Acting Β2 Agonist Research Articles

Green Approach for Simultaneous Determination of Long Acting β-Agonists, their Organic Counterparts and Corticosteroids by HPLC Coupled with PDA Detector.

Accurate, precise and robust method was developed for the simultaneous estimation of long acting β2 agonist drugs (Formoterol fumarate, Salmeterol xinafoate and Vilanterol trifenatate) along with two organic counterparts (Xinafoic acid and Triphenyl acetic acid) and inhaled corticosteroids (Fluticasone propionate and Fluticasone furoate). The separation was carried out using C18 column (250 x 4.6 mm, 5 μ) with eluent comprising of 0.05% orthophosphoric acid: methanol: acetonitrile (40:30:30, v/v/v) at a 1 mL/min flow rate. Linearity was observed in the concentration ranges of 1.5-12 μg/ mL for Formoterol fumarate, 2.82-22.6 μg/mL for Xinafoic acid, 6.25-50 μg/mL for Vilanterol, 3.12-25 μg/mL for Salmeterol, 2.0-15.2 μg/mL for Triphenyl acetic acid, 62.5-500 μg/mL for Fluticasone propionate and 25-200 μg/mL for Fluticasone furoate. The proposed method was accurate, precise and robust and results were within the limit as per the ICH (Q2R1) guidelines. Additionally, the proposed method was found to be green and sustainable when analysed by different green analytical tools namely GAPI, AGREE, AGREEprep and BAGI.

Pharmacologic Treatment of Type 2-High Severe Asthma

Asthma is a common and heterogeneous disease whose treatment has considerably changed over the last decades. While inhaled therapies based on inhaled corticosteroids and long acting β2 agonists are effective in controlling asthma in the majority of patients, about 5% of asthmatics poorly respond to inhaled steroids or inhaled steroids/long acting β2 agonists combinations. These patients are affected by “severe asthma”, which is associated with need of oral corticosteroids, progression of the disease, increased use of healthcare services, deterioration of quality of life, and a significant economic burden on society. Asthma is no longer considered a single disease, but a respiratory syndrome with complex biological network of distinct and interrelating inflammatory and remodeling pathways (endotypes) that are associated with different clinical manifestations (phenotypes) both in the lungs (asthma) and other organs (e.g. nose and skin). Severe asthma endotypes may be broadly regarded as Type 2-high and Type 2-low, a model that has become central to asthma management with the development of novel treatments for the Type 2-high endotypes. The hallmark feature of Type 2-high asthma is eosinophilic inflammation, often associated with increased serum IgE, increased exhaled nitric oxide (FeNO) and blood eosinophilia. The discovery of the main key drivers of Type 2-high inflammation (IgE, cytokines such as interleukin IL-5, -4 and -13) enabled the development of new biological agents directed towards specific molecular targets. These advances have shifted the existing paradigm “one drug fits all” to “patient-tailored” novel therapies. The monoclonal antibodies direct to IgE (omalizumab), IL-5 and IL-5 receptor (mepolizumab, benralizumab, reslizumab), and to the α chain of the IL-4 and IL-13 combined receptor (dupilumab), and more recently, to the thymic stromal lymphopoietin (tezepelumab) have been shown in both clinical trials and real-life studies to control symptoms, reduce asthma exacerbations and improve lung function in severe asthmatics not controlled by full inhalation therapies. More recently, the Single Inhaler Triple Therapy (SITT) containing inhaled steroids, long acting β2 agonists and muscarinic antagonists has been developed, slightly improving the effectiveness/safety of the inhalation therapy. This report aims to review available therapeutic opportunities for patients with severe asthma focusing on patients with Type 2-high severe asthma and how to position these new therapeutic alternatives in clinical practice.

