Demographic and Asthma-Related Characteristics of Asthmatics Using Pressurized Metered Dose Inhalers and Dry Powder Inhalers.

Background: Asthma controller medications can be delivered via pressurized metered dose inhaler (pMDI) or dry powder inhaler (DPI) devices. Objective: This study aimed to evaluate the frequency of exacerbations and satisfaction rate with device use in asthmatics using pMDIs or DPIs. Methods: A multicenter, cross-sectional study was conducted in adults who used pMDIs or DPIs with correct inhaler technique and good adherence for asthma treatment. Demographic and asthma-related characteristics of the subjects and data regarding device satisfaction were collected through a face-to-face interview in the outpatient clinic. Rates of pMDI and DPI users and the data were compared between the two groups. Results: The study included 338 patients (mean age: 48.6 ± 14.5 years, 253 [74.9%] women). Among participants, 96 (28.4%) were using pMDI and 242 (71.6%) were using DPI. The age of patients using pMDI were significantly lower compared with DPI users. No significant difference was observed in terms of device satisfaction and clinical outcomes of asthma between pMDI and DPI users with good inhaler technique and good adherence. Conclusion: More asthmatics use DPIs, however, pMDIs are used in younger asthmatic patients. No significant difference in terms of device satisfaction and clinical outcomes of asthma was observed between pMDI and DPI users.

Maintenance Inhalers for Asthma and COPD in Spain.

BACKGROUND: This study aimed to describe the use of pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) in Spanish subjects in terms of sociodemographic, clinical, and functional characteristics in subjects with asthma or COPD on maintenance treatment with inhaled therapy. METHODS: This was a retrospective, descriptive, national, multi-center, and observational study using a database with 1.8 million patients from hospitals and primary care centers as a secondary information source. RESULTS: The sample included 24,102 subjects with asthma on maintenance therapy (26.0% with pMDI, 55% with DPI, and 19.0% with a combination of DPI + pMDI inhalers) and 12,858 subjects with COPD on maintenance therapy (26% with pMDI; 39% with DPI; and 35% with a combination of pMDI + DPI inhalers, mostly extemporary triple therapy). In proportion, subjects ≥ 75 y old used more pMDI than DPI, while younger subjects (40-64 y old) used more DPI. An inhalation chamber was prescribed in 51.0% of subjects with asthma and 47.2% of subjects with COPD treated with pMDI. The use of an inhalation chamber increases with the degree of air-flow limitation by disease and age. In subjects with comorbidities, pMDI inhaler use increased in those ≥ 75 y old for subjects with asthma and subjects with COPD. Switching from pMDI to DPI and vice versa was relatively common: 25% of subjects with asthma and 21.6% of subjects with COPD treated with pMDI had switched from DPI in the previous year. On the contrary, 14.1% and 11.4% of subjects with asthma and subjects with COPD, respectively, treated with DPI had switched from pMDI the last year. CONCLUSIONS: The use of pMDI or DPI can vary according to age, both in asthma and COPD. Switching from pMDI to DPI and vice versa is relatively common. Despite the availability of dual- and triple-therapy inhalers on the market, a considerable number of subjects were treated with multiple devices.

Optimal Inhalation Profile of Pressurized Metered Dry Powder Inhaler Using a Valved Holding Chamber: A Dynamic Analysis.

