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Respiratory Care Jun 2018Drug delivery by inhalation is the principal strategy to treat obstructive lung diseases, which affect about 15% of the population in the United States. Aerosol delivery... (Review)
Review
Drug delivery by inhalation is the principal strategy to treat obstructive lung diseases, which affect about 15% of the population in the United States. Aerosol delivery devices have evolved over more than 60 years from the basic pressurized metered-dose inhaler and nebulizer to numerous types of inhalers and devices, including valved holder chambers, dry powder inhalers, soft mist inhalers, as well as smart inhalers and nebulizers. Although these devices improve a patient's ability to self-administer medication, many problems with optimal delivery still exist. Appropriate selection and repeated patient education can help lessen the problems with these devices. Aerosol science is evolving, with methods of measurement that include radio-scintigraphy and magnetic resonance imaging, to provide a better understanding of aerosol delivery and effects. Understanding the science and clinical application of aerosol drug delivery can substantially aid clinicians in optimizing these therapies for their patients.
Topics: Administration, Inhalation; Aerosols; Asthma; Bronchodilator Agents; Equipment Design; Humans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive
PubMed: 29794206
DOI: 10.4187/respcare.06290 -
Advanced Drug Delivery Reviews Aug 2023Aerosolization of immunotherapies poses incredible potential for manipulating the local mucosal-specific microenvironment, engaging specialized pulmonary cellular... (Review)
Review
Aerosolization of immunotherapies poses incredible potential for manipulating the local mucosal-specific microenvironment, engaging specialized pulmonary cellular defenders, and accessing mucosal associated lymphoid tissue to redirect systemic adaptive and memory responses. In this review, we breakdown key inhalable immunoengineering strategies for chronic, genetic, and infection-based inflammatory pulmonary disorders, encompassing the historic use of immunomodulatory agents, the transition to biological inspired or derived treatments, and novel approaches of complexing these materials into drug delivery vehicles for enhanced release outcomes. Alongside a brief description of key immune targets, fundamentals of aerosol drug delivery, and preclinical pulmonary models for immune response, we survey recent advances of inhaled immunotherapy platforms, ranging from small molecules and biologics to particulates and cell therapies, as well as prophylactic vaccines. In each section, we address the formulation design constraints for aerosol delivery as well as advantages for each platform in driving desirable immune modifications. Finally, prospects of clinical translation and outlook for inhaled immune engineering are discussed.
Topics: Humans; Lung; Aerosols; Immunotherapy; Drug Delivery Systems; Vaccines
PubMed: 37100206
DOI: 10.1016/j.addr.2023.114831 -
Environmental Science & Technology Sep 2022Accurate determination of acidity (pH) and ion activities in aqueous droplets is a major experimental and theoretical challenge for understanding and simulating...
Accurate determination of acidity (pH) and ion activities in aqueous droplets is a major experimental and theoretical challenge for understanding and simulating atmospheric multiphase chemistry. Here, we develop a ratiometric Raman spectroscopy method to measure the equilibrium concentration of sulfate (SO) and bisulfate (HSO) in single microdroplets levitated by aerosol optical tweezers. This approach enables determination of ion activities and pH in aqueous sodium bisulfate droplets under highly supersaturated conditions. The experimental results were compared against aerosol thermodynamic model calculations in terms of simulating aerosol ion concentrations, ion activity coefficients, and pH. We found that the Extended Aerosol Inorganics Model (E-AIM) can well reproduce the experimental results. The alternative model ISORROPIA, however, exhibits substantial deviations in SO and HSO concentrations and up to a full unit of aerosol pH under acidic conditions, mainly due to discrepancies in simulating ion activity coefficients of SO-HSO equilibrium. Globally, this may cause an average deviation of ISORROPIA from E-AIM by 25 and 65% in predicting SO and HSO concentrations, respectively. Our results show that it is important to determine aerosol pH and ion activities in the investigation of sulfate formation and related aqueous phase chemistry.
