Purpose:The aim was to synthesize quantitative and qualitative research that identified the most effective educational strategies for nurse-led inhaler technique(IT)education in Chronic Obstructive Pulmonary Disease(C...Purpose:The aim was to synthesize quantitative and qualitative research that identified the most effective educational strategies for nurse-led inhaler technique(IT)education in Chronic Obstructive Pulmonary Disease(COPD)patients,as perceived by patients,healthcare providers,and nurses.Methods:A systematic literature search in Embase,PubMed,Cochrane Library,Web of Science,and CINAHL from 2018 to 30 June 2024 was conducted.In total,327 articles were identified.The results of 14 studies that met the inclusion criteria were synthesized.Data were analyzed with des-criptive and semi-quantitative methods to yield summarizing findings on the effectiveness of different educational strate-gies.All investigations had assessed patient adherence to IT.Results:Data indicated that nurse-led IT teaching strategies are effective in promoting IT adherence and correctness in COPD patients utilizing the personalized Teach-Back method.However,studies in disease control and comparison of patient IT satisfaction and self-efficacy need further investigation.Conclusion:The results of this study may contribute to the understanding of the most effective educational strategies in nurse-led IT education for COPD patients.The synthesized findings can be used for the development of new educational interventions and assessment instruments for IT adherence.展开更多
Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized ...Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized inhalation,exploring its underlying mechanisms.Methods:The anti-fibrotic properties of nebulized YQHTSJ were assessed using a bleomycin(BLM)-induced PF mouse model.RNA sequencing identified differentially expressed genes(DEGs),and subsequent gene enrichment analysis,along with transcription factor(TF)prediction,revealed YQHTSJ-regulated DEGs.Active components and targets of YQHTSJ were retrieved from the HERB database,leading to the identification of key TFs interacting with DEGs.Quercetin,a constituent of YQHTSJ,was evaluated for its effects on transforming growth factor-β1-induced myofibroblast activation and BLM-induced PF.The direct binding interaction between quercetin and the key TF Jun proto-oncogene(JUN)was confirmed through molecular docking studies and the cellular thermal shift assay(CETSA)experiments.Results:Nebulized YQHTSJ was found to significantly inhibit PF and inflammation in the mouse model.RNA sequencing identified 135 DEGs regulated by YQHTSJ,and 27 key TFs associated with these DEGs were predicted.Among YQHTSJ’s potential targets,41 were identified as TFs,with six-JUN,Fos proto-oncogene,MYC proto-oncogene,RELA proto-oncogene,nuclear factor kappa B subunit 1,and peroxisome proliferator activated receptor alpha-recognized as key TFs targeted by YQHTSJ.Molecular docking and CETSA experiments confirmed that quercetin directly targets JUN protein and inhibits its phosphorylation,thereby contributing to the suppression of myofibroblast activation and PF.Conclusion:The potential mechanisms of YQHTSJ and its component quercetin in combating PF may involve the regulation of critical TFs like JUN and the suppression of pathogenic gene expression.展开更多
Objective: To evaluate errors in the use of inhalation techniques in patients with chronic obstructive pulmonary disease(COPD), and to provide evidence for improving the effectiveness of drugs.Methods: A meta-analysis...Objective: To evaluate errors in the use of inhalation techniques in patients with chronic obstructive pulmonary disease(COPD), and to provide evidence for improving the effectiveness of drugs.Methods: A meta-analysis was performed after searching for literature at Pub Med, Embase, Web of Science, Cochrane Library, CINAHL, China National Knowledge Infrastructure(CNKI), Wan Fang, VIP, and Sion Med databases which were published from January 2011 to October 2020, addressing errors in the use of inhalation technologies for the treatment of COPD. After reviewing the literature, extracting per tinent information, and evaluating the risk of bias for the included studies, statistical analysis was performed using Stata 15.1.Results: Thir teen papers(12 in English and 1 in Chinese), representing 2527 patients, met the search criteria and were included in the meta-analysis. The results showed that the combined effect size of COPD patients making at least one operational error was 76%(95% CI: 0.69–0.83). The error rate varied with inhaler type;the combined effect size error for powered inhalers was 66%(95% CI: 0.57, 0.74), 67%(95% CI. 0.57, 0.77) for metered-dose inhalers(MDI), and 51%(95% CI: 0.38, 0.64) for soft mist inhalers(SMI).Conclusions: More than 75% of patients with COPD were unable to consistently use inhalers correctly, with the highest error rate for MDI. Therefore, health care providers must continue to educate patients on proper use of inhaler, ensuring their correct use and reducing the risk of acute COPD exacerbations.展开更多
The effect of inhaled nano-TiO2 on lung histology and serum biochemical indexes is evaluated in healthy and adult Kunming mice（eight in each group）after exposure to TiO2 aerosols（1 500 mg/m3）in a sealed chamber.An...The effect of inhaled nano-TiO2 on lung histology and serum biochemical indexes is evaluated in healthy and adult Kunming mice（eight in each group）after exposure to TiO2 aerosols（1 500 mg/m3）in a sealed chamber.Another eight mice are exposed to indoor air to be served as a control group.Lung tissue and blood are collected after euthanizing the animals.The results show that lactate dehydrogenase（LDH）activity increases in all experimental groups.Alanine aminotransferase（ALT）activity and blood urea nitrogen（BUN）levels are increased in the group exposed to TiO2 aerosols for 28 d,and creatinine（Cr）levels are increased in 14 d and 28 d samples（P0.05）.No obvious changes are observed in other serum indexes.Lungs of mice exposed to 28 d exposure show significant but moderate increase in pulmonary inflammation,and many TiO2 particles are found in the interstitium of pulmonary alveoli.展开更多