Effects of long-acting bronchodilators on cardiac autonomic control in COPD

IntroductionSeveral studies in COPD have shown a significant and early increase in the risk of cardiovascular mortality attributable to inhaled bronchodilators including long acting β2 agonists (LABAs) and muscarinic antagonists (LAMAs). Cardiac autonomic system impairment may be a potential mechanism involved. MethodsWe performed a phase 4, investigator-initiated, prospective, randomized, blinded, cross-over trial (LAB-Card trial - NCT02872090) to evaluate the effect of two LAMAs and one LABA on the cardiac autonomic system in patients with COPD by using three major assessment approaches: heart rate variability (HRV, a predictor of cardiovascular death), baroreflex sensitivity (BRS) and autonomic function (tilt test). Results34 patients attended four visits to receive either tiotropium 18µg, glycopyrronium 44µg, indacaterol 150 µg or placebo (lactose) in a randomized order followed by the assessment of HRV and BRS in supine position and after passive rising. Neither LAMAs (tiotropium or glycopyrronium) nor LABA (indacaterol) induced a higher LF/HF ratio (reflect of sympathetic/parasympathetic balance) measured in supine position at rest compared to placebo (primary outcome). Solely indacaterol induced an increase in heart rate compared to placebo. No significant differences were observed for HRV and BRS between active drugs and placebo in supine position or after passive rising. ConclusionWe did not found evidence of a deleterious effect of 2 LAMAs and one LABA on the autonomic cardiovascular control in COPD patients. Further investigations are needed to explore mechanisms by which long-acting bronchodilators may increase cardiovascular events in COPD.

Drug prescribing pattern in obstructive airway disorders in a tertiary care hospital, Chengalpattu, Tamil Nadu: A cross-sectional and observational study

Background: The term obstructive airway disorder comprises of bronchial asthma and chronic obstructive airway disease (COPD). Asthma is a chronic inflammatory disorder of airways while COPD is disease of alveoli. Asthma is characterized by recurrent episodes of wheezing, breathlessness, and nocturnal cough while patients of COPD present with chronic progressive breathlessness and wheezing. International guidelines are established for the management of obstructive airway disorders. Aims and Objectives: The aim of the study was to evaluate drug prescribing pattern in bronchial asthma and COPD patients at a tertiary care hospital. Materials and Methods: After obtaining permission from hospital authority and permission from the Institutional Ethics Committee, 54 admitted patients’ prescription were screened between period of June 2021 to December 2021. Informed consent taken from the patients and were interviewed for collection of basic data such as name, age, and occupation. The purpose of the observational study was to see whether there is adherence to current practice guidelines of obstructive airway disorders. Data were compiled and tabulated using excel sheet and were presented using percentages and frequencies with necessary graphs and charts. Results: Short acting β2 agonist (91%) and corticosteroids (59%) were the most prescribed agents in bronchial asthma while corticosteroids (75%) and short acting antimuscarinic agents (78.57%) were most common prescription in COPD patients. The most common antibiotic used for in obstructive airway disease was beta lactam antibiotic-cefotaxime. Conclusion: In obstructive airway disorders, inhalation route was most preferred route as compared to oral, intramuscular, or intravenous route. The preferred antibiotic was cefotaxime.

A randomized prospective study to compare the efficacy and safety of budesonide plus formoterol and tiotropium plus formoterol in patients having mild to moderate chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is a leading respiratory illness affecting the quality of lives around the world. The present study aims to compare the efficacy and safety of combination of inhaled corticosteroid (ICS) and long acting β2 agonist (LABA) with long acting β2 agonist and long acting muscarinic antagonist (LAMA) in treatment of mild to moderate COPD in a tertiary care hospital.Methods: Total 132 patients with COPD were recruited on the basis of inclusion and exclusion criteria for 8 weeks study from outpatient clinic. A complete pulmonary examination including spirometry examination was done to rule out severe and very severe forms of COPD. Spirometry was performed at the time of recruitment for evaluation of forced expiratory volume in one second (FEV1) and measurement of SpO2 at the time of recruitment at 2 weeks and 8 weeks. Appropriate statistical methods were used to compare the qualitative and quantitative primary and secondary efficacy end points, p value <0.05 was considered significant.Results: On analysis, there was a significant difference (p<0.05) was observed in FEV1 and SpO2 from baseline in ICS plus LABA group (n=66). A similarly significant difference (p<0.05) was observed in LABA and LAMA group (n=66). On comparison between ICS plus LABA and LABA plus LAMA no significant difference in FEV1 and SpO2 was observed between the two groups. More adverse drug reactions were observed in ICS plus LABA group than LAMA plus LABA group.Conclusions: Combination of ICS and LABA combination is as effective as combination of LABA and LAMA in patients having mild to moderate COPD. However, LABA and LAMA combination is preferable because it is associated with fewer side effects.