Topics: Aerosols; Hydrogen-Ion Concentration; Spectrum Analysis, Raman; Sulfates; Sulfur Oxides; Water
PubMed: 36047919
DOI: 10.1021/acs.est.2c01378 -
Scientific Reports Jul 2021Air quality in urban areas and megacities is dependent on emissions, physicochemical process and atmospheric conditions in a complex manner. The impact on air quality... (Review)
Review
Air quality in urban areas and megacities is dependent on emissions, physicochemical process and atmospheric conditions in a complex manner. The impact on air quality metrics of the COVID-19 lockdown measures was evaluated during two periods in Athens, Greece. The first period involved stoppage of educational and recreational activities and the second severe restrictions to all but necessary transport and workplace activities. Fresh traffic emissions and their aerosol products in terms of ultrafine nuclei particles and nitrates showed the most significant reduction especially during the 2nd period (40-50%). Carbonaceous aerosol both from fossil fuel emissions and biomass burning, as well as aging ultrafine and accumulation mode particles showed an increase of 10-20% of average before showing a decline (5 to 30%). It is found that removal of small nuclei and Aitken modes increased growth rates and migration of condensable species to larger particles maintaining aerosol volume.
Topics: Aerosols; Air Pollutants; Air Pollution; COVID-19; Environment; Environmental Monitoring; Greece; Humans; Nitrates; Particulate Matter; SARS-CoV-2; Time Factors; Vehicle Emissions
PubMed: 34262082
DOI: 10.1038/s41598-021-93650-6 -
Respiratory Care Jun 2015Nonadherence to prescribed medications results in disease instability and poor clinical control, with increases in hospital admissions, emergency room visits,... (Review)
Review
Nonadherence to prescribed medications results in disease instability and poor clinical control, with increases in hospital admissions, emergency room visits, school/work absenteeism, morbidity, and mortality. Poor patient adherence to therapy can be due to lack of cognition, competence, or contrivance. Patients who have not been trained or fail to understand use of drug and device combinations (cognition) often do not have the ability to use an aerosol device correctly (competence). Many patients have the competence to use the device correctly and know why they should use the device in the way they were taught; however, they still contrive to use it in an ineffective and suboptimal manner that reduces its efficiency and effectiveness. Ensuring effective aerosol therapy and optimizing its role in disease management involve not only delivery of aerosolized medications to the lungs, but also understanding why, when, and how to use the medications, competence to use the device, motivation to adhere to therapy, and not contriving to use the device in a way that will prevent effective drug delivery. This paper explains some of the problems with patient education and adherence to aerosol therapy and suggests strategies to evaluate, monitor, and improve patient adherence effectively in primary care. Factors affecting patient adherence to prescribed medications, effective educational interventions, and strategies to promote patient adherence to aerosol therapy are also discussed.
Topics: Administration, Inhalation; Aerosols; Cognition; Health Knowledge, Attitudes, Practice; Humans; Mental Competency; Nebulizers and Vaporizers; Patient Compliance; Patient Education as Topic
PubMed: 26070585
DOI: 10.4187/respcare.03854 -
Respiratory Care Jul 2010This paper reviews the history of aerosol therapy; discusses patient, drug, and device factors that can influence the success of aerosol therapy; and identifies trends... (Review)
Review
This paper reviews the history of aerosol therapy; discusses patient, drug, and device factors that can influence the success of aerosol therapy; and identifies trends that will drive the science of aerosol therapy in the future. Aerosol medication is generally less expensive, works more rapidly, and produces fewer side effects than the same drug given systemically. Aerosol therapy has been used for thousands of years by steaming and burning plant material. In the 50 years since the invention of the pressurized metered-dose inhaler, advances in drugs and devices have made aerosols the most commonly used way to deliver therapy for asthma and COPD. The requirements for aerosol therapy depend on the target site of action and the underlying disease. Medication to treat airways disease should deposit on the conducting airways. Effective deposition of airway particles generally requires particle size between 0.5 and 5 microm mass median aerodynamic diameter; however, a smaller particle size neither equates to greater side effects nor greater effectiveness. However, medications like peptides intended for systemic absorption, need to deposit on the alveolar capillary bed. Thus ultrafine particles, a slow inhalation, and relatively normal airways that do not hinder aerosol penetration will optimize systemic delivery. Aerosolized antimicrobials are often used for the treatment of cystic fibrosis or bronchiectasis, and mucoactive agents to promote mucus clearance have been delivered by aerosol. As technology improves, a greater variety of novel medications are being developed for aerosol delivery, including for therapy of pulmonary hypertension, as vaccines, for decreasing dyspnea, to treat airway inflammation, for migraine headache, for nicotine and drug addiction, and ultimately for gene therapy. Common reasons for therapeutic failure of aerosol medications include the use of inactive or depleted medications, inappropriate use of the aerosol device, and, most importantly, poor adherence to prescribed therapy. The respiratory therapist plays a key role in patient education, device selection, and outcomes assessment.