In order to remove efficiently haled-particles emissions from coal combustions, a new way was used to put forward the process of agglomeration and the atomization was produced by the nozzle and then sprayed into the ...In order to remove efficiently haled-particles emissions from coal combustions, a new way was used to put forward the process of agglomeration and the atomization was produced by the nozzle and then sprayed into the flue before precipitation devices of power station boiler in order to make inhaled-particles agglomerate into bigger particles, which can be easily removed but not change existing running conditions of boiler. According to this idea, a model is set up to study agglomeration rate and effect forces between fly ash inhaled-particles and atomized agglomerator particles. The developed agglomeration rate was expressed by relative particle number decreasing speed per unit volume. The result showed that viscosity force and flow resistance force give main influences on agglomeration effect of inhaled-particles, while springiness force and gravity have little effect on agglomeration effect of theirs. Factors influencing the agglomeration rate and effect forces are studied, including agglomerator concentration, agglomerator flux and agglomerator density, atomized-particles diameters and inhaled-particles diameter and so on.展开更多
Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prep...Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prepared by thin layer film hydration method(TFH) using 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol sodium(DPPG), Hydrogenated Soyaphosphotidylcholine(HSPC), Soyaphosphatidylcholine(SPC), cholesterol(CHOL) and drug in different weight ratios. The optimum lipid composition for BUD(74.22 ± 0.97%) was DPPG:HSPC: CHOL(4:5:1) and for COL(50.94 ± 2.04%) was DPPG: SPC: CHOL(3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency(97.89-98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler(DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2(86.53 ± 1.9%), Colchicine DPI Formulation C2(90.54 ± 2.3 %) and BUD and COL DPI Combination M2(89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal drypowder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at(25 °C± 2 °C, 60% ± 5% RH) and refrigerated conditions(2-8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.展开更多
Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“...Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.展开更多
Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical histo...Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical history of chronic obstructive pulmonary disease treated with formoterol and a moderate daily dose of inhaled budesonide. He had also advanced stage non-small lung cancer treated with concurrent chemo-radiation with a cisplatin-etoposide containing regimen. The diagnosis of PCP was suspected based on the context of rapidly increasing dyspnea, lymphopenia and the imaging findings. Polymerase chain reaction testing on an induced sputum specimen was positive for Pneumocystis jirovecii. The patient was treated with oral trimethoprim-sulfamethoxazole and systemic corticotherapy and had showed clinical and radiological improvement. Six months after the PCP diagnosis, he developed a malignant pleural effusion and expired on hospice care. Through this case, we remind the importance of screening for PCP in lung cancer patients under chemotherapeutic regimens and with increasing dyspnea. In addition, we alert to the fact that long-term inhaled corticosteroids may be a risk factor for PCP in patients with lung cancer. Despite intensive treatment, the mortality of PCP remains high, hence the importance of chemoprophylaxis should be considered.展开更多
It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein un...It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin(HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van't Hoff analysis of the binding constants(negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes.展开更多
Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique s...Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e.,classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm.The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.展开更多
Ciclesonide is a new corticosteroid currently in clinical development for the treatment of asthma by oral inhalation. The objectives of the present study were to develop ciclesonide dry powder inhalers （DPIs, 80 μg...Ciclesonide is a new corticosteroid currently in clinical development for the treatment of asthma by oral inhalation. The objectives of the present study were to develop ciclesonide dry powder inhalers （DPIs, 80 μg） and investigate the anti-asthmatic effect in animals. For preparing a ciclesonide capsule-type DPI, sphere-shaped lactose was used as a diluent carrier, mixed with micronized ciclesonide, and filled into a capsule, and then put into a dry powder inhaler for oral inhalation. The asthmatic model was established with guinea pigs, and the therapeutic efficacy of ciclesonide was performed on the asthmatic guinea pig model. Results showed that the pulmonary deposition ratio of ciclesonide DPIs was approximately 26% and their content uniformity met the requirements of China Pharmacopoeia. The established pathological model exhibited the typical features of asthma with a widened pulmonary alveolar interval, narrowed alveolar space and detached bronchial mucosal epithelium with topical necrosis, goblet cell hyperplasia, and inflammatory cell infiltration. After treating with ciclesonide, the impaired indicators in asthmatic guinea pigs were significantly recovered or alleviated, exhibiting decreased total cells, decreased eosinophils and a decreased IL-5 level while there was an increased IFN-γ level in the bronchoalveolar lavage fluid （BALF）. This study develops a new pulmonary ciclesonide delivery system for treating asthma, and proves the therapeutic efficacy in asthmatic guinea pigs.展开更多
Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothes...Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothesized that switching devices between dry powder and soft mist inhalers without a wash-out period to mimic clinical practice would improve clinical symptoms and lung function. The aim of this study was to examine the effects of switching between once-daily glycopyrronium/indacaterol (GLY/IND) or umeclidinium/vilanterol (UMEC/VI), dry powder inhalers, and tiotropium/olodaterol (TIO/OLO), a soft mist inhaler, in COPD patients. Methods: This was a prospective, open-label, 8-week, observational study with follow-up. Subjects included 57 COPD patients, who attended outpatient clinics at Shizuoka General Hospital for routine check-ups between February and December 2015, receiving GLY/IND (50/110 μg) or UMEC/VI (62.5/25 μg). After an 8-week run-in period, medications were switched to TIO/OLO (5/5 μg). Study outcomes included patient’s global rating (PGR), modified MRC (mMRC), COPD assessment test (CAT), and spirometric and forced oscillatory parameters after 8 weeks. PGR used in this study was a 7-point scale ranging from 1 to 7, with 4 in the middle. Patients who consented to switch from TIO/OLO to GLY/IND or UMEC/VI were followed-up thereafter. Results: In total, 53 patients completed the study (mean age, 75 years;48 males and 5 females;GOLD 1/2/3/4 = 19/27/6/1;mMRC 0/1/2/3/4 = 14/22/12/4/1;UMEC/VI 26, GLY/IND 27). PGR, mMRC, and CAT improved in 20 (38%), 9 (17%), and 15 patients (28%), respectively. Respiratory system resistance at 5 Hz (R5), 20 Hz (R20), and the difference between R5 and R20 (R5 - R20) significantly improved. In a follow-up of 16 patients after switching from TIO/OLO to UMEC/VI (9) or GLY/IND (7), PGR, mMRC, and CAT improved in 5 (31%), 3 (12%), and 4 patients (25%), respectively, and R20 significantly improved (p = 0.011). Conclusions: Switching dual bronchodilators between dry powder and soft mist inhalers improves symptoms and airway narrowing in some COPD patients.展开更多
