Inhalation Test Research Articles

Use of a vibrating mesh nebulizer for allergen challenge

BackgroundAllergen inhalation tests are a valuable research tool. The allergen dose producing an early asthmatic response (EAR) can be predicted from methacholine responsiveness and allergen skin test endpoint (STE). The Wright® jet nebulizer, which is both inefficient and increasingly difficult to obtain, has been used historically. We assessed the Solo® vibrating mesh nebulizer as an alternative for allergen and methacholine challenges.MethodsEighteen mild atopic asthmatics completed the study. Doubling concentration allergen prick skin tests were performed to determine the STE in allergen units/mL. The Wright® protocol was used to measure the methacholine provocation dose causing a 20% forced expired volume in one second (FEV1) fall (PD20) (μg) and the allergen PD20 (units). The Solo® protocol (0.5 mL nebulized to completion, tidal breathing inhalation) was used to determine both methacholine PD20 and allergen PD20. The nebulizer order was randomized and separated by ≥ 2 weeks.ResultsAll data were log transformed. The allergen PD20, predicted from the methacholine PD20 and the STE, was within 2 doubling doses of the PD20 measured with the Wright® and 2.64 doubling doses of that measured with Solo®. The Wright® allergen PD20 correlated with the Wright® methacholine PD20 (r = 0.74) and the STE (r = 0.78) and more strongly with the product of the two (Wright® methacholine PD20 × STE, r = 0.91, p < 0.00001). The Solo® allergen PD20 showed similar relationships with the Solo® methacholine PD20 (r = 0.61), the STE (r = 0.75) and the product of the two (Solo® methacholine PD20 × STE, r = 0.83, p < 0.00002). The Wright® and the Solo® methacholine geometric mean PD20s were not significantly different (49.3 and 54.5 μg respectively, p = 0.62). The Wright® allergen PD20 was slightly but significantly lower than the Solo® allergen PD20 (geometric means 6.7 and 10.5 units respectively, p = 0.003).ConclusionThe Solo® allergen PD20 showed the same relationship with methacholine responsiveness and STE as did the Wright®. The Solo® allergen PD20 was slightly but significantly higher than the Wright® allergen PD20. The Solo® vibrating mesh nebulizer was well tolerated and is an acceptable alternative for allergen challenge.Trial registration clinicaltrials.gov: NCT03491358

Algorithm for diagnosing bronchial asthma in citizens of military age.

Despite the presence of various international and Russian documents regulating the diagnosis of bronchial asthma, in everyday practice, doctors are constantey face a significant problem when confirming or excluding this disease in people of military age during their medical examination. This is due to the peculiarity of the natural course of the disease in military age: frequent long-term remissions, the predominance of mild or asymptomatic, normal indicators of respiratory function in the remission phase. It was necessary to revise the algorithm for diagnosing asthma in this category of persons in order to avoid making the wrong expert decisions. It has been taken into account that service in the army, with increased physical and emotional loads, exposure to various adverse environmental conditions can be a factor in both debut and exacerbation of the disease. Attention is drawn to the need for an integrated approach in conducting a survey before making a decision on the final rendering of a medical opinion. At the same time, a specific allergological examination, evaluation of spirographic studies, testing aimed at confirming the preserved bronchial hyperreactivity, and in controversial cases, inhalation tests with a clinically significant allergen are mandatory.

Successful management of severe asthma in a young boy with eosinophilic chronic rhinosinusitis who received omalizumab: a case report

