Enhancing Inhalation Drug Delivery: A Comparative Study and Design Optimization of a Novel Valved Holding Chamber.

This paper presents an innovative approach to the design optimization of valved holding chambers (VHCs), crucial devices for aerosol drug delivery. We present the design of an optimal cylindrical VHC body and introduce a novel valve based on particle impaction theory. The research combines computational simulations and physical experiments to assess the performance of various VHCs, with a special focus on the deposition patterns of medication particles within these devices. The methodology incorporates both experimental and simulation approaches to validate the reliability of the simulation. Emphasis is placed on the deposition patterns observed on the VHC walls and the classification of fine and large particles for salbutamol sulfate particles. The study reveals the superior efficacy of our valve design in separating particles compared to commercially available VHCs. In standard conditions, our valve design allows over 95% of particles under 7 µm to pass through while effectively filtering those larger than 8 µm. The optimized body design accomplishes a 60% particle mass flow fraction at the outlet and an average particle size reduction of 58.5%. When compared numerically in terms of size reduction, the optimal design outperforms the two commercially available VHCs selected. This study provides valuable insights into the optimization of VHC design, offering significant potential for improved aerosol drug delivery. Our findings demonstrate a new path forward for future studies, aiming to further optimize the design and performance of VHCs for enhanced pulmonary drug delivery.

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.

Biodegradable spacer insertion to reduce rectal toxicity during radiotherapy for prostate cancer

Evidence-based recommendations on biodegradable spacer insertion to reduce rectal toxicity during radiotherapy for prostate cancer. This involves pushing the rectum slightly away from the prostate by inserting a balloon or injecting a gel (spacer) between them.

[Inhalation therapy in dogs and cats with chronic lower airway disease - a literature review]. / Inhalative Therapie chronischer Erkrankungen der unteren Atemwege bei Hund und Katze ­ eine Literaturübersicht.

Chronic respiratory diseases are prevalent medical conditions in dogs and cats requiring lifelong treatment. Mainstay of therapy for chronic inflammatory respiratory diseases are glucocorticoids. Concurrent treatment with bronchodilators may be necessary to control clinical signs sufficiently. Due to the successful use in people as well as subsequent reduction of adverse effects of long-term glucocorticoid therapy, inhalative therapy has become increasingly important in veterinary medicine as well. Primarily spacers or valved holding chambers, in combination with metered dose inhalers, are used in dogs and cats. The technical properties of these devices, as well as their use and maintenance will be described in the following article. Furthermore, the existing literature regarding efficacy of inhalative medications for therapy of chronic inflammatory airway diseases in dogs and cats will be summarized.

Optimal administration of bronchodilators with valved holding chambers in preschool children: a review of literature.

Our aim was to synthesize the published literature on factors that potentially affect the delivery of bronchodilators using valved holding chambers (VHC) in preschool children. We also aimed to identify those attributes that are not yet incorporated or clearly stated in the guidelines and those topics that are still lacking sufficient data. There is strong evidence supporting several recommendations in current guidelines. Based on present knowledge, bronchodilators should be delivered by VHC administering each puff separately. Face mask should be omitted as soon as the child can hold the mouthpiece of the VHC tightly between the lips and teeth. Based on the review, we suggest adding a specific note to current guidelines about the effect of chamber volume and the impact of co-operation during drug administration. Calming the child and securing a tight face-to-mask seal is critical for successful drug delivery. There is not enough evidence to make specific recommendations on the most reliable VHC and face mask for children. There is an urgent need for studies that evaluate and compare the effectiveness of VHCs in various clinical settings in wide age-groups and respiratory patterns. In addition, there is insufficient data on ideal chamber volume, material, and effective antistatic treatment. What is Known: • Valved holding chambers (VHC) should not be considered interchangeable when used with pressurized metered dose inhalers (pMDI). • Drug delivery is influenced by VHC volume, aerodynamic and electrostatic properties; mask fit; respiratory pattern and co-operation during inhalation; and the number of puffs actuated. What is New: • The impact of co-operation, VHC volume, and good mask-to-face fit during drug inhalation is not stressed enough in the guidelines. • Studies are urgently needed to evaluate the effectiveness of different VHCs in various clinical settings focusing on VHC electrostatic properties, respiratory patters, face masks, and ideal pMDI+VHC combinations.

Effect of different accessory devices on the dose delivered from pressurised metred-dose inhalers.