AIM To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome(ARDS).METHODS Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeti...AIM To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome(ARDS).METHODS Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of i NO(20 ppm) or nebulized epoprostenol(10 μg/mL) was done in all patients. Thereafter, inhaled milrinone(1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide(iN O) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen(PaO_2) were recorded before and after each inhaled therapyadministration.RESULTS The majority of ARDS were of pulmonary cause(n = 13) and pneumonia(n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass(n = 2), smoke inhalation injury(n = 1), thoracic trauma and pulmonary contusions(n = 2) and aspiration(n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and i NO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO 2 from baseline was 8.8 mmH g [interquartile range(IQR) = 16.3], 6.0 mm Hg(IQR = 18.4), 6 mm Hg(IQR = 15.8) and 9.2 mm Hg(IQR = 20.2) respectively with i NO, epoprostenol, inhaled milrinone, and i NO added to milrinone. Only i NO and the combination of inhaled milrinone and i NO had a statistically significant effect on PaO 2. CONCLUSION When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milrinone appeared safe but failed to improve oxygenation in ARDS.展开更多
There are a large number of smokers who want to quit smoking but have failed in their attempts to do so,with many having been unsuccessful at quitting multiple times over their lifetime.The existing marketed nicotine ...There are a large number of smokers who want to quit smoking but have failed in their attempts to do so,with many having been unsuccessful at quitting multiple times over their lifetime.The existing marketed nicotine replacement therapies(NRT)have only marginal effectiveness and none provide a comparable physiological response to that derived from cigarette smoking;that is,rapid absorption of nicotine from the lung leading to peak levels of nicotine in the bloodstream to target the receptors in the brain.Instead,existing NRTs produce a slower and delayed rise in nicotine blood levels which is less effective at reducing the craving sensations.Published data for electronic cigarettes show that they typically deliver nicotine with a profile closer to that for nicotine patches,with a slow rise that can take 30–60 min,or longer,to reach the same peak nicotine concentration that is produced in less than 3 min from a single cigarette.A number of attempts have been made to develop an inhaled product which would deliver the nicotine through the lung and mimic the physiological response from smoking,but many of them produced intolerable aversive reactions or delivered an ineffective dose.This paper discusses examples of the potential for the recent inhaled nicotine products in development to be effective as NRTs,but is not meant to be a comprehensive review.展开更多
Objective:To determine the most common mistakes made during the use of a metered-dose inhaler(MDI),and the effect of the repeated trainings performed with demonstration method by providing one-to-one feedback on these...Objective:To determine the most common mistakes made during the use of a metered-dose inhaler(MDI),and the effect of the repeated trainings performed with demonstration method by providing one-to-one feedback on these mistakes.Methods:This is a quasi-experimental study with a control group.A total of 100 chronic obstructive pulmonary disease(COPD)patients(50 in the control group and 50 in the experimental group)were included in the research.“Patient Information Form(PIF)”(to determine the descriptive characteristics of patients)through the face-to-face interview method,using“MDI Skill Assessment Form”(MDISAF)(it is composed of 10 skill steps about the use of MDI)through observation method was used.Patients in both the groups were asked to use MDI and their abilities regarding use of MDI were assessed.Then in the intervention group,usage of MDI was explained by a nurse via demonstration and placebo MDI.Trainings were repeated on days 1,3,and 5 as from hospitalization of the patient.In the intervention group,three methods were used in this study:“face-to-face training,”“one-to-one,”and“with feedbacks and repeated.”Routine training regarding use of MDI was given by the nurses in the clinic to patients in the control group.The use of an MDI was assessed using MDISAF before training and after the training on the first,third and fifth days of hospitalization.On the seventh day,the last measurement was performed.Percentage,chi square,and mean were used to assess the data.Results:After repetitive training with one-to-one feedback,several differences between the groups in favor of the experimental group were found in 7 of the 10 skill levels of the MDI.There was a significant difference after“training”between the groups in the third,fourth,fifth,sixth,seventh,eighth and ninth MDI steps in posttest measurement(P<0.05).Evaluating the skills of the groups to use MDI from pretest to posttest,it was determined that while the intervention group made less mistakes in steps in which mistakes were made mostly,the control group continued to make mistakes.Conclusions:Inhaler technique intervention with repeated,face to face,and one-to-one feedback trainings can significantly enhance the MDI techniques in COPD patients.The patients in the intervention group made less mistakes during MDI application and their application skills improved.It may be asser ted that the training provided to the intervention group was effective for using the device correctly,while the training provided in the clinic for the control group was inadequate.展开更多
