Improvement in Inhaler Techniques After Training and Counseling in Patients With Chronic Obstructive Pulmonary Disease or Asthma.

Background Chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma significantly impair quality of life and impose a substantial burden on healthcare systems. Proper inhalation technique is important for effective management of these diseases, yet remains poorly performed by many patients. This study evaluated the impact of structured counseling and training sessions on inhaler use among patients with COPD and asthma, aiming to enhance technique correctness and disease control. Methodology This cross-sectional study analyzed 150 patients with asthma and COPD who fulfilled the inclusion criteria for inhalation techniques. Patients were counseled regarding the proper seven-step inhalation technique for each inhaler type [metered-dose inhaler (MDI), MDI with spacer, and dry powder inhaler (DPI)] through practical demonstration at baseline visits. Correct use of inhalers was assessed by a predefined checklist for each inhaler device at the baseline visit and after three months. The correctness of the inhalation technique was evaluated by scoring each of the seven steps. The disease control assessment was done using the COPD assessment test (CAT) and asthma control test (ACT) at the baseline visit and after three months. Results In this study of 150 patients, there were 97 (64.7%) males and 53 (35.3%) females. In total, 67 (44.7%) were diagnosed with asthma and 83 (55.3%) with COPD. The mean age was 45.33 ± 12.62 years. Post-counseling improvements in inhaler technique were marked, with MDI users enhancing their technique score from an average of 4.4 to 6.1, MDI with spacer from 4.56 to 6.26, and DPI from 4.92 to 6.24 (p < 0.001 for all). Disease control also showed significant gains; CAT scores decreased for MDI users from 23.4 to 20.5, MDI with spacer from 23.92 to 20.96, and DPI from 24.89 to 21.96. Concurrently, ACT scores increased for MDI users from 16.4 to 18.0 (p = 0.002), MDI with spacer from 17.29 to 19.04, and DPI from 16.42 to 18.37 (p < 0.001 for both), reflecting substantive advances in managing COPD and asthma symptoms. Furthermore, patients with primary education exhibited a significant boost in technique mastery post-counseling (p < 0.001), underscoring the potential of well-crafted counseling to transcend educational barriers in promoting effective inhaler use. Conclusions Post-counseling, inhaler technique improved significantly across all types, with MDI with spacer users demonstrating the most progress. Technique scores increased notably (p < 0.001), and disease control scores for COPD and asthma, measured by CAT and ACT, also showed significant improvements (p < 0.001). Remarkably, primary education level participants exhibited substantial technique gains post-intervention, emphasizing the effectiveness of counseling irrespective of initial educational status in enhancing inhaler use and disease management.

Real World Evidence asthma and COPD inhaled treatment therapy in Spain.

Background: This study aimed to describe the use of pressured metered dose inhalers (pMDI) and dry powder inhalers (DPI) in Spanish patients in terms of socio-demographic, clinical, and functional characteristics in patients with asthma or COPD on maintenance treatment with inhaled therapy. Methods: A retrospective, descriptive, national, multicentre, 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, 54.9% with DPI, and 19.0% with a combination of DPI + pMDI inhalers) and 12,858 subjects with COPD on maintenance therapy (26.1% with pMDI, 38.7% with DPI and 35.2% with a combination of pMDI + DPI inhalers, mostly extemporary triple therapy). In proportion, subjects ≥ 75 years old use more pMDI than DPI, while younger subjects (40-64 years old) use more DPI. An inhalation chamber was prescribed in 51.0% of asthma subjects and 47.2% of COPD subjects treated with pMDI. The use of an inhalation chamber increases with the degree of airflow limitation by disease and age. In subjects with comorbidities, pMDI inhaler use increased in those ≥75 years old for asthma and COPD subjects. Switching from pMDI to DPI and vice versa was relatively common: 25.5% of asthma subjects and 21.9% of COPD subjects treated with pMDI had switched from DPI in the previous year. On the contrary, 14.1% and 11.7% of asthma and COPD patients 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.

Evaluation of the Metered Dose Inhaler Technique: Initial Assessment and Post-counseling Improvements Among the Indian Population.