BackgroundThe incidence of chronic rhinosinusitis with nasal polyps has recently increased in Japan and other East Asian countries, and this disease is called eosinophilic chronic sinusitis (ECRS) in Japan. ECRS usually occurs in adults and is frequently accompanied by refractory bronchial asthma. However, its occurrence in children under 10 years of age is rare. Here, we present an unusual case of ECRS complicated by intractable asthma in an 8-year-old boy.Case presentationOral administration of prednisolone (10 mg/day) initially relieved the ECRS and bronchial asthma, but both returned during prednisolone dose reduction. Because nasal cavity-opening surgery was ineffective, oral administration prednisolone at 10 mg/day was continued. Pancytopenia was observed 16 months after the start of treatment, and the patient was admitted to our hospital. He was diagnosed with refractory cytopenia in childhood, but gradually improved after cyclosporine treatment. Although the dose of cyclosporine was therapeutic for asthma, it did not alleviate the asthma attacks, and the patient’s quality of life markedly decreased. We administered omalizumab even though its use was contraindicated by negative results in an inhalable antigen test. After the third administration of omalizumab, the asthma was better controlled and respiratory function improved; however, the nasal symptoms of ECRS persisted. Attempts to relieve these symptoms by increasing the therapeutic dose of omalizumab were only partially successful. We replaced omalizumab with mepolizumab; doing so slightly improved the sinusitis symptoms, but quality of life remained unsatisfactory. We repeated the nasal cavity-opening surgery. After surgery, the asthma and sinusitis were unchanged.ConclusionsOmalizumab effectively treated the severe combined asthma in a young patient, but its effect on sinusitis was insufficient. More cases and long-term follow-up data are needed to better evaluate the effectiveness of mepolizumab for treatment of ECRS.

Association of Asthma Control and Metered-Dose Inhaler Use Technique among Adult Asthmatic Patients Attending Outpatient Clinic, in Resource-Limited Country: A Prospective Study.

Asthma is a heterogeneous disease which is characterized by chronic airway inflammation. It is a common chronic respiratory disease affecting 1–18% of population in different countries. It can be treated mainly with inhaled medications in several forms, including pressurized metered-dose inhaler (MDI). Patients encountered difficulty in using inhaler devices even after repeated demonstration and/re-evaluation. This could highly compromise patient treatment outcome/asthma control. To evaluate relationship between MDI use technique and asthma control among adult asthmatic patients who attend respiratory clinic in Jimma University Medical Center (JUMC), Southwest Ethiopia. A prospective observational study was conducted from March to August 22, 2018. All adult asthmatic patients who met the inclusion criteria were included in the study. Patient baseline assessment was conducted (patient demography, inhalation technique, adherence, and asthma control status). Inhalation technique was obtained using a standard checklist of steps recommended in National Institute of Health (NIH) guidelines. Patient adherence using asthma inhalation test and asthma control status was assessed by 2017 GINA guideline. Independent predictors of outcome were identified, strength of association between dependent and independent variables was determined by using ordinal logistic regression analysis, and statistical significance was considered at P < 0.05. One hundred forty patients were included in the analysis. Among these, 26 (18.4%) patients were controlled, 65 (46.1%) partially controlled, and 35% uncontrolled. Proportion of patients with uncontrolled asthma were higher among inefficient as compared to efficient, whereas patients with controlled asthma were higher among efficient as compared to inefficient. Asthma control status is significantly associated with inhalation technique (P=0.006). Since most of the patients were inefficient and it is significantly associated with asthma control status, the hospital tried to adopt video MDI teaching program, and the patient should ask healthcare professionals how to take medication and they should bring their device to receive demonstration during visit. Health professionals should re-evaluate the patient during their hospital visit and encourage bringing their device to give demonstration.

Food processing and occupational respiratory allergy- An EAACI position paper.

Occupational exposure to foods is responsible for up to 25% of cases of occupational asthma and rhinitis. Animal and vegetable high-molecular-weight proteins present in aerosolized foods during food processing, additives, preservatives, antioxidants, and food contaminants are the main inhalant allergen sources. Most agents typically cause IgE-mediated allergic reactions, causing a distinct form of food allergy (Class 3 food allergy). The allergenicity of a food protein, allergen exposure levels, and atopy are important risk factors. Diagnosis relies on a thorough medical and occupational history, functional assessment, assessment of sensitization, including component-resolved diagnostics where appropriate, and in selected cases specific inhalation tests. Exposure assessment, including allergen determination, is a cornerstone for establishing preventive measures. Management includes allergen exposure avoidance or reduction (second best option), pharmacological treatment, assessment of impairment, and worker's compensation. Further studies are needed to identify and characterize major food allergens and define occupational exposure limits, evaluate the relative contribution of respiratory versus cutaneous sensitization to food antigens, evaluate the role of raw versus cooked food in influencing risk, and define the absolute or relative contraindication of patients with ingestion-related food allergy, pollinosis, or oral allergy syndrome continuing to work with exposure to aerosolized food allergens.

