SBIR-STTR Award

Acute respiratory distress syndrome, ARDS, is of multifactorial etiology and afflicts 50,000 to 90,000 Americans each year and 18% of all ventilated patients. Despite sophisticated intensive care, the mortality rate ranges between 15 and 72% with a mean of 43%. Patients with ARDS have impaired surfactant function and continued inflammation-induced metabolism of surfactant indicating that a single treatment with surfactant is inadequate. The delivery of pulmonary surfactant to treat lung diseases such as ARDS and RDS has been via the instillation of 20 to 80 mg/ml of suspensions of surfactant at doses generally ranging from 100 mg to 200 mg/kg. Multiple bolus intrapulmonary instillations of surfactant are traumatic for the patient and physician alike and lead to undesirable peri- and post- treatment events. Aerosolized surfactant may require a considerably lower dose to achieve a similar physiological effect. It also eliminates the hypercapnia seen on bolus instillation. In neonates aerosolized surfactant has been delivered over 3 hour treatment periods. This situation is markedly exacerbated when attempting to deliver the same dose/kg of aerosolized surfactant to adults. SUPRAER uses a single-pass low shear nozzle to generate an ~10 µm diameter aqueous aerosol. This aerosol plume is arrested by a counter-flow gas stream and rapidly dried by warm compressed gas and dilution gas as well as infrared radiation. The resulting fine particle aerosol is concentrated using a low resistance virtual impactor and delivered at the output on demand. Two classes of single-pass, low shear aerosol generation nozzles that aerosolize 100% of the surfactant will be evaluated. We will optimize the heat and mass transfer of the evaporation process as well as the other components of the aerosol processing system to provide aerosols containing a high mass loading of surfactant that can be predicted to deposit in the alveolar regions of the lungs. Our target is to demonstrate that clinically relevant doses of surfactant aerosols can be generated and delivered in 50-100 minutes. The delivery of surfactant in a gentler, non-invasive manner would empower the clinician to provide improved life support and potentially a marked improvement in survival. This important new technological innovation will also be applicable to treat other diseases of the lungs that require drugs whose efficacy depends on high doses being delivered in a short time. Short treatment times lead to better patient adherence, efficacy and improved health care.

Public Health Relevance Statement:


Public Health Relevance:
Acute respiratory distress syndrome afflicts 50,000 to 90,000 citizens each year. Despite intensive care treatment only 57% survive. This project aims to treat a major underlying cause of this disease, the deficiency of the surfactant in the lungs that enables them to breathe. We will provide the technology to deliver clinically relevant doses of aerosolized surfactant to the lungs of these patients. This will provide a new treatment modality that will improve their ability to breathe and help cure their devastating disease.

NIH Spending Category:
Acute Respiratory Distress Syndrome; Infant Mortality/ (LBW); Lung; Pediatric; Perinatal - Neonatal Respiratory Distress Syndrome; Perinatal Period - Conditions Originating in Perinatal Period; Rare Diseases

Project Terms:
Adult; Adult Respiratory Distress Syndrome; Adverse effects; aerosolized; Aerosols; Aftercare; Air; Alveolar; Alveolus; American; Animal Model; Animals; Anti-inflammatory; Anti-Inflammatory Agents; antimicrobial; aqueous; Asthma; Bolus Infusion; Breathing; Caliber; Carbon Dioxide; Characteristics; Chronic Obstructive Airway Disease; Clinical; clinically relevant; Compliance behavior; cost effective; Cystic Fibrosis; Deficiency Diseases; Deposition; Disease; Dose; empowered; Etiology; evaporation; Event; Gases; Generations; Healthcare; Heating; heliox; Hour; Hypercapnia; improved; Inflammation; Infrared Rays; Intensive Care; Lead; Life; Lipids; Liquid substance; Lung; Lung diseases; Marketing; Metabolism; Microfluidics; Modality; Molecular; Mortality Vital Statistics; neonate; Newborn Respiratory Distress Syndrome; Output; particle; Patients; peptide B; Peripheral; Pharmaceutical Preparations; Phase; Physicians; Physiological; Process; Production; Property; public health relevance; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactants; Reducing Agents; Resistance; Respiratory distress; Solutions; Stream; success; Surface; Surface Tension; surfactant; surfactant deficiency; Suspension substance; Suspensions; System; technological innovation; Technology; Time; treatment duration; virtual