Study of prescribing pattern of drugs used in the treatment of bronchial asthma at tertiary care hospital of northern India

Background: Asthma is a chronic inflammatory disease requiring long term treatment. For an effective control of asthma symptoms background knowledge of the prescribing pattern of anti-asthmatic drugs is a must.Methods: A prospective, observational study was conducted in the Department of Respiratory Medicine OPD, King George's Medical University, Lucknow. 114 patients of asthma were recruited for the study. A case report form was filled from patient’s prescription containing the demographic details of the patients, presenting complaints, investigations and drugs prescribed along with their dose, duration, frequency, route of administration.Results: 114 patients’ prescriptions were assessed which showed average number of drugs per prescription - 3.22. 42.8% and 50% of the drugs were prescribed in accordance with World Health Organization model list of essential medicines and National list of essential medicines. Short acting β2 agonist (salbutamol), 61.4% was the most commonly and frequently prescribed single anti asthmatic drug. Combination of inhaled corticosteroid and long acting β2 agonist, 86.8% was the most commonly prescribed fixed dose combination anti asthmatic drug. Inhalational route (75%) was the most preferred one over oral route (25%).Conclusions: Asthma being a chronic disease requires prolonged treatment which imposes economic burden on the patients. Judicious prescription of drugs not only improves the patient clinically but also removes the unnecessary burden. Data obtained from these studies can be used as a guide to make future decisions regarding standard prescription.

A pharmacoepidemiological study of prescription patterns of β2 sympathomimetic bronchodilators in exacerbation of non-severe asthma in tertiary care hospitals, not needing hospitalization

Background: Arformoterol, the (R, R) enantiomer of the racemic (R, R / S, S) diastereomer, formoterol, is a short and long acting β2 agonist bronchodilator. Levosalbutamol, the (R, R) enantiomer of racemic diastereomer (R, R / S, S) salbutamol, has a greater affinity for the β2 receptor. Occupation of β2 receptors by agonists result in the activation of the Gs-adenylyl cyclase-cAMP-PKA pathway, followed by phosphorylative events leading to bronchial smooth muscle relaxation. The aim of this pharmacoepidemiological study was to analyse the prescription patterns, and prescription content analysis, of arformoterol, levosalbutamol, formoterol or salbutamol, in non-severe asthma exacerbation in tertiary care hospitals, not needing hospitalization.Methods: It was a multi-centre, retrospective, observational and analytical study of 100 asthmatic patients’ hospital medical records, treated with 3 doses of arformoterol, levosalbutamol, formoterol or salbutamol nebulization, followed by peak expiratory flow rates (PEFR) measurement at the baseline and 6 minutes, after each dose; along with adverse effects recording. The number of prescriptions of 100 patients was recorded, the percentage of prescriptions was calculated, and the prescription content analysis was done.Results: PEFR of the patients showed significant increase after the first, second and third doses of bronchodilator nebulisation, with negligible adverse effects. Salbutamol was most commonly prescribed (45 prescriptions, 45%), followed by levosalbutamol (35 prescriptions, 35%), formoterol (15 prescriptions, 15%) and arformoterol (5 prescriptions, 5%). All aspects of prescription content analysis showed 100% completeness.Conclusions: Arformoterol was more effective, but equally safe, as compared to levosalbutamol, formoterol and salbutamol. Prescription frequency of salbutamol was followed by levosalbutamol, formoterol and arformoterol. Prescription content analyses showed 100% completeness.

Patients’ sensory perception and satisfaction with use of metered dose inhalers and dry powder inhalers in moderate persistent asthma

Background: Inhalers containing corticosteroid and a long acting β2 agonist (LABA) are widely used in asthma treatment. This study assessed the patient sensory perception and satisfaction of budesonide/formoterol fixed dose combination by pressurized metered dose inhalers (pMDI) with spacer and dry powder inhalers (DPI) in patients of moderate persistent asthma.Methods: This was a 6 week prospective, randomized, open label, comparative, parallel group clinical study. All patients had a forced expiratory volume in 1 second (FEV1) of 60-80% predicted normal. The patients were assessed for sensory perception and satisfaction in group I (pMDIs with spacers) and group II (DPIs) using patient evaluation questionnaire (PEQ) and patient satisfaction and preference questionnaire (PASAPQ) at the end of 6th week.Results: In PEQ, statistical analysis of the mean attribute ratings showed that both the devices were easy to use by patients. More medication was felt reaching throat using DPIs. Patients on DPI liked the taste and felt it to be less strong than patients on pMDIs. The overall liking was statistically comparable in two groups. In PASAPQ, the patients on DPI group were very satisfied with the treatment than pMDI (p<0.05).Conclusion: Overall liking of both DPIs and pMDIs was comparable and patients on DPI were satisfied more with the treatment device. Patient sensory perception and satisfaction may be taken into account in selecting device to improve compliance to treatment.