Comparison between the next generation impactor and the twin glass impinge as model pulmonary drug delivery devices

Background and objective: The British Pharmacopoeia contains four apparatus for testing inhalers. Two of these are the next generation impactor, and the twin glass impinge which differs in their use. The next generation impactor apparatus should ideally have at least five stages; even though the twin glass impinge has only two stages, it is still listed in the British Pharmacopoeia. The next generation impactor is more accurate, reliable and sophisticated than the twin glass impinger. This study gives a detailed comparison of the two pieces of equipment. Methods: Carriers including mannitol, lactose monohydrate, trehalose and sucrose with active pharmaceutical ingredient; salbutamol sulphate were delivered by dry powder inhaler using the next generation impactor and twin glass impinger at a constant flow rate of 60L/min. Results: The twin glass impinge respirable fractions of the powders were higher than the next generation impactor for each carrier. As expected, mannitol powder had the lowest percentage remaining in the capsule compared to lactose monohydrate, trehalose and sucrose had the greatest percentage remaining for both inhaler devices. Conclusion: Even though both apparatus are important for in-vitro studies of drug delivery into the lungs using inhaler devices, the next generation impactor is better suited when a specific size range is required. The twin glass impinger is useful for simple inhaler testing, and the inclusion within the British Pharmacopoeia is justified.

In Vivo Morphometry of Distal Airspaces with Nanoparticles As a Proposed Biomarker for Emphysema

Background: Airspace dimension assessment with nanoparticles (AiDA) is a novel method to measure distal airway morphology non-invasively. In this study, AiDA-derived airspace radii were measured in an unselected, cross-sectional study population. Persons with emphysema detected by computed tomography (CT) were compared to non-emphysematous subjects. Method: Nanoparticle inhalation tests, from which distal airspace radius (rAiDA) were calculated, were conducted on 618 individuals aged 50-64 years participating in the population-based Swedish CArdiopulmonary BioImaging Study (SCAPIS). The radius was studied in relation to visual and densitometric assessment of emphysema, as well as to lung function tests and symptoms. Findings: The forty-seven individuals with visually detected emphysema had a significantly larger rAiDA (326 ± 49 µm), compared to non-emphysematous persons (291 ± 36 µm), p = 0.00001. Odds ratio per 1 µm for emphysema, adjusted for age, sex, height and weight was 1·021 (1·013 - 1·028), p<0·0001. Similar results were found when other lung function measures were assessed. Interpretation: AiDA can indicate distal airspace enlargement and is a potential biomarker for emphysema. A diagnostic accuracy study in patients with suspected lung disease is needed to establish AiDA as a diagnostic technique. Funding: The study has received support from the Swedish Heart and Lung Foundation, The Swedish Research Council, FORTE, the Crafoord foundation, the Swedish Governmental Agency for Innovation Systems, the ERA-NET project EuroNanoMed2, and governmental funding of clinical research within the National Health Services. Declaration of Interest: The funders of the study had no commercial interests. Ethical Approval: The study was approved by the Regional Ethical Review Board in Umea, Sweden, 2010/228-31, and performed according to the Declaration of Helsinki.

