Skip to main content
Beni-Suef University Journal of Basic and Applied Sciences
Download PDF

Effect of pressures and type of ventilation on aerosol delivery to chronic obstructive pulmonary disease patients

Beni-Suef University Journal of Basic and Applied Sciences volume 11, Article number: 57 (2022) Cite this article

Abstract

Background

Continuous Positive Airway Pressure (CPAP), BiPhasic Positive Airway Pressure (BiPAP), and high flow nasal cannula (HFNC) show some evidence to have efficacy in COVID-19 patients. Delivery during noninvasive mechanical ventilation (NIV) or HFNC gives faster and more enhanced clinical effects than when aerosols are given without assisted breath. The present work aimed to compare the effect of BiPhasic Positive Airway Pressure (BiPAP) mode at two different pressures; low BiPAP (Inspiratory Positive Airway Pressure (IPAP)/Expiratory Positive Airway Pressure (EPAP) of 10/5 cm water) and high BiPAP (IPAP/EPAP of 20/5 cm water), with HFNC system on pulmonary and systemic drug delivery of salbutamol. On the first day of the experiment, all patients received 2500 μg salbutamol using Aerogen Solo vibrating mesh nebulizer. Urine samples 30 min post-dose and cumulative urinary salbutamol during the next 24 h were collected on the next day. On the third day, the ex-vivo filter was inserted before the patient to collect the delivered dose to the patient of the 2500 μg salbutamol. Salbutamol was quantified using high-performance liquid chromatography (HPLC).

Results

Low-pressure BiPAP showed the highest amount delivered to the lung after 30 min followed by HFNC then high-pressure BiPAP. But the significant difference was only observed between low and high-pressure BiPAP modes (p = 0.012). Low-pressure BiPAP showed the highest delivered systemic delivery amount followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.017) and high-pressure BiPAP (p = 0.008). No significant difference was reported between HFNC and high-pressure BiPAP. The ex-vivo filter was the greatest in the case of low-pressure BiPAP followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.033) and high-pressure BiPAP (p = 0.008). Also, no significant difference was found between HFNC and high-pressure BiPAP.

Conclusions

Our results of pulmonary, systemic, and ex-vivo drug delivery were found to be consistent. The low BiPAP delivered the highest amount followed by the HFNC then the high BiPAP with the least amount. However, no significant difference was found between HFNC and high BiPAP.

Background

Exacerbated chronic obstructive pulmonary disease (COPD) patients, requesting ventilator support, need to administer medicated aerosols [1, 2]. Aerosols are preferred as a better route that helps in managing pulmonary diseases because it is rapid, allow the use of lower doses, deliver higher doses to lungs, and lower systemic effects [2,3,4,5]. The help of noninvasive mechanical ventilation (NIV) or high flow nasal cannula (HFNC) allows faster and more enhanced clinical effects than when aerosols are given without assisted breath [6]. This is considered of great value for critically ill patients who strongly need respiratory assistance for long periods. [7] Continuous Positive Airway Pressure (CPAP) And Biphasic Positive Airway Pressure (BiPAP)) and HFNC show emerging evidence to have efficacy in COVID-19 patients [8, 9]. Ventilatory support using a facemask and nasal mask ventilation has been greatly studied, used, and found to lower intubation in 60 to 90 percent of acute respiratory failure patients [10,11,12]. Also, HFNC was found to reduce intubation more than NIV and conventional oxygen therapy in patients with acute respiratory failure [13]. That helps in better oxygen delivery [14].

Nasal cannulas were used as an alternative to NIV [15], with nearly the same efficacy but fewer side effects and invasion [16, 17], due to their probable disadvantages of the facemask, e.g. skin damage, eyes irritation, decreased tolerance of interface, and interrupting expectoration, food, and speech [13, 18, 19]. Firstly, the traditional nasal cannula was used at low flow rates of oxygen up to 6 L/min. Nowadays, the HFNC system is used at high flow rates with satisfying results [7, 20,21,22]. HFNC lessens oxygen dilution with respiratory dead space and some positive airway pressure that is provided. In addition, the heated humidification helps in secretions' clearance and reduces the risk of bronchial hyper-response symptoms [14]. Also, humidity prevents airways dehydration which causes airway bronchospasm [23]. Aerosol delivery during noninvasive mechanical ventilation (NIV) or HFNC gives faster and more enhanced clinical effects than when aerosols are given without assisted breath. The current study aimed to compare BiPAP mode, at two different pressures, with HFNC in drug delivery in an attempt to find out which would be more beneficial and to help dose adjustment when the change from one mode to another.