Type 2 diabetes continues to place a major burden on the health care system of the United States and worldwide. Type 2 diabetes involves two major defects: decreased insulin production from the pancreas and increased ...Type 2 diabetes continues to place a major burden on the health care system of the United States and worldwide. Type 2 diabetes involves two major defects: decreased insulin production from the pancreas and increased insulin resistance. Many patients with type 2 diabetes have decreased insulin production which requires exogenous insulin therapy in order to manage their disease. Despite this need, there is often a reluctance to initiate insulin therapy from both providers and patients. One reason for this reluctance may be a fear of needles or of administering injections. Delivering insulin through the lungs has been studied for decades, with the first inhaled insulin product coming to market in 2006. This product’s launch was considered unsuccessful, and the product was discontinued by the manufacturer the following year. A new inhaled insulin, Technosphere? insulin, was approved for use in type 1 and type 2 diabetes in 2014. This product was shown superior to placebo and non-inferior to a premixed bi-phasic subcutaneous insulin in patients with type 2 diabetes, and may offer an alternative to patients who are averse to giving subcutaneous injections.展开更多
Coronavirus disease 2019(COVID-19)related acute respiratory distress syndrome(ARDS)is a severe complication of infection with severe acute respiratory syndrome coronavirus 2,and the primary cause of death in the curre...Coronavirus disease 2019(COVID-19)related acute respiratory distress syndrome(ARDS)is a severe complication of infection with severe acute respiratory syndrome coronavirus 2,and the primary cause of death in the current pandemic.Critically ill patients often undergo extracorporeal membrane oxygenation(ECMO)therapy as the last resort over an extended period.ECMO therapy requires sedation of the patient,which is usually achieved by intravenous administration of sedatives.The shortage of intravenous sedative drugs due to the ongoing pandemic,and attempts to improve treatment outcome for COVID-19 patients,drove the application of inhaled sedation as a promising alternative for sedation during ECMO therapy.Administration of volatile anesthetics requires an appropriate delivery.Commercially available ones are the anesthetic gas reflection systems AnaConDa®and MIRUSTM,and each should be combined with a gas scavenging system.In this review,we describe respiratory management in COVID-19 patients and the procedures for inhaled sedation during ECMO therapy of COVID-19 related ARDS.We focus particularly on the technical details of administration of volatile anesthetics.Furthermore,we describe the advantages of inhaled sedation and volatile anesthetics,and we discuss the limitations as well as the requirements for safe application in the clinical setting.展开更多
The therapeutic potential of small nucleic acids such as small interfering RNA(siRNA) to treat lung diseases has been successfully demonstrated in many in vivo studies. A major barrier to their clinical application is...The therapeutic potential of small nucleic acids such as small interfering RNA(siRNA) to treat lung diseases has been successfully demonstrated in many in vivo studies. A major barrier to their clinical application is the lack of a safe and efficient inhaled formulation.In this study, spray freeze drying was employed to prepare dry powder of small nucleic acids.Mannitol and herring sperm DNA were used as bulking agent and model of small nucleic acid therapeutics, respectively. Formulations containing different solute concentration and DNA concentration were produced. The scanning electron microscope(SEM) images showed that the porosity of the particles increased as the solute concentration decreased. Powders prepared with solute concentration of 5% w/v were found to maintain a balance between porosity and robustness. Increasing concentration of DNA improved the aerosol performance of the formulation. The dry powder formulation containing 2% w/w DNA had a median diameter of 12.5 μm, and the aerosol performance study using next generation impactor(NGI) showed an emitted fraction(EF) and fine particle fraction(FPF) of 91% and 28% respectively. This formulation(5% w/v solute concentration and 2% w/w nucleic acid) was adopted subsequently to produce siRNA powder. The gel retardation and liquid chromatography assays showed that the siRNA remained intact after spray freeze drying even in the absence of delivery vector. The siRNA powder formulation exhibited a high EF of 92.4%and a modest FPF of around 20%. Further exploration of this technology to optimise inhaled siRNA powder formulation is warranted.展开更多
Orally inhaled drug products(OIPs),such as corticosteroids and bronchodilators,are at the forefront of asthma and chronic obstructive pulmonary disease treatments,two diseases that afflict worldwide populations.Introd...Orally inhaled drug products(OIPs),such as corticosteroids and bronchodilators,are at the forefront of asthma and chronic obstructive pulmonary disease treatments,two diseases that afflict worldwide populations.Introducing generics of these products is essential,as the pricing of these medications remain a barrier to adequate patient care.Currently,there is no consensus between regulatory bodies as to the bioequivalence and equivalence requirements of OIPs that are intended for local action in the lungs.This manuscript critically reviews these requirements and presents future directions for clinicians,scientists,and regulators to consider to optimize the development and approval of OIPs.展开更多
文摘Purpose:The aim was to synthesize quantitative and qualitative research that identified the most effective educational strategies for nurse-led inhaler technique(IT)education in Chronic Obstructive Pulmonary Disease(COPD)patients,as perceived by patients,healthcare providers,and nurses.Methods:A systematic literature search in Embase,PubMed,Cochrane Library,Web of Science,and CINAHL from 2018 to 30 June 2024 was conducted.In total,327 articles were identified.The results of 14 studies that met the inclusion criteria were synthesized.Data were analyzed with des-criptive and semi-quantitative methods to yield summarizing findings on the effectiveness of different educational strate-gies.All investigations had assessed patient adherence to IT.Results:Data indicated that nurse-led IT teaching strategies are effective in promoting IT adherence and correctness in COPD patients utilizing the personalized Teach-Back method.However,studies in disease control and comparison of patient IT satisfaction and self-efficacy need further investigation.Conclusion:The results of this study may contribute to the understanding of the most effective educational strategies in nurse-led IT education for COPD patients.The synthesized findings can be used for the development of new educational interventions and assessment instruments for IT adherence.
