Background: Asthma and chronic obstructive pulmonary disease (COPD) have traditionally been viewed as distinct disorders. Past studies have often focused on specific aspects of each disease based on a single diagnostic label, with strict clinical trial enrolment criteria and limited generalisability. There are few prospective, observational studies that include patients across asthma, COPD and asthma-COPD overlap diagnoses. Consequently, the ways in which these different clinical profiles relate to specific phenotypes and endotypes are not well understood. NOVELTY  aims to describe patient characteristics, treatment patterns and disease burden across the spectrum of asthma and COPD over time, and to identify phenotypes and molecular endotypes associated with differential outcomes for symptom burden, clinical evolution and healthcare utilisation (HCU).Method: NOVELTY is a global, prospective, observational, longitudinal cohort study that will include up to 12,000 patients ≥12 years of age with a diagnosis or suspected diagnosis of asthma and/or COPD across the spectrum of severities , from primary and specialist care. The study will collect data on clinical assessments, spirometry, biospecimens (blood and urine), patient-reported outcomes (PROs) and HCU at baseline and longitudinally for 3 years. Data captured at annual visits will be recorded in study-specific electronic case report forms, with some PROs and HCU data collected remotely every 3 months. Recruitment is expected to end in March 2018 (except in China), followed by baseline analysis.Results: NOVELTY will provide a rich data source that may enable novel classification of patients across the spectrum of obstructive lung disease according to clinical outcomes, PROs and biomarker profiles over time. It will create a biobank and data platform of evidence from clinical practice, which can also be utilised in the future by the broader community of physicians, patients, regulators and the scientific community.Conclusion: Results from NOVELTY will provide insights into the diagnosis, assessment and management of patients with asthma and/or COPD in primary and specialist care around the world and may help support the future development of novel therapies and personalised healthcare in obstructive lung disease. The data platform created by NOVELTY will also be a valuable resource for research beyond the core objectives of the study itself.Disclosures: MGdV, LB, AG, NK, CK, JN, SR are employees of AstraZeneca (AZ); DKF is an employee of an AZ Group company.AA: speaking, participating in advisory boards and/or research from AZ, Chiesi, Menarini, Novartis (Nov) and Teva.GPA: honoraria and advisory boards for AZ, Boehringer Ingelheim (BI), GlaxoSmithKline (GSK), Nov and Pieris.ATB: paid consultant of AZ.RB: research funding from AZ, Genentech, GSK and Health Research Council of New Zealand; lectures and/or participation in advisory boards from AZ, GSK and Health Research Council of New Zealand.EHB: research grants from AZ, GSK and Nov; research consulting from AZ, BI, GSK, Nov, Sanofi/Regeneron, Teva and Vectura.CJ: speaking and/or participating in advisory boards for AZ, BI, GSK, Nov and Teva.BM: participation in NOVELTY planning meetings for AZ and in medical advisory boards for AZ, BI, CSL Bering, GSK, Nov, Spiration, Sunovion and Verona; research studies funded by AZ, BI, GSK, Medscape, Pearl and Sunovion; grant funding from AZ; non-branded talk for AZ.IP: speaking at sponsored meetings from Aerocrine, Almirall, AZ, BI, GSK and Nov; attending advisory panels with Almirall, AZ, BI, Dey, Genentech, GSK, MSD, Napp, Nov, Regeneron, Respivert and Schering-Plough; organising an educational event from AZ; attending scientific meetings from AZ, BI, GSK and Napp.DP: board membership with Aerocrine, Amgen, AZ, BI, Chiesi, Meda, Mundipharma (Mund), Napp, Nov, and Teva; consultancy agreements with Almirall, Amgen, AZ, BI, Chiesi, GSK, Meda, Mund, Napp, Nov, Pfizer, Teva, and Theravance; grants and unrestricted funding for investigator-initiated studies  from Aerocrine, AKL Ltd, AZ, BI, British Lung Foundation, Chiesi, Meda, Mund, Napp, Nov, Pfizer, Respiratory Effectiveness Group, Takeda, Teva, Theravance, UK National Health Service, Zentiva; payment for lectures/speaking engagements from Almirall, AZ, BI, Chiesi, Cipla, GSK, Kyorin, Meda, Merck, Mund, Nov, Pfizer, Skyepharma, Takeda, and Teva; payment for manuscript preparation from Mund and Teva; payment for the development of educational materials from Mund and Nov; payment for travel/accommodation/meeting expenses from Aerocrine, AZ, BI, Mund, Napp, Nov, and Teva; funding for patient enrolment or completion of research from Chiesi, Nov, Teva, and Zentiva; stock/stock options from AKL Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd, UK and 74% of Observational and Pragmatic Research Institute Pte Ltd, Singapore; and is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, HTA, and Medical Research Council.HKR: advisory boards for AZ, GSK and Nov; data safety monitoring boards for AZ, GSK, Merck and Nov; independent educational presentations for AZ, BI, GSK, Mund, Nov and Teva; and independent research funding from AZ and GSK.Collaborators:5, John Busby5, Paul Pfeffer6, David Jackson7, Andrew Menzies-Gow8;UK Severe Asthma Registry: Liam Heaney9, Enrico Heffler9, Concetta Sirena10;Severe Asthma Network Italy: G. Walter CanonicaSevere11,12, Erin Harvey11,12, Heather Powell12;Asthma Web-based Database: Peter Gibson13, You Sook Cho14;Korean Academy of Asthma, Allergy and Clinical Immunology: Chin Kook Rhee15, Pearlanne Zelarney15National Jewish Health: Eileen WangBackground: The lack of a universally accepted definition for severe asthma hinders the investigation into its exact prevalence and pathology. The International Severe Asthma Registry (ISAR) was created as a global effort to capture information on severe asthma using a standardized method of data capture. We aimed to examine the global prevalence of severe asthma and its corresponding patient characteristics.Method: This was a descriptive study utilizing patients with severe asthma data recorded in the ISAR from the UK, USA, Italy, Australia and South Korea from December 2014 to December 2017. Patients were included in the ISAR if they were ≥18 years of age and were on GINA  Step 5 therapy or Step 4 with uncontrolled symptoms. Descriptive statistics for demographic factors and clinical characteristics were tabulated and summarized.Results: From a total of 2,244 patients with severe asthma, 1,502 (66.9%) patients were classified as GINA Step 5 patients and 742 (33.1%) as GINA Step 4 patients with uncontrolled symptoms. From the total study population, 1,250 (55.7%) were females and 1,120 (49.9%) were of Caucasian origin. Most of the patients were between the ages 55 and 79 (1107 (49.3%)) and were non-smokers ). A significant proportion (602 (49.9%)) of the patients had poorly controlled asthma. The asthma age of onset for Step 4 patients fell predominantly within the “>40” age category (291 (41.9%)), whereas the majority of Step 5 patients’ asthma age of onset fell within the “12-40” age category ). The most prevalent comorbidity was allergic rhinitis for Step 4 (317 (52.7%)) and Step 5 patients (329 (27.3%)). Blood eosinophil count was greater than 0.3 109/L for 319 (48.9%) Step 4 and 911 (63.8%) Step 5 patients. Intermediate (25-50 parts per billion) or high (>50 parts per billion) Fractional Exhaled Nitric Oxide (FeNO) results were recorded for 1,107 (78.6%) patients while 1,307 (69.3%) patients had serum IgE levels within 150-400 IU/ml or above 400 IU/ml, indicative of pulmonary inflammation. At least one exacerbation was reported for 962 (78.4%) patients and 472 (49.1%) of these patients had a minimum of four or more exacerbations.Conclusion: The demographic and clinical characteristics of patients with severe asthma from five geographically diverse countries support previously reported characteristics of severe asthma patients. To decipher informative trends in asthma phenotypes and clinical management, country-specific distributions should be compared next.Disclosures: Liam Heaney has taken part in advisory boards and given lectures at meetings supported by GlaxoSmithKline, Respivert, Merck Sharpe & Dohme, Nycomed, Boehringer Ingelheim, Teva, Vectura, Novartis and AstraZeneca. He declares sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Napp Pharmaceuticals; and speaker fees from AstraZeneca, Aerocrine, Hoffman la Roche and Teva.Paul Pfeffer has taken part in advisory boards and given lectures at meetings supported by Novartis, GlaxoSmithKline, Boehringer Ingelheim, and AstraZeneca.Andrew Menzies-Gow declares grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Hoffman La Roche; consultancy agreements with AstraZeneca; personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffman La Roche, Napp Pharmaceuticals, Novartis, Teva and Vectura; non-financial support from AstraZeneca, Boehringer Ingelheim and Napp Pharmaceuticals; and payment for travel expenses to international conferences from AstraZeneca, Boehringer Ingelheim and Napp Pharmaceuticals.Peter Gibson declares grants from AstraZeneca, GlaxoSmithKline and Novartis; and personal fees from AstraZeneca and GlaxoSmithKline.Chin Kook Rhee declares consultancy and lecture fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, MSD, Mundipharma, Novartis, Sandoz, Takeda and Teva-Handok.Trung Tran is an employee of AstraZeneca.David Price declares board membership with Aerocrine, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Mundipharma, Napp Pharmaceuticals, Novartis and Teva; consultancy agreements with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Napp Pharmaceuticals, Novartis, Pfizer, Teva and Theravance; grants and unrestricted funding for investigator-initiated studies  from Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Mylan, Mundipharma, Napp Pharmaceuticals, Novartis, Pfizer, Respiratory Effectiveness Group, Teva, Theravance, UK National Health Service and Zentiva; payment for lectures/speaking engagements from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Merck, Mundipharma, Novartis, Pfizer, Skyepharma and Teva; payment for manuscript preparation from Mundipharma and Teva; payment for the development of educational materials from Mundipharma and Novartis; payment for travel/accommodation/meeting expenses from Aerocrine, AstraZeneca, Boehringer Ingelheim, Mundipharma, Napp Pharmaceuticals, Novartis and Teva; funding for patient enrolment or completion of research from Chiesi, Novartis, Teva and Zentiva; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd  and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); and is a peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme and Health Technology Assessment.Erin Harvey, David Jackson, Eileen Wang, Enrico Heffler, G. Walter Canonica, John Busby, Pearlanne Zelarney, Sirena Concetta and You Sook Cho declare no relevant conflicts of interest concerning this paper.Background: Allergic rhinitis (AR) is highly prevalent and more than 50% of people with AR self-medicate with over-the-counter medications in the community pharmacy, without seeking professional advice. Many patients select suboptimal treatments for their condition, and this increases incidence of developing complications and/or comorbidities. It is unclear what influences a patient’s decision to self-select medications for AR rather than seek professional advice. This study aims to (i) compare the demographics, clinical characteristics and medication selected, between pharmacy customers who choose to self-select and those who interact with a pharmacist when purchasing medication for AR, and (ii) identify the key factors associated with AR patients’ medication self-selection behaviour.Method: A cross-sectional observational study was conducted in a convenience sample of community pharmacies from the Sydney