Dose Inhaler Research Articles

Environmental impact of inhaled medicines: A Thoracic Society of Australia and New Zealand position statement.

Globally, more than 1.2 billion inhalers are purchased for asthma and chronic obstructive pulmonary disease (COPD) annually. In Australia and New Zealand, pressurized metered dose inhalers (pMDIs) are the leading delivery device prescribed and pMDI salbutamol can be purchased over the counter in Australia. These inhalers are a major contributor to healthcare related greenhouse gases. This is due to the propellants that they currently contain which have extremely high global warming potential (GWP). In this position paper, we report the findings of a Thoracic Society of Australia and New Zealand (TSANZ) working group on the environmental impact of inhaled respiratory medicines. We reviewed the use of inhaled medicines in Australia and New Zealand and their contribution to climate change and other environmental degradation. We propose strategies for health professionals and consumers to reduce environmental impact in the management of airway diseases. These include accurate diagnosis to avoid unnecessary treatment, better disease control to minimize the need for reliever therapy and actively choosing inhaler devices with lower environmental impacts when clinically appropriate. Inhaler selection should be tailored to the individual, aiming to achieve the best possible clinical outcome. Choosing an appropriate inhaler for an individual involves consideration of factors such as dexterity, inspiratory capacity and cost. In our current climate emergency and with the availability of lower carbon alternatives, health professionals should also consider environmental impact.

Spatio-temporal analysis of bicyclists' PM2.5 exposure levels in a medium sized urban agglomeration.

Many cities have promoted decarbonized transportation modes to mitigate climate change, reduce air pollution and promote healthy behaviors. However, cyclists may be particularly exposed to higher concentrations of on-road air pollutants than other commuters due to their proximity to traffic, higher breathing rates, and prolonged commutes. In addition, there is scarce information analyzing the geographic exposure levels of cyclists in medium-sized urban agglomerations of Latin American cities. We aimed to assess cyclists' exposure to PM2.5 at the spatio-temporal level using low-cost sensors in the Mendoza Metropolitan Area, Argentina. We calculated PM2.5 inhalation doses (IDs) for different routes with distinctive characteristics, considering different age ranges and gender of cyclists. The dose was represented as temporally and spatially disaggregated exposure maps, one of the first to represent it in Latin America using this method. All link types analyzed exhibited significant differences in PM2.5 concentrations, although the most frequent concentrations were less than 5µgm-3, with secondary peaks of 6.5 and 9µgm-3. As expected, ID increases with age and is greater in males than in females. Our findings further reinforce the fact that route choice (busy vs. quiet) and time of day (peak vs. off-peak) appreciably affect the pollutant exposure of cyclists. All these results could be helpful in the selection of alternative cycling routes with lower PM2.5 at different hours of day but also enable us to investigate further implications of exposure to PM2.5 for the health of urban bicycle commuters.

Radiation dose estimation for indoor radon, thoron and their progenies using a stochastic method-a small-scale survey in Wuhan, China.

Passive radon monitors with CR-39s are widely used in major epidemiological surveys. However, the conventional CR-39 track density determining strategy makes it difficult to accurately estimate the concentration because of the heterogeneity of tracks on CR-39s. This study introduced a stochastic method, Latin hypercube sampling, to improve the track density determining strategy and provide the probability distribution of 222Rn concentration and equilibrium equivalent thoron concentration. The first 222Rn and 220Rn discriminated survey was conducted in Wuhan, China, in 2018 using RADUET® and deposition-based passive 220Rn progeny monitors and applying the stochastic method to the measurement. The results indicate that the stochastic method could decrease the effects of the track heterogeneity on the CR-39s and provide reliable results. The 220Rn progeny contributed more than 40% of the total inhalation dose in the survey, which cannot be ignored in urban family dwellings.