Effect of doxycyline in chronic obstructive pulmonary disease - An exploratory study

PurposeVarious mechanisms, including oxidative stress, inflammation, and protease-antiprotease imbalance are proposed for the progressive decline in lung function in chronic obstructive pulmonary disease (COPD). Doxycycline, a broad spectrum tetracycline antibiotic, is reported to have non-antimicrobial matrix metalloproteinases (MMP) inhibitory action in various inflammatory conditions. The effect of doxycycline in COPD is hereby assessed in the present randomized prospective study. Patients and methodsThe first group of COPD patients (n = 30; mild (n = 3), moderate (n = 6), severe (n = 7), very severe (n = 14) as per GOLD II & III criteria was prescribed the standard therapy, a combination of (i) short acting anti-muscarinic agent (SAMA) + short acting β2 agonist (SABA) inhaled and (ii) corticosteroid inhaled (ICS) + long acting β2 agonist (LABA) (iii) ICS + LABA + LAMA. Whereas doxycycline (100 mg), was used daily once or twice as per Body Mass Index (BMI), as an add-on to existing standard therapy for the second group of patients (n = 30; mild (n = 2), moderate (n = 7), severe (n = 8), very severe (n = 13). All recruited patients were followed-up after 3 months of treatment. Lung function index FEV1(%) predicted, FEV1/FVC (%), quality of life status including COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ) were assessed. Routine blood cell count also was performed. ResultsBiochemical analysis included estimation of oxidative stress markers, inflammatory cytokines and proteases in plasma of both the groups. Reduction in oxidative stress is evidenced by a significant decrease in Lipid hydro peroxides (LPO), total oxidative stress (TOS) and increase in glutathione peroxidase (GSH-PX), reduced glutathione (GSH) and total anti-oxidant capacity (TAO) nitrite and nitrate (NOx) along with peroxynitrate following 3 months of add-on doxycycline treatment. Reduced levels of cytokines such as interleukin IL-6, TNF-α, IL-8 were also observed. Multivariate analysis identified TNF-α major effective discriminant among pre and post doxycycline treated COPD patients. The expression of TNF-α was inversely correlated with FEV1/FVC (%) changes. The levels of MMP-2 and MMP-9/tissue inhibitors of metalloproteinases (TIMP)-1 ratio (MMP-9/ TIMP-1), also decreased significantly and the decline could be associated with TOS. A significant increase in bilirubin and reduced glutathione (GSH) level was noticed in standard therapy group. ConclusionThese data suggest that the improvement in lung function and quality of life in COPD patients may probably be attributed to the antioxidant, anti-inflammatory and anti-MMP activity of doxycycline. The potential therapeutic role of long-term doxycycline, in addition to its traditional antibiotic effect, definitely warrants further attention.

The Effects of Switching from Fluticasone/Salmeterol Aerosol to Fluticasone/Formoterol Aerosol in Patients with Severe Asthma

Objective: Two pressurized Metered Dose Inhalers (pMDIs) containing a combination of a corticosteroid and long acting β2 agonist: Fluticasone propionate/Salmeterol Combination (FSC), and Fluticasone propionate/Formoterol Combination (FFC), are currently available in Japan. In order to examine the usefulness of the FFC pMDI, we sought to investigate the efficacy, adverse events, and handling after switching to the FFC pMDI from the FSC in patients with asthma. Methods: Fifty-six outpatients who were using the FSC pMDI (250/50 μg) twice daily were enrolled in the study. The following items were evaluated before and after the use of the FFC pMDI (250/10 μg) twice daily for 8 weeks: Asthma Control Test (ACT) Questionnaire; Asthma Health Questionnaire (AHQ)-33-Japan; spirometry; and forced oscillation technique. On the final day of the study, the original questionnaire was administered for a subjective evaluation between the FSC pMDI and FFC pMDI. Results: We found improvements in ACT (22.54 to 22.98, p=0.0076) and AHQ-33 Japan (16.27 to 14.23, p=0.0162) scores after FFC use. In addition, inspiratory capacity (p <0.0001) and forced expiratory volume in 1 second (p=0.0122) significantly increased. Further, 51.8% of patients preferred the FFC, while 12.5% preferred the FSC. Conclusion: There was a subjective and objective improvement in patients after switching to FFC pMDI from FSC pMDI. These findings indicate that FFC is more useful for patients with asthma. Further studies are needed to confirm the results of this study.