Objective The objective of this study was to evaluate errors in the use of metered-dose inhalers (MDIs) among patients diagnosed with asthma or chronic obstructive pulmonary disease (COPD). Additionally, we aimed to assess improvements following corrective interventions. Settings and design This cross-sectional study was done by simple random sampling. Methods and materials This study was done at a tertiary care center in South India in an outpatient department and ward for tuberculosis and chest disease to find out the right way to use an MDI and investigate the reasons why people with asthma and COPD don't use it correctly. There were a total of 12 steps. The patient was given an empty canister to try the inhalation technique and was scored one point for every correct step and zero for every incorrect step, for a total of 12 steps. Following the demonstration, an educator used a variety of tools, including verbal communication, pictorial demonstrations, and practical demonstrations, to correct the mistakes. After education was provided, post-interventional data was collected. Results During pre-intervention of the 12 steps out of the 183 participants, step one had 183 correct participants (100%), step two had 104 correct participants (56.83%), step three had 129 correct participants (70.49%), step four had 71 correct participants (38.79%), step five had 167 correct participants (91.25%), step six had 123 correct participants (67.21%), step seven had 132 correct participants (72.13%), step eight had 81 correct participants (43.71%), step nine had 123 correct participants (67.21%), step 10 had 108 correct participants (59.01%), step 11 had 128 correct participants (69.94%), and step 12 had 175 correct participants (95.62%). During the post-intervention of the 12 steps, out of the 183 participants, step one remained at 183 correct participants (100%), step two increased to 149 correct participants (81.42%), step three to step seven increased to 183 correct participants (100%), step eight increased to 142 correct participants (77.59%), step nine increased to 174 correct participants (95.08%), step 10 increased to 177 correct participants (96.72%), step 11 increased to 143 correct participants (78.14%) and step 12 increased to 177 correct participants (96.72%). Conclusion This study highlights the prevalent errors in the use of metered-dose inhalers (MDIs) among patients diagnosed with asthma or chronic obstructive pulmonary disease (COPD). The results demonstrate significant improvements in the MDI technique. Following educational interventions such as verbal communication, pictorial demonstrations, and practical exercises, patients were able to correct their inhaler technique effectively and emphasized the importance of patient education and counseling to ensure the maintenance of correct usage over time.

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.

Effect of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler combined with nasal high-flow nasal cannula on elderly patients with COPD and respiratory failure.

Objective: To explore the clinical effect of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) combined with high-flow nasal cannula (HFNC) in the treatment of elderly patients with chronic obstructive pulmonary disease (COPD) and respiratory failure. Methods: The clinical records of 94 elderly patients with COPD and respiratory failure who were treated in Yongkang First People's Hospital from February 2022 to January 2023 were retrospectively selected. Among them, 46 patients received HFNC alone (Control-group) and 48 patients received HFNC combined with BGF MDI (Study-group). The treatment effect, arterial blood gas status, pulmonary function, and acute physiology and chronic health evaluation (APACHE) II score before and after treatment were analyzed in both groups. Results: The total efficacy of treatment in the Study-group (95.8%) was higher than that in the Control-group (78.3%) (P<0.05). After treatment, the partial pressure of arterial carbon dioxide (PaCO2), residual volume, and APACHE II scores in the two groups decreased compared to those before treatment, with the Study-group lower overall. However, arterial oxygen saturation (SaO2), oxygen partial pressure (PaO2), the percentage of peak expiratory flow (PEF), and forced expiratory volume in one second (FEV1) as percent of predicted (%FEV1) were higher than before treatment, and higher in the Study-group (P<0.05). Conclusions: Compared with HFNC alone, BGF MDI combined with HFNC can effectively regulate the arterial blood gas status of elderly patients with COPD and respiratory failure, restore pulmonary function, and improve the overall treatment effect.

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 Nonclinical Assessment of Trans-1,3,3,3-tetrafluoropropene (HFO-1234ze (E)), a Near Zero Global Warming Potential Propellant for Use in Metered Dose Inhalation Products.