Flow Profiles Identify Sources of Poor Metered Dose Inhaler Technique: An observational study in long-term pMDI users

BackgroundInhaled medications are commonly used as therapy for obstructive lung disease (OLD) yet poor technique from pressurized metered dose inhalers (pMDI) can severely limit drug delivery and therapeutic efficacy. A novel flow sensor has been developed to characterize inhalation flow profiles from pMDIs. Research QuestionAmong OLD subjects, flow profiles during pMDI inhalation maneuvers would expose poor patterns of pMDI use, which can be used to remediate pMDI technique. Study Design and MethodsA novel flow sensor was coupled to a placebo pMDI inhaler to characterize inhalation technique in 70 OLD participants from a pulmonary clinic. pMDI inhalation flow profiles generated actuation timing, mean inspiratory airflow (MIF) and inspired volume before and after visualizing these features. McNemar’s was used to characterize the impact of training on pMDI inhalation metrics. The post-actuation inspired volume was normalized to inspiratory capacity (IC). ResultsAmong participants with 17.4 (SD = 17.9) years of pMDI use, flow profiles uncovered mistimed actuations in 47.1% and poor inspiratory flow rates in 30.0% of subjects. After visualizing flow profiles, participants improved actuation timing (c2(1) =12.042, p < .001), mean inhaled volume (87.9 to 105.6% of IC, p<0.001) and the combined inhalation metrics (c2(1) =8.45, p = 0.003). InterpretationFlow profiles helped uncover and remediate specific defects in pMDI technique in the majority of chronic OLD users. Flow profiles from inhaled medications can be used to enhance drug delivery to the lung.

Direct measurement of indoor thoron and radon progeny and estimation of inhalation dose in three cities in Gabon: Comparison of the use of thoron typical and measured equilibrium factor values

This study focuses on public exposure to natural radioactivity caused by the inhalation of radon and thoron progeny in homes in Franceville, Moanda and Mounana in Gabon. The equilibrium factor (FTn) between thoron and its progeny was determined experimentally for a proper estimate of the effective dose. In order to assess internal exposure due to radon and thoron progeny, 150 passive radon-thoron discriminative detectors (RADUET) and thoron progeny monitors were deployed for about 3 months in the above-mentioned towns. The results of the measurements obtained showed that the average concentrations of thoron progeny (EETC) were 1.54 ± 0.08 Bq m−3, 3.05 ± 0.09 Bq m−3 and 1.84 ± 0.11 Bq m−3 in Franceville, Moanda and Mounana, respectively. The ranges of the measured thoron equilibrium factors were 0.004–0.710, 0.005–0.750, and 0.006–0.794 in Franceville, Moanda and Mounana, respectively. The arithmetic and geometric mean values were, respectively, 0.183 and 0.117 in Franceville, 0.184 and 0.122 in Moanda, and 0.221 and 0.140 in Mounana. The experimentally determined equilibrium factor (FTnexp) allowed us to compare the value of the experimentally determined effective dose with the theoretically determined one calculated using the equilibrium factor proposed by United Nation Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2000 report. FTnexp values were around 6–11 times greater than the UNSCEAR typical value. The ranges, arithmetic and geometric mean EERC values determined were 30.40–55.60 Bq m−3, 24.00 ± 0.90 Bq m−3 and 41.68 (1.00) in Franceville, 36.40–62.50 Bq m−3, 45.30 ± 0.70 Bq m−3 and 44.72 (1.00) in Moanda, and 35.00–90.00 Bq m−3, 50.00 ± 2.00 Bq m−3 and 48.50 (1.00) in Mounana. The mean values of the annual effective inhalation dose due to thoron progeny determined using FTnexp were 0.32 mSv (compared to 0.049 mSv), 0.63 mSv (compared to 0.103 mSv), and 0.39 mSv (compared to 0.055 mSv) in Franceville, Moanda and Mounana, respectively. The main conclusion of this study is that indirect estimations of thoron progeny concentrations considerably underestimate the estimation of the annual effective inhalation dose.

Evaluation of asthma control after reinforcement of proper inhaler techniques in a tertiary care center in northern India.

Asthma is an obstructive lung disease with high prevalence. Symptom control in asthma remains poor despite significant advancements in treatment guidelines and inhalational devices. This is often attributed to inadequate patient adherence to the inhaler technique and insufficient education on its long-term use. Through this study, we aimed to assess the impact of reinforcement of proper inhaler technique on asthma symptom control and quality of life. A prospective cohort of 400 asthma patients using dry powder inhalers and metered dose inhalers was recruited in the outpatient clinic of our hospital. At the time of recruitment, the correctness of inhaler technique usage was assessed, and the pre-test Inhaler Technique Score (ITS) was recorded for each patient. Then, a ten-step inhalation technique was taught through demonstration, and the post-test ITS score was recorded again. This was done for each patient at monthly intervals for 3 months. Along with it, two tailored questionnaires, the Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ), were administered at each visit to assess disease control and quality of life. Significant enhancements in inhalation technique were noted from the first to the third visit using the ten-step inhalation usage scores, which improved from 6.91 to 9.87 (out of 10) (p<0.001), paralleled by ACT score increases from 17.06 to 19.37 (out of 25) (p<0.001) from visits one to two, and from 19.37 to 20.52 (out of 25) (p<0.001) from visits two to three, signifying improvement in symptom control. Quality of life similarly improved from 4.45 to 5.12 to 5.45 (out of 7) (p<0.001) across the three visits as assessed by AQLQ. In conclusion, promoting proper inhaler technique through structured education programs is crucial for optimizing long-term asthma management and enhancing patients' quality of life.

