Browsing by Author "Heialy, Saba Al"

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Asthma Associated Cytokines Regulate the Expression of SARS-CoV-2 Receptor ACE2 in the Lung ‎Tissue of Asthmatic Patients
(2022) Heialy, Saba Al; Hachim, Mahmood Yaseen
Abstract:‎ It is still controversial whether chronic lung inflammation increases the risk for COVID-19. One of the ‎risk factors for acquiring COVID-19 is the level of expression of SARS-CoV-2 entry receptors, ACE2 and ‎TMPRSS2, in lung tissue. It is, however, not clear how lung tissue inflammation affects expression ‎levels of these receptors. We hence aimed to determine the level of SARS-CoV-2 receptors in lung ‎tissue of asthmatic relative to age, gender, and asthma severity, and to investigate the factors ‎regulating that. Therefore, gene expression data sets of well-known asthmatic cohorts (SARP and U-‎BIOPRED) were used to evaluate the association of ACE2 and TMPRSS2 with age, gender of the ‎asthmatic patients, and also the type of the underlying lung tissue inflammatory cytokines. Notably, ‎ACE2 and to less extent TMPRSS2 expression were upregulated in the lung tissue of asthmatics ‎compared to healthy controls. Although a differential expression of ACE2, but not TMPRSS2 was ‎observed relative to age within the moderate and severe asthma groups, our data suggest that age ‎may not be a key regulatory factor of its expression. The type of tissue inflammation, however, ‎associated significantly with ACE2 and TMPRSS2 expression levels following adjusting with age, gender ‎and oral corticosteroids use of the patient. Type I cytokine (IFN-g), IL-8, and IL-19 were associated with ‎increased expression, while Type II cytokines (IL-4 and IL-13) with lower expression of ACE2 in lung ‎tissue (airway epithelium and/or lung biopsies) of moderate and severe asthmatic patients. Of note, ‎IL-19 was associated with ACE2 expression while IL-17 was associated with TMPRSS2 expression in ‎sputum of asthmatic subjects. In vitro treatment of bronchial fibroblasts with IL-17 and IL-19 cytokines ‎confirmed the regulatory effect of these cytokines on SARS-CoV-2 entry receptors. Our results ‎suggest that the type of inflammation may regulate ACE2 and TMPRSS2 expression in the lung tissue ‎of asthmatics and may hence affect susceptibility to SARS-CoV-2 infection.‎
Asthma severity as a contributing factor to cancer incidence: A cohort study
(2021) Hassan Khamis, Amar; Heialy, Saba Al
Background: A putative link between asthma and asthma severity with the occurrence of cancer has been suggested but has not been fully investigated. The objective of this study is to assess the incidence of all types of cancer in a cohort of asthmatic patients. Methods and findings: A single center cohort retrospective study was conducted to investigate the role of asthma as a potential risk factor for various cancers. Participants were followed for a period of 9 years from 01/01/2010 to 30/12/2018 and cancer incidence and its determinants were collected in asthmatic patients and controls from the same population source but without any respiratory disease. Overall, 2,027 asthma patients and 1,637 controls were followed up for an average of 9 years. The statistical analysis showed that 2% of asthma patients were diagnosed with various cancers, resulting in an incidence rate of cancer of 383.02 per 100,000 persons per year which is significantly higher than the 139.01 per 100,000 persons per year observed in matched controls (p-value < 0.001). The top four cancers reported among asthmatics were breast, colon, lung and prostate cancer. Lung cancer in asthmatics had the longest diagnosis period with a mean of 36.6 years compared to the shortest with prostate cancer with 16.5 years. Conclusions: This study shows that asthma patients are at increased risk of different types of cancers with asthma severity and goiter as the main factors that may increase the risk of developing cancers among asthmatic patients.