metropolitan area. Data were collected using a researcher administered survey that included: demographics, pattern of AR symptoms, their impact on quality of life (QOL), triggering factors and medication(s) selected. Univariate and multivariate logistic regression was used to identify factors associated with participants’ medication self-selection behaviour.Of the 296 recruited participants, 202 were identified with AR, of which 67.8% were female, 54.5% were aged > 40 years, 64.9% had a doctor’s diagnosis of AR, and 69.3% self-selected medication(s). Significant differences were noted in AR symptoms, impact of AR on QOL and medication(s) selected between the two groups. Participants who experienced moderate-severe wheeze were more likely  to self-select medication(s), and those with AR symptoms impacting on their QOL were less likely  to self-select medication(s).Conclusion: Although people with AR who reported an impact on their QOL were more likely to consult a pharmacist, however the high incidence of self-selection of OTC treatments for AR symptoms in community pharmacy does not reflect the severity of the condition experienced by patients. This indicate that there are also people with AR underestimate the severity of their symptoms and subsequently do not see the need to consult a pharmacist. Nonetheless, on top of having AR, participants who were also experiencing wheeze, were less likely to consult a pharmacist. Pharmacists must be aware of this finding especially in light of the recent “Thunderstorm Asthma” event resulting in serious exacerbations and even death. Pharmacists should alert them regarding these co-existing conditions and provide them with proper education.Disclosures: Sinthia Bosnic-Anticevich: Conflict of interests: A member of the Teva Pharmaceuticals Devices International Key Experts Panel; received research support from Research in Real Life; payment for lectures/speaking engagements and for developing educational presentations from Teva and Mundipharma; received Honoria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, for her contribution to advisory boards/key international expert forum. Rachel Tan: Conflict of interests: Nothing to disclose. Biljana Cvetkovski: Conflict of interests: Nothing to disclose. Vicky Kritikos: Conflict of interests: Received honoraria from AstraZeneca, GlaxoSmithKline and Pfizer. Kwok Yan: Conflict of interests: Received honoraria for speaking and consulting from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Meda, Mundipharma and Pfizer. Peter Smith: Conflict of interests: A clinical allergist with research and clinical interest in rhinology and has also been a speaker for Meda, GlaxoSmithKline, Novartis, Mundipharma and AstraZeneca. David Price: Conflict of interests: A board membership with Aerocrine, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, and Teva Pharmaceuticals; consultancy agreements with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance; grants and unrestricted funding for investigator-initiated studies  from UK National Health Service, British Lung Foundation, Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, Pfizer, Respiratory Effectiveness Group, Takeda, Teva Pharmaceuticals, Zentiva, and Theravance; payment for lectures/speaking engagements from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Meda, Merck, Mundipharma, Novartis, Pfizer, Skyepharma, Takeda, and Teva Pharmaceuticals; payment for manuscript preparation from Mundipharma and Teva Pharmaceuticals; payment for the development of educational materials from Novartis and Mundipharma; payment for travel/accommodation/meeting expenses from Aerocrine, Boehringer Ingelheim, Mundipharma, Napp, Novartis, Teva Pharmaceuticals, and AstraZeneca; funding for patient enrolment or completion of research from Chiesi, Teva Pharmaceuticals, Zentiva, and Novartis; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd, UK, and 74% of Observational and Pragmatic Research Institute Pte Ltd, Singapore; and is peer reviewer for grant committees of the Medical Research Council, Efficacy and Mechanism Evaluation programme, and Health Technology Assessment.Background: To understand patient perspectives on Asthma medicationsMethod: 20 patients interviewed (first quarter 2016) in seven 90-minute focus groups, four in English(Toronto) and three in French. Patient inclusion were those prescribed a regular controller, either ICS monotherapy or combination LABA/ICS.Results: A number of different themes emerged. Asthma was described as “airway closing" in terms of symptoms and only rarely was there a mention of inflammation. They understood the 'blue one' immediately relieved their symptoms, that the preventer was a steroid and that combination puffers contained both. An interesting analogy was the preventer being like an antidepressant to be used to prevent 'sliding back' into depression.There were many concerns about ICS including safety and becoming dependent on them; an analogy given was like the eyes getting weaker when one depended on their glasses. Many participants only believed that the asthma was present only when there were symptoms. Conversely, they held little hope of being able to live 'free and clear' of the illness and that they must live with a lesser quality of life and a permanent physical ailment.With education, patients could understand the concept of the SMART strategy and could be taught that a B2 agonist such as Ventolin is a 'band aid solution' with and ICS/LABA such as Symbicort being able to 'do more for me'. Those that were unfamiliar with SMART suggested that they would inquire about it with their physicians.Conclusion: While Asthma is an inflammatory disease requiring regular anti-inflammatory treatment, patients have fears about using ICS and seem to be more comfortable using a single inhaler that can.Disclosures: funded by Astra ZenecaBackground: The peripheral blood eosinophil count (EC) has been proposed as a biomarker to identify an inhaled corticosteroids responsive COPD phenotype. We wished to determine the prevalence of elevated ECs in community practice COPD and explore what subject parameters, if any, might be associated.Method: 100 subjects with COPD, >10 pack-years of smoking and either FEV1/FVC<0.7 (GOLD COPD), or MMEF<65%predicted (non-GOLD COPD), had EC, patient reported outcomes  and PFTs obtained within the same year, and had undergone oscillometry (OS) and quantitative CT scanning (qCT). The mean EC was determined by GOLD2017 Stage and Grade. A frequency distribution histogram of EC was constructed and 3 cut points chosen to establish 4 EC groups by which to compare data. Any parameter suggesting a relationship to EC was subjected to ANOVA. The same 3 cut points were applied singly, resulting in 3 pairs of subject groupings of Hi and Lo EC. Students t-test was then applied to detect differences in parameters means if a difference had been detected by AVOVA.Results: The PFT-OS interval was 9±9 mean±SD months, and PFT-CT, 14±14. Distribution of mean EC by GOLD2017 Stages and Grades was ; non-GOLD, 4, 125 cells/μL; I, 26, 225: II, 47, 225; III, 16, 169; IV. 7, 286, and non-GOLD, 4, 125; A, 13, 255; B, 5, 120; C, 48, 225; D, 30, 214 respectively. The frequency distribution of EC is shown in Figure 1.Lco appeared to differ by EC groups (ANOVA p=0.035). Dividing subjects into 2 groups using a cut point ≥400 resulted in significant differences in mean DLco  while means did not differ using cut points of either ≥200 or ≥300 .Cut points of ≥200, ≥300 and ≥400 cells/μL resulted in elevated EC prevalence of 60, 36 and 13% respectively. Of all the biometric, PRO, PFT, OS and qCT parameters (data not shown) only the DConclusion: Of biometric, PRO, PFT, OS and qCT parameters, only DLco demonstrated an association with elevated EC. Whether this represents a chance finding due to the number of parameters surveyed or, indeed, reflects a relative preservation of the DLco suggesting a more asthma-like phenotype of COPD, requires confirmation in larger independent populations.Disclosures: Nothing to disclose.Background: Asthma exacerbations are major contributors to asthma morbidity and mortality, and their management presents a major clinical need that is not adequately met by current approaches. Asthma exacerbations are usually managed with bronchodilators and systemic steroids. There is increasing evidence that bacterial infections may contribute to exacerbation severity, with recent randomised controlled trials suggesting that antibiotics may be beneficial in managing exacerbations. These findings warrant further exploration in larger more representative routine care populations.Method: Using retrospective electronic medical records from the Optimum Patient Care Research Database, we have conducted a comparative effectiveness study into managing asthma exacerbations with oral corticosteroids (OCS) alone versus oral corticosteroids plus antibiotics in paediatric and adult asthma populations .Results: The prescribing of OCS alone or OCS plus antibiotics was not a random event. Antibiotics seem to be more commonly prescribed in those who appeared to have more severe asthma, were smokers, and during the winter, presumably due to more infections. Therefore, the groups were matched on GINA treatment step, smoking status, season of index prescription date (IPD) and number of asthma/wheeze consultations in the baseline period.In the 12-week outcome period survival analysis showed the time to the next asthma/wheeze consultation was increased in adults, but not children, who received an OCS plus antibiotic  compared to OCS alone at IPD . In the same period the time to the next asthma/wheeze consultation that resulted in an OCS with or without antibiotic prescription was decreased in adults (p=0.002) and 13-18 yr olds (p=0.046), but not younger children, who received an OCS plus antibiotic , 1.23 , respectively), compared to OCS alone at IPD.The time to first hospitalisation or A&E attendance for a lower respiratory complaint were no different in those who received OCS plus antibiotics compared to OCS alone at IPD, during the 12-week outcome period.Conclusion: The addition of antibiotics to oral steroids in the management of asthma exacerbations does have a small effect on reducing subsequent asthma/wheeze consultations, in adults, but more work is required to draw firm conclusions from this data.Disclosures: Nothing to disclose.Background: Community acquired pneumonia (CAP) is a leading infectious cause of mortality in the UK. In 2014, CRB65 scores  were incorporated into the National Institute for Health & Care Excellence (NICE) pneumonia guidelines1. Those with a score of 0 were deemed suitable for management at home, while consideration of hospital-based care was advised for all other patients, particularly those with a score of more than 2. The aim of this study was to describe the diagnosis and management of CAP in primary-care and to evaluate the extent to which the NICE guidelines have been implemented.Method: An observational study was performed using the Optimum Patient Care Research Database (OPCRD), a UK primary-care database containing Electronic Medical Records (EMR) from 4 million patients. Episodes of CAP (>180 days after any prior episode) in adults (≥18 years) between 1 January 2009 and 31 December 2016 and with at least 28 days of continuous EMR before and after diagnosis date were included. As this study focused on patients managed in primary care, episodes of CAP were excluded if no antibiotic prescriptions were recorded, the patients were referred to secondary care, or the diagnosis was retrospective.Results: There were 3,181 episodes of CAP from 3,067 patients in the study period. The incidence of CAP managed in primary care was 18.4 (95% CI: 17.8-19.0) episodes per 100,000 patients in the OPCRD database per year. In 383 episodes (12.0%), at least one consultation for a lower respiratory tract infection (LRTI) was recorded in the 28 days prior to CAP diagnosis, of which 298 (77.8%) were prescribed antibiotics. Consultations for CAP or LRTI in the 28 days following diagnosis were recorded for 950 episodes (29.9%).CRB65 scores were recorded in six episodes (0.2%) and no episode had all components recorded individually. Recording of CRB65 and CRB65 components improved over time . The most commonly recorded observations and assessments on diagnosis date were pulse rate  and chest examination . The most commonly prescribed antibiotic class at diagnosis was penicillin , of which 1,422 (72.8%) were amoxicillin.Conclusion: Recording of CRB65 and its components in CAP patients managed in primary care is low. The usefulness of CRB65 scores in primary care needs further investigation.Disclosures: Chris Winchester is an employee, Director and shareholder of Oxford PharmaGenesis and a Director of Oxford Health Policy Forum CIC. Dermot Ryan, David Price and Naomi Launders have no conflicts of interest to disclose.https://www.nice.org.uk/guidance/cg191.NICE. Pneumonia in adults: diagnosis and management. 