Methods

In-vivo

The study was approved by the ''Research Ethical Committee'' of the Faculty of Pharmacy, Beni-Suef University (REC-H-PhBSU-18003). All participants signed a written informed consent. Thirty-six patients were admitted to Beni-Suef University Hospital with acute exacerbated COPD. They were randomly selected, by simple randomization using an online website (https://www.randomizer.org/). They were randomly subdivided into 3 groups; 12 patients on low-pressure BiPAP (Inspiratory Positive Airway Pressure (IPAP)/Expiratory Positive Airway Pressure (EPAP) 10/5 cm water), 12 patients on high-pressure BiPAP (IPAP/EPAP 20/5 cm water), and the 12 patients on HFNC at the flow of 5L/min. Heart Rate (HR) and Respiratory Rate (RR) were recorded before the dose. They all received 2500 μg salbutamol (Farcolin respiratory solution, 5000 μg/ml; Pharco Pharmaceuticals, Cairo, Egypt) using Aerogen Solo vibrating mesh nebulizer (SOLO; Aerogen Limited, Ireland). All the patients did not take the salbutamol dose for 48 h before the tested dose to ensure drug washout from the body. Instead, they used Ipratropium bromide (Atrovent Inhalation Solution, 2500 μg/ml, Boehringer Ingelheim, Egypt) to alleviate the bronchoconstriction. In the case of the two BiPAP groups, SOLO was inserted in the inspiratory limb (Fig. 1) [24]. The adjustment of the bi-level ventilator (Bellavista 1000e, Imtmedical, Buchs, Switzerland) was at BiPAP using the two different pressures listed above. The SOLO was inserted upstream before the humidifier (MR810 Fisher& Paykel, Fisher& Paykel Healthcare Limited, New Zealand) (Fig. 2) [25, 26] in case of using HFNC. A mixture of oxygen and room air was supplied from the gas wall supply at a low flow of 5 L/min [25, 27]. The dose was given to each patient on day 1. Urine samples were collected 30 min post-dose and cumulatively within the next 24 h post-dose indicating the pulmonary and systemic absorption, respectively. The amount of salbutamol in urine samples was collected by solid-phase extraction and then quantified by HPLC [28, 29]. The HR and RR were recorded 30 min post-dose.

Fig. 1
figure 1

Schematic diagram of in-vivo setting showing the position of the aerosol generator in case of using BiPAP circuit. Edited from [30]

Full size image
Fig. 2
figure 2

Schematic diagram of in-vivo setting showing the position of the aerosol generator in case of using HFNC circuit. [17]

Full size image

On day 3, the ex-vivo study was conducted. Using the same setting except a filter placed in a filter holder (Pari GmbH, Starnberg, Germany) connected to the nasal cannula, in case of HFNC, and before the patient face mask in case of BiPAP groups. Salbutamol was collected from each filter by sonication with 20% acetonitrile and quantified by high-performance liquid chromatography (HPLC) [28, 30].

Patients were excluded if taking beta-blockers, other sympathomimetics or non-potassium sparing diuretics, pregnant females, pediatrics, having hypersensitivity to salbutamol, or suffering moderate or severe renal impairment defined as creatinine clearance or GFR of < 20 ml/min.

Ex vivo method

The Ex-vivo study was conducted during the salbutamol wash-out period on day 2 of the study. subjects received the same dosing with the same condition performed in the in-vivo method of the previous day, but with electrostatic filter (Filta Guard breathing filter, Intersurgical, Wokingham, United Kingdom) enclosed in a filter holder (Pari GmbH, Starnberg, Germany) placed between the patient and the NIV circuit to entrap the whole inhalable dose that could reach the subject.

In the in-vivo and ex-vivo methods, nebulization was continued till no aerosol detected. Salbutamol, collected on the filter and pointed out as the total emitted dose (TED), was recovered with sonication and rinsing the filter with 25% acetonitrile (Sigma-Aldrich Chemie Gmbh, Steinheim, Germany). All collected samples were assayed by HPLC. A 4.6 × 25 mm Zobrax Eclipse as well as C18, ODS1 column (Agilent) was utilized. A mobile phase composing of a mix of acetonitrile and water with 0.1% orthophosphoric acid (90:10 v/v) was pumped through the column at a flow rate of 1 ml/min by Infinity preparative pump (G1361A, Agilent 1260). Infinity photodiode array detector VL (Agilent 1260, G131SD) was set at 225 nm with 100 µl as an injection volume. Calibration solutions from 4 to 100 µg/ml (w/v) were provided. The detection limit was 0.35 µg/ml, while the lower limit of quantification was 2.55 µg/ml [28].

Outcome measurements

The primary outcome was the measurement of the salbutamol delivered to the lung and the body. The secondary outcome was dose adjustment when changes from one pressure to another on BiPAP or when using a nasal cannula.