INTRODUCTIONS: Improved aerosol delivery of bronchodilators to chronic obstructive pulmonary disease (COPD) subjects is a cornerstone in the treatment approach. Drug delivery and response are improved with the use of accessory devices [spacers and valved holding chambers (VHCs)] with metred-dose inhalers (pMDIs). However, different accessory devices are available in the market with different properties that could affect aerosol delivery. Thus, this study aimed to assess the relative lung deposition and systemic bioavailability and compare bronchodilator response of salbutamol delivered using different accessory devices attached to pMDIs. METHODS: Twelve healthy subjects and twelve COPD subjects inhaled 300 µg salbutamol (3 pMDI puffs) using five different accessory devices with either masks or mouthpieces (Able, Aerochamber plus flow Vu, Dolphin chamber, Tipshaler spacer, and modified Drink bottle spacer). Urine samples were collected thirty minutes post-dosing and cumulatively for the next twenty-four hours, to determine and compare the relative lung deposition [0-0.5 hour excretion of urinary salbutamol (USAL0.5)] and systemic bioavailability [0.5-24 hours excretion of urinary salbutamol (USAL24)] of salbutamol from the selected accessory devices. Also, the difference between pre and post-inhalation forced expiratory volume in one second (ΔFEV1 %) of predicted was determined for each accessory device. RESULTS: Urinary excretion of salbutamol (both USAL0.5 and USAL24 samples) in COPD subjects was significantly (P < .05) lower than in healthy subjects for all accessory devices. USAL0.5 and USAL24 in non-antistatic spacers (modified Drink bottle spacer and Dolphin chamber spacers) were significantly lower (P < .05) than that for antistatic spacers (Aerochamber plus flow Vu, Able and Tips-haler). No significant difference in USAL0.5 and USAL24 was observed between facemasks and mouthpieces. There was a significant difference (P < .05) in ΔFEV1 % of predicted values between COPD subjects and healthy subjects. However, within the COPD group and the healthy group there was no significant difference in ΔFEV1 % of predicted values between all accessory devices or between with mouthpiece or with a mask. CONCLUSIONS: COPD subjects had lower aerosol delivered compared with healthy subjects. Anti-static accessory devices delivered a higher amount of aerosol compared with non-antistatic accessory devices. Even though the presence of a significant difference in aerosol delivery between non-antistatic and antistatic accessory devices no significant difference was found in the ΔFEV1 % between all accessory devices.

The pharmacists' ability to use pressurized metered-dose inhalers with a spacer device and factors affecting it.

Objective: The aim of this study is to evaluate the pharmacists' ability to use pMDIs with a spacer device and the factors that affect this ability.Method: Face to face interviews were conducted with the pharmacists. A nine item questionnaire was completed and the checklist for how to use pMDIs with a spacer device was filled out.Results: A total of 307 pharmacists voluntarily participated in this study. Fifty-six (18.2%) of the pharmacists stated that they did not know how to use pMDIs with a spacer device. These pharmacists were excluded and remaining 251 pharmacists included in the study. Only 100 (39.8%) pharmacists demonstrated all of the inhaler spacer device usage steps correctly. The step in which pharmacists made the most mistakes was "take 5-6 deep and slow breaths, hold for 10 s and slow breaths." Those pharmacists who were more likely to correctly use pMDIs with a spacer device were younger (p = 0.023), had dispensed more asthma medications per day (p < 0.001), had dispensed more asthma medications per day for patients younger than six years of age (p = 0.016), and sold inhaler spacer devices at their pharmacy (p = 0.042).Conclusion: Approximately one third of the pharmacists in the current study were able to correctly demonstrate all of the steps for proper usage of pMDIs with a spacer device, which indicates that pharmacists should be included in the training program and be provided continuous training on the use of pMDIs with a spacer device.

Inhalation technique practical skills and knowledge among physicians and nurses in two pediatric emergency settings.

Introduction: Correct technique with a pressurized metered-dose inhaler (pMDI) equipped with a valved holding chamber (VHC) or spacer provides an important advantage for adequate control of asthma and virus-induced wheezing in young children. The aim of this study was to assess the ability and knowledge of physicians and nurses to use a pMDI with a masked VHC in two pediatric emergency units.Methods: Study design: Two-center observational study. Inhaler use technique was assessed in 50 physicians and 50 nurses using a child mannequin and a validated videotaped nine-step scoring method. The participants' knowledge was evaluated by a questionnaire.Results: The inhalation technique was perfectly mastered by 49% of the study participants and almost perfectly mastered by another 34% (mean score 8.3 ± 0.7; range 5-9). Nurses were more likely than doctors to demonstrate the technique perfectly (66% vs. 32%, p < 0.05). The two most common errors were forgetting to shake the pMDI between two consecutive puffs (38% of the participants) and putting the patient in an incorrect position (11%). About half of the participants reported that they checked each patient's inhalation technique at every opportunity and knew how to clean the VHC. A large majority did not employ a reliable method to determine the amount of medication remaining in pMDIs without a counter.Conclusion: Healthcare professionals' practical skills and knowledge on inhalation therapy were not completely mastered and could be improved with a mandatory training program.