Features, reasons, and significance of radon and thoron attributable radiological dose in the indoor environment

Humans receive around 50% of natural radiation dose due to 222Rn (radon), 220Rn (thoron) and their decay products. Several field campaigns measuring these gases and the decay products in different regions of India have been conducted in the recent past. Some of these studies measured indoor activity concentration and/or dose due to these gases and the associated decay products. This work compares the fraction of 222Rn and decay products and 220Rn and decay products in inhalation dose for 10 studies conducted in Uttarakhand state. It is seen that AEDT (annual effective dose due to 220Rn and decay products) for these regions varies between 21 and 48% and it is significantly higher than the averaged worldwide reference value of 6%. Based on elaborative measurements performed in the Bageshwar district (present work), Almora and Nainital districts (our previous campaigns); the reasons for this high value have been explored. It was observed that a higher source term for mud houses could be the main reason for the high AEDT range. Interestingly, preliminary analysis revealed that the fraction is higher for the dwellings situated at higher altitudes thus indicating the role of the unavailability of modern building construction materials at remote locations. The study highlights the significant contribution of thoron in the Indian Himalayas.

Machine learning-enhanced stochastic uncertainty and sensitivity analysis of the ICRP human respiratory tract model for an inhaled radionuclide

The International Commission on Radiological Protection (ICRP) has developed the reference Human Respiratory Tract Model (HRTM), detailed in ICRP Publications 66 and 130, to estimate the deposition and clearance of inhaled radionuclides. These models utilize reference anatomical and physiological parameters for particle deposition (PD). Biokinetic models further estimate retention and excretion of internalized particulates, aiding the derivation of inhalation dose coefficients (DC). This study aimed to assess variability in deterministic131I biokinetic and dosimetry models through stochastic analysis using the updated HRTM from ICRP Publication 130. The complexities of the ICRP PD model were reconstructed into a new, independent computational model. Comparison with reference data for total PD fractions for reference worker, solely a nose breather, covering activity median aerodynamic diameters from 0.3μm to 20μm, showed a 1.04% relative and 0.7% absolute difference, demonstrating good agreement with ICRP deposition fractions. The deterministic DC module was reconstructed in Python and expanded for stochastic analysis, systematically expanding deposition components from HRTM and assigning probability distribution functions to uncertain parameters. These were integrated into an in-house stochastic radiological exposure dose calculator, utilizing latin hypercube sampling. A case of an occupational radionuclide intake was explored, in which biodistribution and committed effective DC (CEDC) were computed for131I type F, considering a lognormal particle size distribution with a median of 5μm. Results showed the published ICRP reference CEDC marginally exceeds the 75th percentile of observed samples, with log-gamma distribution as the best-fit probability distribution. A Random Forest regression model with SHapley Additive exPlanations was employed for sensitivity analysis to predict feature importance. The analysis identified the HRTM particle transport rates scaling factor, followed by the aerodynamic deposition efficiency in the alveolar interstitial region as the most impactful parameters. This study offers a unique stochastic approach on inhaled particulate metabolism, enhancing radiation consequence management, medical countermeasures, and dose reconstruction for epidemiological studies.

Environmental impact of pressurised metered dose inhalers versus dry powder and soft mist inhalers at a tertiary Melbourne hospital.

The carbon footprint of devices to deliver inhaled respiratory medications has come into focus as climate change has been identified as a worldwide emergency. Metered dose inhalers (MDIs) contain hydrofluorocarbons that have significant global warming potential compared to dry powder inhalers (DPIs) and soft mist inhalers (SMIs), which do not use a propellant gas. A 12-month pharmacy inpatient dispensing audit demonstrated that inpatient MDI use significantly outweighed that of DPIs and SMIs and accounted for approximately 99% of inhaler-related greenhouse gas emissions at our hospital.