Development of a Nose-only Inhalation Toxicity Test Chamber That Provides Four Exposure Concentrations of Nano-sized Particles

Using a numerical analysis based on computerized fluid dynamics, a nose-only inhalation toxicity chamber with four different exposure concentrations is designed and validated for flow field uniformity and cross-contamination among the exposure ports for each concentration. The designed flow field values are compared with the measured values from exposure ports located horizontally and vertically. For this purpose, nanoscale sodium chloride particles are generated as test particles and introduced to the inhalation chamber to evaluate the cross-contamination and concentration maintenance among the chambers, for each concentration group. The results indicate that the designed multiconcentration inhalation chamber can be used in animal inhalation toxicity testing without cross-contamination among concentration groups. Moreover, the designed multiconcentration inhalation toxicity chamber can also be converted to a single-concentration inhalation chamber. Further testing with gas, organic vapor, or non-nanoscale particles will ensure the use of the chamber in the inhalation testing of other test articles.

Acute and 28-Day Repeated Inhalation Toxicity Study of Glycolic Acid in Male Sprague-Dawley Rats.

The use of glycolic acid is present in a variety of consumer products, including medicines, cleaners, cosmetics, and paint strippers. It has recently led to concerns about toxicity from inhalation exposure. Herein, the pulmonary toxicity of glycolic acid was investigated in rats. We conducted acute (~458 mg/m3) and sub-acute (~49.5 mg/m3) inhalation tests to identify the potential toxicities of glycolic acid. Inhalation exposure to glycolic acid in the acute and subacute inhalation tests did not cause any specific changes in clinical examinations, including body weight, organ weight, hematology, serum biochemistry, and histopathology. The polymorphonuclear neutrophils (PMNs) and inflammatory cytokines in Bronchoalveolar lavage fluid (BALF) increased in rats exposed to single and repeated inhalations. In the sub-acute test, the changes induced by glycolic acid were minor or returned to normal during the recovery period. The No Observed Adverse Effect Concentration (NOAEC) for the nasal and pulmonary toxicity of glycolic acid was determined to be over 50 mg/m3 at the end of a 28-day inhalation test in male rats.

A Meta-Analysis of Efficacy of Carbon Dioxide Inhalation as a Challenge Test in Panic Disorder

The objective of this study is to perform a systematic review and meta-analysis on whether patients with panic disorder (PD) and their healthy first-degree relatives have an increased sensitivity to carbon dioxide inhalation test compared to healthy controls (HC) or patients with psychiatric disorders other than panic disorder. The databases of PubMed, EMBASE and PsycNET were searched using Boolean operators "panic AND carbon dioxide" and "panic AND CO2". Selected research articles were classified according to the carbon dioxide concentrations used in testing and the clinical characteristics of the samples. The assumption of heterogeneity across the studies was assessed by chi square based Q and I2 statistics. Publication biases were explored by Begg-Mazumdar's and Egger's tests in addition to funnel graphics. Odds ratios representing effect size of the carbon dioxide inhalation procedure were calculated according to fixed effect and random effect models after obtaining percent weight effects of each study. Meta-Analysis was conducted on 33 research studies that include 2114 participants totally. Participants with PD experienced significantly more frequent panic attacks (PA) compared to HC following in both 5% (OR=14.713, 95% CI 7.532 - 28.739) and 35% carbon dioxide inhalation (OR=11.507, 95% CI 7.775 - 17.031). HC who have a first-degree relative with PD experienced PA approximately 3 times more than HC who have not a first-degree relative with PD (OR=2.658, 95% CI 1.678 - 4.212) following carbon dioxide inhalation test. Participants with PD experienced significantly more frequent PA than the patients with other psychiatric disorders following the carbon dioxide inhalation test (OR = 3.524, 95% CI 1.945 - 6.384). There is an increased sensitivity of carbon dioxide inhalation in patients with PD and their healthy first-degree relatives. The role and possible mechanisms of carbon dioxide in etiology and physiopathology of PD should be studied extensively.