Mask Use with Spacers/Valved Holding Chambers and Metered Dose Inhalers among Children with Asthma.

Inhaler misuse is highly prevalent and associated with high morbidity and costs. For metered dose inhalers, proper use can be supported with devices such as spacers/valved holding chambers (VHCs) and masks to effectively deliver inhaled medication to the lungs. However, guidelines are vague about which children with asthma should use spacers/VHCs with masks to deliver medication from metered dose inhalers as well as when they should transition to spacers/VHCs with mouthpieces. In this paper, we provide a focused review of the evidence for mask use, highlighting unclear and conflicting information in guidelines and studies. We synthesize the differences in recommendations and practice. Based on these findings, we call for future research to determine the appropriate age and necessary skills for transitioning children from using metered dose inhalers with spacers/VHCs and masks to using spacers/VHCs and mouthpieces. Guidelines about mask use should be standardized to help ensure optimal medical delivery for patients, provide consistent inhaler prescriptions and education across settings, and support team-based care to help lower pediatric asthma morbidity and costs.

Effectiveness of Spacer Devices on Preventing Undesirable Cardiovascular Effects of Inhaled Salbutamol.

Background: Currently, there are no regulatory guidelines indicating spacer devices/valved holding chamber (VHC) should be used routinely during pulmonary function tests, and few studies evaluated if spacer devices reduce beta-agonist bronchodilators' side effects. Methods: A prospective study compared salbutamol's cardiovascular effects and bronchodilation response during spirometry tests with and without a spacer device/VHC. Heart rate (HR), the corrected QT interval (QTc), and systolic and diastolic blood pressure were measured 10 minutes after the first spirometry test, before the drug administration, and 20 minutes after inhalation in both groups. Spirometric parameters (forced expiratory volume in the first second [FEV1], forced vital capacity [FVC], and FEV1/FVC) were also measured for both groups. Results: HR and QTc increase were significantly higher in the pressurized meter dose inhalers alone group versus the VHC group [mean SD] [73.1 ± 10 bpm to 74.3 + 10 bpm, p = 0.021] and [median (25%-75% interquartile range)] [389 ms (381-404) to 398 ms (387-407), p = 0.045] vs. [mean SD] [75.4 ± 9 to 73.8 + 8 bpm, p = 0.4] and [median (25%-75% interquartile range)] [388 ms (347-408) to 385 ms (366-408), p = 0.35], respectively. FEV1 variation before and after salbutamol were similar between both groups. Discussion: Although VHC significantly reduces HR and QTc variation when using beta-agonist bronchodilators in healthy patients, no clinical repercussions of this variation were found in this study, since no event of tachycardia or pathological QTc was recorded. Conclusion: VHC has a diminished clinical impact for healthy patients when considering cardiovascular effects and spirometric parameters. Beta-agonist bronchodilators may be administrated despite the use of spacer devices in patients without known cardiovascular diseases. Its significance for other populations still needs to be determined.

Homemade valved holding chambers for children with airway hyperresponsiveness: A randomized crossover trial.

BACKGROUND: During the COVID-19 pandemic, a metered-dose inhaler (MDI) with a valved holding chamber (VHC) is a preferred route of bronchodilator delivery. We have developed a new homemade VHC, made of a paper coffee cup, and a drinking water bottle. This study was conducted to compare the bronchodilator response in children with airway hyperresponsiveness after the use of our homemade VHC and that of a standard commercial one. METHODS: In a randomized, two-period, two-sequence crossover trial, we recruited 20 children, aged 6-15 years, who had a greater than 12% increase in FEV1 after inhaled salbutamol. They were randomized into Group A and B. Group A used our VHC on the first day and Aerochamber® on the second day. Group B used the same VHCs but in alternate sequence. Spirometries were performed before and after 400 µg of salbutamol, MDI was administered via those VHCs. RESULTS: Baseline demographic data and spirometric values did not have statistically significant differences between group A and B and between the first and second day (p > .05). After giving salbutamol MDI, both VHCs produced significant increases in FVC, FEV1 , and FEF25-75% (p < .005). The improvement in FEV1 did not significantly differ between our homemade VHC and Aerochamber® (p > .05). CONCLUSION: Our homemade VHC is effective for an MDI bronchodilator delivery. Since it is very cheap and easy to make, it may be used as a disposable device to minimize airborne transmission especially when commercial VHC is not available.

