Aerosol Delivery Devices Research Articles

Delivery of Inhaled Medication in Children: Revisiting Pharmacological and Practical Issues for Better Health Outcome

For safe and effective therapy of respiratory disorders in children, delivering the medication at the site of disease i.e. directly into the respiratory tract via aerosolized medication is critical. But, the anatomical and physiological differences in the respiratory tract of infants/children and adults make the delivery of aerosolized medication complicated. This review article gives an overview of the delivery of inhaled medication in children and discuss the pharmacological and specific clinically relevant aspects of medication delivery using nebulizers, pressurized metered dose inhalers (MDIs), and dry powder inhalers (DPIs) in children. As a physician, one should always keep in mind the various factors like properties of the device, aerosol particle, patient factors such as disease state, ventilatory pattern, and administration technique that can affect drug deposition via aerosol delivery devices.

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Effects of saline nebulization on SARS-CoV-2 RNA spreading and exhaled bio-aerosol particles in COVID-19 patients

Nebulised therapy is the mainstay for treating obstructive airway diseases, but there is heightened concern about the potential risk for SARS-CoV-2 transmission during nebulisation in COVID-19 patients. We investigated the effects of 0.9% saline nebulisation on SARS-CoV-2 RNA spreading in 11 COVID-19 patients (5 females, mean age 62.45±9.31 yr). In 6 out of the 11 patients we also ascertained whether saline nebulisation changed the number of exhaled bioaeroosl particles. Air samples were collected using suction pumps equipped with 0.45μm PTFE filters and positioned around the patient's bed. Exhaled particles were quantified by using an optical particle counter. At baseline (i.e. before nebulisation) SARS-CoV-2 was detected more frequently in the pumps close to the patient than in those far away. After saline nebulisation, the detection of SARS-CoV-2 in the pumps close to the patient was comparable to that observed at baseline. In the pumps far from the patient, saline nebulisation slightly, but not significantly, increased SARS-CoV-2 RNA detection compared to baseline. Overall, no significant changes in the SARS-CoV-2 RNA detection were observed after saline nebulisation. At baseline, exhaled particles emission varied among patients, with two of them showing higher emission of particles than the remaining patients. Saline nebulisation induced a marked decrease in exhaled particles in the 2 patients who displayed high emission at baseline, whereas no changes were observed in the remaining patients. Saline nebulisation did not significantly change SARS-CoV-2 RNA spreading. Thus, there is no compelling reason to alter aerosol delivery devices for patients with established nebuliser-based regimens.

Using the Model of Motivation to Improve the Accuracy of Nurses Conducting Aerosol Therapy in Mechanically Ventilated Patients

Aerosol therapy is increasingly used in pulmonary critical care and in patients with respiratory disease. However, improper application of the aerosol delivery device will decrease the therapeutic effect as well as increase the incidence of pulmonary infection. An initial assessment conducted in our intensive care unit found an accuracy rate for nursing staff aerosol-therapy execution of only 55.9%. Possible reasons identified for this low rate included lack of learning experience and resources, lack of related standard operating procedures, lack of related performance assessments, complicated / unfamiliar device assembly procedure, diffuse storage of device components, and a lack of illustrations. This project was developed to increase the accuracy rate of performing aerosol therapy to over 90% in our intensive care unit. We designed diverse learning materials using the model of motivation, developed an evaluation system, simplified the assembly of components based on evidence-based research, improved the storage situation, and added reference illustrations. The accuracy rate in aerosol therapy execution for our nursing staff increased from 55.9% to 95.0% after the intervention. This project used the model of motivation to develop the teaching materials. By using diverse teaching methods, including both in-person classes and online interactive quizzes, we realized high learning satisfaction and efficacy. Along with simplifying equipment handling, improving the working environment, enhancing nurses' aerosol therapy techniques, establishing standard operating procedure guidelines, and adding an evaluation system, we standardized the entire procedure for potential promotion to other intensive care units.