Combination of obesity and co-morbidities leads to unfavorable outcomes in COVID-19 patients
(2020) Heialy, Saba Al; Hachim, Mahmood Yaseen
Objective: Obesity has been described as a significant independent risk factors of COVID-19. We aimed to study the association between obesity, co-morbidities and clinical outcomes of COVID-19. Methods: Clinical data from 417 patients were collected retrospectively from the Al Kuwait Hospital, Ministry of Health and Prevention (MOHAP), Dubai, United Arab Emirates, who were admitted between March and June 2020. Patients were divided according to their body mass index (BMI). Various clinical outcomes were examined: presenting symptoms, severity, major co-morbidities, ICU admission, death, ventilation, ARDS, septic shock and laboratory parameters. Results: The average BMI was 29 ± 6.2 kg/m2. BMI alone was not associated with the outcomes examined. However, class II obese patients had more co-morbidities compared to other groups. Hypertension was the most significant co-morbidity associated with obesity. Patients with BMI above the average BMI (29 kg/m2) and presence of underlying co-morbidities showed significant increase in admission to ICU compared to patients below 29 kg/m2 and underlying co-morbidities (21.7% Vs. 9.2%), ARDS development (21.7% Vs. 10.53%), need for ventilation (8.3% Vs. 1.3%), and mortality (10% Vs. 1.3%). Conclusions: Our data suggests that presence of underlying co-morbidities and high BMI work synergistically to affect the clinical outcomes of COVID-19.
Effect of bronchial thermoplasty on structural changes and inflammatory mediators in the airways of subjects with severe asthma
(2019-03-20) Heialy, Saba Al
Background: Bronchial thermoplasty (BT) is a novel technique used in the treatment of subjects with severe refractory asthma. Radio frequency is provided to airway walls during bronchoscopy in order to reduce airway remodeling. Several clinical studies have reported an improvement in subjects’ symptoms following BT.However, how BT affects the airway architectures and inflammatory mediators in the airways has not been yet fully elucidated. Methods: Fourteen subjects with severe asthma were recruited in this study according to the criteria of ATS severe asthma definition. The study subjects undertook bronchial biopsy during the bronchoscopy procedure at baseline and 6 weeks after the initial BT treatment. The obtained samples were stained with antibodies forα-smooth muscle actin (α-SMA); protein gene product (PGP) 9.5, a specific nerve marker; von Willebrand factor(vWF), a marker for blood vessels; interleukin-17A (IL-17A) and transforming growth factor-β1 (TGF-β1). Results: The expression ofα-SMA and PGP9.5 were significantly reduced post-BT. There was no significant difference in the number of blood vessels between baseline and post-BT. In addition, BT did not affect the production of IL-17A and TGF-β1 in the airways. The changes in the expression ofα-SMA and PGP9.5 had no significant correlation with the improvement of pulmonary function. Conclusion and Clinical Relevance: This study suggests that BT reduces airway smooth muscle mass and the airway innervation without affecting vasculature and the production of inflammatory mediators in the airways of subjects with severe asthma.
Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells
(2020) Hachim, Mahmood Yaseen; Heialy, Saba Al; Senok, Abiola C.
Abstract: Current guidelines for COVID-19 management recommend the utilization of various repurposed drugs. Despite ongoing research toward the development of a vaccine against SARS-CoV-2, such a vaccine will not be available in time to contribute to the containment of the ongoing pandemic. Therefore, there is an urgent need to develop a framework for the rapid identification of novel targets for diagnostic and therapeutic interventions. We analyzed publicly available transcriptomic datasets of SARS-CoV infected humans and mammals to identify consistent differentially expressed genes then validated in SARS-CoV-2 infected epithelial cells transcriptomic datasets. Comprehensive toxicogenomic analysis of the identified genes to identify possible interactions with clinically proven drugs was carried out. We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. These findings indicate that analysis of publicly available transcriptomic and toxicogenomic data represents a rapid approach for the identification of novel targets and molecules that can modify the action of such targets during the early phases of emerging infections like COVID-19.