Topics: Administration, Inhalation; Aerosols; Humans; Lung Diseases; Nebulizers and Vaporizers; Particle Size; Patient Compliance
PubMed: 20587104
DOI: No ID Found -
Chemical Research in Toxicology Jun 2019Aerosols from electronic cigarettes and heat-not-burn tobacco products have been found to contain lower levels of almost all compounds from the list of Harmful and... (Comparative Study)
Comparative Study
Aerosols from electronic cigarettes and heat-not-burn tobacco products have been found to contain lower levels of almost all compounds from the list of Harmful and Potentially Harmful Constituents known to be present in tobacco products and tobacco smoke than smoke from conventional cigarettes. Free radicals, which also pose potential health risks, are not considered in this list, and their levels in the different product types have not yet been compared under standardized conditions. We compared the type and quantity of free radicals in mainstream aerosol of 3R4F research cigarettes, two types of electronic cigarettes, and a heat-not-burn tobacco product. Free radicals and NO in the gas phases were separately spin trapped and quantified by electron paramagnetic resonance (EPR) spectroscopy by using a smoking machine for aerosol generation and a flow-through cell to enhance reproducibility of the quantification. Particulate matter was separated by a Cambridge filter and extracted, and persistent radicals were quantified by EPR spectroscopy. Levels of organic radicals for electronic cigarettes and the heat-not-burn product, as measured with the PBN spin trap, did not exceed 1% of the level observed for conventional cigarettes and were close to the radical level observed in air blanks. The radicals found in the smoke of conventional cigarettes were oxygen centered, most probably alkoxy radicals, whereas a signal for carbon-centered radicals near the detection limit was observed in aerosol from the heat-not-burn product and electronic cigarettes. The NO level in aerosol produced by electronic cigarettes was below our detection limit, whereas for the heat-not-burn product, it reached about 7% of the level observed for whole smoke from 3R4F cigarettes. Persistent radicals in particulate matter could be quantified only for 3R4F cigarettes. Aerosols from vaping and heat-not-burn tobacco products have much lower free radical levels than cigarette smoke, however, the toxicological implications of this finding are as yet unknown.
Topics: Aerosols; Electronic Nicotine Delivery Systems; Free Radicals; Smoking; Nicotiana; Tobacco Products; Vaping
PubMed: 30932480
DOI: 10.1021/acs.chemrestox.9b00085 -
Environmental Science & Technology Feb 2021Severe haze events with exceedingly high-levels of fine aerosols occur frequently over the past decades in the North China Plain (NCP), exerting profound impacts on... (Review)
Review
Severe haze events with exceedingly high-levels of fine aerosols occur frequently over the past decades in the North China Plain (NCP), exerting profound impacts on human health, weather, and climate. The development of effective mitigation policies requires a comprehensive understanding of the haze formation mechanisms, including identification and quantification of the sources, formation, and transformation of the aerosol species. Haze evolution in this region exhibits distinct physical and chemical characteristics from clean to polluted periods, as evident from increasing stagnation and relative humidity, but decreasing solar radiation as well as explosive secondary aerosol formation. The latter is attributed to highly elevated concentrations of aerosol precursor gases and is reflected by rapid increases in the particle number and mass concentrations, both corresponding to nonequilibrium chemical processes. Considerable new knowledge has been acquired to understand the processes regulating haze formation, particularly in light of the progress in elucidating the aerosol formation mechanisms. This review synthesizes recent advances in understanding secondary aerosol formation, by highlighting several critical chemical/physical processes, that is, new particle formation and aerosol growth driven by photochemistry and aqueous chemistry as well as the interaction between aerosols and atmospheric stability. Current challenges and future research priorities are also discussed.