基金supported by the Guangdong Basic and Applied Basic Research Foundation under Grant(2023A1515011243)National Natural Science Foundation of China under Grant(82004141)+2 种基金Bao’an Traditional Chinese Medicine Development Foundation under Grant(2022KJCX-ZJZL-11)Science,Technology,and Innovation Commission of Shenzhen Municipality under Grant(JCYJ20190808160407500)Shenzhen Bao’an Traditional Chinese Medicine Hospital Research Program under Grant(BAZYY20220701).
文摘Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized inhalation,exploring its underlying mechanisms.Methods:The anti-fibrotic properties of nebulized YQHTSJ were assessed using a bleomycin(BLM)-induced PF mouse model.RNA sequencing identified differentially expressed genes(DEGs),and subsequent gene enrichment analysis,along with transcription factor(TF)prediction,revealed YQHTSJ-regulated DEGs.Active components and targets of YQHTSJ were retrieved from the HERB database,leading to the identification of key TFs interacting with DEGs.Quercetin,a constituent of YQHTSJ,was evaluated for its effects on transforming growth factor-β1-induced myofibroblast activation and BLM-induced PF.The direct binding interaction between quercetin and the key TF Jun proto-oncogene(JUN)was confirmed through molecular docking studies and the cellular thermal shift assay(CETSA)experiments.Results:Nebulized YQHTSJ was found to significantly inhibit PF and inflammation in the mouse model.RNA sequencing identified 135 DEGs regulated by YQHTSJ,and 27 key TFs associated with these DEGs were predicted.Among YQHTSJ’s potential targets,41 were identified as TFs,with six-JUN,Fos proto-oncogene,MYC proto-oncogene,RELA proto-oncogene,nuclear factor kappa B subunit 1,and peroxisome proliferator activated receptor alpha-recognized as key TFs targeted by YQHTSJ.Molecular docking and CETSA experiments confirmed that quercetin directly targets JUN protein and inhibits its phosphorylation,thereby contributing to the suppression of myofibroblast activation and PF.Conclusion:The potential mechanisms of YQHTSJ and its component quercetin in combating PF may involve the regulation of critical TFs like JUN and the suppression of pathogenic gene expression.
基金supported by Health Department of Sichuan Province(No.Chuan Gan Research-2021-219)National Natural Science Foundation of China(No.72004020)。
文摘Objective: To evaluate errors in the use of inhalation techniques in patients with chronic obstructive pulmonary disease(COPD), and to provide evidence for improving the effectiveness of drugs.Methods: A meta-analysis was performed after searching for literature at Pub Med, Embase, Web of Science, Cochrane Library, CINAHL, China National Knowledge Infrastructure(CNKI), Wan Fang, VIP, and Sion Med databases which were published from January 2011 to October 2020, addressing errors in the use of inhalation technologies for the treatment of COPD. After reviewing the literature, extracting per tinent information, and evaluating the risk of bias for the included studies, statistical analysis was performed using Stata 15.1.Results: Thir teen papers(12 in English and 1 in Chinese), representing 2527 patients, met the search criteria and were included in the meta-analysis. The results showed that the combined effect size of COPD patients making at least one operational error was 76%(95% CI: 0.69–0.83). The error rate varied with inhaler type;the combined effect size error for powered inhalers was 66%(95% CI: 0.57, 0.74), 67%(95% CI. 0.57, 0.77) for metered-dose inhalers(MDI), and 51%(95% CI: 0.38, 0.64) for soft mist inhalers(SMI).Conclusions: More than 75% of patients with COPD were unable to consistently use inhalers correctly, with the highest error rate for MDI. Therefore, health care providers must continue to educate patients on proper use of inhaler, ensuring their correct use and reducing the risk of acute COPD exacerbations.