2014:References:Background: While asthma and obesity frequently occur together, the exact relationship between the two is unclear, as are the mechanisms involved. Poor diet, physical inactivity, gastro-oesophageal reflux disease (GERD), excess adipose tissue and immunological factors related to obesity may all act independently to induce or exacerbate asthma symptoms. Conversely, weight loss through diet or weight loss surgery, may improve asthma symptoms. This study aims to investigate the relationship between asthma symptoms and initial BMI, weight loss, and weight loss method; with consideration of the role that co-morbid GERD plays in modifying the effects of these relationships.Method: The study will consist of two retrospective cohort studies using the Optimum Patient Care Research Database (OPCRD). OPCRD is a large primary care database comprising almost 4.5 million patients from over 600 UK general practices. Both phases of the study will examine small airway function, asthma exacerbations and medications, and asthma-related quality of life.Phase I will compare asthma outcomes in obese and non-obese adult asthma patients with and without GERD in the five years following asthma diagnosis, and examine the relationship between BMI, GERD and asthma control. Patients with a diagnosis of chronic obstructive pulmonary disease, cancer or aged over 65 will be excluded.Phase II will examine the effects of weight loss in obese adult asthmatic patients. Asthma outcomes will be compared in obese patients in the five years following with weight loss through diet or weight loss through surgery. Asthma symptoms in those showing no significant weight loss will also be examined. The exact amount of weight loss required will be determined in phase I. Patients with multiple bariatric surgeries or surgeries to remove gastric bands will be excluded.In both phases, sub-analyses of severe asthma, asthma phenotypes, and obesity class will be performed.Results: Results will be published in a peer reviewed journal.Conclusion: This study will provide valuable information on the effect that obesity and GERD have on asthma symptoms, and the role that weight loss, through diet or surgery, plays in improving symptoms. Results from this study will be used to inform future studies on the role of extra-fine vs. fine inhaled corticosteroids in obese asthmatic patients, the effects of GERD surgery on asthma and the effect of obesity, GERD and weight loss on asthma in children.Disclosures: Naomi Launders, Celeste Porsberg, Omar Usmani and Therese Lapperre have no conflicts of interest to disclose. Dr. Roche: Reports and personal fees from Boehringer Ingelheim, Novartis, Pfizer and personal fees from Teva, GSK, AstraZeneca, Chiesi, Mundipharma, Cipla, Sanofi, Sandoz, 3M, Zambon.Background: the WHO estimates that COPD is now the third leading cause of death globally and most deaths occur in developing countries. COPD prevalence rose 35% 10 years in Africa through the combination of tobacco smoking, indoor and outdoor air-pollution, tuberculosis and HIV in a deprived population. The phenotypes seen are different to those in developed countries and include restrictive disorders such as fibrosis and lung destruction. Little is known of the causes and natural history of these disorders.Aim: To outline epidemiological approaches undertaken, planned and potential to address chronic lung disease in AfricaMethod: Description of resources of existing datasets come from cross-sectional surveys, longitudinal cohort and other trials.Results: Many existing datasets with high quality data in Uganda have potential to address current disease burden for example, post TB lung damage in the WHO TB survey. Multinational projects provide opportunities to compare the risk factors and impacts of lung disease between countries. Forward planning will allow the data being collected in trials and clinical practice to answer new questions: (i) Extending cross-sectional surveys to longitudinal cohorts with appropriate items will answer questions such as do obstructive lung disease progress? What are predictors of progression? (ii) adding new items in existing cohorts for example in URAC project there is potential to examine microbiome in sputum, genetic markers while tracking disease progression is relatively easy in Uganda.Conclusion: The neglected pandemic of chronic lung disease in Africa may be addressed by using existing resources and relatively small investments to generate and optimise longitudinal datasets.Disclosures: Nothing to disclose.Background: Data are needed to understand the trends of asthma drug use over time. The objective was to describe the use of asthma controller therapy between 2006 and 2015 in France.Method: Repeated database analyses were conducted each year from 2006 to 2015, using the EGB . Adult patients aged 18-40, without Long Term Disease status and/or hospital admissions related to COPD and with at least one dispensation of inhaled corticosteroids (IC), Long-Acting Beta2 Agonist (LABA) or Fixed Dose Combination of LABA/IC (FDC) were identified. Four specific profiles were investigated: single IC without LABA (IC group), single LABA without IC (LABA group), single IC and LABA in separate canisters (IC+LABA group), FDC without dispensation of IC nor LABA (FDC group). Each year, patients’ characteristics, and percentage of patients in each group were described.Results: The overall percentage of asthma controller therapy users remained stable between 2006 and 2015 (1.5% of the EGB population). Mean age (31.3 to 31.0 years) and gender  varied little. Hospitalizations for asthma (0.6% to 0.5%) were rare. Patients with ≥1 annual dispensation of oral corticosteroids increased from 44.0% in 2006 to 50.5% in 2015. Between 2006 and 2015, percentage of patients decreased in the LABA group (4.1% to 2.0%), in the LABA+IC group (6.2% to 2.0%), and in the IC group (44.8% to 39.1%) whereas it increased in the FDC group (44.8% to 56.8%).Conclusion: In France, prevalence of asthma controller therapy use remained stable between 2006 and 2015 but FDC tended to replace other asthma medications. Use of oral corticosteroids increased during the period.Disclosures: Nothing to disclose.Background: Randomised controlled trials (RCTs) are required to establish the efficacy and safety of novel asthma treatments, but pragmatic randomized trials and observational comparative effectiveness research (CER) studies are also necessary to test the external validity of their findings. While quality standards for RCTs are well-defined, e.g., by the CONSORT statements, this is less so in the field of observational comparative effectiveness research. To address this, the Respiratory Effectiveness Group (REG) and European Academy of Allergy and Clinical immunology (EAACI) convened a joint Task Force to set and test quality standards for observational CER in asthma, leading to the development of the Real Life Evidence AssessmeNt Tool (RELEVANT).Method: A systematic review of previously published quality checklists was performed to identify criteria to include in RELEVANT. The initial tool was reviewed by the Task Force and the central recommendation was to reduce the number of criteria minimize inter-rater variability. The tool was pilot tested by subgroups of the task force, followed by an extended pilot of 22 participants identified through an open invitation to all REG collaborators. Finally, an online version was created using Google forms. RELEVANT was then used to appraise studies relating to four selected PICOT questions: the influence of adherence, smoking, inhaler device and particle size on asthma treatment effectiveness.Results: RELEVANT comprises primary and secondary criteria. Any failure of an article to meet primary criteria precludes the study’s use to support a guideline. Inter-rater agreement of the initial tool was variable across individual criteria (33-100%), but following iterative feedback, inter-rater agreement in the extended pilot was greater than 70% for 94% of primary criteria and 93% of secondary criteria. The final tool consists of 21 sub-items across seven domains: Background, Design, Measures, Analysis, Results, Discussion/Interpretation, Conflicts of Interest. A total of 46 articles relating to the four PICOT questions were identified and assessed using RELEVANT. For all PICOT questions, assessed observational studies yielded results with possible impact on clinical practice in areas where similar evidence from RCTs is lacking.Conclusion: RELEVANT is the first quality checklist to assist in the appraisal of published observational CER developed through iterative feedback derived from pilot implementation and inter-rater agreement evaluation. Further steps now need to be discussed to determine how the tool can be disseminated and its use implemented in collaboration with scientific societies, guidelines developers and other stakeholders.Disclosures: Dr. Campbell has received consultancy or research grants over the past three years from: Agency for Healthcare Research and Quality, ALSAM Foundation, Amgen, AstraZeneca, Bayer, Biogen Idec., Boehringer Ingelheim, Center for Disease Control and Prevention, Colorado Medicaid, Creative Group Inc., Enterprise Community Partners Inc., Institute for Clinical and Economic Review, Kaiser Permanente, Mallinckrodt, National Institute of Health, National Multiple Sclerosis Society, PhRMA Foundation, Precision for Value, Teva, Research in Real Life Ltd., Respiratory Effectiveness Group, and Zogenix Inc. Dr Roche: Reports and personal fees from Boehringer Ingelheim, Novartis, Pfizer and personal fees from Teva, GSK, AstraZeneca, Chiesi, Mundipharma, Cipla, Sanofi, Sandoz, 3M, Zambon.Background: Paediatric asthma is a common, chronic lower respiratory disease, associated with significant morbidity and socio-economical burden. While it is beyond doubt that asthma in childhood represents a distinct entity, with diverging underlying mechanisms and triggers, outcomes and response to treatments, it is still approached as an extension of adult asthma in clinical practice. Characteristically, treatment recommendations are mostly based on indirect evidence from trials in adults and the available definitions still fail to address the particularities of paediatric asthma. The objective of this project is to identify and prioritize unmet research and policy needs in paediatric asthma.Method: We conducted a comprehensive online open-question qualitative survey that was targeted to world-leading experts, clinical researchers in the field of paediatric asthma, enquiring on unanswered clinically-relevant questions around paediatric asthma and specifically around its definition, classification, natural history, diagnosis, assessment, drug therapy and non-drug management, monitoring, management of exacerbations