[Show abstract][Hide abstract] ABSTRACT: The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population. Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods - all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges. This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.
World Allergy Organization Journal 12/2015; 8(1):25. DOI:10.1186/s40413-015-0073-0
[Show abstract][Hide abstract] ABSTRACT: Purpose
In this study, we aimed to develop novel therapeutic and diagnostic approaches by improving the targeting of doxorubicin-loaded single-walled carbon nanotubes (SWCNTs) to metastatic regions, and monitor their preferential homing and enhanced therapeutic effect using noninvasive free-breathing magnetic resonance imaging (MRI) and bioluminescence imaging.
High-energy flexible magnets were specifically positioned over the metastatic tumor sites in the lungs. SWCNTs biodistribution, tumor progression, and subsequent treatment efficiency were assessed following administration of the magnetically attracted doxorubicin-loaded anti-CD105 conjugated nanocarriers.
The use of high-energy magnets offered improved theranostic effect of doxorubicin-loaded nanocarriers, by magnetically targeting them towards metastatic tumor sites in the lungs. MRI allowed sensitive monitoring of nanocarriers biodistribution in the abdominal organs, their preferential homing towards the metastatic sites, and their enhanced therapeutic effect.
Combination of noninvasive MRI to localize sensitively the tumor sites, with specific positioning of magnets that can enhance the magnetic targeting of nanocarriers, allowed increasing the treatment efficiency.
[Show abstract][Hide abstract] ABSTRACT: Acute exacerbations of bronchial asthma remain a major cause of frequent Emergency Department (ED) visits by pediatric patients. However, other factors including psychosocial, behavioural and educational, are also reportedly associated with repetitive ED visits. Therefore, it is necessary to determine whether such visits are justifiable.
The objective of this cross-sectional study was to identify risk factors associated with visits to ED by asthmatic children.
Asthmatic children (n = 297) between 1-17 years old were recruited and information collected at the time of visiting an ED facility at two major hospitals.
Asthmatic patients visited the ED 3.9 3.2 times-per-year, on average. Inadequately controlled asthma was perceived in 60.3% of patients. The majority of patients (56.4%) reported not receiving education about asthma. Patients reflected misconceptions about the ED department, including the belief that more effective treatments are available (40.9%), or that the ED staff is better qualified (27.8%). About half of patients (48.2%) visited the ED because of the convenience of being open 24 hours, or because they are received immediately (38.4%). Uncontrolled asthma was associated with poor education about asthma and/or medication use. Patients educated about asthma, were less likely to stop corticosteroid therapy when their symptoms get better (OR:0.55; 95% CI:0.3-0.9; P = 0.04).
This study reports that most patients had poor knowledge about asthma and were using medications improperly, thus suggesting inefficient application of management action plan. Unnecessary and frequent visits to the ED for asthma care was associated with poor education about asthma and medication use. Potential deficiencies of the health system at directing patients to the proper medical facility were uncovered and underline the necessity to improve education about the disease and medication compliance of patients and their parents/guardians.
Annals of Thoracic Medicine 04/2015; DOI:10.4103/1817-1737.150735 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IL-17 is a pro-inflammatory mediator that is believed to play a critical role in regulating tissue inflammation during asthma, COPD, as well as other inflammatory disorders. The level of expression of IL-17 has been shown to be upregulated in lung bronchial tissue of asthmatic patients. Several reports have provided further evidence that this cytokine could play a key role in enhancing the migration of inflammatory as well as structural cells of the bronchial lung tissue during asthma and COPD. B cell infiltration to sites of inflammation during inflammatory disorders such as bowel disease, asthma and COPD has been reported. Accordingly, in this study we hypothesized that IL-17 may exert a chemotactic effect on primary B cells during asthma. We observed that B cells from asthmatic patients expressed significantly higher levels of IL-17RA and IL-17RC, compared to those of healthy subjects. Using an in-vitro migration assay, B cells were shown to migrate towards both IL-17A and IL-17F. Interestingly, blocking IL-17A and IL-17F signaling using either anti-IL-17R antibodies or MAP kinase inhibitors prevented in vitro migration of B cell towards IL-17. These observations indicate a direct chemotactic effect of IL-17 cytokines on primary peripheral blood B cells with higher effect being on asthmatic B cells. These findings revealed a key role for IL-17 in enhancing the migration of B cells to the lung tissue during asthma or COPD.
PLoS ONE 12/2014; 9(10):e114604. DOI:10.1371/journal.pone.0114604 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
Rs37972 and rs37973 variants in the glucocorticoid-induced transcript 1 gene have been associated with inhaled glucocorticosteroid responsiveness in asthmatics; however, some discrepancies have been also reported. This study aims to determine whether rs37972 and rs37973 SNPs are associated with asthma risk in Saudi Arabian asthmatics.
