Efficient management and maintenance of ultrasonic nebulizers to prevent microbial contamination

AIM:To seek the cause of Burkholderia cepacia complex(Bcc) infection outbreak and evaluate the efficacy of new methods for nebulizer maintenance. METHODS: We investigated the annual number of Bcc isolates recovered from clinical samples in our hospital between 1999 and 2013. Swab samples were randomly collected for bacterial culture before patient use from 10 each of the two machine types in August 2001; these included 20 samples from each of the following: Drain tubes, operating water chambers, oscillators, and nebulizing chambers. In addition, 10 samples each of nebulizer solutions before and after use were cultured. For environmental investigation, 10 samples were collected from sinks in the nurse stations of the wards where patients positive for Bcc were hospitalized. Numbers of Bcc isolates were compared before and after introduction of new methods for nebulizer maintenance in October 2001. In addition, randomly amplified polymorphic DNA(RAPD) assay was applied to find the genetic divergence of the Bcc isolates obtained from clinical samples and nebulizers. RESULTS: From January 1999 to December 2013, a total of 487 Bcc isolates were obtained from clinical specimens from 181 patients. Notably, 322(66.1%) Bcc isolates were obtained from clinical specimens from 1999 to 2001, including 244(115 patients) from sputum and 34(11 patients) from blood. During this period, 14 isolates were obtained from nebulizer components. Among these, six were derived from nebulizer drain tubes, five from operating water chambers, and one from the oscillator before patient use, and two from nebulizer solutions after patient use. When Bcc was isolated from the nebulizer solution after patient use, Bcc was simultaneously detected in other parts of the nebulizer. Bcc was not isolated from any nebulizer solution before use. RAPD assays revealed similar DNA profiles in isolates obtained from patients and nebulizers. Investigation revealed damaged diaphragms in many nebulizers. The new maintenance methods for nebulizers, including restriction of the usage period, thorough disinfection, and routine check for diaphragm breakage, remarkably reduced Bcc isolation(165 isolates from patients in 12 years and 0 isolate from nebulizers in periodical sampling). In particular, Bcc has been isolated from blood from only one patient since the new methods were introduced.CONCLUSION: Appropriate maintenance of ultrasonic nebulizers is crucial for preventing Bcc contamination of nebulizers and subsequent respiratory tract and blood infections.

Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria

BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.

Administration of Nebulised Ketamine for Managing Pain in the Intensive Care Unit of Obstetrics and Gynaecology

Introduction: The use of inhaled ketamine to manage a variety of painful conditions has been endorsed by the American College of Emergency Physicians and the American Academy of Emergency Medicine. Nebulized analgesia has multiple benefits, including rapid, effective and titratable analgesic delivery. The aim of our study is to assess the efficacy and safety of intranasal analgesic-dose ketamine compared to multimodal analgesia in patients presenting with acute postoperative pain or headache after a spinal anaesthetic in the intensive care unit of obstetrics and gynaecology. Materials and Methods: This was a prospective descriptive study, with hospital Ethics Committee approval and written informed consent from study participants. We compared the effect of nebulized ketamine and multimodal analgesia postoperatively in 120 patients belonging to the physical status I - II of the American Society of Anesthesiologists, in the intensive care unit of obstetrics and gynaecology, at the Ibn Rochd University Hospital Center in Casablanca from June 2021 to June 2022. Results: We included 120 patients in our study divided into two groups of 60 patients: the average age was 35 years, with extremes ranging from 18 to 45 years, All patients were hospitalized for postoperative care: all women underwent locoregional anaesthesia with a standard dose according to the service protocol (10 mg of bupivacaine, 25γ of fentanyl, 100γ of morphine), where pain was the common denominator. Among these patients, 59 were admitted for management of postpartum haemorrhage, 43 for postoperative monitoring, 15 for post-spinal anaesthesia headache and 3 for pelviperitonitis. The results of the pain assessment 30 minutes after the ketamine nebulization were marked by a request for analgesia in 12 patients, which is 20% of group A, including 5 patients, whose visual analogue scale (VAS) on admission was between 5 and 7, and 7 patients whose VAS at admission was ≥8;all these patients received a second dose of ketamine by nebulization;the evaluation 30 min after the second dose was marked by a request for analgesia in 4 patients, which is 7% of Group A;in all these patients the VAS at admission was ≥8. Of the total number of patients of Group A, only 4 received morphine when they were requested for analgesia after the second dose of nebulized ketamine. Conclusion: The primary outcome of nebulized ketamine use is a significant reduction in VAS pain score. We believe that nebulized ketamine has a potential effect of reducing pain in the intensive care unit of obstetrics and gynaecology;this may be an additional analgesic modality for clinicians to provide rapid, effective and non-invasive pain relief.

