Background
The manufacturing of any standard mechanical ventilator cannot rapidly be upscaled to several thousand units per week, largely due to supply chain limitations. The aim of this study was to design, verify and perform a pre-clinical evaluation of a mechanical ventilator based on components not required for standard ventilators, and that met the specifications provided by the Medicines and Healthcare Products Regulatory Agency (MHRA) for rapidly-manufactured ventilator systems (RMVS).
Methods
The design utilises closed-loop negative feedback control, with real-time monitoring and alarms. Using a standard test lung, we determined the difference between delivered and target tidal volume (VT) at respiratory rates between 20 and 29 breaths per minute, and the ventilator's ability to deliver consistent VT during continuous operation for >14 days (RMVS specification). Additionally, four anaesthetised domestic pigs (3 male-1 female) were studied before and after lung injury to provide evidence of the ventilator's functionality, and ability to support spontaneous breathing.
Findings
Continuous operation lasted 23 days, when the greatest difference between delivered and target VT was 10% at inspiratory flow rates
>
825 mL/s. In the pre-clinical evaluation, the VT difference was -1 (-90 to 88) mL [mean (LoA)], and positive end-expiratory pressure (PEEP) difference was -2 (-8 to 4) cmH
2
O. VT delivery being triggered by pressures below PEEP demonstrated spontaneous ventilation support.
Interpretation
The mechanical ventilator presented meets the MHRA therapy standards for RMVS and, being based on largely available components, can be manufactured at scale.
Funding
Work supported by Wellcome/EPSRC Centre for Medical Engineering,King’s Together Fund and Oxford University.
Introduction: In cases of idiopathic pulmonary fibrosis, we have observed an elevation in mean red cell volume, serum gamma glutamyl transferase and peripheral monocyte counts, initially in a pilot study but also in new incident cases. These changes could not be explained by drug therapy, vitamin deficiency or other diseases. Method: We compared the peripheral blood abnormalities in 149 patients with lung fibrosis to 448 age and sex matched controls. We also examined the effect of cotrimoxazole treatment for 12 weeks on these abnormalities. From the pilot study of cotrimoxazole in lung fibrosis patients, the relationship of the peripheral blood monocyte count and serum cytokine transforming growth factor beta-1 was examined. Epstein Barr viral status was examined in a selection of patients in case it explained our observations. Results: The findings confirm the elevation in mean red cell volume, gamma glutamyl transferase and peripheral monocyte counts in patients compared with matched controls. Oral cotrimoxazole ameliorated these 3 blood abnormalities. Serological evidence of Epstein Barr viral infection was present in tested patients but active viral replication was absent. The monocyte count had a linear relationship with the serum transforming growth factor beta-1 levels, which increased by 600 pg/ml for every of 0.1 × 10 9 /l increase in the monocyte count. Conclusion: These observations may reflect oxidative stress which was reduced by cotrimoxazole. A related sulphonamide "dapsone" is known to reduce oxidative stress through direct effects on neutrophil and mo-nocyte function; similar effects may explain these findings and require a formal study.
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