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Simple Summary: In people with respiratory diseases, treatment through inhalation is widely recommended and standardized. In veterinary medicine, few studies have investigated the effectiveness of treatments by the inhalation route. Among other factors, tolerance to the method used to administer the aerosol is key to its therapeutic success. This study has standardized a cough provocation test in cats using nebulized capsaicin at increasing concentrations and, through its use, compared the effectiveness and tolerance of the four methods most used in veterinary hospitals to administer oxygen and nebulized solutions. The results provide a cough challenge protocol that can be used in future studies for diagnostic and therapeutic purposes in cats with respiratory diseases. The protocol established that nebulization with a facial mask is the most effective, and nebulization in a chamber is the best tolerated. The flow-by method is a good alternative, but the hood method has poor cat tolerance. Successful aerosol therapy might rely more heavily on proper drug delivery than on the effectiveness of the medication. This study compared four techniques for nebulization delivery in cats. Tolerance rate (TR) was subjectively evaluated (1–3). Increasing capsaicin concentrations were nebulized for objective evaluation of efficiency. The positive response (PR) was considered when more than five coughs were induced. The following delivery methods were tested: flow-by (FB); face mask (FM); plastic-covered Elizabethan collar (EC); and plexiglass chamber (PC). The number of PRs (NPR) and the concentration of capsaicin that induced a PR (CCP) were statistically compared (p < 0.05). The PC method was the best tolerated (TR = 3.0 ± 0.0), followed by the FB (2.7 ± 0.5) and FM (2.6 ± 0.5). The EC was very stressful, and the test had to be suspended in four out of nine cats. The lowest CCP was found with the FM (91.8 ± 157.2 µM), followed by the FB (166.7 ± 190.9 µM), PC (242.6 ± 244.8 µM), and EC (350.0 ± 225.7 µM), with significant differences only between the FM and EC (p = 0.02). The highest NPR (8) corresponded to the FM, followed by the FB (7), the PC (5), and the EC (3), with significant differences between the FM and EC (p = 0.016). In conclusion, the capsaicin cough test induces reproducible and quantifiable cat responses. The FM is the most efficient for nebulization delivery, offering good compliance and the best quantitative results. FB nebulization is less efficient but may be practical if the FM is not tolerated. PC offers minor efficiency but may be useful for very stressed or aggressive cats. The EC presents low efficiency and compliance. [ABSTRACT FROM AUTHOR]

High flow oxygen (HFO) therapy is a well-established treatment in respiratory disease. Concurrent aerosol delivery can greatly expediate their recovery. The aim of this work was to complete a comprehensive characterisation of one such HFO therapy system, the Airvo2TM, used in combination with the Aerogen SoloTM vibrating mesh nebuliser. Representative adult, infant, and paediatric head models were connected to a breathing simulator via a collection filter placed at the level of the trachea. A tracheostomy interface and nasal cannulas were used to deliver the aerosol. Cannula size and gas flow rate were varied across the full operating range recommended by the manufacturer. The tracheal and emitted doses were quantified via UV-spectrophotometry. The aerosol droplet diameter at the exit of the nares and tracheal interface was measured via cascade impaction. High gas flow rates resulted in low emitted and tracheal doses (%). Nasal cannula size had no significant effect on the tracheal dose (%) available in infant and paediatric models. Higher gas flow rates resulted in smaller aerosol droplets at the exit of the nares and tracheostomy interface. Gas flow rate was found to be the primary parameter affecting aerosol delivery. Thus, gas flow rates should be kept low and where possible, delivered using larger nasal cannulas to maximise aerosol delivery. [ABSTRACT FROM AUTHOR]

High-flow nasal oxygen therapy is being increasingly adopted in intensive and home care settings. The concurrent delivery of aerosolised therapeutics allows for the targeted treatment of respiratory illnesses. This study examined in-line aerosol therapy via a nasal cannula to simulated adult and paediatric models with healthy, obstructive and restrictive lung types. The Aerogen Solo vibrating mesh nebuliser was used in combination with the InspiredTM O2FLO high-flow therapy system. Representative adult and paediatric head models were connected to a breathing simulator, which replicated several different states of lung health. The aerosol delivery was quantified at the tracheal level using UV-spectrophotometry. Testing was performed at a range of supplemental gas flow rates applicable to both models. Positive end-expiratory pressure was measured pre-, during and post-nebulisation. The increases in supplemental gas flow rates resulted in a decrease in aerosol delivery, irrespective of lung health. Large tidal volumes and extended inspiratory phases were associated with the greatest aerosol delivery. Gas flow to inspiratory flow ratios of 0.29–0.5 were found to be optimum for aerosol delivery. To enhance aerosol delivery to patients receiving high-flow nasal oxygen therapy, respiratory therapists should keep supplemental gas-flow rates below the inspiratory flow of the patient. [ABSTRACT FROM AUTHOR]

Simple Summary: Coughing is common in dogs with tracheal collapse (TC). Inhaled corticosteroids are the standard of care in humans, but their use in dogs is less widespread than oral corticosteroids. This study compared the efficacy, adherence, and tolerance to treatment of inhaled versus oral corticosteroids in 30 dogs with cough and TC, randomized to each treatment. Responses were monitored in the hospital (enrolment and weeks 2 and 4) and at home (weeks 1 to 4) using a semiquantitative clinical scale based on four key clinical parameters (respiratory distress, cough episodes, cough frequency, tracheal sensitivity). Both treatments provided comparable clinical improvements, with significantly greater improvements at the end in the fluticasone group. Adherence and tolerance were equivalent, but thirst and the frequency of urination increased in those taking prednisone. In conclusion, inhaled fluticasone is effective in controlling cough in dogs with TC without side effects, which encourages its use to be extended compared to prednisone. Coughing is common in dogs with tracheal collapse (TC). The use of inhaled corticosteroids is less widespread than oral ones. This study aims to compare the effects of oral and inhaled corticosteroids in dogs with cough and TC. Thirty dogs were prospectively included and randomized to the prednisone oral group (OG, 14) or fluticasone inhaled group (IG, 16). A clinical score (CS) based on four clinical parameters (respiratory distress, cough episodes, cough frequency, tracheal sensitivity) was monitored at the hospital (enrolment and weeks 2 and 4). Water intake, urination habits, and adherence and tolerance to treatments were monitored weekly. Significant improvements in clinical parameters were identified in both groups throughout the study. Between-group (OG–IG) comparisons revealed no significant differences, indicating equivalent improvement. At the study's endpoint, the IG dogs had a significantly lower CS (5.69 ± 0.79) than OG dogs (6.43 ± 1.02, p < 0.05). Adherence and tolerance were comparable. From weeks 2 to 4, OG dogs were significantly thirstier and urinated more frequently than IG dogs. In conclusion, fluticasone provided good tolerability and efficacy in controlling cough in dogs with TC, and they showed a lower incidence of signs of hypercortisolism compared to prednisone. These data encourage the use of inhaled fluticasone in dogs with cough and TC. [ABSTRACT FROM AUTHOR]