Statistical analysis

The target sample size was calculated with the power of study of 0.95, an effect size of 0.69, and an alpha value of 0.05 in which a total sample size of 36 patients (12 patients in each group) was determined as a minimum sample size using G Power.) [31].

All data are expressed as mean ± SD. One-way analysis of variance (ANOVA) with the application of least significant difference (LSD) correction was used to compare the drug delivery (30 min, 24 h urine samples, and ex-vivo delivery), baseline and 30 min post-dose patients' HR and RR and the change in HR between the three different techniques. Kruskal–Wallis Test was used to compare the change in RR between the three techniques. Paired t-test was used to compare the 30 min post-dose HR and RR to the baseline ones. All tests were done with SPSSV17.0 (SPSS Inc., Chicago, USA). Statistical significance was taken at a 95% confidence interval (p ≤ 0.05).

Results

Forty-four patients participated in the study, eight of them did not complete the study, and thirty-six patients completed it. Their body mass index (BMI) and age expressed as mean ± SD are shown in Table.1. No significant difference was found in the patients' BMI or age.

Table 1 Body Mass Index (BMI) (kg/m2) and age (years) of the patients who participated in the study (n = 12). Values are expressed as mean ± SD
Full size table

Table 2 shows the baseline and 30 min post-dose HR and RR using each technique. No significant difference was found between the three modes in the baseline or 30 min post-dose HR or RR. HR significantly increased and RR significantly decreased (p < 0.001), in all three modes 30 min post-dose compared to baseline. Low BiPAP decreased the RR (mean ± SD 3.33 + 1.07) followed by HFNC (mean ± SD 3.25 + 0.96) then high BiPAP (mean ± SD 2.92 + 0.79) with no significant difference. Low BiPAP increased HR the most (mean ± SD 3.33 + 1.49) followed by high BiPAP (mean ± SD 3.25 + 1.76) then HFNC (mean ± SD 2.58 + 0.90) with no significant difference between the three modes.

Table 2 Baseline and 30 min post-dose heart rate (HR) (beat/min) and respiratory rate (RR) (breath/min) of the patients who participated in the study (n = 12)
Full size table

As shown in Table 3, low-pressure BiPAP showed the highest amount delivered to the lung after 30 min followed by HFNC then high-pressure BiPAP. But the significant difference was only observed between low and high-pressure BiPAP modes (p = 0.012). Concerning the systemic delivery, low-pressure BiPAP showed the highest delivered amount followed by HFNC then high-pressure BiPAP as illustrated in Table 3. Low-pressure BiPAP was significantly higher than HFNC (p = 0.017) and high-pressure BiPAP (p = 0.008). No significant difference was reported between HFNC and high-pressure BiPAP.

Table 3 The amount of salbutamol (µg) collected in urine samples 30 min and within 24 h post sample and on ex-vivo filter (n = 12). Values are expressed as mean ± SD
Full size table

Table 3 shows that the amount of drug collected on the ex-vivo filter was the greatest in the case of low-pressure BiPAP followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.033) and high-pressure BiPAP (p = 0.008). Also, no significant difference was found between HFNC and high-pressure BiPAP.

Discussion

Drug delivery during oxygen therapy can offer great help to patients who may be affected if the circuit is disconnected and improve tolerance [25, 26, 32, 33]. Also, when the drug is delivered during assisted breathing, it shows enhancement in the clinical effects in a faster way [5, 7]. The SOLO nebulizer was inserted in the Y limb, in case of using BiPAP modes, to provide the highest delivery [24, 29].

In the current study, the results of pulmonary, systemic, and ex-vivo drug delivery were all found to be consistent. Generally, low BiPAP delivered the highest amount followed by HFNC then high BiPAP with the least amount. However, no significant difference was found between HFNC and high BiPAP in drug delivery. These results of the present study match the results of our in-vitro study (in press) in which the total inhalable dose(TID) and Fine Particle Dose (FPD) were the greatest using low BiPAP followed by HFNC then high BiPAP with the least amount [34].

Increasing IPAP caused a reduction in the amount of drug delivered either to the lung, systemic circulation or deposited on an ex-vivo filter. This is supported by the results found by Velasco and Berlinski [24] who found that increasing IPAP decreased the drug delivery efficiency either if SOLO was inserted before the mask, before the Y-piece, and at the ventilator.

In contrast, Chatmongkolchart, et al. [35] revealed that increasing IPAP increased the drug delivery if a nebulizer was inserted distal from the BiPAP ventilator (proximal to the lung model). This may be due to the usage of a single limb ventilator with the nebulizer inserted between the exhalation port and the lung model in their study. Consequently, there was a retrograde return. However, in the same study of Chatmongkolchart, et al., in accordance with our study, they reported that increasing BiPAP decreased the drug delivery [36].