雾化吸入改善鼻咽癌放疗后咽鼓管功能

鼻咽癌以放射治疗为主,副作用是影响咽鼓管功能,常合并有分泌性中耳炎,即使未合并分泌性中耳炎的照射耳,其鼓室导抗图峰压值在放疗前、后也呈明显波动性变化。

Inhalation therapy for pulmonary fibrosis:chemical medicines and herbal medicines

Pulmonary fibrosis(PF)is a chronic,progressive,and irreversible pulmonary interstitial disease with unclear pathogenesis.Currently,there are few treatment options for managing PF.Inhalation therapy,as a routine treatment for respiratory diseases,is being used to study the treatment of PF.Some herbal medicines and their active ingredients have been reported to have anti-PF effects.This review aims to provide an overview of the latest developments in inhalation therapy,focusing on the utilization of chemical medicines and herbal medicines for the treatment of PF in both clinical practice and basic research.The inhalation of chemical drugs such as pirfenidone,nintedanib,N-acetylcysteine,and interferon-γhas been shown to demonstrate anti-PF effects.Additionally,the inhalation of various natural products derived from herbal medicines,encompassing polyphenols,alkaloids,flavonoids,saponins,terpenoids,and herbal extracts,contributes to the therapeutic management of PF through diverse mechanisms.The inhalation of both chemical and herbal medicines presents promising advantages in the treatment of PF.Further clinical trials are required to investigate the effectiveness,safety,and mechanism of action of inhalation therapy utilizing natural products derived from herbal medicines.

The Effect of Nebulized Budesonide Inhalation in Treating Children with Asthma and its Influence on Immune Indexes

Objective:To explore and analyze the effect of nebulized budesonide inhalation on children with asthma and its influence on immune indexes.Methods:300 children who were with asthma admitted to the Pediatric Respiratory Department of our hospital from January 2021 to January 2023 were selected as the research subjects.The patients were divided into a nebulization group(n=150)and a reference group(n=150)by drawing lots.The nebulization group received routine treatment along with budesonide nebulization inhalation therapy,while the reference group only received routine treatment.The treatment effect,the immune indicators,the time taken for the disappearance of symptoms,and the pulmonary function indicators of both groups were compared.Results:The total efficacy of treatment received in the nebulization group was significantly higher than that in the reference group(P<0.05).Before treatment,there was no statistically significant difference in the CD4^(+),CD8^(+),CD4^(+)/CD8^(+),between the two groups(P>0.05);after treatment,the nebulization group’s CD4^(+),CD8^(+),CD4^(+)/CD8^(+)and other immune indicators were significantly better than the reference group(P<0.05).The time taken for the disappearance of symptoms like wheezing,coughing,crackles,shortness of breath,and other symptoms in the nebulization group was significantly shorter than in the reference group(P<0.05).Before treatment,there was no statistically significant difference in the pulmonary function indexes such as FEV1,PEF,and FVC between the two groups(P>0.05);after treatment,the pulmonary function indexes of the patients in the nebulization group were significantly better than those in the reference group(P<0.05).Conclusion:Nebulized budesonide inhalation therapy has shown significant efficacy in the treatment of pediatric asthma,with notable improvements in immune indicators.Therefore,it is worthy of recommendation and further promotion.

Droplet generation due to two health care procedures

Preliminary experiments are carried out to characterize the droplets generated in two aerosol-generating health care procedures,i.e.taking nasopharyngeal aspirates（NPA）and nebulizer therapy.Glass slides and water-sensitive paper（WSP）are used to collect large droplets when taking NPA.Droplet stain-marks on glass slides are counted under a microscope,and then a size analysis is performed.During nebulizer therapy dust monitors are used to detect small droplets and droplet nuclei at different positions around the nebulizer and in the room.From the preliminary results it is found that taking NPA can stimulate coughing and generate large droplets.Nebulizers can generate more than tens of millions fine droplets ranging from 0.3 to 20 μm per minute,a large volume of which can escape from the holes on the nebulizer＇s facemask and disperse in the whole room.Droplets coagulate on the inner surface of the mask and the volunteer＇s face,suggesting a great possibility of drug solution contamination by patients＇ secretion during nebulizer therapy.

