seem to contribute to the improved mucociliary transport rates observed in patients. Additionally, dimensions for airway surface liquid and periciliary layer depth were not altered with HMW-HA, suggesting that hydration status did not have a significant effect on the mucus layer.

The investigators proposed that the HMW-HA properties, such as the ability to change the nanostructure of mucin and anti-inflammatory and pro-homeostatic properties, may have had a larger effect on improved lung function and improved serum inflammatory markers over time.

“Additional studies should confirm our findings with higher number of patients in additional clinical sites and explore the use of HMW-HA in chronic COPD, both to reduce COPD progression and to decrease exacerbations, which are the major driver of morbidity, mortality and cost in this devastating disease,” wrote the investigators.

The investigators noted the small sample size and single-center nature of the study as limitations. Additionally, lack of background information on lung function or baseline blood gas values limited the investigators’ ability to comment on the severity of COPD in the included patients.

Reference

Galdi F, Pedone C, McGee CA, et al. Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study. Respir Res. Published online February 1, 2021. doi:10.1186/s12931-020-01610-x