Oral Manifestations in Asthmatic Patients Using Metered Dose Inhaler and Dry Powder Inhaler

Background: The prevalence of asthma indicates the importance of studying oral manifestations of inhalers as one of the indications of asthma. This study compares two methods of using inhalers, Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) in asthmatic patients. Methods: 100 asthmatic patients (50 MDI-treated, 50 DPI-treated) and 50 healthy individuals were selected by convincing sampling. The three sampled groups were gender- and age-matched. We performed a clinical examination, recorded the information, and analyzed the data by SPSS21 software using a t-test and one-way ANOVA for quantitative and Pearson’s chi-square test for qualitative indicators. Results: DMFT index (p-value 0.001), fissured tongue (p-value 0.005), xerostomia (p-value 0.001), and dental erosion (p-value: 0.011) in MDI-treated patients were significantly higher than the other two groups, while the geographic tongue (p-value 0.008) was significantly higher in DPI-treated patients than in the other two groups. It showed that periodontal disease and median rhomboid glossitis had no significant difference between the three groups. Conclusion: Due to the higher incidence of manifestations in MDI, it is expected that physicians give more attention to prescribing inhalers and give them the necessary training to maintain oral and dental hygiene.

Comparative analysis of particle exposure in commuters: Evaluating different modes of transportation in Tehran

Daily commuting significantly contributes to the overall exposure to particulate matter (PM) in urban areas, underscoring the need to understand the factors influencing PM exposure. This study assessed personal exposure levels and inhalation doses of PM2.5, and PM10 across various transportation modes in Tehran, Iran. The study included buses, open-window taxis, subways, walking, and cycling for over 125 trips. Data were collected during the morning and evening peak hours using low-cost sensors, with an average trip distance of 7.50 km. On average, buses exhibited the highest mean PM2.5 concentration (25.0 μgm3), followed by subways (17.0 μgm3), taxis (14.4 μgm3), cycling (13.5 μgm3), and walking (8.80 μgm3). Pearson correlation analysis showed a strong relationship between traffic volume and PM concentrations in taxi and bus modes (r = 0.78 and 0.56, respectively). Subway commuters experienced the lowest PM2.5 inhalation dose (2.50 μg), whereas bus commuters experienced the highest (6.20 μg). Pedestrians had the highest average inhalation dose of PM2.5 with 20.7 μg due to longer trip durations. The daily average PM2.5 levels in all transportation modes exceeded the WHO thresholds by 1.60 times. These findings offer crucial insights into personal exposure concentrations among commuters and serve as a basis for effective air quality management plans and broader global investigations of air pollution.

Radionuclides distribution in soils and radon level assessment in dwellings of Mungo and Nkam Divisions, Cameroon.

Radionuclide and radon levels have been investigated in soil samples and residential environments within the Mungo and Nkam Divisions of the Littoral Region. These analyses employed gamma spectrometry facilitated by a NaI (Tl) detector for soil samples, yielding average activity concentrations of 226Ra, 232Th, and 40K at 23.8, 72, and 105Bqkg-1, respectively. Various radiological parameters were calculated to evaluate radiological hazards. Additionally, the indoor radon concentrations were quantified utilizing the CR-39 solid-state nuclear track detector (Radtrack), revealing an average concentration of 25Bqm-3 and an associated inhalation dose of 0.66mSv y-1. Risk assessments for lung cancer attributable to indoor radon exposure incorporated models such as the Harley model. An observed moderate correlation between indoor radon levels and external 226Ra concentrations implies that radon intrusion indoors might be substantially influenced by the 226Ra present in the subjacent soil, considering the construction of residential structures directly upon these terrains.