ALL THAT WHEEZES IS NOT ASTHMA: BRONCHIAL STENOSIS IN DISGUISE

SESSION TITLE: Allergy and Airway SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Bronchial stenosis is a rare condition usually presenting as a complication of sarcoid, tuberculosis, congenital lesions, traumatic injuries and inhalational injuries. Here we present a case of bronchial stenosis of unknown etiology initially presenting as asthma. CASE PRESENTATION: The patient was a 23-year-old female presented to the clinic with worsening symptoms of dyspnea, wheezing and dizziness. These symptoms remained refractory to inhaled corticosteroids and short acting β2 agonists. Her medical history included episodes of bronchitis consisting of cough and dyspnea worsened with exposure to cold air, dust and perfumes. She was diagnosed with asthma 5 years prior, controlled with inhaled corticosteroids and short acting β2 agonists. For her ongoing symptoms, she was on antibiotics and oral steroids with no relief. Physical examination was significant for audible wheezing, stridorous at times. Pulmonary function studies demonstrated moderately severe obstructive ventilatory defect. Laryngoscopy demonstrated normal motion of vocal cords. Serological studies, quantiferon and infectious work up returned negative. CT chest demonstrated narrowing of left main stem bronchus approximately 2 cm in length with the narrowest diameter being 3 mm. Fiberoptic bronchoscopy revealed concentric stricture of left main stem bronchus and inability to pass the therapeutic and diagnostic bronchoscopes past the stenosis. Endobronchial biopsies revealed changes consistent with chronic inflammation and no evidence of granulomas or capillaritis. Rigid bronchoscopy was performed with balloon dilatation and triamcinolone acetonide was inserted into the stricture. She remained symptom free for four months after the procedure. Rigid bronchoscopy with serial dilation was repeated due to recurrence of symptoms which re-demonstrated left main stem narrowing. The patient's symptoms have since resolved. DISCUSSION: Severe airway obstruction in a young patient is relatively unusual. Severe endobronchial anatomic changes are usually not suspected clinically. In these cases, radiographic findings or bronchoscopy are helpful in further evaluation. The absence of clinical, radiographic or pathologic evidence of either sarcoid, tuberculosis and vasculitides makes these diagnoses extremely unlikely in our case. This case demonstrates the possibility of milder forms of congenital bronchial stenosis escaping notice until late in life. CONCLUSIONS: This case typifies an old saying, “all that wheezes is not asthma". Bronchial stenosis should remain on the differential in a young person with airflow obstruction. Reference #1: Albert, RK and Petty, TL. Endobronchial tuberculosis progressing to bronchial stenosis. Chest. 1976; 70: 537–539 Reference #2: Westcott, JL and Noehren, TH. Bronchial stenosis in chronic sarcoidosis. Chest. 1973; 63: 893–897 DISCLOSURES: No relevant relationships by Muhammad Ali, source=Web Response No relevant relationships by Mark Barash, source=Web Response No relevant relationships by Stephen Dolan, source=Web Response No relevant relationships by UZAIR GHORI, source=Web Response No relevant relationships by Aasim Mohammed, source=Web Response No relevant relationships by Nabeel Siddiqui, source=Web Response

What is New in the Management of Childhood Asthma?

Asthma still causes considerable morbidity and mortality globally and minimal improvement has been seen in key outcomes over the last decade despite increasing treatment costs. This review summarizes recent advances in the management of asthma in children and adolescents. It focuses on the need for personalized treatment plans based on heterogenous asthma pathophysiology, the use of the terminology ‘asthma attack’ over exacerbation to instill widespread understanding of severity, and the need for every attack to trigger a structured review and focused strategy. The authors discuss difficulties in diagnosing asthma, accuracy and use of Fractional exhaled nitric oxide both as second line test and as a method to monitor treatment adherence or guide the choice of pharmacotherapy. The authors discuss acute and long-term management of asthma. Asthma treatment goals are to minimize symptom burden, prevent attacks and (where possible) reduce risk and impact of progressive pathophysiology and adverse outcomes. The authors discuss pharmacological management; optimal use of short acting β2 agonists, long acting muscarinic antagonist (tiotropium), use of which is relatively new in pediatrics, allergen specific immunotherapy, biological monoclonal antibody treatment, azalide antibiotic azithromycin, and the use of vitamin D. They also discuss electronic monitoring and adherence devices, direct observation of therapy via mobile device, temperature controlled laminar airflow device, and the importance of considering when symptoms may actually result from dysfunctional breathing rather than asthma.