Place of nebulizer therapy in the treatment of bronchial asthma in children

The review article presents an analysis of the data of foreign and domestic researchers characterizing the effectiveness of nebulizer therapy for bronchial asthma in children. The paper considers new data comparing the effectiveness of aerosol delivery devices. The advantage of inhalation therapy, which determines its widespread use in childhood, is its rapid delivery to the respiratory tract, high local and low systemic concentrations of the drug in target organs. Difficulties in observing the correct inhalation technique due to the difficulty of synchronizing inhalation and drug delivery, especially in young children, remain an urgent problem in the practice of treating chronic bronchopulmonary diseases, which leads to a severe and uncontrolled course, disability and adverse outcomes. The main disadvantage of ultrasonic nebulizers is the inactivation of suspensions, antibiotics and other drugs. Widely used jet nebulizers create noise during inhalation, have a large residual volume in the nebulizer chamber. In this regard, the improvement of delivery forms continues, taking into account the anatomical and physiological characteristics of the respiratory organs, the age of patients and comorbid conditions. The characteristics of the optimal inhaler include simplicity and ease of use, reliability, the possibility of effective inhalation of various drugs in combination with economical consumption. From this point of view, one of the universal means of transporting aerosols is membrane or electronic mesh (mesh) nebulizers, which provide excellent regional drug deposition in all age groups of children. The rapid achievement of clinical effect, compactness, mobility expand the possibilities of using mesh nebulizers at all levels of medical care.

Aerosol delivery systems for treating obstructive airway diseases during the SARS-CoV-2 pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes CoronaVirus Disease 2019 (COVID-19), has resulted in a worldwide pandemic and currently represents a major public health crisis. It has caused outbreaks of illness through person-to-person transmission of the virus mainly via close contacts, and droplets produced by an infected person’s cough or sneeze. Aerosolised inhaled therapy is the mainstay for treating obstructive airway diseases at home and in healthcare settings, but there is heightened particular concern about the potential risk for transmission of SARS-CoV-2 in the form of aerosolised respiratory droplets during the nebulised treatment of patients with COVID-19. As a consequence of this concern, the use of hand-held inhalers, especially pressurised metered dose inhalers, has risen considerably as an alternative to nebulisers, and this switch has led to inadequate supplies of inhalers in some countries. However, there is no evidence supporting an increased risk of viral transmission during nebulisation in COVID-19 patients. Furthermore, some patients may be unable to adequately use their new device and may not benefit fully from the switch to treatment via hand-held inhalers. Thus, there is no compelling reason to alter aerosol delivery devices for patients with established nebuliser-based regimens. The purpose of this paper is to discuss the current evidence and understanding of the use of aerosolised inhaled therapies during the SARS-CoV-2 pandemic and to provide some guidance on the measures to be taken to minimise the risk of transmitting infection, if any, during aerosol therapies.

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.

Review of aerosol delivery in the emergency department.

Aerosol delivery is a vital therapeutic strategy for both adult and pediatric patients presenting to the emergency department with respiratory distress. Aerosolized bronchodilators are frequently used as rescue medications for patients with diagnoses of asthma, chronic obstructive pulmonary disease (COPD), or pneumonia. Historically, emergency department providers utilized jet nebulizers (JNs) for medication delivery, but were challenged by a need for increasingly higher bronchodilator doses to elicit the desired response. Advancements in technology have led to the development of newer specialized aerosol delivery devices and treatment strategies which provide clinicians with improved options for aerosol delivery but may also cause some uncertainty regarding appropriate device selection. Initial investigations comparing these devices presented valuable evidence of in vitro benefit but were unable to demonstrate corresponding improvement in clinical results. More recently there has been an influx of clinical evidence that suggests improved clinical outcomes associated with more efficient aerosol delivery devices such as vibrating mesh nebulizers (VMN) compared to the standard JN device. VMN will likely become an increasingly important tool in emergency department treatment of patients with respiratory distress. Additional controlled studies are needed both to examine the effects of VMN on patient outcomes, as well as to analyze how performance differences between aerosol devices may affect dosing strategies. Future efforts should also focus on applying new evidence in the form of updated consensus guidelines and standardized treatment strategies.

Administration of dry powders during respiratory supports.

Inhaled drugs are routinely used for the treatment of respiratory-supported patients. To date, pressurized metered dose inhalers and nebulizers are the two platforms routinely employed in the clinical setting. The scarce utilization of the dry powder inhaler (DPI) platform is partly due to the lack of in vivo data that proves optimal delivery and drug efficacy are achievable. Additionally, fitting a DPI in-line to the respiratory circuit is not as straightforward as with the other aerosol delivery platforms. Importantly, there is a common misconception that the warm and humidified inspiratory air in respiratory supports, even for a short exposure, will deteriorate powder formulation compromising its delivery and efficacy. However, some recent studies have dispelled this myth, showing successful delivery of dry powders through the humidified circuit of respiratory supports. Compared with other aerosol delivery devices, the use of DPIs during respiratory supports possesses unique advantages such as rapid delivery and high dose. In this review, we presented in vitro studies showing various setups employing commercial DPIs and effects of ventilator parameters on the aerosol delivery. Inclusion of novel DPIs was also made to illustrate characteristics of an ideal inhaler that would give high lung dose with low powder deposition loss in tracheal tubes and respiratory circuits. Clinical trials are urgently needed to confirm the benefits of administration of dry powders in ventilated patients, thus enabling translation of powder delivery into practice.

