Aerosol Therapy Research Articles

Chemical and physical stability of selected drugs for aerosol therapy with Sirmione thermal water

Self-propagating High-temperature Synthesis () process is used to prepare Aluminium dodecaboride (). The phase analysis results of preparing with Al and B₂O₃ as raw materials show that under air and argon conditions, the self-propagating and acid-washed self-propagating powders all have α-Al₂O₃ impurities when Mg, Al and B₂O₃ are used as raw materials.

Numerical assessment of natural respiration and particles deposition in the computed tomography scan airway with a glomus tumour

The human respiratory tract has a complex airflow pattern. If any obstruction is present in the airways, it will change the airflow pattern and deposit particles inside the airways. This is the concern of breath quality (inspired air), and it is decreasing due to the unplanned production of material goods. This is a primary cause of respiratory illness (asthma, cancer, etc.). Therefore, it is important to identify the flow characteristics in the human airways and airways with a glomus tumour with particle deposition. A numerical diagnosis is presented with an asymmetric unsteady-state light breathing condition (10 l/min). An in vitro human respiratory tract model has been reconstructed using computed tomography scan techniques and an artificial glomus tumour developed 2 cm above a carina on the posterior wall of the trachea. The transient flow characteristics are numerically simulated with a realizable (low Reynolds number) k–ɛ turbulence model. The flow disturbance is captured around the tumour, which influenced the upstream and downstream of the flow. The flow velocity pattern, wall shear stress and probable area of inflammation (hotspot) due to suspended particle deposition are determined, which may assist doctors more effectively in aerosol therapy and prosthetics of human airways illness.

Impact of different nebulisers' connections on aerosol therapy.

Aerosol therapy has the advantage of a higher safety because of the local deposition of inhaled medication to the lung; however, the main drawback is the low and variable amount of delivered drug to patients. Hence, this study aimed to investigate the effect of different accessory connections on aerosol delivery from different nebulisers. This study consisted of 3 main models: in vitro, in vivo and ex vivo models. In vitro model, 6 nebulisers (3 Jet (Dolphin (2030 2001), Philips (SideStream) and Tylenol (TL009002)) and 3 vibrating mesh nebulisers (VMNs) (Aerogen Pro, Solo, an Nivo)) were charged with 5mg/2 mL salbutamol and connected to 2 different connections (T-piece and Circulaire II Hybrid) with an inhalation filter attached to a breathing simulator. Inhaled amounts of drug (inhalation filter) and that remained inside nebuliser were measured. Concerning ex vivo and in vivo models, 24 subjects were involved in the study and they received 5mg/2mL salbutamol from 1 Jet nebuliser and 1 VMNs using both connections. Two urine samples were collected post 30minutes and pooled 24hours urine collection. For the ex vivo model, inhaled amounts of salbutamol were collected on filters placed between the subjects and the nebuliser. Inhaled amounts of salbutamol expressed by the amount of drug detected on inhalation filters (for both in vitro and ex vivo) were significantly higher from both Jet and VMNs connected to the Circulaire II Hybrid connection than that released from nebulisers connected to T-piece. VMNs delivered a higher amount compared with jet nebulisers. The amount released from jet nebulizers were variables, unlike VMNs. Regarding in vivo results, amounts of drug detected in 30minutes urine samples were consistent with in vitro and ex vivo models reflecting higher and significant amounts of drug delivered to the patient's lung for Circulaire II Hybrid connection compared with T-piece regarding both nebulisers. Using a valved chamber with jet and VMNs significantly improved the inhaled amount of the emitted aerosol. VMNs were more effective than jet nebulisers with both connections.

The Use of Aerosolized Medications in Adult Intensive Care Unit Patients: A Prospective, Multicenter, Observational, Cohort Study.

