Medicine › Pulmonary and Respiratory Medicine

Inhalation and Respiratory Drug Delivery

Works Count: 54893

Wikipedia

Description

This cluster of papers focuses on advancements in pulmonary drug delivery techniques, including the use of inhaler devices, nanoparticles, aerosol therapy, and dry powder inhalers. It explores topics such as respiratory tract deposition, lung diseases, nanomedicine, and the delivery of inhaled insulin.

Keywords

Pulmonary Drug Delivery; Inhaler Devices; Nanoparticles; Aerosol Therapy; Particle Engineering; Respiratory Tract Deposition; Dry Powder Inhalers; Lung Diseases; Nanomedicine; Inhaled Insulin

Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications

2003-08-20

N. R. Labiris , Myrna Dolovich

As the end organ for the treatment of local diseases or as the route of administration for systemic therapies, the lung is a very attractive target for drug delivery. It … As the end organ for the treatment of local diseases or as the route of administration for systemic therapies, the lung is a very attractive target for drug delivery. It provides direct access to disease in the treatment of respiratory diseases, while providing an enormous surface area and a relatively low enzymatic, controlled environment for systemic absorption of medications. As a major port of entry, the lung has evolved to prevent the invasion of unwanted airborne particles from entering into the body. Airway geometry, humidity, mucociliary clearance and alveolar macrophages play a vital role in maintaining the sterility of the lung and consequently are barriers to the therapeutic effectiveness of inhaled medications. In addition, a drug's efficacy may be affected by where in the respiratory tract it is deposited, its delivered dose and the disease it may be trying to treat.

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Resistance of central and peripheral airways measured by a retrograde catheter

1967-03-01

Peter T. Macklem , J. Mead

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Mechanical Properties of Lungs

1961-04-01

Jere Mead

An Official Research Policy Statement of the American Thoracic Society/European Respiratory Society: Standards for Quantitative Assessment of Lung Structure

2010-02-03

Connie C. W. Hsia , Dallas M. Hyde , Matthias Ochs +1 more

Keywords: morphometry; stereology; unbiased sampling; reference lung volume; cell volume; surface area; cell size; cell number; in vivo imaging Keywords: morphometry; stereology; unbiased sampling; reference lung volume; cell volume; surface area; cell size; cell number; in vivo imaging

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The Relations between Structural Changes in Small Airways and Pulmonary-Function Tests

1978-06-08

María Dolores García‐Cosío Carmena , Heberto Ghezzo , James C. Hogg +4 more

To examine the relation between small-airways abnormalities and specific lung functions, we performed pulmonary-function tests in 36 patients, of whom two were nonsmokers, one to three days before open-lung biopsy … To examine the relation between small-airways abnormalities and specific lung functions, we performed pulmonary-function tests in 36 patients, of whom two were nonsmokers, one to three days before open-lung biopsy for localized pulmonary lesions. The primary lesion in the small airways was a progressive inflammatory reaction leading to fibrosis with connective-tissue deposition in the airway walls. Increase in disease in small airways correlated with deterioration in lung function. Lesions could be reliably detected (P less than 0.05) by tests for closing capacity, the volume at which air and helium flow ere equal (a test of airway caliber and elastic recoil), and the slope of phase III of the single-breath washout curve (which tests evenness of ventilation). These tests showed abnormalities at a time when the pathologic changes were still potentially reversible and when other tests were not appreciably changed.

Correlation between particle size, in vivo particle persistence, and lung injury.

1994-10-01

G. Oberdörster , J Ferin , Bruce E. Lehnert

Dosimetry parameters such as deposition, clearance, retention, and translocation and dissolution of inhaled particles in and to different lung compartments may be important for the persistence of particles in the … Dosimetry parameters such as deposition, clearance, retention, and translocation and dissolution of inhaled particles in and to different lung compartments may be important for the persistence of particles in the lung and may correlate with adverse pulmonary effects. We investigated such correlations using a model involving TiO2 particles of two particle sizes (20 nm diameter, ultrafine; 250 nm diameter, fine) of the same crystalline structure (anatase). A 12-week inhalation experiment in rats resulted in a similar mass deposition of the two particle types in the lower respiratory tract. The ultrafine particles elicited a persistently high inflammatory reaction in the lungs of the animals compared to the larger-sized particles. In the postexposure period (up to 1 year) retention in the alveolar space per se was not different between fine and ultrafine TiO2. However, the following differences between the particle types were noted: a significantly different total pulmonary retention, both quantitatively (significantly prolonged retention of the ultrafine TiO2) and qualitatively (increased translocation to the pulmonary interstitium and persistence there of the ultrafine TiO2); greater epithelial effects (Type II cell proliferation; occlusion of pores of Kohn) and the beginning of interstitial fibrotic foci with ultrafine TiO2; significant sustained impairment of alveolar macrophage function after ultrafine TiO2 exposure as measured by the clearance of test particles. A correlation between particle surface area and effects was observed. A comparison of the adverse reactions with dosimetric parameters of TiO2 in different lung compartments in the postexposure period showed a correlation of the persistence of effects in both the alveolar and interstitial space with the persistence of particles in the respective compartment.

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Inhaled nanoparticles—A current review

2008-02-20

Wei Yang , Jay I. Peters , Robert O. Williams

Large Porous Particles for Pulmonary Drug Delivery

1997-06-20

David A. Edwards , Justin Hanes , Giovanni Caponetti +7 more

A new type of inhalation aerosol, characterized by particles of small mass density and large size, permitted the highly efficient delivery of inhaled therapeutics into the systemic circulation. Particles with … A new type of inhalation aerosol, characterized by particles of small mass density and large size, permitted the highly efficient delivery of inhaled therapeutics into the systemic circulation. Particles with mass densities less than 0.4 gram per cubic centimeter and mean diameters exceeding 5 micrometers were inspired deep into the lungs and escaped the lungs' natural clearance mechanisms until the inhaled particles delivered their therapeutic payload. Inhalation of large porous insulin particles resulted in elevated systemic levels of insulin and suppressed systemic glucose levels for 96 hours, whereas small nonporous insulin particles had this effect for only 4 hours. High systemic bioavailability of testosterone was also achieved by inhalation delivery of porous particles with a mean diameter (20 micrometers) approximately 10 times that of conventional inhaled therapeutic particles.

SUBEPITHELIAL FIBROSIS IN THE BRONCHI OF ASTHMATICS

1989-03-01

WilliamR. Roche , J H Williams , Richard Beasley +1 more

Evaporation-Induced Self-Assembly: Nanostructures Made Easy

1999-05-01

C. Jeffrey Brinker , Yunfeng Lu , Alan Sellinger +1 more

Simple and efficient methods of organizing materials are key to the realization of a nanotech world. These authors report on recent developments in simple evaporation-induced self-assembly processes, which enable the … Simple and efficient methods of organizing materials are key to the realization of a nanotech world. These authors report on recent developments in simple evaporation-induced self-assembly processes, which enable the rapid production of patterned porous or nanocomposite materials. The Figure shows a calcined particle exhibiting vesicular mesophase, which was generated by aerosol self-assembly of the tri-block copolymer P123.

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Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics

2001-08-23

Nasir Hussain

Inhaling medicines: delivering drugs to the body through the lungs

2006-12-29

John S. Patton , Peter R. Byron

Bronchial Biopsies in Asthma: An Ultrastructural, Quantitative Study and Correlation with Hyperreactivity

1989-12-01

Peter K. Jeffery , Andrew J. Wardlaw , Fiona Nelson +2 more

Little is known of the structural changes in mild asthma. We have studied the light and electron microscopic structure of lobar bronchial biopsies taken at fiberoptic bronchoscopy from 11 atopic … Little is known of the structural changes in mild asthma. We have studied the light and electron microscopic structure of lobar bronchial biopsies taken at fiberoptic bronchoscopy from 11 atopic asthmatics, four of whom were symptomatic and seven of whom were asymptomatic. The former and three of the latter had bronchial hyperresponsiveness to methacholine (PC20 < 4 mg/ml). Quantitative comparisons were made with biopsies from ten control subjects with normal airway reactivity; five had hay fever and five were nonatopic healthy volunteers. Complete absence of surface epithelium was found in three cases of symptomatic asthma, and stratified squamous epithelium was present in the fourth. A biopsy from one of the healthy control subjects had also lost its surface epithelium. The degree of epithelial loss in all subjects correlated with the degree of airway reactivity (rs = 0.67, p < 0.001). The reticular lamina of the epithelial basement membrane showed a trend toward thickening in the seven hyperreactive asthmatics (p < 0.001: median test). There was a tendency to high numbers of inflammatory cells in the lamina propria, but not in the submucosa, of asthmatics, but the differences between groups did not achieve statistical significance. There were significant alterations (px2 < 0.001) in the proportions of each type of inflammatory cell found in the lamina propria and submucosa of symptomatic asthmatics: an increase of irregularly shaped lymphocytes contributed most to the observed alteration. Where surface epithelium was present, intraepithelial lymphocytes formed the major proportion of intraepithelial “migratory” cells: 64% in normal control subjects, 78% in subjects with hay fever, and 87% in asymptomatic asthmatics. There were no obvious differences in the frequency of ciliary abnormalities or the presence of epithelial or subepithelial edema, mast cells, nerve fibers, vascular congestion, extravasation of erythrocytes, or platelets. However, platelets were found aggregated together with electron-dense fibrous material at the airway lumenal edge in biopsies of the symptomatic asthma group. Mucous cell hyperplasia was not a feature of either the asymptomatic asthma or the hay fever group. The results support the hypothesis that epithelial fragility is closely linked to airway hyperreactivity and demonstrate that thickening of the reticular lamina begins early in the condition. The appearance of irregularly shaped lymphocytes in symptomatic asthmatics requires further study to characterize their phenotype and involvement in the pathogenesis of asthma.