Practical,regulatory and clinical considerations for development of inhalation drug products

The formulation and device collectively constitute an inhalation drug product.Development of inhaled drugs must consider the compatibility between formulation and device in order to achieve the intended pharmaceutical performance and usability of the product to improve patient compliance with treatment instruction.From the points of formulation,device and patient use,this article summarizes the inhalation drugs,including pressurized metered dose inhaler(pMDI),dry powder inhaler(DPI),and nebulizer that are currently available in the US and UK markets.It also discusses the practical considerations for the development of inhalers and provides an update on the corresponding regulations of the FDA(U.S.Food and Drug Administration)and the EMA(European Medicines Agency).

Inhalation properties of water-soluble drug loaded liposomes atomized by nebulizer

The pulmonary route presents several advantages in designing drug delivery systems in both systemic and topical administration.The use of particulate carriers is an attractive method for designing pulmonary drug delivery systems,because such carriers could control drug release and selective drug targeting when the carriers reach the target site in the lung.The prevention of local irritation,reduced drug toxicity,and improved drug stability are also preferable results of utilizing such carrier systems.Among a number of particulate carriers,liposomes have an advantage in safety,because they consist of phospholipids,which are bio-components.

Ultrasonic Nebulizer Assisted LIBS: a Promising Metal Elements Detection Method for Aqueous Sample Analysis

A newly developed approach for trace metal elements detection for aqueous samples analysis is presented in this paper. The idea of this approach is to improve ablation efficiency by transforming the liquid sample into a dense cloud of droplets using an ultrasonic nebulizer. The resulting droplets are then subjected to analysis by laser induced breakdown spectroscopy （LIBS）. A purpose-built ultrasonic nebulizer assisted LIBS （UN-LIBS） system has been applied to the analysis of aqueous samples at trace levels of concentration. Experimental investigations of solution samples were carried out with various dissolved trace metal elements （Mn, Zn, Cu, Pb, Fe, Mg and Na） using this approach. The characteristics of UN-LIBS signal of the elements were investigated regarding the lifetime and S/B ratio and the calibration curves for trace metal elements analyses. The obtained LODs are comparable or much better than the LODS of the reported signal enhancement approaches when the laser pulse energy was as low as 30 mJ. The good linearity of calibration curves and the low LODs shows the potential ability of this method for metal elements analysis application. The density of the electrons was calculated by measuring the Stark width of the line of Ha. The possible mechanism of the LIBS signal enhancement of this approach was briefly discussed.

Ultrasonic Nebulization Extraction Coupled with Gas Chromatography-Mass Spectrometry for Analysis of Volatile Components in Traditional Chinese Patent Medicine

The ultrasonic nebulization extraction（UNE） was developed and applied to the extraction of volatile components from traditional Chinese patent medicine Xiaoyao Pills. Several parameters of ultrasonic nebulization extraction including the sample particle size, solvent volume, extraction time and ultrasonic power were studied and selected. As a result, 2.4 g of sample with particle size of 80 mesh was extracted with 15 mL of n-hexane for 20 min at an ultrasonic power of 35 W. The volatile components were analyzed by gas chromatography-mass spectrometry （GC-MS） under the optimal conditions and 57 compounds were identified. The precision, repeatability and stability of the proposed method were also studied. Compared with ultrasonic-assisted extraction（UAE） and hydrodistillation（HD） extraction, the proposed method is more efficient, faster and easier to be operated at room temperature with smaller sample and energy consumption. It is suggested that the ultrasonic nebulization extraction can be used as a novel alternative method for the extraction of volatile components from traditional Chinese patent medicine.

Application of Magnetic Particle Imaging to Pulmonary Imaging Using Nebulized Magnetic Nanoparticles