The second-line antileishmanial compound pentamidine is administered intramuscularly or, preferably, by intravenous infusion, with its use limited by severe adverse effects, including diabetes, severe hypoglycemia, myocarditis and renal toxicity. We sought to test the potential of phospholipid vesicles to improve the patient compliance and efficacy of this drug for the treatment of leishmaniasis by means of aerosol therapy. The targeting to macrophages of pentamidine-loaded liposomes coated with chondroitin sulfate or heparin increased about twofold (up to ca. 90%) relative to noncoated liposomes. The encapsulation of pentamidine in liposomes ameliorated its activity on the amastigote and promastigote forms of Leishmania infantum and Leishmania pifanoi, and it significantly reduced cytotoxicity on human umbilical endothelial cells, for which the concentration inhibiting 50% of cell viability was 144.2 ± 12.7 µM for pentamidine-containing heparin-coated liposomes vs. 59.3 ± 4.9 µM for free pentamidine. The deposition of liposome dispersions after nebulization was evaluated with the Next Generation Impactor, which mimics human airways. Approximately 53% of total initial pentamidine in solution reached the deeper stages of the impactor, with a median aerodynamic diameter of ~2.8 µm, supporting a partial deposition on the lung alveoli. Upon loading pentamidine in phospholipid vesicles, its deposition in the deeper stages significantly increased up to ~68%, and the median aerodynamic diameter decreased to a range between 1.4 and 1.8 µm, suggesting a better aptitude to reach the deeper lung airways in higher amounts. In all, nebulization of liposome-encapsulated pentamidine improved the bioavailability of this neglected drug by a patient-friendly delivery route amenable to self-administration, paving the way for the treatment of leishmaniasis and other infections where pentamidine is active. [ABSTRACT FROM AUTHOR]

Aerosol therapy is used to deliver medical therapeutics directly to the airways to treat respiratory conditions. A potential consequence of this form of treatment is the release of fugitive aerosols, both patient derived and medical, into the environment and the subsequent exposure of caregivers and bystanders to potential viral infections. This study examined the release of these fugitive aerosols during a standard aerosol therapy to a simulated adult patient. An aerosol holding chamber and mouthpiece were connected to a representative head model and breathing simulator. A combination of laser and Schlieren imaging was used to non-invasively visualize the release and dispersion of fugitive aerosol particles. Time-varying aerosol particle number concentrations and size distributions were measured with optical particle sizers at clinically relevant positions to the simulated patient. The influence of breathing pattern, normal and distressed, supplemental air flow, at 0.2 and 6 LPM, and the addition of a bacterial filter to the exhalation port of the mouthpiece were assessed. Images showed large quantities of fugitive aerosols emitted from the unfiltered mouthpiece. The images and particle counter data show that the addition of a bacterial filter limited the release of these fugitive aerosols, with the peak fugitive aerosol concentrations decreasing by 47.3-83.3%, depending on distance from the simulated patient. The addition of a bacterial filter to the mouthpiece significantly reduces the levels of fugitive aerosols emitted during a simulated aerosol therapy, p= .05, and would greatly aid in reducing healthcare worker and bystander exposure to potentially harmful fugitive aerosols. [ABSTRACT FROM AUTHOR]

Conventional inhaler devices have a low efficacy in targeting small airways. Smart nebulizers can be used to increase deposition to small airways by adjusting the flow and depth of each inhalation based on patients 'individual inspiratory capacity. We investigated whether targeting of high dose inhaled corticosteroids (ICS) to small airways with a smart nebulizer could reduce exacerbation rate in children with severe asthma (SA). We conducted a retrospective study in children with SA using a smart nebulizer (Akita® Jet nebulizer) for the administration of high dose ICS in our outpatient clinic at the Erasmus MC — Sophia Children's Hospital. Clinical data before and after start of treatment were collected. The primary outcome was exacerbation rate, defined as: number of asthma exacerbations for which oral corticosteroid courses (OCS) were prescribed. The exacerbation rate 1 year before treatment was compared with the exacerbation rate 1 year after start of treatment. Secondary outcomes were changes in spirometry parameters, hospital admissions and medication use. Data on OCS use was available for 28/31 patients. Median number of asthma exacerbations requiring OCS courses 1 year before decreased from 2 (interquartile range(IQR) 2) to 0.5 (IQR 3) 1 year after treatment (p = 0.021). Hospital admission decreased from 1 (IQR 3) to 0 (IQR 1)(p = 0.028). FEV1, FEF25-75 and FEF75 were not significantly improved after one year of treatment with the smart nebulizer (p = 0.191; p = 0.248; p = 0.572). Targeting small airways with high dose ICS using a smart nebulizer resulted in a significant reduction in exacerbations requiring OCS after one year of treatment. [ABSTRACT FROM AUTHOR]

Background & Problems: Aerosol therapy is increasingly used in pulmonary critical care and in patients with respiratory disease. However, improper application of the aerosol delivery device will decrease the therapeutic effect as well as increase the incidence of pulmonary infection. An initial assessment conducted in our intensive care unit found an accuracy rate for nursing staff aerosol-therapy execution of only 55.9%. Possible reasons identified for this low rate included lack of learning experience and resources, lack of related standard operating procedures, lack of related performance assessments, complicated / unfamiliar device assembly procedure, diffuse storage of device components, and a lack of illustrations. Purpose: This project was developed to increase the accuracy rate of performing aerosol therapy to over 90% in our intensive care unit. Methods: We designed diverse learning materials using the model of motivation, developed an evaluation system, simplified the assembly of components based on evidence-based research, improved the storage situation, and added reference illustrations. Result: The accuracy rate in aerosol therapy execution for our nursing staff increased from 55.9% to 95.0% after the intervention. Conclusions: This project used the model of motivation to develop the teaching materials. By using diverse teaching methods, including both in-person classes and online interactive quizzes, we realized high learning satisfaction and efficacy. Along with simplifying equipment handling, improving the working environment, enhancing nurses' aerosol therapy techniques, establishing standard operating procedure guidelines, and adding an evaluation system, we standardized the entire procedure for potential promotion to other intensive care units. [ABSTRACT FROM AUTHOR]

The main challenge of the health risk assessment of the aerosol transport and deposition to the lower airways is the high computational cost. A standard large-scale airway model needs a week to a month of computational time in a high-performance computing system. Therefore, developing an innovative tool that accurately predicts transport behaviour and reduces computational time is essential. This study aims to develop a novel and innovative machine learning (ML) model to predict particle deposition to the lower airways. The first-ever study uses ML techniques to explore the pulmonary aerosol TD in a digital 17-generation airway model. The ML model uses the computational data for a 17-generation airway model and four standard ML regression models are used to save the computational cost. Random forest (RF), k-nearest neighbour (k-NN), multi-layer perceptron (MLP) and Gaussian process regression (GPR) techniques are used to develop the ML models. The MLP regression model displays more accurate estimates than other ML models. Finally, a prediction model is developed, and the results are significantly closer to the measured values. The prediction model predicts the deposition efficiency (DE) for different particle sizes and flow rates. A comprehensive lobe-specific DE is also predicted for various flow rates. This first-ever aerosol transport prediction model can accurately predict the DE in different regions of the airways in a couple of minutes. This innovative approach and accurate prediction will improve the literature and knowledge of the field. [ABSTRACT FROM AUTHOR]

COVID-19 can cause serious respiratory complications resulting in the need for invasive ventilatory support and concurrent aerosol therapy. Aerosol therapy is considered a high risk procedure for the transmission of patient derived infectious aerosol droplets. Critical-care workers are considered to be at a high risk of inhaling such infectious droplets. The objective of this work was to use noninvasive optical methods to visualize the potential release of aerosol droplets during aerosol therapy in a model of an invasively ventilated adult patient. The noninvasive Schlieren imaging technique was used to visualize the movement of air and aerosol. Three different aerosol delivery devices: (i) a pressurized metered dose inhaler (pMDI), (ii) a compressed air driven jet nebulizer (JN), and (iii) a vibrating mesh nebulizer (VMN), were used to deliver an aerosolized therapeutic at two different positions: (i) on the inspiratory limb at the wye and (ii) on the patient side of the wye, between the wye and endotracheal tube, to a simulated intubated adult patient. Irrespective of position, there was a significant release of air and aerosol from the ventilator circuit during aerosol delivery with the pMDI and the compressed air driven JN. There was no such release when aerosol therapy was delivered with a closed-circuit VMN. Selection of aerosol delivery device is a major determining factor in the release of infectious patient derived bioaerosol from an invasively mechanically ventilated patient receiving aerosol therapy. [ABSTRACT FROM AUTHOR]