文摘The effect of inhaled nano-TiO2 on lung histology and serum biochemical indexes is evaluated in healthy and adult Kunming mice（eight in each group）after exposure to TiO2 aerosols（1 500 mg/m3）in a sealed chamber.Another eight mice are exposed to indoor air to be served as a control group.Lung tissue and blood are collected after euthanizing the animals.The results show that lactate dehydrogenase（LDH）activity increases in all experimental groups.Alanine aminotransferase（ALT）activity and blood urea nitrogen（BUN）levels are increased in the group exposed to TiO2 aerosols for 28 d,and creatinine（Cr）levels are increased in 14 d and 28 d samples（P0.05）.No obvious changes are observed in other serum indexes.Lungs of mice exposed to 28 d exposure show significant but moderate increase in pulmonary inflammation,and many TiO2 particles are found in the interstitium of pulmonary alveoli.
文摘In order to remove efficiently haled-particles emissions from coal combustions, a new way was used to put forward the process of agglomeration and the atomization was produced by the nozzle and then sprayed into the flue before precipitation devices of power station boiler in order to make inhaled-particles agglomerate into bigger particles, which can be easily removed but not change existing running conditions of boiler. According to this idea, a model is set up to study agglomeration rate and effect forces between fly ash inhaled-particles and atomized agglomerator particles. The developed agglomeration rate was expressed by relative particle number decreasing speed per unit volume. The result showed that viscosity force and flow resistance force give main influences on agglomeration effect of inhaled-particles, while springiness force and gravity have little effect on agglomeration effect of theirs. Factors influencing the agglomeration rate and effect forces are studied, including agglomerator concentration, agglomerator flux and agglomerator density, atomized-particles diameters and inhaled-particles diameter and so on.
文摘Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prepared by thin layer film hydration method(TFH) using 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol sodium(DPPG), Hydrogenated Soyaphosphotidylcholine(HSPC), Soyaphosphatidylcholine(SPC), cholesterol(CHOL) and drug in different weight ratios. The optimum lipid composition for BUD(74.22 ± 0.97%) was DPPG:HSPC: CHOL(4:5:1) and for COL(50.94 ± 2.04%) was DPPG: SPC: CHOL(3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency(97.89-98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler(DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2(86.53 ± 1.9%), Colchicine DPI Formulation C2(90.54 ± 2.3 %) and BUD and COL DPI Combination M2(89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal drypowder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at(25 °C± 2 °C, 60% ± 5% RH) and refrigerated conditions(2-8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.
基金supported by Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No. ZYYCXTD-D-202002)Scientific Research Project of Tianjin Municipal Education Commission (No.2019KJ083)
文摘Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.
文摘Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical history of chronic obstructive pulmonary disease treated with formoterol and a moderate daily dose of inhaled budesonide. He had also advanced stage non-small lung cancer treated with concurrent chemo-radiation with a cisplatin-etoposide containing regimen. The diagnosis of PCP was suspected based on the context of rapidly increasing dyspnea, lymphopenia and the imaging findings. Polymerase chain reaction testing on an induced sputum specimen was positive for Pneumocystis jirovecii. The patient was treated with oral trimethoprim-sulfamethoxazole and systemic corticotherapy and had showed clinical and radiological improvement. Six months after the PCP diagnosis, he developed a malignant pleural effusion and expired on hospice care. Through this case, we remind the importance of screening for PCP in lung cancer patients under chemotherapeutic regimens and with increasing dyspnea. In addition, we alert to the fact that long-term inhaled corticosteroids may be a risk factor for PCP in patients with lung cancer. Despite intensive treatment, the mortality of PCP remains high, hence the importance of chemoprophylaxis should be considered.
基金supported by a grant from the University of Torino(Ricerca Locale ex-60%,Bando 2015)
文摘It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin(HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van't Hoff analysis of the binding constants(negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes.
基金the funding support for this study from GEA-NUS PPRL (N-148-000-008-001)SERC Grant No. 102 169 0049 (R-148-000-157-305)partial support from the NSF through the NNIN program
文摘Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e.,classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm.The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.
基金Tianjin Pharmaceuticals Research Organization Co.,Ltd,and in part by the Key Grant of Beijing Natural Science Foundation(Grant No.7091005)
文摘Ciclesonide is a new corticosteroid currently in clinical development for the treatment of asthma by oral inhalation. The objectives of the present study were to develop ciclesonide dry powder inhalers （DPIs, 80 μg） and investigate the anti-asthmatic effect in animals. For preparing a ciclesonide capsule-type DPI, sphere-shaped lactose was used as a diluent carrier, mixed with micronized ciclesonide, and filled into a capsule, and then put into a dry powder inhaler for oral inhalation. The asthmatic model was established with guinea pigs, and the therapeutic efficacy of ciclesonide was performed on the asthmatic guinea pig model. Results showed that the pulmonary deposition ratio of ciclesonide DPIs was approximately 26% and their content uniformity met the requirements of China Pharmacopoeia. The established pathological model exhibited the typical features of asthma with a widened pulmonary alveolar interval, narrowed alveolar space and detached bronchial mucosal epithelium with topical necrosis, goblet cell hyperplasia, and inflammatory cell infiltration. After treating with ciclesonide, the impaired indicators in asthmatic guinea pigs were significantly recovered or alleviated, exhibiting decreased total cells, decreased eosinophils and a decreased IL-5 level while there was an increased IFN-γ level in the bronchoalveolar lavage fluid （BALF）. This study develops a new pulmonary ciclesonide delivery system for treating asthma, and proves the therapeutic efficacy in asthmatic guinea pigs.