Serum levels of periostin and exercise-induced bronchoconstriction in asthmatic children

BackgroundPeriostin is induced by IL-13 and has been studied as a biomarker of asthma. The present study explored the relationship between serum levels of periostin and exercise-induced bronchoconstriction (EIB) in asthmatic children. MethodsThe study population consisted of 86 children 6–15 years old divided into an asthmatic group (n = 56) and healthy controls (n = 30). We measured the levels of periostin in serum and performed pulmonary function tests including baseline measurements, post-bronchodilator inhalation tests, exercise bronchial provocation tests (BPTs), and mannitol BPTs. ResultsThe 56 asthmatic children were divided into four groups: asthmatics with positive exercise BPT and positive mannitol BPT (n = 30), asthmatics with positive exercise BPT but negative mannitol BPT (n = 7), asthmatics with negative exercise BPT but positive mannitol BPT (n = 10), and asthmatics with negative exercise BPT and negative mannitol BPT (n = 9). Serum levels of periostin in asthmatic children with both positive exercise and mannitol BPT were significantly greater than those in asthmatic children with both negative exercise and mannitol BPT (95.0 [75.0–104.0] vs. 79.0 [68.0–82.5] ng/mL, P = 0.008) and controls (74.0 [69.75–80.0] ng/mL, P < 0.001). Periostin levels were significantly correlated with both the maximum decrease in %FEV1 and mannitol PD15 value. ConclusionSerum levels of periostin in asthmatic children with both positive exercise and mannitol BPT were significantly greater than those in asthmatic children with both negative exercise and mannitol BPT and also greater than in healthy controls.

Subchronic toxicity of Al2O3, TiO2 and SiO2 nanoparticles in different combinations for rats and its attenuation with a complex of innocuous bioprotectors

While engineered SiO2 nanoparticle toxicity is being widely investigated, mostly on cell lines or in acute animal experiments, the practical importance of as well as the theoretical interest in industrial condensation aerosols with a high SiO2 particle content seems to be neglected. That is why, to the best of our knowledge, long-term inhalation exposure to nano-SiO2 has not been undertaken in experimental nanotoxicology studies. To correct this data gap, female white rats were exposed for 3 or 6 months 5 times a week, 4 h a day to an aerosol containing predominantly submicron (nanoscale included) particles of amorphous silica at an exposure concentration of 2.6 ± 0.6 or 10.6 ± 2.1 mg/m3. This material had been collected from the flue-gas ducts of electric ore smelting furnaces that were producing elemental silicon, subsequently sieved through a < 2 μm screen and redispersed to feed a computerized “nose only” inhalation system. In an auxiliary experiment using a single-shot intratracheal instillation of these particles, it was shown that they induced a pulmonary cell response comparable with that of a highly cytotoxic and fibrogenic quartz powder, namely DQ12. However, in long-term inhalation tests, the aerosol studied proved to be of very low systemic toxicity and negligible pulmonary fibrogenicity. This paradox may be explained by a low SiO2 retention in the lungs and other organs due to the relatively high solubility of these nanoparticles. nasal penetration of nanoparticles into the brain as well as their genotoxic action were found in the same experiment, results that make one give a cautious overall assessment of this aerosol as an occupational or environmental hazard.

Numerical Study on Particle Suction Performance of Reverse Blowing Pickup Mouth

The particle suction performance of reverse blowing pickup mouth is studied by Computational Fluid Dynamics (CFD). The inhalation test of dust particle and large particle were studied by simulation, and a theoretical arithmetic design discipline was put forward. The result shows that theoretical arithmetic can be used as a preliminary selection guide. The front inlet means velocity increases with the increasing of the diameter-length aspect ratio (iDL). While the Outlet mean velocity and the pressure decrease with the increase of iDL. The front inlet mean velocity from 48.5m/s down to 40.2m/s when iDL is from 0.11 to 0.16. The shorter the residence time is, the large particle can be inhaled easier. The residence time is 1.83s, which is 0.29s shorter than 2.12s in the same position of the 160mm diameter when the brick is on the left side of the driving direction. While the residence time is 1.13s, which is 0.19s shorter than that of 1.32s in the same position of 160mm diameter when the brick is in front of the Outlet.