Background: The combined use of a pressurized metered-dose inhaler and valved holding chamber (pMDI+VHC) is recommended to improve efficiency and safety; however, aerosol release is likely to vary with the inhalation maneuver. This in vitro study investigated the aerodynamic characteristics and aerosol release features of pMDI+VHC (Aerochamber, Trudell Medical International). Methods: The static and dynamic changes in the airway resistance (Raw) during inhalation (withdrawal) through pMDI+VHC were measured. Subsequently, the aerosol released from pMDI+VHC was measured using simplified laser photometry during withdrawal with either fast ramp-up then steady or slow ramp-up followed by gradual decrement at different intensities and times to peak flow (TPWF). Results: Raw increased linearly with changes in the withdrawal flow (WF) rate between 10 and 50 L/min. The slope was steep in the low WF range (<50 L/min) and became milder in the higher range. The aerosol mass tended to increase with an increase in the peak WF (PWF) of slow ramp-up profile. When three different WF increment slopes (TPWF: 0.4, 1.4, and 2.4 seconds) were compared, the released aerosol mass tended to decrease, and the aerosol release time was prolonged at longer TPWF. When the PWF was increased, the aerosol release time became shorter, and the withdrawn volume required for 95% aerosol release became larger; however, it did not exceed 0.4 L at suitable TPWF (0.4 seconds). Conclusion: Raw analysis suggests that inhalation at 30-50 L/min is suitable for pMDI+VHC in this setting. Rapid (TPWF, 0.4 seconds) inhalation, but not necessarily long (maximum 2.0 seconds) and deep (but larger than 0.55 L), is also recommended. Practically, direct inhalation to be weaker than usual breathing, as fast as possible, and far less than 2.0 seconds.

Aerosol Plumes of Inhalers Used in COPD.

INTRODUCTION: The selection of inhaler device is of critical importance in chronic obstructive pulmonary disease (COPD) as the interaction between a patient's inhalation profile and the aerosol characteristics of an inhaler can affect drug delivery and lung deposition. This study assessed the in vitro aerosol characteristics of inhaler devices approved for the treatment of COPD, including a soft mist inhaler (SMI), pressurized metered-dose inhalers (pMDIs), and dry powder inhalers (DPIs). METHODS: High-speed video recording was used to visualize and measure aerosol velocity and spray duration for nine different inhalers (one SMI, three pMDIs, and five DPIs), each containing dual or triple fixed-dose combinations of long-acting muscarinic receptor antagonists and long-acting ß2-agonists, with or without an inhaled corticosteroid. Measurements were taken in triplicate at experimental flow rates of 30, 60, and 90 l/min. Optimal flow rates were defined based on pharmacopoeial testing requirements: 30 l/min for pMDIs and SMIs, and the rate achieving a 4-kPa pressure drop against internal inhaler resistance for DPIs. Comparison of aerosol plumes was based on the experimental flow rates closest to the optimal flow rates. RESULTS: The Respimat SMI had the slowest plume velocity (0.99 m/s) and longest spray duration (1447 ms) compared with pMDIs (velocity: 3.65-5.09 m/s; duration: 227-270 ms) and DPIs (velocity: 1.43-4.60 m/s; duration: 60-757 ms). With increasing flow rates, SMI aerosol duration was unaffected, but velocity increased (maximum 2.63 m/s), pMDI aerosol velocity and duration were unaffected, and DPI aerosol velocity tended to increase, with a more variable impact on duration. CONCLUSIONS: Aerosol characteristics (velocity and duration of aerosol plume) vary by inhaler type. Plume velocity was lower and spray duration longer for the SMI compared with pMDIs and DPIs. Increasing experimental flow rate was associated with faster plume velocity for DPIs and the SMI, with no or variable impact on plume duration, whereas pMDI aerosol velocity and duration were unaffected by increasing flow rate.

The impact of actuator nozzle and surroundings condition on drug delivery using pressurized-metered dose inhalers.

The most commonly used method to deliver aerosolized drugs to the lung is with pressurized metered-dose inhalers (pMDIs). The spray actuator is a critical component of pMDI, since it controls the atomization process by forming aerosol plumes and determining droplet size distribution. Through computational fluid dynamics (CFD) simulations, this study investigated the effect of two different nozzle types (single conventional and twin nozzles) on drug deposition in the mouth-throat (MT) region. We also studied the behavior of aerosol plumes in both an open-air environment and the MT geometry. Our study revealed that spray aerosol generated in an unconfined, open-air environment with no airflow behaves distinctly from spray introduced into the MT geometry in the presence of airflow. In addition, the actuator structure significantly impacts the device's efficacy. In the real MT model, we found that the twin nozzle increases drug deposition in the MT region, and its higher aerosol velocity negatively affects its efficiency.

