{"id":196,"date":"2019-10-07T22:26:21","date_gmt":"2019-10-07T16:56:21","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=196"},"modified":"2019-10-07T22:26:21","modified_gmt":"2019-10-07T16:56:21","slug":"recent-advances-in-the-management-of-asthma","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/recent-advances-in-the-management-of-asthma\/","title":{"rendered":"Recent Advances in the Management of Asthma"},"content":{"rendered":"\n<p><strong>Recent Advances in the Management\nof Asthma<\/strong><\/p>\n\n\n\n<ul><li>Asthma is\na chronic lung disease characterized by inflammation and narrowing of the\nairways causing recurring periods of wheezing, chest tightness, shortness of\nbreath, and&nbsp;coughing.<\/li><li>Worldwide,\nthe <strong>economic costs associated with\nasthma are estimated to exceed those of TB and HIV\/AIDS combined<\/strong><\/li><li><strong>India<\/strong> accounts for <strong>10%<\/strong> of the asthma cases<\/li><\/ul>\n\n\n\n<p><strong>Need for newer drugs<\/strong><\/p>\n\n\n\n<ul><li>Concern\nabout the long-term <strong>safety of ICS<\/strong>\nand that they must be taken by inhalational route<\/li><li><strong>Poor adherence with ICS<\/strong><\/li><li>Concern\nabout the <strong>long-term safety of LABAs,<\/strong>\nalthough when administered in combination with ICSs there does not seem to be a\nproblem<\/li><li>Approximately\n<strong>5 to 10% of patients are not controlled\ndespite taking effective inhaled therapy<\/strong><strong><\/strong><\/li><li>Different\nphenotypes or endotypes of asthma<\/li><\/ul>\n\n\n\n<ul><li><strong>The types of new drugs needed for asthma include new classes of drug that are \u2013<\/strong><\/li><li>Effective in severe, poorly controlled asthma;<\/li><li>An oral treatment that is as effective as ICSs but without any side effects; <\/li><li>Drugs that modify the course or even cure the disease.+<\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"587\" height=\"410\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-44.png?w=587\" alt=\"\" class=\"wp-image-197\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-44.png 587w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-44-300x210.png 300w\" sizes=\"(max-width: 587px) 100vw, 587px\" \/><\/figure><\/div>\n\n\n\n<ul><li>There are\nat least 2 major types of asthma\u2014<strong>Th2-high\nand Th2-low\u2014<\/strong>dependent on the presence of selected Th2 molecular signatures <\/li><li><strong>periostin<\/strong> and high levels of sputum and blood eosinophils in response to <strong>Th2 cytokines such as IL-4, IL-5, and\nIL-13.<\/strong> <\/li><li>Asthmatic\npatients with the <strong>uncontrolled severe\ndisease despite high doses of ICSs<\/strong> and <strong>having\nhigh eosinophils <\/strong>\u00e0 respond to\nanti\u2013IL-5 and anti\u2013IL-13 therapy. <\/li><li>There is a\nnegligible clinical response to anti\u2013IL-1, anti\u2013IL-4, anti\u2013IL-17, or TNF-\u03b1\ntreatment. <\/li><li><strong>Non-Th2 patients<\/strong> \u00e0 more mixed lymphocyte profile involving Th1 and Th2 cells. <\/li><li>respond to\nanti-CXCR2 antagonists but not to anti\u2013IL-1, anti\u2013IL-8, or TNF-\u03b1 treatment.\nStudies using anti\u2013IL-17 or other antineutrophil approaches are yet to be\ncompleted.<\/li><\/ul>\n\n\n\n<p><strong>Th 2 Mediated Asthma<\/strong><\/p>\n\n\n\n<p><strong>Anti IL-5 Ab<\/strong><\/p>\n\n\n\n<ul><li>Interleukin <strong>(IL)-5 is<\/strong> specifically focused on the <strong>development, differentiation, recruitment,\nactivation, and survival of eosinophils<\/strong><\/li><li>Approximately <strong>50% of severe asthma exacerbations are\neosinophilic<\/strong> in nature<\/li><\/ul>\n\n\n\n<p><strong>Mepolizumab\n(2015) and Reslizumab (2016)<\/strong><\/p>\n\n\n\n<ul><li><strong>Reduce exacerbation rates<\/strong> and eosinophil\ncounts in both blood and sputum<strong> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <\/strong><\/li><li>Mepolizumab\nreduces oral steroid requirement by 50%, exacerbations by 50 %, given once a\nmonth<\/li><\/ul>\n\n\n\n<p><strong>Benralizumab (<\/strong>Nov 2017<strong>)<\/strong><\/p>\n\n\n\n<ul><li><strong>Add-on maintenance treatment<\/strong> of patients\nwith <strong>severe asthma aged 12 years and\nolder<\/strong>, and with an <strong>eosinophilic\nphenotype<\/strong><\/li><li>FDA approval based on the Phase\nIII program demonstrating up to <strong>51% reduction\nin asthma exacerbations,<\/strong> significant improvement in lung function and a <strong>75% reduction in daily oral steroid use.