Deposition of particles in the human respiratory tract in the size range 0.005–15 μm

1986-01-01

J. Heyder , J. Gebhart , G. Rudolf +2 more

Properties, Function and Origin of the Alveolar Lining Layer

1955-06-01

R. E. Pattle

Morphometry of the human pulmonary acinus

1988-04-01

Beatrice Haefeli‐Bleuer , Ewald R. Weibel

The geometry and morphometry of intraacinar airways in human lungs were studied on silicone rubber casts from two adult lungs. We defined acini as the complex of alveolated airways distal … The geometry and morphometry of intraacinar airways in human lungs were studied on silicone rubber casts from two adult lungs. We defined acini as the complex of alveolated airways distal to the terminal bronchioles--that is, beginning with the first-order respiratory or transitional bronchiole. The morphological properties of pulmonary acini are described. The acinar volume averages 187 mm3 (SD +/- 79 mm3). Intraacinar airways branch dichotomously over about 9 generations (range 6-12). The internal airway diameter falls from 500 micron to 270 micron between acinar generations 0 and 10, whereas the outer diameter (including the sleeve of alveoli) remains constant at 700 micron. Towards the periphery the size of alveoli increases and clusters of alveoli become more numerous. The longitudinal path length of acinar airways (defined as the distance along the ducts from the transitional bronchiole to the alveolar sacs) averages 8.8 mm (+/- 1.4 mm). The morphometric data collected in this study are used to construct an idealized model of human acinar airways that can be related to existing models of the human bronchial tree.

Drug Development and Industrial Pharmacy

1995-01-01

C. T. Rhodes

In recent years, the use of nebulisers to generate aerosols has been greatly extended because of their numerous advantages. Two types of nebulisers are commonly used, each based on a … In recent years, the use of nebulisers to generate aerosols has been greatly extended because of their numerous advantages. Two types of nebulisers are commonly used, each based on a different principle : - jet nebulisers, based on the Venturi effect to fragment liquid preparations into small droplets. - ultrasonic nebulisers, using the vibrations of a quartz to produce aerosol. The use of nebulisers lacks standardisation, which may account for certain inefficiency. First of all, we defined the parameters required to evaluate nebulisation efficiency. Although droplet size is a commonly used parameter, it is not sufficient to forecast efficiency. It must be associated with the quantity of drug nebulised and nebulisation time. Secondly, we listed factors influencing nebulisation efficiency.

A biomimetic nanosponge that absorbs pore-forming toxins

2013-04-14

Che‐Ming Jack Hu , Ronnie H. Fang , Jonathan A. Copp +2 more

Standardization of bronchial inhalation challenge procedures

1975-10-01

Hyman Chai , Richard S. Farr , Luz A. Froehlich +6 more

Inhaler mishandling remains common in real life and is associated with reduced disease control

2011-03-07

Andrea S. Melani , Marco Bonavia , Vincenzo Cilenti +7 more

Myofibroblasts and Subepithelial Fibrosis in Bronchial Asthma

1990-11-01

Charlotte E. P. Brewster , Peter Howarth , Ratko Djukanović +3 more

A thickened bronchial epithelial basement membrane has long been regarded as a histopathologic characteristic of bronchial asthma. As we had previously demonstrated that this phenomenon is due to the deposition … A thickened bronchial epithelial basement membrane has long been regarded as a histopathologic characteristic of bronchial asthma. As we had previously demonstrated that this phenomenon is due to the deposition of interstitial collagens and fibronectin, we have now sought to determine the nature of the cell responsible for this process by studying endobronchial biopsies from eight normal and seven asthmatic volunteers by immunohistochemistry and electron microscopy. Biopsies were stained with PR 2D3, a monoclonal antibody to myofibroblasts of the pericrypt sheath of the colon and a monoclonal antibody to alpha-smooth muscle actin. The thickness of the subepithelial collagen and the organelle content of the cells therein were determined by electron microscopy.The subepithelial collagen thickness in the normal subjects ranged from 2.16 to 6.26 µm, while that in the asthmatic subjects ranged from 3.75 to 11.1 µm (Mann-Whitney test; P = 0.05). Elongated cells in the collagen layer were identified by staining with PR 2D3. As this antibody also stains smooth muscle, consecutive frozen sections were stained for alpha-smooth muscle actin and the number of positive cells per millimeter of basement membrane was subtracted from the count for PR 2D3. This yielded a count of 4.9 to 9.4 cells/mm in the normal subjects and 11.9 to 20.6 cells/mm in the asthmatics (P = 0.001). There was a highly significant correlation between the depth of subepithelial collagen and the number of PR 2D3-positive, alpha-smooth muscle actin-positive cells (Spearman rank correlation; r = 0.764 and P = 0.006). Electron microscopy confirmed the myofibroblastic nature of these cells. We propose that bronchial myofibroblasts are responsible for the characteristic subepithelial fibrosis seen in allergic asthma.

Pathologic Changes in the Peripheral Airways of Young Cigarette Smokers

1974-10-10

Dennis E. Niewoehner , Jerome Kleinerman , Donald B. Rice

The lungs of young smokers and controls of comparable age from a population of sudden non-hospital deaths were systematically studied to determine the relation between cigarette smoking and pathologic changes … The lungs of young smokers and controls of comparable age from a population of sudden non-hospital deaths were systematically studied to determine the relation between cigarette smoking and pathologic changes in peripheral airways. The characteristic lesion observed was a respiratory bronchiolitis associated with clusters of pigmented alveolar macrophages and was present in the lungs of all smokers studied but rarely seen in nonsmokers (p<0.002). The lungs of smokers also showed small but significant increases in mural inflammatory cells and denuded epithelium in the membranous bronchioles as compared to controls (p<0.05). We postulate that this respiratory bronchiolitis is a precursor of centriacinar emphysema and may be responsible for the subtle functional abnormalities observed in young smokers. (N Engl J Med 291: 755–758, 1974)

THE PATHOLOGY OF ASTHMA, WITH SPECIAL REFERENCE TO CHANGES IN THE BRONCHIAL MUCOSA

1960-01-01

M. S. Dunnill

The pathological features of 20 cases dying in status asthmaticus have been studied. In gross sections the lungs showed no emphysema, but mucus plugs in the air passages and focal … The pathological features of 20 cases dying in status asthmaticus have been studied. In gross sections the lungs showed no emphysema, but mucus plugs in the air passages and focal areas of collapse were outstanding features. Five cases showed cystic bronchiectasis which was of a similar distribution to the focal areas of collapse, occurring in the upper lobes as commonly as in the lower lobes.Histologically, shedding of the ciliated bronchial mucosal cells was prominent and this is attributed to a transudation of oedema fluid from the submucosa. Areas of regeneration of the mucosa, with the presence of simple stratified epithelium, were seen frequently. The loss of the ciliated respiratory epithelium and the transudation of oedema fluid into the bronchial lumen, with interference with the action of the remaining ciliated cells, are considered to be the essential factors in the failure of clearance of the bronchial secretions in asthma. It is postulated that bronchospasm plays little or no part in the shedding of the bronchial mucosa or in the pathogenesis of the asthmatic attack.

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Characterization of the A549 Cell Line as a Type II Pulmonary Epithelial Cell Model for Drug Metabolism

1998-09-01

Kimberly A. Foster , Christine G. Oster , Mary M. Mayer +2 more

The normal human lung: ultrastructure and morphometric estimation of diffusion capacity

1978-02-01

Peter Gehr , M Bachofen , Ewald R. Weibel

Formulation strategy and use of excipients in pulmonary drug delivery

2010-03-10

Gabrielle Pilcer , Karim Amighi

CORRELATED MORPHOMETRIC AND BIOCHEMICAL STUDIES ON THE LIVER CELL

1969-07-01

Ewald R. Weibel , W. Stäubli , Hans Rudolf Gnägi +1 more

The basic morphological properties of liver cells are defined in the form of a morphometric model to permit integrated quantitative characterization of functionally important parameters. Stereologic methods which allow efficient … The basic morphological properties of liver cells are defined in the form of a morphometric model to permit integrated quantitative characterization of functionally important parameters. Stereologic methods which allow efficient and reliable quantitative evaluation of sectioned liver tissue are presented. Material, obtained by a rigorous three-stage sampling procedure from five normal rat livers, is systematically subjected to this analysis at four levels of magnification. This yields quantitative data which are expressed as "densities," i.e. content per 1 ml of tissue, as "specific dimensions" related to 100 g body weight, and as absolute dimensions per average "mononuclear" hepatocyte. Base line data relating to the normal rat liver are presented for the entire spectrum of parameters. As examples, 1 ml of liver tissue contains 169 x 10(6) hepatocyte nuclei, some 90 x 10(6) nuclei of other cells, and 280 x 10(9) mitochondria. Hepatocyte cytoplasm accounts for 77% of liver volume, and the mitochondria for 18%. The surface area of endoplasmic reticulum membranes in 1 ml of liver tissue measures 11 m(2) of which are (2/3) of the rough form carrying some 2 x 10(13) ribosomes. The surface area of mitochondrial cristae in the unit volume is estimated at 6 m(2). The validity and applicability of the method are discussed, and the data are compared with available information from other studies.

