Agglomeration rate and action forces between atomized particles of agglomerator and inhaled-particles from coal combustion

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.

Do inhaled corticosteroids increase the risk of Pneumocystis pneumonia in people with lung cancer?

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.

Insight into the interaction of inhaled corticosteroids with human serum albumin: A spectroscopic-based study

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.

Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome

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.

The Role of Inhaled Insulin in the Management of Type 2 Diabetes

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.

Extracorporeal membrane oxygenation and inhaled sedation in coronavirus disease 2019-related acute respiratory distress syndrome

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.

Rethinking bioequivalence and equivalence requirements of orally inhaled drug products

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.

Spray freeze drying of small nucleic acids as inhaled powder for pulmonary delivery

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.

Inhaled nicotine replacement therapy

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.

EFFECTS OF INHALED TiO_2 NANOTUBES ON LUNG TISSUE AND SERUM BIOCHEMICAL INDEXES OF MICE

To evaluate the acute lung toxicity and the effect on serum biochemical indexes of inhaled TiO2 nanotubes , healthy and adult Kunming mice are exposed to aerosols of TiO2nanotubes in a sealed chamber , the concentration of which is 250mg / m 3 while another group of mice are exposed to room air only served as control.The blood , alveolar lavaged fluid and lungs of the mice are collected and examined after exposed for 7 , 14and 28d , respectively.The serum analysis shows that glucose ( Glu ) values with 7dexposure , alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) activities with 28dinhalation , and total bile acid ( TBA ) values with 7 , 28d as well as the creatine kinase ( CK ) levels with 28dexposure are significantly different from those of controls ( P< 0.05 ) .The pathological findings exhibit that more TiO 2 nanotubes are found in the interstitium of pulmonary alveoli with the experimental time prolonged.The results suggest that TiO 2 nanotubes do produce adverse responses to the lung and serum biochemical indexes of mice.Moreover , the responses become severer with the exposed-time prolonged.

Drug/polymer nanoparticles prepared using unique spray nozzles and recent progress of inhaled formulation

Inhaled formulations are promising for pulmonary and systemic non-pulmonary diseases.Functional engineered particles including drugs and drug-loaded nanocarriers have been anticipated because they can improve drug delivery efficacy against target sites in the lungs or blood.In this review,unique spray nozzles(e.g.,four-fluid spray nozzle and twosolution mixing type nozzle)for the preparation of nanocomposite particles which mean microparticles containing drug nanoparticles are described.These nozzles can produce nanocomposite particles in one-step and their spray drying system is suitable for scalingup.Nanocomposite particles are useful in improving drug absorption and delivery efficacy against alveolar macrophages.In addition,recent studies on several pulmonary diseases(tuberculosis,lung cancer,cystic fibrosis,pneumonia,vaccine and others)and related inhaled formulations were also reviewed.

The effects of inhaled aromatherapy on complications of hemodialysis patients: a systematic review

Objective:To evaluate the effect of inhaled aromatherapy on complications in patients undergoing hemodialysis.Methods:We search the PubMed,Web of Science,Cochrane Library,Embase and China Biomedical Literature Database from their inception to December,2019 to collect randomized controlled trials about the effects of inhaled aromatherapy on hemodialysis complications.Literatures screening,data extraction and risk of bias assessment for the included studies were conducted by two reviewers independently.We summarized all findings with qualitative analysis.Results:A total of 15 studies with 967 participants were included in the systematic review.Inhaled aromatherapy can reduce anxiety,depression,arteriovenous fistula puncture pain,stress and fatigue,and improve the quality of sleep and perceived well-being in hemodialysis patients.Conclusion:Inhaled aromatherapy had certain effects on complications in hemodialysis patients,which can be used as a simple and convenient treatment,but further research was needed to determine standardized implementation procedures and standards.