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.

Large eddy simulations of airflow and particle deposition in pulsating bi-directional nasal drug delivery

Chronic rhinosinusitis is a common disease worldwide, and the frequently prescribed nasal sprays do not sufficiently deliver the topical medications to the target sites so that the final treatment in severe cases is surgery. Therefore, there is a huge demand to improve drug delivery devices that could target the maxillary sinuses more effectively. In the present study, different particle diameters and device pulsation flow rates, mainly used in pulsating aerosol delivery devices such as the PARI SINUS®, are considered to evaluate optimal maxillary sinus deposition efficiency (DE). Numerical simulations of the particle-laden flow using a large eddy simulation with a local dynamic k-equation sub-grid scale model are performed in a patient-specific nasal cavity. By increasing the pulsation flow rate from 4 l/min to 15 l/min, nasal DE increases from 37% to 68%. Similarly, by increasing the particle size from 1 µm to 5 µm, nasal DE increases from 34% to 43% for a pulsation flow rate of 4 l/min. Moreover, normalized velocity, vorticities, and particle deposition pattern in different regions of the main nasal cavity and maxillary sinuses are visualized and quantified. Due to the nosepiece placement in the right nostril, more particles penetrate into the right maxillary sinus than into the left maxillary sinus despite the maxillary ostium being larger in the left cavity. Lower pulsation flow rates such as 4 l/min improve the DE in the left maxillary sinus. The use of 3 µm particles enhances the DE in the right maxillary sinus as well as the overall total maxillary drug delivery.

Impact of Advanced Patient Counseling Using a Training Device and Smartphone Application on Asthma Control.

Pressurized metered-dose inhalers (pMDIs) are among the most commonly used aerosol delivery devices. Poor lung deposition from a pMDI is often a result of incorrect inhalation technique. The aim of this study was to compare the impact of combining a newly released training device with a smartphone application (advanced counseling) in asthma control to the impact of traditional verbal training. A total of 371 subjects with asthma were divided into 2 groups: advanced counseling (n = 187) and verbal counseling (n = 184). Both groups had 3 visits, each meeting being a month apart. At each visit, lung function (ie, FEV1, ratio of FEV1 to forced vital capacity [FEV1/FVC], and peak expiratory flow) were measured, an asthma control test was given, and subjects were trained in the correct inhalation technique. Inhalation flow through the pMDI was also recorded at each visit because the correct pMDI technique requires an inspiratory flow of < 60 L/min. In the advanced counseling group, lung function significantly improved after both the first and the second visit (P < .001), whereas in the verbal group, lung function improved significantly only after the second visit (P < .001). Although the inspiratory flow through the pMDI improved significantly in both groups, it was closest to the target range in the advanced counseling group. In addition, more subjects in the advanced counseling group had monthly increases of ≥ 3 points in their asthma control test scores compared to the verbal counseling group. The use of a training device with a smartphone application in conjunction with traditional verbal counseling in pMDI technique resulted in significant improvements in asthma control compared to traditional verbal counseling in pMDI technique alone.

Albuterol Delivery Efficiency in a Pediatric Model of Noninvasive Ventilation With a Single-Limb Circuit.

Pediatric patients treated with noninvasive ventilation (NIV) are frequently given aerosol therapy. Limited pediatric data are available on the efficiency of aerosol delivery efficiency. We evaluated the effect of different nebulizers, positions in the single-limb ventilator circuit, and ventilator settings on the efficiency of aerosol delivery in a model of pediatric NIV. We hypothesized that using a vibrating mesh nebulizer, placing the nebulizer after the circuit leak, and not using the highest inspiratory positive airway pressure would increase aerosol delivery efficiency. We connected a breathing simulator in series to a low-dead-space filter holder (lung dose) and to an anatomically correct face/airway model of a 5-y-old child. A mask with an entrainment elbow was connected to a ventilator operated in a NIV bi-level mode and assembled with a single-limb heated-wired circuit. Inspiratory/expiratory pressures of either 15/5 or 20/5 cm H2O were used. We studied 3 different jet nebulizers and 2 vibrating mesh nebulizers loaded with albuterol solution (2.5 mg/3 mL). Albuterol was measured with spectrophotometry. The outcome measure was the efficiency of aerosol delivery (ie, lung dose expressed as percentage of the nominal dose). Vibrating mesh nebulizers placed after the exhalation port of the circuit had the highest delivery efficiency, even compared with a vibrating mesh nebulizer integrated into the mask. Placing the nebulizer after the exhalation port of the circuit increased efficiency for all nebulizers. Vibrating mesh nebulizers were more efficient than jet nebulizers, regardless of their position in the circuit. Increasing the inspiratory pressure resulted in a variable effect on aerosol-delivery efficiency. In a model of pediatric NIV using a single-limb circuit, aerosol delivery devices were more efficient when placed after the exhalation port of the ventilator circuit. Vibrating mesh nebulizers were more efficient than jet nebulizers.