Background: Only limited data are available on the real-life clinical utilization of aerosolized medications in intensive care unit (ICU) patients. Exploring the utilization of aerosolized medications in the ICU may contribute to develop appropriate education and improve the quality of aerosol therapy. Methods: A 2-week, prospective, multicenter, observational, cohort study was conducted to record how the aerosolized medications were utilized in the Chinese ICUs, including indications, medications used in solo or combination, dosage, and side-effects in adult patients. Results: A total of 1006 patients from 28 ICUs were enrolled, of which 389 (38.7%) received aerosol therapy. The most common indications for aerosol therapy were difficulty in secretion management (23.1%) and chronic obstructive pulmonary disease exacerbation (18.5%). The combination of inhaled corticosteroids and short-acting muscarinic antagonist was the most commonly used medication (19.5%, 76/389). Ninety-two percent (358/389) of the patients did not have any side effects during aerosol therapy. More patients in the group with mechanical ventilation received bronchodilators than spontaneous breathing patients (81.3% vs. 55.5%, p < 0.001), and more patients who breathed spontaneously through a tracheostomy received mucus-regulating agents than other patients (70% vs. 37.9%, p = 0.004). Conclusion: In mainland China, more than one-third of adult ICU patients received aerosol therapy. Medications utilized during aerosol therapy were variable in patients with different respiratory support. To promote appropriate use of aerosolized medications, high-quality randomized, controlled trials and clinical guidance on aerosolized medication indications and dosing are needed to improve clinical outcomes.

Dyspnea and situs inversus in a boy aged 3 days

A boy was admitted on day 3 after birth due to shortness of breath for 2 days and cyanosis for 1 day. He had clinical manifestations of dyspnea in the early postnatal period and situs inversus, and was finally diagnosed with Kartagener syndrome. His condition was improved after oxygen therapy, anti-infective therapy, and aerosol therapy. The genetic testing showed that there was a large-fragment loss of heterozygosity, exon 48_50, and a hemizygous mutation, c.7915C > T(p.R2639X), in the DNAH5 gene. Kartagener syndrome is a rare autosomal recessive disease, and this is the first case of Kartagener syndrome diagnosed in the neonatal period in China.

Aerosol drug delivery to tracheotomized patients with COVID-19: Pragmatic suggestions for clinicians.

Because of the wide and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the number of hospitalized patients with coronavirus disease 2019 (COVID-19) has rapidly increased medically complex and resource-intensive treatment requirements in health care settings. Although tracheostomy is frequently needed for critically ill patients requiring extended mechanical ventilation, it has been described as an aerosol-generating procedure that puts health care professionals at an increased risk of viral transmission. In addition, the delivery of aerosolized medications to this patient population has become controversial because of concerns on the transmission of SARS-CoV-2 via droplets. Although aerosol therapy in spontaneously breathing patients with COVID-19 was described in recent publications, innovations in aerosol drug delivery to COVID-19 patients with tracheostomy have not been presented. Therefore, empirically based guidance on how to deliver aerosols safely and effectively to tracheotomized patients with COVID-19 is still lacking. This paper provides recommendations and rationales for device selection, interface selection, delivery techniques, and infection control based on the evolving body of literature.

Pros and Cons of Nebulizer Treatment in Asthma Exacerbation During the COVID-19 Pandemic

ABSTRACT Nebulizers generate aerosols and may potentially transmit respiratory viral particles including SARS-CoV-2. There is a great concern about the use of a nebulizer in the treatment of asthma exacerbations in the hospital or home setting during the COVID-19 pandemic and its use is not recommended unless essential. However, aerosol therapy should not be avoided in obligatory indications. Therefore, indications of nebulizer use during the pandemic should be evaluated on an individual basis in case of a severe asthma attack, and infection control recommendations should be followed by clinicians while using nebulizers. In this article, we aimed to assess the safety in addition to the “pro” and “con” sides of nebulizer treatment in asthma exacerbation during the COVID-19 pandemic. Keywords: Asthma, coronavirus disease 2019, COVID-19, SARS-CoV-2, nebulizers

Evaluation of Aerosol Therapy during the Escalation of Care in a Model of Adult Cystic Fibrosis.

Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF). CF patients inhale antibiotics regularly as treatment against persistent bacterial infections. The goal of this study was to investigate the effect of clinical intervention on aerosol therapy during the escalation of care using a bench model of adult CF. Droplet size analysis of selected antibiotics was completed in tandem with the delivered aerosol dose (% of total dose) assessments in simulations of various interventions providing oxygen supplementation or ventilatory support. Results highlight the variability of aerosolised dose delivery. In the homecare setting, the vibrating mesh nebuliser (VMN) delivered significantly more than the jet nebuliser (JN) (16.15 ± 0.86% versus 6.51 ± 2.15%). In the hospital setting, using VMN only, significant variability was seen across clinical interventions. In the emergency department, VMN plus mouthpiece (no supplemental oxygen) was seen to deliver (29.02 ± 1.41%) versus low flow nasal therapy (10 L per minute (LPM) oxygen) (1.81 ± 0.47%) and high flow nasal therapy (50 LPM oxygen) (3.36 ± 0.34%). In the ward/intensive care unit, non-invasive ventilation recorded 19.02 ± 0.28%, versus 22.64 ± 1.88% of the dose delivered during invasive mechanical ventilation. These results will have application in the design of intervention-appropriate aerosol therapy strategies and will be of use to researchers developing new therapeutics for application in cystic fibrosis and beyond.

Comparison of Vibrating Mesh and Jet Nebulizers During Noninvasive Ventilation in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Background: Advances in aerosol technology have improved drug delivery efficiency during noninvasive ventilation (NIV). Clinical evaluation of the efficacy of aerosol therapy during NIV in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) is very limited. The aim of our study was to compare the efficacy of bronchodilators administered through a vibrating mesh nebulizer (VMN) and jet nebulizer (JN) during NIV in patients with acute exacerbation of COPD. Methods: Prospective randomized cross-over study included 30 patients treated with NIV for acute exacerbation of COPD in an acute care hospital. Patients were consented and enrolled after stabilization of acute exacerbation (3-5 days after admission). Subjects were randomly assigned into two treatment arms receiving salbutamol (2.5 mg): with VMN (Aerogen Solo) and JN (Sidestream) positioned between the leak port and the nonvented oronasal mask during bilevel ventilation with a single-limb circuit. Measurements (clinical data, pulmonary function tests [PFTs], and arterial blood gases) were performed at baseline, 1, and 2 hours after treatment. Results: All measured PFT parameters significantly increased in both groups, but numerically results were better after inhalation with VMN than with JN: for forced expiratory volume in 1 second (FEV1) (mean increase from baseline to 120 minutes-165 ± 64 mL vs. 116 ± 46 mL, p = 0.001) and for forced vital capacity (FVC) (mean increase-394 ± 154 mL vs. 123 ± 57 mL, p < 0.001). There was also a statistically significant reduction in respiratory rate and in Borg dyspnea score after therapy with VMN in comparison with the conventional JN. In both groups, there were improvements in PaCO2, but with VMN these changes were significantly higher. Conclusion: Bronchodilator administration in patients with acute exacerbation of COPD during NIV with VMN resulted in clinically significant improvements in FVC and in Borg dyspnea score. Additional studies required to determine the impact on clinical outcomes.

Salbutamol Delivered by Jet Nebulizer: Closed System Design and Impact of a Model Biofilm.

Aerosol therapy is commonly used by intensivists during invasive mechanical ventilation. More information is needed to optimize outcomes. The first aim of this study was to assess the deposition of salbutamol on components of a closed mechanical ventilation system, both in the presence and absence of biofilm generated by Acinetobacter baumannii. The second aim was to evaluate the deposition of salbutamol, using a single dose and a double dose, delivered via a jet nebulizer placed between the flexible tube and the heat and moisture exchanger. A mechanical ventilator was connected to a standard system, and a jet nebulizer was placed between the heat and moisture exchanger and the flexible tube. Clinical isolates of A. baumanii were used to generate a biofilm layer on the endotracheal tube. Two amounts of salbutamol were delivered via the jet nebulizer. An analytical liquid chromatography tandem mass spectrometry method was developed to evaluate salbutamol deposition. The presence of a biofilm on the endotracheal tube had no impact on salbutamol deposition (P = .83). There was no difference in surface deposition of salbutamol on component parts of the closed system in a comparison of a single dose and a double dose delivered via a jet nebulizer. Our findings indicate that an A. baumannii biofilm had no impact on the extent of salbutamol deposition. Salbutamol deposition was comparatively low and could be delivered without removal of the heat and moisture exchanger.