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Anti IL-13 Ab<\/strong><\/p>\n\n\n\n<ul><li><strong>IL<\/strong>-13 \u00e0\nmediate airway hyperresponsiveness, inflammation, mucus hypersecretion, and\nsubepithelial fibrosis. <\/li><li>Interleukin-<strong>13 <\/strong><strong>\u00e0 induces bronchial epithelial cells to secrete Periostin<\/strong> \u00e0 Can be used as a <strong>biomarker\nfor eosinophilia<\/strong><\/li><li><strong>Tralokinumab <\/strong>failed its two Phase III\ntrials in severe, uncontrolled asthma.<\/li><li><strong>Lebrikizumab<\/strong> failed to show efficacy in\ntwo Phase III studies.<\/li><li>May not be sufficient to\nprovide clinically meaningful improvements in reducing asthma exacerbations.<\/li><\/ul>\n\n\n\n<p><strong>IL-4 Targeted Pathway<\/strong><\/p>\n\n\n\n<p><strong>Pitrakinra <\/strong><\/p>\n\n\n\n<ul><li>A soluble IL-4 receptor\n(sIL-4R) that acts as an IL-4R antagonist is in Phase II<\/li><\/ul>\n\n\n\n<p><strong>Dupilumab<\/strong><\/p>\n\n\n\n<ul><li>Fully humanized anti\u2013IL-4Ra Mab<\/li><li><strong>Reduced asthma exacerbations<\/strong> in\nmoderate-to-severe asthma, and <strong>who had a\nblood eosinophil count<\/strong> &gt;300 cells\/mL or a sputum <strong>eosinophil level &gt;3%.<\/strong> <\/li><li>Improved lung function and <strong>reduced levels of Th2-associated\ninflammatory markers<\/strong>. (Liberty Asthma Quest Trial)<\/li><\/ul>\n\n\n\n<p><strong>Prostaglandin\nD2 receptor antagonist<\/strong><strong><\/strong><\/p>\n\n\n\n<ul><li>Chemoattractant receptor\u2013homologous molecule expressed on Th2 cells <strong>(CRTh2),<\/strong> is a <strong>high-affinity prostaglandin D2 receptor<\/strong> that is expressed on major human cell types that mediate asthma pathogenesis.<\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"315\" height=\"282\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-45.png?w=315\" alt=\"\" class=\"wp-image-198\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-45.png 315w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-45-300x269.png 300w\" sizes=\"(max-width: 315px) 100vw, 315px\" \/><\/figure><\/div>\n\n\n\n<ul><li><strong>Fevipiprant <\/strong><strong>\u00e0 Phase II completed<\/strong><\/li><li>Reduced eosinophilic airway\ninflammation and was well tolerated in patients with persistent\nmoderate-to-severe asthma and raised sputum eosinophil counts despite inhaled\ncorticosteroid treatment.<\/li><\/ul>\n\n\n\n<p><strong>Anti \u2013 IgE antibody<\/strong><\/p>\n\n\n\n<p><strong>Ligelizumab<\/strong> <\/p>\n\n\n\n<ul><li>binds IgE with <strong>higher affinity than omalizumab<\/strong><\/li><li><strong>Head to head comparisons<\/strong> suggests it may\nbe <strong>more efficacious<\/strong> than omalizumab\nwith respect to both inhaled and skin allergen responses in patients with mild\nallergic asthma.<\/li><li>Completed phase II<\/li><\/ul>\n\n\n\n<p><strong>Omalizumab for allergic asthma in children 6 to 11years of age (July\n2016)<\/strong><\/p>\n\n\n\n<ul><li>Indication<\/li><li>patients\nwith moderate to severe persistent asthma and sensitization to perennial\naeroallergens who are inadequately controlled on inhaled glucocorticoids<\/li><li><strong>US-FDA has now lowered the approved age range\nfrom 12 to 6 years of age.<\/strong><\/li><li><strong>Black Boxed warning related to anaphylaxis<\/strong> has been added<\/li><li>Patients\nshould be observed for 2 hrs after the first three injections &amp; for 30 mins\nafter each subsequent dose because 75% of anaphylaxis cases occurred within\nthose periods <\/li><\/ul>\n\n\n\n<p><strong>Th 17 Mediated Asthma<\/strong><\/p>\n\n\n\n<ul><li><strong>A subset of patients<\/strong> with severe disease\nthat <strong>do not respond well to ICS.<\/strong><\/li><li>These patients may <strong>have a Th-17 predominate disease<\/strong> with\nhigh levels of IL-17 <\/li><li>Leading to <strong>more neutrophil predominance and inflammation<\/strong>, less reversible\nairflow obstruction, and less bronchial hyper-responsiveness with methacholine\nchallenge testing<strong>.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>IL- 17 Antagonists<\/strong><\/p>\n\n\n\n<p><strong>Brodalumab, <\/strong><\/p>\n\n\n\n<ul><li>an anti\u2013IL-17R\u03b1 Mab <\/li><li>Despite good results in\npreclinical studies, had no effect on asthma control questionnaire score, FEV1,\nsymptom scores, or a number of symptom-free days in 302 subjects with\ninadequately controlled moderate-severe asthma taking regular ICSs.