Two-hundred seventy-one diagnosed asthmatics (3-65 years old) and 387 healthy control subjects of equivalent age were recruited. DNA from peripheral blood was purified, and genotyping of rs37972 and rs37973 SNPs was performed by PCR amplification of segments of interest, followed by Sanger sequencing.
The global frequencies of the minor (risk) alleles were 28% ("T" allele, rs37972) and 30% ("G" allele, rs37973). Yates-corrected Chi-square (χ(2)) tests revealed significant differences between asthmatic and healthy groups, in allele frequencies for rs37973 SNP only (χ(2) = 3.98, Yates' p value = 0.046). Regarding genotype frequencies, a significant difference between asthmatic and healthy groups was observed for variant rs37972 only (χ(2) = 8.19, Yates' p value = 0.016). To determine a possible association of the minor "T" and "G" alleles with asthma, both the recessive and dominant genetic models were tested. For rs37973, none of the genotypes were significantly associated with asthma. Concerning rs37972, the dominant model (C/T + T/T versus C/C) indicated a significant "protective" association with asthma, in which C/T + T/T individuals had lower odds of being asthmatics than C/C individuals (OR = 0.67; 95% CI = 0.48-0.94; p = 0.019*).
The minor alleles "T" and "G" of rs37972 and rs37973 SNPs, respectively, were not significantly associated with increased asthma risk in asthma patients from Saudi Arabia.
Journal of Asthma 08/2014; 52(2):1-26. DOI:10.3109/02770903.2014.955189 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The signal transducer and activator of transcription 6 (STAT6) transduces signals in response to IL-4 and IL-13 cytokine stimulations, resulting in many cell-specific responses. Some common STAT6 SNPs were associated with asthma predisposition and/or IgE levels, although discrepancies have also been reported.
To determine whether STAT6 rs324011 and rs324015 polymorphisms are associated with atopic asthma in Saudi Arabian patients.
A total of 536 Saudi individuals aged 11–70 years old (230 atopic asthmatics, 306 healthy subjects) were recruited. DNA was purified from peripheral blood and genotyping for rs324011 and rs324015 polymorphisms was performed by PCR amplification, followed by cycle sequencing of the purified PCR fragments using BigDye chain terminator and capillary electrophoresis.
By the contrast of alleles tests, no significant differences between asthma and healthy groups were detected for both variants (rs324011: X2 = 0.25, Pearson’s P-value = 0.617; rs324015: X2 = 0.068, Pearson’s P = 0.814).When testing for genotypes, rs324011 homozygous T/T genotype was significantly associated with asthma, when the Recessive model is considered (T/T vs. C/C + C/T) (adjusted, OR = 2.49, 95% CI = 1.18–5.25, Pearson’s P = 0.014∗, Yates’ P = 0.022∗). In contrast, rs324015 variant was not significantly associated with asthma.
Rs324011 homozygous T/T genotype was significantly associated with asthma risk whereas rs324015 genotypes were not in the Saudi population.
Human Immunology 08/2014; DOI:10.1016/j.humimm.2014.05.012 · 2.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Targeting and noninvasive imaging of a specific alveolar macrophage subpopulation in the lung has revealed the importance for early and better diagnosis and therapy of chronic obstructive pulmonary disease (COPD). In this study, the in vivo effect of pulmonary administration of iron oxide nanoparticles on the polarization profile of macrophages was assessed, and a noninvasive free-breathing magnetic resonance imaging (MRI) protocol coupled with the use of biocompatible antibody-conjugated superparamagnetic iron oxide (SPIO) nanoparticles was developed to enable specific targeting and imaging of a particular macrophage subpopulation in lipopolysaccharide-induced COPD mice model.
Enzyme-linked immunosorbent assay, Real-time polymerase chain reaction, and flow cytometry analysis were performed to assess the biocompatibility of PEGylated dextran-coated SPIO nanoparticles. Specific biomarkers for M1 and M2 macrophages subsets were selected for conjugation with magnetic nanoparticles. MRI protocol using ultra-short echo time sequence was optimized to enable simultaneous detection of inflammation progress in the lung and detection of macrophages subsets. Flow cytometry and immunohistochemistry analysis were finally performed to confirm MRI readouts and to characterize the polarization profile of targeted macrophages.
