The current study compares the performance of a VMN connected to a HC using a mouthpiece and a valved facemask at various flows ranging from 0 to 6 L/min. The amount of medicine breathed is heavily influenced by the breathing pattern of the patient, the nebulizer, and the interface used for aerosol therapy [2]. We used a HC rather than a T-piece in our investigation since the HC was found to increase the supplied aerosolized dose [1]. The nebulizer is also situated next to the HC, which reduces drug particle deposition due to gravitational sedimentation [1].
Sarhan et al. [14] found that when using a VMN connected to a HC and mouthpiece without oxygen, the delivered dose was significantly higher (p < 0.05) than when using oxygen at a flow of 6 L/min, with values of 2197.7 ± 470.7 µg and 1081.5 ± 333.9 µg, respectively. Similar findings were obtained when using a valved facemask and mouthpiece; however, there was an additional effect when using varied oxygen flows. By increasing the supplied inhalable dose until flow was 2 L/min while using the mouthpiece and 3 L/min when using the valved facemask, we discovered that the flow of oxygen had a significant effect on the delivered dose. Following that, as the oxygen flow increased, the given inhalable dose gradually reduced until it reached its lowest value (1814.5 ± 162.3, and 2128.1 ± 243.1 for mouthpiece and facemask, respectively) when the oxygen flow rate was the maximum (6 L/min) that we investigated (Fig. 3).
Bennett et al. [20] used a VMN linked to a HC with a mouthpiece and valved facemask to quantify the delivered dose using humidified air instead of oxygen at flows of 0, 2, and 6 L/min. The largest inhalable dose was found at flows of 2 L/min for both the mouthpiece and the valved facemask. However, they did not measure the oxygen flows of 1, 3, 4, and 5. Even without these four oxygen flows, their results were comparable to ours. Even though Bennett G and his colleagues [20] used Albuterol 2 mg/ml in much smaller doses, which is different from using salbutamol 5000 µg/ml in the work presented here, this would affect the comparison of the two studies. However, the benefit of the use of the VMN in the study, which allows the nebulization of almost all the nebulized solutions placed in the nebulization chamber overcome, is different [3,4,5,6,7,8,9,10,11,12,13].
Another study tested three oxygen flows (2, 4, and 6 L/min), finding that the oxygen flow of 4 L/min produced the largest inhalable dose [21]. Despite the fact that the flow found differs from ours, this investigation backs up our findings. The only difference was that they discovered a higher oxygen flow than we did. That could be due to their use of a higher tidal volume (750 mL), which is 250 mL higher than the normal tidal volume used in most in vitro studies (500 mL) but more realistic for some adult patients [22,23,24,25,26,27,28,29,30,31,32,33], as well as their use of a valved facemask only, for which we found the best oxygen flow was 3 L/min [21], implying that the higher tidal flow improved the benefit of oxygen delivered as a supplement to the aerosol within the HC.
During the exhale phase, higher oxygen flows may flush the aerosol out of the HC. The aerosol collects in the HC when there is no oxygen flow or when the flow is low and is available to the subjects on inspiration. This HC has a volume of 130 mL. The flow of 6 L/min is equivalent to 100 mL/s. Our breathing simulator was calibrated to a 500-mL tidal volume, and a 1:1 inhalation–exhalation ratio. As a result, most of the saved aerosol in the HC during exhalation would be flushed out before intake with the 2 s expiration, which is equivalent to 200 mL of oxygen. As a result, the higher the oxygen flow rate, the smaller the amount of aerosol retained by the HC between breaths. In light of this discovery, researchers compared inhaled doses across different tidal volumes and flow to see how the inhalable dose correlated. When comparing the results shown here and in Brady et al. study, the effect of tidal volume on delivered aerosol was obvious because they used different tidal volumes, with the best aerosol delivery at 3 L/min in our study using a tidal volume of 500 mL and 4 L/min in Brady et al. study using a tidal volume of 750 mL [21]. The effect of varied oxygen flows is visible in our results, but those in vivo investigations are needed to confirm the findings.
Furthermore, according to our findings, the given dose using oxygen with a valved facemask was much higher than using a mouthpiece. These findings could be related to the valved facemask's large volume of air space for aerosol retention during exhalation compared to the mouthpiece, which allows for less waste of aerosol by the oxygen flow during the exhalation phase of the respiration cycle.
The maximum deposition was reported with no oxygen flow, indicating that not much aerosol remained within the chamber while oxygen was flowing as supplemental to aerosol within the HC, supporting the theory of aerosol flushing by oxygen flow.
4.1 Limitations
A major limitation of the study was that it was in vitro, which limits the clinical relevance of the findings, so we suggest extending this work to clinical studies. Note that oxygen flow is selected for best oxygenation and not for best aerosol delivery. One should never compromise oxygenation to improve aerosol delivery. This methodology was intended to assess product quality and not to evaluate likely performance in patients with varying degrees of lung disease affecting their ability to breathe. Furthermore, the I/E ratio is too short, as values closer to 1:2 are more common, and the expiratory portion may be lengthened with therapy for severe COPD. We use the plate-setting methodology. This might not provide any information about the effect of applying force to the facemask to affect a seal on the face that could have a marked influence on medication transfer to the patient. This study was done using an adult breathing model, and future studies should evaluate the findings as they apply to pediatrics.
