Associations between biomarkers in exhaled breath condensate (EBC) and allergic disease phenotypes and lung function

© 2016 Dr. Fahad Mohammed AldakheelAsthma is a common chronic disorder of the airways that involves a complex interaction of airflow obstruction, bronchial hyperresponsiveness and underlying airway inflammation. It is increasingly clear that asthma is a heterogeneous group of conditions (phenotypes) with common symptoms. The underlying mechanisms of different phenotypes are not clearly understood and the treatment responsiveness and causative factors are likely to vary between phenotypes. The increasing interest in airway inflammatory biomarkers assessment has led to the development and evolution of tools to measure these biomarkers which identify various asthma phenotypes. Exhaled breath condensate (EBC) is a totally non-invasive, easy to perform, feasible and inexpensive method for sampling lung and airways fluid, which reflects the airway epithelial lining fluid (ELF). EBC comprises a variety of airway inflammatory mediators, such as oxidative stress and pH, which provides non-invasive indicators of ongoing biochemical and inflammatory activity in the airways. Although EBC samples the entire respiratory tract from the mouth to the alveoli, the precise origin of each sampled molecule cannot be determined. A number of studies have assessed the relationship between EBC biomarkers and adult airway diseases, such as asthma. However, these studies have had limited sample sizes and, as a result, were unable to compare associations between numerous phenotypes of airway diseases. It remains possible that the associations with EBC biomarkers may change with age, but this has not been examined in a single study using the same methods. Furthermore, previous studies have been conducted in clinical populations rather than epidemiologic settings. Therefore, the overall aim of this PhD research was to assess the associations between oxidative stress biomarkers and pH in EBC and asthma phenotypes, rhinitis phenotypes, atopic sensitisation, lung function and objective markers of airway inflammation, including bronchial hyperresponsiveness (BHR) and the fraction of exhaled nitric oxide (FeNO), in both the early adulthood and middle-aged groups. Within this thesis, cross-sectional analyses nested within the two Australian longitudinal studies have been performed. These studies are: (1) The Melbourne Atopy Cohort Study (MACS), a study of individuals with a family history of allergic disease (defined as the early adulthood group in this thesis); and (2) The Tasmanian Longitudinal Health Study (TAHS), a population-based study (defined as the middle-aged group in this thesis). EBC samples were collected at the 18-year follow-up of MACS and the BHR LAB Study of the 5th-decade follow-up of TAHS. Using these data, this thesis contributes knowledge to the field, specifically addressing the following issues: Methodological issues from the laboratory analysis of EBC biomarkers Findings from this doctoral research showed that EBC biomarkers were influenced by the long period of storage, particularly for hydrogen peroxide (H2O2). The vast majority of analysed samples for H2O2 were shown to be below the lower limit of detection (LOD). In addition, both decreased levels of EBC total nitric oxide products (NOx) and increased EBC pH were associated with a long period of sample storage. Therefore, the duration of sample storage was adjusted for in all analyses presented in this thesis. Associations between EBC NOx and different phenotypes of asthma and rhinitis, sensitisation, lung function, BHR and FeNO This PhD research showed that atopic asthma and atopic rhinitis phenotypes were associated with higher levels of EBC NOx. Also, atopic sensitisation was related to increased levels of EBC NOx and this association was stronger in individuals with poly- aero-sensitisation. These findings were generally consistent across the two age groups. In the early adulthood group only, elevated levels of EBC NOx were associated with reduced pre- and post-BD FEV1/FVC. Additionally, EBC NOx was not related to BHR and FeNO. Therefore, EBC NOx may be considered a marker for allergic airway inflammation in different age groups. Associations between EBC pH and different phenotypes of asthma and rhinitis, sensitisation, lung function, BHR and FeNO Reduced EBC pH was associated with the presence of asthma and strongly associated with severity of asthma symptoms, as well as atopic asthma and atopic rhinitis in the early adulthood group. Also, similar associations were observed in those with atopic sensitisation, particularly in those who were sensitised to more than one tested allergen. However, none of the above associations were observed in the middle-aged group, suggesting that these effects may be age-dependent. Alternatively, it may be due to differences in methods used between the projects (e.g. degree of deaeration of the sample post collection). In addition, there were no associations between EBC pH, lung function, BHR, and FeNO in either project. These findings suggest that associations between airway acidification and asthma and sensitisation phenotypes may be influenced by the age of an individual. Conclusion Overall, my doctoral work observed some novel and interesting associations. Results from this thesis will aid the current understanding of an underlying inflammatory process, help to discriminate between different phenotypes of airway diseases and help guide future research. Although EBC is a promising method, it lacks appropriate standardisation and reference values and is therefore not currently suitable for use in clinical practice