Purpose: To investigate the feasibility of applying magnetic particle imaging (MPI) to pulmonary imaging using nebulized magnetic nanoparticles (MNPs) and to quantify the mucociliary clearance in the lung, using small animal experiments. Materials and Methods: Intrapulmonary administration of MNPs was performed in seven-week-old male ICR (Institute of Cancer Research) mice (n = 8) using a nebulized microsprayer connected to a high-pressure syringe containing 50 μL of MNPs (500 mM Resovist&reg;). We imaged the lungs using our MPI scanner 2.5 hours, 1 day, 3 days, and 7 days after the intrapulmonary administration of MNPs. The average MPI value was calculated by drawing a region of interest (ROI) on the lungs by taking the threshold value for extracting the contour as 20% of the maximum MPI value within the ROI. The MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. Mice were sacrificed immediately after the last MPI and X-ray CT studies on day 7, and 5 lobes of the lung in each mouse were extracted to confirm the accumulation of iron using Berlin blue staining. Results: We could visualize the distribution of MNPs in the lungs as positive contrast using MPI with use of nebulized MNPs. The presence of iron in the lung was confirmed by Berlin blue staining. The average MPI value decreased with time and tended to saturate. The clearance rate was calculated to be 0.505 day&minus;1 from the time course of the average MPI value in the lungs. Conclusion: Our preliminary results suggest that MPI can be applied to pulmonary imaging by nebulizing MNPs and can be useful for quantifying the mucociliary clearance in the lung.

From bronchiolitis guideline to practice: A critical care perspective

Acute viral bronchiolitis is a leading cause of admission to pediatric intensive care units, but research on the care of these critically ill infants has been limited. Pathology of viral bronchiolitis revealed respiratory obstruction due to intraluminal debris and edema of the airways and vasculature. This and clinical evidence suggest that airway clearance interventions such as hypertonic saline nebulizers and pulmonary toilet devices may be of benefit, particularly in situations of atelectasis associated with bronchiolitis. Research to distinguish an underlying asthma predisposition in wheezing infants with viral bronchiolitis may one day lead to guidance on when to trial bronchodilator therapy. Considering the paucity of critical care research in pediatric viral bronchiolitis, intensive care practitioners must substantially rely on individualization of therapies based on bedside clinical assessments. However, with the introduction of new diagnostic and respiratory technologies, our ability to support critically ill infants with acute viral bronchiolitis will continue to advance.

Nebulized Mycobacterium vaccae protects against asthma by attenuating the imbalance of IRF4/IRF8 expression in dendritic cells

Objective:To assess the effects of nebulized inhaled Mycobacterium vaccae on allergic airway inflammation,airway hyperresponsiveness,and Th1/Th2 cell imbalance in mice with ovalbumin(OVA)-induced asthma.Methods:Mice received OVA sensitization and challenge for establishment of the asthmatic model.For intervention,mice received Mycobacterium vaccae nebulization once every other day from the first day of sensitization to the day before challenge.After challenge,pulmonary histological analysis and airway responsiveness measurement were performed.In addition,Th1/Th2 cytokines and OVA-specific IgE levels in bronchoalveolar lavage fluid were measured by ELISA.Th1/Th2 subset ratios and the expression of interferon-regulatory factor 4(IRF4),IRF8 and Toll-like receptor 4(TLR4)in dendritic cells were evaluated by flow cytometry.Results:Severe inflammatory infiltration and airway hyperresponsiveness were observed in OVA-induced asthmatic mice.Asthmatic mice showed higher Th2 cytokine concentration and increased percentage of Th2 cells,along with lower Th1 cytokine concentration and reduced percentage of Th1 cells compared with the normal control.Moreover,an imbalance of IRF4^(+)and IRF8^(+)in dendritic cells was found in asthmatic mice.Nebulized inhaled Mycobacterium vaccae reduced airway hyperresponsiveness and inflammation in OVA-induced asthmatic mice.In addition,nebulized inhaled Mycobacterium vaccae enhanced TLR4 and IRF8 expression,and alleviated the imbalance of Th1/Th2 as well as IRF4^(+)and IRF8^(+)in dendritic cells.Conclusions:Nebulized inhaled Mycobacterium vaccae protects against asthma by alleviating the imbalance of Th1/Th2 and IRF4/IRF8 in OVA-induced asthmatic mice.

Synthesis of aligned carbon nanotube with straight-chained alkanes by nebulization method

Aligned carbon nanotubes(CNTs)were synthesized by nebulized spray pyrolysis of solutions of organometallics in carbon precursor solvents.Four types of straight-chained alkanes including n-pentane,n-hexane,n-heptane and n-octane were used as precursor solvents for synthesis of aligned CNTs.The results from scanning electron microscopy,transmission electron microscopy and Raman spectroscopy show that the CNTs obtained from them have different diameters and degrees of graphitization. It is found that the n-heptane is the most suitable for the growth of aligned CNTs with high quality and yield.The thermodynamic properties of precursory carbon sources such as boiling point and formation enthalpy are considered to play a decisive role in the synthesis of CNTs.It will be very helpful for the controllable preparation of aligned CNTs at relatively low cost.

