Comparison of Aerosol Deposition Between a Cynomolgus Macaque and a 3D Printed Cast Model of the Animal.

PURPOSE: Preclinical aerosol studies using animals are essential for evaluating toxic or therapeutic effects on human respiratory tract. Macaques are relevant animal models for respiratory studies, but they are sensitive, expensive and difficult-to-access. METHODS: In the context of preliminary studies before animal experiments, we set up an alternative in vitro anatomical model of macaque airways to reduce, refine and replace (3Rs) the animals. We printed an in vitro anatomical cast until the third bronchial division from X-ray computed tomography data of a healthy cynomolgus macaque. This in vitro model was then connected to a respiratory pump to mimic macaque's breathing. We assessed the relevance of this in vitro model, by comparing aerosol deposition patterns obtained with the anatomical model and in three macaques using planar gamma camera imaging. DTPA-99mTechnetium aerosols were produced using three jet nebulizers, generating three different particle sizes: 13.1, 3.2 and 0.93 µm in terms of the mass median aerodynamic diameter (MMAD). RESULTS: The data showed no statistical differences between the animal and anatomical in vitro models in terms of total aerosol deposited in the airways. However, the distribution of the deposition in the airways showed a higher deposited fraction in the upper respiratory tract in the animals than the in vitro model for all particle sizes. CONCLUSIONS: The anatomical printed model appears to be a relevant in vitro tool to predict total aerosol deposition in macaque airways.

Validation of Strasbourg environmental exposure chamber (EEC) ALYATEC® in mite allergic subjects with asthma.

Objective: Environmental Exposure Chamber (EEC) should have standardized and controlled allergenic and non-allergenic exposures to perform reproducible clinical studies. The aim was to demonstrate that mite exposure in the Alyatec® EEC could induce early (EAR) and/or late asthmatic reactions (LAR) in at least 60% of subjects allergic to mite.Methods: The EEC has a volume of 147-m3 with 20 seats. The nebulized particle number, airborne Der p1, endotoxins, and volatile organic compound (VOC) concentrations were measured. Twenty-four asthmatics allergic to mite were randomly exposed to 15, 25, and 46 ng/m3 Der p1. Specificity was assessed in not mite-sensitized asthmatics.Results: No significant endotoxin or VOC contamination was measured. The mean inter-assay CVs were 12.5% for the airborne particle number and 28.7% for airborne Der p1 concentrations. For the three Der p1 concentrations, at least 88% of the subjects developed EAR and/or LAR, and at least 46% developed a dual response. No reaction occurred with placebo or in the control group. No severe bronchial reaction occurred.Conclusions: The Alyatec® EEC demonstrated a tight control of allergenic and non-allergenic exposures. The EEC was clinically validated, with airborne Der p1 levels close to levels found in natural settings.

Intra-tracheal amikacin spray delivery in healthy mechanically ventilated piglets.

BACKGROUND: Nebulization during mechanical ventilation is impeded by large extra-pulmonary drug deposition and long administration durations which currently limit implementation of inhaled antibiotic therapy. Direct intra-tracheal delivery using a sprayer represents an appealing alternative investigated in small animal models, but large animal data are lacking. METHODS: Amikacin was administered through intravenous infusion (20 mg/kg), nebulization (60 mg/kg) and direct intra-tracheal spray (30 mg/kg) to 10 intubated piglets, in a randomized cross-over design. Amikacin concentrations were measured in the serum and pulmonary parenchyma. Anatomic deposition was investigated using immuno-histochemistry. RESULTS: Spray delivery resulted in higher amikacin outputs than nebulization and infusion. Pulmonary inhaled delivery techniques yielded much higher lung concentrations and much lower serum concentrations than intravenous infusion. However, unlike nebulization and infusion, intra-tracheal spray delivery was associated with more than 100- and 1000-fold variability in lung concentrations between and within animals. Amikacin specific immuno-histochemistry showed consistent bronchial and alveolar drug deposition with all modalities. CONCLUSION: Nebulization remains the most reliable and simple technique to deliver inhaled amikacin uniformly to the lung during mechanical ventilation. Further development of tracheal sprays is required to take advantage of potential benefits related to high drug output and low extra-pulmonary deposition in large animals.

