Search Results (54)

Background: Inhaled corticosteroids (ICSs) are a cornerstone in asthma management, particularly during exacerbations, when high doses are often prescribed. However, patient concerns about potential side effects such as increased appetite, weight gain, and metabolic disturbances may reduce adherence, compromising treatment outcomes. While oral corticosteroids (OCSs) are well known to induce such effects, the metabolic impact of short-term high-dose ICSs remains poorly studied. Objective: This prospective pilot study aimed to assess whether a 14-day course of high-dose ICSs in adults with stable asthma induces changes in appetite, dietary intake, leptin levels, or body weight. Methods: Thirty-five adults (19 males, 16 females; mean age 48.7 ± 15.1 years) with stable mild asthma received ≥400 µg/day extrafine beclomethasone dipropionate/formoterol via pressurized metered-dose inhaler for 14 days. Participants underwent assessments at baseline and after 14 days, including body weight, BMI, fasting serum leptin levels, dietary intake (evaluated using 24 h dietary recalls), and appetite (measured via a visual analogue scale). Results: No significant changes were observed in body weight (mean change: −0.38 kg; 95% CI: −0.81 to 0.05; p = 0.083) or BMI (p = 0.912) following high-dose ICS use. Similarly, serum leptin levels (mean change: 0.13 ng/mL; 95% CI: −3.47 to 3.72; p = 0.945), subjective appetite scores (mean change: −4.93 mm; 95% CI: −13.64 to 3.79; p = 0.267), and dietary energy intake (mean change: +255 kJ/day; 95% CI: −380 to 891; p = 0.431) did not differ significantly post-intervention. Conclusions: Short-term high-dose ICS therapy in adults with mild asthma may not significantly affect appetite, dietary intake, leptin levels, or body weight. These findings support the metabolic safety of short-term high-dose ICSs and may help alleviate patient concerns, improving adherence during exacerbation management. Full article

This review explores recent advancements in inhaled nanoparticle formulations and inhalation devices, with a focus on various types of nanoparticles used for inhalation to treat inflammatory lung diseases and the types of devices used in their delivery. Medical nebulizers have been found to be the most appropriate type of inhalation devices for the pulmonary delivery of nanoparticles, since formulations can be prepared using straightforward techniques, with no need for liquefied propellants as in the case of pressurized metered dose inhalers (pMDIs), or complicated preparation procedures as in the case of dry powder inhalers (DPIs). We demonstrated examples of how formulations should be designed considering the operation mechanism of nebulizers, and how an interplay of factors can affect the aerosol characteristics of nanoparticle formulations. Overall, nanoparticle-based formulations offer promising potential for the treatment of inflammatory lung diseases due to their unique physicochemical properties and ability to provide localized drug delivery in the lung following inhalation. Full article

Background: Despite the ongoing innovations and the availability of numerous effective inhaled treatment options, achieving optimal disease control in most patients frequently remains disappointing. Unfortunately, although inhaled therapy is the cornerstone of respiratory disease management, the selection of the most appropriate inhaler is still overlooked or underestimated by some healthcare professionals, and inhaler misuse remains a significant challenge in managing chronic respiratory diseases which directly influences patients’ quality of life, clinical outcomes, and risk of disease progression. Materials and Methods: This is a unicentric, observational, cross-sectional study designed to evaluate the inhaled therapy prescribed in hospitalized patients and to analyze device changes after hospitalization, as well as the factors associated with these changes. A single face-to-face visit was performed during the patient’s hospitalization, where the inhaled therapy used prior to hospitalization was evaluated: technique (critical errors), compliance (TAI questionnaire), maximum peak inspiratory flow [PIF (L/min)], and level of inhaler handling-related knowledge. A binary logistic regression model was used to explore the association between changing device at discharge and the other independent variables Results: The inhaler most used during hospitalization was the metered-dose inhaler (MDI) with a chamber (51.9% of patients), with the dry powdered inhalers (DPI) being the inhalers used in 43% of maintenance inhaled therapies in the community setting prior to hospitalization. In addition, 90% of patients showed a maximum PIF ≥ 30 L/min, and 35.6% performed critical inhaler errors. These patients had statistically significantly lower maximum PIF values (52.1 L/min in patients with critical inhaler errors vs. 60.8 L/min without critical inhaler errors; p > 0.001) and were more likely to exhibit poor inhaler compliance compared to those without critical errors (50.5% vs. 31.0%, respectively). More than half of the patients who used MDI with spacer chamber made critical inhaler errors; 69.9% showed regular or poor treatment adherence, although 75.6% demonstrated good knowledge about inhaler handling. Only in 27% of the patients did the healthcare professional change the type of inhaler after hospitalization within clinical practice. The medical and nursing staff responsible for the patient’s hospitalization were not informed of the assessment carried out in the study. The probability of not performing a device change at discharge was lower in patients with previous at-home treatment with combined inhaled therapy with LABA + ICS (OR 0.3 [0.18–0.83], p = 0.016) and in patients under triple inhaled therapy (OR 0.3 [0.17–0.76], p = 0.007). No significant differences were observed in inhaler changes when considering the frequency of critical inhaler errors, inhaler handling-related knowledge or maximum PIF values. Conclusions: Our study highlights the urgent need for a more personalized inhaler selection and consistent monitoring by healthcare professionals to minimize inhaler misuse, increase treatment compliance and adherence, and improve disease management outcomes. It is essential to provide training and promote the role of nursing in the evaluation and education of inhaled therapy. Additionally, the use of standardized approaches and tools, such as the CHECK DIAL, is crucial to facilitate the adaptation of devices to patients’ needs. Full article