Topics: Aerosols; Air Pollutants; China; Environmental Monitoring; Explosive Agents; Humans; Particulate Matter
PubMed: 33539077
DOI: 10.1021/acs.est.0c07204 -
Anesthesiology Jan 2021Disease severity in coronavirus disease 2019 (COVID-19) may be associated with inoculation dose. This has triggered interest in intubation barrier devices to block...
BACKGROUND
Disease severity in coronavirus disease 2019 (COVID-19) may be associated with inoculation dose. This has triggered interest in intubation barrier devices to block droplet exposure; however, aerosol protection with these devices is not known. This study hypothesized that barrier devices reduce aerosol outside of the barrier.
METHODS
Aerosol containment in closed, semiclosed, semiopen, and open barrier devices was investigated: (1) "glove box" sealed with gloves and caudal drape, (2) "drape tent" with a drape placed over a frame, (3) "slit box" with armholes and caudal end covered by vinyl slit diaphragms, (4) original "aerosol box," (5) collapsible "interlocking box," (6) "simple drape" over the patient, and (7) "no barrier." Containment was investigated by (1) vapor instillation at manikin's right arm with video-assisted visual evaluation and (2) submicrometer ammonium sulfate aerosol particles ejected through the manikin's mouth with ventilation and coughs. Samples were taken from standardized locations inside and around the barriers using a particle counter and a mass spectrometer. Aerosol evacuation from the devices was measured using standard hospital suction, a surgical smoke evacuator, and a Shop-Vac.
RESULTS
Vapor experiments demonstrated leakage via arm holes and edges. Only closed and semiclosed devices and the aerosol box reduced aerosol particle counts (median [25th, 75th percentile]) at the operator's mouth compared to no barrier (combined median 29 [-11, 56], n = 5 vs. 157 [151, 166], n = 5). The other barrier devices provided less reduction in particle counts (133 [128, 137], n = 5). Aerosol evacuation to baseline required 15 min with standard suction and the Shop-Vac and 5 min with a smoke evacuator.
CONCLUSIONS
Barrier devices may reduce exposure to droplets and aerosol. With meticulous tucking, the glove box and drape tent can retain aerosol during airway management. Devices that are not fully enclosed may direct aerosol toward the laryngoscopist. Aerosol evacuation reduces aerosol content inside fully enclosed devices. Barrier devices must be used in conjunction with body-worn personal protective equipment.
Topics: Aerosols; COVID-19; Cough; Health Personnel; Humans; Intubation, Intratracheal; Occupational Exposure; Personal Protective Equipment
PubMed: 33125457
DOI: 10.1097/ALN.0000000000003597 -
Advanced Drug Delivery Reviews 2020Ideally, inhaled therapy is driven by the needs of specific disease management. Lung biology interfaces with inhaler performance to allow optimal delivery of therapeutic... (Review)
Review
Ideally, inhaled therapy is driven by the needs of specific disease management. Lung biology interfaces with inhaler performance to allow optimal delivery of therapeutic agent for disease treatment. Inhalation aerosol products consist of the therapeutic agent, formulation, and device. The manufacturing specifications on each of the components, and their combination, allow accurate and reproducible control of measures of quality and in-vitro performance. These product variables in combination with patient variables, including co-ordination skill during inhaler use, intrinsic lung biology, disease and consequent pulmonary function, contribute to drug safety and efficacy outcomes. Due to the complexity of pulmonary drug delivery, predicting biological outcomes from first principles has been challenging. Ongoing research appears to offer new insights that may allow accurate prediction of drug behavior in the lungs. Disruptive innovations were characteristic of research and development in inhaled drug delivery at the end of the last century. Although there were relatively few new inhaled products launched in the first decade of the new millennium it was evident that the earlier years of exploration resulted in maturation of commercially successful technologies. A significant increase in new and generic products has occurred in the last decade and technical, regulatory and disease management trends are emerging. Some of these developments can trace their origins to earlier periods of creativity in the field while others are a reflection of advances in other areas of basic and computer, sciences and engineering. Select biological and technical advances are highlighted with reflections on the potential to impact future clinical and regulatory considerations.
Topics: Administration, Inhalation; Aerosols; Drug Delivery Systems; Drugs, Generic; Humans; Lung; Nebulizers and Vaporizers
PubMed: 32663488
DOI: 10.1016/j.addr.2020.07.006