Vibrating-mesh nebulizer maintenance by CF patients: Results from a French survey.

PURPOSE OF THE STUDY: Vibrating-mesh nebulizers are widely used at home for cystic fibrosis (CF) treatment, with a therapeutic efficiency closely linked to the mesh performance. This national study looks at the maintenance at home by CF patients and their families of the mesh of the eFlow®rapid nebulizer. Ninety-two patients from 34 French CF centers, treated at home with inhaled drugs delivered with a vibrating-mesh nebulizer, answered to a phone standardized questionnaire specifying the different techniques of maintenance of the nebulizer. PRINCIPAL RESULTS: Patients were aged from 2 to 68 years (58.7% of children). They inhaled a mean of 1.8 nebulizations per day. Maintenance was assumed by patients in 36% of the cases. All steps of the theoretical maintenance of a nebulizer were respected in 66% of the cases. The mesh was not cleaned in 45.6%, not disinfected or not thermically disinfected in 32.5%, and not rinsed after chemical disinfection in 45.5% of the case. Only 49% of the patients knew the role of the MeshCare® system in the mesh maintenance, and only 39% had already used it when the nebulization duration reached 10 min. CONCLUSIONS: Efforts about education, particularly for the maintenance of the mesh, are needed for CF patients using a vibrating-mesh nebulizer at home.

Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys.

PURPOSE: The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. METHODS: Three baboons received CMS by IV infusion and by 2 types of aerosols generators and colistin by subcutaneous infusion. Gamma imaging was performed after nebulisation to determine colistin distribution in lungs. Blood samples were collected during 9 h and colistin and CMS plasma concentrations were measured by LC-MS/MS. A population pharmacokinetic analysis was conducted and simulations were performed to predict lung concentrations after nebulization. RESULTS: Higher aerosol distribution into lungs was observed by scintigraphy, when CMS was nebulized with Pari LC® star than with Eflow Rapid® nebulizer. This observation was confirmed by the fraction of CMS deposited into the lung (respectively 3.5% versus 1.3%).CMS and colistin simulated concentrations in epithelial lining fluid were higher after using the Pari LC star® than the Eflow rapid® system. CONCLUSIONS: A limited fraction of CMS reaches lungs after nebulization, but higher colistin plasma concentrations were measured and higher intrapulmonary colistin concentrations were simulated with the Pari LC Star® than with the Eflow Rapid® system.

Impact of airborne particle size, acoustic airflow and breathing pattern on delivery of nebulized antibiotic into the maxillary sinuses using a realistic human nasal replica.

PURPOSE: Improvement of clinical outcome in patients with sinuses disorders involves targeting delivery of nebulized drug into the maxillary sinuses. We investigated the impact of nebulization conditions (with and without 100 Hz acoustic airflow), particle size (9.9 µm, 2.8 µm, 550 nm and 230 nm) and breathing pattern (nasal vs. no nasal breathing) on enhancement of aerosol delivery into the sinuses using a realistic nasal replica developed by our team. METHODS: After segmentation of the airways by means of high-resolution computed tomography scans, a well-characterized nasal replica was created using a rapid prototyping technology. A total of 168 intrasinus aerosol depositions were performed with changes of aerosol particle size and breathing patterns under different nebulization conditions using gentamicin as a marker. RESULTS: The results demonstrate that the fraction of aerosol deposited in the maxillary sinuses is enhanced by use of submicrometric aerosols, e.g. 8.155 ± 1.476 mg/L of gentamicin in the left maxillary sinus for the 2.8 µm particles vs. 2.056 ± 0.0474 for the 550 nm particles. Utilization of 100-Hz acoustic airflow nebulization also produced a 2- to 3-fold increase in drug deposition in the maxillary sinuses (e.g. 8.155 ± 1.476 vs. 3.990 ± 1.690 for the 2.8 µm particles). CONCLUSIONS: Our study clearly shows that optimum deposition was achieved using submicrometric particles and 100-Hz acoustic airflow nebulization with no nasal breathing. It is hoped that our new respiratory nasal replica will greatly facilitate the development of more effective delivery systems in the future.