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Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities

2008-11-26

Lidia Morawska , Graham Johnson , Zoran Ristovski +6 more

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Models of the human bronchial tree.

1971-08-01

Keith Horsfield , G Dart , D. E. Olson +2 more

What the pulmonary specialist should know about the new inhalation therapies

2011-02-10

Beth L. Laube , Hettie M. Janssens , Frans H. de Jongh +7 more

A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order … A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date recommendations that enable the pulmonary physician to choose the type of aerosol delivery device that is most suitable for their patient. The focus of the consensus statement is the patient-use aspect of the aerosol delivery devices that are currently available. The subject was divided into different topics, which were in turn assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. To achieve consensus, draft reports and recommendations were reviewed and voted on by the entire panel. Specific recommendations for use of the devices can be found throughout the statement. Healthcare providers should ensure that their patients can and will use these devices correctly. This requires that the clinician: is aware of the devices that are currently available to deliver the prescribed drugs; knows the various techniques that are appropriate for each device; is able to evaluate the patient's inhalation technique to be sure they are using the devices properly; and ensures that the inhalation method is appropriate for each patient.

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Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss.

1983-10-01

A. M. Parfitt , Catharina H. E. Mathews , A. R. Villanueva +3 more

We devised a new method for examining the structural changes that occur in trabecular bone in aging and in osteoporosis. With simultaneous measurement of total perimeter and bone area in … We devised a new method for examining the structural changes that occur in trabecular bone in aging and in osteoporosis. With simultaneous measurement of total perimeter and bone area in thin sections, indirect indices of mean trabecular plate thickness (MTPT) and mean trabecular plate density (MTPD) can be derived, such that trabecular bone volume = MTPD X MTPT. MTPD is an index of the probability that a scanning or test line will intersect a structural element of bone, and is the reciprocal of the mean distance between the midpoints of structural elements, multiplied by pi/2. We applied this method to iliac bone samples from 78 normal subjects, 100 patients with vertebral fracture, and 50 patients with hip fracture. The reduction in trabecular bone volume observed in normal subjects with increasing age was mainly due to a reduction in plate density, with no significant decrease in plate thickness. The further reduction in trabecular bone volume observed in patients with osteoporotic vertebral fracture was mainly due to a further reduction in plate density. There was a relatively smaller reduction in plate thickness that was statistically significant in males but not in females. Only in patients with hip fracture did trabecular thinning contribute substantially to the additional loss of trabecular bone in osteoporosis relative to age. These data indicate that age-related bone loss occurs principally by a process that removes entire structural elements of bone; those that remain are more widely separated and some may undergo compensatory thickening, but most slowly become reduced in thickness. We propose that the process of removal is initiated by increased depth of osteoclastic resorption cavities which leads to focal perforation of trabecular plates; this is followed by progressive enlargement of the perforations with conversion of plates to rods. The resulting structural changes are more severe in osteoporotic patients than in normal subjects, but have been completed in most patients before they develop symptoms.

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Rapid method for measurement of bronchial responsiveness.

1983-10-01

K Yan , Cheryl M. Salome , Ann J. Woolcock

A rapid, simple method for measuring bronchial responsiveness to inhaled histamine is described. The method was used to obtain dose response curves in 50 atopic subjects with varying respiratory and … A rapid, simple method for measuring bronchial responsiveness to inhaled histamine is described. The method was used to obtain dose response curves in 50 atopic subjects with varying respiratory and nasal symptoms. The cumulative dose of histamine which caused a 20% fall in the one second forced expiratory volume (PD20-FEV1) varied between 0.046 and greater than 3.9 mumol and correlated with the severity of symptoms. The reproducibility of the PD20-FEV1, determined from duplicate measurements in 15 subjects with varying degrees of bronchial responsiveness was found to be satisfactory. When the PD20-FEV1 from this rapid method was compared with that obtained from the dosimeter method no significant difference was found. The dose delivered by this method was shown to be cumulative.

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Particle formation in spray drying

2007-05-25

Reinhard Vehring , Willard R. Foss , David Lechuga‐Ballesteros

Pharmaceutical Particle Engineering via Spray Drying

2007-11-26

Reinhard Vehring

This review covers recent developments in the area of particle engineering via spray drying. The last decade has seen a shift from empirical formulation efforts to an engineering approach based … This review covers recent developments in the area of particle engineering via spray drying. The last decade has seen a shift from empirical formulation efforts to an engineering approach based on a better understanding of particle formation in the spray drying process. Microparticles with nanoscale substructures can now be designed and their functionality has contributed significantly to stability and efficacy of the particulate dosage form. The review provides concepts and a theoretical framework for particle design calculations. It reviews experimental research into parameters that influence particle formation. A classification based on dimensionless numbers is presented that can be used to estimate how excipient properties in combination with process parameters influence the morphology of the engineered particles. A wide range of pharmaceutical application examples—low density particles, composite particles, microencapsulation, and glass stabilization—is discussed, with specific emphasis on the underlying particle formation mechanisms and design concepts.

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Nanoparticle Uptake by the Rat Gastrointestinal Mucosa: Quantitation and Particle Size Dependency

1990-12-01

Praful U. Jani , Gavin Halbert , John Langridge +1 more

Abstract Polystyrene microspheres in the size range 50 nm to 3 μm were fed by gavage to female Sprague Dawley rats daily for 10 days at a dose of 1.25 … Abstract Polystyrene microspheres in the size range 50 nm to 3 μm were fed by gavage to female Sprague Dawley rats daily for 10 days at a dose of 1.25 mg kg−1. Previous histological evidence of the uptake of these particles and their absorption across the gastrointestinal tract and passage via the mesentery lymph supply and lymph nodes to the liver and spleen was confirmed by analysis of tissues for the presence of polystyrene by gel permeation chromatography. Measurement of radioactivity of tissues following administration of 100 nm and 1 μm I125-labelled polystyrene latex particles for 8 days was corroborative although less secure because of the potential lability of the labelled particles. The extent of absorption of 50 nm particles under the conditions of these experiments was 34% and of the 100 nm particles 26% (as measured by determination of polystyrene content), of which total, about 7% (50 nm) and 4% (100 nm), was in the liver, spleen, blood and bone marrow. Particles larger than 100 nm did not reach the bone marrow, and those larger than 300 nm were absent from blood. No particles were detected in heart or lung tissue.

Tobacco Smoke, Indoor Air Pollution and Tuberculosis: A Systematic Review and Meta-Analysis

2007-01-11

Hsien-Ho Lin , Majid Ezzati , Megan Murray

Background Tobacco smoking, passive smoking, and indoor air pollution from biomass fuels have been implicated as risk factors for tuberculosis (TB) infection, disease, and death. Tobacco smoking and indoor air … Background Tobacco smoking, passive smoking, and indoor air pollution from biomass fuels have been implicated as risk factors for tuberculosis (TB) infection, disease, and death. Tobacco smoking and indoor air pollution are persistent or growing exposures in regions where TB poses a major health risk. We undertook a systematic review and meta-analysis to quantitatively assess the association between these exposures and the risk of infection, disease, and death from TB. Methods and Findings We conducted a systematic review and meta-analysis of observational studies reporting effect estimates and 95% confidence intervals on how tobacco smoking, passive smoke exposure, and indoor air pollution are associated with TB. We identified 33 papers on tobacco smoking and TB, five papers on passive smoking and TB, and five on indoor air pollution and TB. We found substantial evidence that tobacco smoking is positively associated with TB, regardless of the specific TB outcomes. Compared with people who do not smoke, smokers have an increased risk of having a positive tuberculin skin test, of having active TB, and of dying from TB. Although we also found evidence that passive smoking and indoor air pollution increased the risk of TB disease, these associations are less strongly supported by the available evidence. Conclusions There is consistent evidence that tobacco smoking is associated with an increased risk of TB. The finding that passive smoking and biomass fuel combustion also increase TB risk should be substantiated with larger studies in future. TB control programs might benefit from a focus on interventions aimed at reducing tobacco and indoor air pollution exposures, especially among those at high risk for exposure to TB.