PROBLEMS ASSOCIATED WITH THE DIAGNOSIS OF PROLONGED/CHRONIC COUGH IN CLINICAL SETTINGS

Many patients visit primary care clinics or local hospitals with a complaint of prolonged/chronic cough. Among the different types of chronic cough, cough variant asthma (CVA) and postinfectious cough may be the most common types, and their differential diagnosis is difficult. Some physicians tend to prescribe inhaled corticosteroids before establishing a definitive diagnosis. We retrospectively investigated useful findings for diagnosis in 77 patients with a complaint of prolonged/ chronic cough to detect meaningful findings for differential diagnosis and to identify problems associated with diagnosis in clinical practice. CVA was diagnosed in 39 patients, and postinfectious cough was diagnosed in 19. Compared with postinfectious cough, CVA was associated with significant characteristics such as "diurnal variation of symptoms," "response to inhalation of short acting β2 agonist (SABA)," and "recurrent episodes of symptoms." CVA was associated with high FeNO levels as well, and high FeNO levels were specific to CVA. However, these useful characteristics were not significant in the patients who had been prescribed ICS before visiting our hospital. Medical examination and determination of FeNO levels are useful for the differential diagnosis of prolonged/chronic cough, before treatment with ICS.

The Role of Tiotropium+Olodaterol Dual Bronchodilator Therapy in the Management of Chronic Obstructive Pulmonary Disease.

Bronchodilator therapy is central to the management of chronic obstructive pulmonary disease and are recommended as the preferred treatment by the Global Obstructive Lung Disease Initiative (GOLD). Long acting anti-muscarinics (LAMA) and long acting β2 agonists (LABA) are both more effective than regular short-acting drugs but many patients remain symptomatic despite monotherapy with these drugs. Combination therapy with LAMA and LABA increases the therapeutic benefit while minimizing dose-dependent side effects of long-acting bronchodilator therapy. The TOviTO programme has investigated the benefits of treatment with a combination of tiotropium and olodaterol administered via a single inhaler. Tiotropium+olodaterol 5/5 µg significantly improved forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours, trough FEV1 health status and breathlessness versus the mono-components and placebo. Tiotropium+olodaterol 5/5 µg also increased endurance time and reduced dynamic hyperinflation during constant work rate cycle ergometry. On the basis of these and other studies the 2017 GOLD report recommends escalating to dual bronchodilator therapy in patients in groups B and C if they remain symptomatic or continue to have exacerbations and as initial therapy for patients in group D.

Real-World Treatment Patterns Among Newly Diagnosed COPD Patients According to GOLD Airflow Limitation Severity Classification in a US Commercially Insured/Medicare Advantage Population