Validation of anatomical models to study aerosol deposition in human nasal cavities.

PURPOSE: Intranasal deposition of aerosols is often studied using in vitro nasal cavity models. However, the relevance of these models to predict in vivo human deposition has not been validated. This study compared in vivo nasal aerosol deposition and in vitro deposition in a human plastinated head model (NC1) and its replica constructed from CT-scan (NC2). METHODS: Two nebulizers (Atomisor Sonique® and Easynose®) were used to administer a 5.6 µm aerosol of (99m)Tc-DTPA to seven healthy volunteers and to the nasal models. Aerosol deposition was quantified by γ-scintigraphy in the nasal, upper nasal cavity and maxillary sinus (MS) regions. The distribution of aerosol deposition was determined along three nasal cavity axes (x, y and z). RESULTS: There was no significant difference regarding aerosol deposition between the volunteers and NC1. Aerosol deposition was significantly lower in NC2 than in volunteers regarding nasal region (p < 0.05) but was similar for the upper nasal cavity and MS regions. Mean aerosol distribution for NC1 came within the standard deviation (SD) of in vivo distribution, whereas that of NC2 was outside the in vivo SD for x and y axes. CONCLUSIONS: In conclusion, nasal models can be used to predict aerosol deposition produced by nebulizers, but their performance depends on their design.

Testing an innovative device against airborne Aspergillus contamination.

Aspergillus fumigatus is a major airborne nosocomial pathogen that is responsible for severe mycosis in immunocompromised patients. We studied the efficacy of an innovative mobile air-treatment device in eliminating A. fumigatus from the air following experimental massive contamination in a high-security room. Viable mycological particles were isolated from sequential air samples in order to evaluate the device's effectiveness in removing the fungus. The concentration of airborne conidia was reduced by 95% in 18 min. Contamination was reduced below the detection threshold in 29 min, even when the machine was at the lowest airflow setting. In contrast, during spontaneous settling with no air treatment, conidia remained airborne for more than 1 h. This indoor air contamination model provided consistent and reproducible results. Because the air purifier proved to be effective at eliminating a major contaminant, it may prove useful in preventing air-transmitted disease agents. In an experimental space mimicking a hospital room, the AirLyse air purifier, which uses a combination of germicidal ultraviolet C irradiation and titanium photocatalysis, effectively eliminated Aspergillus conidia. Such a mobile device may be useful in routine practice for lowering microbiological air contamination in the rooms of patients at risk.

A large-volume low-pressure nasal irrigation delivers drug into the nasal cavity? An in vivo study.

The nasal administration route emerged as an interesting route in systemic and brain drug delivery, and different modalities of nasal delivery are available. The nasal irrigation is one of them, but there is a lack of studies investigating the distribution of a large-volume irrigation. The main aim of this study was to assess the deposition of radiolabeled saline in the nasal cavities and paranasal sinuses following nasal irrigation by imaging. Five healthy males volunteered to perform large-volume low-pressure nasal irrigation, with a douching device containing 50 mL of radiolabeled isotonic saline. Participants underwent a scintigraphy immediately after. Both the nasal cavities and maxillary sinuses were systematically reached by the solution during nasal irrigation. The sinuses set in a lower position during nasal irrigation showed a tendency to be more irrigated than the sinuses set in a higher position (7.67% vs 22.72%; p = 0.086). Moreover, substantial inter- and intraindividual heterogeneity regarding solution deposition was observed. Large-volume low-pressure nasal irrigation is a good modality to reach the maxillary sinuses as well as the nasal cavities. In order to ensure adequate reaching of both nasal cavities and paranasal sinuses, nasal irrigation should be performed bilaterally.

Setup of Aerosol Delivery System to Prevent Measles Virus Infection in Nonhuman Primate Model.

Measles virus is one of the most contagious airborne human viruses which keeps causing outbreaks in numerous countries over the world despite the existence of an efficient vaccine. Fusion inhibitory lipopeptides were shown to inhibit viral entry into target cells, and their adequate administration into the respiratory tract may provide a novel preventive approach against airborne infections. Aerosol delivery presents the best administration route to deliver such preventive compounds to the upper and lower respiratory tract. This approach offers a conceptually new strategy to protect the population at risk against infection by respiratory viruses, including measles. It is a noninvasive needle-free approach, which may be used when antiviral protection is required, without any medical assistance. In this chapter, we describe the nebulization approach of lipopeptide compounds in nonhuman primates and the subsequent measles virus challenge.