Effect of Chronic Obstructive Pulmonary Disease Severity on Inspiratory Flow Rates via Inhaler Devices.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder that affects millions of people worldwide and inhalation therapy is central to the symptomatic management of the disease. Therefore, knowledge of the minimum Peak inspiratory flow (PIF) requirements for specific inhalers especially dry powder inhalers (DPI's) is necessary when prescribing inhalation therapy. The purpose of this study is to assess the effect of COPD severity on PIF in patients with COPD. METHODOLOGY: A total of 150 subjects (75 patients with stable COPD, and 75 apparently healthy subjects) participated in the study. PIF was assessed using the In-check Inhaler Assessment Kit (manufactured by Clement Clarke International Ltd, Harlow, UK). Lung function was assessed by spirometry with subjects divided into four groups based on the severity of their airway obstruction using the GOLD criteria. The Modified Medical Research Council (MMRC) dyspnea scale was used to assess dyspnea severity. Exercise capacity was assessed using the 6-minute walk test. Statistical analysis was performed with SPSS 23.0 software. In all the statistical tests, a p value of <0.05 was considered significant. RESULTS: The mean age for the COPD patient and control population are 72.48 ± 8.01 and 70.69 ± 5.82 respectively. The control group had higher PIF than COPD group; however, only the clickhler and pMDI had statistically significant difference between the mean PIF of the patients compared with the control group. Generally, there was an observed trend of a decrease in mean PIF as the COPD stage progresses with a statistically significant difference observed for Easibreathe (F= 3.52, p= 0.019) and pressurized Metered dose inhaler (pMDI) (F= 4.26, p= 0.008). There was a significant positive correlation between FEV1%, FVC, Exercise capacity (6-minute walk distance) and PIF for Clickhaler, Autohaler, Easybreathe and pMDI. For pMDI, there was a statistically significant difference between means of PIF across the MMRC dyspnea scale with PIF decreasing with increasing severity of dyspnea (F= 2.85, p= 0.033). CONCLUSION: COPD patients have slightly lower PIF than controls. Poor exercise tolerance and lower spirometric pulmonary function parameters may contribute to low PIF.

INTRODUCTION: La bronchopneumopathie chronique obstructive (BPCO) est un trouble respiratoire chronique qui touche des millions de personnes dans le monde et la thérapie par inhalation est essentielle à la gestion symptomatique de la maladie. Par conséquent, il est nécessaire de connaître les exigences minimales en matière de débit inspiratoire de pointe (DIP) pour certains inhalateurs, en particulier les inhalateurs de poudre sèche (IPS), lors de la prescription d'un traitement par inhalation. L'objectif de cette étude est d'évaluer l'effet de la gravité de la BPCO sur le débit de pointe inspiratoire chez les patients atteints de BPCO. MÉTHODOLOGIES: Un total de 150 sujets (75 patients atteints de BPCO stable et 75 sujets apparemment sains) ont participé à l'étude. Le PIF a été évalué à l'aide du kit d'évaluation In-check Inhaler (fabriqué par Clement Clarke International Ltd, Harlow, UK). La fonction pulmonaire a été évaluée par spirométrie, les sujets étant répartis en quatre groupes en fonction de la gravité de l'obstruction des voies respiratoires selon les critères GOLD. L'échelle de dyspnée modifiée du Medical Research Council (MMRC) a été utilisée pour évaluer la sévérité de la dyspnée. La capacité d'exercice a été évaluée à l'aide du test de marche de 6 minutes. L'analyse statistique a été réalisée avec le logiciel SPSS 23.0. Dans tous les tests statistiques, une valeur p de <0,05 a été considérée comme significative. RÉSULTATS: L'âge moyen des patients atteints de BPCO et de la population de contrôle est respectivement de 72,48 ± 8,01 et 70,69 ± 5,82. Le groupe de contrôle avait un PIF plus élevé que le groupe BPCO; cependant, seuls le clickhler et le pMDI présentaient une différence statistiquement significative entre le PIF moyen des patients et celui du groupe de contrôle. D'une manière générale, on a observé une tendance à la diminution du FRP moyen au fur et à mesure de l'évolution de la BPCO, avec une différence statistiquement significative pour l'Easibreathe (F= 3,52, p= 0,019) et l'aérosol-doseur pressurisé (pMDI) (F= 4,26, p= 0,008). Il existe une corrélation positive significative entre le VEMS, la CVF, la capacité d'exercice (distance de marche de 6 minutes) et le PIF pour Clickhaler, Autohaler, Easybreathe et pMDI. Pour le pMDI, il y avait une différence statistiquement significative entre les moyennes de PIF sur l'échelle de dyspnée du MMRC, le PIF diminuant avec l'augmentation de la sévérité de la dyspnée (F= 2,85, p= 0,033). CONCLUSION: Les patients atteints de BPCO ont un PIF légèrement inférieur à celui des témoins. Une mauvaise tolérance à l'exercice et des paramètres spirométriques de la fonction pulmonaire plus faibles peuvent contribuer à la faiblesse du PIF. Mots clés: Maladie pulmonaire obstructive chronique, Inhalateurs de poudre sèche, Débit inspiratoire de pointe, Aérosol-doseur pressurisé.