Molecular imaging of excitability difference between alkaloids/salts (nicotine, nicotinic benzoate, caffeine and arecoline hydrobromide)

Comparison of the excitability of four different alkaloids/salts, including nicotine, nicotinic benzoate, caffeine and arecoline hydrobromide. Based on positron emission tomography (PET) imaging and 18F-Fallypride, a novel technique for measuring alkaloid/salt excitability in SD rats was developed. Different doses and types of alkaloids/salts were administered to the SD rats in a single nebulised inhalation.The results showed that: (1) PET imaging technology can detect the excitability intensity of SD rats after single inhalation of alkaloids/salts in non-invasive real time and the optimal PET scanning time of four different alkaloids/salts (nicotine, nicotinic benzoate, caffeine and arecoline hydrobromide) were slightly different. (2) The excitatory saturation effect of four alkaloids/salts was observed in SD rats after single inhalation and the saturation effect doses of nicotine, nicotine benzoate, caffeine and arecine hydrobromide were 0.063 mg/kg, 0.075 mg/kg, 0.33 mg/kg and 0.075 mg/kg, respectively. (3) In the case of single inhalation of the same dose of four alkaloids/salts, male SD rats inhaled arecoline hydrobromide with the strongest excitability, while female SD rats inhaled nicotinic benzoate. A PET method for noninvasive real-time detection of alkaloid/salt excitability in SD rats was established.The finding of an excitatory saturation effect for four alkaloids/salts (nicotine, nicotinic benzoate, caffeine and arecoline hydrobromide) and the presence of excitatory intensity and gender differences at the same dose of inhalation of four alkaloids/salts, which provide a new theoretical basis for determiningthe content of alkaloids/salts.

Inhaled corticosteroid delivery is markedly affected by breathing pattern and valved holding chamber model.

There is a scarcity of high-quality research on the efficient delivery of inhaled corticosteroids using valved holding chambers (VHCs) in children. The delivered dose (DD) of fluticasone from a metered dose inhaler (pMDI) was tested using four VHCs: AeroChamber plus Flow-Vu (AC), Babyhaler (BH), EasyChamber (EC), and Optichamber Diamond (OD). The in vitro setup included an anatomical child throat model, Next Generation Impactor, and a breathing simulator to generate tidal breathing of a four and a 6-year-old child, and adult type single inhalation. OD showed the lowest proportion of fluticasone trapped in the throat with all breathing patterns. AC showed similar fine particle dose (FPD) in the respirable range (1-5 µm) irrespective of the breathing pattern. For BH, the median FPD 1-5 µm was highest during adult breathing. OD and EC showed higher overall DD and higher doses in the 1-5 µm range with paediatric breathing profiles compared to adult inhalation. The median DD and FPD 1-5 µm were significantly lower with BH compared to any other VHCs during tidal breathing. Compared to EC, the FPD of the other VHCs were skewed towards <2 µm particles. Fluticasone delivery is markedly affected by breathing pattern and VHC model. The observed differences in throat deposition and FPD delivered may have significant clinical implications for side effects and controlling airway inflammation. All VHCs intended for paediatric use should undergo testing using internationally recognised standardised methods incorporating clinically relevant paediatric breathing patterns.

Emotion regulation among adults with asthma: Links with short-acting inhaler medication overuse and utilization of acute medical care

Objective Existing research suggests that emotion plays an important role in airway inflammation and asthma symptom control. The objective of this study was to determine whether difficulties regulating emotion were associated with overuse of short-acting inhaled medications and acute medical care usage in adults with asthma. Methods The sample included 401 adults with asthma recruited from an online panel of adults with chronic respiratory disease. Sequential binary logistic regression models were used to examine the associations of emotion regulation with short-acting inhaled medication use and acute medical care use, controlling for patient characteristics and comorbid mental health conditions. Results Greater difficulties with emotion regulation were significantly associated with greater odds of short-acting inhaler medication overuse (p < 0.001), emergency department visits (p < 0.001), and hospitalizations (p = 0.001). Conclusions Emotion dysregulation may play an important role in asthma management. Evidence-based interventions to reduce difficulties in emotion regulation may help improve problematic patterns of short-acting medication overuse and acute service use. The current findings should be interpreted in the context of several limitations, including the use of self-report measures. Future research should use electronic medical records or metered dose inhalers to objectively assess short-acting inhaler overuse and acute medical care use.

Nebulized Budesonide Prevents Airway Inflammation in Children with High Total IgE Levels After Open Heart Surgery with Cardiopulmonary Bypass: A Prospective Randomized Controlled Trial.