or other clinically relevant questions.Results: The survey was completed by 22 international experts (80% of those invited), from 16 countries and 5 continents. The numerous highlighted unanswered questions collectively confirm unmet needs in all aspects of the clinical approach to paediatric asthma. Primarily, there is an urgent need for the development of consensus on the definition, criteria for diagnosis and classification of paediatric asthma, which is anticipated to differ from adult asthma and possibly among different age groups. Moreover, characterization of clinical phenotypes and identification of predictors of disease severity, persistence and responsiveness to treatment needs also represent unanswered clinical questions. Evidence syntheses and new direct evidence is required to guide all aspects of pharmacological  and non-pharmacological treatment of stable paediatric asthma and exacerbations. Asthma prevention, adherence to treatment, inhaler technique, (tele)monitoring, community (school) interventions and the role of early routine assessment of comorbidities were additional areas of uncertainty. Surprisingly, the responses did not considerably differ from a similar exercise conducted 10 years ago.Conclusion: Many clinical questions related to paediatric asthma remain unanswered, as a result of the disease’s complexity, the limitations in conducting clinical research in children and the subsequent significant shortcoming of good-quality evidence in all domains assessed. There is a need for an international paediatric asthma network aiming to promote high-quality clinical research, the development of an international paediatric asthma registry and evidence-based recommendations.Disclosures: Nothing to disclose.Background: Severe asthma is a heterogenous disease with varying clinical manifestations. Several registries have been developed globally to study the natural history of this disease. However, few studies have compared the information collected by such registries. The aim of this study was to compare the data fields currently captured by severe asthma registries across the globe.Method: Medline, EMBASE, Web of Science, web searches as well as consultations with leaders of severe asthma research databases were used to identify severe asthma repositories. Investigators were contacted to collect information on data collection specifications. Data dictionaries from respective databases were used for systematic comparison and pooling of variables. A database of data fields (as indicator variables) and countries  was created. Categories of variables, such as demographics and diagnostics, were used for ease of reporting, and Stata14 and Microsoft Excel were used to organize and tabulate data fields.Results: From the eighteen identified databases, data collection specifications from a total of ten severe asthma research repositories, covering 255 sites globally, were received. All country-specific databases collect information on asthma medications as per Global Initiative for Asthma guidelines for severe asthma. Among the non-asthma medications, anti-histamine data was most prevalently collected (seven repositories). With the emergence of novel asthma medications, the Spanish, Netherlands, German and Italian registries collected medication safety information. Sputum eosinophil, blood eosinophil and IgE levels were collected by all research databases, reaffirming the pivotal role these tests play in management of severe asthma. For assessing asthma control, seven used the Asthma Control Test, six used the GINA Asthma Control, and four used the Asthma Control Questionnaire. The approach for ascertaining adherence for inhaled and/or oral corticosteroids differed across countries. The United Kingdom, Australia, the Netherlands, Ireland, Nordics and USA use objective methods such as prescription records and/or blood cortisol levels, while Spain and South Korea use subjective compliance questions (two do not collect data on adherence).Conclusion: Severe asthma databases across the globe converge on collecting similar data field categories, while they differ significantly on the specific data fields included. A standard list of variables captured across countries will increase the statistical power of future studies by allowing for data interoperability.Disclosures: Nevaashni Eleangovan, Lakmini Bulathsinhala, Naeimeh Hosseini and Victoria Carter are employees of Optimum Patient Care.Liam Heaney has taken part in advisory boards and given lectures at meetings supported by GlaxoSmithKline, Respivert, Merck Sharpe & Dohme, Nycomed, Boehringer Ingelheim, Teva, Vectura, Novartis and AstraZeneca. He declares sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Napp Pharmaceuticals; and speaker fees from AstraZeneca, Aerocrine, Hoffman la Roche and Teva.Andrew Menzies-Gow declares grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Hoffman La Roche; consultancy agreements with AstraZeneca; personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffman La Roche, Napp Pharmaceuticals, Novartis, Teva and Vectura; non-financial support from AstraZeneca, Boehringer Ingelheim and Napp Pharmaceuticals; and payment for travel expenses to international conferences from AstraZeneca, Boehringer Ingelheim and Napp Pharmaceuticals.Peter Gibson declares grants from AstraZeneca, GlaxoSmithKline and Novartis; and personal fees from AstraZeneca and GlaxoSmithKline.Matthew Peters declares personal fees and non-financial support from AstraZeneca and GlaxoSmithKline.Chin Kook Rhee declares consultancy and lecture fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, MSD, Mundipharma, Novartis, Sandoz, Takeda and Teva-Handok.Roland Buhl declares personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, Roche and Teva, as well as grants to Mainz University from Boehringer Ingelheim, GlaxoSmithKline, Novartis and Roche.Anke H. Maitland-van der Zee declares unrestricted grants from GlaxoSmithKline and personal fees for advisory board activities from AstraZeneca.Luis Perez de Llano declares grants from AstraZeneca, Chiesi and Teva; personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, GlaxoSmithKline, Mundipharma, Novartis, Sanofi and Teva; non-financial support from Boehringer Ingelheim, Esteve, GlaxoSmithKline, Menarini, Mundipharma, Novartis and Teva.Borja G Cosio declares grants from Chiesi; personal fees for advisory board activities from Chiesi and AstraZeneca; and payment for lectures/speaking engagements from Chiesi, Novartis, Menarini and AstraZeneca.Richard Costello is named on the INCA device patent application; PCT/EP2013/067932, filed on the 29th of August 2013.David Price declares board membership with Aerocrine, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Mundipharma, Napp Pharmaceuticals, Novartis and Teva; consultancy agreements with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Napp Pharmaceuticals, Novartis, Pfizer, Teva and Theravance; grants and unrestricted funding for investigator-initiated studies  from Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Mylan, Mundipharma, Napp Pharmaceuticals, Novartis, Pfizer, Respiratory Effectiveness Group, Teva, Theravance, UK National Health Service and Zentiva; payment for lectures/speaking engagements from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Merck, Mundipharma, Novartis, Pfizer, Skyepharma and Teva; payment for manuscript preparation from Mundipharma and Teva; payment for the development of educational materials from Mundipharma and Novartis; payment for travel/accommodation/meeting expenses from Aerocrine, AstraZeneca, Boehringer Ingelheim, Mundipharma, Napp Pharmaceuticals, Novartis and Teva; funding for patient enrolment or completion of research from Chiesi, Novartis, Teva and Zentiva; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd  and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); and is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme and Health Technology Assessment.Celeste Porsbjerg, Eileen Wang and G.Walter Canonica declare no relevant conflicts of interest concerning this abstract.Background: Oscillometry is a fast and easy form of objective lung function measurement whose deployment is limited, in part, due to a lack of normative data. We wished to establish an upper limit of normal (ULN) for the integrated area of low frequency reactance (AX), the oscillometry estimate of ventilatory inhomogeneity, by a random sampling of visitors to a community hospital open house marking World COPD Day 2017.Method: A COPD nurse asked random visitors to participate, obtained written informed consent, administered a respiratory health survey and the patient reported outcomes (PRO) CAT, mMRC, ACT and chronic bronchitis questionnaire. Subjects completed first oscillometry  and then spirometry  by respiratory therapists respecting ATS/ERS criteria. Subject data were divided into groups of those with and without a history of respiratory disease. Group differences were tested with Bonferroni corrected Student’s t-tests or χ2, as appropriate for normally distributed data, and Mann-Whitney U tests for non-normally distributed data. The AX ULN was calculated using the mean+2SDs of ln transformed AX after exclusion of outliers amongst those without a history of respiratory disease. Associations between the FEV1, lnAX and PROs were measured using Bonferroni corrected Pearson correlations. The study had IRB approval.Results: 47 subjects completed the study; 11 with  and 36 without a history of respiratory disease. Groups didn’t differ in terms of age, sex distribution, smoking history but did for ACT, FEV1%predicted, FEV1/FVC, MMEF %predicted, resistance at 5 Hz (R5), reactance at 5 Hz (X5), frequency dependence of resistance (R5-20), and AX (Table 1).X frequency histogram demonstrated a bimodal distribution .The lnAX correlated with CAT and mMRC more strongly than FEV1 .AConclusion: Both spirometry and oscillometry demonstrated significant differences between subjects with and without a history of respiratory disease. Oscillometry correlated more strongly with PROs than spirometry. AX demonstrated a bimodal distribution amongst subjects without a history of respiratory disease as we have seen previously in 3 independent populations. The AX ULN is similar to our previous observations suggesting a disease defining threshold of 10-20 cmH20/L.Future Directions: All subjects with AX≥8 cmH2O/L are to undergo formal respiratory consultation, imaging and complete pulmonary function testing permitting estimation of negative and positive predictive values for this AX ULN.Disclosures: Nothing to disclose.Background: Smoking in the perioperative period has been associated with increased postoperative complications, hospital costs and health care resources. Tobacco cessation has been prioritized as a quality improvement performance measure by the Joint Commission and in recent American College of Surgeons position statement. Hospitalization for surgery and the period of forced cessation that it involves is a ‘window of opportunity’ for delivering smoking cessation interventions. No studies have yet investigated the utilization of smoking cessation pharmacotherapy (SCP) in surgical patients. Given the lack of data, we sought to describe the prescription of SCP in smokers with a COPD diagnosis undergoing a surgical procedure.Method: Retrospective study using a large database of 466 hospitals in the US. We included adults 18 years of age or older, admitted from January to December 2016 for an elective or urgent surgery with an estimated length of stay of more than 2 days. We restricted the analysis to active smokers with a diagnosis of COPD (defined based on the ICD-10 codes). Primary outcome was utilization of any SCP: varenicline tartrate, and nicotine replacement therapy, including nicotine patch, gum, lozenge, and inhaler. We collected demographics, insurance and comorbidities data