Relative bioavailability of budesonide/glycopyrrolate/formoterol fumarate triple therapy delivered using next generation propellants with low global warming potential.

INTRODUCTION: The climate crisis poses an immediate threat to human health and well-being, demanding urgent adaptions across sectors, including healthcare. The development of pressurized metered dose inhalers (MDIs) with greater sensitivity to the climate emergency using novel propellants with lower global warming potentials (GWPs), but comparable pharmacokinetic (PK) parameters to currently marketed MDIs, is a vital step toward reducing the impact of healthcare for respiratory disorders on climate change. This study evaluated the relative bioavailabilities of the individual components of a fixed-dose combination of budesonide/glycopyrrolate/formoterol fumarate (BGF) 160/9/4.8 µg per actuation between three different propellant formulations. METHODS: Healthy male participants (aged 18-60 years) were randomized into a single-blind, three-period, single-dose, single-center, crossover study (NCT04600505). The PK and safety and tolerability profiles of BGF MDI formulated with two novel propellants with low GWP (hydrofluoroolefin-1234ze [HFO]; hydrofluorocarbon-152a [HFC]) were compared with BGF MDI formulated with the propellant used in the currently marketed reference product (hydrofluoroalkane-134a [HFA]). The study included a screening period, three treatment periods (with 3- to 7-day washout periods between each dose), and a follow-up. The primary PK parameters assessed were maximum observed plasma concentration (Cmax), area under the plasma concentration curve (AUC) from time zero extrapolated to infinity (AUCinf), and AUC from time zero to the time of the last quantifiable analyte concentration (AUClast). The study was not powered to statistically demonstrate bioequivalence. RESULTS: Forty-seven participants completed the study, and 24 participants were evaluable for PK assessments. Systemic exposure, based on geometric mean ratios (90% confidence interval), to each BGF component from the test propellants delivered in a standard MDI was comparable with the reference propellant for AUClast (HFO vs. HFA: budesonide, 107.30 [94.53, 121.90]; glycopyrrolate, 106.10 [86.18, 130.60]; formoterol, 98.13 [86.44, 111.40]; HFC vs. HFA: budesonide, 98.80 [84.59, 115.40]; glycopyrrolate, 99.71 [80.84, 123.00]; formoterol, 107.00 [88.82, 128.90]); AUCinf (where evaluable) and Cmax followed the same trend. There were no serious adverse events or adverse events leading to treatment discontinuation. No new safety signals were observed. CONCLUSIONS: Systemic BGF component exposure was similar for both test propellants (HFO and HFC) compared with the HFA reference propellant, with an acceptable safety profile in the studied population. Therefore, both novel low GWP propellants show strong potential as candidates for development of MDIs with greater sensitivity to the climate crisis, a vital step toward ameliorating the detrimental impact of healthcare on the environment. Further investigation in larger studies is warranted.