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Mechanisms of macromolecule absorption by the lungs

1996-04-01

John S. Patton

Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis

1980-05-01

Joseph S. Lam , Raymond J. Chan , Kei Fong Lam +1 more

Direct electron microscopic examination of postmortem lung material from cystic fibrosis patients infected with Pseudomonas aeruginosa has shown that these bacterial cells form distinct fiber-enclosed microcolonies in the infected alveoli. … Direct electron microscopic examination of postmortem lung material from cystic fibrosis patients infected with Pseudomonas aeruginosa has shown that these bacterial cells form distinct fiber-enclosed microcolonies in the infected alveoli. Similar examination of bronchoscopy material from infected cystic fibrosis patients showed that the fibres of the enveloping matrix are definitely associated with the bacterial cells. The fibers of the extracellular matrix stain with ruthenium red and are therefore presumed to be polyanionic. When mucoid strains of P. aeruginosa were recovered from cystic fibrosis patients and grown in a suitable liquid medium, they were found to produce large microcolonies whose component cells were embedded in a very extensive matrix of polyanionic fibers that could be stabilized by reaction with antibodies to prevent collapse during the dehydration steps of preparation for electron microscopy. When these mucoid strains of P. aeruginosa were used to produce pulmonary infections of rats by the agar bead method, the infected alveoli contained large fiber-enclosed bacterial microcolonies. We conclude that the cells of P. aeruginosa that infect cystic fibrosis patients form microcolonies that are enveloped in a fibrous anionic matrix and that these microcolonies can be duplicated in in vitro cultures and in animal model systems.

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A principle for counting tissue structures on random sections

1962-03-01

Ewald R. Weibel , Domingo M. Gómez

A new principle is derived from mathematical considerations which will allow the calculation of the number of bodies contained in the unit volume by counting the number of transections on … A new principle is derived from mathematical considerations which will allow the calculation of the number of bodies contained in the unit volume by counting the number of transections on the unit area of a random section. The simple equation involves two coefficients related to the volumetric density of the bodies in the volume, and to their configuration. Means for the accurate determination of these coefficients are given. The verification of this principle in model experiments showed a high degree of reliability of the method with average errors of estimate of 2–4%. The method has been applied to the counting of alveoli in five normal human lungs, which were found to number an average of 300 million, with a striking constancy from lung to lung. Submitted on May 31, 1961

Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society.

1993-03-01

Quanjer Ph , Tammeling Gj , Cotes Je +3 more

THE THEORY AND APPLICATIONS OF THE EXCHANGE OF INERT GAS AT THE LUNGS AND TISSUES

1951-03-01

Seymour S. Kety

Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro

2015-12-21

Kambez H. Benam , Rémi Villenave , Carolina Lucchesi +7 more

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Relative Importance of Diffusion and Chemical Reaction Rates in Determining Rate of Exchange of Gases in the Human Lung, With Special Reference to True Diffusing Capacity of Pulmonary Membrane and Volume of Blood in the Lung Capillaries

1957-09-01

F. J. W. Roughton , Robert Förster

An equation, i/Dm + i/θVc = i/Dl, has been derived which relates the measured pulmonary diffusing capacity (Dl), the true diffusing capacity of the pulmonary membrane (Dm), the rate of … An equation, i/Dm + i/θVc = i/Dl, has been derived which relates the measured pulmonary diffusing capacity (Dl), the true diffusing capacity of the pulmonary membrane (Dm), the rate of uptake of CO by the red cells per mm Hg CO tension (θ) and the blood volume of the pulmonary capillary bed (Vc). By making measurements of Dl at different alveolar O2 tensions, thereby causing to vary, this equation can be solved graphically for Dm and Vc, which are assumed to be independent of O2 tension. Calculations of Dm and Vc were made utilizing a) values of θ previously obtained from the in vitro rates of CO uptake of suspensions of human red cells at 37°C and b) values of Dl in normal resting subjects at alveolar O2 tensions from about 100 mm Hg to over 600 mm Hg measured by both steady state and breath holding CO techniques. Dm is about twice the value of Dl measured in subjects breathing air at sea level. Vc is about 75 ml in approximate agreement with the previously reported estimate of Roughton. Similar results were obtained using values of Dl at different alveolar O2 tensions reported in the literature. This means that, in determining the rate of CO absorption in the lungs, the resistance of the red cell to the uptake of CO is of the same order of importance as the resistance of the pulmonary membrane to the diffusion of gas across it. Arguments are advanced to show that red cell resistance is of at least equal importance in the case of O2 uptake. Submitted on February 15, 1957

Physical Properties of Human Lungs Measured During Spontaneous Respiration

1953-06-01

Jere Mead , James L. Whittenberger

Site and Nature of Airway Obstruction in Chronic Obstructive Lung Disease

1968-06-20

James C. Hogg , Peter T. Macklem , William M. Thurlbeck

We have wedged a small catheter in airways 2 to 3 mm in diameter in excised human lungs to have measure airway resistance central (Rc) and peripheral (Rp) to this … We have wedged a small catheter in airways 2 to 3 mm in diameter in excised human lungs to have measure airway resistance central (Rc) and peripheral (Rp) to this site. In five normal lungs, R accounted for only 25 per cent total airway resistance (RL) and averaged 0.18 cm of water per liter per second. In seven patients with emphysema Rp was increased from four to 40 times. Rp was also increased in one case of bronchiectasis and another of bronchiolitis. In all, Rc scattered around the normal value. Bronchographic and histologic studies showed that Rp was increased because of mucus plugging, narrowing and obliteration of the small airways. Disease of small airways may be common to various chronic obstructive lung diseases. Because Rp is normally so small, there may be considerable obstruction in peripheral airways that would affect ventilation distribution and gas exchange but would have little effect on function tests designed to reveal obstruction. When total airway resistance is elevated to a clinically detectable level by disease in the small airways, obstruction is much more severe than is generally recognized.

Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release

2016-02-08

Nazila Kamaly , Basit Yameen , Jun Wu +1 more

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTDegradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug ReleaseNazila Kamaly§, Basit Yameen§, Jun Wu§, and Omid C. Farokhzad*§‡View Author Information§ Laboratory of Nanomedicine and Biomaterials, … ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTDegradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug ReleaseNazila Kamaly§, Basit Yameen§, Jun Wu§, and Omid C. Farokhzad*§‡View Author Information§ Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States‡ King Abdulaziz University, Jeddah 21589, Saudi Arabia*E-mail: [email protected]Cite this: Chem. Rev. 2016, 116, 4, 2602–2663Publication Date (Web):February 8, 2016Publication History Received8 June 2015Published online8 February 2016Published inissue 24 February 2016https://pubs.acs.org/doi/10.1021/acs.chemrev.5b00346https://doi.org/10.1021/acs.chemrev.5b00346review-articleACS PublicationsCopyright © 2016 American Chemical SocietyRequest reuse permissionsArticle Views40762Altmetric-Citations1996LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Copolymers,Drug delivery,Drug release,Pharmaceuticals,Polymers Get e-Alerts

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Analysis of proteins and respiratory cells obtained from human lungs by bronchial lavage.

1974-10-01

Herbert Y. Reynolds , Harold H. Newball

Deposition and retention models for internal dosimetry of the human respiratory tract. Task group on lung dynamics.

1966-02-01

David V. Bates , B. Fish , Theodore F. Hatch +2 more

Bone Histomorphometry : Standardization of Nomenclature, Symbols, and Units

1987-01-01

A. M. Parfitt , M. K. Drezner , Francis H. Glorieux +5 more

A Randomized, Double-Blind Crossover Study of Change in Post-Dose Lung Function with Hydrofluoroolefin-1234ze, a Next-Generation Propellant for Metered Dose Inhalers, in Participants with Asthma

2025-06-24

Roy A. Pleasants , Alan Bell , Mandeep Jassal +6 more | Journal of Aerosol Medicine and Pulmonary Drug Delivery

Background: Pressurized metered dose inhalers (pMDIs) currently contain propellants with relatively high global warming potential (GWP), such as hydrofluoroalkane-134a (HFA-134a). Hyrofluoroolefin-1234ze (HFO-1234ze) is a near-zero GWP propellant in development for … Background: Pressurized metered dose inhalers (pMDIs) currently contain propellants with relatively high global warming potential (GWP), such as hydrofluoroalkane-134a (HFA-134a). Hyrofluoroolefin-1234ze (HFO-1234ze) is a near-zero GWP propellant in development for use in future pMDIs. Methods: This Phase IIIb, multicenter, randomized, double-blind, single-dose crossover study aimed to assess post-dose lung function and clinical manifestations of bronchospasm following single doses of HFA-134a and HFO-1234ze via pMDI (four inhalations with no active drugs) in participants with well or partially controlled asthma. The primary endpoint was change from baseline in forced expiratory volume in one second area under the curve from 0 to 15 minutes (FEV1 AUC0-15 minutes) post-dose and was assessed using a linear mixed-effect model. Secondary endpoints included cumulative incidence of bronchospasm events (reduction in FEV1 of >15% from baseline at 5 or 15 minutes post-dose with associated wheezing, shortness of breath, or cough). Safety and tolerability were also assessed. Results: Among 52 participants randomized to treatment, noninferiority of HFO-1234ze pMDI versus HFA-134a was established for change from baseline in FEV1 AUC0-15 minutes post-dose between treatments (least squares mean [LSM]; 95% confidence intervals [CI] change: HFO-1234ze pMDI, -0.014 [-0.033, 0.006] L; HFA-134a, -0.004 [-0.024, 0.015] L; LSM [95% CI] difference: -0.009 [-0.037, 0.018; p = 0.492]). No bronchospasm events were reported. Two patients (3.8%) in each group experienced ≥1 adverse event (AE). No serious AEs, AEs of special interest, or AEs leading to discontinuation were reported. Conclusions: HFO-1234ze pMDI was well tolerated in participants with well or partially controlled asthma. As with HFA-134a pMDI, no significant effects on lung function or bronchospasm events were observed. As HFO-1234ze pMDI has a near-zero GWP, it represents a compelling, environmentally conscious alternative propellant for use in pMDI devices for treatment of chronic respiratory disease. Trial Registration: NCT05850494.