SESSION TITLE: COPD: Lessons for the Real-World Management of Disease SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 31, 2017 at 02:45 PM - 04:15 PM PURPOSE: GOLD recommendations suggest the use of long acting β2 agonist (LABA) and/or long acting muscarinic antagonist (LAMA) for most COPD patients, reserving regimens containing inhaled corticosteroids (ICS) for a more severe subset of patients. Data on implementation of GOLD recommendations into clinical practice are limited. The purpose of this study was to characterize real-world treatment patterns among a spirometry-confirmed COPD population by GOLD airflow limitation severity classifications. METHODS: Over a study period of 1/1/2011 to 11/30/2015, a cohort of newly diagnosed COPD patients was identified using administrative claims from a large US payer. Patients were required to have ≥1 inpatient, ED or office visit claim for COPD from 1/1/2012 to 11/30/2013 and continuous health plan enrollment for 1 year prior to and 2 years after the first COPD diagnosis date. Patients with ≥1 claim for spirometry were eligible for medical record abstraction to confirm COPD diagnosis (FEV1/FVC ratio <0.7) and to determine GOLD 1-4 classification (based on post-bronchodilator FEV1 % predicted). Following COPD diagnosis, treatment patterns including COPD maintenance therapy (LAMA, LABA, ICS) observed and medication persistence (using a 60 day permissible gap) were evaluated for each GOLD classification. The rate of moderate/severe COPD exacerbation post-diagnosis was calculated. RESULTS: 85,247 newly diagnosed COPD patients were identified and 14,293 (17%) had a claim for spirometry use. Medical records containing complete spirometry results were obtained for 4,130 patients, with 1,505 (36%) having a spirometry-confirmed diagnosis. Among the 1,505 confirmed COPD patients, 333 (22%) were GOLD 1, 823 (55%) were GOLD 2, 317 (21%) were GOLD 3 and 32 (2%) were GOLD 4. Following COPD diagnosis, maintenance therapy was observed in 43% of GOLD 1, 56% of GOLD 2, 73% of GOLD 3 and 75% of GOLD 4 patients. GOLD 1 and 2 patients on maintenance therapy most frequently used ICS-LABA (48% & 45%, respectively), followed by LAMA only (29% for each) and ICS only (16% & 9%), while approximately 5% of GOLD 1 and 9% of GOLD 2 patients used triple therapy (ICS-LABA+LAMA). Similarly, a majority of GOLD 3 and 4 patients on maintenance therapy used ICS-LABA (37% & 42%), followed by LAMA only (28% & 25%) and triple therapy (20% & 17%). Overall, the observed maintenance therapy after diagnosis was an ICS-containing regimen for 67% of patients. Assessing persistence, mean (±SD) days on maintenance therapy was 143 days (±130), 188 days (±142), 215 days (±143) and 282 days (±132) for GOLD 1-4 and 191 days (±142) overall. Rates of severe/moderate COPD exacerbation per 100 person-years for GOLD 1-4 patients were 40.4, 48.9, 83.6 and 89.1, respectively. CONCLUSIONS: Large numbers of patients did not use maintenance therapy and the majority of those who did, across all GOLD classifications, used ICS-containing regimens (especially ICS-LABA), which is inconsistent with GOLD recommendations. Medication persistence was poor overall, especially in GOLD 1 patients. CLINICAL IMPLICATIONS: The observed inconsistencies with GOLD recommendations for COPD medication in this study highlight a gap between guidelines and clinical practice and the need for improved diagnosis and treatment of COPD patients. DISCLOSURE: Anna Wallace: Employee: I am an employee of HealthCore, a wholly owned subsidiary of Anthem, a health insurance company. I own Anthem stock. HealthCore received funding to conduct the work that led to this abstract. Valentina Zubek: Employee: Dr. Zubek reports she is an Employee of Boehringer Ingelheim. Shuchita Kaila: Employee: Dr. Kaila reports she is an Employee of Boehringer Ingelheim. Asif Shaikh: Employee: Dr. SHAIKH reports he is an Employee of Boehringer Ingelheim.reports other from Boehringer-Ingelheim, during the conduct of the study. Mayura Shinde: Employee: Dr. Shinde was an employee of HealthCore during the conduct of this work. HealthCore received funds from Boehrniger Ingelheim to conduct this work. Vincent Willey: Employee: Dr. Willey reports his employer, HealthCore, received funding from Boehringer Ingelheim to perform the study. Joseph Singer: Employee: Dr. Singer reports he is an employee and shareholder of HealthCore/Anthem. HealthCore received funds from Boehringer Ingelheim to conduct this work. The following authors have nothing to disclose: Mark Napier No Product/Research Disclosure Information

Numerical simulation of emitted particle characteristics and airway deposition distribution of Symbicort® Turbuhaler® dry powder fixed combination aerosol drug

One of the most widespread dry powder fixed combinations used in asthma and chronic obstructive pulmonary disease (COPD) management is Symbicort® Turbuhaler®. The aim of this study was to simulate the deposition distribution of both components of this drug within the airways based on realistic airflow measurements. Breathing parameters of 25 healthy adults (11 females and 14 males) were acquired while inhaling through Turbuhaler®. Individual specific emitted doses and particle size distributions of Symbicort® Turbuhaler® were determined. A self-developed particle deposition model was adapted and validated to simulate the deposition of budesonide (inhaled corticosteroid; ICS) and formoterol (long acting β2 agonist; LABA) in the upper airways and lungs of the healthy volunteers. Based on current simulations the emitted doses varied between 50.4% and 92.5% of the metered dose for the ICS, and between 38% and 96.1% in case of LABA component depending on the individual inhalation flow rate. This variability induced a notable inter-individual spread of the deposited lung doses (mean: 33.6%, range: 20.4%–48.8% for budesonide and mean: 29.8%, range: 16.4%–42.9% for formoterol). Significant inter-gender differences were also observed. Average lung dose of budesonide was 29.2% of the metered dose for females and 37% for males, while formoterol deposited with 26.4% efficiency for females and 32.5% for males. Present results also highlighted the importance of breath-holding after inhalation of the drug. About a half of the total lung deposition occurred during breath-hold at 9.6s average breath-hold time. Calculated depositions confirmed appropriate lung deposition of Symbicort® Turbuhaler® for both genders, however more effort for optimal inhalation technique is advised for persons with low vital capacity. This study demonstrated the possibility of personalized prediction of airway deposition of aerosol drugs by numerical simulations. The methodology developed in this study will be applicable also to other marketed drugs in the future.