Delivery technology of inhaled therapy for asthma and COPD.

Inhaled therapy is the cornerstone of the management of asthma and chronic obstructive pulmonary disease (COPD). Drugs such as bronchodilators and corticosteroids are administered directly to the airways for local effect and rapid onset of action while systemic exposure and side effects are minimized. There are four major types of inhaler devices used clinically to generate aerosols for inhalation, namely, pressurized metered-dose inhalers (pMDIs), nebulizers, Soft Mist™ inhalers (SMIs) and dry powder inhalers (DPIs). Each of them has its own unique characteristics that can target different patient groups. For instance, patients' inhaler technique is critical for pMDIs and SMIs to achieve proper drug deposition in the lung, which could be challenging for some patients. Nebulizers are designed to deliver aerosols to patients during tidal breathing, but they require electricity to operate and are less portable than other devices. DPIs are the only device that delivers aerosols in dry powder form with better stability, but they rely on patients' inspiration effort for powder dispersion, rendering them unsuitable for patients with compromised lung function. Choosing a device that can cater for the need of individual patient is paramount for effective inhaled therapy. This chapter provides an overview of inhaled therapy for the management of asthma and COPD. The operation principles, merits and limitations of different delivery technologies are examined. Looking ahead, the challenges of delivering novel therapeutics such as biologics through the pulmonary route are also discussed.

Advances in soft mist inhalers.

INTRODUCTION: Soft mist inhalers (SMIs) are propellant-free inhalers that utilize mechanical power to deliver single or multiple doses of inhalable drug aerosols in the form of a slow mist to patients. Compared to traditional inhalers, SMIs allow for a longer and slower release of aerosol with a smaller ballistic effect, leading to a limited loss in the oropharyngeal area, whilst requiring little coordination of actuation and inhalation by patients. Currently, the Respimat® is the only commercially available SMI, with several others in different stages of preclinical and clinical development. AREAS COVERED: The primary purpose of this review is to critically assess recent advances in SMIs for the delivery of inhaled therapeutics. EXPERT OPINION: Advanced particle formulations, such as nanoparticles which target specific areas of the lung, Biologics, such as vaccines, proteins, and antibodies (which are sensitive to aerosolization), are expected to be generally delivered by SMIs. Furthermore, repurposed drugs are expected to constitute a large share of future formulations to be delivered by SMIs. SMIs can also be employed for the delivery of formulations that target systemic diseases. Finally, digitalizing SMIs would improve patient adherence and provide clinicians with fundamental insights into patients' treatment progress.

Dynamic Analysis of Aerosol Release from a Pressurized Metered Dose Inhaler Combined with a Valved Holding Chamber Using Simplified Laser Photometry.

Background: A pressurized metered dose inhaler combined with a valved holding chamber (pMDI+VHC) is used to prevent upper airway complications and improve the efficiency of inhaled drug delivery; however, the aerodynamic behavior of the released particles has not been well investigated. This study aimed at clarifying the particle release profiles of a VHC using simplified laser photometry. Methods: An inhalation simulator comprised a computer-controlled pump and a valve system that withdrew aerosol from a pMDI+VHC using a jump-up flow profile. A red laser illuminated the particles leaving VHC and evaluated the intensity of the light reflected by the released particles. Results: The data suggested that the output (OPT) from the laser reflection system represented particle concentration rather than particle mass, and the latter was calculated as OPT × instantaneous withdrawn flow (WF). Summation of OPT hyperbolically decreased with flow increment, whereas summation of OPT × instantaneous flow was not influenced by WF strength. Particle release trajectories consisted of three phases, namely increment with a parabolic curve, flat, and decrement with exponential decay phases. The flat phase appeared exclusively at low-flow withdrawal. These particle release profiles suggest the importance of early phase inhalation. The hyperbolic relationship between WF and particle release time revealed the minimal required withdrawal time at an individual withdrawal strength. Conclusions: The particle release mass was calculated as laser photometric output × instantaneous flow. Simulation of the released particles suggested the importance of early phase inhalation and predicted the minimally required withdrawal time from a pMDI+VHC.