There Is a Risk of Spread During a Nebulization Session in a Patient with COVID-19.

Introduction: A hypothetical risk of SARS-CoV-2 airborne transmission through nebulization was suggested based on a potential environmental contamination by the fugitive aerosol emitted in the environment during the procedure. The aim of this study was to verify this risk from the fugitive aerosol emitted by COVID-19 patients during one nebulization session. Methods: In this cohort study, COVID-19 patients treated with nebulization were recruited at their admission to the hospital. Patients had to perform a nebulization session while a BioSampler® and a pump were used to vacuum the fugitive aerosol and collect it for SARS-CoV-2 RNA detection. Results: Ten consecutive patients hospitalized with COVID-19 were recruited. The median viral load was 6.5 × 106 copies/mL. Two out of the 10 samples from the fugitive aerosol collected were positive to SARS-CoV-2. Conclusion: The risk of fugitive aerosol contamination with SARS-CoV-2 during nebulization has now been verified.

Influence of mesh nebulizer characteristics on aerosol delivery in non-human primates.

Non-Human Primates (NHPs) are particularly relevant for preclinical studies during the development of inhaled biologics. However, aerosol inhalation in NHPs is difficult to evaluate due to a low lung deposition fraction and high variability. The objective of this study was to evaluate the influence of mesh nebulizer parameters to improve lung deposition in macaques. We developed a humidified heated and ventilated anatomical 3D printed macaque model of the upper respiratory tract to reduce experiments with animals. The model was compared to in vivo deposition using 2D planar scintigraphy imaging in NHPs and demonstrated good predictivity. Next, the anatomical model was used to evaluate the position of the nebulizer on the mask, the aerosol particle size and the aerosol flow rate on the lung deposition. We showed that placing the mesh-nebulizer in the upper part of the mask and in proximal position to the NHP improved lung delivery prediction. The lower the aerosol size and the lower the aerosol flow rate, the better the predicted aerosol deposition. In particular, for 4.3 ± 0.1 µm in terms of volume mean diameter, we obtained 5.6 % ± 0.2 % % vs 19.2 % ± 2.5 % deposition in the lung model for an aerosol flow rate of 0.4 mL/min vs 0.03 mL/min and achieved 16 % of the nebulizer charge deposited in the lungs of macaques. Despite the improvement of lung deposition efficiency in macaques, its variability remained high (6-21 %).

Aerosol therapy in adult critically ill patients: a consensus statement regarding aerosol administration strategies during various modes of respiratory support.

BACKGROUND: Clinical practice of aerosol delivery in conjunction with respiratory support devices for critically ill adult patients remains a topic of controversy due to the complexity of the clinical scenarios and limited clinical evidence. OBJECTIVES: To reach a consensus for guiding the clinical practice of aerosol delivery in patients receiving respiratory support (invasive and noninvasive) and identifying areas for future research. METHODS: A modified Delphi method was adopted to achieve a consensus on technical aspects of aerosol delivery for adult critically ill patients receiving various forms of respiratory support, including mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula. A thorough search and review of the literature were conducted, and 17 international participants with considerable research involvement and publications on aerosol therapy, comprised a multi-professional panel that evaluated the evidence, reviewed, revised, and voted on recommendations to establish this consensus. RESULTS: We present a comprehensive document with 20 statements, reviewing the evidence, efficacy, and safety of delivering inhaled agents to adults needing respiratory support, and providing guidance for healthcare workers. Most recommendations were based on in-vitro or experimental studies (low-level evidence), emphasizing the need for randomized clinical trials. The panel reached a consensus after 3 rounds anonymous questionnaires and 2 online meetings. CONCLUSIONS: We offer a multinational expert consensus that provides guidance on the optimal aerosol delivery techniques for patients receiving respiratory support in various real-world clinical scenarios.

Administration of Bacteriophages via Nebulization during Mechanical Ventilation: In Vitro Study and Lung Deposition in Macaques.