The tested SPIO nanoparticles, under the current experimental conditions, were found to be biocompatible for lung administration in preclinical settings. Cluster of differentiation (CD)86- and CD206-conjugated magnetic nanoparticles enabled successful noninvasive detection of M1 and M2 macrophage subpopulations, respectively, and were found to co-localize with inflammatory regions induced by lipopolysaccharide challenge. No variation in the polarization profile of targeted macrophages was observed, even though a continuum switch in their polarization might occur. However, further confirmatory studies are required to conclusively establish this observation.
Coupling of magnetic iron oxide nanoparticles with a specific antibody targeted to a particular macrophage subpopulation could offer a promising strategy for an early and better diagnosis of pulmonary inflammatory diseases using noninvasive MRI.
International Journal of Nanomedicine 03/2014; 9(1):1491-503. DOI:10.2147/IJN.S59394 · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Noninvasive imaging of macrophages activity has raised increasing interest for diagnosis of chronic obstructive respiratory diseases (COPD), which make them attractive vehicles to deliver contrast agents for diagnostic or drugs for therapeutic purposes. This study was designed to monitor and evaluate the migration of differently polarized M1 and M2 iron labeled macrophage subsets to the lung of a LPS-induced COPD animal model and to assess their polarization state once they have reached the inflammatory sites in the lung after intravenous injection. Ex vivo polarized bone marrow derived M1 or M2 macrophages were first efficiently and safely labeled with amine-modified PEGylated dextran-coated SPIO nanoparticles and without altering their polarization profile. Their biodistribution in abdominal organs and their homing to the site of inflammation in the lung was tracked for the first time using a free-breathing non-invasive MR imaging protocol on a 4.7T magnet after their intravenous administration. This imaging protocol was optimized to allow both detection of iron labeled macrophages and visualization of inflammation in the lung. M1 and M2 macrophages were successfully detected in the lung starting from 2 hours post injection with no variation in their migration profile. Quantification of cytokines release, analysis of surface membrane expression using flow cytometry and immunohistochemistry investigations confirmed the successful recruitment of injected iron labeled macrophages in the lung of COPD mice and revealed that even with a continuum switch in the polarization profile of M1 and M2 macrophages during the time course of inflammation a balanced number of macrophage subsets predominate.
PLoS ONE 03/2014; 9(3):e90829. DOI:10.1371/journal.pone.0090829 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The IL-4 receptor alpha subunit (IL-4Rα), when associated with the common gamma chain receptor, or the IL-13Rα1 subunit, transduces signals to STAT6 in response to IL-4 and IL-13 stimulations. This results in a number of cell-specific responses including Th2 differentiation, lymphocyte proliferation and IgE production. Given the prominent role of IL-4Rα in allergic disorders, several single-nucleotide polymorphisms (SNPs) have been found associated with asthma and other atopic disorders, including rs1805010 (I75V) and rs1801275 (Q576R) SNPs; however, lack of significant association have also been reported for some ethnic groups. The objective of this study was to determine whether IL-4Rα rs1805010 and rs1801275 polymorphisms are associated with asthma in patients from Saudi Arabia.
One hundred and ninety severe asthmatic patients (11-70 years old) and 194 healthy subjects of equivalent age range were recruited for blood donation. DNA was purified and genotyping for rs1801275 and rs1805010 polymorphisms in the IL-4Rα gene was performed by PCR amplification, followed by cycle sequencing of the purified PCR fragments using BigDye chain terminator and capillary electrophoresis.
Pearson's Chi-square tests showed that the minor alleles, G, for both rs1805010 and rs1801275 SNPs, were significantly more frequent in asthmatics than in the healthy group (Yates' P < 0.05); conversely, the major alleles, A, were significantly more frequent in healthy than in asthmatics (P < 0.05). Concerning association analysis, odds for A/G-G/G genotypes were significantly higher to be associated with asthma predisposition (rs1801275: OR = 2.12; 95% CI = 1.39-3.22; P < 0.001*; rs1805010: OR = 1.6; 95% CI = 1.01-2.53; P < 0.05*; dominant model). Analysis of gender-genotype interactions, with genders nested within A/G-G/G, indicated higher odds for females than males of significant association with asthma (rs1801275: OR = 5.19, 95% CI = 2.09-12.94*; rs1805010: OR = 3.73, 95% CI = 2.06-6.74*). Rs1805010 and rs1801275 were in linkage disequilibrium (D' = 0.27; P < 0.0004*), with G-G haplotype being more frequent in asthmatics than in healthy subjects (OR = 2.43, 95% CI = 1.59-3.71*).
The risk alleles, G, of IL-4Rα rs1805010 and rs1801275 SNPs and corresponding A/G-G/G genotypes were significantly associated with asthma predisposition in asthmatics from Saudi Arabia.