In the times of the ongoing COVID-19 pandemic and related cases of coronavirus infection with its complications affecting patients effective ways to relieve these symptoms are being searched. The article presents a review of publications on the effectiveness of inhalation with dry salt aerosol, one of the forms of halotherapy, in relation to the alleviation of symptoms of chronic respiratory diseases which often coincide with symptoms after COVID-19. The results of the analyzed studies show the effectiveness of halotherapy in the indicated form in relieving the symptoms of respiratory diseases such as dyspnoea or cough. More and more popular in Poland generally accessible inhalatoria with a dry salt aerosol can be considered as part of rehabilitation for patients after COVID-19. [ABSTRACT FROM AUTHOR]

Aim: To study the effectiveness of complex rehabilitation treatment with using Haloaerosol therapy in cases of children with recurrent respiratory diseases, immediate and long-term results, based on of external respiration function investigation and metabolic status. Materials and Methods: We examined 37 patients aged 7-11 years with recurrent respiratory diseases out the acute period. Before and at the end of the treatment, spirometry was performed, biochemical parameters were analyzed, which determine the state of the lipid peroxidation system and antioxidant protection. Rehabilitation treatment was performed according to two complexes, which included physical therapy and physical physiotherapy. In addition, the second treatment complex included haloaerosol therapy, which involves staying in a haloaerosol environment with a certain (35 mg/m3 - 40 mg/m3) concentration of rock salt aerosol. Results: Rehabilitation treatment based on haloaerosol therapy in children with recurrent respiratory diseases leads to an increase in spirometry tests, reducing the imbalance of the lipid peroxidation system, antioxidant protection. The effectiveness is confirmed in the long-term period, because during the year after treatment the frequency and duration of acute episodes were decreased, the number of days during which the child did not attend school decreases (from 30.35±2.39 to 16.90±1.44 days; p<0.001) too. These changes were less pronounced in the children from comparation group. Conclusions: Children with recurrent respiratory disease need rehabilitation treatment. Preference should be given on complexes with the inclusion of haloaerosol therapy, which have direct affects on the mucous membrane of the respiratory tract and indirect - have reduces of endogenous intoxication manifestations. [ABSTRACT FROM AUTHOR]

Anatomical and physiological changes alter airflow characteristics and aerosol distribution in the developing lung. Correlation between age and aerosol dosimetry is needed, specifically because youth are more susceptible to medication side effects. In this study, we estimate aerosol dosages (particle diameters of 1, 3, and 5 μ m) in a 3 month-old infant, a 6 year-old child, and a 36 year-old adult by performing whole lung subject-specific particle simulations throughout respiration. For 3 μ m diameter particles we estimate total deposition as 88, 73, and 66 % and the conducting versus respiratory deposition ratios as 4.0, 0.5, and 0.4 for the infant, child, and adult, respectively. Due to their lower tidal volumes and functional residual capacities the deposited mass is smaller while the tissue concentrations are larger in the infant and child subjects, compared to the adult. Furthermore, we find that dose cannot be predicted by simply scaling by tidal volumes. These results highlight the need for additional clinical and computational studies that investigate the efficiency of treatment, while optimizing dosage levels in order to alleviate side effects, in youth. [ABSTRACT FROM AUTHOR]

The Saudi Pediatric Pulmonology Association (SPPA) is a subsidiary of the Saudi Thoracic Society (STS), which consists of a group of Saudi experts with well-respected academic and clinical backgrounds in the fields of asthma and other respiratory diseases. The SPPA Expert Panel realized the need to draw up a clear, simple to understand, and easy to use guidance regarding the application of different aerosol therapies in respiratory diseases in children, due to the high prevalence and high economic burden of these diseases in Saudi Arabia. This statement was developed based on the available literature, new evidence, and experts' practice to come up with such consensuses about the usage of different aerosol therapies for the management of respiratory diseases in children (asthma and nonasthma) in different patient settings, including outpatient, emergency room, intensive care unit, and inpatient settings. For this purpose, SPPA has initiated and formed a national committee which consists of experts from concerned specialties (pediatric pulmonology, pediatric emergency, clinical pharmacology, pediatric respiratory therapy, as well as pediatric and neonatal intensive care). These committee members are from different healthcare sectors in Saudi Arabia (Ministry of Health, Ministry of Defence, Ministry of Education, and private healthcare sector). In addition to that, this committee is representing different regions in Saudi Arabia (Eastern, Central, and Western region). The subject was divided into several topics which were then assigned to at least two experts. The authors searched the literature according to their own strategies without central literature review. To achieve consensus, draft reports and recommendations were reviewed and voted on by the whole panel. [ABSTRACT FROM AUTHOR]

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BACKGROUND: Aerosolized drugs are widely used to treat and control a variety of pulmonary diseases. However, there is increasing evidence that patients are unable to use their drug delivery device correctly. The failure of aerosolized treatment is usually the result of poorly communicated instructions. The aim of this investigation was to evaluate the knowledge of health-care providers in the science of aerosol drug delivery (ADD) and assess the impact of further education on their knowledge. MATERIALS AND METHODS: One hundred and seventeen health-care providers attended a 4-hour educational course on ADD science. The course was conducted from June to August 2018 in Jeddah, Riyadh, and Dammam. Pre-course assessment done with a 12-item multiple-choice questionnaire. Post-course assessment was conducted after the end of course in which participants were asked to rate their knowledge of ADD on a scale of 1-10 (before and after the course). RESULTS: Sixty-six health-care providers (physicians, pharmacists, respiratory therapists, and health educators) completed the course. The participants' clinical experience, on average (±standard deviation), was 7.6 ± 7.3 years. Clinical experience favored physicians over other groups. The precourse score for all participants was 3.2 ± 1.9 out of 12 and the postcourse score was 6.97 ± 2.7. There was a significant statistical difference between pre- and postcourse assessment scores (P < 0.05). Differences between the four specialties were insignificant (P = 0.216), without a correlation between clinical experience and preassessment scores (P = 0.202). CONCLUSION: The present data indicate that health-care providers' knowledge of ADD is completely inadequate. There is an urgent need to introduce an ADD educational package in the curricula. An annual competency-based evaluation for health-care providers is critical as well. [ABSTRACT FROM AUTHOR]

Objective: CAD/CAM is based on optical or mechanical scanning of tooth surfaces. The aim of this in vitro study was to investigate the influence of three different scan sprays on the proliferation, viability, and adenylate kinase (ADK) release of human fibroblasts. Method and Materials: Three different scan sprays (ScanDry, ScanSpray Luer Classic, and CEREC Optispray) were tested in vitro to determine their effects on proliferation, viability, and ADK release of human periodontal fibroblasts. A defined amount of the test material was sprayed into 96 multiwell plates, dried, and incubated with fibroblasts. The LIVE/DEAD Viability Assay, a two-color fluorescence-based method, was used to determine the cytotoxic potential (the AlamarBlue Assay for the proliferation rate and the ToxiLight BioAssay for the release of ADK). Results: There were differences between the scan sprays concerning inhibition of the proliferation and viability of fibroblasts. All materials inhibited the fibroblast proliferation and viability compared with the control group (P < .001), and there were also significant differences among the scan spray groups. The scan sprays led to a greater release of ADK, but a significant difference could be found only between ScanSpray Luer Classic and CEREC Optispray (P < .009). Conclusion: The results of this study proved that the scan sprays do not induce a significantly higher ADK release than the control group. The inhibiting effect on the fibroblast proliferation can be attributed to a material-independent phenomenon. Further experiments are necessary to validate the present data. [ABSTRACT FROM AUTHOR]