Metal Ion Release of Manufactured Metal Oxide Nanoparticles Is Involved in the Allergic Response to Inhaled Ovalbumin in Mice

The aim of the present study was to establish the mechanism of the allergy aggravation effect. Our previous study showed that soluble ZnO nanoparticles caused allergy aggravation, but insoluble TiO2 and SiO2 nanoparticles did not induce an allergic response. Metal ion release is associated with the cytotoxicity of manufactured nanoparticles;however, the role of metal ion release in allergy aggravation remains to be elucidated. Therefore, we examined the allergy aggravation potential of several soluble manufactured nanoparticles (ZnO, CuO, NiO, MgO, and CaCO3). These nanoparticles were administered to mouse lungs by pharyngeal aspiration and subsequently, the mice inhaled ovalbumin (OVA). We also compared the properties of soluble NiO nanoparticles with insoluble micro-scale NiO particles. NiO nanoparticles markedly increased the levels of OVAspecific immunoglobulin (Ig) E but micro-scale NiO particles did not. Among the nanoparticles (ZnO, CuO, MgO, and CaCO3), ZnO induced increase of OVA-specific IgE level. CuO showed tendency to increase OVA-specific IgE;however, no significant difference was observed. Additionally, ZnO and NiO nanoparticles enhanced expression of a gene related to inflammation (Cxcl2), heavy metal detox (metallothionein 2), and oxidative stress (heme oxygenase-1). Gene expression of arginase1, which is enhanced by T helper 2 cytokine, was remarkably enhanced in mice administered ZnO and NiO particles. These effects were not observed in mice administered MgO and CaCO3 nanoparticles. In conclusion, the solubility and type of metal ion released from the nanoparticles influence the allergy aggravation effect. The results showed that the release of Zn2+ and Ni2+ aggravated the allergic reaction.

Home-Nebulized Inhaled Glucocorticoid Therapy in Pediatric Respiratory Diseases

Objective:To evaluate the therapeutic effect of home-nebulized inhaled glucocorticoid therapy in pediatric respiratory diseases.Methods:60 cases of children with respiratory diseases admitted between October 2022 and October 2023 were selected as study subjects and randomly divided into the control group and the observation group,30 cases each.The control group was provided with conventional treatment only,while the observation group was provided with home-nebulized inhalation glucocorticosteroid treatment,and the treatment effects,clinical symptom relief time,disease recurrence rate,and treatment satisfaction of the children’s families were recorded and compared between the two groups.Results:A comparison of the two groups in terms of gender and age showed that the differences were not statistically significant(P>0.05).In terms of clinical efficacy,the total effective rate of the observation group was 90.00%,which was significantly higher than that of the control group of 66.67%(P<0.05).Compared with the control group,the disappearance time of the clinical symptoms of the observed group was significantly shortened(P<0.05).In addition,the satisfaction scores of the families of the children in the observation group were significantly higher than those of the control group(P<0.05).Conclusion:Home-nebulized inhalation glucocorticoid therapy shows significant clinical efficacy in pediatric respiratory diseases,significantly reduces the time of disappearance of clinical symptoms,and improves the satisfaction of patients’families,which provides an effective treatment option for children.

A Time Series Observation of Chinese Children Undergoing Rigid Bronchoscopy for an Inhaled Foreign Body： 3149 Cases in 1991-2010

Background：In China,tracheobronchial foreign body （TFB） aspiration,a major cause of emergency episode and accident death in children,remains a challenge for anesthetic management.Here,we share our experience and discuss the anesthetic consideration and management of patients with TFB aspiration.Methods：This was a single-institution retrospective study in children with an inhaled foreign body between 1991 and 2010 that focused on the complications following rigid bronchoscopy （RB）.Data including the clinical characteristics of patients and TFB,anesthetic method,and postoperative severe complications were analyzed by different periods.Results：During the 20-year study period,the charts of 3149 patients who underwent RB for suspected inhaled TFB were reviewed.There were 2079 male and 1070 female patients （1.94：1）.A nut （84％） was the most commonly inhaled object.The study revealed a 9％ （n =284） overall rate of severe postoperative complications related to severe hypoxemia,laryngeal edema,complete laryngospasm,pneumothorax,total segmental atelectasis,and death with incidences of 3.2％,0.9％,1.3％,0.3％,0.3％,and 0.1％,respectively.The rates of preoperative airway impairment,negative findings of TFB,and adverse postoperative events have been on the rise in the past 5 years.Conclusions：The survey results confirmed that hypoxemia remains the most common postoperative complication in different periods.Both controlled ventilation and spontaneous ventilation were effective during the RB extraction of the foreign body at our hospital in the modern technique period.An active respiratory symptom was commonly seen in the groups with negative findings.

Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients

Background： Studies of interleukin （IL）-4 and IL-6 in the exhaled breath condensate （EBC） of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid （ICS） treatment on IL-4 and IL-6 in the EBC ＆asthmatic patients. Methods： In a prospective, open-label study, budesonide 200 μg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma （mean age 42.7 years） for 12 weeks. Changes in asthma scores, lung function parameters （forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEFs0], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate） and the concentrations of IL-4 and IL-6 in EBC were measured. Results： Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmolJL after 8 weeks of treatment （P 〈 0.05） and 1.54 ± 0.81 pmol/L after 12 weeks of treatment （P 〈 0.01）. However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEVt, PEF and FEFso values （correlation coefficients -0.468, -0.478, and -0.426, respectively）. Conclusions： The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.

