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Restricted accessAnnouncementFirst published October, 2024pp. 219-219
Restricted accessResearch articleFirst published October, 2024pp. 220-224
, Myrtha E. Reyna, Cathy C. Doyle , [...]Preliminary data in a randomly selected pediatric cohort study in 8-year-olds suggested a rate of positivity to a methacholine challenge test that was unexpectedly high, roughly 30%. The current recommendation for a negative methacholine test is a 20% decrease in the forced expiratory volume in one second at a dose greater than 400 μg. This was derived from studies in adults using the obsolete English Wright nebulizer. One explanation for the high incidence of positivity in the study in 8-year-olds could be that children deposit more methacholine on a μg/kg basis than adults, due to differences in their breathing patterns. The purpose of this study was to determine if pediatric breathing patterns could result in a higher dose of methacholine depositing in the lungs of children based on μg/kg body weight compared with adults.
An AeroEclipse Breath Actuated nebulizer delivered methacholine aerosol, generated from a 16 mg/mL solution, for one minute, using age-appropriate breathing patterns for a 70 kg adult and a 30 and 50 kg child produced by a breathing simulator. Predicted lung deposition was calculated from the collected dose of methacholine on a filter placed at the nebulizer outport, multiplied by the fraction of the aerosol mass contained in particles ≤5 μm. The dose of methacholine on the inspiratory filter was assayed by high performance liquid chromatography (HPLC). Particle size was measured using laser diffraction technology.
The mean (95% confidence intervals) predicted pulmonary dose of methacholine was 46.1 (45.4, 46.8), 48.6 (45.3, 51.9), and 36.1 (34.2, 37.9) μg/kg body weight for the 30 kg child, 50 kg child, and 70 kg adult, respectively.
On a μg/kg body weight, the predicted pulmonary dose of methacholine was greater with the pediatric breathing patterns than with the adult pattern.
Restricted accessResearch articleFirst published October, 2024pp. 225-231, Luis Pazos-Area, Cristina Represas-Represas , [...]Despite the importance of an adequate peak inspiratory flow (PIF) during inhaled therapy in patients with COPD, the available evidence in patients with severe exacerbations and their evolution after admission is limited. We conducted this study to evaluate the PIF during an exacerbation, its variability, and predictors of suboptimal PIF.
A prospective study that included patients admitted for COPD exacerbation. Clinical, demographic, and functional variables were recorded. Using the In-Check DIAL G16®, PIF without resistance (PIF-nr) and that obtained by simulating the resistance of the patients’ usual inhalers (PIF) were determined within the first 48 hours of admission and prior to discharge; also assessed during a stable phase in a subgroup of patients. The results were compared and, through a multivariate study, the factors related to a suboptimal PIF were analyzed.
A total of 137 patients were included; 27% were women and the mean age was 69.4 ± 9.8 years. Moreover, 30.8% of the participants with dry powder inhalers had a suboptimal PIF at admission and it was independently associated with female sex (odds ratio [OR] = 8.635; 95% confidence interval [CI] [2.007, 37.152];
One third of COPD patients admitted with a severe exacerbation had a suboptimal PIF, being female sex and lower FEV1 independent predictors. PIF-nr improved progressively after the exacerbation.
Restricted accessResearch articleFirst published October, 2024pp. 232-240, Bo Yang, Chen Hong , [...]The lack of visual dynamic spray characterization has made the understanding of the physical processes governing atomization and drug particle formation difficult. This study aimed to investigate the changes in the spray plume morphology and aerodynamic particle size of solution-based pressurized metered-dose inhalers (pMDIs) under different conditions to achieve better drug deposition.
Solution-based pMDIs were studied, and the effects of various factors, such as propellant concentration, orifice diameters, and atomization chamber volume, on drug deposition were examined by analyzing the characteristics of spray plume and aerodynamic particle size.
Reducing the actuator orifice and spray area led to a concentrated spray plume and increased duration and speed. Moreover, the aerodynamic particle sizes D50 and D90 decreased, whereas D10 remained relatively unchanged. Decreasing the atomization chamber volume of the actuator led to reduced spray area and an increased duration but a decreased plume velocity. D90 exhibited a decreasing trend, whereas D10 and D50 remained relatively unchanged. Reducing the propellant concentration in the prescription, the spray area and the plume velocity first decreased and then increased. The duration initially increased and then decreased. The values of D50 and D90 showed an initial decreasing followed by an increasing trend, whereas D10 remained relatively unchanged.