This article presents real-world experience of the effectiveness of calcipotriol (50 μg/g)/betamethasone dipropionate (0.5 mg/g) (Cal/BD) aerosol foam formulation in three cases of scalp psoriasis, and briefly reviews the literature relating to Cal/BD topical therapy in adults with scalp psoriasis. Patients had long histories of scalp psoriasis and reported negative impacts on their lives (e.g. clothing choices, psychological well-being, employment status). Previous treatments had provided inadequate or only temporary relief. Cal/BD aerosol foam relieved itching in the first few days and was associated with visible improvement of flaky patches on the scalp at the end of the recommended 4-week treatment period. Controlled clinical trials in patients with scalp psoriasis are rare. There have been several trials in adults with scalp psoriasis involving Cal/BD gel or suspension scalp formulations, which have proven more effective and well tolerated compared with the individual components or vehicle alone. The Cal/BD aerosol formulation has enhanced skin penetration and higher bioavailability compared with the older formulations; studies show improved efficacy with Cal/BD aerosol foam, compared with older formulations, in patients with plaque psoriasis. The present cases confirm the benefits of Cal/BD aerosol foam in adults with scalp psoriasis, treated in real-world settings. [ABSTRACT FROM AUTHOR]

Smoke inhalation injury (SII) is a major morbidity and cause of mortality in patients with burns. Damage caused by inhalation of thermal or chemical irritants, including toxic fumes and chemicals, leads to respiratory cilia and epithelial cell injuries, which turn to severe bronchospasm and alveolar damage and results in acute respiratory distress syndrome. Respiratory management plays a vital role in the treatment of SII. In this review, we provide an overview of SII with emphasis on respiratory management, including aerosol therapy, bronchial hygiene therapy, advanced ventilation modes, and heated humidified high-flow nasal cannula. In summary, the information may be helpful for further improvements in outcomes. [ABSTRACT FROM AUTHOR]

Patients on mechanical ventilation need aerosolized therapy through an endotracheal tube and a ventilated circuit. In the critical care setting, patients received inhalation therapy in the form of wet aerosols via nebulizers or pressurized metered-dose inhalers (pMDI). However, an ineffective and inconsistent aerosol delivery due to drug loss in a ventilated system is a major problem for aerosolized therapy in these patients. Dry powder inhaler (DPI) has been a promising inhaler that has no 'rain-out' of wet aerosol on the circuit. This review will summarize the state of the art for aerosol delivery to mechanically ventilated patients with special emphasis on emerging opportunities for dry powder aerosols. Beside inhaler itself, drug delivery to mechanically ventilated patients depends on the ventilator circuit-related factors such as the pattern of inspiration, the volume of inhalation and the volumetric flow rate. Patients on mechanical ventilation differ from patients who can breathe by themselves (unassisted spontaneous breathing) or patient who receive direct-to-mouth inhalation. Drug delivery during mechanical ventilation is affected by the factors that directly related to ventilator circuit that controls a patient's breathing. Thus, these ventilator circuit-related factors that play an important role in drug delivery efficiency will be discussed in this review. [ABSTRACT FROM AUTHOR]

Nicotine is a highly addictive principal component of both tobacco and electronic cigarette that is readily absorbed in blood. Nicotinecontaining electronic cigarettes are promoted as a safe alternative to cigarette smoking. However, the isolated effects of inhaled nicotine are largely unknown. Here we report a novel rat model of aerosolized nicotine with a particle size (~1 μm) in the respirable diameter range. Acute nicotine inhalation caused increased pulmonary edema and lung injury as measured by enhanced bronchoalveolar lavage fluid protein, IgM, lung wet-to-dry weight ratio, and high-mobility group box 1 (HMGB1) protein and decreased lung E-cadherin protein. Immunohistochemical analysis revealed congested blood vessels and increased neutrophil infiltration. Lung myeloperoxidase mRNA and protein increased in the nicotine-exposed rats. Complete blood counts also showed an increase in neutrophils, white blood cells, eosinophils, and basophils. Arterial blood gas measurements showed an increase in lactate. Lungs of nicotine-inhaling animals revealed increased mRNA levels of IL-1A and CXCL1. There was also an increase in IL-1 protein. In in vitro air-liquid interface cultures of airway epithelial cells, there was a dose dependent increase in HMGB1 release with nicotine treatment. Air-liquid cultures exposed to nicotine also resulted in a dose-dependent loss of barrier as measured by transepithelial electrical resistance and a decrease in E-cadherin expression. Nicotine also caused a dose-dependent increase in epithelial cell death and an increase in caspase-3/7 activities. These results show that the nicotine content of electronic cigarettes may have adverse pulmonary and systemic effects. [ABSTRACT FROM AUTHOR]

Much evidence supports the use of non-invasive ventilation (NIV) in patients who have acute and chronic respiratory failure and aerosolized medications are increasingly used in this patient population. Successful application of aerosol therapy during NIV depends on the effectiveness of the drug deposition in the lungs. Previous evidence showed that many factors impact aerosol delivery to patients receiving NIV. Those factors include mode of ventilation, ventilator parameters, type of ventilator circuit, the position of the aerosol device, the location of leak port, type of exhalation valve, humidity, enhanced condensational growth, type of aerosol device, and interface as well as delivery technique. The purpose of this paper is to review the available evidence related to aerosol therapy during NIV and provide recommendations to optimize aerosol drug delivery to patients receiving NIV. [ABSTRACT FROM AUTHOR]

New therapeutic strategies are needed to treat drug resistant tuberculosis (TB) and to improve treatment for drug sensitive TB. Pyrazinamide (PZA) is a critical component of current first-line TB therapy. However, the rise in PZA-resistant TB cases jeopardizes the future utility of PZA. To address this problem, we used the guinea pig model of TB and tested the efficacy of an inhaled dry powder combination, referred to as yrazinoic acid/ester ry owder (PDP), which is comprised of pyrazinoic acid (POA), the active moiety of PZA, and pyrazinoic acid ester (PAE), which is a PZA analog. Both POA and PAE have the advantage of being able to act on PZA-resistant Mycobacterium tuberculosis. When used in combination with oral rifampicin (R), inhaled PDP had striking effects on tissue pathology. Effects were observed in lungs, the site of delivery, but also in the spleen and liver indicating both local and systemic effects of inhaled PDP. Tissue granulomas that harbor M. tuberculosis in a persistent state are a hallmark of TB and they pose a challenge for therapy. Compared to other treatments, which preferentially cleared non-necrotic granulomas, R+PDP reduced necrotic granulomas more effectively. The increased ability of R+PDP to act on more recalcitrant necrotic granulomas suggests a novel mechanism of action. The results presented in this report reveal the potential for developing therapies involving POA that are optimized to target necrotic as well as non-necrotic granulomas as a means of achieving more complete sterilization of M. tuberculosis bacilli and preventing disease relapse when therapy ends. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To describe the successful management of a dog with acute respiratory distress syndrome secondary to inhalant toxin exposure. Case summary: An 8‐year‐old male neutered Greyhound was referred with severe respiratory distress 56 hours after exposure to an aerosol toxicant. The patient developed respiratory difficulties requiring veterinary attention within 12 hours of initial exposure. Treatment at the referral hospital included mechanical ventilation and supportive care. The patient was discharged 5 days after admission to the referral hospital. New or unique information: This is the first report, to the authors’ knowledge, of canine acute respiratory distress syndrome secondary to inhalant toxin exposure not associated with smoke inhalation. The report summarizes the provided care and subsequent successful outcome. [ABSTRACT FROM AUTHOR]

Nanoparticle-laden two-phase flow systems, especially atmospheric aerosols, are usually found with several modes for particle size distribution (PSD). For the first time, a mathematical method is proposed to study the interaction of nanoparticle dynamics between modes by establishing two joint population balance equations (PBEs). The PBEs are solved using the sectional method, which divides the PSD into discrete bins. The nanoparticle-laden system involves Brownian coagulation, ventilation, and injection. The interaction between modes within a size distribution is studied quantitatively with and without injection and ventilation. The study shows that particles with smaller size are easier to be removed by background particles, but the lag time to be removed is affected by not only the total number concentration of small particles but also their sizes. Background particles play an important role in determining the evolution of small particle system, whose presence makes the secondary model absent for the small particles. [ABSTRACT FROM AUTHOR]