Aerosol Delivery Devices for Obstructive Lung Diseases.

Drug delivery by inhalation is the principal strategy to treat obstructive lung diseases, which affect about 15% of the population in the United States. Aerosol delivery devices have evolved over more than 60 years from the basic pressurized metered-dose inhaler and nebulizer to numerous types of inhalers and devices, including valved holder chambers, dry powder inhalers, soft mist inhalers, as well as smart inhalers and nebulizers. Although these devices improve a patient's ability to self-administer medication, many problems with optimal delivery still exist. Appropriate selection and repeated patient education can help lessen the problems with these devices. Aerosol science is evolving, with methods of measurement that include radio-scintigraphy and magnetic resonance imaging, to provide a better understanding of aerosol delivery and effects. Understanding the science and clinical application of aerosol drug delivery can substantially aid clinicians in optimizing these therapies for their patients.

Clinical Pharmacology of Bronchodilator Medications.

Obstructive lung diseases, including asthma and COPD, are characterized by air-flow limitation. Bronchodilator therapy can often decrease symptoms of air-flow obstruction by relaxing airway smooth muscle (bronchodilation), decreasing dyspnea, and improving quality of life. In this review, we discuss the pharmacology of the β agonist and anticholinergic bronchodilators and their use, particularly in asthma and COPD. Expanding knowledge of receptor subtypes and G-protein signaling, agonist and antagonist specificity, and drug delivery have led to the introduction of safer medications with fewer off-target effects, medications with longer duration of action that may improve adherence, and more effective and efficient aerosol delivery devices.

Scaling an idealized infant nasal airway geometry to mimic inertial filtration of neonatal nasal airways

Idealized extrathoracic airways are a valuable tool for the development and testing of pharmaceutical aerosol delivery devices. These airways are designed to mimic the average filtration properties of the extrathoracic airways of the population on which they are based. We have investigated the ability to scale a previously developed infant nasal airway to generate a model with the correct filtration properties to mimic the neonatal population. Prospective scale factors were identified based on the dimensions of realistic nasal replicas, and based on 50th percentile body mass, body length, and head circumference. Inertial deposition was measured for four geometrically similar idealized nasal airway models. These data were compared to deposition in nasal airway replicas based on computed tomography (CT) images of seven infants between the ages of 5 and 79 days. Isotropically scaling the model that mimics the infant population (average age approximately 9 months) by 0.75 produced a model that mimics the neonatal population (average age approximately 1 month). This scale factor was consistent with the ratio of model characteristic diameters (airway volume divided by surface area, DV/As) and with the ratio of 50th percentile body lengths for the two average ages. A predictive correlation based on Reynolds and Stokes numbers was identified that provides deposition efficiency of this geometry for DV/As between 1.20mm and 0.72mm. This equation can be used to provide expected deposition characteristics of our idealized nasal model before construction at scales not specifically considered here.

Brand and generic use of inhalation medication and frequency of switching in children and adults: A population-based cohort study

ABSTRACTBackground: The expiration of patents of brand inhalation medications and the ongoing pressure on healthcare budgets resulted in a growing market for generics. Aim: To study the use of brand and generic inhalation medication and the frequency of switching between brand and generic and between devices. In addition, we investigated whether switching affected adherence. Methods: From dispensing data from the Dutch PHARMO Database Network a cohort aged ≥ 5 years, using ≥ 1 year of inhalation medication between 2003 and 2012 was selected. Switching was defined as changing from brand to generic or vice versa. In addition, we studied change in aerosol delivery device type (e.g., DPI, pMDI, and nebulizers). Adherence was calculated using the medication possession ratio (MPR). Results: The total cohort comprised 70,053 patients with 1,604,488 dispensations. Per calendar year, 5% switched between brand and generic inhalation medication and 5% switched between devices. Median MPRs over the first 12 months ranged between 33 and 55%. Median MPR over the total period was lower after switch from brand to generic and vice versa for formoterol (44.5 vs. 42.1 and 63.5 vs. 53.8) and beclomethasone (93.8 vs. 59.8 and 81.3 vs. 55.9). Conclusion: Per year, switching between brand and generic inhalation medication was limited to 5% of the patients, switching between device types was observed in 5% as well. Adherence to both generic and brand inhalation medication was low. Effect of switching on adherence was contradictory; depending on time period, medication and type, and direction of switching. Further research on reasons for switching and potential impact on clinical outcomes is warranted.