文摘Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothesized that switching devices between dry powder and soft mist inhalers without a wash-out period to mimic clinical practice would improve clinical symptoms and lung function. The aim of this study was to examine the effects of switching between once-daily glycopyrronium/indacaterol (GLY/IND) or umeclidinium/vilanterol (UMEC/VI), dry powder inhalers, and tiotropium/olodaterol (TIO/OLO), a soft mist inhaler, in COPD patients. Methods: This was a prospective, open-label, 8-week, observational study with follow-up. Subjects included 57 COPD patients, who attended outpatient clinics at Shizuoka General Hospital for routine check-ups between February and December 2015, receiving GLY/IND (50/110 μg) or UMEC/VI (62.5/25 μg). After an 8-week run-in period, medications were switched to TIO/OLO (5/5 μg). Study outcomes included patient’s global rating (PGR), modified MRC (mMRC), COPD assessment test (CAT), and spirometric and forced oscillatory parameters after 8 weeks. PGR used in this study was a 7-point scale ranging from 1 to 7, with 4 in the middle. Patients who consented to switch from TIO/OLO to GLY/IND or UMEC/VI were followed-up thereafter. Results: In total, 53 patients completed the study (mean age, 75 years;48 males and 5 females;GOLD 1/2/3/4 = 19/27/6/1;mMRC 0/1/2/3/4 = 14/22/12/4/1;UMEC/VI 26, GLY/IND 27). PGR, mMRC, and CAT improved in 20 (38%), 9 (17%), and 15 patients (28%), respectively. Respiratory system resistance at 5 Hz (R5), 20 Hz (R20), and the difference between R5 and R20 (R5 - R20) significantly improved. In a follow-up of 16 patients after switching from TIO/OLO to UMEC/VI (9) or GLY/IND (7), PGR, mMRC, and CAT improved in 5 (31%), 3 (12%), and 4 patients (25%), respectively, and R20 significantly improved (p = 0.011). Conclusions: Switching dual bronchodilators between dry powder and soft mist inhalers improves symptoms and airway narrowing in some COPD patients.
文摘AIM To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome(ARDS).METHODS Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of i NO(20 ppm) or nebulized epoprostenol(10 μg/mL) was done in all patients. Thereafter, inhaled milrinone(1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide(iN O) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen(PaO_2) were recorded before and after each inhaled therapyadministration.RESULTS The majority of ARDS were of pulmonary cause(n = 13) and pneumonia(n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass(n = 2), smoke inhalation injury(n = 1), thoracic trauma and pulmonary contusions(n = 2) and aspiration(n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and i NO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO 2 from baseline was 8.8 mmH g [interquartile range(IQR) = 16.3], 6.0 mm Hg(IQR = 18.4), 6 mm Hg(IQR = 15.8) and 9.2 mm Hg(IQR = 20.2) respectively with i NO, epoprostenol, inhaled milrinone, and i NO added to milrinone. Only i NO and the combination of inhaled milrinone and i NO had a statistically significant effect on PaO 2. CONCLUSION When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milrinone appeared safe but failed to improve oxygenation in ARDS.
文摘There are a large number of smokers who want to quit smoking but have failed in their attempts to do so,with many having been unsuccessful at quitting multiple times over their lifetime.The existing marketed nicotine replacement therapies(NRT)have only marginal effectiveness and none provide a comparable physiological response to that derived from cigarette smoking;that is,rapid absorption of nicotine from the lung leading to peak levels of nicotine in the bloodstream to target the receptors in the brain.Instead,existing NRTs produce a slower and delayed rise in nicotine blood levels which is less effective at reducing the craving sensations.Published data for electronic cigarettes show that they typically deliver nicotine with a profile closer to that for nicotine patches,with a slow rise that can take 30–60 min,or longer,to reach the same peak nicotine concentration that is produced in less than 3 min from a single cigarette.A number of attempts have been made to develop an inhaled product which would deliver the nicotine through the lung and mimic the physiological response from smoking,but many of them produced intolerable aversive reactions or delivered an ineffective dose.This paper discusses examples of the potential for the recent inhaled nicotine products in development to be effective as NRTs,but is not meant to be a comprehensive review.