Abstract: We used an online aerosol‐climate model (BCC_AGCM2.0_CUACE/Aero) to simulate effective radiative forcing and climate response to changes in the concentrations of short‐lived climatic pollutants (SLCPs), including methane, tropospheric ozone, and black carbon, for the period 2010–2050 under Representative Concentration Pathway scenarios (RCPs) 8.5, 4.5, and 2.6. Under these three scenarios, the global annual mean effective radiative forcing were 0.1, −0.3, and −0.5 W m−2, respectively. Under RCP 8.5, the change in SLCPs caused significant increases in surface air temperature (SAT) in middle and high latitudes of the Northern Hemisphere and significant decreases in precipitation in the Indian Peninsula and equatorial Pacific. Global mean SAT and precipitation increased by 0.13 K and 0.02 mm d−1, respectively. The reduction in SLCPs from 2010 to 2050 under RCPs 4.5 and 2.6 led to significant decreases in SAT at high latitudes in the Northern Hemisphere. Precipitation increased slightly in most continental regions, and the Intertropical Convergence Zone moved southward under both of these mitigation scenarios. Global mean SAT decreased by 0.20 and 0.44 K, and global averaged precipitation decreased by 0.02 and 0.03 mm d−1 under RCPs 4.5 and 2.6, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Bronchiolitis obliterans (BO) is a highly debilitative and fatal syndrome associated with a series of severe lower airway disorders. The pathogenesis of BO is complicated and not entirely understood. An appropriate animal model of BO may aid research into its pathogenesis. Here, we establish a mouse model of BO to provide insight into this disease. Materials and Methods: 6-8 week old BABL/c mice were exposed to 5% nitric acid (NA) aerosol through a nebulizer for 3 hours, and controls were exposed to distilled water instead. Symptoms, airway resistance and pathological process were observed dynamically. The levels of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), 8-isoprostane and myeloperoxidase (MPO) in lung tissue and bronchoalveolar lavage fluids (BLAF) were determined by ELISA on day 3, 7, 14, 28 and 56 after the aerosol nebulization. Results: Typical BO lesions were observed in NA nebulized mice characterized histologically by initial necrotizing bronchiolitis and final airway fibrosis at day 28 after the aerosol nebulization. NA nebulized mice also exhibited labored breathing and significantly increased airway resistance. Expression of MMP-2, MMP-9, TIMP-1, 8-isoprostane and MPO were significantly elevated in NA nebulized mice in different time frame. Conclusion: A murine BO model was established by NA aerosol inhalation. It provides an easy, economic, and reproducible mice model for BO research. [ABSTRACT FROM AUTHOR]

Carbonyl emissions from tobacco cigarettes represent a substantial health risk contributing to smoking-related morbidity and mortality. As expected, this is an important research topic for tobacco harmreduction products, in an attempt to compare the relative risk of these products compared to tobacco cigarettes. In this study, a systematic review of the literature available on PubMed was performed analyzing the studies evaluating carbonyl emissions from e-cigarettes. A total of 32 studies were identified and presented. We identified a large diversity of methodologies, with substantial discrepancies in puffing patterns, aerosol collection and analytical methods as well as reported units of measurements. Such discrepancies make comparisons difficult, and in some cases the accuracy of the findings cannot be determined. Importantly, control for the generation of dry puffs was not performed in the vast majority of studies, particularly in studies using variable power devices, which could result in testing conditions and reported carbonyl levels that have no clinical relevance or context. Some studies have been replicated, verifying the presence of dry puff conditions. Whenever realistic use conditions were ensured, carbonyl emissions from e-cigarettes were substantially lower than tobacco cigarette smoke, while newer generation (bottom-coil, cotton wick) atomizers appeared to emit minimal levels of carbonyls with questionable clinical significance in terms of health risk. However, extremely high levels of carbonyl emissions were reported in some studies, and all these studies need to be replicated because of potentially important health implications. [ABSTRACT FROM AUTHOR]

Pharmaceutical aerosol powders intended for inhalation are required to have unique performance characteristics that are highly dependent on their physico-chemical properties. A wide range of analytical methods have been applied to study particle structure, size distribution, surface properties and subsequent behaviour of powders with the intention of predicting their performance. However, particle interactions are dictated by complex fundamental forces that impact on the efficiency and reproducibility of delivery and thereby the quality, efficacy and safety of the final product. This manuscript reviews the interplay of physico-chemical properties of powder and the complex process and analytical variables that must be monitored and controlled to effectively predict powder performance. [ABSTRACT FROM AUTHOR]

Context:Dry powder inhalers (DPIs) consisting of a powder mixture containing coarse carrier particles (generally lactose) and micronized drug particles are used for lung drug delivery. The effective drug delivery to the lungs depends on size and shape of carrier particles. Thus, various methods have been proposed for engineering lactose particles to enhance drug delivery to lungs. Objective:The objective of current work was to assess suitability of electrospray technology toward crystal engineering of lactose. Further, utility of the prepared lactose particles as a carrier in DPI was evaluated. Materials and methods:Saturated lactose solutions were electrosprayed to obtain electrosprayed lactose (EL) particles. The polymorphic form of EL was determined using Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry. In addition, morphological, surface textural, and flow properties of EL were determined using scanning electron microscopy and Carr’s index, respectively. The aerosolization properties of EL were determined using twin-stage impinger and compared with commercial lactose particles [Respitose®(SV003, Goch, Germany)] used in DPI formulations. Results and discussion:EL was found to contain both isomers (α and β) of lactose having flow properties comparable to Respitose®(SV003). In addition, the aerosolization properties of EL were found to be significantly improved when compared to Respitose®(SV003) which could be attributed to morphological (high elongation ratio) and surface characteristic (smooth surface) alterations induced by electrospray technology. Conclusion:Electrospray technology can serve as an alternative technique for continuous manufacturing of engineered lactose particles which can be used as a carrier in DPI formulations. [ABSTRACT FROM PUBLISHER]

Background Aerosolized medications are increasingly being used to treat respiratory diseases in dogs. No previous studies assessing respiratory tract deposition of radiolabeled aerosols have been performed in conscious dogs. Hypothesis/Objectives Assess respiratory tract deposition of radiolabeled, inhalant corticosteroid (fluticasone propionate labeled with 99mTc) delivered from a nebulizer and metered dose inhaler ( MDI) to healthy dogs. Animals Ten healthy Foxhounds. Methods Prospective, randomized, cross-over pilot study. Initial inhalation method (nebulizer or MDI) was randomly assigned. Treatments were crossed over after a 7-day washout period. Treatments initially were performed using sedation. Dogs were imaged using 2-dimensional planar scintigraphy, with respiratory tract deposition quantified by manual region-of-interest analysis. Deposition calculated as percentage of delivered dose. Six of 10 dogs were randomly selected and reassessed without sedation. Results Inhalation method had significant effect on respiratory tract deposition ( P = 0.027). Higher deposition was achieved by nebulization with mean deposition of 4.2% (standard deviation [ SD], 1.4%; range, 1.9-6.1%); whereas MDI treatment achieved a mean of 2.3% ( SD, 1.4%; range, 0.2-4.2%). Nebulization achieved higher respiratory tract deposition than MDI in 7 of 10 dogs. No statistical difference ( P = 0.68) was found between mean respiratory tract deposition achieved in dogs when unsedated (3.8%; SD, 1.5%) or sedated (3.6%; SD, 1.7%). Conclusions and Clinical Importance Study confirms respiratory tract deposition of inhalant medications delivered from a nebulizer and MDI in healthy dogs, breathing tidally with and without sedation. Respiratory tract deposition in these dogs was low compared to reported deposition in adult humans, but similar to reported deposition in children. [ABSTRACT FROM AUTHOR]