Effects of Compression applied to Gas Diffusion Layers in PEM Fuel Cells

There is a global and urgent need to embrace alternative renewable power sources to mitigate the detrimental environmental effects of the greenhouse gases, in particular carbon dioxide. Proton electrolyte membrane (PEM) fuel cells have been an attractive clean technology to decarbonise a multitude of applications, particularly those in the automotive sector. Although PEM fuel cells have, compared to other types of fuel cells, high efficiency and low-operating temperature, there are still some very important challenges that need to be overcome so that the PEM has a wider application. One of the main issues that affect the lifetime of PEM fuel cells is the mechanical degradation of the gas diffusion layers (GDLs). Since GDLs are responsible for the transport of reacting gases, heat and electronic charge from/to the catalyst layers, any damage to their structure may have detrimental consequences on the above transport processes and, subsequently, the performance of the fuel cell. Typically, GDLs are subject to two types of compressive stresses: assembling and cyclic stresses. The assembling stress occurs due to the clamping pressure applied to assemble the various components of the fuel cell. The cyclic stress is due to the hydration/dehydration cycles of the membrane as it swells or shrinks. In this thesis, a novel and carefully designed compression test (mimicking the assembling and cyclic stresses that the GDL is subjected to within the fuel cell) has been performed on a set of commercially available GDLs. This was followed by a series of tests to examine the effects of compression on the mass transport (gas permeability test), morphology (SEM analysis), thermal stability (TGA analysis), and wettability (contact angle test) of the tested GDLs. Such tests and the related outcomes are of much importance to the researchers in the field, especially those who model PEM fuel cells as these tests provide much more accurate and realistic data for the physical properties being investigated. The same investigation was then performed in the presence of sealing gaskets in order to explore how the effects of compression are mitigated with the sealing gaskets. Finally, the experimental values for the GDL gas permeability and contact angle (before and after compression) were fed into a comprehensive three-dimensional PEM fuel cell model to investigate their effects on the overall performance of the cell. The key findings of the study are as follows: (i) the MPL-coated GDLs are more resistive to mechanical deformation than uncoated GDLs, (ii) the contact angle of the GDLs reduce by 3° - 15° after compression, (iii) GDLs are less deformed in presence of sealing gaskets, (iv) GDLs lose around 40% of its PTEF content after compression and (v) the performance of the modelled fuel cell is hardly affected by variation in GDL gas permeability

Antimicrobial Analysis of Biosynthesized Lectin-Conjugated Gold Nanoparticles

To enhance the bioactivity of molecules through nanoparticles is being tested which has potential use in sustained-release drug delivery systems and to enhance the therapeutic effectiveness of drugs. Our current investigation s is to conjugate lectin to that of a gold nanoparticle (GNP) surface without disturbing the bioactive properties and enhances the antibacterial activity of lectin. Au-lectin nanoparticles were checked for their hemagglutination activity, characterized by transmission electron microscopy (TEM) and UV-visible spectrophotometer. The antibacterial effect of nanoparticle lectin, Au salt nanoparticle, and conjugated Au-lectin was estimated by Kirby-Bauer disc method; MICs were determined by microbroth dilution and compared with ciprofloxacin. These tests were done using known species of bacterial strain of multidrug resistant. The hemagglutination activity of lectin was improved to fourfold after purification. Lectin and Au nanoparticles combined had a significant effect on the inhibition of bacterial growth. No significant differences were observed in the inhibition zone diameters from killed bacteria and its supernatant towards any of the tested organisms. Lectin-conjugated gold particles showed good efficacy as antimicrobial agents and the nanoparticle-killed bacteria to work against the viable population of the same bacterium and/or other bacterial species too

Synthetic nanocomposite MgH2/5 wt. % TiMn2 powders for solid-hydrogen storage tank integrated with PEM fuel cell

Abstract Storing hydrogen gas into cylinders under high pressure of 350 bar is not safe and still needs many intensive studies dedic ated for tank’s manufacturing. Liquid hydrogen faces also severe practical difficulties due to its very low density, leading to larger fuel tanks three times larger than traditional gasoline tank. Moreover, converting hydrogen gas into liquid phase is not an economic process since it consumes high energy needed to cool down the gas temperature to −252.8 °C. One practical solution is storing hydrogen gas in metal lattice such as Mg powder and its nanocomposites in the form of MgH2. There are two major issues should be solved first. One related to MgH2 in which its inherent poor hydrogenation/dehydrogenation kinetics and high thermal stability must be improved. Secondly, related to providing a safe tank. Here we have succeeded to prepare a new binary system of MgH2/5 wt. % TiMn2 nanocomposite powder that show excellent hydrogenation/dehydrogenation behavior at relatively low temperature (250 °C) with long cycle-life-time (1400 h). Moreover, a simple hydrogen storage tank filled with our synthetic nanocomposite powders was designed and tested in electrical charging a battery of a cell phone device at 180 °C through a commercial fuel cell

Silver Nanoparticles Loaded on Chitosan-g-PVA Hydrogel for the Wound-Healing Applications