Cardiopulmonary bypass (CPB) is a crucial technique used to repair congenital heart defects (CHD); however, it may induce inflammatory response, leading to airway inflammation and need for prolonged mechanical ventilation. In this study, we aimed to evaluate the effect of budesonide nebulization in children with high serum total immunoglobulin E (tIgE) levels undergoing surgical repair of CHD via CPB. We conducted a randomized, single-center, controlled trial at a tertiary teaching hospital. One-hundred and one children with high tIgE were enrolled and randomized into the budesonide nebulization group (BUD group, n = 50) or the normal saline nebulization group (NS group, n = 51) between January 2020 and December 2020. Budesonide or normal saline was administered through a vibrating mesh nebulizer during mechanical ventilation every 8h. Blood and bronchoalveolar lavage fluid (BALF) samples were examined and data on airway mechanics and clinical outcomes were recorded. IL-6 and IL-8 levels in the blood and BALF samples significantly increased after CPB in both groups. Budesonide inhalation reduced IL-6 and IL-8 levels in the blood and BALF samples in children with high tIgE (P < 0.05). The mean airway pressure, PCO2, and oxygen index in the BUD group were significantly lower than those in the NS group after the first inhalation dose and persisted until almost 24h after surgery. The peak inspiratory pressure and drive pressure were lower in the BUD group than in the NS group at nearly 24h after surgery, with no significant difference at other time points. Additionally, the duration of mechanical ventilation, number of noninvasive ventilations after extubation, and number of patients using aerosol-inhaled bronchodilators after CICU in the BUD group were significantly lower than those in the NS group (P < 0.05). Children with high preoperative tIgE levels are at risk of airway inflammation after cardiopulmonary bypass. Inhaling budesonide during postoperative mechanical ventilation can reduce the intensity of inflammatory reactions, shorten the duration of mechanical ventilation, reduce airway pressure and the utilization of NIV after extubation.

Emergency physicians’ preferences in bronchodilator delivery for asthma exacerbations: a cross-sectional study

Objective Asthma is a chronic respiratory disorder characterized by airway inflammation and narrowing often leading to acute exacerbations that necessitate a visit to the emergency department (ED). While life threatening cases usually require bronchodilator delivery by nebulizers, mild to moderate acute asthma exacerbations can be treated by bronchodilators delivered either by metered dose inhalers (MDI). Numerous studies have attempted to compare between the two modalities and have drawn similar conclusions in that both are comparable in efficacy with minimal differences. What is evident, however, is that physicians remain inclined to favor nebulizers in the majority of acute asthma exacerbations. Methods In this questionnaire-based study, a survey was distributed to physicians who treat asthma exacerbations to examine demographics, knowledge, beliefs, and current practice in regard to bronchodilator therapy. Results The majority (90.8%) of physicians prefer short-acting beta agonists via nebulizer, with 9.2% favoring MDI + spacer. Participants include consultants, residents, and specialists across various emergency disciplines. While 90.1% find MDI + spacer equally effective as nebulizers, advantages cited include cost-effectiveness (49.6%), shorter ED stays (63.4%), quicker administration (67.9%), and ease of use (58.8%). Challenges include availability (66.4%) and ineffectiveness in younger patients (45%). Despite this, 65.6% are willing to switch to MDI for initial asthma management in the ED, while 34.4% are resistant. Conclusion Concerns about availability and effectiveness in younger patients remain barriers. However, a significant number are willing to adopt MDIs with spacers, indicating potential for broader use with better availability and training.

Small Airways Disease Affects Aerosol Deposition in Children with Severe Asthma: A Functional Respiratory Imaging Study.

Background: Small airways disease (SAD) in severe asthma (SA) is associated with high disease burden. Effective treatment of SAD could improve disease control. Reduced end-expiratory flows (forced expiratory flow [FEF]25-75 and FEF75) are considered sensitive indicators of SAD. Inhaled medication should be delivered to the smaller peripheral airways to treat SAD effectively. Aerosol deposition is affected by structural airway changes. Little is known about the effect of SAD on aerosol delivery to the smaller peripheral airways. Functional respiratory imaging (FRI) is a validated technique using 3D reconstructed chest computed tomography (CT) and computational fluid dynamics to predict aerosol deposition in the airways. Aim: This study aims to compare central and peripheral (= small airways) deposition between children with SA and SAD and children with SA without SAD, with different inhaler devices and inhalation profiles. Methods: FRI was used to predict the deposition of beclomethasone/formoterol dry powder inhaler (DPI), beclomethasone/formoterol pressurized metered dose inhaler with valved holding chamber (pMDI/VHC), and salbutamol pMDI/VHC for different device-specific inhalation profiles in chest-CT of 20 children with SA (10 with and 10 without SAD). SAD was defined as FEF25-75 and FEF75 z-score < -1.645 and forced vital capacity (FVC) z-score > -1.645. No SAD was defined as forced expiratory volume (FEV)1, FEF25-75, FEF75, and FVC z-score > -1.645. The intrathoracic, central, and peripheral airways depositions were determined. Primary outcome was difference in central-to-peripheral (C:P) deposition ratio between children with SAD and without SAD. Results: Central deposition was significantly higher (∼3.5%) and peripheral deposition was lower (2.9%) for all inhaler devices and inhalation profiles in children with SAD compared with children without SAD. As a result C:P ratios were significantly higher for all inhaler devices and inhalation profiles, except for beclomethasone administered through DPI (p = .073), in children with SAD compared with children without SAD. Conclusion: Children with SA and SAD have higher C:P ratios, that is, higher central and lower peripheral aerosol deposition, than children without SAD. The intrathoracic, central, and peripheral deposition of beclomethasone/formoterol using DPI was lower than using pMDI/VHC.