Leveraging the Added Value of Experiential Co-Curricular Programs to Humanize Medical Education
(2021) Senok, Abiola; John-Baptiste, Anne-Marie; Heialy, Saba Al; Naidoo, Nerissa; Otaki, Farah; Davis, Dave
Background: The aftermath of the 1910 Flexner report resulted in significant gaps in the structure of medical education. Experiential co-curricular opportunities can contribute to addressing these gaps. Purpose: To explore, from a holistic social constructionism perspective, the added value of a co-curricular program, designed and implemented based on Kolb’s Experiential Learning Theory. Methodology/Approach: In this case study, randomly selected medical students, who had participated in an experiential co-curricular program, undertook focus group sessions. Data were inductively analyzed using thematic analysis based on constructivist epistemology. Findings/Conclusions: Benefits at the individual/student level included three interlinked themes: personal, academic, and professional development. The personal development theme related to building character and resilience, and the academic development theme related to application of theory and previously acquired knowledge. Four categories surfaced within the professional development theme. Emergent categories at the community level were institutional advancement, contribution to host centers, and giving back to the community. Implications: Cocurricular programs, that are based on Kolb’s Experiential Learning Theory (ELT) and that foster learning as participation in the social world, humanize medical education, and nurture holistic millennial physicians.
Role of IL-17 in asthma pathogenesis and its implications for the clinic
(2019) Heialy, Saba Al
Introduction: Asthma is a respiratory disorder typically characterized by T-helper type 2 (Th2) inflammation that is mediated by cytokines, including IL-4, IL-5 and IL-13. Pathophysiologically, airway inflammation involving prominent eosinophilia, elevated IgE synthesis, airway hyperresponsiveness, mucus hypersecretion and airway remodeling manifest clinically in patients as wheezing, breathlessness, chest tightness and episodic coughing. However, the Th2 paradigm falls short in interpreting the full spectrum of asthma severity. Areas covered: Severe asthmatics represent a distinct phenotype with their mixed pattern of neutrophilic-eosinophilic infiltration and glucocorticoid insensitivity making them refractory to currently available therapies. Th17 cells and their signature cytokine, IL-17, have been implicated in the development of severe asthma. Here, we review the contribution of IL-17 in the pathological features of asthma, gathered from both human and animal studies published in Pubmed during the past 10 years, and briefly discuss the clinical implications of targeting IL-17 imbalance in asthmatic patients. Expert opinion: With advancement in our understanding of the role of IL-17 in asthma pathology, it is clear that IL-17 is a targetable pathway which may lead to improvement in clinical symptoms of asthma. However, further elucidation of the complex interactions unfurled by IL-17 is essential in the empirical development of effective therapeutic options for refractory asthmatics.
Shaping the future-ready doctor: a first-aid kit to address a gap in medical education.