Purpose: Despite being the most prominent dosage form for topical ocular delivery, eye-drops have several well-recognized drawbacks. Addressing these limitations, in this work we introduce a novel method to accurately deliver ophthalmic medications to the surface of the eye at relatively low volume and low velocity. By aerosolizing a medicament and dispensing it in the form of a toroidal vortex, commonly known as a 'smoke ring', several major drawbacks associated with topical drug delivery can be avoided. Methods: A device capable of emitting a toroidal vortex was developed such that actuation force and aerosol loading could be modulated. Different solution formulations were tested for deposited dose on an in vitro eye. Results: It was found that the dose delivered to the surface of an in vitro eye was directly proportional to the velocity and the size of the droplets emitted from the device. With a dilute solution formulation (0.05% fluorescein sodium), doses could be reproducibly deposited by actuating the device at different velocities (from ~5 ng to ~18 ng per actuation). While a more concentrated solution of 0.5% fluorescein sodium, between 20 ng and 160 ng could be deposited depending on selected actuation velocity. And with the highest concentration, 5% fluorescein sodium, 1.15 +/− 0.075 μg was deposited. It was also shown that the amount of drug deposited onto the eye surface could be modulated by modulating the chamber fill time. Conclusion: Precise toroidal vortex based aerosol delivery may facilitate optimized administration of medicines to the surface of the eye. [ABSTRACT FROM AUTHOR]

Inhalation of aerosolised medications are the mainstay of treatment for a number of chronic lung diseases and have several advantages over systemically-administered medications. These include more rapid onset of action for drugs such as β-adrenergic agonists when compared with oral medication, high luminal doses for inhaled antibiotics when used to treat endobronchial infection, and an improved therapeutic index compared with systemic delivery for these and other classes of drugs such as corticosteroids. The use of aerosolised drugs to treat patients whose tracheas are intubated is less well established, in part because systemic delivery via the intravenous route can be a simpler alternative for many drugs. Consequently, research in this area is largely limited to a number of in vitro studies and very few clinical trials. Unfortunately, a lack of focus in this area has resulted in a number of practices which at best are ineffective, and at worst dangerous for the patient. Although there have been some attempts to re-invigorate research in order to improve delivery systems, current devices are, to a great extent, based on long-standing technology developed more than 50 years ago. In this review, we explore current knowledge and provide guidance as to when and how the inhaled route may be of value when treating patients whose tracheas are intubated, and we set out the challenges facing those attempting to advance the topic. We conclude by reviewing current areas of interest that may lead to more effective and widespread use of aerosols in the treatment of intubated patients. [ABSTRACT FROM AUTHOR]

Aerosol treatment is the primary relief method of respiratory infections, the leading cause of hospitalization among preschool children. The effectiveness of drug absorption during aerosol treatment is determined by children's cognitive development, breathing patterns, and treatment compliance. A survey revealed that the completion rate of nurses on health education regarding aerosol treatment was 53.3%, and the prevalence of aerosol treatment- related cognition and skills among preschool children was 36.7%. According to analysis, the causes of the ineffectiveness were identified: 1) the nurses did not utilize play therapy effectively; 2) the children had difficulty understanding certain material; and 3) the absence of health education standard and auxiliary tools for observing aerosol treatment effectiveness. According to the management-by-objective (MBO) system, the completion rate of RNs on health education and patient comprehension of treatment should be 95% and 85% respectively. By planning play therapy communication courses, enhancing nurses' communication skills, establishing standard health education processes, and developing innovative auxiliary tools, the nurses' aerosol treatment-related health education completion rate increased to 97.3% and the prevalence of the children's aerosol treatment-related cognitive skills increased to 90.5%. This demonstrated that enhancement of interactive games in children's adaptation to medical treatment, aerosol treatment-related cognitive skills, and the treatment effectiveness. [ABSTRACT FROM AUTHOR]

Context:Grout, tile and floor stone sealants contain a solvent, a water-repelling agent and in the case of aerosols a propellant. The water-repelling agent used is typically a fluoropolymer resin, a silicon-based resin, or a combination of both. Objective:To report the clinical course in patients exposed to fluoropolymer-containing sealants referred to the United Kingdom National Poisons Information Service. Methods:A retrospective analysis was performed of telephone enquiries received between 2009 and 2015. Results:101 enquiries involving 96 exposures were received. The majority of the exposures (n = 88) occurred when the sealant was delivered from an aerosol. Twelve patients were exposed occupationally and the remainder were exposed while using the product at home. Eighty-nine exposures were as a result of inhalation alone, two followed ingestion, three skin contact and one eye contact; one involved inhalation and eye contact. All 90 patients exposed by inhalation developed clinical features: 31 had a World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists Poisoning Severity Score of 1 (minor toxicity), 51 patients had features of moderate toxicity (PSS 2) and eight were graded PSS 3 (severe poisoning). The most common features were dyspnea (n = 52; 57.8%; 95% CI = 47.0–68.5), chest pain/tightness (n = 34; 37.8%; 95% CI = 27.2–48.4), coughing (n = 27; 30.0%; 95% CI = 20.0–40.0) and sinus tachycardia (n = 11; 12.2%; 95% CI = 4.1–18.2); hypoxemia was present in 20 (22.2%; 95% CI = 13.1–31.4). At the time of the enquiry a chest X-ray had been performed on 15 patients: in eight patients (all of whom were PSS 3) the X-ray was reported as being abnormal and showed bilateral shadowing. Conclusions:This study demonstrates that if fluoropolymer-containing sealants are inhaled then clinical features may occur and in a small proportion (9%) these features may be severe. [ABSTRACT FROM PUBLISHER]

Precise determination of concentration of gases, such as NO, in urban atmosphere is crucial in studying chemical reactions leading to secondary pollutants. In this study, a novel and sensitive yet simple and cost effective spectrometer was developed where two laser wavelengths and two parallel identical optical cavities were used. Monitoring of NO even in the presence of aerosol spectral interference was demonstrated. The intensity transmitted through one cavity, evacuated to 0.1 mbar, was designated as the reference signal ( I ) while that through the other cavity, sampling air at atmospheric pressure, was designated as sample signal ( I). Quasi-simultaneous measurements of these I and I were done for both laser wavelengths sequentially: one at 406.4 nm near the peak of the largest electronic transition of NO and the other at 446.9 nm, away from the peak yet exhibiting significant absorption. The addition of the second wavelength where NO has absorption was to ascertain the presence of aerosol scattering and compensate for it. Aerosol extinctions at both operating wavelengths were assumed to be the same, their ratio taken as unity for simplicity, and aerosol light extinction was retrieved. The spectrometer with average sampling interval of 5 s exhibited detection sensitivity of low parts per billion concentrations. [ABSTRACT FROM AUTHOR]

New treatments for organic aerosol (OA) formation have been added to a modified version of the CESM/CAM5 model (CESM-NCSU). These treatments include a volatility basis set treatment for the simulation of primary and secondary organic aerosols (SOAs), a simplified treatment for organic aerosol (OA) formation from glyoxal, and a parameterization representing the impact of new particle formation (NPF) of organic gases and sulfuric acid. With the inclusion of these new treatments, the concentration of oxygenated organic aerosol increases by 0.33 μg m-3 and that of primary organic aerosol (POA) decreases by 0.22 μg m-3 on global average. The decrease in POA leads to a reduction in the OA direct effect, while the increased OOA increases the OA indirect effects. Simulations with the new OA treatments show considerable improvement in simulated SOA, oxygenated organic aerosol (OOA), organic carbon (OC), total carbon (TC), and total organic aerosol (TOA), but degradation in the performance of HOA. In simulations of the current climate period, despite some deviations from observations, CESM-NCSU with the new OA treatments significantly improves the magnitude, spatial pattern, seasonal pattern of OC and TC, as well as, the speciation of TOA between POA and OOA. Sensitivity analysis reveals that the inclusion of the organic NPF treatment impacts the OA indirect effects by enhancing cloud properties. The simulated OA level and its impact on the climate system are most sensitive to choices in the enthalpy of vaporization and wet deposition of SVOCs, indicating that accurate representations of these parameters are critical for accurate OA-climate simulations. [ABSTRACT FROM AUTHOR]

