12 results found
Hakim A, Khan Y, Esteban I, et al., 2019, Low-dose budesonide/formoterol counteracts airway inflammation and improves lung function in COPD, American Journal of Respiratory and Critical Care Medicine, Vol: 199, Pages: 662-664, ISSN: 1073-449X
The latest Global Initiative for Chronic Obstructive Lung Disease (GOLD) document recommends new treatment algorithms, with inhaled corticosteroids (ICS) use only in moderate-to-severely symptomatic COPD patients with repeated exacerbations, where the emphasis is to review ICS use and to reduce ICS dosing (1). Indeed, safety concerns of pneumonia (2) with high-dose ICS has further concerted focus upon using appropriate doses of ICS. It is well-established that ICS in combination with long-acting β2-adrenoceptor agonist (LABA) can decrease exacerbations, improve symptomsand increase quality of life in patients with COPD (3-4), but nonetheless, the rationale to consider step-down of ICS is supported by several clinical studies (5). The Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial studied severe COPD patients on therapy with ICS, LAMA and LABA, where stepwise withdrawal of ICS did not lead to an increase in exacerbations compared to continued ICS use (6). Determining the optimal dose of ICS and LABA combination therapy is of great biological and clinical importance in order to address safety concerns associated with high-dose ICS use. There is in vitro evidence to support the clinical practice of using low-dose ICS. Low-dose ICS in combination with LABA enhances corticosteroid function by enhancing glucocorticoid receptor (GR) activity (7) and suppresses the release of inflammatory mediators (8). However, it is unknown whether this observation of enhanced corticosteroid function with low-dose ICS/LABA has a direct effect on airways inflammation and lung function. Our study investigated the cellular function that may be relevant and underpin the clinical approach to lowering the dose of ICS therapy in COPD patients. We compared the single administra
Ahmed A, Hakim A, Becker A, 2018, Evaluation of eczema, asthma, allergic rhinitis and allergies among the Grade-1 children of Iqaluit, Allergy, Asthma & Clinical Immunology, Vol: 14, ISSN: 1710-1484
Background:Little is known about the prevalence of asthma, allergic rhinitis, eczema and allergies among Canadian Inuit children, especially those living in the arctic and subarctic areas.Methods:A cross-sectional study among Grade 1 students attending schools in Iqaluit, the capital of Nunavut, was conducted during the 2015/2016 school year. We used the International Study of Allergy and Asthma in Children questionnaire with added questions relevant to the population. In addition, skin prick tests were conducted to test for sensitization to common food and environmental allergens.Results:The prevalence of current asthma was 15.9% (> 2:1 males) with the highest prevalence among those with any non-Inuit heritage at 38.5%. The prevalence of current and past allergic rhinitis was 6.8%, also predominant among males, with the lowest prevalence among the mixed ethnicity. Home crowdedness was inversely related to past asthma. Being ever outside Nunavut was associated with higher prevalence of current and past asthma. No statistically significant relationship was found with passive smoking or exclusive breast feeding during the first 4 months of life. The current eczema prevalence was 20.5%, with the highest prevalence recorded among the Inuit at 25% compared to 15.4% among the mixed ethnicity and 14.3% among the non-Inuit. We noted a high rate of sensitization to cat at 26.7% while absent sensitization to other common inhalant allergens.Conclusion:Variations in the prevalence and risk factors of asthma, allergic rhinitis and eczema among different ethnicities living at the same subarctic environment may be related to genetic, gene-environment interaction and/or lifestyle factors that require further investigation.