L'Her et al. found that oxygenation improved when positive end-expiratory pressure (PEEP) was increased from 5 to 10 cm H2O, also dyspnea showed the best enhancement by increasing pressure support (PS) from 10 to 15 cm H2O [37]. However, their study did not include quantification of the drug delivered.

Pressure support ventilation (PSV) is a positive airway pressure, detected by a clinician, assisted by a mechanical ventilator for the patient's spontaneous inspiratory efforts like IPAP [38]. L'Her et al. found that when PS increases, dyspnea is improved as mentioned formerly. In the present study, using IPAP generally improved RR, but there was no significant difference between low and high BiPAP in improving RR.

The PEEP is the positive pressure that remains in the airways at the end of exhalation [39] like EPAP. It helps in recruitment and stabilization of collapsed lung tissue [37, 40], a decrease of alveolar stress [40] and the effort required of mechanically ventilated patients [41] and enhancement of gas exchange [42] so enhances oxygenation [43, 44]. This can be due to that sufficient PEEP helps to evacuate the circuit from the expired CO2, preventing rebreathing, out to the atmosphere with the aid of enough time of expiration [45].

Consequently, there must be a careful choice whether to increase the PEEP level for enhanced oxygenation or to increase the PSV level for improved dyspnea and reduced respiratory muscle effort [37]. So, we recommend further studies comparing the effect of increasing EPAP while holding IPAP.

The HFNC system was earlier found to enhance all respiratory parameters and oxygenation and be well tolerated when used for long periods than traditional facemasks [14, 46]. The more the oxygen flow in the HFNC system, the better the oxygenation would be [14, 47].

Both Ari et al. [27] and Perry et al. [32] found that increasing the flow of the HFNC system caused a reduction in the drug delivery and the best flow that was found for adults was 5 L min−1. So, in the current study, oxygen was delivered at that low flow of 5 L min−1.

The HFNC system, compared to low BiPAP, delivered a lower amount of the drug. The heated humidified circuit used in HFNC leads to aerosol condensation within the circuit and loss which was augmented by the smaller diameter and longer length of nasal cannula over the BiPAP circuit [26, 32, 48, 49]. Also, when comparing nasal to mask delivery, aerosol particles are filtered more efficiently through the nose, than the mouth, leading to a reduction in the dose available to penetrate the lower respiratory tract [50]. In addition, the turbulent gas flow in the nose and rhino-pharynx may favor drug deposition decreasing the amount of drug that can reach the lungs [25, 49].

On the other hand, deposition of the large particles of aerosol in the HFNC circuit decreases the delivered dose, improves tolerance. In this way, it decreases the deposition of these large particles on the face (potentially including eyes) and upper airways which happens when using facemasks [51]. Also, it shows a better-tolerated technique than facemasks [52] which may cause the feeling of confining, coldness, irritation, preventing communication and oral intake, that may be needed to act as a worn for long periods that may lead to, especially in children, fussing, crying, and screaming so reduced aerosol lung deposition, unlike HFNC circuit, humidified and heated conditions which improves patient comfort, may improve lung deposition and increase tolerance to use for long periods [51, 52].

In the present study, the percentage of the amount of drug delivered to the patient by low BiPAP, high BiPAP, and HFNC after 30 min were 0.932, 0.649, and 0.742% of the nominal dose, respectively. The cumulative percent of the amount within 24 h delivered to the patient by low BiPAP, high BiPAP, and HFNC were 10.883, 6.488, and 6.947% of the nominal dose, respectively. The former data were found to be greatly lower than the percentage of the amount collected from the ex-vivo filter; 42.052, 29.906, and 32.512% of nominal dose delivered by low BiPAP, high BiPAP, and HFNC, respectively. That could be because the particles less than 1 µm cannot deposit in the lung unless the patients hold his breath for 5–10 s [32, 53, 54] and since this patient could not make a 5–10 s breath-hold to get deposited most of the aerosol less than 1 µm was exhaled [7]. Also, the aerosol particles produced by the SOLO of 5 μm and above decreases the percent that would reach the lung as particle sizes of 1–3 μm [54,55,56].

Although low BiPAP delivered the highest amount of aerosol to the lung indicating better efficacy, it also delivered the highest amount systemically, so more side effects can occur to the patients [1]. The results of the current study can help in dose adjustment when changing from one technique to another. Depending on pulmonary drug delivery results, the amount of salbutamol delivered to the lung using 2.50 mg salbutamol on low BiPAP mode was equivalent to the amount delivered using 3.59 mg salbutamol on high BiPAP mode and to the amount delivered using 3.14 mg salbutamol on HFNC mode. Depending on systemic drug delivery results, the amount of salbutamol delivered to the body using 2.50 mg salbutamol delivered on low BiPAP mode was equivalent to the amount delivered using 4.19 mg salbutamol on high BiPAP mode and to the amount delivered using 3.92 mg salbutamol on HFNC mode.