Background: Correct inhaler technique is vital for managing respiratory conditions like asthma. Patients from culturally and linguistically diverse backgrounds are at higher risk of sub-optimal adherence and errors in inhaler technique. This study aimed to validate an Arabic version of the inhaler technique questionnaire for self-assessment of the metered-dose inhaler (MDI) technique by assessing agreement between observed and self-reported techniques among Arabic-speaking individuals with asthma in Australia. Methods: Observational assessments of 30 participants using an MDI, followed by completion of the translated inhaler technique questionnaire by the same participants. The questionnaire comprised nine questions pertaining to the inhaler technique. The level of agreement between the observed and self-reported technique for each of the nine MDI technique steps was subsequently determined using intraclass correlation. Results: The majority of participants were women, aged 25–44 years (70%). An overall Kappa score of 0.768 indicated good agreement between observed and self-reported datasets, with stepwise agreement ranging from 52.4–100%. Steps involving taking a big breath before inhaler use (step 2) and exhaling slowly (step 8) were the least well correlated. Conclusions: The preliminary validated MDI inhaler technique questionnaire may be used as a self-assessment tool by Arabic speakers, aiding healthcare professionals, and empowering individuals living with asthma to self-manage their condition. Full article

Background/Objectives: Metered-dose inhalers (MDIs) and dry powder inhalers (DPIs) are common inhaled corticosteroid (ICS) inhaler devices. The difference in formulation and administration technique of these devices may influence oral cavity microbiota composition. We aimed to compare the saliva microbiome in children with moderate-to-severe asthma using ICS via MDIs versus DPIs. Methods: Saliva samples collected from 143 children (6–17 yrs) with moderate-to-severe asthma across four European countries (The Netherlands, Germany, Spain, and Slovenia) as part of the SysPharmPediA cohort were subjected to 16S rRNA sequencing. The microbiome was compared using global diversity (α and β) between two groups of participants based on inhaler devices (MDI (n = 77) and DPI (n = 65)), and differential abundance was compared using the Analysis of Compositions of Microbiomes with the Bias Correction (ANCOM-BC) method. Results: No significant difference was observed in α-diversity between the two groups. However, β-diversity analysis revealed significant differences between groups using both Bray–Curtis and weighted UniFrac methods (adjusted p-value = 0.015 and 0.044, respectively). Significant differential abundance between groups, with higher relative abundance in the MDI group compared to the DPI group, was detected at the family level [Carnobacteriaceae (adjusted p = 0.033)] and at the genus level [Granulicatella (adjusted p = 0.021) and Aggregatibacter (adjusted p = 0.011)]. Conclusions: Types of ICS devices are associated with different saliva microbiome compositions in moderate-to-severe pediatric asthma. The causal relation between inhaler types and changes in saliva microbiota composition needs to be further evaluated, as well as whether this leads to different potential adverse effects in terms of occurrence and level of severity. Full article