Hakim A, Usmani OS, 2016, New molecules to treat asthma and COPD, Advances in Pulmonary Drug Delivery, Pages: 49-65, ISBN: 9781498758048
Hakim A, Khan Y, Esteban I, et al., 2016, Effects of a single inhaled budesonide/formoterol dose on glucocorticoid receptor activity in sputum of COPD patients, ERS International Congress 2016, Publisher: European Respiratory Society, Pages: OA3313-OA3313, ISSN: 0903-1936
Hakim A, Barnes PJ, Adcock IM, et al., 2015, THE IMPACT OF DRUG CLEARANCE ON DURATION OF ACTION OF CORTICOSTEROIDS, The Aerosol Society Drug Delivery to the Lungs 25, Publisher: Mary Ann Liebert, Pages: A22-A22, ISSN: 1941-2711
Hakim A, Usmani OS, 2015, Enhancing nuclear translocation: perspectives in inhaled corticosteroid therapy, THERAPEUTIC DELIVERY, Vol: 6, Pages: 443-451, ISSN: 2041-5990
Hakim A, Usmani OS, 2014, Structure of the Lower Respiratory Tract, Reference Module in Biomedical Research, ISBN: 9780128012383
© 2014 Elsevier Inc. All rights reserved.The respiratory system is essential for supplying the body with oxygen and removing carbon dioxide. It is mainly responsible for pulmonary ventilation, movement of air into and out of the lungs, and external respiration. The respiratory system consists of the chest wall structures responsible for moving air in and out of the lungs and the airways that carry the air to the alveoli, which are the gas exchanging region of the lung. The airways themselves are subdivided into two major regions, the upper and lower respiratory tracts. The lower respiratory tract includes the larynx, trachea, bronchi, bronchioles, and alveoli. These structural features facilitate maximum delivery of air to all parts of the lungs as well as providing maximal surface area for gaseous exchange, which is aided by the richly perfused source of blood and lymphatic vessels.
Khan YM, Hakim A, Down G, et al., 2014, Novel engineered drug formulations of beta 2-agonist and corticosteroid reduce LPS-induced inflammation in a human monocytic cell line (thp-1), American Thoracic Society 2014 International Conference
Haque R, Hakim A, Moodley T, et al., 2013, Inhaled long-acting beta(2) agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 132, Pages: 1166-1173, ISSN: 0091-6749
Hakim A, Barnes PJ, Adcock IM, et al., 2013, Importin-7 mediates glucocorticoid receptor nuclear import and is impaired by oxidative stress, leading to glucocorticoid insensitivity, FASEB JOURNAL, Vol: 27, Pages: 4510-4519, ISSN: 0892-6638
Mercado N, Hakim A, Kobayashi Y, et al., 2012, Restoration of corticosteroid sensitivity by p38 Mitogen activated protein kinase inhibition in peripheral blood mononuclear cells from severe asthma, PLoS One, Vol: 7, Pages: 1-9, ISSN: 1932-6203
BackgroundSevere asthma accounts for a small number of asthmatics but represents a disproportionate cost to health care systems. The underlying mechanism in severe asthma remains unknown but several mechanisms are likely to be involved because of a very heterogeneous profile. We investigated the effects of a p38MAPK inhibitor in corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from severe asthmatics and the profile of its responders.Methodology/Principal FindingsCorticosteroid sensitivity was determined by measuring dexamethasone inhibition of CD3/28 and TNF-α induced IL-8 production in PBMCs by using ELISA. PBMCs from severe asthmatics were relatively less sensitive to dexamethasone (Dex) as compared to those of non-severe asthmatics and healthy volunteers. The IC50 values of Dex negatively correlated with decreased glucocorticoid receptor (GR) nuclear translocation assessed using immunocytochemistry (r = −0.65; p<0.0005) and with decreased FEV1 (% predicted) (r = 0.6; p<0.0005). A p38α/β inhibitor (SB203580) restored Dex-sensitivity in a subpopulation of severe asthma that was characterized by a defective GR nuclear translocation, clinically by lower FEV1 and higher use of oral prednisolone. We also found that SB203580 partially inhibited GR phosphorylation at serine 226, resulting in increased GR nuclear translocation in IL-2/IL-4 treated corticosteroid insensitive U937s.Conclusions/Significancep38MAPKα/β is involved in defective GR nuclear translocation due to phosphorylation at Ser226 and this will be a useful biomarker to identify responders to p38MAPKα/β inhibitor in the future.
Hakim A, Adcock IM, Usmani OS, 2012, Corticosteroid Resistance and Novel Anti-Inflammatory Therapies in Chronic Obstructive Pulmonary Disease Current Evidence and Future Direction, DRUGS, Vol: 72, Pages: 1299-1312, ISSN: 0012-6667
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