Consequently, dose adjustment guidelines must be developed to be used when changing from one technique to another. If similar doses are used, there may not be of clinical difference in the bronchodilation but patient safety may be affected due to change in systemic delivery [29].

In accordance with the present study results, the HFNC reduced respiratory rate efficiently in Corley et al. [57], Bell et al. [58], Makdee et al. [59] studies. Also, Sztrymf et al. [46] reported that breathing frequency decreased significantly when using HFNC. In addition, Vargas et al. [60] revealed breathing frequency decrease too when HFNC was used in acute hypoxemic respiratory failure, which can be attributed to the reduction of breathing work and enhancement of oxygenation.

The present study results showed that all the three techniques improved RR significantly from the baseline, but no significant difference was found between the three techniques. On the other hand, in Schwabbauer et al. studied [61], HFNC significantly improved RR than NIV. This can be attributed to the difference in the conditions from the current study. They used HFNC at gas flow 55 L/min which was much greater than the current study.

Limitations

Spirometry pre- and post-dose could not be measured because interruption of ventilator support during mechanical ventilation is not possible in our institution.

Conclusions

Aerosols delivery simultaneously during NIV or HFNC can help greatly in patients who may be affected if the circuit is disconnected and improves tolerance. HFNC was found to improve tolerance and give comparable results to low-pressure BIPAP mode. Increasing IPAP was found to decrease both the pulmonary and systemic delivered dose. Consequently, there must be a careful dose adjustment when changing the pressure levels used in BiPAP or when using the HFNC system. All three techniques were found to improve RR significantly from baseline dose, but no significant difference was found between the three techniques. Further studies are recommended to test the effect of increasing EPAP on the amount of delivered dose.

Availability of data and materials

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BiPAP:

BiPhasic Positive Airway pressure

IPAP:

Inspiratory Positive Airway Pressure

EPAP:

Expiratory Positive Airway Pressure

NIV:

Noninvasive mechanical ventilation

HFNC:

High flow nasal cannula

HPLC:

High-performance liquid chromatography

COPD:

Chronic obstructive pulmonary disease

HR:

Heart Rate

RR:

Respiratory Rate

SOLO:

Aerogen Solo vibrating mesh nebulizer

BMI:

Body mass index

References

  1. Harb HS, Elberry AA, Rabea H et al (2018) Performance of large spacer versus nebulizer T-piece in single-limb noninvasive ventilation. Respir Care 63(11):1360–1369

    Article  PubMed  Google Scholar 

  2. Labiris NR, Dolovich MB (2003) Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 56(6):588–599

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Larsson S, Svedmyr N (1977) Bronchodilating effect and side effects of beta2-adrenoceptor stimulants by different modes of administration (tablets, metered aerosol, and combinations thereof) a study with salbutamol in asthmatics. Am Rev Respir Dis 116(5):861–869

    CAS  PubMed  Google Scholar 

  4. Darquenne C (2012) Aerosol deposition in health and disease. J Aerosol Med Pulm Drug Deliv 25(3):140–147

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Duarte AG (2004) Inhaled bronchodilator administration during mechanical ventilation. Respir Care 49(6):623–634

    PubMed  Google Scholar 

  6. Michotte J-B, Jossen E, Roeseler J et al (2014) In vitro comparison of five nebulizers during noninvasive ventilation: analysis of inhaled and lost doses. J Aerosol Med Pulm Drug Deliv 27(6):430–440

    CAS  Article  PubMed  Google Scholar 

  7. Harb HS, Saeed H, Madney YM et al (2020) Update efficacy of aerosol therapy with noninvasive ventilator approach (non-invasive ventilation and nasal high flow). J Drug Deliv Sci Technol 59:101922

    CAS  Article  Google Scholar 

  8. Hamilton FW, Gregson FK, Arnold DT et al (2022) Aerosol emission from the respiratory tract: an analysis of aerosol generation from oxygen delivery systems. Thorax 77(3):276–282

    Article  PubMed  Google Scholar 

  9. Carter C, Aedy H, Notter J (2020) COVID-19 disease: Non-invasive ventilation and high frequency nasal oxygenation. Clin Integr Care 1:100006

    Article  Google Scholar 

  10. Pennock BE, Crawshaw L, Kaplan PD (1994) Noninvasive nasal mask ventilation for acute respiratory failure: institution of a new therapeutic technology for routine use. Chest 105(2):441–444