and classified the surgeries in urgent versus emergent and into eleven main categories. We also identified oncological diagnosis possibly related to smoking.We developed a hierarchical generalized linear model to determine independent patient, surgery and hospital factors associated with the use of SCP. We also describe variation in SCP use across hospitals with 10 or more eligible patients and calculated the median odds ratio (MOR) to quantify the influence of the hospital on the probability of receiving SCP.Results: Among 43,708 surgical patients with a diagnosis of active smoking and COPD only 1805 patients (4.1%) had SCP administered at least once during their hospital stay and the nicotine patch was the predominant mode (91.5%). Compared with patients who did not receive SCP, those who received SCP were younger: mean age 67.5 vs 60.5 years and more likely to have Medicaid insurance. They were more likely to have psychiatric diagnoses , alcohol disorders , drug abuse disorders  or oncological diagnoses  but were less likely to have diabetes, obesity  or renal failure. Patients undergoing urgent surgeries were also more likely to have SCP prescribed . The median hospital rate of SCP use was 3.4%; IQR: 1.2, 6.5%, and hospitals located in the South, non-teaching and rural hospitals had higher rates of use. The MOR was 1.2; 95% CI: 1.1, 1.3.Conclusion: Despite strong evidence that smoking is associated with surgical complications and the potential benefit to initiating therapy during hospitalization, we found that SCP is rarely used in the postoperative period in patients with active smoking and with a COPD diagnosis. Further studies should determine strategies to implement perioperative smoking cessation with outpatient follow-up to improve quit rates and subsequently patients outcomes.Disclosures: Nothing to disclose.Background: While inhaler therapies are the mainstay of treatment for both asthma and Chronic Obstructive Pulmonary Disease, adherence to these medications is often sub-optimal. Reduced adherence increases the risk of exacerbations and hospitalisations and worsen prognoses. Monitoring of dosage, technique and adherence through “smart inhalers” offers an opportunity to provide patient specific services to improve adherence. Despite the availability of a plethora of smart inhaler products, there is a paucity of evidence on the feasibility and user acceptability of specific systems, both from the viewpoint of patients and of physicians.This study will provide an overview of all smart inhalers currently available, and those coming to market soon and whether they meet the key needs of respiratory physicians and other health care professionals.Method: Systematic review: PubMed will be searched using the following search terms;  AND “inhaler”); with no language restrictions in place. Studies evaluating, describing or using inhalers with a digital component will be included in the analysis. Studies using devices that are no longer available will be excluded.Keywords and inhaler names will be recorded and, if applicable, will be included in a second round of searching. Reference lists of review articles will be used to identify additional studies. The studies will be reviewed independently by two researchers and disagreements discussed and referred to a third researcher where necessary. Data on the inhaler type, the technology used, data capture and access, and opinions of the user will be extracted for analysis.Delphi exercise: An electronic Delphi panel will be constructed, consisting of primary and secondary care physicians, nurses, pharmacists and physiotherapists. Members will be recruited through professional contacts and networks. The Delphi process will comprise of three rounds. Round one will contain open-ended questions. Round two will contain of key themes gathered from round one, with importance of these themes rated on a Likert scale. Round three will include refined statements, with agreement measured on a multi-point scale.Results: The results of this study will be communicated in a peer-reviewed journal.Conclusion: This study will review the current availability, functionality, utility and acceptability of smart inhalers. It will be used to inform further research into the use of technologies to predict and detect exacerbations, and to optimise adherence and therefore patient outcomes.Disclosures: Nothing to disclose.Background: Inhaled Corticosteroids (ICS) have been overprescribed in the management of COPD. Research has highlighted that ICS are not benign and have significant side effects and that adequate bronchodilation may be as good/better for exacerbation prevention in many patients. Patients with concomitant COPD and Asthma require treatment with ICS, but they represent a minority of all COPD patients. Removal of ICS would benefit many patients but requires a systematic approach to ensure the correct patients are considered and withdrawal is done safely.Method: Many studies have revealed that there is over-prescription of ICS in GOLD A and B patients that runs contrary to current recommendations. Additionally, ICS combinations are often started at early stages of the disease when benefits may be negligible. Newly available LABA/LAMA medications have demonstrated excellent symptom and exacerbation benefits, providing ICS free pharmacotherapy for COPD management in appropriate patients.A desktop helper has been created for international dissemination by a group of primary care respiratory interested clinicians to educate, guide, and support clinicians with ICS withdrawal in appropriate COPD patients after a literature review and consensus decision making process.Results: The Desktop helper is available in the tools section of the International Primary Care Respiratory GroupConclusion: ICS are overused in COPD. This desktop helper will give clinicians an approach to if, how and when to reduce this use in clinical daily practice.Disclosures: This work was supported by Novartis Global.Background: In asthma care adherence to inhaled corticosteroids (ICS) is usually suboptimal, which is associated with increased individual and societal asthma burden. Electronic healthcare records allow investigation of the role of ICS adherence in long-term routine care, however most evidence to date is cross-sectional, has limited granularity, does not distinguish between stages of adherence and between sequential and simultaneous associations. This project aimed to address prior methodological limitations by focusing on the relationships between ICS implementation and asthma control measured between each two consecutive prescription events.Method: A retrospective observational study was conducted using UK primary care records from the Optimum Patient Care Research Database. The index prescription date (IPD) was the date of the first ICS prescription, the baseline period was one year prior to IPD and the follow-up period 2 years post IPD. Inclusion criteria were: physician-diagnosed asthma, age ≥6 years, ≥2 ICS and/or SABA prescriptions in each follow-up year, and no LABA, LTRA or maintenance oral corticosteroids during the baseline year. ICS adherence (implementation) and risk domain asthma control  were computed for each period between two prescriptions  .Multilevel analyses examined to what extent (1) the variation in RDAC can be explained by implementation rates in the same or preceding interval, and (2) implementation can be explained by simultaneous and preceding RDAC (or RDAC components), controlling for socio-demographic and clinical characteristics.Results: The dataset contained 94,498 prescription intervals; 14,425 intervals with 0% adherence and 55,971 intervals with 100% adherence were excluded, leaving 24,102 intervals (4.0-99.6% adherence) from 10,472 patients. Implementation within the same interval had a small positive association with RDAC, and several patient characteristics were found to influence RDAC (Table 1). Overusing SABA, having ≥1 antibiotic prescription, and asthma-related outpatient visits in the same interval had a negative influence on implementation (Table 1). Overusing SABA in the previous interval was associated with lower implementation in the current interval.Conclusion: A weak reciprocal association may reflect slightly lower implementation in prescription intervals which include events indicative of loss of control. The lack of an association between implementation and control in consecutive intervals may suggest that patients adapt their use of medication to their current needs without this impacting on their subsequent control; similarly, current asthma control does not influence patient’s medication use in a next prescription interval.Disclosures: Nothing to disclose.


Objective: To discover the correlation of clinical and physiological measures for benign prostatic hyperplasia in hypertensive and normotensive patients.Methods: From September 2016 to October 2017, 435 patients were enrolled for further selection. The parameters evaluated for eligible patients included prostate volume, systolic blood pressure, diastolic blood pressure, international prostate symptom score, etc. Then the eligible patients were divided into two groups according to hypertension condition, and the clinical and physiological parameters were compared between two groups. The Pearson’s correlation coefficient was used to test the linearity of the relationships of these clinical and physiological components with prostate volume, total prostate specific antigen, and international prostate symptom score.Results: Finally, 350 patients were involved in this study, including 117 with hypertension and 233 without hypertension. Weight, body mass index, systolic blood pressure, and diastolic blood pressure were significantly different between the hypertension and normotension groups. In the normotension group, there were positive correlations between weight, body mass index, age, and prostate volume; between fasting blood sugar, systolic blood pressure, diastolic blood pressure, and total prostate specific antigen; between fasting blood sugar and international prostate symptom score. In the hypertension group, there were positive correlations between age and total prostate specific antigen and international prostate symptom score; between weight and prostate volume; between systolic blood pressure and total prostate specific antigen.Conclusion: This study indicated that there might be no significant association between hypertension and prostate volume. Epidemiological studies have shown that multiple factors may increase the risk of benign prostatic hyperplasia (BPH), such as advanced age, obesity, increased free prostate specific antigen (PSA) level, cardiovascular disease (CVD), and the use of β-blocker medications . It is kThe study subjects were selected from the Bladder Cancer and Benign Prostatic Hyperplasia Study in Chinese Population (BPSC), which was a prospective study investigating the clinical effect of interventional therapy and the risk factors for bladder cancer and BPH . This re2). The symptoms of the patients were assessed using international prostate symptom score (IPSS). Hypertension was diagnosed according to the systolic blood pressure  and diastolic blood pressure . Fasting blood samples were drawn from patients to determine fasting blood sugar , total prostate specific antigen , serum K+ (mmol/L), serum Na+ (mmol/L), serum Cl− (mmol/L), serum Ca2+ (mmol/L), and serum Mg2+ (mmol/L). Prostate volume (PV) was measured based on the prostate ellipsoid formula, by multiplying the largest anteroposterior , transverse , and cephalocaudal  prostate diameters using B-ultrasonography  and then calculating using the ellipsoid formula {PV = π/6 × [H (cm) × W (cm) × L (cm)]}  was calculated as weight in kilograms divided by height in meters squared (kg/mL (cm)]} .