Bacteriophages have been identified as a potential treatment option to treat lung infection in the context of antibiotic resistance. We performed a preclinical study to predict the efficacy of delivery of bacteriophages against Pseudomonas aeruginosa (PA) when administered via nebulization during mechanical ventilation (MV). We selected a mix of four anti-PA phages containing two Podoviridae and two Myoviridae, with a coverage of 87.8% (36/41) on an international PA reference panel. When administered via nebulization, a loss of 0.30-0.65 log of infective phage titers was measured. No difference between jet, ultrasonic and mesh nebulizers was observed in terms of loss of phage viability, but a higher output was measured with the mesh nebulizer. Interestingly, Myoviridae are significantly more sensitive to nebulization than Podoviridae since their long tail is much more prone to damage. Phage nebulization has been measured as compatible with humidified ventilation. Based on in vitro measurement, the lung deposition prediction of viable phage particles ranges from 6% to 26% of the phages loaded in the nebulizer. Further, 8% to 15% of lung deposition was measured by scintigraphy in three macaques. A phage dose of 1 × 109 PFU/mL nebulized by the mesh nebulizer during MV predicts an efficient dose in the lung against PA, comparable with the dose chosen to define the susceptibility of the strain.

Inhaled drug delivery: a randomized study in intubated patients with healthy lungs.

BACKGROUND: The administration technique for inhaled drug delivery during invasive ventilation remains debated. This study aimed to compare in vivo and in vitro the deposition of a radiolabeled aerosol generated through four configurations during invasive ventilation, including setups optimizing drug delivery. METHODS: Thirty-one intubated postoperative neurosurgery patients with healthy lungs were randomly assigned to four configurations of aerosol delivery using a vibrating-mesh nebulizer and specific ventilator settings: (1) a specific circuit for aerosol therapy (SCAT) with the nebulizer placed at 30 cm of the wye, (2) a heated-humidified circuit switched off 30 min before the nebulization or (3) left on with the nebulizer at the inlet of the heated-humidifier, (4) a conventional circuit with the nebulizer placed between the heat and moisture exchanger filter and the endotracheal tube. Aerosol deposition was analyzed using planar scintigraphy. RESULTS: A two to three times greater lung delivery was measured in the SCAT group, reaching 19.7% (14.0-24.5) of the nominal dose in comparison to the three other groups (p < 0.01). Around 50 to 60% of lung doses reached the outer region of both lungs in all groups. Drug doses in inner and outer lung regions were significantly increased in the SCAT group (p < 0.01), except for the outer right lung region in the fourth group due to preferential drug trickling from the endotracheal tube and the trachea to the right bronchi. Similar lung delivery was observed whether the heated humidifier was switched off or left on. Inhaled doses measured in vitro correlated with lung doses (R = 0.768, p < 0.001). CONCLUSION: Optimizing the administration technique enables a significant increase in inhaled drug delivery to the lungs, including peripheral airways. Before adapting mechanical ventilation, studies are required to continue this optimization and to assess its impact on drug delivery and patient outcome in comparison to more usual settings.

Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection.

Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitors, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, block respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We used a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptides to the respiratory tract and demonstrated the absence of adverse effects and lung pathology in macaques. The nebulized peptide efficiently prevented MeV infection, resulting in the complete absence of MeV RNA, MeV-infected cells, and MeV-specific humoral responses in treated animals. This strategy provides an additional shield which complements vaccination to fight against respiratory infection, presenting a proof-of-concept for the aerosol delivery of fusion inhibitory peptides to protect against measles and other airborne viruses, including SARS-CoV-2, in case of high-risk exposure, that can be readily translated to human trials.

Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection.

Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitor, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, blocks respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We use a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptide to the respiratory tract and demonstrate the absence of adverse effects and lung pathology in macaques. The nebulized peptide efficiently prevents MeV infection, resulting in the complete absence of MeV RNA, MeV-infected cells, and MeV-specific humoral responses in treated animals. This strategy provides an additional means to fight against respiratory infection in non-vaccinated people, that can be readily translated to human trials. It presents a proof-of-concept for the aerosol delivery of fusion inhibitory peptides to protect against measles and other airborne viruses, including SARS-CoV-2, in case of high-risk exposure.