Worldwide Clinical Practice of High-Flow Nasal Cannula and Concomitant Aerosol Therapy in the Adult ICU Setting.

High-flow nasal cannula (HFNC) oxygen therapy has been broadly used. However, no consensus has been achieved on the practical implementation of HFNC and how to provide aerosol delivery during HFNC therapy in adult patients. An online anonymous questionnaire survey endorsed by 4 academic societies from America, Europe, mainland China, and Taiwan was administered from May to December 2019. Clinicians who had worked in adult ICUs for > 1 year and had used HFNC to treat patients within 30 days were included. A total of 2,279 participants clicked on the survey link, 1,358 respondents completed the HFNC section of the questionnaire, whereas 1,014 completed the whole survey. Postextubation hypoxemia and moderate hypoxemia were major indications for HFNC. The initial flow was mainly set at 40-50 L/min. Aerosol delivery via HFNC was used by 24% of the participants (248/1,014), 30% (74/248) of whom reported reducing flow during aerosol delivery. For the patients who required aerosol treatment during HFNC therapy, 40% of the participants (403/1,014) reported placing a nebulizer with a mask or mouthpiece while pursuing HFNC whereas 33% (331/1,014) discontinued HFNC to use conventional aerosol devices. A vibrating mesh nebulizer was the most commonly used nebulizer (40%) and was mainly placed at the inlet of the humidifier. The clinical utilization of HFNC was variable, as were indications, flow settings, and criteria for adjustment. Many practices associated with concomitant aerosol therapy were not consistent with available evidence for optimal use. More efforts are warranted to close the knowledge gap.

A path to successful patient outcomes through aerosol drug delivery to children: a narrative review.

Although using aerosolized medications is a mainstay of treatment in children with asthma and other respiratory diseases, there are many issues in terms of device and interface selection, delivery technique and dosing, as well as patient and parental education that have not changed for half a century. Also, due to many aerosol devices and interfaces available on the market and the broad range of patient characteristics and requirements, providing effective aerosol therapy to children becomes a challenge. While aerosol delivery devices are equally effective, if they are age-appropriate and used correctly, the majority of aerosol devices require multiple steps to be used efficiently. Unfortunately, many children with pulmonary diseases have problems with the correct delivery technique and do not gain therapeutic benefits from therapy that result in poor disease management and increased healthcare costs. Therefore, the purpose of this paper is to review the current knowledge on aerosol delivery devices used in children and guide clinicians on the optimum device- and interface-selection, delivery technique, and dosing in this patient population. Strategies on how to deliver aerosolized medications in crying and distressed children and how to educate parents on aerosol therapy and promote patient adherence to prescribed medications are also provided. Future directions of aerosol therapy in children should focus on these issues and implement policies and clinical practices that highlight the potential solutions to these problems.

Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome.

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.

Carrier Gases and Their Effects on Aerosol Drug Delivery.

Carrier gases provide the medium for delivery of inhaled aerosol therapies. The physical properties of these gases substantially affect both fluid and aerosol mechanics in the lung. Gas density affects both the pressure/flow relationship in the airways and the extent of turbulence within the flow. These physical properties also affect the operation of some components of respiratory and aerosol drug delivery equipment. The lower resistance associated with breathing low density gases has prompted many studies of therapeutic applications. This includes the respiration of helium-oxygen gas mixtures to improve oxygenation and carbon dioxide removal, and the use of these gases to improve the delivery of inhaled medications. Results of these studies have been mixed but meta-analyses indicate a benefit of helium-oxygen respiration for croup and bronchiolitis and for bronchodilator delivery in obstructive disease. Some of the variability demonstrated in these studies is likely associated with specific technical aspects of how the gases are delivered. The utility of alternate carrier gases for aerosol delivery would be facilitated by simultaneous assessment of both aerosol deposition and clinical effect during studies. Previous successful applications may offer a basis for improved delivery system designs that fully realize the effects that might be available with these gases.