+, serum Na+, serum Cl−, serum Ca2+, and serum Mg2+ between the hypertensive and normotensive group, and then compared these parameters among the three subgroups with different levels of hypertension. The Student’s t-test was used to describe the difference of above parameters between the hypertensive group and the normotensive group. The Pearson’s correlation analysis was applied to examine linear relationships between these clinical and physiological components and PV, t-PSA, and IPSS. A p < 0.05 was considered statistically significant.All analyses were carried out using the SPSS 19.0 software. We compared age, weight, height, BMI, FBS, IPSS, t-PSA, PV, SBP, DBP, serum KTable 1. The mean age of the patients was 70.943 ± 7.362 years. The mean ages for the two groups were respectively 70.657 ± 7.327 years and 71.513 ± 7.431 years, and there was no statistically difference (p = 0.305). Weight, BMI, SBP, and DBP were significantly lower in the hypertensive group (p < 0.05). No significant difference was detected between the two groups in terms of all the other variables.A total of 350 patients were included in this study, among whom 117 patients with hypertension, including 80 grade 1, 30 grade 2, and 7 grade 3 hypertension cases. Baseline characteristics of all these patients were presented in Table 2 demonstrated the association between the parameters of hypertensive patients including PV, t-PSA, and IPSS and the other parameters of all these patients. In the analysis, a positive link was established between PV and weight which indicated that patients with higher weight were likely to have larger PV . A negative correlation was found between FBS and PV . Two parameters showing a significant link with t-PSA were age  and SBP . Similarly, age was positively associated with IPSS ; whereas serum Ca2+ was negatively correlated with IPSS .r = 0.232, p = 0.041) and age  were significantly correlated with PV in grade 1 and grade 2 patients, respectively; age , FBS , and PV  were significantly related to t-PSA in grade 1 level patients; negative correlation were also observed between serum Cl− , weight  and t-PSA levels in grade 1 level and grade 2 level, respectively. In addition, serum Ca2+ was negatively correlated with IPSS  in grade 2 patients. Table 3 presented the results of stratified analysis.According to the stratified analysis by grade of hypertension, we found that weight , like in grade 2 hypertension. Besides, both weight and BMI were associated with PV (p = 0.046 and p = 0.011 respectively). A negative association was established between serum Cl− and PV . There were also positive correlations between FBS, SBP, DBP and t-PSA levels . Moreover, FBS was positively related to IPSS , while height was negatively correlated with IPSS .The same comparison between the parameters of normotension patients were shown in 2+ and IPSS in BPH patients with hypertension. In the BPH patients without hypertension, age, weight, BMI, and serum Cl− were notably correlated with PV; FBS, SBP, and DBP were significantly associated with t-PSA level; height and FBS were remarkably linked to IPSS.In this study, clinical and physiological parameters of BPH were compared between hypertension and normotension patients undergoing surgery. As a result, significant correlations were observed between FBS, weight and PV; between age, SBP and t-PSA level; between age, serum CaOR = 1.76, 95%CI = 1.26–2.45) and moderate to severe obstructive symptoms , and a more than twofold increase in the risk of moderate to severe irritative symptoms ; after adjustment for lifestyle risk factors and medical conditions, the associations remained significant. Then the Third National Health and Nutrition Examination Survey (NHANES III) suggested that men with a history of hypertension had a significantly higher risk of BPH-related LUTS than those who never had this disease  (The connection of hypertension and BPH has been studied for more than 50 years since Bourke JB and Griffin JP suggested an association between hypertension and BPH etiology for the first time . However20–2.59) . Neverth+ levels outside the interval of 4.1–4.7 mmol/L were associated with increased mortality risk in patients with hypertension  but not linked to grade 2 level . FBS is the indicator of new-onset DM and one of the indicators of MetS. Hypertension is closely related to DM, with approximately 50% of patients who have hypertension developing hyperinsulinemia and 75% of patients who have T2DM developing hypertension (FBS was positively associated with t-PSA and IPSS in normotension group; whereas it showed a negative association with PV in hypertension group. When we stratified hypertension patients, we found FBS was positive link to grade 1 level (rtension . New-onsrtension , this mirtension . Our resTo our knowledge, this is the first study comparing clinical and physiological parameters of BPH in hypertensive and normotensive patients. The major limitation of the present study was the relatively small sample size, which might influence the accuracy of results, especially when there were only 7 patients with grade 3 level group after stratifying the BPH patients according to hypertension. Interestingly, none of targeted parameters were found to have positive or negative associations in this group, this probably due to too small samples. Hence, we suggest to perform large-scale studies in the future to further verify our results, especially the meta-analysis  when relIn conclusion, current study suggested that weight and BMI were different in the hypertensive and normotensive BPH patients, which were both correlated with PV in non-hypertension group; only weight was associated with PV in hypertension group. Age was positively correlated with PV in normotension group but not in hypertension group; however, age was positively related to t-PSA and IPSS in hypertension group, but it did not correlate with PV in normotension group. Furthermore, t-PSA was positively correlated with PV in hypertension group. These results indicated that there might be no significant association between hypertension and PV. However, further researches with larger sample sizes are warranted to clarify the association between hypertension and BPH.X-TZ, HW, and X-HW designed this study. HW, JX, and L-LM collected data. Y-HJ and L-LM re-checked data. HW and QH performed analysis. X-TZ wrote the manuscript. X-HW reviewed the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Future treatments in asthma will focus on drugs that target these aforementioned cytokines.Asthma is a common but complex chronic inflammatory heterogeneous lung disease, punctuated by the pathophysiological phenomenon of airway narrowing, coupled with symptoms of wheezing and coughing. The mechanism behind these symptoms is due to migration of eosinophils, mast cells, and CD4 T-helper cells into the submucosa of the airway, leading to hyperresponsiveness to common allergens, microorganisms, oxidants, pollutants, and consequently, airway remodeling. There is evidence that this migration is mediated by inflammatory cytokines derived from T-helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2), such as interleukins 4, 5, and 13. These cytokines lead to an increase in immunoglobulin E (IgE) production. Additionally, thymic stromal lymphopoietin (TSLP) released from airway epithelium can activate Th2 cells, innate lymphoid cells, or both. All have proven significant in the promotion of chronic airway inflammation and remodeling. In the past, most treatment strategies for this condition focused on two drug classes: β2 agonists (both short- and long-acting), and inhaled corticosteroids. Other treatments have included maintenance drugs, such as leukotriene receptor antagonists, long-acting anticholinergic agents, and theophylline. None of these, however, directly impact the interleukin or IgE pathways in a meaningful manner. Clinical trials of novel agents impacting these pathways have demonstrated efficacy and improved outcomes in asthma exacerbations, control, and forced expiratory volume in 1 second (FEV Asthma is a significant economic burden in the United States (US), based on morbidity, mortality, treatment, and lost productivity due to absenteeism from work and school. Nurmagambetov et al. examined data from 2008 - 2013 and found that the cost of asthma medical treatments alone was $3,266 per individual (in 2015 inflation-adjusted US dollars) [Asthma is typically managed using both pharmacological and non-pharmacological approaches. Allergen avoidance has been the main focus of the non-pharmacological approach. Pharmacological treatments have included β2 agonists, inhaled corticosteroids, leukotriene receptor antagonists, long-acting anticholinergic agents, and theophylline. Most patients respond to these treatments, but a certain subset experiences severe asthma, which is refractory (even to higher dosages) of these regimens. Research has continued in the deployment of novel asthma treatments, focusing on cytokine pathways when developing therapeutic targets for the management of such severe asthma. This paper will focus on the cytokines that have been implicated in severe asthma, currently targeted for potential novel therapeutic agents. These include T-helper 2 (Th2), type 2 innate lymphoid cells (ILC2), interleukin 4 receptor alpha (IL-4Rα), IL-4, IL-5, IL-13, thymic stromal lymphopoietin (TSLP), and non-Th2 pathways.Interleukins 4, 5, and 13 (derived from innate lymphoid cells and T-helper cells), as well as immunoglobulin type E (IgE), have become major targets for therapeutics in recent years for the roles they play in immune response and allergic pathogenesis . StudiesAsthmatic patients with allergic-type asthma have notably higher circulating levels of IgE compared to the general population -8. SensiThis review will focus on the following drugs: omalizumab , reslizumab ; Cinqaero® - EU, Teva Pharmaceuticals Ltd., Petach Tikva, Israel), mepolizumab , benralizumab , and dupilumab. As seen in Table OmalizumabOmalizumab  is a recombinant humanized deoxyribonucleic acid (DNA)-derived IgG1 monoclonal antibody. Currently, it is the only anti-IgE agent available for use in asthma approved in the US for use in patients who display all of the following characteristics: at least six years of age, have a diagnosis of moderate to severe persistent asthma, achieve inadequate control of asthma symptoms despite the use of medium- or high-dose inhaled glucocorticoids, have a serum IgE level between 30 and 700 international units per milliliter (IU/mL), and are sensitive (as demonstrated by a positive skin test) to specific allergens year-round .The US Federal Drug Administration (FDA) clinical trials demonstrated a lower frequency of exacerbations in asthmatic patients with omalizumab, as well as a decrease in overall corticosteroid exposure. However, it is not appropriate for treatment of acute symptoms. Corticosteroids should not be discontinued abruptly upon initiation of therapy but should instead be carefully titrated down as the patient responds to therapy. The clinician should also monitor for complications, such as eosinophilia, vasculitic rash, worsening pulmonary function, cardiac dysfunction, and neuropathic pain, particularly following any reduction in corticosteroid use .Omalizumab ultimately prevents activation of basophils and mast cells. This drug binds with high affinity to the heavy chain C-epsilon-3 (C-ε-3) domain of IgE, which in turn binds to the FcεRI receptors on basophils and mast cells. When sufficiently low amounts of circulating IgE are achieved, the activation of early- and late-phase allergic response is attenuated, causing a disruption of the allergic cascade, reducing eosinophil-mediated inflammation, and preventing mast cell degranulation. In addition, the expression of FcεRI is down-regulated once the omalizumab therapy is underway. The time frame in which down-regulation occurs appears to differ between basophils and mast cells, but mast cells are the