<\/li><li><strong>Secukinumab \u2013 Phase 2 terminated <\/strong><\/li><\/ul>\n\n\n\n<p><strong>Thromboxane A2 receptor antagonist<\/strong><\/p>\n\n\n\n<ul><li>Thromboxane A2 (TXA2) is a\nbronchoconstrictor prostanoid<\/li><li>Involved in the pathogenesis of\nacute and chronic inflammatory processes of asthma<\/li><\/ul>\n\n\n\n<p><strong>Seratrodast<\/strong><\/p>\n\n\n\n<ul><li>thromboxane A2 (TXA2) receptor\nantagonist<\/li><li>Has shown to exhibit better\ncontrol on asthma than that of cysteinyl leukotriene receptor antagonists<\/li><li>Global Initiative for Asthma <strong>(GINA) guidelines has recommended\nseratrodast as a controller of asthma in step 1 for long term management.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>PDE-4 Inhibitor \u2013 Roflumilast<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"557\" height=\"273\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-46.png?w=557\" alt=\"\" class=\"wp-image-199\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-46.png 557w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-46-300x147.png 300w\" sizes=\"(max-width: 557px) 100vw, 557px\" \/><\/figure>\n\n\n\n<ul><li>Clinical trials were being\nconducted with Roflumilast for Asthma and COPD.<\/li><li>Anti-inflammatory effects of\nroflumilast observed in COPD are also seen in asthma.<\/li><li>Roflumilast attenuated\nallergen-induced bronchoconstriction (FEV1) in patients with asthma.\nSignificant reductions in allergen-induced airway inflammation, including a <strong>reduction in both eosinophil and neutrophil\ncounts, were also observed and physiologic responses to the allergen-induced\nchallenge<\/strong> were confirmed by a significant reduction in TNF\u03b1. Side effects\nwere similar to COPD but did not include weight loss.<\/li><li>However, <strong>it received FDA approval only for COPD in 2011.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Bronchial thermoplasty<\/strong><\/p>\n\n\n\n<ul><li><strong>Controlled radiofrequency energy<\/strong> is\ndelivered to the intra-parenchymal airways during a series of bronchoscopies<\/li><li>Resulting in a <strong>prolonged reduction of airway smooth muscle\nmass.<\/strong><\/li><li>Approved by <strong>FDA in 2010<\/strong><\/li><li><strong>Included in step 5 of GINA guidelines<\/strong><\/li><li>First BT performed in India in\nJune 2017<\/li><\/ul>\n\n\n\n<p><strong>New strategies:<\/strong><\/p>\n\n\n\n<ul><li><strong>SMART (Single inhaler maintenance and reliever therapy<\/strong>). <\/li><li>Budesonide\/formoterol is better\nthan CS\/short-acting b2 agonist. <\/li><li>Rationale: ICS used as rescue\ntherapy prevents the buildup of inflammation that precedes an acute\nexacerbation. Since formoterol is long-acting, even if the patient forgets a\nfew of his maintenance dose, no harm is done. This addresses the problem of\npoor compliance.<\/li><\/ul>\n\n\n\n<p><strong>New corticosteroids. (Mapracorat)<\/strong><\/p>\n\n\n\n<p>\u2022&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; To\ndecrease systemic side effects<\/p>\n\n\n\n<p>\u2022&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Steroids\nrapidly metabolized when it enters the systemic circulation<\/p>\n\n\n\n<p>Steroids metabolized\nafter its action (soft steroid S\/E are due to binding of steroid to DNA\nreceptors, while anti-inflammatory effects are d\/t transrepression through\nnon-genomic effects.<\/p>\n\n\n\n<p>\u2022&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Hence\ndissociated steroids are being developed. <strong>(SEGRAs)\nSelective Glucocorticoid receptor agonist<\/strong><\/p>\n\n\n\n<p>\u2022&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Limitation:\nSome anti-inflammatory activity might be d\/t transactivation of\nanti-inflammatory genes.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Recent Advances in the Management of Asthma Asthma is a chronic lung disease characterized by inflammation and narrowing of the airways causing recurring periods of wheezing, chest tightness, shortness of breath, and&nbsp;coughing. Worldwide, the economic costs associated with asthma are estimated to exceed those of TB and HIV\/AIDS combined India accounts for 10% of the[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/196"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=196"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/196\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=196"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=196"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=196"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}