Herbal Medicines for Asthmatic Inflammation: From Basic Researches to Clinical Applications.

Asthma is one of the most common chronic inflammatory disorders, associated with reversible airflow obstruction, airway hyperresponsiveness, and airway remodeling. This disease has a significant impact on individuals, their families, and society. Standardized therapeutics such as inhaled corticosteroid in combination with long acting β2 agonist have been applied for asthma control; however, complementary and alternative medicines, especially herbal medicines, are still widely used all over the world. A growing body of literature suggests that various herbals or related products might be effective in inhibiting asthmatic inflammation. In this review, we summarize recent advances about the mechanistic studies of herbal medicines on allergic airway inflammation in animal models and their potential application into clinic for asthma control.

IL-10 and IL-17F Promoter Single Nucleotide Polymorphism and Asthma: A Case-Control Study in South India.

Several studies have assessed the association between IL-17F and IL-10 promoter polymorphisms and asthma, but the results were conflicting. Furthermore, few studies have evaluated the association of cytokine polymorphisms with asthma and its clinical phenotypes. This study was conducted to evaluate the association of IL-10 (interleukin 10) and IL-17F (interleukin 17F) promoter polymorphisms (rs1800871, rs1800896 and rs1889570) with asthma and its clinical phenotypes including severity, atopic status, spirometric parameters, and response to treatment in south Indian population. A sub-study was conducted to assess cytokine levels in subjects with different gene variants. IL-10 and IL-17F polymorphisms were genotyped in 419 asthmatic patients and 393 controls using Mass ARRAY. Our results showed an association between IL-10 SNPs and mild asthma. No association was found with any of three SNPs in moderate to severe asthma. Comparison of genotype distribution of IL-17F rs1887570 AA variant among atopic and non-atopic patients showed significant difference (p = 0.024). Correlation analysis of IL-10 and IL-17F SNPs to clinical variables showed a positive correlation between IL-17F rs1887570 AA and number of allergen sensitized (rs = 0.142, p = 0.004). Significant improvement in lung function was observed after 2 months of ICS (Inhaled corticosteroids) and LABA (long acting β2 agonist) treatment in all subjects with no statistically significant difference among SNPs variants. Cytokines levels were similar in different SNP variants. We observed an association between IL-10 rs1800871 and rs1800896 SNPs and mild asthma, as well as IL-17F rs1887570 AA variant and number of allergens sensitized.

Critical pathway of acute asthma attack for the Emergency Center: patients' outcomes and effectiveness

Purpose: Early recognition and management of asthma attack is critical before it becomes worse. We developed critical pathway (CP) of asthma attack at Emergency Center (EC) for making undelayed decision and management of asthma attack. Methods: Acute asthma attack assessment and treatment (4AT) CP began on April 1st 2012 and recruited the patients for 18 months. This study enrolled the patients who were older than 15 years and visited EC for dyspnea and wheezing. Initial assessment was done measuring peak expiratory flow rate (PEFR), oxygen saturation (SaO2). Once CP is activated, oxygen, inhalation of short acting β2 agonist, and injection of corticosteroid were administered to the patients. Every hour after CP activated, we reassess the patients’ response and make decisions whether to admit or discharge. Results: Until January 10th 2014, 62 patients enrolled in this study. Seven patients hospitalized for asthma and 40 patients discharged. The other 15 patients were deactivated as they were diagnosed of heart failure, myocardial infarction, aortic dissection, anaphylaxis, chronic obstructive pulmonary disease and pneumonia for the causes of dyspnea. Mean Interval from EC arrival to 4AT activation was 32.6±29.1 minutes and the mean interval from 4AT activation to position decision was 254.5±302.0 minutes. Among 47 patients who were diagnosed with asthma attack, 13 patients were not aware of asthma before this attack. Forty patients were discharged at EC after management of CP. Among them, 34 patients revisited clinic, but 6 patients did not. We called back to the lost 6 patients but only 3 patients were connected. Even they visited EC due to asthma attack, 2 patients had no insight of importance of regular management and the other one promised to revisit. Conclusion: CP was successful for early management of asthma attack. However, 15% of discharged patients never show up again. So, education program about the importance of ongoing management of asthma for prevention of asthma attack is needed. (Allergy Asthma Respir

S108 Statin use and cigarette smoking are associated with lower incidence of radiation pneumonitis

BackgroundThree months after radical radiotherapy for lung cancer, 50–60% of patients have radiation pneumonitis (RP) on CT thorax. Our aim was to assess the clinical and dosimetric factors associated with...