The Cystic Fibrosis Airway Microbiome and Pathogens

Cystic fibrosis (CF) is an autosomal recessive genetic disorder resulting from genetic defects in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR dysfunction in patients with CF leads to a number of pleiotropic manifestations with the prime pathology being mucus plugging in the airways and paranasal sinuses. Patients with CF are prone to polymicrobial infections and the airway microbiome in such patients changes continuously and evolves over time. The composition of the airway microbiome in CF patients is dependent on a number of factors including geographic variation, type of genetic mutation (e.g., ΔF508), antibiotic exposures, and chronic infection with certain pathogenic bacteria (e.g., Pseudomonas aeruginosa). Proteomic and genomic approaches to understanding the microbiome of patients with CF have provided new insights into the pathogenesis of this disease. High‐throughput pyrosequencing, Sanger sequencing, and phylogenetic microarray analysis have enabled the recognition of multiple lineages and clonal populations of a single bacterial species within the same patient. This provides a unique opportunity to explore novel therapeutic approaches to this disease (for instance, use of probiotics and environmental manipulation) and potentially translate them into bedside clinical interventions

Corticosteroids and Their Use in Respiratory Disorders

Corticosteroids are adrenal hormones that play important physiologic roles including modulation of glucose metabolism, protein catabolism, alteration of calcium metabolism, regulation of bone turnover, suppression of immune system, and down-regulation of the inflammatory cascade. Because of their diverse effects, corticosteroids have been used therapeutically for treating a wide variety of auto-immune, rheumatologic, inflammatory, neoplastic and infectious diseases. In the field of pulmonology, corticosteroids have been used for the treatment of reactive airway diseases (such as asthma and allergic bronchopulmonary aspergillosis), chronic obstructive pulmonary disease, sarcoidosis, collagen vascular diseases (such as vasculitic disorders), eosinophilic pneumonitis, idiopathic interstitial pneumonias and infectious disorders (such as laryngotracheobronchitis). Different formulations of corticosteroids are commercially available including tablets, intravenous injections, intramuscular formulations and inhaled preparations. Long-term use of corticosteroids is often limited by their adverse effects, which include abnormal fat deposition, weight gain, diabetes mellitus, cataracts, glaucoma, osteoporosis, osteonecrosis, elevated risk of fractures, increased susceptibility to infections, proximal myopathy, depression, psychosis, adrenal atrophy with risk of Addisonian crisis, abdominal striae, acne vulgaris, delayed wound healing, easy bruising, electrolyte abnormalities and increased risk of peptic ulcer disease. As our understanding of corticosteroids advances, we may be able to identify individuals at higher risk of experiencing adverse effects

Asthma and obesity in the Middle East region: An overview

This paper aims to cover the current status of asthma and obesity in the Middle East, as well as to introduce the various studies tying the two diseases; further expanding on the proposed mechanisms. Finally, the paper covers recent literature related to sphingolipids and its role in asthma, followed by recommendations and future directions. In preparation of this paper, we searched PubMed and Google Scholar, with no restrictions, using the following terms; asthma, obesity, Middle East, sphingolipids. We also used the reference list of retrieved articles to further expand on the pool of articles that were used for this review

Pet ownership and associated respiratory diseases

Background Studies have shown that pets are very important sensitizing agents in patients with asthma. Respiratory disorders and allergic diseases are common in the State of Qatar

Prevalence of diagnosed and undiagnosed diabetes mellitus and its risk factors in a population-based study of Qatar

Objective: The objective of the study was to determine the prevalence of diagnosed and undiagnosed diabetes, pre-diabetes and to identify the associated risk factors in the sample of adult Qatari population

An Overview of the Homozygous Cystic Fibrosis Transmembrane Conductance Regulator Mutation c.3700 A>G (p.Ile1234Val) in Qatar

Purpose of Review Cystic fibrosis (CF) is a monogenic recessive disease with multisystem involvement. The cause is a mutation in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The aim is to review the literature involving the CFTR I1234V mutation and to provide recommendations for future research activities. Recent Findings The prevalence rates of CFTR mutations vary across the globe. The CFTR I1234V mutation is the most common mutation in Qatar, and one of the most common in the Arabian Gulf region. Summary Areas for future research include testing of the CFTR transcript and activity levels in different samples including nasal cells and organoids. Another area is applying Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology as a tool for gene editing.Other Information Published in: Current Genetic Medicine Reports License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s40142-019-00174-7</p