[Evaluation of Valved Holding Chambers Simulating Repurposing Use of Ciclesonide Metered-dose Inhaler by Patients with Pneumonia].

Achieving appropriate inhalation in patients with coronavirus disease 2019 (COVID-19) is a common challenge in the use of repurposed metered-dose inhaler (MDI) formulations. The purpose of this study was to evaluate the effect of five valved holding chambers (VHCs) on the inhalation of ciclesonide from Alvesco MDI. The aerodynamic particle size distribution of ciclesonide discharged from Alvesco MDI was evaluated using a Next Generation Impactor in the presence and absence of VHCs. The use of VHCs retained or slightly increased the amount of ciclesonide in the fine particle diameter range (aerodynamic particle size below 3 µm) (FPD) and reduced the amount at the induction port after coordinated inhalation. However, the use of VHC reduced the FPD of the formulation by increasing the time between the MDI discharge and the pump suction by various degrees among the five VHCs. These results indicated that use of the VHCs and minimizing the inhalation delay time should ensure sufficient inhalation of ciclesonide particles.

Real-Time Analysis of the Respiratory Flow Through a Valved Holding Chamber.

Background: The ability of patients to take, correctly and regularly, aerosol treatments is a key for good control of asthma and chronic obstructive pulmonary disease. Devices that help to improve inhalation technique could train the patient to take their medication properly, reducing risk of exacerbations. In this study we evaluate a new device that by recording real-time respiratory flow into the valved holding chamber (VHC) mouthpiece, could be used to improve patient technique. Methods and Results: Using computational fluid dynamics analysis we demonstrated that compared to a mouthpiece with no flow probe, the presence of a probe modifies the flow profile and velocity regardless of the probe shape or position. During flow measurement using a SDP610 pressure sensor (Sensirion, Switzerland), all probes can accurately record adult and child respiratory patterns. Resistance was determined from the back pressure generated by the VHC with or without probes; and resistance was not impacted by the probes. Aerodynamic particle size distribution and drug delivery measurement were assessed using the United States Pharmacopeia throat model (Copley Scientific, UK), next generation impactor (NGI; Copley Scientific), and a breath simulator (BRS200; Copley Scientific). To test different formulations, these experiments were performed with fluticasone propionate (Flixotide®; GSK, UK), salbutamol (Ventolin®; GSK), and beclomethasone dipropionate (BDP) (QvarSpray®; GSK). Depending on the molecule or the probe configuration, we noticed a decrease of the emitted doses, fine particle deposition, mass median aerodynamic diameter, but no significant change in the mass of drug delivered. A decrease in the fine particle fraction (FPF) was observed in most testing conditions. However, a slight increase was noticed for two conformations with BDP (round and close [Rc] and diamond and far [Df]) and salbutamol (Rc and round and far [Rf]). Conclusion: By inserting a flow probe directly into the mouthpiece of a VHC we could perform real-time analysis of respiratory flow during the VHC use without disturbing drug delivery, or increasing resistance.

Spacers and Valved Holding Chambers-The Risk of Switching to Different Chambers.

Spacers are pressurized metered-dose inhaler (pMDI) accessory devices developed to reduce problems of poor inhaler technique with pMDIs. Spacers that feature a 1-way inspiratory valve are termed valved holding chambers (VHCs); they act as aerosol reservoirs, allowing the user to actuate the pMDI device and then inhale the medication in a 2-step process that helps users overcome challenges in coordinating pMDI actuation with inhalation. Both spacers and VHCs have been shown to increase fine particle delivery to the lungs, decrease oropharyngeal deposition, and reduce corticosteroid-related side effects such as throat irritation, dysphonia, and oral candidiasis commonly seen with the use of pMDIs alone. Spacers and VHCs are not all the same, and also are not interchangeable: the performance may vary according to their size, shape, material of manufacture and propensity to become electrostatically charged, their mode of interface with the patient, and the presence or otherwise of valves and feedback devices. Thus, pairing of a pMDI plus a spacer or a VHC should be considered as a unique delivery system. In this Rostrum we discuss the risk potential for a patient getting switched to a spacer or VHC that delivers a reduced dose medication.