Protein based nanoparticles for pulmonary drug delivery: advances, challenges, and future perspectives

2025-06-23

Aniket Bhardwaj , Saurabh Verma , Anukrati Agnihotri +2 more | Journal of Nanoparticle Research

Tolerogenic Dendritic Cell- and M2 Macrophage Polarization-Inducible Hybrid Nanoparticles Alleviate Asthma in Mice

2025-06-23

Eun‐Koung An , Wei Zhang , Hae‐Bin Park +6 more | ACS Nano

Asthma is a chronic allergic inflammatory disease of the airways that can have fatal effects by impairing the oxygen transport function of the lungs. In this study, asthma is treated … Asthma is a chronic allergic inflammatory disease of the airways that can have fatal effects by impairing the oxygen transport function of the lungs. In this study, asthma is treated using a drug delivery system that has recently garnered increased attention. To suppress the activity of immune cells involved in asthma, dexamethasone (Dex) is loaded on a poly lactic-co-glycolic acid polymer and wrapped in lipid-containing monophosphoryl lipid A (MPLA), a toll-like receptor 4 (TLR4) ligand. Our results revealed that the hybrid nanoparticles containing Dex and MPLA (DM-HNPs) effectively target dendritic cells (DCs) and macrophages and inhibit the activation of these cells in mice. Moreover, DM-HNP increases the production of interleukin-10 (IL-10) in the alum-stimulated DCs and macrophages, indicating its promotion of tolerogenic DC and M2 macrophage differentiation, respectively. DM-HNPs further induce the generation of regulatory T cells. Therefore, DM-HNP is effective in suppressing the onset of asthma and treating it through regulatory T cell generation. Overall, DM-HNPs alleviate asthma-induced by immune regulatory cells and can serve as a potential treatment for patients with asthma.

A Companion Robot for Children With Asthma: Descriptive Development and Feasibility Pilot Study

2025-06-23

Jinnaphat Sangngam , Somsiri Rungamornrat , Rungnapa Santipipat +1 more | JMIR Pediatrics and Parenting

Consistent medication use and proper inhaler technique are essential in pediatric asthma, and young children require supportive tools to maintain these practices. This study aimed to investigate the caregivers' ability … Consistent medication use and proper inhaler technique are essential in pediatric asthma, and young children require supportive tools to maintain these practices. This study aimed to investigate the caregivers' ability to use a companion robot-assisted app for children with asthma, their attitudes toward the usage, and the characteristics that hinder or facilitate the implementation. This study employed a descriptive design. The sample group consisted of 30 children with asthma aged 3-6 years who received treatment at an asthma clinic and their caregivers. The companion robot for children with asthma called "Pukkabot," which is an innovation that is developed to teach inhalation techniques and to raise awareness about consistent medication administration through positive reinforcement, was examined. Data collection included personal information questionnaires, the System Usability Scale (SUS) for evaluating usage and overall satisfaction, and interviews to gather attitudes toward apps and characteristics that hinder or facilitate. Data were analyzed with descriptive statistics and content analysis. The study revealed that the scores for usability and overall satisfaction were 80.6, which is above the standard threshold and rated at grade A or an excellent level. Additionally, caregivers stated that the companion robots were easy to use, not complicated, had appropriately sized screens, and demonstrated clear images and sounds. The detailed steps for inhalation were exhibited, and reminders included those of medication times. The children with asthma enjoyed the app and were very interested, making most caregivers want to continue their use. Caregivers were generally satisfied with the usability, finding it easy to use and engaging, which successfully attracted the interest of the children with asthma. Therefore, the companion robot may be used further, with the following recommendations: improving its physical design, adding content, incorporating tracking and symptom assessment systems, and creating a downloadable mobile app for greater accessibility and convenience.

Increasing Nebulizer Spray Efficiency Using a Baffle with a Conical Surface: A Computational Fluid Dynamics Analysis

2025-06-20

Hung‐Chieh Wu , Fu-Lun Chen , Yuan-Ching Chiang +4 more | Bioengineering

Breath-actuated nebulizers used in aerosol therapy are vital to children and patients with disabilities and stand out for their ability to accurat ely deliver medication while minimizing waste. Their performance … Breath-actuated nebulizers used in aerosol therapy are vital to children and patients with disabilities and stand out for their ability to accurat ely deliver medication while minimizing waste. Their performance can be measured according to the mass output and droplet size. This study aimed to analyze how the baffle impact surface geometries affect the pressure and flow streamlines inside the nebulizer using computational fluid dynamics (CFD). Computer-aided design models of conical symmetric, conical asymmetric, and arc-shaped baffle designs were analyzed using CFD simulations, with the optimal spray output validated through the differences in mass. Conical baffles exhibited superior pressure distribution and output streamlines at 0.25 cm protrusion, suggesting that the nebulizer spray performance can be enhanced by using such a conical baffle impact surface. This result serves as a valuable reference for future research.

Hydrogel applications: a promising frontier in pneumonia therapy

2025-06-20

Junming Wang , Pengfei Wang , K K Liao +1 more | Frontiers in Bioengineering and Biotechnology

Pneumonia remains a significant global health challenge due to its high incidence, mortality rates, and the limitations of conventional therapies, such as antibiotic resistance and inefficient drug delivery. In recent … Pneumonia remains a significant global health challenge due to its high incidence, mortality rates, and the limitations of conventional therapies, such as antibiotic resistance and inefficient drug delivery. In recent years, hydrogels have emerged as a promising biomaterial platform for pneumonia treatment, offering exceptional biocompatibility, tunable physicochemical properties, and multifunctionality. This review comprehensively examines the recent advancements in hydrogel applications for pneumonia therapy. It focuses on their roles as drug delivery vehicles, anti-inflammatory agents, and facilitators of tissue repair and regeneration. Hydrogels enable targeted and sustained release of antibiotics, anti-inflammatory drugs, and bioactive molecules, enhancing local drug concentrations while minimizing systemic side effects. Their ability to mimic the extracellular matrix (ECM) supports lung tissue repair and regeneration, addressing the long-term complications of pneumonia, such as fibrosis. Additionally, hydrogels can be engineered to respond to specific physiological conditions, such as pH or enzyme activity, allowing for intelligent drug release profiles tailored to the pulmonary microenvironment. Despite these promising developments, challenges related to material safety, drug loading efficiency, and scalability of manufacturing processes must be addressed to facilitate clinical translation. This review highlights the therapeutic potential of hydrogels in pneumonia treatment and provides insights into future research directions, aiming to bridge the gap between laboratory innovations and clinical applications.

Breathing new life nanomedicines for pulmonary drug delivery: targeting approaches, experimental models, and regulatory aspects

2025-06-20

Amol D. Gholap , Sagar R. Pardeshi , Prabhanjan Giram +7 more | Beni-Suef University Journal of Basic and Applied Sciences

Abstract Background The lungs serve a critical function in air transport and gas exchange, presenting an appealing route for noninvasive drug administration. However, the unique physiology and anatomy of the … Abstract Background The lungs serve a critical function in air transport and gas exchange, presenting an appealing route for noninvasive drug administration. However, the unique physiology and anatomy of the lungs influence the efficacy and safety of pulmonary drug delivery. A comprehensive approach combining both an optimized pharmaceutical formulation and an appropriate delivery device is essential for effective pulmonary therapies. Main body Pulmonary drug delivery can achieve both local and systemic effects. During pulmonary drug delivery, several factors viz . particle size, electrostatic charge, inhalation parameters, airway functionality, disease state, and proper use of delivery device must be considered. Current advancements in nanotechnology have led to the development of innovative nanocarriers tailored for pulmonary administration. These nanocarriers offer benefits such as targeted deposition in specific areas of the tracheobronchial tree, controlled drug release, protection of active pharmaceutical ingredients (APIs) from lung clearance mechanisms, and cell-specific targeting. Research on nanomedicine for pulmonary delivery has progressed significantly, resulting in the development of several (nano)formulations, devices, and products in various stages of clinical development, with some already commercially available. Recent studies have focused on improving inhalation device testing, aerosol formulation development, and the application of in vitro, ex vivo, in vivo, and in silico models to better understand pulmonary drug deposition and disposition. Conclusion This review highlights the anatomical and physiological features of the lungs, recent advances in nanocarrier design and inhalation technologies. In addition, the applications in respiratory and systemic disease management have also been included. While significant progress has been made, challenges remain in optimizing pulmonary drug delivery systems, necessitating further research to address these complexities and enhance the therapeutic outcomes.