Acute respiratory distress syndrome, ARDS, afflicts about 200,000 Americans each year. The pathology consists of rapid onset of respiratory symptoms including radiographic bilateral opacities and pulmonary edema. The primary risk factors for the development of ARDS are pneumonia, aspiration, major trauma, sepsis, and inhalation injury. Despite the adoption of lung-protective-ventilation, the mortality rate remains about 30-40%. Common to all patients with ARDS is abnormal and sustained degradation of surfactant. The addition of repeated aerosol surfactant replacement therapy is hypothesized to reduce surface tension in the airways and alveoli. This decreases the transpulmonary pressure required to open atelectatic airways and collapsed alveoli with a resultant increase in respiratory capacity, improved gas exchange and the consequent resolution of the hypoxemia together with improved CO2 removal. Patients with ARDS related to a direct insult (e.g. pneumonia, aspiration) could most benefit from surfactant replacement therapy administered early in the course of the clinical syndrome when inflammation is present but prior to the onset of severe lung dysfunction. We propose to develop, manufacture and test alpha versions of SUPRAER- Clinic that, for the first time, enables the treatment of mild, early stage ARDS patients with clinically relevant doses of fine particle aerosols of surfactant prior to the need for these patients to be intubated. SUPRAER-Clinic aerosolizes a viscous surfactant suspension, evaporates water from the aerosol and concentrates this solid phase aerosol prior to its delivery. SUPRAER-Clinic is designed to efficiently and rapidly deliver high doses of these fine particle aerosols to patients with compromised lung function in a clinical setting. SUPRAER-Clinic has the provision for positive pressure respiratory assist to improve peripheral lung deposition of surfactant aerosols in these patients with heterogeneously impaired respiratory function. The development of SUPRAER-Clinic for surfactant will open up the potential for SUPRAER-Clinic to deliver other agents to the lungs, especially those that comprise highly viscosity fluids that are recalcitrant to aerosol delivery by other methods. !

Thesaurus Terms:
Acute; Acute Lung Injury; Address; Adoption; Adult Respiratory Distress Syndrome; Aerosolized; Aerosols; Air; American; Antibiotics; Antineoplastic Agents; Aspiration Pneumonia; Bilateral; Carbon Dioxide; Clinic; Clinical; Clinical Trials; Clinically Relevant; Death Rate; Deposition; Design; Development; Devices; Diagnostic Radiologic Examination; Dose; Dose-Rate; Environmental Air Flow; Esthetics; Excision; Exhalation; Face Mask; Fine Particles; Flexibility; Functional Disorder; Gases; Generations; Health Care Costs; Heliox; Hypoxemia; Impairment; Improved; Inflammation; Inhalation; Injury; Intratracheal Intubation; Liquid Substance; Lung; Lung Injury; Masks; Methods; Mimetics; Mortality; Operation; Oxygen; Pathology; Patients; Peripheral; Pharmaceutical Preparations; Phase; Physical Property; Pneumonia; Pressure; Protein B; Pulmonary Edema; Pump; Resolution; Respiratory; Respiratory Assist; Respiratory Distress; Respiratory Physiology; Respiratory Signs And Symptoms; Risk Factors; Safety; Safety Testing; Sepsis; Severities; Smoke Inhalation; Solid; Surface Tension; Surfactant; Surfactant Replacement; Surfactant Replacement Therapy; Survival Rate; Suspensions; Syndrome; System; Testing; Time; Trauma; Tube; Validation; Viscosity; Water;