In vitro evaluation of disposable transport ventilators with combination aerosol therapy

BackgroundThe COVID-19 pandemic has highlighted the need for alternative short-term, reliable means to aid in the treatment of patients requiring ventilatory support. Concurrent aerosol drug delivery is often prescribed to...

Feasibility of an inhaled antibiotic/adjuvant dry powder combination using an experimental design approach

The global increase of multidrug resistant bacteria and the lack of new classes of antibiotic especially those targeting Gram-negative pathogens are leaving the clinicians disarmed to treat numerous bacterial infections. Recently, the design of adjuvants able to enhance antibiotics activities appears to be one of the most promising investigated solutions to circumvent this problem. In this context, we have recently identified a new polyamino-isoprenyl derivative NV716 able to potentiate, at a very low concentration the activity of doxycycline against resistant P. aeruginosa bacterial strains by increasing its intracellular concentration. In this study we will report an experimental protocol to optimize a dry powder for inhalation ensuring the simultaneous delivery of an antibiotic (doxycycline) and an adjuvant (the polyaminoisoprenyl derivative NV716 since aerosol therapy could allow a rapid drug administration and target the respiratory system by avoiding the first pass effect and minimizing undesirable systemic effects. Thus, an experimental design was carried out permitting to identify the influence of several factors on the aerosolization efficiency of our combination and allowing us to find the right composition and manufacture leading to the best optimization of the simultaneous delivery of the two compounds in the form of an inhalable powder. More precisely, the powders of the two active ingredients were prepared by freeze drying and their aerosolization was improved by the addition of carrier particles of lactose inhalation grade. Under these conditions, the best formulation was defined by combining the optimal factors leading to the best aerodynamic properties’ values (the lowest MMAD (Mass Median Aerodynamic Diameter) and the highest FPF (Fraction of Fine Particles)) without even using sophisticated engineering techniques. Finally, our results suggest that these molecules could be successfully delivered at the requested concentration in the lungs and then able to decrease drug consumption as well as increase treatment efficacy.

Hospital staff practical skills and theoretical knowledge in inhaled aerosol therapy: a single centre cross-sectional observational study.

Inhaled therapy is widely used for treatment of many respiratory disorders. Drug delivery in lungs is dependent on the correct use of aerosol devices and patients' training is vital for a correct therapy administration. Therefore, is very important to assess the skills of professionals involved in training patients to the correct use of inhaler devices. The aim of this study was to check the practical skills and the theoretical knowledge of health care personnel in our University Hospital in using aerosol therapy and to determine differences among professional figures in the management of inhaler devices. Three hundred and fifteen (315) volunteers including physicians, residents, nurses and respiratory physiotherapists were enrolled; an independent professional, not working in our University Hospital, assessed their theoretical knowledge related to aerosol throughout a questionnaire. Practical skills were assessed through placebo simulation with the devices that participants declared to use frequently with patients. None of the respondents correctly answered all questions evaluating theoretical knowledge on the proper use of aerosol therapy. Respiratory physiotherapists obtained significantly better results with 17.2 (1.3) average points compared to 10.3 (3.7) obtained by doctors, 9.0 (3.0) by nurses and 9.1 (4.5) by residents. Analysing in detail physicians' results, pneumologists showed better theoretical knowledge than other specialists. Concerning the practical skills, about 80% of those stating they knew how to use metered dose inhalers, made mistakes in the basic steps for proper inhalation technique and over 50% of respondents were unable to properly simulate placebo administration of dry powder inhalers. Also here, respiratory physiotherapists and pneumologists had significant better performances, when compared to other health professionals. Our data are in line with those published in the literature in other international clinical settings, noting inadequate practical and theoretical knowledge of the available devices for aerosol therapy.