Biodegradable polymeric microspheres for systemic peptide delivery through the pulmonary route

2025-06-20

Basam Mahmoud Kasem | Global Journal of Health Sciences and Research

Drug delivery is an integrated process that needs using the appropriate carries with the accurate route of administration, and pulmonary system represents one of the most promising routes for the … Drug delivery is an integrated process that needs using the appropriate carries with the accurate route of administration, and pulmonary system represents one of the most promising routes for the systemic delivery of many drug molecules because of the large surface area, good vascularization, immense capacity for solute exchange, and ultra-thinness of the alveolar epithelium that are considered as unique features of the lung to facilitate systemic delivery; however, the physical and biochemical barriers, lack of optimal dosage forms, and delivery devices have restricted the systemic delivery through this route, and the biodegradable polymeric microspheres might be one of the possible strategies to overcome these limitations. The aim of this review is to highlight the possibilities of using biodegradable-based microspheres for the systemic administration of peptide molecules using the pulmonary route.

Viscoelasticity reduces the droplet size in mucosalivary film fragmentation during intense respiratory events

2025-06-20

NULL AUTHOR_ID | Physical Review Fluids

Unilateral Lung Volume Analysis Using Micro-CT for Enhanced Assessment of Pulmonary Fibrosis in Preclinical Models

2025-06-20

Xihui Huang , Xia Shu , Yiqian Yang +7 more | Journal of Visualized Experiments

Pulmonary fibrosis (PF) is a progressive and irreversible interstitial lung disease characterized by poor prognosis and limited treatment options. The traditional mouse model of pulmonary fibrosis induced by intratracheal instillation … Pulmonary fibrosis (PF) is a progressive and irreversible interstitial lung disease characterized by poor prognosis and limited treatment options. The traditional mouse model of pulmonary fibrosis induced by intratracheal instillation of bleomycin can result in uneven drug distribution and high mortality rates. The refined unilateral intratracheal instillation method for bleomycin administration in mice enables the creation of a more uniform and controlled pulmonary fibrosis model, providing a better simulation of the disease in humans. Here we present a protocol to utilize micro-computed tomography (micro-CT) to quantify ventilated regions in a unilateral bleomycin-induced pulmonary fibrosis model via intratracheal instillation on the lesional side. This approach allows for the quantification of overall lung volume and ventilated lung regions, providing a sensitive and accurate measure of disease progression and treatment response. This study involves anesthesia, precise drug administration, micro-CT scanning, and post-processing using 3D Slicer software for image analysis. The unilateral lung volume analysis following bleomycin treatment demonstrated a significant reduction in lung volume compared to controls. Masson's Trichrome staining confirmed the presence and increased deposition of collagen in the BLM-treated mice. Herein, we evaluated pulmonary fibrosis in preclinical models by performing unilateral lung volumetric analysis using micro-CT, providing researchers with a precise and thorough assessment method for evaluating therapeutic interventions in PF studies.

How systemic antibodies prevent severe respiratory infections in COPD: A Viewpoint

2025-06-19

C. G. A. Persson | European Respiratory Journal

Development of Mannitol-Based Microparticles for Dry Powder Inhalers: Enhancing Pulmonary Delivery of NSAIDs

2025-06-19

Petra Party , Zsófia Ilona Piszman , Rita Ambrus | Pharmaceuticals

Background/Objectives: Chronic lung diseases are among the leading causes of death worldwide. In the treatment of these diseases, non-steroidal anti-inflammatory drugs can be effective. We have previously developed an excipient … Background/Objectives: Chronic lung diseases are among the leading causes of death worldwide. In the treatment of these diseases, non-steroidal anti-inflammatory drugs can be effective. We have previously developed an excipient formulation alongside a modern manufacturing protocol, which we aim to further investigate. We have chosen two new model drugs, meloxicam (MX) and its water-soluble salt, meloxicam-potassium (MXP). The particles in dry powder inhaler (DPI) formulation were expected to have a spherical shape, fast drug release, and good aerodynamic properties. Methods: The excipients were poloxamer-188, mannitol, and leucine. The samples were prepared by spray drying, preceded by solution preparation and wet grinding. Particle size was determined by laser diffraction, shape by scanning electron microscopy (SEM), crystallinity by powder X-ray diffraction (PXRD), interactions by Fourier-transform infrared spectroscopy (FT-IR), in vitro drug dissolution by paddle apparatus, and in vitro aerodynamic properties by Andersen cascade impactor and Spraytec® device. Results: We achieved the proper particle size (<5 μm) and spherical shape according to laser diffraction and SEM. The XRPD showed partial amorphization. FT-IR revealed no interaction between the materials. During the in vitro dissolution tests, more than 90% of MX and MXP were released within the first 5 min. The best products exhibited an aerodynamic diameter of around 4 µm, a fine particle fraction around 50%, and an emitted fraction over 95%. The analysis by Spraytec® supported the suitability for lung targeting. Conclusions: The developed preparation process and excipient system can be applied in the development of different drugs containing DPIs.

Self-assembling TLR2 agonists promote mucosal immune responses without pulmonary immunopathologic injuries in mice

2025-06-18

Zhangping Huang , Caiguanxi Deng , Peng Lin +7 more | npj Vaccines

Abstract Nasal vaccines offer advantages in eliciting mucosal immunity, particularly through the induction of dimeric IgA. However, the complex mucosal environment poses challenges in achieving optimal immunogenicity and safety. This … Abstract Nasal vaccines offer advantages in eliciting mucosal immunity, particularly through the induction of dimeric IgA. However, the complex mucosal environment poses challenges in achieving optimal immunogenicity and safety. This study introduced Diprovocim, a TLR2 agonist, as an effective and safe adjuvant for mucosal vaccines. Our results demonstrated that Diprovocim self-assembled into particles of suitable size for mucosal delivery, enhancing antigen phagocytosis of immune cells in both lymph nodes and lungs. After effectively activating the TLR2 signaling pathway, Diprovocim led to a reduced release of inflammatory cytokines in vivo without any tissue damage or weight loss, highlighting its safety profile. In mice, both intramuscular and intranasal immunization with Diprovocim-adjuvanted vaccines induced high titers of systemic antibodies. Higher IgG and IgA antibodies were detected in bronchoalveolar lavage fluid (BALF). Moreover, Diprovocim enhanced the immunogenicity of ovalbumin (OVA) and recombinant SARS-CoV-2 protein (RFD-Fc) vaccines, achieving higher CD4 + and CD8 + T cell immune responses and cross-protection against SARS-CoV-2 variants. These findings highlight the potential of self-assembled Diprovocim as a safe and effective adjuvant for mucosal vaccines, offering a promising strategy for combating respiratory infections.

In-Depth Study of Captopril Adsorption on a Biosourced Adsorbent: Statistical Physics Approach and Pore Characterization, with Modeling of Adsorption Isotherms, Energetic and Steric Analysis

2025-06-18

A. Naifar , Kods Oueslati , Éder C. Lima +2 more | Langmuir

This current research implements statistical physics principles to microscopically elucidate and interpret the retention mechanism of Captopril onto the activated carbon derived from Butia catarinensis (ABc-600) for water decontamination. The … This current research implements statistical physics principles to microscopically elucidate and interpret the retention mechanism of Captopril onto the activated carbon derived from Butia catarinensis (ABc-600) for water decontamination. The empirical points were modeled exploiting four different statistical isotherm frameworks: the single-energy monolayer, dual-energy monolayer, trienergetic monolayer and dual-energy bilayer. Supported by an error quantification approach (R2, Reduced Chi-Square, RSS and Radj2) the single-energy monolayer was identified as the most rigorous scenario. Stereographic analysis revealed that the adsorption sites consistently capture a fraction of the adsorbed species with n < 1 across all tested temperatures indicating a multianchorage mechanism without aggregation. The decrease in the monolayer adsorbed amount with incrementing temperature highlights the endothermic nature of the Captopril/ABc-600 retention mechanism. Moreover, the energetic assessment corroborates the predominance of physisorption (<40 kJ/mol) indicating that van der Waals forces primarily govern the docking operation. PSD examination revealed a predominantly macroporous structure (0.7 μm) with a discernible shift toward smaller pore radii at elevated temperatures. The AED curves consistently displayed physisorption within the 22-29 kJ/mol energy range across all temperature conditions.

