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The aim of this study was to analyse the effect of breathing parameters, age, gender and disease status on the lung doses of the two ICS + LABA fixed combination dry powder drugs. Breathing parameters of 113 COPD patients were measured while inhaling through emptied NEXThaler® and Ellipta® inhalers and the corresponding lung doses were calculated. Lung dose of Foster® NEXThaler® was superior to the lung dose of Relvar® Ellipta® in around 85 % of the patients. The average value of the ratio of bronchiolar to bronchial deposition fractions was 5.0 for Foster® NEXThaler® and 2.6 for Relvar® Ellipta®. Lung dose was sensitive to the inhalation parameters, such as peak inhalation flow, inhaled volume and breath-hold time. For both studied drugs the dose to the lungs was relatively high for moderate PIF values, but it declined for low (<35 L/min) and high (>95 L/min) PIFs. The lung dose increased by the increase of the inhaled volume, but saturated over 1.0 L of inhaled air. Longer breath-hold time led to higher lung deposition, but the dependence was drug-specific. FEV 1 (%) and FEV 1 /FVC (%) did not influence the lung dose significantly (p = 0.05). Exacerbating patients had lower lung doses (28.8 ± 5.8 % for Foster® NEXThaler® and 23.7 ± 3.8 % for Relvar® Ellipta®) than their non-exacerbating counterparts (33.7 ± 6.1 % for Foster® NEXThaler® and for 24.9 ± 3.9 % for Relvar® Ellipta®). The exact clinical consequences of the differences between the deposition distributions of the two drugs could be assessed only by systematic clinical trials., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Balázs Sánta reports a relationship with Chiesi Hungary Kft that includes: employment., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The deposition of dry powder aerosol drugs depends on the inhalation parameters of the patients through the inhaler. These data are not directly measured in clinical practice. Their prediction based on the routinely measured spirometric data could help in choosing the appropriate device and optimizing the therapy. The aim of this study was to perform inhalation experiments to find correlations between inhalation parameters of COPD patients through two DPI devices and their native spirometric data, gender, age and disease severity. Another goal was to establish relationships between peak inspiratory flows through NEXThaler® and Ellipta® inhalers and their statistical determinants. Breathing parameters of 113 COPD patients were measured by normal spirometry and while inhaling through the two DPIs. Statistical analysis of the measured data was performed. The average values of peak inspiratory flow through the devices (PIF dev ) were 68.4 L/min and 78.0 L/min for NEXThaler® and Ellipta®, respectively. PIF dev values were significantly higher for males than for females, but differences upon age, BMI and disease severity group were not significant. PIF dev values correlated best with their native spirometric counterparts (PIF) and linear relationships between them were revealed. Current results may be used in the future to predict the success of inhalation of COPD patients through DPI devices, which may help in the inhaler choice. By choosing the appropriate device-drug pair for each patient the lung dose can be increased and the efficiency of the therapy improved. Further results of the clinical study will be the subject of a next publication., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alpár Horváth, Gábor Tomisa, Balázs Sánta report a relationship with Chiesi Hungary Kft that includes: employment., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Total, regional and local deposition fractions of urban-type aerosol particles with diameters of 50, 75, 110 and 145 nm were modelled and studied in their dry state and after their hygroscopic growth using a Stochastic Lung Model and a Computational Fluid and Particle Dynamics method. Healthy subjects and patients with severe chronic obstructive pulmonary disease (COPD) were considered. The hygroscopic growth factors (HGFs) adopted were determined experimentally and represent a real urban-type environment. The hygroscopic growth of particles resulted in decrease of the deposition fractions in all major parts of the healthy respiratory system and the extent of the deposited fractions was rising monotonically with particle size. In the extrathoracic (ET) region, the relative decrease was between 7% and 13%. In the lungs the deposition decreased by 11-16%. The decrease of deposition fraction due to hygroscopic growth was more accentuated in the conductive airways (up to 25%) and less pronounced towards the terminal airways. The spatial distribution of the deposited particles remained highly inhomogeneous with some areas containing thousands times more particles than the average number of particles per unit surface area. For COPD patients, the hygroscopic growth produced similar deposition alterations in the ET region than for healthy subjects. In the conductive airways, however, the particle growth caused a substantial relative decrease in the deposition fractions. In contrast, the relative depositions of hygroscopic particles increased in the acinar region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Existing therapies yield low drug encapsulation or accumulation in the lungs, hence the site-specific drug delivery remains the challenge for tuberculosis. Lately, dry powder inhalers (DPIs) are showing promising drug deposition in the deeper lung tissues. Biocompatible polymers with the ability to naturally recognize and bind to the surface receptors of alveolar macrophages, the reservoir of the causative organism, were selected. DPIs comprised of chitosan (CS)/thiolated chitosan (TC) in conjugation with Hyaluronic acid (HA) were synthesized loaded with isoniazid (INH) by using the Design of Experiment (DoE) approach. Nanosuspensions were prepared by ionic gelation method using cross-linker, sodium-tripolyphosphate (TPP) and were optimized by using Box-Behnken 3-level screening design and later freeze-dried to obtain nanopowders. Physico-chemical compatibility of nanoplex systems was investigated using in-vitro characterization techniques. In-vitro release and permeation studies were correlated in terms of the pattern of drug content dissolved over time. In addition, the cytotoxicity studies on A549 cells demonstrated the safety profile of the nanoplexes. Moreover, in-silico studies and aerodynamic profiles verify the suitability of DPIs for further in-vivo tuberculosis therapeutics. DoE analyses affirmed the lack of linearity in the model for the certain response of studied parameters in a holistic way, which was not possible else ways., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Drug emission from DPIs is dependent on the inspiratory flow parameters through them, which are not directly measured by standard spirometry. Their estimation based on native spirometric data could help in choosing the appropriate device and optimizing the drug deposition., Objectives: The aim of this study was to survey patient preferences and to find correlations between breathing parameters of COPD patients through DPI devices and their baseline spirometric data, age, gender, disease severity and anthropometric characteristics. Another objective was to establish relationships between peak inspiratory flows (PIF dev ) through Breezhaler ® , Genuair ® and Turbuhaler ® inhalers and their determinants., Methods: Breathing parameters of 49 patients with previously diagnosed COPD and currently using one of the above inhalers were recorded by normal spirometry and while inhaling through the selected DPIs. Statistical analysis of the measured data was completed. All specific data are provided as (mean ± standard deviation)., Results: More than 60% of the patients stated that their current device is the easiest to use. The means of the measured PIF dev values were 91.4 L/min, 77.1 L/min and 77.5 L/min for Breezhaler ® , Genuair ® , and Turbuhaler ® , respectively. PIF dev values were significantly higher for males than for females, but differences upon age, BMI and disease severity group were not significant (at p = 0.05). Peak inspiratory flows through the inhalers (PIF dev ) correlated best with their native spirometric counterparts (PIF) and linear PIF dev -PIF relationships could be determined (Breezhaler ® : r = 0.60, p = 0.002, Genuair ® : r = 0.55, p = 0.001, Turbuhaler ® : r = 0.57, p = 0.002). Physical background of the deduced equations was also provided., Conclusions: Present correlations may be used to assess the success of inhalation of COPD patients through the studied devices and to choose the appropriate device for each patient. As a consequence, the amount of the drug emitted by the device can be optimized, the deposition efficiency within the lungs increased and the related therapeutic effect improved., (Copyright © 2019 Elsevier Ltd. All rights reserved.)