A resveratrol/carboxymethylated glucan (CM-glucan) combination is known to inhibit rhinovirus replication and expression of inflammatory mediators in nasal epithelia. The aim of this study was to develop an aerosol formulation containing an association of the two molecules which could reach the lower respiratory tract. Mass median aerodynamic diameter (MMAD) of a resveratrol/CM-glucan combination was lower than that shown by resveratrol or CM-glucan alone (2.83 versus 3.28 and 2.96 µm, respectively). The resveratrol/CM-glucan association results in the finest and most monodispersed particles in comparison to the two single components. The association also evidenced lower values for all particle size distribution parameters, suggesting that the pharmacological synergy observed in previous studies may be accompanied by a pharmaceutical one. Moreover, we showed that the CM-glucan matrix did not exert an inhibitory effect on resveratrol nebulization, demonstrating the good suitability of these two molecules in association for simultaneous aerosol volatilization. [ABSTRACT FROM AUTHOR]

Background Pressurized intraperitoneal aerosol chemotherapy ( PIPAC) is a minimally invasive approach under investigation as a novel treatment for patients with peritoneal carcinomatosis of various origins. The aim was to review the available evidence on mechanisms, clinical effects and risks. Methods This was a systematic review of the literature on pressurized intraperitoneal chemotherapy published between January 2000 and October 2016. All types of scientific report were included. Results Twenty-nine relevant papers were identified; 16 were preclinical studies and 13 were clinical reports. The overall quality of the clinical studies was modest; five studies were prospective and there was no randomized trial. Preclinical data suggested better distribution and higher tissue concentrations of chemotherapy agents in PIPAC compared with conventional intraperitoneal chemotherapy by lavage. Regarding technical feasibility, laparoscopic access and repeatability rates were 83-100 and 38-82 per cent. Surgery-related complications occurred in up to 12 per cent. Postoperative morbidity was low (Common Terminology Criteria for Adverse Events grade 3-5 events reported in 0-37 per cent), and hospital stay was about 3 days. No negative impact on quality of life was reported. Histological response rates for therapy-resistant carcinomatosis of ovarian, colorectal and gastric origin were 62-88, 71-86 and 70-100 per cent respectively. Conclusion PIPAC is feasible, safe and well tolerated. Preliminary good response rates call for prospective analysis of oncological efficacy. [ABSTRACT FROM AUTHOR]

The North China Plain (NCP) frequently experiences heavy haze pollution, particularly during wintertime. In winter 2015-2016, the NCP region suffered several extremely severe haze episodes with air pollution red alerts issued in many cities. We have investigated the sources and aerosol evolution processes of the severe pollution episodes in Handan, a typical industrialized city in the NCP region, using real-time measurements from an intensive field campaign during the winter of 2015-2016. The average (±1σ) concentration of submicron aerosol (PM1) during 3 December 2015-5 February 2016 was 187.6 (±137.5) μg m-3, with the hourly maximum reaching 700.8 μg m-3. Organic was the most abundant component, on average accounting for 45 % of total PM1 mass, followed by sulfate (15 %), nitrate (14 %), ammonium (12 %), chloride (9 %) and black carbon (BC, 5 %). Positive matrix factorization (PMF) with the multilinear engine (ME-2) algorithm identified four major organic aerosol (OA) sources, including traffic emissions represented by a hydrocarbon-like OA (HOA, 7 % of total OA), industrial and residential burning of coal represented by a coal combustion OA (CCOA, 29 % of total OA), open and domestic combustion of wood and crop residuals represented by a biomass burning OA (BBOA, 25 % of total OA), and formation of secondary OA (SOA) in the atmosphere represented by an oxygenated OA (OOA, 39 % of total OA). Emissions of primary OA (POA), which together accounted for 61 % of total OA and 27 % of PM1, are a major cause of air pollution during the winter. Our analysis further uncovered that primary emissions from coal combustion and biomass burning together with secondary formation of sulfate (mainly from SO2 emitted by coal combustion) are important driving factors for haze evolution. However, the bulk composition of PM1 showed comparatively small variations between less polluted periods (daily PM2.5 ≤ 75 μg m-3) and severely polluted periods (daily PM2.5 > 75 μg m-3), indicating relatively synchronous increases of all aerosol species during haze formation. The case study of a severe haze episode, which lasted 8 days starting with a steady buildup of aerosol pollution followed by a persistently high level of PM1 (326.7-700.8 μg m-3), revealed the significant influence of stagnant meteorological conditions which acerbate air pollution in the Handan region. The haze episode ended with a shift of wind which brought in cleaner air masses from the northwest of Handan and gradually reduced PM1 concentration to < 50 μg m-3 after 12 h. Aqueous-phase reactions under higher relative humidity (RH) were found to significantly promote the production of secondary inorganic species (especially sulfate) but showed little influence on SOA. [ABSTRACT FROM AUTHOR]

The Maritime Continent (MC) is an exceedingly complex region from the perspective of both its meteorology and its aerosol characteristics. Convection in the MC is ubiquitous and assumes a wide variety of forms under the influence of an evolving large-scale dynamic and thermodynamic context. Understanding the interaction between convective systems and their environment, both individually and in the aggregate, requires knowledge of the dominant patterns of spatial and temporal variability. Ongoing cloud model ensemble studies require realistic perturbations to the atmospheric thermodynamic state to devise system sensitivities. Apart from modeling studies, evanescent signals in the tropical system are obscured by the underlying broad-scale meteorological variability, which if constrained could illuminate fine-scale physical processes. To this end, radiosonde observations from 2008 to 2016 are examined from three upper-air sounding sites within the MC for the purpose of exploring the dominant vertical temperature, humidity, and wind structures in the region. Principal component analysis is applied to the vertical atmospheric column to transform patterns present in radiosonde data into canonical thermodynamic and wind profiles for the MC. Both rotated and non-rotated principal components are considered, and the emerging structure functions reflect the fundamental vertical modes of short-term tropical variability. The results indicate that while there is tremendous spatial and temporal variability across the MC, the primary modes of vertical thermodynamic and wind variability in the region can be represented in a lower-dimensional subspace. In addition, the vertical structures are very similar among different sites around the region, though different structures may manifest more strongly at one location than another. The results indicate that, while different meteorology may be found in various parts of the MC at any given time, the processes themselves are remarkably consistent. The ability to represent this variability using a limited number of structure functions facilitates analysis of covariability between atmospheric structure and convective systems and also enables future systematic model-based ensemble analysis of cloud development, convection, and precipitation over the MC. [ABSTRACT FROM AUTHOR]

Background: New interventions for tuberculosis are urgently needed. Non-human primate (NHP) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value. Methods: Mauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathology-based measures. Results: All macaques developed characteristic clinical signs and disease features of tuberculosis (TB). Disease burden and the ability to control disease were dependent on exposure dose. Mauritian cynomolgus macaques showed less variation in pulmonary disease burden and total gross pathology scores within exposure dose groups than either Indian rhesus macaques or Chinese cynomolgus macaques Conclusions: The genetic homogeneity of Mauritian cynomolgus macaques makes them a potentially useful model of human tuberculosis. [ABSTRACT FROM AUTHOR]