Annals of Thoracic Medicine 03/2014; 9(2):81-86. DOI:10.4103/1817-1737.128849 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The main objective of this study was to evaluate CYP2D6 genetic polymorphism in a Saudi Arabian population by determining the frequencies of CYP2D6*41, CYP2D6*29, CYP2D6*3, CYP2D6*6 and CYP2D6*14 alleles. Genomic DNA was isolated from 192 healthy Saudis representing different geographical regions, and genotyping of the selected CYP2D6 variants was carried out by direct sequencing. The allelic frequency of CYP2D6*41 was found to be 18.4%, and that of CYP2D6*29 to be 2.9%. The other investigated alleles were either not detected or rarely present in the study population. In addition, two commonly shared single nucleotide polymorphisms (SNPs) and two very rare SNPs among CYP2D6 alleles were detected. Further studies are therefore, required to evaluate the metabolic and clinical relevance of CYP2D6*41 in Saudi Arabians.
[Show abstract][Hide abstract] ABSTRACT: Glucuronidation is an important phase II pathway responsible for the metabolism of many endogenous substances and drugs to less toxic metabolites, which undergo renal excretion. The aim of the current work was to evaluate genotype and allele frequencies of certain UDP-glucuronosyltransferase 1A1 (UGT1A1) variants in an Arab population.
Genomic DNA was isolated from 192 healthy unrelated Saudi males of various geographic regions and genotyping of UGT1A1*6, *27, *36, *28, *37, and *60 was carried out using polymerase chain reaction (PCR) amplification followed by direct sequencing.
The most common allele for (TA) repeats was the wild type (TA)6 with a frequency of 74.3% followed by the mutant (TA)7 (i.e., UGT1A1*28) with a frequency of 25.7%. The distribution of UGT1A1*60 allele was 62.4% among subjects with the homozygous mutant genotype of 35.4%, while the wild type variant represents 10.6% only. Both UGT1A1*6 and *27 were not detected as all screened subjects showed a homozygous wild type pattern. Similarly, UGT1A1*36* and *37 were either not present or rarely found, respectively. In comparison to other populations, the frequency of UGT1A1*60 and *28 in the studied population was less than that of African Americans but higher than Asians. The geographical origin of the study subjects also implied some differences in genotype distribution of (TA) repeats and UGT1A1*60.
Our data indicate that Saudis harbor some important UGT1A1 mutations known to affect enzyme activity. Additional studies are warranted to assess the clinical implications of these gene polymorphisms in this ethnic group.
Archives of Medical Science 08/2013; 9(4):731-8. DOI:10.5114/aoms.2013.37012 · 2.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polymorphism in (TA)n of the UGT1A1 promoter influences bilirubin level and risk of gallstones in patients with sickle cell disease (SCD) of African descent. Modifiers of bilirubin level and gallstones in Saudi patients with SCD are not known.
Patients with SCD presenting to participating institutions between July 2009 and July 2012 were enrolled in our study.
A total of 223 SCD patients were enrolled. Laboratory workup at steady state included complete blood count, reticulocytes, serum bilirubin, lactate dehydrogenase (LDH), G6PD level, and hemoglobin (Hb) electrophoresis. The (TA)n UGT1A1 promoter polymorphism and presence of a-thalassemia were also deter.mined.
TA6/6 in the UGT1A1 promoter was identified in 189 patients (84.7%), TA7/7 in 26 (11.7%), TA5/5 in 6 (2.7%), and TA5/6 in 2 (0.9%). Increased (TA)n of the UGT1A1 promoter (P < .0001), male gender (P=.02), higher LDH (P=.001), and lower Hb level (P=.009) were associated with higher bilirubin level, while the co-inheritance of a-thalassemia (P=.003) was linked with lower bilirubin level. UGT1A1 (TA)n (P < .0001) and Hb level (P=.005) remained significant on multivariate analysis. Gallstones were more frequent in patients with TA7/7 (72%) compared to patients with TA6/6 (57%) and TA5/5 or 5/6 (37%); however, this difference was not statistically significance (P=.18). Older age (P=.0001) and absence of a-thalassemia (P=.03) were associated with higher risk of gallstones.
(TA)n in the UGT1A1 promoter and intensity of hemolysis modify steady-state serum bilirubin level in SCD. Co-inheritance of a-thalassemia reduces the risk of gallstones in Saudi patients with SCD.
Annals of Saudi medicine 07/2013; 33(4):372-6. DOI:10.5144/0256-4947.2013.372 · 0.49 Impact Factor