    CAS  Article  PubMed  Google Scholar 

  11. Pennock BE, Kaplan PD, Carlin BW et al (1991) Pressure support ventilation with a simplified ventilatory support system administered with a nasal mask in patients with respiratory failure. Chest 100(5):1371–1376

    CAS  Article  PubMed  Google Scholar 

  12. Wysocki M, Tric L, Wolff MA et al (1993) Noninvasive pressure support ventilation in patients with acute respiratory failure. Chest 103(3):907–913

    CAS  Article  PubMed  Google Scholar 

  13. Ni Y-N, Luo J, Yu H et al (2017) Can high-flow nasal cannula reduce the rate of endotracheal intubation in adult patients with acute respiratory failure compared with conventional oxygen therapy and noninvasive positive pressure ventilation?: a systematic review and meta-analysis. Chest 151(4):764–775

    Article  PubMed  Google Scholar 

  14. Roca O, Riera J, Torres F et al (2010) High-flow oxygen therapy in acute respiratory failure. Respir Care 55(4):408–413

    PubMed  Google Scholar 

  15. Nishimura M (2015) High-flow nasal cannula oxygen therapy in adults. J Intensive Care 3(1):1–8

    Article  Google Scholar 

  16. Nishimura M (2019) High-flow nasal cannula oxygen therapy devices. Respir Care 64(6):735–742

    Article  PubMed  Google Scholar 

  17. Madney YM, Laz NI, Elberry AA et al (2020) Aerosol delivery aspects within a high flow therapy system in chronic obstructive pulmonary disease patients. ERJ Open Res. https://doi.org/10.1183/23120541.00422-2020

    Article  PubMed  PubMed Central  Google Scholar 

  18. Madney YM, Fathy M, Elberry AA et al (2017) Nebulizers and spacers for aerosol delivery through adult nasal cannula at low oxygen flow rate: an in-vitro study. J Drug Deliv Sci Technol 39:260–265

    CAS  Article  Google Scholar 

  19. Ward JJ (2013) High-flow oxygen administration by nasal cannula for adult and perinatal patients. Respir Care 58(1):98–122

    Article  PubMed  Google Scholar 

  20. Dewan NA, Bell CW (1994) Effect of low flow and high flow oxygen delivery on exercise tolerance and sensation of dyspnea: a study comparing the transtracheal catheter and nasal prongs. Chest 105(4):1061–1065

    CAS  Article  PubMed  Google Scholar 

  21. Dysart K, Miller TL, Wolfson MR et al (2009) Research in high flow therapy: mechanisms of action. Respir Med 103(10):1400–1405

    Article  PubMed  Google Scholar 

  22. Gotera C, Lobato SD, Pinto T et al (2013) Clinical evidence on high flow oxygen therapy and active humidification in adults. Rev Port Pneumol 19(5):217–227

    CAS  Article  PubMed  Google Scholar 

  23. Moloney E, O’Sullivan S, Hogan T et al (2002) Airway dehydration: a therapeutic target in asthma? Chest 121(6):1806–1811

    Article  PubMed  Google Scholar 

  24. Velasco J, Berlinski A (2018) Albuterol delivery efficiency in a pediatric model of noninvasive ventilation with double-limb circuit. Respir Care 63(2):141–146

    Article  PubMed  Google Scholar 

  25. Réminiac F, Vecellio L, Heuzé-Vourc’h N et al (2016) Aerosol therapy in adults receiving high flow nasal cannula oxygen therapy. J Aerosol Med Pulm Drug Deliv 29(2):134–141

    Article  CAS  PubMed  Google Scholar 

  26. Madney YM, Laz NI, Elberry AA et al (2020) The influence of changing interfaces on aerosol delivery within high flow oxygen setting in adults: an in-vitro study. J Drug Deliv Sci Technol 55:101365

    CAS  Article  Google Scholar 

  27. Ari A, Harwood R, Sheard M et al (2011) In vitro comparison of heliox and oxygen in aerosol delivery using pediatric high flow nasal cannula. Pediatr Pulmonol 46(8):795–801

    Article  PubMed  Google Scholar 

  28. Abdelrahman MM (2018) Solid-phase extraction and HPLC-DAD for determination of salbutamol in urine samples. Anal Chem Lett 8(1):35–45

    CAS  Article  Google Scholar 

  29. ElHansy MH, Boules ME, El Essawy AFM et al (2017) Inhaled salbutamol dose delivered by jet nebulizer, vibrating mesh nebulizer and metered dose inhaler with spacer during invasive mechanical ventilation. Pulm Pharmacol Ther 45:159–163