Airspace Dimension Assessment with nanoparticles reflects lung density as quantified by MRI.

BackgroundAirspace Dimension Assessment with inhaled nanoparticles is a novel method to determine distal airway morphology. This is the first empirical study using Airspace Dimension Assessment with nanoparticles (AiDA) to estimate distal airspace radius. The technology is relatively simple and potentially accessible in clinical outpatient settings.MethodNineteen never-smoking volunteers performed nanoparticle inhalation tests at multiple breath-hold times, and the difference in nanoparticle concentration of inhaled and exhaled gas was measured. An exponential decay curve was fitted to the concentration of recovered nanoparticles, and airspace dimensions were assessed from the half-life of the decay. Pulmonary tissue density was measured using magnetic resonance imaging (MRI).ResultsThe distal airspace radius measured by AiDA correlated with lung tissue density as measured by MRI (ρ = −0.584; p = 0.0086). The linear intercept of the logarithm of the exponential decay curve correlated with forced expiratory volume in one second (FEV1) (ρ = 0.549; p = 0.0149).ConclusionThe AiDA method shows potential to be developed into a tool to assess conditions involving changes in distal airways, eg, emphysema. The intercept may reflect airway properties; this finding should be further investigated.

Towards Standardized Dissolution Techniques for In Vitro Performance Testing of Dry Powder Inhalers

Towards Standardized Dissolution Techniques for In Vitro Performance Testing of Dry Powder Inhalers

Inhalant allergen sensitization is an independent risk factor for the development of angioedema

Background/objectiveThe etiology and risk factors for angioedema remain poorly understood with causative triggers often going undiagnosed despite repeated reactions. The purpose of this study was to determine the relationship between inhalant allergen sensitization and angioedema. MethodsA retrospective review of patients who had in vitro inhalant allergy testing from 2006 to 2010 was performed. Patients with a diagnosis of angioedema who underwent inhalant allergy testing were identified. Analyses for co-morbidities, class of sensitization, seasonal timing of angioedema, and concurrent use of known hypertensive medications that can cause angioedema were performed. ResultsThere were 1000 patients who underwent inhalant allergy testing and qualified for the study. 37/1000 had at least one episode of angioedema and of these patients, 34 had positive inhalant sensitization testing results. Multivariate regression models showed overall sensitization status, seasonal allergen and epidermal/mite sensitization as independent risk factors (p<0.001, p=0.005, p=0.025 respectively) when controlling for ACE inhibitor use and other covariates. Tree, and epidermal/mite sensitizations were independent risk factors for angioedema in mono-sensitized subject analysis (p=0.028, p=0.029, respectively). ConclusionBoth seasonal and perennial allergen sensitizations are independent risk factors for the development of angioedema. In patients with angioedema and an unknown trigger, inhalant allergen sensitization should be considered as a potential contributing factor to the development of angioedema.

Comparison and evaluation of two different methods to establish the cigarette smoke exposure mouse model of COPD

Animal model of cigarette smoke (CS) –induced chronic obstructive pulmonary disease (COPD) is the primary testing methodology for drug therapies and studies on pathogenic mechanisms of disease. However, researchers have rarely run simultaneous or side-by-side tests of whole-body and nose-only CS exposure in building their mouse models of COPD. We compared and evaluated these two different methods of CS exposure, plus airway Lipopolysaccharides (LPS) inhalation, in building our COPD mouse model. Compared with the control group, CS exposed mice showed significant increased inspiratory resistance, functional residual capacity, right ventricular hypertrophy index, and total cell count in BALF. Moreover, histological staining exhibited goblet cell hyperplasia, lung inflammation, thickening of smooth muscle layer on bronchia, and lung angiogenesis in both methods of CS exposure. Our data indicated that a viable mouse model of COPD can be established by combining the results from whole-body CS exposure, nose-only CS exposure, and airway LPS inhalation testing. However, in our study, we also found that, given the same amount of particulate intake, changes in right ventricular pressure and intimal thickening of pulmonary small artery are a little more serious in nose-only CS exposure method than changes in the whole-body CS exposure method.