Thiolated Nanovesicles Integrating Mucolytics for Efficient Lung Mucus Penetration and Acute Lung Injury Therapy

2025-06-18

Xu Chen , Liqiang Wang , Yonglan Yang +6 more | ACS Applied Nano Materials

Modeling the Interaction of Aerosol Particles With Lung Epithelial Cells Using the Lung-On-A-Chip Platform

2025-06-18

Igor L. Kanev , Mikhail Viktorovich Verkholashin , Maxim Evgenievich Taylakov +1 more | Genes and Cells

Background. The assessment of inhalation toxicity of natural and artificial aerosols, as well as the effectiveness of aerosol medications, is an important practical task. However, in many current in vitro … Background. The assessment of inhalation toxicity of natural and artificial aerosols, as well as the effectiveness of aerosol medications, is an important practical task. However, in many current in vitro studies, the test substance is dissolved in a liquid that completely covers the lung tissue cells. For inhalation therapy, this method significantly differs from the physiological scenario of aerosol interaction with the pulmonary epithelium. Aim. The aim is to create a platform for studying the interaction of inhaled aerosol particles with the pulmonary epithelium on the inner surface of the lung alveoli at the liquid-air interface, capable of simulating scenarios of periodic changes in liquid levels during breathing. Methods. The A549 human adenocarcinoma cell line was used as a model of pulmonary epithelial cells. Cell viability was analyzed using fluorescent microscopy. Results. A device has been constructed and tested that mimics the inner surface of pulmonary alveoli, which consists of a layer of cells located at the air-liquid interface. The cells are cultured on a porous polymer membrane positioned on the surface of a reservoir containing culture medium. The hydration level of the cells is controlled by altering the liquid pressure beneath the membrane and is recorded using an optical sensor. The membrane with the cell layer is placed in a chamber that allows the creation of a directed electric field perpendicular to the aerosol flow passing over the cell layer, which is connected to one of the electrodes. The presence of the electric field significantly accelerates the delivery of aerosol particles with an electric charge onto the cell surface. The effectiveness of a nanoaerosol form of the anticancer drug doxorubicin has been demonstrated when deposited on the surface of human adenocarcinoma tumor cells located at the liquid-air phase boundary. A model aerosol of a non-toxic substance (glucose) does not exhibit toxic effects under similar conditions. Conclusion. The proposed "lung-on-a-chip" model represents a comprehensive platform for studying the inhalation toxicity of natural and artificial aerosols, as well as for testing the safety and efficacy of aerosolized drug forms in situ.

Exploring the Efficacy of Low-Temperature Plasmas on Oral Biofilms: A Scoping Review

2025-06-18

C Davis , Fabrízio Dias Panariello , Beatriz Helena Dias Panariello | Medical Sciences

The rise of antibiotic resistance and the limitations of conventional therapies for managing biofilm-related oral infections highlight the urgent need for novel solutions, with low-temperature plasma (LTP) emerging as a … The rise of antibiotic resistance and the limitations of conventional therapies for managing biofilm-related oral infections highlight the urgent need for novel solutions, with low-temperature plasma (LTP) emerging as a promising alternative due to its potent antimicrobial effects, tissue-safety, and reduced risk of fostering resistance. This scoping review investigates the efficacy of LTP application for the management of oral biofilms associated with dental caries, peri-implantitis, endodontic infections, and oral candidiasis. This review was conducted in accordance with the PRISMA-ScR guidelines and registered with the Open Science Framework (OSF). Studies were identified through comprehensive searches of PubMed/MEDLINE, EBSCO (Medline Ultimate and e-journals), and Google Scholar, with no publication date restrictions, and were supplemented by manual reference screening. Eligible studies included original research, published in English, examining LTP's effectiveness in oral biofilms. After systematically screening the literature, 51 studies were included in this scoping review, comprising mostly in vitro research, alongside ex vivo, in situ, and clinical studies. Data extraction revealed LTP's broad-spectrum antimicrobial potential and promising clinical implications for dentistry. This review highlights key findings, identifies research gaps, and underscores the therapeutic potential of LTP in managing complex oral biofilm-related infections.

Stock inhalers in action: Results of a pilot study across multiple Illinois counties

2025-06-17

Andrea A. Pappalardo , Paige Hardy , Caroline Youssef +2 more | Journal of Asthma

Pediatric asthma health disparities are common. Schools often lack asthma diagnostic information and infrastructure to handle asthma symptoms. Undesignated or stock rescue inhalers available to anyone in respiratory distress can … Pediatric asthma health disparities are common. Schools often lack asthma diagnostic information and infrastructure to handle asthma symptoms. Undesignated or stock rescue inhalers available to anyone in respiratory distress can help prevent absences. A stock inhaler pilot program was conceptualized and evaluated using implementation science frameworks. Districts from high-asthma-burden counties were engaged and offered guided implementation over the 2022-2023 or 2023-2024 school year. Districts were required to complete training and report stock inhaler incidents. Pre/post implementation interviews and surveys were performed to assess acceptability, feasibility, fidelity to emergency protocols, satisfaction, and utilization. Descriptive statistics were calculated for surveys and utilization data. Thematic data analysis was performed on interview transcripts. Fourteen pilot schools from six districts served 10,265 children. Twenty-eight stock inhaler events were documented. The majority of children (75%) using the stock inhaler had known asthma. Of the 24 events for which disposition was reported, 12 students returned to class (50%), 10 left school with a parent (42%), and only two were transported by emergency services (8%). Pre-implementation interviews revealed that school nurses were concerned about family asthma education (76%) and staff training (29%). One interviewee described the program as "a sturdy safety net… if you can't breathe, nothing else matters". All schools intended to continue stocking inhalers. Stock inhaler programming was well received and improved student outcomes. Resources for Every School Confronting Unexpected Emergencies-Illinois (RESCUE-IL) secured state funding in Illinois to expand stock inhaler programming to over 80% of Illinois public schools. Multi-level, community-focused interventions can maximize the impact of health policies.

Pulmonary delivery of excipient-free tobramycin DPIs for the treatment of Pseudomonas aeruginosa lung infection with CF

2025-06-17

Cheng Song , Haozhou Huang , Zhihao Zhang +7 more | Frontiers in Pharmacology

Pseudomonas aeruginosa infection has become a widespread problem in patients with cystic fibrosis (CF). A safe and effective manufacturing method is required to produce antibiotic dry powder inhalations (DPIs) which … Pseudomonas aeruginosa infection has become a widespread problem in patients with cystic fibrosis (CF). A safe and effective manufacturing method is required to produce antibiotic dry powder inhalations (DPIs) which can be effectively delivered to treat lung infections. In this study, an excipient-free tobramycin inhalable powder was prepared using spray freeze-drying (SFD) method. The mass median aerodynamic diameters (MMAD) of optimized inhalable powder prepared by SFD was 1.30 µm, and the fine particle fractions (FPF) reached 83.31%. In both in vitro and in vivo safety and activity studies, the inhalable powder showed excellent safety performance at both animal and cellular levels, with a minimum inhibitory concentration (MIC) of 0.5 μg/mL. Compared with intravenous injection, inhalation of excipient-free tobramycin inhalable powder had a better effect in the infected mouse model because of its amorphous state. This study demonstrates that excipient-free tobramycin inhalable powder with good delivery and deposition performance can be successfully obtained using the SFD method. Inhalation of excipient-free tobramycin inhalable powder has the potential to be a promising strategy for treating pulmonary infections caused by P. aeruginosa in patients with CF.

Investigation of a digital inhaler monitor and smartphone app providing real-time information on inhaler use

2025-06-16

Lynn Elsey | http://isrctn.com/

Kilogram-Scale Synthesis and Impurity Profiling of a COPD Candidate LY104: Optimization of Salt Forms for Enhanced Purity and Pharmaceutical Potential

2025-06-16

Jilong Zhang , Kaile Li , Xiaokun Liu +6 more | Organic Process Research & Development

Flow behavior in idealized & realistic upper airway geometries

2025-06-15

Brenda Vara Almirall , Hadrien Calmet , H Ang +1 more | Computers in Biology and Medicine

This study investigated the flow characteristics in idealized and realistic upper airway models during oral inhalation, focusing on their ability to replicate airflow dynamics and turbulence that impact pharmaceutical aerosol … This study investigated the flow characteristics in idealized and realistic upper airway models during oral inhalation, focusing on their ability to replicate airflow dynamics and turbulence that impact pharmaceutical aerosol delivery. While idealized airway models, such as the United States Pharmacopeia (USP) model, are widely used in regulatory testing, they lack anatomical fidelity, potentially underestimating critical features, including the laryngeal jet formation, which are essential for accurate particle deposition predictions. Understanding the implications of idealized and realistic models is addressed using Large Eddy Simulations (LES) at inhalation rates of 15 and 30 L/min. Four airway models were analyzed: the USP model, the Virginia Commonwealth University (VCU) model, and two realistic models reconstructed from CT scans of healthy adults. The findings revealed the limitations of the USP model, while the VCU models demonstrated laminar flow behavior with a laryngeal jet with a lower magnitude compared to the realistic models. The realistic models (R01 and R02) exhibited more complex flow features, including an earlier laryngeal jet formation, emphasizing the importance in understanding the limitations of idealized models and the variations between realistic models.