Metered dose inhalers (MDIs) play a crucial role in managing respiratory diseases, but their effectiveness depends on whether the intended dose is delivered to the target, which can be influenced by various factors. Accurate assessment of MDI performance is crucial for optimizing MDI delivery and ensuring drug efficacy. This study numerically examined the role of evaporation dynamics and dosimetry methods in assessing the efficiency of MDI delivery to different regions in a mouth–lung model extending to the eleventh generation (G11) of lung bifurcations. The experimentally determined spray exit speed, applied dose, and droplet size distribution were implemented as the initial/boundary conditions. Large eddy simulations (LES) were used to resolve the transient inhalation flows, and a chemical species model was applied to simulate vapor and temperature variations in the airflow. A multi-component model was used to consider the heat and mass transfer between the droplets and the airflow. The model was validated against literature data and applied to evaluate the impact of evaporation on pulmonary drug delivery using MDI, in comparison to inert particles. Three methods were used to quantify deposition, which were based on the droplet count, the droplet mass, and the drug carried by the droplets. The results demonstrate that evaporation notably alters the spray droplet size distribution and subsequent deposition patterns. Compared to inert particles, evaporation led to significantly more droplets ranging from 1–5 µm entering the pulmonary region. For a given region, large discrepancies were observed in the deposition fraction (DF) using different dosimetry methods. In the lower lung, the count-based DF (33.9%) and mass-based DF (2.4%) differed by more than one order of magnitude, while the drug-based DF fell between them (20.5%). This large difference highlights the need to include evaporation in predictive dosimetry, as well as to use the appropriate method to quantify the delivery efficiency of evaporating droplets. Full article

Considerable attention has recently been given to the contribution of the greenhouse gas (GHG) emissions of the healthcare sector to climate change. GHGs used in medical practice are regularly released into the atmosphere and contribute to elevations in global temperatures that produce detrimental effects on the environment and human health. Consequently, a comprehensive assessment of their global warming potential over 100 years (GWP) characteristics, and clinical uses, many of which have evaded scrutiny from policy makers due to their medical necessity, is needed. Of major interest are volatile anesthetics, analgesics, and inhalers, as well as fluorinated gases used as tamponades in retinal detachment surgery. In this review, we conducted a literature search from July to September 2024 on medical greenhouse gases and calculated estimates of these gases’ GHG emissions in metric tons CO₂ equivalent (MTCO₂e) and their relative GWP. Notably, the anesthetics desflurane and nitrous oxide contribute the most emissions out of the major medical GHGs, equivalent to driving 12 million gasoline-powered cars annually in the US. Retinal tamponade gases have markedly high GWP up to 23,500 times compared to CO₂ and long atmospheric lifetimes up to 10,000 years, thus bearing the potential to contribute to climate change in the long term. This review provides the basis for discussions on examining the environmental impacts of medical gases with high GWP, determining whether alternatives may be available, and reducing emissions while maintaining or even improving patient care. Full article

Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA and OA and evaluate their anti-Mtb efficacy in vitro and in vivo, as well as their acute toxicity. SLMs measured 0.7–0.89 µM in size, with complete in vitro release of OA and UA at 40 and 32 h, respectively. The minimum inhibitory concentration (MIC) of SLMs loaded with OA and UA was 40 µg/mL SLMs + 20 µg/mL OA + 20 µg/mL UA for drug-sensitive Mtb and 80 µg/mL SLMs + 40 µg/mL OA + 40 µg/mL UA for multidrug-resistant (MDR) Mtb. These SLMs showed an efficient reduction in Mtb burden in infected alveolar macrophages. In a murine model of late-stage progressive MDR-TB, aerosolized delivery of SLMs containing OA and UA via a metered-dose inhaler significantly reduced pulmonary bacterial loads and extended survival. In vivo, acute toxicity studies revealed no mortality or signs of toxicity. These findings demonstrate that SLMs are an optimal delivery system for terpenoids, providing potent in vitro and in vivo anti-TB activity with an excellent safety profile. Full article

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, particularly in low- and middle-income countries, where it poses a significant burden. In Latin America, the estimated prevalence of COPD is notably high, but the management and treatment of the disease have progressed slowly. This review examines the current status of inhalation therapy for COPD in Latin America, focusing on pharmacological therapies, inhalation devices, and the potential of advanced drug delivery systems. Pharmacological management predominantly relies on inhaled bronchodilators and corticosteroids, though access to these therapies varies considerably across the region. Inhalation devices, such as metered-dose inhalers (MDIs) and dry powder inhalers (DPIs), play a critical role in effective treatment delivery. However, their usage is often compromised by incorrect technique, low adherence, and limited availability, especially for DPIs. Emerging technologies, including nanoformulations, represent a promising frontier for the treatment of COPD by improving drug delivery and reducing side effects. However, significant barriers, such as high development costs and inadequate infrastructure, hinder their widespread adoption in the region. This review highlights the need for a multifaceted approach to enhance COPD management in Latin America, including optimizing access to existing inhalation therapies, strengthening healthcare infrastructure, improving provider training, and engaging patients in treatment decisions. Overcoming these challenges is crucial to improving COPD outcomes across the region. Full article