    CAS  Article  PubMed  Google Scholar 

  30. ElHansy MH, Boules ME, Farid H et al (2017) In vitro aerodynamic characteristics of aerosol delivered from different inhalation methods in mechanical ventilation. Pharm Dev Technol 22(6):844–849

    CAS  Article  PubMed  Google Scholar 

  31. Faul F, Erdfelder E, Buchner A et al (2009) Statistical power analyses using G* Power 3.1: tests for correlation and regression analyses. Behav Res Methods 41(4):1149–1160

    Article  PubMed  Google Scholar 

  32. Perry SA, Kesser KC, Geller DE et al (2013) Influences of cannula size and flow rate on aerosol drug delivery through the Vapotherm humidified high-flow nasal cannula system. Pediatr Crit Care Med 14(5):e250–e256

    Article  PubMed  Google Scholar 

  33. Madney YM, Fathy M, Elberry AA et al (2019) Aerosol delivery through an adult high-flow nasal cannula circuit using low-flow oxygen. Respir Care 64(4):453–461

    Article  PubMed  Google Scholar 

  34. Marina EB, Nabila IL, Ahmed AE et al (2021) Aerosol delivery through high flow nasal cannula compared to biphasic positive airway pressure, at two different pressure: an in-vitro study. Beni-Suef Univ J Basic Appl Sci 10(1):1–8 (in press)

    Article  Google Scholar 

  35. Chatmongkolchart S, Schettino GP, Dillman C et al (2002) In vitro evaluation of aerosol bronchodilator delivery during noninvasive positive pressure ventilation: effect of ventilator settings and nebulizer position. Crit Care Med 30(11):2515–2519

    Article  PubMed  Google Scholar 

  36. Hassan A, Rabea H, Hussein RR et al (2016) In-vitro characterization of the aerosolized dose during non-invasive automatic continuous positive airway pressure ventilation. Pulmonary Therapy 2:115–126

    Article  Google Scholar 

  37. L’Her E, Deye N, Lellouche F et al (2005) Physiologic effects of noninvasive ventilation during acute lung injury. Am J Respir Crit Care Med 172(9):1112–1118

    Article  PubMed  Google Scholar 

  38. MacIntyre NR (1986) Respiratory function during pressure support ventilation. Chest 89(5):677–683

    CAS  Article  PubMed  Google Scholar 

  39. Acosta P, Santisbon E, Varon J (2007) The use of positive end-expiratory pressure in mechanical ventilation. Crit Care Clin 23(2):251–261

    Article  PubMed  Google Scholar 

  40. Goligher EC, Kavanagh BP, Rubenfeld GD et al (2014) Oxygenation response to positive end-expiratory pressure predicts mortality in acute respiratory distress syndrome. A secondary analysis of the LOVS and ExPress trials. Am J Respir Crit Care Med 190(1):70–76

    Article  PubMed  Google Scholar 

  41. Smith TC, Marini JJ (1988) Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction. J Appl Physiol 65(4):1488–1499

    CAS  Article  PubMed  Google Scholar 

  42. Di Marco F, Devaquet J, Lyazidi A et al (2010) Positive end-expiratory pressure-induced functional recruitment in patients with acute respiratory distress syndrome. Crit Care Med 38(1):127–132

    Article  PubMed  Google Scholar 

  43. Michelet P, Roch A, Brousse D et al (2005) Effects of PEEP on oxygenation and respiratory mechanics during one-lung ventilation. Br J Anaesth 95(2):267–273

    CAS  Article  PubMed  Google Scholar 

  44. Glérant J-C, Leleu O, Rose D et al (2005) Oxygen consumption and PEEPe in ventilated COPD patients. Respir Physiol Neurobiol 146(2–3):117–124

    Article  PubMed  Google Scholar 

  45. Lofaso F, Brochard L, Touchard D et al (1995) Evaluation of carbon dioxide rebreathing during pressure support ventilation with airway management system (BiPAP) devices. Chest 108(3):772–778

    CAS  Article  PubMed  Google Scholar 

  46. Sztrymf B, Messika J, Mayot T et al (2012) Impact of high-flow nasal cannula oxygen therapy on intensive care unit patients with acute respiratory failure: a prospective observational study. J Crit Care 27(3):324.e9-324.e13

    Article  Google Scholar 

  47. Wettstein RB, Shelledy DC, Peters JI (2005) Delivered oxygen concentrations using low-flow and high-flow nasal cannulas. Respir Care 50(5):604–609

    PubMed  Google Scholar 

  48. Dhand R (2008) Aerosol delivery during mechanical ventilation: from basic techniques to new devices. J Aerosol Med Pulm Drug Deliv 21(1):45–60