HFO-1234ze (E) is proposed as a near zero global warming propellant for use in metered dose inhaled (MDI) products. This paper describes the non-clinical safety assessment in mice, rats, and dogs and supplements previously reported data (genetic toxicology, short-term toxicology, and reproductive toxicology). In all species, HFO-1234ze (E) was only detectable in blood for a short period after dosing with no evidence of accumulation. HFO-1234ze (E) was without any toxicological effects at very high doses in subchronic (13-week mouse) and chronic (39-week dog) studies. Chronic (26-week) administration to rats at very high doses was associated with an exacerbation of rodent progressive cardiomyopathy, a well-documented background finding in rodents. In a 2-generation study, extremely high doses were associated with the early euthanasia of some lactating female rats. This finding was considered to be significantly influenced by a state of negative energy balance, reflecting the specific vulnerability of rats during lactation. These findings are considered to not pose a risk to humans with typical MDI use given they occurred at doses which far exceed those expected in patients. Overall, the nonclinical safety data for HFO-1234ze (E) support its further development as an MDI propellant.

Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testing: a retrospective study.

BACKGROUND: The recommended delivery mode for bronchodilators in bronchodilator responsiveness (BDR) testing remains controversial. OBJECTIVE: To compare the efficacy of salbutamol administration using a nebulizer versus a metered-dose inhaler (MDI) with spacer in BDR testing. DESIGN: A retrospective study. METHODS: This study examined the data of patients with chronic obstructive pulmonary disease who completed BDR testing between 1 December 2021 and 30 June 2022, at Xiangya Hospital, Central South University. After administering 400 µg of salbutamol through an MDI with spacer or 2.5 mg using a nebulizer, the changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were analyzed in patients with moderate-to-very severe spirometric abnormalities [pre-bronchodilator FEV1 percentage predicted values (FEV1%pred) ⩽59%]. Significant responsiveness was assessed as >12% and >200 mL improvement in FEV1 and/or FVC or >10% increase in FEV1%pred or FVC percentage predicted values (FVC%pred) from pre- to post-bronchodilator administration. RESULTS: Of the enrolled 894 patients, 83.2% were male (median age, 63 years). After propensity score matching, 240 pairs of patients were selected. The increment in FEV1 and increased FEV1 relative to the predicted value (ΔFEV1%pred) were significantly higher in patients <65 years and those with severe spirometric abnormalities in the nebulization group than patients in the MDI group (all p < 0.05). Compared with MDI with spacer, patients who used nebulization had a 30 mL greater increase in ΔFEV1 (95% CI: 0.01-0.05, p = 0.004) and a 1.09% greater increase in ΔFEV1%pred (95% CI: 0.303-1.896, p = 0.007) from baseline. According to the > 12% and >200 mL increase criterion, the significant BDR rate with nebulization was 1.67 times higher than that with an MDI with spacer (OR = 1.67, 95% CI: 1.13-2.47, p = 0.009). CONCLUSION: Salbutamol delivered using a nebulizer may be preferable to an MDI with spacer in certain circumstances. Nebulization has the potential to increase responsiveness to salbutamol in BDR testing.

Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testingBronchodilator responsiveness testing is commonly undertaken as an important part of spirometry testing to determine the degree of volume and airflow improvement after bronchodilator administration. BDR testing results may affect patients' diagnosis and treatment. This study compared the effects of two delivery models (a metered dose inhaler (MDI) with spacer and nebulization) on responsiveness to bronchodilators and the results of bronchodilator responsiveness testing among patients with chronic obstructive pulmonary disease. We found that the increment in forced expiratory volume in one second were significantly higher in patients aged <65 years and in those with severe spirometric abnormalities in the nebulization group than in those in the MDI group. The study provides evidence that salbutamol delivered by a nebulizer is preferable to an MDI with spacer in patients <65 years and in those with severe spirometric abnormalities and could increase positive responsiveness to bronchodilators. The study will assist in clinical decision-making by selecting the appropriate dosing regimen for different patients.

Recent Advances in the Devices for the Treatment of Chronic Obstructive Pulmonary Disease: A Review.