Inhalable aerosol microparticles with low carrier dosage and high fine particle fraction prepared by spray-freeze-drying.

Co-suspension drug-loading technology, namely Aerosphere™, can improve fine particle fraction (FPF) and delivered dose content uniformity (DDCU). However, because of its poor drug-loading efficacy, the phospholipid carrier dosage in Aerosphere™ is usually dozens of times greater than that of the drug, resulting in a high material cost and blockage of the actuator. In this study, spray-freeze-drying (SFD) technology was used to prepare inhalable distearoylphosphatidylcholine (DSPC)-based microparticles for pressurized metered-dose inhalers (pMDI). Water-soluble, low-dose formoterol fumarate was used as an indicator to evaluate the aerodynamic performance of the inhalable microparticles. Water-insoluble, high-dose mometasone furoate was used to investigate the effects of drug morphology and drug-loading mode on the drug delivery efficiency of the microparticles. The results demonstrated that DSPC-based microparticles prepared using the co-SFD technology not only achieved higher FPF and more consistent delivered dose than those of drug crystal-only pMDI, but the amount of DSPC was also reduced to approximately 4% of that prepared using the co-suspension technology. This SFD technology may also be used to improve the drug delivery efficiency of other water-insoluble and high-dose drugs.

Breath-actuated INhalation TheRapy: survey of phySicians' PErCepTion (INTROSPECT) in Nepal.

OBJECTIVE: Breath-actuated inhalers (BAIs) are gaining attention in the management of obstructive airway diseases (OADs). In Nepal, a BAI containing fluticasone propionate/salmeterol (FPS) has been available for a year. This survey is aimed at determining the perception and experience of physicians in Nepal concerning BAIs. METHODS: A cross-sectional, questionnaire-based survey was conducted. A total of 141 physicians participated and filled the survey. RESULTS: Most physicians felt that the right device should be easy to teach, learn and remember. They considered coordination and multiple steps as the primary challenges with pressurized metered-dose inhalers and dry powder inhalers, respectively. Most of them agreed that BAIs could address these challenges. BAIs were not only preferred by most of the physicians for asthma and chronic obstructive pulmonary disease but were also the preferred choice in newly diagnosed patients. Physicians believed that if current patients were shifted to BAIs, it could improve inhalation technique (88%) and compliance/adherence (81%). Almost all of them (92-97%) agreed that teaching the breathing technique and the cleaning process was easier and faster in BAIs. BAIs were considered easy and simple to use. Also, BAI's dose-counter helps patients to increase adherence to inhalation therapy. CONCLUSIONS: In this INTROSPECT survey, physicians in Nepal believed that BAIs could address the key challenges faced with using pMDIs and DPIs in asthma and COPD patients.

An Investigation into the Factors Associated with Incorrect Use of a Pressurized Metered-Dose Inhaler in Japanese Patients.

