Inhaling unfragmented hyaluronan improves lung function in patients suffering from severe exacerbation of chronic obstructive pulmonary disease (COPD), found a small study from researchers at the National Institutes of Health and their collaborators. Hyaluronan, a sugar secreted by living tissue that acts as a scaffold for cells, is also used in cosmetics as a skin moisturiser and as a nasal spray to moisturise lung airways.
Utilised as a treatment, hyaluronan shortened the amount of time COPD patients in intensive care needed breathing support, decreased their number of days in the hospital, and saved money by reducing their hospital stay.
The study is a good example of how examining the impacts of environmental pollution on the lungs can lead to viable treatments.
Several years ago, co-senior author Dr Stavros Garantziotis, medical director of the clinical research unit at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, showed that exposure to pollution causes hyaluronan in the lungs to break down into smaller fragments. These fragments irritate lung tissue and activate the immune system, leading to constriction and inflammation of the airways. He determined that inhalation of healthy, unfragmented hyaluronan reduces inflammation by outcompeting the smaller hyaluronan fragments.
Garantziotis offered an analogy for how the inflammation occurs. He said hyaluronan surrounds cells like mortar surrounds bricks. Introducing pollution causes cracks in the mortar, breaking it into smaller chunks.
"These smaller chunks irritate the body and activate the immune system, leading to inflammation," Garantziotis said. "Reintroducing the full-length hyaluronan, like a fresh coat of mortar, means it is less irritating and reduces the amount of inflammation."
Since hyaluronan was approved in Italy for airway moisturisation, Garantziotis worked with colleagues in Rome to see if inhalation of full-size hyaluronan could improve lung function in critically ill COPD patients. He explained that the patients were using a breathing apparatus similar to a continuous positive airway pressure (CPAP) machine to treat their acute exacerbation of COPD. This apparatus provided breathing support by blowing air into the airways through a mask.
"Inhaled hyaluronan qualifies as a stimulating aid for patients with exacerbated COPD, as it is safe and easy to administer,” said co-senior author Dr Raffaele Incalzi, department of medicine, Campus Bio-Medico University and Teaching Hospital – Rome. "Furthermore, it acts locally, only in the bronchial tree, and, thus, cannot interfere with any systemic drug."
Garantziotis also wanted to know what was producing airway constriction in the lungs of COPD patients. He theorised that thick mucus may be involved.
Collaborating with scientists at the University of Alabama at Birmingham (UAB), they grew airway cells from emphysema patients in culture and looked at how mucus moved in the cells. They saw that mucus flowed more easily after administering hyaluronan.
Co-author Dr Steven Rowe, director of the Gregory Fleming James Cystic Fibrosis Research Centre at UAB, said if patients with severe COPD took hyaluronan, the treatment would improve mucus transport and aid their recovery.
Current treatments for lung disease include inhaled steroids, antibiotics, and bronchodilators, so using a molecule that is already found in the body is a new concept.
The goal now for Garantziotis is to study this treatment in more patients in the US, so he can understand the optimal conditions and dosing that will produce the most benefit.
Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study
Flavia Galdi, Claudio Pedone, Christopher A McGee, Margaret George, Annette B Rice, Shah S Hussain, Kadambari Vijaykumar, Evan R Boitet, Guillermo J Tearney, John A McGrath, Audrey R Brown, Steven M Rowe, Raffaele A Incalzi, Stavros Garantziotis
Published in Respiratory Research on 1 February 2021
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.
National Institutes of Health material
Respiratory Research study (Open access)
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