Testing of nebulizers for delivering magnesium sulfate to pediatric asthma patients in the emergency department.

BACKGROUND: As the use of intravenous magnesium sulfate (MgSO(4)) for the treatment of refractory asthma is becoming more common, the incidence of MgSO(4)-related systemic hypotension is also rising. One option is to deliver MgSO(4) via aerosol, but compared to most inhaled medications, which are active in the microgram dose range, the MgSO(4) dose requirement is in the milligram range. This, along with inefficient aerosol delivery systems, may be the reason that some studies have found lack of efficacy with aerosol MgSO(4). In preparation for a multicenter study of inhaled MgSO(4) in asthmatic children 2-17 years old, we conducted an in vitro study to choose the best MgSO(4) nebulizer system that would be effective over the entire age range. METHODS: We tested the Pari LC Star jet nebulizer, Omron MicroAir vibrating-mesh nebulizer, and the Aeroneb Go vibrating-mesh nebulizer with the Idehaler valve-less holding chamber. Aerosol delivery was via face mask. RESULTS: The Pari LC Star had an appropriate particle size distribution but a very slow aerosol output rate. The Omron MicroAir had an even slower output rate and a larger particle size distribution, which would be inappropriate for smaller children. In vitro lung deposition with the Aeroneb Go with Idehaler was 16.0 ± 0.4 mg/min in older children and approximately a fifth of that in toddlers. CONCLUSIONS: The Aeroneb Go with Idehaler was chosen for the multicenter clinical study.

Non-human primate models of human respiratory infections.

Respiratory pathogens represent a great burden for humanity and a potential source of new pandemics, as illustrated by the recent emergence of coronavirus disease 2019 (COVID-19). In recent decades, biotechnological advances have led to the development of numerous innovative therapeutic molecules and vaccine immunogens. However, we still lack effective treatments and vaccines against many respiratory pathogens. More than ever, there is a need for a fast, predictive, preclinical pipeline, to keep pace with emerging diseases. Animal models are key for the preclinical development of disease management strategies. The predictive value of these models depends on their ability to reproduce the features of the human disease, the mode of transmission of the infectious agent and the availability of technologies for monitoring infection. This review focuses on the use of non-human primates as relevant preclinical models for the development of prevention and treatment for human respiratory infections.

Pressurized Metered Dose Inhaler Aerosol Delivery Within Nasal High-Flow Circuits: A Bench Study.

Background: Obstructive patients may benefit from nasal high-flow (NHF) therapy, but the use of pressurized metered-dose inhalers (pMDIs) has not been evaluated in this situation. Methods: Using an adult circuit and medium-sized cannula, we have tested different NHF rates, pMDI positions, breathing patterns, spacers, and spacer orientation. First, we evaluated albuterol delivery at the nasal cannula outlet. The second set of experiments made use of a nasopharyngeal cast to estimate the mass of albuterol potentially reaching the lungs. Albuterol was caught on filters placed at the cannula outlet and downstream of the nasal cast, and albuterol was quantified by spectrophotometry. Results: The highest amounts of albuterol delivered at the cannula outlet were observed with a 30 L/min flow rate (vs. 45 and 60 L/min) and placing the device close to the nasal cannula (in comparison with a position on the dry side of the humidification chamber). The use of a spacer was associated with higher delivery. The highest albuterol delivery was observed placing the spacer close to the nasal cannula, oriented for aerosol delivery following the gas flow and a 30 L/min NHF rate. Using this optimal setting, activating the pMDI at the beginning of inspiration (compared to expiration) increased albuterol delivery downstream of the nasopharyngeal cast. Whether in a quiet- or distress-breathing pattern, our measurements showed an amount of albuterol potentially delivered to the lungs exceeding 10% of the actuated dose in optimal conditions. Conclusions: Albuterol delivery with pMDIs is feasible within NHF circuits. Drug delivery sufficient to induce bronchodilation can be achieved using a spacer placed just upstream of the nasal cannula, a low NHF rate, and activation of the pMDI at the beginning of inspiration. Further testing in a clinical setting is required, however.