rate-limiting step. Lin et al. found that omalizumab patients showed a 90% mean decrease in FcεRI expression after 70 days but virtually no decrease within the first seven days . In contOmalizumab is highly specific to IgE and will not bind to other immune globulins (such as IgG and IgA) nor can it bind FcεRI itself; this prevents not only inappropriate immune suppression for other functions but also activation of an asthmatic immune response by the drug. However, if IgE is already attached to FcεRI, it cannot displace it; thus, omalizumab is not suitable for use in the acute treatment of asthma exacerbation. Unfortunately, there is a very low threshold number of IgE molecules needed for immune activation , and a vast number of available sites at which it can bind . This means that an extremely high affinity for the IgE molecule and subsequent binding of nearly all circulating IgE is required for omalizumab’s clinical efficacy .The US Food and Drug Administration (FDA) clinical trials demonstrated a lower frequency of exacerbations in asthmatic patients with omalizumab, as well as a decrease in overall corticosteroid exposure, but it is not meant for the treatment of either acute bronchospasm or status asthmaticus. Dosing is based on body weight and pretreatment serum IgE levels. Dosing adjustments can be made for significant changes in body weight; however, it should not be adjusted for IgE levels taken either during the course of treatment, up to one-year post-treatment, or during an interruption in therapy. Past the one-year mark, IgE levels are considered to be at baseline and may be used to determine dosing once again if therapy resumes. No dosage adjustments are provided in the manufacturer’s labeling for either renal or hepatic impairment. However, it is recommended that doses exceeding 150 mg be distributed over more than one injection site .Although the FDA only approved its use in persistent asthma and failure of inhaled corticosteroid, the 2018 Global Initiative for Asthma (GINA) guidelines recommended that omalizumab only be considered for adjunctive therapy in patients with uncontrolled moderate or severe allergic asthma, despite the concomitant use of a medium-dose or high-dose inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) .While increases in rates of malignancy have been reported in short-term studies of omalizumab, it remains to be seen whether these rates are increased over the long-term. The clinician is encouraged to consider the risk/benefit ratio for their patient when deciding whether to use any monoclonal antibody therapy. Omalizumab has been explored through several randomized, placebo-controlled clinical trials as an add-on treatment for children and adults with allergic asthma. Three such trials are described below:Omalizumab Trial ITrial I was a prospective, multicenter, randomized, parallel-group, double-blind, placebo-controlled trial conducted in 2011 to evaluate the efficacy and safety of omalizumab in patients with inadequately controlled severe asthma using high-dose ICS  and LABAs, either with or without additional controller therapy . The stuThe primary endpoint was the number of asthma exacerbations experienced over the 48-week study period, requiring an increase in an average daily dose of ≥ 20 mg of prednisone or equivalent OCS dose adjustment . The exaOmalizumab Trial IIThis 24-week trial analyzed the effect of omalizumab in patients with persistent allergic asthma, using the National Heart, Lung, and Blood Institute (NHLBI) Asthma Control Guideline, Step 4 or above, as their control therapy  . The priOmalizumab Trial IIIThis trial was a double-blinded, placebo-controlled, multicenter, parallel-group trial designed to evaluate the efficacy and safety of omalizumab in ICS controller-dependent asthma patients, defined as requiring 420 to 840 mcg/day of beclomethasone dipropionate (BDP) or an equivalent ICS dose for ≥ 3 months prior to randomization . Those n1 increased from 68.2% to 72.53% in the omalizumab group, and from 67.7% to 69.1% in the placebo group. These improvements in FEV1 were statistically significant and remained consistent throughout the entire study . The frequency of adverse effects in the two groups were not significantly different, with 89.2% of omalizumab patients and 89.1% of placebo patients reporting at least one adverse effect. The study concluded that omalizumab was safe and effective for patients with severe allergic asthma exhibiting poor control or frequent exacerbations despite appropriate therapy [The primary endpoint was the number of exacerbation episodes experienced by a patient during the steroid reduction period and during the stable steroid phase. One or more exacerbations during the 28-week study period were experienced by 14.6% of the omalizumab patients and 23.3% of the placebo patients (p = 0.009). In addition, the mean number of per-subject exacerbations  and mean duration of exacerbations  were also lower with omalizumab than with the placebo. More omalizumab recipients than placebo recipients achieved at least a 50% reduction in the BDP dose . Secondary variables measured during the study included the number of patients experiencing at least one exacerbation, daily asthma symptoms, rescue medication use, and pulmonary function. For these, omalizumab improved daily asthma scores vs. the placebo after four weeks of treatment, and rescue medication use was significantly reduced vs. the placebo for most of the measured weekly intervals. Increases in morning peak expiratory flow (PEF) were greater in the omalizumab group than in the placebo group from the baseline to the end of the study period. The mean change from baseline PEF in the omalizumab group was 18.5 L/min, while the placebo group had a mean change of 6.9 L/min. Mean predicted FEV therapy .Omalizumab’s pharmacokinetic and pharmacodynamic information  is foundReslizumabReslizumab  is an immune globulin G4-kappa-type (IgG4 κ) monoclonal antibody, approved by the FDA in 2016 as an add-on maintenance therapy in individuals 18 years of age and older with eosinophilic-type asthma. This agent was initially developed by several companies, including Schering-Plough [Reslizumab impairs the bioactivity of IL-5 by blocking its binding ability to the IL-5R α-chain complex expressed on the surface of eosinophils, thereby inhibiting IL-5 signaling and reducing both the production and survival of eosinophils -20. The Reslizumab has demonstrated notable inhibition of eosinophilia in a variety of animal models, including skin, rabbits, monkeys, and pigs -24. CharThe distribution volume of reslizumab is 5 L, with a clearance of about 7 ml/hour, and elimination half-life of 25 to 30 days. Following a dose of intravenous (IV) 1 mg/kg in patients with asthma, the following plasma concentration pharmacokinetic parameters were observed: mean maximal plasma concentration - 30.3 mcg/ml within 6.9 hours post-dose, declining to 0.87 mcg/ml by day 90 and subsequently to 0.43 mcg/ml by day 120 . In vitrClinical trials leading to the approval of reslizumab included four double-blind, randomized, placebo-controlled studies (Studies I-IV).Reslizumab Studies I/IINine hundred and fifty-three patients were enrolled in the reslizumab Studies I and II, with eosinophilic asthma and eosinophil counts of at least 400/mcL and at least one asthma exacerbation which required corticosteroid therapy over a 12-month period. These were simultaneous studies which lasted 52 weeks, the objective of which was to determine the efficacy and safety of reslizumab in decreasing asthma exacerbations. Patients were treated with IV reslizumab, 3 mg/kg, or placebo every four weeks for a total of 13 doses. Oral corticosteroid maintenance therapy, up to an equivalent dose of prednisone, 10 mg, were allowed during the studies. Most patients (82%) were managed with a medium- to a high-dose regimen of an inhaled corticosteroid and a long-acting β agonist (ICS/LABA) at baseline , 27.The primary endpoint of both studies was the frequency of asthma exacerbations, further defined as a deterioration of asthma based on one of two criteria. The initial criterion was the need for and use of systemic corticosteroids or augmented use of inhaled corticosteroids for three or more days. A twofold increase in corticosteroid use for three or more days was considered an exacerbation of asthma in individuals already taking corticosteroid treatment. The second criterion observed the frequency of emergency management, described as an impromptu visit to an emergency department, a health care provider for nebulizer treatment, or hospitalization associated with asthma .Patients in the reslizumab group had lower rates of total asthma exacerbations compared to those in the placebo group, with observed relative reductions of 50% in Study I, and 41% in Study II. Patients in the reslizumab group had fewer exacerbations necessitating systemic corticosteroid use compared to those in the placebo group, with relative reductions of 45% and 39% observed in Studies I and II, respectively. Relative reductions of 66% and 69% in Studies I and II, respectively, were observed in the reslizumab group (when compared with the placebo group) for exacerbations requiring hospitalizations or emergency department visits .Reslizumab Study III1 during a 16-week period. Baseline FEV1 measurements were obtained at four, eight, 12, and 16 weeks. The mean of the FEV1 measurements was estimated via the mixed-effect model for repeated measurements, with a positive variation indicative of improved asthma control. There were two reslizumab groups and one placebo group in Study III. One of the reslizumab groups of patients were treated with 3 mg/kg IV every four weeks  over a 16-week period. The second group of reslizumab patients received 0.3 mg/kg of the drug IV every four weeks  over a 16-week period. The patients in Group 3 (placebo) were administered IV placebo every four weeks  over a 16-week period [Study III consisted of 315 eosinophilic asthma patients with eosinophil counts of at least 400/mcL, divided into three groups. The study was designed to compare the efficacy of reslizumab (3 mg/kg and 0.3 mg/kg to placebo in lung function improvement) in eosinophilic asthma patients. Patients requiring oral corticosteroids as maintenance therapy were excluded. The primary endpoint was the measured change in FEVk period .1 improvements of 0.286 L and 0.242 L were observed in the reslizumab (3 mg/kg and 0.3 mg/kg) groups, respectively, whereas FEV1 improved by 0.126 L in the placebo group after 16 weeks. The average changes in FEV1 were compared with the placebo and each of the reslizumab study groups. In the reslizumab 3 mg/kg group, an FEV1 change of 0.160 L greater than placebo , 0.060 - 0.258; p = 0.0018) was observed. In the reslizumab 0.3 mg/kg group, an FEV1 change 0.116 L greater than placebo  was observed [Compared to baseline, FEVobserved .Reslizumab Study IV1 variations over a 16 week period, and the reslizumab 3 mg/kg group had an average FEV1 increase of 0.076 L greater than the placebo group . An updated and current primary outcome measure assessed FEV1, determined in liters, in comparison to baseline eosinophil count, measured in 109/L. In the reslizumab 3 mg/kg group, a change of 0.0229 FEV1 L/eosinophil x 109/L was observed, compared to an FEV1 change of −0.2778 L/eosinophil 109/L in the placebo group [The objective of Study IV was to determine the efficacy of reslizumab, 3 mg/kg, towards improving pulmonary function in 497 patients with moderate-to-severe eosinophilic asthma. Individuals on maintenance oral corticosteroid therapy were excluded from this study; however, inclusion was not based on eosinophil counts. Approximately 80% of the patients had eosinophil counts less than 400/mcL. Reslizumab, 3 mg/kg IV, was administered every four weeks  over a 16 week period. The initial primary endpoint measured effectiveness via FEVbo