Chronic obstructive pulmonary disease or COPD has been known to adversely affect people's quality of life. It influences a great number of individuals overall and is a main source of horribleness and mortality. It is associated with major healthcare and socioeconomic burdens. So, it is important to cure such types of diseases. This review article deals with the proper understanding of the newly developed devices and various advances taking place in the treatment of COPD. There are many new methods and procedures being developed recently for the cure or treatment of COPD, of which some are mentioned in the following review article. The articles also deal with the beneficial effects as well as the challenges faced during the use of those newly developed methods during the treatment of the disease. Various types of management of COPD are also mentioned in the article. This article also deals with the various new advances that are currently taking place in devices used in the therapy of COPD.

Canister valve and actuator deposition in metered dose inhalers formulated with low-GWP propellants.

A challenge in pressurised metered-dose inhaler (pMDI) formulation design is management of adhesion of the drug to the canister wall, valve and actuator internal components and surfaces. Wall-material interactions differ between transparent vials used for visual inspection and metal canister pMDI systems. This is of particular concern for low greenhouse warming potential (GWP) formulations where propellant chemistry and solubility with many drugs are not well understood. In this study, we demonstrate a novel application of X-ray fluorescence spectroscopy using synchrotron radiation to assay the contents of surrogate solution and suspension pMDI formulations of potassium iodide and barium sulphate in propellants HFA134a, HFA152a and HFO1234ze(E) using aluminium canisters and standard components. Preliminary results indicate that through unit life drug distribution in the canister valve closure region and actuator can vary significantly with new propellants. For solution formulations HFO1234ze(E) propellant shows the greatest increase in local deposition inside the canister valve closure region as compared to HFA134a and HFA152a, with correspondingly reduced actuator deposition. This is likely driven by chemistry changes. For suspension formulations HFA152a shows the greatest differences, due to its low specific gravity. These changes must be taken into consideration in the development of products utilising low-GWP propellants.

Clinical outcomes of children using a metered dose inhaler with a sleeve attachment device to improve ease of use.

Background: Activating pressurized metered dose inhalers (pMDIs) is often challenging for children. The Easy Squeezy (ES) is a novel sleeve attachment device that reduces activation force by 3 times. Although users have favored using the ES over using a pMDI alone, the clinical impact of the ES remains unknown. The aim of this study was to compare lung function and quality of life between ES users and users of a pMDI alone. Objectives: Our aim was to measure and compare lung function of asthmatic children after they used the ES and pMDI alone. Methods: In this crossover study we recruited 65 asthmatic children between the ages of 5 and 12 years. The participants were randomized into 2 groups. One of the groups used the ES for 6 weeks whereas the other group used a pMDI. After 6 weeks the participants crossed over to the other group. Lung function test parameters were measured after randomization and after each 6 weeks of device use. Quality of life (measured by the Patient Asthma Quality of Life Questionnaire [PAQLQ]) and Childhood Asthma Control Test were measured after each period of device use. Results: There was no significant difference in the baseline lung function between the groups. The ES group had a significantly lower percentage difference between prebronchodilator and postbronchodilator FEV1 values. Although no significant differences were observed in PAQLQ scores between the groups, more patients in the ES group had improvement of their PAQLQ score than did patients in the group using a pMDI alone. Total Childhood Asthma Control Test scores were significantly higher for the ES group. Conclusions: The ES device may allow users' asthma to be better controlled than by using a pMDI alone.

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.

Uncapped Metered-Dose Inhalers: A Risk for Foreign Body Aspiration. A Case Report and Review of the Literature.

The risk of foreign body aspiration associated with uncapped handheld metered-dose inhalers (MDIs) is underestimated. We report a case in which a plastic cable clip accidentally lodged in the mouthpiece of an uncapped pressurized MDI was aspirated during its use. A literature search revealed 16 other cases of foreign body aspiration associated with uncapped handheld inhalers, all but one of which were pressurized inhalers. Patients should be informed of the risk of foreign body aspiration associated with uncapped pocket inhalers. The use of an uncuffed armoured tracheal tube with a separate oxygen tubing during flexible bronchoscopy for foreign body removal ensures a safe airway. Foreign bodies that exceed the lumen size of the tracheal tube can be pulled to the distal opening with forceps and removed when the tube is withdrawn.

Breathe easy: inhalational therapy for feline inflammatory airway disease.