Rationale: Inhalation of the correct dose of a short-acting beta 2 agonist (SABA) from a pressurized metered-dose inhaler (pMDI) is essential for the relief of symptoms in patients with asthma and/or chronic obstructive pulmonary disease. The aim of this study was to evaluate the prevalence and factors associated with the incorrect use of a pMDI. Methods: This study retrospectively assessed the electronic medical records of 161 patients with various respiratory diseases. The patients had never used a pMDI and underwent training by pharmacists educated in the use of a pMDI followed by bronchodilator reversibility testing at our hospital. The patients' characteristics and various lung capacity parameters were evaluated for association with the incorrect use of a pMDI. Results: Thirty-nine of the 161 (24.2%) patients, including 46% of 28 patients older than 80 years, used the pMDI incorrectly, mainly because of incoordination between activation of the device and inhalation (n = 11), inadequate strength to manipulate the device (n = 9), too short duration of inhalation (n = 6), and difficulty in breath holding (n = 3). Advanced age; lower height; and decreased lung volumes, including vital capacity (VC), inspiratory capacity, inspiratory reserve volume (IRV), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow rate, were associated with the incorrect use of a pMDI. Neither the body weight, tidal volume, expiratory reserve volume, %FVC predicted, %FEV1 predicted, nor FEV1% was associated with the incorrect use of a pMDI. Multivariate binomial logistic regression analysis identified decreased IRV as the only independent predictor associated with the incorrect use of a pMDI. Conclusions: Physicians should be aware that elderly patients or patients with decreased IRV might be unable to obtain the correct SABA dose from a pMDI. A large-scale prospective study is required to confirm these findings from our retrospective study with a small group of patients.

Calculating the Charcoal Blockade Efficiency for Bioequivalence Study of Inhaled Ipratropium Bromide Using A Model Method.

Charcoal blockade is a useful approach to block gastrointestinal (GI) absorption of orally inhaled drug products (OIDPs) and therefore can be used effectively to determine drug absorption exclusively via the pulmonary route. Charcoal blockade efficiency (CBE) should be measured to show whether adequate blockade of GI exposure is achieved in bioequivalence (BE) study. The purpose of this study is to employ a model method to calculate the CBE for a pilot pharmacokinetic (PK) BE study of inhaled ipratropium bromide. This model method, based on a convolution integral, is built in-house using MATLAB package. The results demonstrated a full blockade of GI absorption of ipratropium bromide for both test and reference drug products. This study has shown that the model method may provide a useful approach for validation of charcoal blockade method used in PK BE study for OIDPs. The ability to use modeling may simplify human PK studies in general, and is particularly valuable when for ethical, technical or regulatory reasons administration of an orally swallowed form of the drug is not possible.

How to Choose the Right Inhaler Using a Patient-Centric Approach?

There are many different inhaler devices and medications on the market for the treatment of asthma and chronic obstructive pulmonary disease, with over 230 drug-delivery system combinations available. However, despite the abundance of effective treatment options, the achieved disease control in clinical practice often remains unsatisfactory. In this context, a key determining factor is the match or mismatch of an inhalation device with the characteristics or needs of an individual patient. Indeed, to date, no ideal device exists that fits all patients, and a personalized approach needs to be considered. Several useful choice-guiding algorithms have been developed in the recent years to improve inhaler-patient matching, but a comprehensive tool that translates the multifactorial complexity of inhalation therapy into a user-friendly algorithm is still lacking. To address this, a multidisciplinary expert panel has developed an evidence-based practical treatment tool that allows a straightforward way of choosing the right inhaler for each patient.

Switching to the Dry-Powder Inhaler Easyhaler®: A Narrative Review of the Evidence.

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler® device, a high- or medium-high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases. Enhanced feature (slides, video, animation) (MP4 43768 kb).

Impact of inhalers used in the treatment of respiratory diseases on global warming.

The term "carbon footprint" describes the emission of greenhouse gases into the environment as a result of human activities. The healthcare sector is responsible for 5-8% of the value of global greenhouse gas emissions, of which medical aerosols account for only 0.03% of the total emissions. The reduction of greenhouse gases, including those used for the production and use of medicinal products and medical devices, is part of the responsibilities that Poland and the respective countries should undertake in order to implement the assumptions of international law. At the level of medical law, this obligation correlates with the need to exercise due diligence in the process of providing health services, including the selection of low-emission medical products and devices (inhalers) and providing patients with information on how to handle used products and devices, with particular emphasis on those that imply greenhouse gas emissions. Pressurized metered dose inhalers (pMDI) containing the hydrofluoroalkane 134a demonstrate the largest carbon footprint, followed by a metered dose liquid inhaler and dry powder inhalers (DPI). The carbon footprint of DPI with a given drug is 13-32 times lower than it is in the case of the corresponding pMDI. Replacement of pMDI by DPI is one of the effective methods to reduce the carbon footprint of inhalers, and the replacement should be based on current medical knowledge. A recycling system for all types of inhalers must be urgently implemented.