Prevalence of Sleep-Disordered Breathing in Prader–Willi Syndrome

Introduction. Sleep-disordered breathing (SDB) is common in patients with Prader–Willi Syndrome (PWS). However, the prevalence of SDB varies widely between studies. Early identification of SDB and factors contributing to its incidence is essential, particularly when considering growth hormone (GH) therapy. Objectives. The aims of the study were to describe the prevalence and phenotypes of sleep-disordered breathing (SDB) in patients with Prader–Willi syndrome (PWS) and to determine the effects of age, gender, symptoms, GH therapy and body mass index on SDB severity. Methods. This study was a retrospective chart review of all patients with genetically confirmed Prader–Willi syndrome who underwent diagnostic overnight polysomnography (PSG) in the sleep laboratory at Sidra Medicine. Clinical and PSG data of enrolled patients were collected. Results. We identified 20 patients (nine males, eleven females) with PWS who had overnight sleep polysomnography (PSG) at a median age (IQR) of 5.83 (2.7–12) years. The median apnea-hypopnea index (AHI) was 8.55 (IQR 5.8–16.9) events/hour. The median REM-AHI was 27.8 (IQR 15–50.6) events/hour. The median obstructive apnea-hypopnea index (OAHI) was 7.29 (IQR 1.8–13.5) events/hour. The median central apnea-hypopnea index (CAHI) was 1.77 (IQR 0.6–4.1) events/hour. Nineteen patients (95%) demonstrated SDB by polysomnography (PSG) based on AHI ≥1.5 events/hour. Nine patients (45%) were diagnosed with obstructive sleep apnea (OSA). Three patients (15%) were diagnosed with central sleep apnea (CSA). Seven patients (35%) were diagnosed with mixed sleep apnea. No correlations were observed between AHI and age, gender, BMI, symptoms, or GH therapy. However, REM-AHI was significantly correlated with BMI (P=0.031). Conclusion. This study shows a high prevalence of SDB among our patients with PWS. Obstructive sleep apnea was the predominant phenotype. BMI was the only predictor for high REM-AHI. Further studies of large cohorts are warranted to define SDB in PWS and design the appropriate treatment

The role of human metapneumovirus in pediatric respiratory tract infection in Qatar

The human metapneumovirus (hMPV) has been recently discovered as an etiological agent of acute respiratory infections in infants and children, with similar clinical symptoms to those caused by respiratory syncytial virus. The aim of this study was to determine the prevalence of hMPV and its potential role as a causative agent of respiratory tract infections in children in Qatar. Methods: In the present study, we examined 84 nasopharyngeal aspirates from children with respiratory tract infections, presenting at Al-Saad Pediatric Emergency Center in Doha, Qatar, as outpatients, for the presence of respiratory viruses. Results: A total of 56 out of 84 (66.7%) cases were positive for the presence of respiratory viruses. Out of the 56 positive cases 54 (96%) contained hMPV; whereas 12 out of 56 (21.4%) contained human parainfluenza virus. A total of 14 out of 56 of the positive patients were infected with more than one virus. hMPV was in samples infected with one or more respiratory tract infection viruses and was the most frequently isolated virus from infants less than 6 months of age. Conclusion: This is the first report demonstrating the prevalence of hMPV in children suffering from respiratory tract infections in Qatar. Detection of this virus may have significant clinical implications in this patient population in Qatar.The 2nd Undergraduate Research Experiences Program cycle of Qatar National Research Fund

TRPV2: A Cancer Biomarker and Potential Therapeutic Target

The Transient Receptor Potential Vanilloid type-2 (TRPV2) channel exhibits oncogenicity in different types of cancers. TRPV2 is implicated in signaling pathways that mediate cell survival, proliferation, and metastasis. In leukemia and bladder cancer, the oncogenic activity of TRPV2 was linked to alteration of its expression profile. In multiple myeloma patients, TRPV2 overexpression correlated with bone tissue damage and poor prognosis. In prostate cancer, TRPV2 overexpression was associated with the castration-resistant phenotype and metastasis. Loss or inactivation of TRPV2 promoted glioblastoma cell proliferation and increased resistance to CD95-induced apoptotic cell death. TRPV2 overexpression was associated with high relapse-free survival in triple-negative breast cancer, whereas the opposite was found in patients with esophageal squamous cell carcinoma or gastric cancer. Another link was found between TRPV2 expression and either drug-induced cytotoxicity or stemness of liver cancer. Overall, these findings validate TRPV2 as a prime candidate for cancer biomarker and future therapeutic target