To understand the instantaneous particle deposition in nasal cavity, effects of two injection models on particle deposition characteristic were discussed in this paper. Based on a realistic human nasal cavity geometry obtained from CT scans, a comparison of deposition pattern in the nasal cavity between single injection and continuous injection was investigated through the Lagrangian approach. The instantaneous airflow field was simulated with the tidal volume of 159 and 318 mL by two sine wave curves at inlet. For the case of single injection, particles have finished deposition in the first half of inhalation, and a negative correlation between the tidal volumes and deposition can be observed when the particle diameter was larger than 10 µm. Moreover, particles were mainly deposited in the turbinate area that was beneficial for aerosol therapy. The inertial parameter was not suitable to predict the particle deposition in the case of single injection. With respect to continuous injection, a reduction in total deposition caused by the deceleration process of inhalation can be observed after 1.5 s. The deposition was closely associated with the time-varying flow field, and particles were mainly deposited in the anterior region and turbinate area. Besides, the particle deposition increased with the inertial parameter for continuous injection. The results indicated that the injection modes had an influence on both the total deposition and local deposition pattern in the nasal cavity. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The specific microclimate of alpine waterfalls with high levels of ionized water aerosols has been suggested to trigger beneficial immunological and psychological effects. In the present three-armed randomized controlled clinical study, we focused on effects on (i) immunological reagibility, on (ii) physiological stress responses, and on (iii) stress-related psychological parameters. Methods: People with moderate to high stress levels (n = 65) spent an active sojourn with daily hiking tours in the National Park Hohe Tauern (Großkirchheim, Austria). Half of the group was exposed to water aerosol of an alpine waterfall for 1 h/day (first arm, n = 33), whereas the other half spent the same time at a distant site (second arm, n = 32). A third arm (control, n = 26) had no intervention (except vaccination) and stayed at home, maintaining their usual lifestyle. The effect of the interventions on the immune system was tested by oral vaccination with an approved cholera vaccine and measuring specific salivary IgA antibody titers. Lung function was determined by peak expiratory flow measurement. Electric skin conductance, heart rate, and adaption of respiration rate were assessed as physiological stress parameters. Psychological stress-related parameters were analyzed by questionnaires and scales. Results: Compared to the control group, both intervention groups showed improvement of the lung function and of most physiological stress test parameters. Analysis of the mucosal immune response revealed a waterfall-specific beneficial effect with elevated IgA titers in the waterfall group. In line with these results, exposure to waterfall revealed an additional benefit concerning psychological parameters such as subjective stress perception (measured via visual analog scale), the Global Severity Index (GSI), and the Positive Symptom Total (PST). Conclusions: Our study provides new data, which strongly support an “added value” of exposure to waterfall microclimate when combined with a therapeutic sojourn at high altitude including regular physical activity. [ABSTRACT FROM AUTHOR]

Inhalation delivery of aerosolized antibacterials is preferred over conventional methods of delivery for targeting lung infection. The present study is concerned with the development and characterization of a novel, spray dried, aerosolized, chitosan polyelectrolyte complex (PEC) based microparticles containing antibacterials for the treatment of lung infections. Chitosan polyelectrolyte complex microparticles were formulated by spray drying process. Prepared spray dried chitosan PEC microparticles were studied for surface morphology, drug encapsulation efficiency, moisture content, Carr's index, solid state interaction by XRD, aerosolization behaviour and in-vitro drug release. In-vitro cytotoxicity studies of microparticles were carried out on H1299 alveolar cell lines. Antibacterial efficacy of microparticles was assessed on the basis of determination of pharmacokinetic parameters in bronchial alveolar lavage (BAL) of rats using PK/PD analysis. The PEC microparticles were mostly spherical and exhibited high drug encapsulation efficiency. Release profiles showed an initial burst phase followed by a secondary sustained release phase. Good aerosolization behaviour as dry powder inhaler was demonstrated by microparticles with high values of recovered dose, emitted dose, and fine particle fraction. No overt cytotoxicity of microparticles was detected against H1299 alveolar cell line. More than 8 to 9 folds higher Cmax values were obtained in BAL fluid with microparticles as compared to intravenously administered antibacterial solution. The findings of the study suggest that chitosan polyelectrolyte complex based microparticles as dry powder inhaler can be an efficient antibacterial delivery system for sustained and effective management of lung infection. [ABSTRACT FROM AUTHOR]

In this article, the theoretical foundation for salts is given with an emphasis on the amount of drug in solution. Consideration is given for the solubility of the non-ionized form, acid dissociation constant and solubility product, which are the limiting constraints. For dissolution of nonionized drugs, the surface pH differs from the bulk pH, giving rise to a lower than expected rate. For salts, theoretical considerations are relatively complex, and an experimental approach to estimating the surface pH is more likely to be of value in predicting the dissolution rate. General guidelines are described for screening, preparing and characterizing drugs as salts, which critically depend on the goal of the product development. Thereafter, our work involving the preparation of salts as a means to generate aerosols from a solution is provided. The solubility of six structurally related compounds was determined in four acids. Thereafter, the amount of the compound in solutionwas determined as a function of pH, using the acid that provided the highest solubility. Because the pH required to achieve the needed concentration for aerosol generation was low, ammonia vapor was introduced into the air stream to neutralize aerosol droplets. Solvent was then removed from the aerosol by a silica column. The resulting aerosol had a concentration of 96 µg/l and a mass median particle size of 1.8 µm. The reported pharmacokinetic study substantiated the feasibility of evaluating its safety and efficacy of inhalation administration in the rat model. [ABSTRACT FROM AUTHOR]

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach delivering intraperitoneal chemotherapy by means of a pressurized aerosol. This study was conducted to evaluate the distribution pattern of doxorubicin in the abdominal cavity after PIPAC in a postmortem swine model. Methods: Doxorubicin was aerosolized through a Micropump© (MIP) into the peritoneal cavity of two swines at a pressure of 12 mm Hg CO and 32 °C. To measure the distribution of the drug, 9 different positions within the abdominal cavity were sampled. In-tissue doxorubicin penetration was evaluated using fluorescence microscopy on frozen thin sections. Results: A maximum of drug penetration was observed in the area around the MIP. The penetration in the small intestine reached a depth of 349 ± 65 µm. Penetration depth in the right upper abdomen and left upper abdomen were 349 ± 65 and 140 µm ± 26 µm, respectively. Distant areas to the MIP showed variable penetration rates between 50 and 150 µm. Conclusions: Doxorubicin reached all areas within the peritoneum. Highest penetration rates were measured in the area around the Micropump. Further studies are warranted to evaluate and optimize the distribution and penetration of cytotoxic agent into the tissue after PIPAC. [ABSTRACT FROM AUTHOR]

Oxygen therapy can be delivered using low-flow, intermediate-flow (air entrainment mask), or high-flow devices. Low/intermediate-flow oxygen devices have several drawbacks that cause critically ill patients discomfort and translate into suboptimal clinical results. These include limitation of the FiO2 (due to the high inspiratory flow often observed in patients with respiratory failure), and insufficient humidification and warming of the inspired gas. High-flow nasal cannula oxygenation (HFNCO) delivers oxygen flow rates of up to 60 L/min and over the last decade its effect on clinical outcomes has widely been evaluated, such as in the improvement of respiratory distress, the need for intubation, and mortality. Mechanisms of action of HFNCO are complex and not limited to the increased oxygen flow rate. The main aim of this review is to guide clinicians towards evidence-based clinical practice guidelines. It summarizes current knowledge about HFNCO use in ICU patients and the potential areas of uncertainties. For instance, it has been recently suggested that HFNCO could improve the outcome of patients with hypoxemic acute respiratory failure. In other settings, research is ongoing and additional evidence is needed. For instance, if intubation is required, studies suggest that HFNCO may help to improve preoxygenation and can be used after extubation. Likewise, HFNCO might be used in obese patients, or to prevent respiratory deterioration in hypoxemic patients requiring bronchoscopy, or for the delivery of aerosol therapy. However, areas for which conclusive data exist are limited and interventions using standardized HFNCO protocols, comparators, and relevant clinical outcomes are warranted. [ABSTRACT FROM AUTHOR]