Inhaled colistin is used to treat pneumonia and respiratory infections through nebulization or dry powder inhalers. Nevertheless, the development of a metered-dose inhaler (MDI) for colistin, which could enhance patient convenience and treatment efficacy, has not yet been developed. Colistin is known for its ability to induce cellular toxicity. Gold nanoparticles (AuNPs) can potentially mitigate colistin toxicity. Therefore, this study aimed to evaluate the antimicrobial effectiveness of colistin conjugated with chitosan-capped gold nanoparticles (Col-CS-AuNPs) and their potential formulation for use with MDIs to deliver the aerosol directly to the deep lung. Fourier-transform infrared spectroscopy, nuclear magnetic resonance, and elemental analysis were used to characterize the synthesized Col-CS-AuNPs. Drug release profiles fitted with the most suitable release kinetic model were evaluated. An MDI formulation containing 100 µg of colistin per puff was prepared. The aerosol properties used to determine the MDI performance included the fine particle fraction, mass median aerodynamic diameter, and geometric standard deviation, which were evaluated using the Andersen Cascade Impactor. The delivered dose uniformity was also determined. The antimicrobial efficacy of the Col-CS-AuNP formulation in the MDI was assessed. The chitosan-capped gold nanoparticles (CS-AuNPs) and Col-CS-AuNPs had particle sizes of 44.34 ± 1.02 and 174.50 ± 4.46 nm, respectively. CS-AuNPs effectively entrapped 76.4% of colistin. Col-CS-AuNPs exhibited an initial burst release of up to 60% colistin within the first 6 h. The release mechanism was accurately described by the Korsmeyer–Peppas model, with an R² > 0.95. The aerosol properties of the Col-CS-AuNP formulation in the MDI revealed a high fine particle fraction of 61.08%, mass median aerodynamic diameter of 2.34 µm, and geometric standard deviation of 0.21, with a delivered dose uniformity within 75–125% of the labeled claim. The Col-CS-AuNP MDI formulation completely killed Escherichia coli at 5× and 10× minimum inhibitory concentrations after 6 and 12 h of incubation, respectively. The toxicity of CS-AuNP and Col-CS-AuNP MDI formulations in upper and lower respiratory tract cell lines was lower than that of free colistin. The stability of the Col-CS-AuNP MDI formulation was maintained for at least 3 months. The Col-CS-AuNP MDI formulation effectively eradicated bacteria over a 12-h period, showing promise for advancing lung infection treatments. Full article

This work introduces Spiromni, a single device incorporating three different pressurised metered-dose inhaler (pMDI) accessories: a pMDI spacer, an electronic monitoring device (EMD), and a spirometer. While there are devices made to individually address the issues of technique, adherence and monitoring, respectively, for asthma patients as laid out in the Global Initiative for Asthma’s (GINA) global strategy for asthma management and prevention, Spiromni was designed to address all three issues using a single, combination device. Spiromni addresses the key challenge of measuring both inhalation and exhalation profiles, which are different by an order of magnitude. Moreover, the innovative design prevents exhalation from entering the spacer chamber and prevents medication loss during inhalation using umbrella valves without a loss in flow velocity. Apart from recording the peak exhalation flow rate, data from the sensors allow us to extract other key lung volume and capacities measures similar to a medical pulmonary function test. We believe this low-cost portable multi-functional device will benefit both asthma patients and clinicians in the management of the disease. Full article