During the development process, attention should be paid to the changes in the spray area, spray angle, duration, and speed of the spray plume. This study recommended analyzing the characteristics of the spray plume and combining the data of two or more aerodynamic particle size detection methods to verify the deposition
Open accessReview articleFirst published October, 2024pp. 241-283, Tam L. Nguyen, Andy Stautberg , [...]The Sugen 5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension (PAH) demonstrates most of the distinguishing features of PAH in humans, including increased wall thickness and obstruction of the small pulmonary arteries along with plexiform lesion formation. Recently, significant advancement has been made describing the epidemiology, genomics, biochemistry, physiology, and pharmacology in Su/Hx challenge in rats. For example, there are differences in the overall reactivity to Su/Hx challenge in different rat strains and only female rats respond to estrogen treatments. These conditions are also encountered in human subjects with PAH. Also, there is a good translation in both the biochemical and metabolic pathways in the pulmonary vasculature and right heart between Su/Hx rats and humans, particularly during the transition from the adaptive to the nonadaptive phase of right heart failure. Noninvasive techniques such as echocardiography and magnetic resonance imaging have recently been used to evaluate the progression of the pulmonary vascular and cardiac hemodynamics, which are important parameters to monitor the efficacy of drug treatment over time. From a pharmacological perspective, most of the compounds approved clinically for the treatment of PAH are efficacious in Su/Hx rats. Several compounds that show efficacy in Su/Hx rats have advanced into phase II/phase III studies in humans with positive results. Results from these drug trials, if successful, will provide additional treatment options for patients with PAH and will also further validate the excellent translation that currently exists between Su/Hx rats and the human PAH condition.
Restricted accessReview articleFirst published October, 2024pp. 284-298, Haimei Zhao, Ping Li , [...]Traditional vaccines have played an important role in the prevention and treatment of infectious diseases, but they still have problems such as low immunogenicity, poor stability, and difficulty in inducing lasting immune responses. In recent years, the nucleic acid vaccine has emerged as a relatively cheap and safe new vaccine. Compared with traditional vaccines, nucleic acid vaccine has some unique advantages, such as easy production and storage, scalability, and consistency between batches. However, the direct administration of naked nucleic acid vaccine is not ideal, and safer and more effective vaccine delivery systems are needed. With the rapid development of nanocarrier technology, the combination of gene therapy and nanodelivery systems has broadened the therapeutic application of molecular biology and the medical application of biological nanomaterials. Nanoparticles can be used as potential drug-delivery vehicles for the treatment of hereditary and infectious diseases. In addition, due to the advantages of lung immunity, such as rapid onset of action, good efficacy, and reduced adverse reactions, pulmonary delivery of nucleic acid vaccine has become a hot spot in the field of research. In recent years, lipid nanocarriers have become safe, efficient, and ideal materials for vaccine delivery due to their unique physical and chemical properties, which can effectively reduce the toxic side effects of drugs and achieve the effect of slow release and controlled release, and there have been a large number of studies using lipid nanocarriers to efficiently deliver target components into the body. Based on the delivery of tuberculosis (TB) nucleic acid vaccine by lipid carrier, this article systematically reviews the advantages and mechanism of liposomes as a nucleic acid vaccine delivery carrier, so as to lay a solid foundation for the faster and more effective development of new anti-TB vaccine delivery systems in the future.
Restricted accessReview articleFirst published October, 2024pp. 299-306Inhalable particulate drug carriers—nano- and micro-particles, liposomes, and micelles—should be designed to promote drug deposition in the lung and engineered to exhibit the desired drug release property. To deposit at the desired site of action, inhaled particles must evade various lines of lung defense, including mucociliary clearance, entrapment by mucus layer, and phagocytosis by alveolar macrophages. Various physiological, mechanical, and chemical barriers of the respiratory system reduce particle residence time in the lungs, prevent particle deposition in the deep lung, remove drug-filled particles from the lung, and thus diminish the therapeutic efficacy of inhaled drugs. To develop inhalable drug carriers with efficient deposition properties and optimal retention in the lungs, particle engineers should have a thorough understanding of the barriers that particles confront and appreciate the lung defenses that remove the particles from the respiratory system. Thus, this section summarizes the mechanical, chemical, and immunological barriers of the lungs that inhaled particles must overcome and discusses the influence of these barriers on the fate of inhaled particles.