文摘Objective:To determine the most common mistakes made during the use of a metered-dose inhaler(MDI),and the effect of the repeated trainings performed with demonstration method by providing one-to-one feedback on these mistakes.Methods:This is a quasi-experimental study with a control group.A total of 100 chronic obstructive pulmonary disease(COPD)patients(50 in the control group and 50 in the experimental group)were included in the research.“Patient Information Form(PIF)”(to determine the descriptive characteristics of patients)through the face-to-face interview method,using“MDI Skill Assessment Form”(MDISAF)(it is composed of 10 skill steps about the use of MDI)through observation method was used.Patients in both the groups were asked to use MDI and their abilities regarding use of MDI were assessed.Then in the intervention group,usage of MDI was explained by a nurse via demonstration and placebo MDI.Trainings were repeated on days 1,3,and 5 as from hospitalization of the patient.In the intervention group,three methods were used in this study:“face-to-face training,”“one-to-one,”and“with feedbacks and repeated.”Routine training regarding use of MDI was given by the nurses in the clinic to patients in the control group.The use of an MDI was assessed using MDISAF before training and after the training on the first,third and fifth days of hospitalization.On the seventh day,the last measurement was performed.Percentage,chi square,and mean were used to assess the data.Results:After repetitive training with one-to-one feedback,several differences between the groups in favor of the experimental group were found in 7 of the 10 skill levels of the MDI.There was a significant difference after“training”between the groups in the third,fourth,fifth,sixth,seventh,eighth and ninth MDI steps in posttest measurement(P<0.05).Evaluating the skills of the groups to use MDI from pretest to posttest,it was determined that while the intervention group made less mistakes in steps in which mistakes were made mostly,the control group continued to make mistakes.Conclusions:Inhaler technique intervention with repeated,face to face,and one-to-one feedback trainings can significantly enhance the MDI techniques in COPD patients.The patients in the intervention group made less mistakes during MDI application and their application skills improved.It may be asser ted that the training provided to the intervention group was effective for using the device correctly,while the training provided in the clinic for the control group was inadequate.
文摘Type 2 diabetes continues to place a major burden on the health care system of the United States and worldwide. Type 2 diabetes involves two major defects: decreased insulin production from the pancreas and increased insulin resistance. Many patients with type 2 diabetes have decreased insulin production which requires exogenous insulin therapy in order to manage their disease. Despite this need, there is often a reluctance to initiate insulin therapy from both providers and patients. One reason for this reluctance may be a fear of needles or of administering injections. Delivering insulin through the lungs has been studied for decades, with the first inhaled insulin product coming to market in 2006. This product’s launch was considered unsuccessful, and the product was discontinued by the manufacturer the following year. A new inhaled insulin, Technosphere? insulin, was approved for use in type 1 and type 2 diabetes in 2014. This product was shown superior to placebo and non-inferior to a premixed bi-phasic subcutaneous insulin in patients with type 2 diabetes, and may offer an alternative to patients who are averse to giving subcutaneous injections.
文摘Coronavirus disease 2019(COVID-19)related acute respiratory distress syndrome(ARDS)is a severe complication of infection with severe acute respiratory syndrome coronavirus 2,and the primary cause of death in the current pandemic.Critically ill patients often undergo extracorporeal membrane oxygenation(ECMO)therapy as the last resort over an extended period.ECMO therapy requires sedation of the patient,which is usually achieved by intravenous administration of sedatives.The shortage of intravenous sedative drugs due to the ongoing pandemic,and attempts to improve treatment outcome for COVID-19 patients,drove the application of inhaled sedation as a promising alternative for sedation during ECMO therapy.Administration of volatile anesthetics requires an appropriate delivery.Commercially available ones are the anesthetic gas reflection systems AnaConDa®and MIRUSTM,and each should be combined with a gas scavenging system.In this review,we describe respiratory management in COVID-19 patients and the procedures for inhaled sedation during ECMO therapy of COVID-19 related ARDS.We focus particularly on the technical details of administration of volatile anesthetics.Furthermore,we describe the advantages of inhaled sedation and volatile anesthetics,and we discuss the limitations as well as the requirements for safe application in the clinical setting.
基金funded by the Health and Medical Research Fund, Hong Kong (15140962)Research Grant Council, Hong Kong (17110414)
文摘The therapeutic potential of small nucleic acids such as small interfering RNA(siRNA) to treat lung diseases has been successfully demonstrated in many in vivo studies. A major barrier to their clinical application is the lack of a safe and efficient inhaled formulation.In this study, spray freeze drying was employed to prepare dry powder of small nucleic acids.Mannitol and herring sperm DNA were used as bulking agent and model of small nucleic acid therapeutics, respectively. Formulations containing different solute concentration and DNA concentration were produced. The scanning electron microscope(SEM) images showed that the porosity of the particles increased as the solute concentration decreased. Powders prepared with solute concentration of 5% w/v were found to maintain a balance between porosity and robustness. Increasing concentration of DNA improved the aerosol performance of the formulation. The dry powder formulation containing 2% w/w DNA had a median diameter of 12.5 μm, and the aerosol performance study using next generation impactor(NGI) showed an emitted fraction(EF) and fine particle fraction(FPF) of 91% and 28% respectively. This formulation(5% w/v solute concentration and 2% w/w nucleic acid) was adopted subsequently to produce siRNA powder. The gel retardation and liquid chromatography assays showed that the siRNA remained intact after spray freeze drying even in the absence of delivery vector. The siRNA powder formulation exhibited a high EF of 92.4%and a modest FPF of around 20%. Further exploration of this technology to optimise inhaled siRNA powder formulation is warranted.
文摘Orally inhaled drug products(OIPs),such as corticosteroids and bronchodilators,are at the forefront of asthma and chronic obstructive pulmonary disease treatments,two diseases that afflict worldwide populations.Introducing generics of these products is essential,as the pricing of these medications remain a barrier to adequate patient care.Currently,there is no consensus between regulatory bodies as to the bioequivalence and equivalence requirements of OIPs that are intended for local action in the lungs.This manuscript critically reviews these requirements and presents future directions for clinicians,scientists,and regulators to consider to optimize the development and approval of OIPs.