A 2-year step-down withdrawal from inhaled corticosteroids in asthmatic children receiving immunotherapy

Background:Inhaled corticosteroids (ICSs) for treating asthma are controversial because of their negative effects on the growth of asthmatic children and without clearly defined withdrawal strategy.A 2-year ICS step-down and withdrawal strategy has been developed for asthmatic children receiving 3-year subcutaneous immunotherapy (SCIT).Methods:Eleven children were included into the SCIT group and 13 children into the ICS group.ICSs were discontinued when children met the following criteria:requiring only 1 puff per day,with good control,for at least 6 months;having a forced expiratory volume in 1 second (FEV1)/forced vital capacity ≥80%;and SCIT discontinued for ≥24 months.The main endpoints were the results of both the childhood asthma control test (C-CAT) and the methacholine bronchial provocation test.Results:In the SCIT group,all the 11 children had ICS discontinued,with one child developed asthma attack after pneumonia and received ICS again after completion of SCIT.In the ICS group,five children discontinued ICS and developed asthma attacks later and received ICS again;the other eight children developed severe symptoms during ICS step-down.Thus,the discontinuation of ICS was only achieved in the SCIT group.The dose of methacholine that caused a decrease of 20% in FEV1 continued to improve after discontinuation of ICS for the SCIT group and presented better results than the ICS group (P=-0.050).After completion of SCIT,the C-CAT had improved significantly after 30 months of treatment compared with the ICS group (P<0.05).Conclusion:In the present study,we developed a 2-year step-down and withdrawal strategy from ICSs strategy for allergic asthma children receiving SCIT;the strategy was efficacious and safe.

Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines

Pulmonary administration route has been extensively exploited for the treatment of local lung diseases such as asthma,chronic obstructive pulmonary diseases and respiratory infections,and systemic diseases such as diabetes.Most inhaled medicines could be cleared rapidly from the lungs and their therapeutic effects are transit.The inhaled medicines with extended pulmonary exposure may not only improve the patient compliance by reducing the frequency of drug administration,but also enhance the clinical benefits to the patients with improved therapeutic outcomes.This article systematically reviews the physical and chemical strategies to extend the pulmonary exposure of the inhaled medicines.It starts with an introduction of various physiological and pathophysiological barriers for designing inhaled medicines with extended lung exposure,which is followed by recent advances in various strategies to overcome these barriers.Finally,the applications of the inhaled medicines with extended lung exposure for the treatment of various diseases and the safety concerns associated to various strategies to extend the pulmonary exposure of the inhaled medicines are summarized.

Hemodynamic Effects of Inhaled Nitric Oxide in Patients with Pulmonary Hypertension.

Twelve patients with pulmonary hypertension (primary pulmonary hypertension in 3 cases, secondary to recurrent pulmonary embolism in 4 cases, chronic obstructive pulmonary disease in 2 cases and complicated with congeni-

Clinical Efficacy Analysis of Tiotropium Bromide Combined with Budesonide and Formoterol Inhalation in Treating COPD

Objective:To analyze the clinical efficacy of tiotropium bromide(TB)combined with budesonide formoterol(BUD/FM)inhalation in treating chronic obstructive pulmonary disease(COPD).Methods:62 COPD patients admitted to the hospital between June 2020 and December 2022 were selected as samples for this study.The patients were divided into a combination group and a conventional group using the random number table method,with 31 cases in each group.The patients in the combination group were treated with TB combined with BUD/FM inhalation,whereas the patients in the conventional group were treated with BUD/FM inhalation only.The treatment efficacy and changes in lung function indicators of both groups were compared.Results:The total efficacy of treatment in the combined group was higher than that in the conventional group,and the difference was statistically significant(P<0.05).Before treatment,there was no difference in pulmonary function indicators between the two groups(P>0.05).After three months of treatment,all lung function indicators of the combined group were higher than those of the conventional group,and the difference was statistically significant(P<0.05).Conclusion:Combining TB with BUD/FM inhalation therapy increases the efficacy of treatment for patients with COPD.Besides,it also improves lung function and leads to a better prognosis.