COVID-19; current situation and recommended interventions.

BackgroundThe new coronavirus (SARS‐COV‐2) that emerged at the end of 2019 was stated in China and infected millions of people around the world, with the highest spread rate amongst humans compared with other coronaviruses. This paper aimed to review and analyse the published studies about COVID‐19 diagnosis, prevention, and treatment.MethodThe reviewed studies were clinical trials, in‐vivo, in‐vitro, guidelines, reports from the world health organization (WHO), and the centre for disease control and prevention (CDC) in addition to systemic reviews. All data extracted and analysed to stand on the latest updates and recommendations for fighting this severe attack of COVID‐19.ResultsMost important antiviral therapy of COVID‐19 clinical trials is still running without clear results, but a few trials have indicated the role of numerous drugs in the treatment of COVID‐19. Specific recommendations for aerosol therapy should be followed for the management of COVID‐19.ConclusionNature of COVID‐19 is still not very clear, however, management of the condition is similar to the previous attacks of coronaviruses.

An in vitro visual study of fugitive aerosols released during aerosol therapy to an invasively ventilated simulated patient

COVID-19 can cause serious respiratory complications resulting in the need for invasive ventilatory support and concurrent aerosol therapy. Aerosol therapy is considered a high risk procedure for the transmission of patient derived infectious aerosol droplets. Critical-care workers are considered to be at a high risk of inhaling such infectious droplets. The objective of this work was to use noninvasive optical methods to visualize the potential release of aerosol droplets during aerosol therapy in a model of an invasively ventilated adult patient. The noninvasive Schlieren imaging technique was used to visualize the movement of air and aerosol. Three different aerosol delivery devices: (i) a pressurized metered dose inhaler (pMDI), (ii) a compressed air driven jet nebulizer (JN), and (iii) a vibrating mesh nebulizer (VMN), were used to deliver an aerosolized therapeutic at two different positions: (i) on the inspiratory limb at the wye and (ii) on the patient side of the wye, between the wye and endotracheal tube, to a simulated intubated adult patient. Irrespective of position, there was a significant release of air and aerosol from the ventilator circuit during aerosol delivery with the pMDI and the compressed air driven JN. There was no such release when aerosol therapy was delivered with a closed-circuit VMN. Selection of aerosol delivery device is a major determining factor in the release of infectious patient derived bioaerosol from an invasively mechanically ventilated patient receiving aerosol therapy.

Application of aerosol therapy in respiratory diseases in children: A Saudi expert consensus.

The Saudi Pediatric Pulmonology Association (SPPA) is a subsidiary of the Saudi Thoracic Society (STS), which consists of a group of Saudi experts with well-respected academic and clinical backgrounds in the fields of asthma and other respiratory diseases. The SPPA Expert Panel realized the need to draw up a clear, simple to understand, and easy to use guidance regarding the application of different aerosol therapies in respiratory diseases in children, due to the high prevalence and high economic burden of these diseases in Saudi Arabia. This statement was developed based on the available literature, new evidence, and experts' practice to come up with such consensuses about the usage of different aerosol therapies for the management of respiratory diseases in children (asthma and nonasthma) in different patient settings, including outpatient, emergency room, intensive care unit, and inpatient settings. For this purpose, SPPA has initiated and formed a national committee which consists of experts from concerned specialties (pediatric pulmonology, pediatric emergency, clinical pharmacology, pediatric respiratory therapy, as well as pediatric and neonatal intensive care). These committee members are from different healthcare sectors in Saudi Arabia (Ministry of Health, Ministry of Defence, Ministry of Education, and private healthcare sector). In addition to that, this committee is representing different regions in Saudi Arabia (Eastern, Central, and Western region). The subject was divided into several topics which were then assigned to at least two experts. The authors searched the literature according to their own strategies without central literature review. To achieve consensus, draft reports and recommendations were reviewed and voted on by the whole panel.