Raffaele A Incalzi1, Stavros Garantziotis2, Flavia Galdi1, Claudio Pedone1, Christopher A McGee3, Margaret George3, Annette B Rice3, Shah S Hussain4, Kadambari Vijaykumar4, Evan R Boitet4, Guillermo J Tearney5,6,7,8,9, John A McGrath10, Audrey R Brown10, Steven M Rowe4,11,12. 1. Division of Geriatrics, Department of Medicine, Campus Bio-Medico University and Teaching Hospital, Rome, Italy. 2. Division of Intramural Research, National Institute of Environmental Health Sciences, 111 TW Alexander Dr, Research Triangle Park, NC, 27709, USA. garantziotis@niehs.nih.gov. 3. Division of Intramural Research, National Institute of Environmental Health Sciences, 111 TW Alexander Dr, Research Triangle Park, NC, 27709, USA. 4. Department of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama in Birmingham Medical Center, Birmingham, USA. 5. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, USA. 6. Department of Dermatology, Massachusetts General Hospital, Boston, USA. 7. Harvard Medical School, Boston, USA. 8. Harvard-MIT Division of Health Sciences and Technology, Cambridge, USA. 9. Department of Pathology, Massachusetts General Hospital, Boston, USA. 10. Social and Scientific Systems, Durham, USA. 11. Department of Pediatrics, UAB, Birmingham, USA. 12. Department of Cell development & Integrative Biology, UAB, Birmingham, USA.
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 ).
RCT Entities:
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 COPDpatients 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 ).
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