Radon an indoor risk: In the Urban Devarakonda, Telangana state, India

Natural background radiation risk owing to radon and its progeny at indoors to the general public is a significant issue. The concern about indoor radon risk has been increasing at national and international level since its role to the overall dose is well known. The current study aims to assess the 222Rn and its progeny in different type of indoors with a passive (SSNTD) and active technique (RAD-7). The area of investigation (urban Devarakonda), is located near the proposed uranium mineralization area. The estimated radon levels in the indoors were ranging from 20 to 437 Bq. m−3 and with a geometric mean of 66 Bq.m−3. The estimated EERC values are ranging from 22 to 82 Bq.m−3 and these are higher than the range limit prescribed by ICRP. The computed average EF value in the present study (0.58) is relatively higher than the world average value of 0.4. An effort has been made to comprehend the radon distribution among the representative locations. Annual effective inhalation dose was also estimated using the occupancy factor 0.8 and it is found in the range of 0.52–11.00 m Sv y−1 with geometric mean of 2.20 mSv.y−1. The diurnal variation of 222Rn levels was studied using RAD-7 in a dwelling and seasonal variation of radon levels was also to be discussed in this paper.

Chromatographic fingerprinting of ipratropium and fenoterol in their novel co-formulated inhaler treating major respiratory disorders; application to delivered dose uniformity testing along with greenness and whiteness assessment

Ipratropium bromide (IPR) and fenoterol hydrobromide (FEN) have recently been combined in a promising inhaler to treat two prevalent inflammatory illnesses of the airways: bronchial asthma and chronic obstructive pulmonary disease (COPD). The necessity for a single, sensitive, and trustworthy analytical approach to cover the diverse and necessary tests of in-vitro and in-vivo studies is greatly grown with the rising production of new fixed combinations. Two novel, selective and environmentally friendly LC techniques were developed in order to guarantee precise measurement of IPR and FEN in their challenging formulation. The initial technique involved high-performance thin-layer chromatography (HPTLC) in conjunction with densitometric quantification. Chromatographic separation was attained on HPTLC plates utilizing ethyl acetate - ethanol - acetic acid (5.0:5.0:0.1, by volume) as a developing system. Densitometric quantification of the separated bands was carried out at 220.0 nm over concentration ranges of 0.50–15.0 µg/band for IPR and 0.50–12.0 µg/band for FEN. High-performance liquid chromatography (HPLC) paired with diode array detection (DAD) was the core of the second technique. The optimized separation was achieved on a Zorbax SB C18 (150 × 4.6 mm, 5 μm) column with a combination of 10.0 mM potassium dihydrogen orthophosphate, pH 5.0 ± 0.1, adjusted with o-phosphoric acid and methanol (70:30, v/v) as the mobile phase and pumped at flow rate of 1.0 mL/min. The peaks were monitored at 220.0 nm using diode array detection, achieving linearity range of 5.0–200.0 µg/mL for both drugs. The ICH criteria have been verified and both methods have been confirmed to be valid, and successfully applied for assay the cited drugs in the Atrovent® comp HFA metered dose inhaler as well as delivered dose uniformity testing of the final product. Finally, whiteness appraisal and several state-of-the-art green evaluation metrics were applied to evaluate the sustainability of the proposed methods. The suggested approaches produced promising results and are the first simple and sustainable methodologies for the simultaneous quantification of both drugs in different real samples, all of which strongly suggest their application in quality control laboratories.