Impact of the COVID-19 Lockdown on Inhaler Adherence in Patients with COPD: A South Korean Nationwide Cohort Study

2025-06-15

Hyungmin Kim , Hong Bin Kim , Young Ji Yoon +1 more | Healthcare

Background/Objectives: The outbreak of coronavirus disease 2019 (COVID-19) has restricted access to healthcare, increasing the risk of poor disease control among patients with COPD (Chronic Obstructive Pulmonary Disease). This study … Background/Objectives: The outbreak of coronavirus disease 2019 (COVID-19) has restricted access to healthcare, increasing the risk of poor disease control among patients with COPD (Chronic Obstructive Pulmonary Disease). This study aimed to compare adherence to inhalers in patients with COPD before and during the COVID-19 lockdown and determine the characteristics of patients who were adherent to inhaler medications. Method: A retrospective analysis was conducted on a cohort of patients with severe COPD aged 40 or older using South Korea's National Health Insurance Service (NHIS) database, which documents all healthcare utilization covered for insured individuals. Medication adherence, measured by the proportion of days covered (PDC), was compared before and during the COVID-19 lockdown using a paired t-test. A multivariable logistic regression model was conducted to identify the characteristics of the adherent patients (socio-demographic, including age, sex, income level, insurance type, and residential area), health-conditions (disease severity, underlying diseases, and disability), and pharmacotherapy characteristics (prescriber practice setting, polypharmacy, medication treatment duration, and inhaler type). Result: A total of 15,971 COPD patients were identified (79.2% men). During the COVID-19 lockdown in 2020, there was a significant decrease in medication adherence to COPD inhalers compared to 2019 (49.8% in 2020 vs. 56.3% in 2019, respectively; p < 0.001). Moreover, the proportion of those adherent (≥80%) during the COVID-19 lockdown decreased (22.0% → 18.0%). Patients who remained adherent to inhaler therapy during the COVID-19 lockdown were typically aged in their 60s, beneficiaries of Medical Aid, residents of rural areas, clinic users, and patients without cardiovascular disease. Conclusions: Patients with COPD encountered significant challenges in accessing inhalers during the COVID-19 lockdown. Healthcare authorities should develop targeted strategies to ensure continued medication access for patients at increased risk of poor medication adherence, particularly during periods of restricted healthcare access, such as public health emergencies or pandemic lockdowns.

Development of a novel semaglutide-loaded dry powder inhaler: application of freeze-drying and Pharmacokinetic evaluation in rats

2025-06-13

Ji Yun Beak , Kangseok Lee , Byeong Nam Im +4 more | Journal of Pharmaceutical Investigation

Selecting the Inhalation Device Most Likely to Benefit Your Patients with COPD: Support Your Choice with the Interactive Device Selection Tool

2025-06-12

Nicola Humphrey | European Medical Journal

COPD is a leading cause of morbidity and mortality worldwide. Inhaled therapies are the mainstay of COPD treatment, including pressurised metered dose inhalers (pMDI), pMDIs with a spacer, soft mist … COPD is a leading cause of morbidity and mortality worldwide. Inhaled therapies are the mainstay of COPD treatment, including pressurised metered dose inhalers (pMDI), pMDIs with a spacer, soft mist inhalers (SMI), dry powder inhalers (DPI), and nebulisers. Inhalation devices each have distinct advantages and challenges, and selecting the most appropriate device for a patient with COPD is crucial to maximising the benefit of inhaled therapy. In this expert interview, pulmonologist Donald Mahler, Geisel School of Medicine at Dartmouth, Hanover; and Valley Regional Hospital, Claremont, New Hampshire, USA, offers insights into the nuances of inhaler selection, emphasising how clinical- and patient-specific factors should guide decision-making. He clarifies the roles of different delivery systems, including the role of nebulisers in certain clinical scenarios, and describes how nebuliser efficiency can be objectively measured in terms of the ability to deliver therapeutic doses of medication into the lungs. A case study illustrates the benefits of switching to nebuliser therapy when a patient’s symptoms do not improve with an appropriately used handheld device. Mahler also addresses the impact of mucus overproduction in patients with COPD, highlights therapeutic strategies including nebulised agents and positive expiratory pressure (PEP) therapy, and introduces a new interactive COPD Inhalation Device Selection Tool (PARI GmbH, Starnberg, Germany) designed to help healthcare providers (HCP) to make tailored, evidence-informed choices for their patients.

Mechanistic Analysis of Fluid Dynamics and Multifactorial Impact Mechanisms in Inhaled Pharmaceutical Deposition for Chronic Respiratory Diseases

2025-06-12

Feng-Ying Hu , Songhua Ma , Tianliang Hu | Bioengineering

The clinical efficacy of inhalation therapy in chronic respiratory diseases is fundamentally constrained by particle deposition patterns. This study employs computational fluid dynamics (CFD) and response surface methodology (RSM) to … The clinical efficacy of inhalation therapy in chronic respiratory diseases is fundamentally constrained by particle deposition patterns. This study employs computational fluid dynamics (CFD) and response surface methodology (RSM) to elucidate the mechanistic interplay of deposition determinants through multifactorial sensitivity mapping. The study comprises two key components: (i) the development of an accurate three-dimensional respiratory airway model spanning from the oral cavity to the fifth-generation bronchi and (ii) the integration of a Box–Behnken Design (BBD) experimental framework with computational fluid dynamics simulations. Furthermore, we developed a multifactorial regression model to analyze the synergistic interactions among deposition determinants. The study demonstrated a positive correlation between breath-holding time and drug deposition efficiency, revealing a hierarchical order of critical parameters: peak flow rate > breath-holding time > particle diameter. These findings have important implications for optimizing respiratory drug delivery strategies in clinical settings.

TFF-3 Modulates Responsiveness to Bronchodilators in Airways

2025-06-10

Ma Ka Yin | Aresty Rutgers Undergraduate Research Journal

Rhinovirus (RV) is the major cause of exacerbations, or worsening of symptoms, in asthmatic children and adults. This often reduces the efficacy of therapeutic interventions such as bronchodilators — a … Rhinovirus (RV) is the major cause of exacerbations, or worsening of symptoms, in asthmatic children and adults. This often reduces the efficacy of therapeutic interventions such as bronchodilators — a type of medication used to promote airflow and alleviate asthma symptoms. The exact mechanisms through which RV exposure decreases responsiveness to bronchodilators remain unclear. Previous data demonstrates that airway cells release a specific signature of inflammatory mediators following RV exposure. Other research has shown that Trefoil Factor 3 (TFF-3), one of the mediators identified by our screen, regulates cell motility in other cell types. We show that RV exposure attenuates relaxation in both the airway and human airway smooth muscle (HASM). Given our data, we aim to examine whether or not TFF-3 attenuates the relaxation of HASM and airways. Primary non-diseased human airway smooth muscle (HASM) was used to examine the consequences of TFF-3 in modulating HASM and airway relaxation. Following RV-C15 exposure, it was found that the airway and HASM relaxation was attenuated. TFF-3 exposure also attenuated both airway and HASM relaxation. Additionally, TFF-3 exposure partially weakened iso-induced reversal of carbachol-induced phosphorylation of the myosin light chain. Within the cADDis Live Cell Assays, which provide real-time kinetic measurements of cyclic Adenosine Monophosphate (cAMP) production, TFF-3 attenuated formoterol-induced cAMP production. Researching how bronchodilation pathways change following RV infection can lead to the development of effective treatments and pharmaceutical solutions to alleviate worsening asthma symptoms during a viral exacerbation of the disease.

Inhaler Technique Comparison Between Dry Powder Inhaler and Metered Dose Inhaler Among Adults with Obstructive Airway Disease in a Tertiary Government Hospital Outpatient Setting

2025-06-06

Henry Medina , Ma. Cecilia Lozada , Cary Amiel G. Villanueva +1 more | Philippine journal of chest diseases

Background: In the management of obstructive airway diseases, inhaled medication remains a cornerstone of therapy. Aside from medication type, the manner of delivery through various devices is important. Evaluating current … Background: In the management of obstructive airway diseases, inhaled medication remains a cornerstone of therapy. Aside from medication type, the manner of delivery through various devices is important. Evaluating current practice provides a measure of performance and allows identification of areas for improvement. The study evaluated inhaler techniques of patients on dry powder inhalers (DPI) versus metered dose inhalers (MDI) at the outpatient setting. The prevalence of specific inhaler technique errors was assessed along with associated factors. Methodology: This study was conducted with a cross-sectional design, involving patients with use of DPI and/or MDI for the past six months. Inhaler technique was evaluated and a short instruction on proper technique was provided with repeat evaluation immediately after. Results: A total of 124 participants were assessed, resulting in 76 DPI and 52 MDI technique observations. Overall, a higher prevalence of any error was observed for DPI at 88.2% versus MDI at 86.5%. Immediately post-instruction, repeat assessment showed significant improvement, with reduction of any error to 57.9% (DPI) and 50% (MDI) (p <0.001 for both). The most common DPI errors were failure to perform full exhalation prior (77.6%) and lack of sufficient breath holding after (44.7%). The most common MDI errors were failure to perform full exhalation prior (71.2%) and improper inhalation (53.8%). For MDI users, only advanced age had an association with having any error (OR 1.10, CI 1.03-1.17). Conclusion: Inhaler technique errors remain high in the outpatient setting regardless of device, with older participants at risk of having errors with MDI, but not with DPI. Although technique review and instruction show promise in reducing errors, the durability of these skills is known to decay. Appropriate patient and device selection, along with regular technique assessment and reinforcement by healthcare professionals, remains the recommended practice to maximize the benefit of inhalers.

Utilization and access to metered-dose inhalers and sustainable alternatives among older adults in the United States: a population-based study

2025-06-05

Ashwaghosha Parthasarathi , Isao Iwata , Catherine Chen +7 more | The Lancet Regional Health - Americas