How Should Aerosols Be Delivered During Invasive Mechanical Ventilation?

The delivery of aerosols to mechanically ventilated patients presents unique challenges and differs from inhaled drug delivery in spontaneously breathing patients in several respects. Successful aerosol delivery during invasive mechanical ventilation requires careful consideration of a host of factors that influence the amount of drug inhaled by the patient. Pressurized metered-dose inhalers and nebulizers (jet, ultrasonic, and vibrating mesh) are the most commonly used aerosol delivery devices in these patients, although other delivery devices, such as dry powder inhalers, soft mist inhalers, and intratracheal nebulizing catheters, could also be adapted for in-line use. Bronchodilators, inhaled corticosteroids, antibiotics, pulmonary surfactant, mucolytics, biologicals, genes, prostanoids, and other agents are administered by inhalation during mechanical ventilation for a variety of indications. The goals of inhalation therapy during mechanical ventilation could be best achieved by (1) assuring drug delivery; (2) optimizing drug deposition in the lung; (3) providing consistent dosing; (4) avoiding inappropriate therapies; (5) achieving reproducible dosing; (6) employing clinically feasible methods; (7) enhancing the safety of inhaled drugs; and (8) controlling costs of aerosol therapy. The techniques of administration of aerosols with various delivery devices during mechanical ventilation are well known, but there continues to be significant variation in clinical practice and guidelines are needed to provide best practices for a wide range of clinical settings encountered in mechanically ventilated patients.

A Trans-Nasal Aerosol Delivery Device for Efficient Pulmonary Deposition

Efficient delivery of aerosols to the lungs via the nasal route has been difficult to achieve, but it may offer benefits over the traditional oral route for a range of patient populations. Because slow, continuous delivery of short-acting agents could improve safety, tolerability, compliance, and efficacy when compared with the rapid, intermittent aerosol treatments delivered by mouthpiece or mask, a novel trans-nasal pulmonary aerosol delivery (tPAD) device was developed. The tPAD incorporates an aerosol particle-size selection chamber and a custom nasal cannula that are specifically optimized for aerosol delivery to the lung via the nasal route. The tPAD device produced a steady aerosol output (∼2 mL/h) from an optimized nasal cannula with negligible rainout in the cannula for up to 8 hours. The generated aerosol particles were small enough to minimize nasal deposition [volume median diameter (VMD) = 1.4 μm]. In this proof-of-concept study, gamma scintigraphy was used to quantitate deposition efficiency of 99mTc-labeled DTPA in 7% NaCl (hypertonic saline) in healthy human subjects (n = 6) during a short dosing period (15 minutes). A comparison was made with a standard oral jet nebulizer in the same subjects. The tPAD device achieved high pulmonary deposition (39% ± 8%), based on emitted dose, and matched that of the oral jet nebulizer (36% ± 9%). Low fractions of aerosol deposition in the head and nose region were observed for tPAD (6% ± 6%) and jet nebulizer deliver (1% ± 1%) as well. A profile of high pulmonary deposition efficiency and low nasal dose may enable the sustained use of the tPAD platform with a variety of therapeutic agents for a range of pulmonary disorders.

Aerosol Delivery Devices for the Treatment of Adult Patients in Acute and Critical Care.

Aerosolized medications are commonly used for the treatment of patients with pulmonary diseases in acute care. While there are many drug/device combinations available on the market, new devices have been developed in the past few years. Due to differences in their operation, performance and requirements for proper use, it is important to know how to use these aerosol devices effectively during inhalation therapy both in ambulatory and acute settings. However, clinicians focus on the drug formulation and a relatively little effort was made in improving the design of aerosol devices and individualizing inhalation therapy in acute and critically ill patients. Therefore, this paper reviews aerosol devices used for the treatment of patients with an emphasis on acute and critical care.