In vitro-in vivo correlation of aerosol deposition before and after metered-dose inhaler coaching in healthy children

Abstract

Although pressurized metered dose inhaler (pMDI) education is a routine part of childhood asthma management and encouraging ‘optimal breathing patterns’ (i.e. slowly, deeply, completely, and with a mouth seal on the mouthpiece) is an integral part of recommended pMDI education, there is currently no quantifiable way to determine if a child is inhaling their medication correctly or optimally through a valved holding chamber (VHC). The TipsHaler™ (tVHC) is a prototype VHC device that measures inspiratory time, flow, and volume without changing the properties of the medication aerosol. The measurements in vivo recorded by the tVHC can be downloaded and transferred to a spontaneous breathing lung model to simulate the inhalational patterns in vitro and also determine the deposition of inhaled aerosol mass with each pattern. We hypothesized that pediatric patients’ inhalational patterns when using a pMDI would improve after active coaching via tVHC. This would increase the pulmonary deposition of inhaled aerosols in an in vitro model. To test this hypothesis, we conducted a single-site, prospective, pilot, pre-and-post intervention study paired with a bedside-to-bench experiment. Healthy, inhaler-naïve subjects used a placebo inhaler in conjunction with the tVHC before and after coaching and recorded inspiratory parameters. These recordings were then implemented into a spontaneous breathing lung model during albuterol MDI delivery, and pulmonary deposition of albuterol was quantified. In this pilot study, active coaching resulted in a statistically significant increase in inspiratory time (n = 8, p= 0.0344, 95%CI: 0.082 to ∞). tVHC recorded inspiratory parameters obtained from patients were successfully implemented in the in vitro model, which demonstrated that both inspiratory time (n = 8, r = 0.78, p < 0.001, 95%CI: 0.47–0.92) and volume (n = 8, r = 0.58, p = 0.0186, 95%CI: 0.15–0.85) strongly correlate with pulmonary deposition of inhaled drugs.