    Article  PubMed  Google Scholar 

  49. Fink JB, Dhand R, Grychowski J et al (1999) Reconciling in vitro and in vivo measurements of aerosol delivery from a metered-dose inhaler during mechanical ventilation and defining efficiency-enhancing factors. Am J Respir Crit Care Med 159(1):63–68

    CAS  Article  PubMed  Google Scholar 

  50. Bennett WD, Zeman KL, Jarabek AM (2007) Nasal contribution to breathing and fine particle deposition in children versus adults. J Toxicol Environ Health A 71(3):227–237

    Article  CAS  Google Scholar 

  51. Réminiac F, Vecellio L, Loughlin RM et al (2017) Nasal high flow nebulization in infants and toddlers: an in vitro and in vivo scintigraphic study. Pediatr Pulmonol 52(3):337–344

    Article  PubMed  Google Scholar 

  52. Parke RL, McGuinness SP, Eccleston ML (2011) A preliminary randomized controlled trial to assess effectiveness of nasal high-flow oxygen in intensive care patients. Respir Care 56(3):265–270

    Article  PubMed  Google Scholar 

  53. Heyder J, Gebhart J, Rudolf G et al (1986) Deposition of particles in the human respiratory tract in the size range 0.005–15 μm. J Aerosol Sci 17(5):811–825

    Article  Google Scholar 

  54. Newhouse MT (1998) The current laboratory determination of “respirable mass” is not clinically relevant. J Aerosol Med 11(s1):S-122-S-132

    Article  Google Scholar 

  55. Bhashyam AR, Wolf MT, Marcinkowski AL et al (2008) Aerosol delivery through nasal cannulas: an in vitro study. J Aerosol Med Pulm Drug Deliv 21(2):181–188

    CAS  Article  PubMed  Google Scholar 

  56. Zanen P, Go LT, Lammers J-WJ (1994) The optimal particle size for β-adrenergic aerosols in mild asthmatics. Int J Pharm 107(3):211–217

    CAS  Article  Google Scholar 

  57. Corley A, Caruana LR, Barnett AG et al (2011) Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth 107(6):998–1004

    CAS  Article  PubMed  Google Scholar 

  58. Bell N, Hutchinson CL, Green TC et al (2015) Randomised control trial of humidified high flow nasal cannulae versus standard oxygen in the emergency department. Emerg Med Australas 27(6):537–541

    Article  PubMed  Google Scholar 

  59. Makdee O, Monsomboon A, Surabenjawong U et al (2017) High-flow nasal cannula versus conventional oxygen therapy in emergency department patients with cardiogenic pulmonary edema: a randomized controlled trial. Ann Emerg Med 70(4):465–472

    Article  PubMed  Google Scholar 

  60. Vargas F, Saint-Leger M, Boyer A et al (2015) Physiologic effects of high-flow nasal cannula oxygen in critical care subjects. Respir Care 60(10):1369–1376

    Article  PubMed  Google Scholar 

  61. Schwabbauer N, Berg B, Blumenstock G et al (2014) Nasal high–flow oxygen therapy in patients with hypoxic respiratory failure: effect on functional and subjective respiratory parameters compared to conventional oxygen therapy and non-invasive ventilation (NIV). BMC Anesthesiol 14(1):1–7

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

There was no external funding for this study itself. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Author information

Authors and Affiliations

  1. Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt

    Marina E. Boules, Raghda R. S. Hussein & Mohamed E. A. Abdelrahim

  2. Department of Chest Diseases, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

    Nabila Ibrahim Laz

  3. Clinical Pharmacology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

    Ahmed A. Elberry

  4. Clinical Pharmacy Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt

    Raghda R. S. Hussein

Authors
  1. Marina E. Boules
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nabila Ibrahim Laz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed A. Elberry
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raghda R. S. Hussein
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohamed E. A. Abdelrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: MA, and NL. Administrative support: All authors. Provision of study materials: All authors. Collection and assembly of data: ME. Data analysis and interpretation: ME. Manuscript writing: ME. Final approval of manuscript: All authors. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Mohamed E. A. Abdelrahim.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the Research Ethical Committee of the Faculty of Pharmacy, Beni-Suef University (REC-H-PhBSU-18003). All participants signed a written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Boules, M.E., Laz, N.I., Elberry, A.A. et al. Effect of pressures and type of ventilation on aerosol delivery to chronic obstructive pulmonary disease patients. Beni-Suef Univ J Basic Appl Sci 11, 57 (2022). https://doi.org/10.1186/s43088-022-00234-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s43088-022-00234-y

Keywords

  • Chronic obstructive pulmonary disease, oxygen therapy
  • Nasal cannula
  • Biphasic Positive Airway Pressure
  • Inspiratory pressure