Advances in Piezoelectric Atomizers

Piezoelectric atomizers exhibit the advantages of structural simplicity,portability,low energy consumption,low production costs,and good atomization.They have been extensively used in various fields,including inhalation therapy,inkjet printing,and spray cooling.Here,the research of piezoelectric atomizers is first summarized from the perspectives of theoretical investigation and applications.Subsequently,the existing investigation and applications on piezoelectric atomizers are classified in terms of their functionalities.The functions of inkjet printing,spray cooling,and inhalation therapy are described in detail.Finally,the future trends in this field are analyzed.It is indicated that the vibrating-mesh atomizer has a promising prospect in the market,signaling strong demand especially in upgaraded consumption and medical scenarios.

Evaluation of Improved Ultrasonic Nebulizer for Miniature Simultaneous Microwave Plasma Torch Spectrometer

A new automatic sample solution introduction system for miniature simultaneous microwave plasma torch（MPT） atomic emission spectrometer was developed. The operating parameters were optimized. The detection limits of the spectrometer with an ultrasonic nebulizer for Ag, Al, Ba, Ca, Cr, Cu, Fe, Mg, Mn, Sr, and V are 5-10 times lower than those obtained with a pneumatic nebulizer and are also lower than those obtained by a Model JX-lOlO MPT spectrometer. Two practical samples were analyzed to test the reliability and sensitivity of the system.

EVALUATON OF MICROWAVE PLASMA TORCH FOR ATOMIC FLUORESCENCE SPECTROMETRY WITH AN ULTRASONIC NEBULIZATION SAMPLE INTRODUCTION SYSTEM

In this paper, a new MPT(microwave plasma torch) device has been used as a atomizer for atomic fluorescence spectrometry. Spme elements, such as Zn, Cd, Hg, Pb, As, Co, Mg, Cu, Ag, Mn, Fe have been investigated in detail.

Inhalation Devices and Pulmonary Drug Delivery

Inhaled drug delivery is mainly used to treat pulmonary airway disorders by transporting the drug directly to its targeted location for action.This decreases the dose required to exert a therapeutic effect and minimizes any potential adverse effects.Direct drug delivery to air passages facilitates a faster onset of action;it also minimizes irritation to the stomach,which frequently occurs with oral medications,and prevents the exposure of drugs to pre-systemic metabolism that takes place in the intestine and liver.In addition to that,the lung is regarded as a route for transporting medications throughout the entire body's blood circulation.The type of medication and the device used to deliver it are both important elements in carrying the drug to its target in the lungs.Different types of inhalation methods are used in inhaled delivery.They differ in the dose delivered,inhalation technique,and other factors.This paper will discuss these factors in more detail.

Aerosol therapy during mechanical ventilation in intensive care units: A questionnaire-based survey of 2203 ICU medical staffin China

Background:To describe the current status of aerosol therapy during mechanical ventilation(MV)and the prac-tice,knowledge,and beliefs about aerosol therapy in physicians working in the intensive care unit(ICU)in China.Methods:A physician self-administered questionnaire-based cross-sectional survey was carried out from January 2019 to July 2019.An electronic questionnaire was designed,and physicians who worked regularly in ICUs across several hospitals were contacted through WeChat.Answers to all questions and the general characteristics of physicians who answered the questionnaire were collected and analyzed.Results:A total of 2203 medical staffwho regularly worked in the ICUs completed this questionnaire(9.0%missing data);87.7%of the participants were doctors.Most respondents claimed that they often administered aerosolization therapy.Ultrasonic atomizer(50.7%)and jet nebulizer(48.6%)were the most commonly used atomization devices.Bronchodilators(65.8%)and steroids(66.3%)were the most frequently aerosolized drugs during MV.During nebulization,ventilator settings were never changed by 32.7%of respondents.Only 49.1%of respondents knew the appropriate place for a nebulizer.Further,62.7%of respondents using heated humidifiers reported turning them offduring nebulization.Specific knowledge about droplet size and nebulization yield was poor.Respondents from tertiary hospitals and those with higher technical title or work experience tended to have better accuracy than those from primary hospitals or with lower technical titles(P<0.050).Conclusions:Aerosol therapy was commonly used during MV,and the most frequent drugs were bronchodila-tors and steroids.Scientific knowledge about the optimal implementation of aerosol therapy during MV seemed deficient.