A general procedure to prepare gold nanourchins (GNUs) via a seed-mediated method was followed using dopamine hydrochloride as a reducing agent and silver nitrate salt (AgNO₃) as a shape-directing agent. The novelty of this study comes from the successful incorporation of the prepared gold urchins as an aqueous suspension in a nasal pressurized metered dose inhaler (pMDI) formulation and the investigation of their potential for olfactory targeting for direct nose-to-brain drug delivery (NTBDD). The developed pMDI formulation was composed of 0.025% w/w GNUs, 2% w/w Milli-Q water, and 2% w/w EtOH, with the balance of the formulation being HFA134a propellant. Particle integrity and aerosolization performance were examined using an aerosol exposure system, whereas the nasal deposition profile was tested in a sectioned anatomical replica of human nasal airways. The compatibility of the gold dispersion with the nasal epithelial cell line RPMI 2650 was also investigated in this study. Colloidal gold was found to be stable following six-month storage at 4 °C and during the lyophilization process utilizing a pectin matrix for complete re-dispersibility in water. The GNUs were intact and discrete following atomization via a pMDI, and 13% of the delivered particles were detected beyond the nasal valve, the narrowest region in the nasal cavity, out of which 5.6% was recovered from the olfactory region. Moreover, the formulation was found to be compatible with the human nasal epithelium cell line RPMI 2650 and excellent cell viability was observed. The formulated GNU-HFA-based pMDI is a promising approach for intranasal drug delivery, including deposition in the olfactory region, which could be employed for NTBDD applications. Full article

Currently, several types of inhalable liposomes have been developed. Among them, liposomal pressurized metered-dose inhalers (pMDIs) have gained much attention due to their cost-effectiveness, patient compliance, and accurate dosages. However, the clinical application of liposomal pMDIs has been hindered by the low stability, i.e., the tendency of the aggregation of the liposome lipid bilayer in hydrophobic propellant medium and brittleness under high mechanical forces. Biomineralization is an evolutionary mechanism that organisms use to resist harsh external environments in nature, providing mechanical support and protection effects. Inspired by such a concept, this paper proposes a shell stabilization strategy (SSS) to solve the problem of the low stability of liposomal pMDIs. Depending on the shell material used, the SSS can be classified into biomineralization (biomineralized using calcium, silicon, manganese, titanium, gadolinium, etc.) biomineralization-like (composite with protein), and layer-by-layer (LbL) assembly (multiple shells structured with diverse materials). This work evaluated the potential of this strategy by reviewing studies on the formation of shells deposited on liposomes or similar structures. It also covered useful synthesis strategies and active molecules/functional groups for modification. We aimed to put forward new insights to promote the stability of liposomal pMDIs and shed some light on the clinical translation of relevant products. Full article

This work aims to investigate bronchodilator delivery with the use of different vaping drug delivery systems (VDDS) by determining the dose equivalence delivered in relation to different references: a clinical jet nebulizer, a pMDI (pressurized metered dose inhaler) and a DPI (dry powder inhaler). Three different bronchodilators were used (terbutaline, salbutamol hemisulfate, ipratropium bromide). The e-liquids contained the active pharmaceutical ingredient (API) in powder form. Two different VDDS were tested (JUUL and a GS AIR 2 atomizer paired with a variable lithium-ion battery (i-stick TC 40 W), 1.5 ohm resistance, and 15 W power). Samples were collected using a glass twin impinger (GTI). High-performance liquid chromatography (HPLC) was used to quantify the drugs. A next-generation impactor (NGI) was used to measure the particle size distribution. Terbutaline emerged as the optimal API for bronchodilator delivery in both VDDS devices. It achieved the delivery of a respirable dose of 20.05 ± 4.2 µg/puff for GS AIR 2 and 2.98 ± 0.52 µg/puff for JUUL. With these delivered doses, it is possible to achieve a dose equivalence similar to that of a jet nebulizer and DPI, all while maintaining a reasonable duration, particularly with the GS AIR 2. This study is the first to provide evidence that vaping bronchodilators work only with appropriate formulation, vaping technology, and specific drugs, depending on their thermal degradation properties. Full article

Olfactory dysfunction affects approximately 20% of the population globally, with incidence increasing over the age of 60. The pathophysiology is complex, not yet fully understood, and depends on many factors, including the underlying cause. Despite this, the present literature on olfaction is limited due to significant heterogeneity in methodological approaches. This has resulted in limited effective treatments available for olfactory dysfunction. Medications for olfactory dysfunction can be administered locally (directly to the olfactory epithelium) or systemically (orally or intravenously). Currently, there are various methods for local drug delivery to the olfactory epithelium (nasal drops, nasal sprays, atomisers, pressured meter-dosed inhalers, rinses, and exhalation delivery systems). The aims of this review are to summarise the different methods of drug delivery to the olfactory cleft, evaluate the current literature to assess which method is the most effective in delivering drugs to the olfactory epithelium, and review the medications currently available to treat olfactory dysfunction topically. Going forward, further research is required to better establish effective methods of drug delivery to the olfactory epithelium to treat smell disorders. Full article