group .Reslizumab’s pharmacokinetic and pharmacodynamic information  is foundMepolizumabMepolizumab  is an IgG1 κ monoclonal antibody, FDA-approved for use as an add-on maintenance treatment in patients 12 years or older with severe eosinophilic-type asthma who experienced recurrent exacerbations despite being on inhaled corticosteroid therapy, with or without the addition of oral corticosteroids. Through the addition of mepolizumab, asthma control appeared to be better obtained without the need for long-term steroid use -31.Similar to reslizumab, mepolizumab impairs the bioactivity of IL-5 by blocking its binding ability to the IL-5 α-chain complex, inhibiting eosinophil production, and survival. Dosing for mepolizumab is a single 100 mg subcutaneous injection into the upper arm, thigh, or abdomen every four weeks. No dose adjustments are recommended for geriatric patients, pediatric patients (> 12 years old), or those with renal or hepatic impairment . It is nHypersensitivity reactions, such as angioedema, bronchospasm, hypotension, urticaria, and rash, have been reported with mepolizumab, often requiring discontinuation. In patients with preexisting helminth infection, treatment must be completed before starting mepolizumab therapy. If a helminth infection occurs during mepolizumab therapy and the patient experiences difficulty with anti-helminth treatment, discontinuation of mepolizumab therapy is recommended until the parasitic infection is resolved. Additionally, case reports of herpes zoster infections have been noted; thus, it is recommended that patients beginning therapy receive vaccination against varicella if medically appropriate . Other cIn 2015, the FDA approved mepolizumab as add-on maintenance therapy through the evaluations of three clinical trials (Dose Ranging Efficacy and Safety with Mepolizumab in Severe Asthma (DREAM) , MepolizDREAM TrialThis 52-week multicenter, double-blind, placebo-controlled trial was conducted from November 9, 2009 through December 5, 2011 in eosinophilic-inflamed patients with a history of recurrent severe asthma exacerbations . Six hunMENSA Trial 1 increases of 100 mL and 198 mL in the intravenous and subcutaneous groups, respectively, when compared with the placebo group.MENSA was a randomized, double-blind, double-dummy study involving 576 patients with recurrent asthma exacerbations and eosinophilic inflammation despite high-dose inhaled glucocorticoid use . PatientSIRIUS Trial The SIRIUS study was a randomized, double-blind trial consisting of 135 patients suffering from severe eosinophilic-type asthma . The gluCOSMOS Trial The COSMOS study consisted of patients from the previous clinical trials MENSA and SIRIUS and was performed as a 52-week open-label extension study . Five huMepolizumab’s pharmacokinetic and pharmacodynamic information is found  in the ABenralizumabBenralizumab  is a fully-humanized, afucosylated anti-IL-5Rα monoclonal antibody that inhibits IL-5 receptor signaling and produces antibody-directed cell-mediated cytotoxicity of eosinophils and basophils . Unlike Dosing for benralizumab as add-on maintenance treatment of severe asthma is a 30 mg subcutaneous injection every four weeks for the first three doses, then once every eight weeks thereafter. The injection comes as a single-dose prefilled syringe with a 30 mg/mL solution .Patients with severe airway inflammation cannot always be adequately controlled by inhaled corticosteroids, and in some cases, they also cannot be controlled by systemic corticosteroids. Benralizumab’s dual mechanism of action gives a potentially superior efficacy profile to other agents of the same class; however, few trials have been completed to determine whether this is the case in vivo. A meta-analysis reviewing 10 trials comparing mepolizumab, reslizumab, and benralizumab did, however, determine that there were no significant differences between the three drugs’ safety and efficacy profiles when treating severe eosinophilic asthmatic patients . In addiSIROCCO Trial 1, asthma symptoms, and adverse events. Benralizumab, given either every four weeks or every eight weeks, reduced the annual asthma exacerbation rates (both with p < 0.0001), as well as prebronchodilator FEV1. Overall asthma symptom improvements, however, were only seen within the eight-week regimen of benralizumab. The most common adverse events that occurred in patients taking benralizumab were worsening asthma and nasopharyngitis [The SIROCCO trial examined the efficacy and safety of benralizumab in patients with severe asthma uncontrolled by concomitant high-dose inhaled corticosteroids and long-acting β-2 agonists . In thisryngitis .CALIMA Trial 1, asthma score, and adverse events. Benralizumab lowered the annual asthma exacerbation rates in both the four-week (p = 0.0018) and eight-week (p = 0.0188) regimens when compared to placebo. Additionally, benralizumab significantly improved prebronchodilator FEV1 for patients in both the four-week and eight-week groups over placebo. However, the total asthma symptom score was reduced only within the eight-week regimen. The most common adverse effects in patients taking benralizumab were worsening asthma and nasopharyngitis [The CALIMA trial examined the efficacy and safety of benralizumab in patients with severe, uncontrolled, eosinophilic asthma as an add-on therapy to high-dose inhaled corticosteroids and a long-acting β-2 agonist, with a history of two or more asthma exacerbations in the previous year . In thisryngitis .ZONDA Trial 1 in the patients treated with benralizumab when compared with placebo over the 28 weeks. Asthma symptoms varied widely across all patients observed; thus, differences between groups were not found to be statistically significant. The number of adverse events between both groups were comparable [The ZONDA trial examined whether benralizumab was as effective as oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids for the management of their severe eosinophilic asthma . In thismparable .Phase 2The Phase 2 trial observed the reductions in eosinophil biomarkers by benralizumab in patients with eosinophilic asthma. Blood serum was collected from patients who received benralizumab treatment (n = 24) and healthy volunteers (n = 20). Eosinophilic biomarkers were measured in all patients prior to the administration of benralizumab and once more after treatment was completed. The biomarkers measured were as follows: blood eosinophils, IL-5, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), eotaxin/chemokine (C-C motif) 11 (CCL11), eotaxin-2/CCL24, tumor necrosis factor (TNF), and interferon-γ (IFN-γ). There were no changes in serum TNF or IFN-γ in patients taking benralizumab when compared to placebo. Of the measured biomarkers, increases were seen in EDN concentrations, IL-5, and eotaxin concentrations  in patients taking benralizumab .Benralizumab’s pharmacokinetics and pharmacodynamics information  can be fDupilumabDupilumab  is a fully-humanized IgG4 monoclonal antibody which binds to the α subunit of IL-4 receptors, inhibiting the signaling of both IL-4 and IL-13 -46. ThesBecause these pro-inflammatory changes lead to increases in hyperresponsiveness of the airway, blocking these actions can help in slowing or ceasing progression of the disease and reversing airway obstruction. The results of the human trials demonstrated mixed results. IL-4 and IL-13 were comparable in many respects. IL-4 aids in directing naïve CD4+ Th cells towards a Th2 phenotype, while IL-13 enhances airway inflammation and remodeling ; dupilumDupilumab received FDA approval in October 2018 for the indication of add-on therapy for asthma in patients 12 years and older with moderate to severe persistent asthma, as an adjunct to inhaled corticosteroids and long-acting β-2 agonists -47. DupiDupilumab Trial ITrial I was a randomized study that recruited a total of 104 patients  with moderate to severe asthma and blood eosinophil levels of at least 300 cells per microliter over a 12-week period. Study patients were on both inhaled corticosteroid and long-acting beta-agonist (LABA) therapies. The primary outcome measured asthma exacerbations for each arm of the study. In the dupilumab group, three patients developed exacerbations, while 23 exacerbations occurred within the placebo group .1, morning and evening peak expiratory flow, ACQ score, symptomatic nocturnal awakenings, and the number of rescue inhalations used per day). For all secondary outcomes, small improvements from baseline were noted within the dupilumab group, which stabilized after two weeks, while the placebo group experienced either worsening of symptoms or no change. Inflammatory markers associated with Th2, such as the fraction of exhaled nitric oxide (FENO), serum biomarkers, plasma exotoxin-3, and peripheral blood eosinophil levels, were reduced in the dupilumab group , except for eosinophil levels, where no change was noted with either group. Adverse events reported in the study included injection site reactions, pharyngitis, nausea, and headache . No deaths occurred in either of the groups during the study [Secondary outcomes measured were the time since last asthma exacerbation and lung function change from baseline  with moderate to severe asthma and using both inhaled corticosteroid and LABA therapies. The study compared four different dosing regimens of dupilumab , further stratifying patients by blood eosinophil counts of at least 300 cells/mcL and patients with eosinophil counts less than 300 cells/mcL .1 from baseline to Week 12. In the group with eosinophil counts ≥ 300 cells/mcL, the highest increase in FEV1 was reported in two dosing arms: 200 mg every two weeks (Q2W) (p = 0.0008) and 300 mg Q2W (p = 0.0063). In the < 300 cells/mcL group, similar results were found in two dosing arms: 200 mg Q2W (p = 0.0043) and 300 mg Q2W (p = 0.0086). Secondary outcomes in the trial were exacerbation rates, time of exacerbation occurrence, and associated asthma symptoms. All results in the placebo group were statistically insignificant. All dupilumab dosing groups experienced a significant reduction in exacerbation rates, with the greatest reductions occurring in the 200 mg Q2W and 300 mg Q2W dosing arms. Exacerbations were also notably delayed in the dupilumab groups, regardless of eosinophil count [The primary outcome measured was the change in FEVil count .Adverse events reported in the study included upper respiratory tract infection, injection site erythema, and headaches. These rates occurred at similar rates across all groups . Serious adverse event rates were 6% in the placebo group, while it was 7% in the combined dupilumab regimen. Rates of serious events requiring discontinuation of the drug were 3% in the placebo group and approximately 4% in the combined dupilumab regimen. Two patients died within the dupilumab (300 mg Q4W) arm - one due to acute cardiac failure and the other due to many factors, such as metastatic gastric cancer, pneumonia, and pulmonary heart disease .Dupilumab’s pharmacokinetic and pharmacodynamic information  is found1, and occasionally reductions in inflammatory markers when used in patients with refractory asthma despite maximal usage of available β2-agonists and/or inhaled corticosteroids. Guidelines will be essential in determining which category of patients may receive each of these agents. Biomarkers will also come into play in aiding clinicians in making such determinations. While there is promise in the treatment of eosinophilic-mediated severe asthma, further research is warranted for the development of therapies focused on non-eosinophilic inflammatory pathways, as well as those with low Th2 expression.Clinical trials evaluating the efficacy of new biologic agents, such as omalizumab (Xolair®), reslizumab , mepolizumab , benralizumab (Faserna®), and dupilumab (Dupixent®), have shown significant relative reductions in exacerbation rates, increases in FEV