(2020) Otaki, Farah; Naidoo, Nerissa; Heialy, Saba Al; John-Baptiste, Anne-Marie; Davis, David A; Senok, Abiola
To the Editor: With the advent of Industry 4.0 (i.e., the fourth industrial revolution) came a paradigm shift built on core work-related skills that further dictated the emergence of a "new" world, with diverse professional disruptors and innovators at the forefront. In an effort to address this new paradigm, recommendations in higher education for the "creation of more practical and applied curricula" and for enhancing "relationships between higher education institutions, employers, and other partners . . ." have been proposed. To create a level playing field for global healthcare sectors of the future, Morrison outlined the diverse roles a future-ready doctor will be expected to uphold. Thus, medical education has to evolve to mold a holistic future-ready doctor who can treat and continuously innovate. To this end, medical schools are challenged to amalgamate basic medical sciences with clinical sciences seamlessly and to adapt their curricula to yield millennial physicians who are able to respond to and act on cur-rent and emerging trends in healthcare. In addition to building on Flexner's legacy to ensure progressive pedagogical approaches, innovative means to incorporate the active components of human presence, comparable to that of core work-related attributes (i.e., heart - values, head - knowledge, mind - qualities, and hands - skills), need to be developed. However, it is undeniable that traditional classroom instruction alone cannot produce these characteristics of the future-ready doctor. (Continued)
Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients
(2021) Heialy, Saba Al; Hachim, Mahmood Yaseen
Purpose: Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe and has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked to a decreased glucocorticoid receptor (GR) ratio (GR-α/GR-β ratio), indicating steroid hyporesponsiveness. Using a combination of in silico and in vivo approaches, we aimed to explore the immunomodulatory effect of VitD on asthmatic patients diagnosed with hypovitaminosis D. Methods: In silico tools were used to identify the regulatory effect of VitD supplementation on GR genes. We measured the expression levels of GR-α and the inactive isoform, GR-β, in the blood of adult asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover, the blood levels of inflammatory cytokines associated with asthma severity were determined. Results: Using an in silico approach, we identified specific genes commonly targeted by VitD as well as corticosteroids, the mainstay of asthma therapy. NR3C1 gene encoding GR was found to be significantly upregulated on Th2 CD4 cells and NK cells. Interestingly, blood expression level of NR3C1 was lower in severe asthmatics compared to nonsevere asthmatics and healthy controls, while the blood level of VitD receptor (VDR) was higher. Upon VitD supplementation of severe asthmatic patients, there was a significant increase in the blood levels of GR-α with no change in GR-β mRNA expression. VitD supplementation also suppressed the blood levels of IL-17F and IL-4. Conclusion: VitD may enhance steroid responsiveness by upregulating the expression of steroid receptor GR-α.
Vitamin D3 Attenuates Viral-Induced Inflammation and Fibrotic Responses in Bronchial Smooth Muscle Cells
(2021) Jalaleddine, Nour; Heialy, Saba Al
Abstract: Toll-like receptor 3 (TLR3) activation by viral infections plays a key role in promoting inflammatory immune responses that contribute to pulmonary fibrosis in chronic inflammatory respiratory diseases. Vitamin D3 has been shown to be beneficial to patients with asthma and chronic obstructive pulmonary disease (COPD) through its anti-inflammatory and anti-fibrotic properties. Smooth muscle cells are one of the major contributors to airway remodeling in asthma and COPD. We therefore aimed to investigate the effect of vitamin D3 treatment on viral-induced TLR3 responses in Bronchial Smooth Muscle Cells (BSMCs) as a mechanism contributing to pulmonary fibrosis in asthma and COPD. Primary BSMCs from patients with asthma (n=4), COPD (n=4), and healthy control subjects (n=6) were treated with polyinosinic: polycytidylic acid (polyI:C), TLR3 agonist in the presence or absence of vitamin D3 (1,25D3). Here we report the mRNA expression and protein levels of pro-inflammatory and pro-fibrotic markers (IL-6, IFN-b1, CCL2/MCP-1, fibronectin 1 and type I collagen) among BSMCs groups: asthma, COPD, and healthy controls. We show that at the baseline, prior to polyI:C stimulation, asthma and COPD BSMCs presented increased pro-inflammatory and pro-fibrotic state compared to healthy control subjects, as measured by quantitative PCR and immunoassays (ELISA/Flow Cytometry. Ligation of TLR3 by polyI:C in BSMCs was associated with increased TLR3 mRNA expression, and 1,25D3 treatment significantly reduced its expression. In addition, 1,25D3 decreased the expression of IL-6, IFN-b1, CCL2, FN1 and COL1A1 induced by polyI:C in BSMCs. The regulatory effect of 1,25D3 treatment on polyI:C-stimulated BSMCs was further confirmed at protein levels. Our findings suggest that vitamin D3 attenuates TLR3 agonist-induced inflammatory and fibrotic responses in BSMCs and support the clinical relevance of vitamin D3 supplementation in patients with viral infections having chronic respiratory diseases, such as asthma and COPD.