Study of regional homogeneity based resting-state functional MRI of olfactory dysfunction in patients with depression

Objective To investigate the subtle changes of the brain function at olfactory region of MD patients with olfactory dysfunction at resting state, through the application of fMRI-BOLD. Methods This study enrolled 28 MD patients with olfactory dysfunction(Case group) who had been treated from February 2016 to March 2017, and 23 healthy volunteers (Control group) with matching gender, age and education background to the Case group. All subjects were examined by Symptoms Checklists-90(SCL-90), Hamilton Depression Rating Scale-24 (HAMD-24), 70% isopropyl alcohol inhalation test, and fMRI at resting state. The two independent samples t test was used to compare the two groups' educational years, psychological scales and olfactory test scores. Regional homogeneity (ReHo) analysis was conducted for the whole brain of subjects. The ReHo values at some brain regions of both groups were compared through two independent sample t-test. The ReHo values, extracted from the case group's brain regions with differences, were run through by Pearson correlation analysis. Results There was a negative correlation between the HAMD-24 score (r=-0.413, P=0.029) and the severity of olfactory decline in the MD patients with olfactory dysfunction. In addition, it was found by fMRI that Case group, as compared to Control group, demonstrate declined ReHo values at left orbital frontal gyrus(cluster=80, t=3.27),bilateral cingulate gyrus(right cluster=204, t=4.34, left cluster=204, t=3.63),bilateral middle frontal gyrus(right cluster=56, t=3.67, left cluster=28, t=3.50), rightinsular(cluster=40, t=3.53), bilateral amygdala(right cluster=76, t=3.66, left cluster=86, t=2.93), but increased ReHo values at bilateral inferior frontal gyrus(right cluster=44, t=3.62,left cluster=33, t=3.25), right thalamus(cluster=34, t=3.21)and bilateral gyri rectus(right cluster=45,t=3.78, left cluster=24,t=3.01)(AlphaSim correction, P<0.001). Moreover, there was a positive correlation between the ReHo value at left orbital frontal gyrus and the olfactory test distance (r=0.628, P<0.05). But the ReHo value at left orbital frontal gyruswas negatively correlated with HAMD-24 (r=-0.414, P=0.029). There was no correlation with other clinical data. Conclusion The abnormal brain functional activities of left orbital frontal gyrus at resting state might be related to the olfactory dysfunction of patients with depression. Key words: Depression; Magnetic resonance imaging; Olfactorty function

Sarin Exposures in A Cohort of British Military Participants in Human Experimental Research at Porton Down 1945-1987.

The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK's centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken. Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis. In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28-51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present. These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans.

Particle sizing of pharmaceutical aerosols via direct imaging of particle settling velocities

We present a novel method for characterizing in near real-time the aerodynamic particle size distributions from pharmaceutical inhalers. The proposed method is based on direct imaging of airborne particles followed by a particle-by-particle measurement of settling velocities using image analysis and particle tracking algorithms. Due to the simplicity of the principle of operation, this method has the potential of circumventing potential biases of current real-time particle analyzers (e.g. Time of Flight analysis), while offering a cost effective solution. The simple device can also be constructed in laboratory settings from off-the-shelf materials for research purposes. To demonstrate the feasibility and robustness of the measurement technique, we have conducted benchmark experiments whereby aerodynamic particle size distributions are obtained from several commercially-available dry powder inhalers (DPIs). Our measurements yield size distributions (i.e. MMAD and GSD) that are closely in line with those obtained from Time of Flight analysis and cascade impactors suggesting that our imaging-based method may embody an attractive methodology for rapid inhaler testing and characterization. In a final step, we discuss some of the ongoing limitations of the current prototype and conceivable routes for improving the technique.