Aerosol delivery of inhalation devices with different add-on connections to invasively ventilated COPD subjects: An in-vivo study.

Aerosol delivery to mechanically ventilated patients requires add-on connections to place the inhalation device within the ventilation circuit. The study aimed to evaluate the performance of Combihaler in dual limb invasive mechanical ventilation (IMV). A ventilator with a humidified dual limb circuit was adjusted to volume-controlled mode to imitate the adult breathing parameters. 24 (12 females) intubated chronic obstructive pulmonary disease (COPD) subjects had undergone the study. All patients were prescribed inhaled salbutamol dose delivered by either a metered-dose inhaler (pMDI) or vibrating mesh nebulizer (VMN). Each subject received salbutamol in four different inhalation device/connection conditions; pMDI+VMN+Combihaler, VMN+Combihaler, VMN+T-piece, and pMDI+T-piece. They were individually placed in the inspiratory limb at Y-piece. 5mg salbutamol was delivered by VMN with and without 2 pMDI puffs of salbutamol (100 µg), and 500µg was delivered by pMDI+T-piece. After aerosol delivery, two urine samples were collected from the patient; 30 min post-inhalation (USAL0.5) and cumulatively 24 h post-inhalation (USAL24) as indexes of lung deposition and systemic absorption, respectively. For the ex-vivo study, a collecting filter was placed before an endotracheal tube (ETT) to collect the delivered inhalable dose. In-vitro aerodynamic characteristics were also investigated. pMDI+VMN+Combihaler delivered more salbutamol to the lung and the ex-vivo filter than VMN+T-piece (p˂0.05, p≤0.01, respectively). VMN delivered a higher salbutamol amount to the lung, systemically, and the ex-vivo filter than pMDI+T-piece (p˂0.001). pMDI+VMN+Combihaler and VMN+Combihaler delivered aerosols with a less mass median aerodynamic diameter (MMAD) and higher fine particle fraction (FPF) compared to VMN+T-piece (p≤0.01 for MMAD, p˂0.01 for FPF) and pMDI+T-piece (p˂0.01 for both MMAD and FPF). Results of the study showed that pMDI+VMN+ Combihaler delivered more salbutamol than VMN+T-piece in IMV and demonstrate that 5 puffs (500-µg) of salbutamol with pMDI+T-piece has a lower aerosol delivering power at the level of USAL0.5, USAL24, and the ex-vivo inhalable dose than 5 mg nebulized salbutamol by VMNs in IMV.

Salbutamol Transport and Deposition in the Upper and Lower Airway with Different Devices in Cats: A Computational Fluid Dynamics Approach.

Pressurized metered-dose inhalers (pMDI) with or without spacers are commonly used for the treatment of feline inflammatory airway disease. During traditional airways treatments, a substantial amount of drugs are wasted upstream of their target. To study the efficiency of commonly used devices in the transport of inhaled salbutamol, different computational models based on two healthy adult client-owned cats were developed. Computed tomographic images from one cat were used to generate a three-dimensional geometry, and two masks (spherical and conical shapes) and two spacers (10 and 20 cm) completed the models. A second cat was used to generate a second model having an endotracheal tube (ETT) with and without the same spacers. Airflow, droplet spray transport, and deposition were simulated and studied using computational fluid dynamics techniques. Four regions were evaluated: device, upper airways, primary bronchi, and downstream lower airways/parenchyma ("lung"). Regardless of the model, most salbutamol is deposited in devices and/or upper airways. In general, particles reaching the lung varied between 5.8 and 25.8%. Compared with the first model, pMDI application through the ETT with or without a spacer had significantly higher percentages of particles reaching the lung (p = 0.006).

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.