Silver nanoparticle composites have abundant biomedical applications due to their unique antibacterial properties. In the current work, green tea leaf extract was used as a natural reducing agent to synthesize AgNPs (AgNPs) using microwave irradiation technology. Furthermore, microwave irradiation has been used for the preparation of AgNPs/chitosan (Ch) grafted polyvinyl alcohol (PVA) hydrogel samples. To approve the accomplishment of AgNPs hydrogel polymer, UV-spectrum, TEM, and FT-IR spectrum analyses and the release of silver ions, actions were taken. The wound-healing ability of the prepared hydrogel samples was measured via both the in vitro (fibroblast cells) and the in vivo using rat models. It was found that chitosan-grafted polyvinyl alcohol, including AgNPs, exhibited excellent antibacterial activity against E. coli and S. aureus using the agar diffusion method. It can be said that microwave irradiation was successful in creating a hydrogel that contained silver nanoparticles. A wound that was still open was successfully treated with these composites

Overall results of ELISA (n = 1500).

<p>Overall results of ELISA (n = 1500).</p

Comparison of four assays for detection of HBV-DNA.

<p>Comparison of four assays for detection of HBV-DNA.</p

Detection of HBsAg mutants in the blood donor population of Pakistan

<div><p>Background</p><p>Infection with the Hepatitis B virus (HBV) continues to be one of the leading healthcare issues in Pakistan, affecting over 6 million people. The existence of HBsAg mutants is well documented in many countries. In Pakistan, HBV screening in the majority of the blood banks is performed by Rapid Detection Devices or ELISA tests. These tests are designed to detect HBsAg, but may not detect the mutant HBsAg. Failure to detect the HBsAg mutant may result in the transmission of HBV infection from donor to recipient. Hence, there is a need to identify a HBsAg assay which can detect mutants in a country where simple and conventional HBsAg assays with varying sensitivity and specificity are used to detect HBV infections.</p><p>Material and methods</p><p>Three routinely used diagnostic tests (Rapid Detection Devices, ELISA and CLIA) for HBsAg were compared with the LIAISON^® XL Murex HBsAg Quant Assay to determine the prevalence of HBV mutants in the Pakistani blood donor population.</p><p>The samples of blood donors from different cities of Pakistan were collected. The testing was performed using SD Bioline rapid assay (n = 1500), ELISA (n = 1500), and Abbott ARCHITECT^®CLIA system (n = 1500) at the centers where the donations were collected. All samples (n = 4500) were re-tested for comparative analysis on the LIAISON^® XL Murex HBsAg Quant assay (DiaSorin S.p.A.). PCR testing was performed as a gold standard on all discordant samples.</p><p>Results</p><p>119/4500 (2.64%) of the samples were positive for antibodies against HBsAg. The sensitivity of SD Bioline Rapid, GB HBsAg ELISA, Abbott ARCHITECT^® and LIAISON^® XL Murex HBsAg Quant assay was 17.24%, 43.75%, 90.91%and 100% respectively. The specificity of SD Bioline Rapid, GB HBsAg ELISA, Abbott ARCHITECT^® and LIAISON^® XL Murex HBsAg Quant Assay was 98.82%, 99.59%, 100% and 100%, respectively.</p><p>Conclusion</p><p>LIAISON^® XL Murex HBsAg Quant assay is a highly sensitive, specific and accurate screening assay for detecting wild type as well as mutant HBsAg.</p></div

Overall results of LIAISON^® XL CLIA Murex Assay (n = 4500).

<p>Overall results of LIAISON^® XL CLIA Murex Assay (n = 4500).</p

Knowledge about the Risk of Cardiovascular Disease among Adults with Type 2 Diabetes Visiting the Outpatient Clinics at Tertiary Hospital in Riyadh, Saudi Arabia: A Cross-Sectional Study

Background: One of the primary goals of diabetes management is to prevent cardiovascular events. The rate of cardiovascular diseases (CVDs) is significantly high in the diabetic population. Inadequate knowledge of CVDs risk in diabetes may result in the failure of its early prevention, causing increased morbidity and mortality. The objectives of this study were to assess the CVD risk knowledge and determine the predictors of the knowledge among adults with type 2 diabetes. Methods: A cross-sectional study was conducted to examine the study objectives. Convenience sampling was used to recruit adults with type 2 diabetes mellitus (DM) who visited the King Saud University Medical City (KSUMC) outpatient clinics. Data were collected using the Heart Disease Fact Questionnaire. SPSS software (version 24.0) was used for data analysis. Results: A total of 383 patients were recruited. The level of CVD risk knowledge was high among all participants (19.04 &plusmn; 3.47). There were significant differences in knowledge scores between different groups, including age (p = 0.01), marital status (p = 0.01), and type of residence (p = 0.04). Participants who were older than 40 years, married, and lived in traditional houses had higher knowledge scores. Conclusion: The study findings indicated a high level of CVD risk knowledge in our study population. The presence of multidisciplinary intensive education programmes targeting type 2 DM patients, such as that conducted at KSUMC, might be responsible for the higher levels of knowledge among our study population. Thus, increasing the efforts towards the education of patients will improve the level of knowledge, including CVD risk knowledge