PRACTICAL RELEVANCE: Feline inflammatory airway diseases, including (but not limited to) asthma, chronic bronchitis and bronchiectasis, are common and incurable disorders. These diseases require lifelong therapy and may result in substantial morbidity and, in some cases, mortality. Goals of therapy include reduction or resolution of clinical signs and the underlying pathologic processes driving those clinical signs. Inhalational therapy has the advantage of topical delivery of drugs to target tissues at higher doses with fewer systemic effects than oral medications. There are multiple options for delivery devices, and proper selection and training on the use of these devices - including acclimation of the cat to the device - can maximize therapeutic efficacy. AIM: As inhalational therapy is uncommonly used by many veterinarians and owners, this review article provides a foundation on the selection and use of devices and inhalant medications for specific feline inflammatory airway diseases. Cats present a unique challenge with respect to the use of inhalers, and easy-to-follow steps on acclimating them to the devices are provided. The review also discusses the mechanics of inhalational therapy and helps clarify why certain medications, such as albuterol (salbutamol), fluticasone or budesonide, are chosen for certain diseases. The ultimate aim is that the practitioner should feel more comfortable managing common airway diseases in cats. EVIDENCE BASE: In compiling their review, the authors searched the veterinary literature for articles in English that discuss inhalational therapy in cats, and which focus primarily on inhaled glucocorticoids and bronchodilators. While most literature on inhalational therapy in cats is based on experimental feline asthma models, there are some studies demonstrating successful treatment in cats with naturally occurring inflammatory airway disease.

Comparative Study of Inhaled Fluticasone Versus Oral Prednisone in 30 Dogs with Cough and Tracheal Collapse.

Coughing is common in dogs with tracheal collapse (TC). The use of inhaled corticosteroids is less widespread than oral ones. This study aims to compare the effects of oral and inhaled corticosteroids in dogs with cough and TC. Thirty dogs were prospectively included and randomized to the prednisone oral group (OG, 14) or fluticasone inhaled group (IG, 16). A clinical score (CS) based on four clinical parameters (respiratory distress, cough episodes, cough frequency, tracheal sensitivity) was monitored at the hospital (enrolment and weeks 2 and 4). Water intake, urination habits, and adherence and tolerance to treatments were monitored weekly. Significant improvements in clinical parameters were identified in both groups throughout the study. Between-group (OG-IG) comparisons revealed no significant differences, indicating equivalent improvement. At the study's endpoint, the IG dogs had a significantly lower CS (5.69 ± 0.79) than OG dogs (6.43 ± 1.02, p < 0.05). Adherence and tolerance were comparable. From weeks 2 to 4, OG dogs were significantly thirstier and urinated more frequently than IG dogs. In conclusion, fluticasone provided good tolerability and efficacy in controlling cough in dogs with TC, and they showed a lower incidence of signs of hypercortisolism compared to prednisone. These data encourage the use of inhaled fluticasone in dogs with cough and TC.

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.

Cichoric acid aerosol for inhalation therapy in respiratory syncytial virus.

Cichoric acid (CA) is a caffeic acid derivative, which has significant anti respiratory syncytial virus (RSV) effect and low toxicity. However, due to the low oral bioavailability and poor intestinal absorption of CA, it is not suitable to be made into oral preparations. In this study, CA was made into metered dose inhaler (MDI), allowing the drug to target the site of action, thus achieving more effective treatment. Through preliminary experiments, the drug content and prescription composition of the preparation were determined. Clarity and stability of solution were used as indexes to screen the composition of latent solvent. Single factor and orthogonal test were used to optimize the amount of latent solvent in CA-MDI, and the optimal prescription was verified. The aerosol prepared according to the optimal formula was characterized and preliminary stability was studied. The final formula of CA-MDI was: CA 15 mg, absolute ethanol 1 g, propylene glycol 0.4 g and 1,1,1,2-tetrafluoroethane 10 g. CA-MDI was prepared with the best prescription, with the specification of 150 actuation per bottle and 75 µg per actuation. After quality inspection, three batches of inhaled aerosols showed that the main drug content per bottle was 77.91 ± 1.63 µg (n = 3), and the total number of bottles was 185 ± 3 (n = 3), all of which met the standards of China Pharmacopoeia and the proposed specifications. The preliminary stability study showed that the quality of inhaled aerosols in CA was stable and reliable.