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1. The burden of severe asthma in sub-Saharan Africa: Findings from the African Severe Asthma Project

Author

Bruce J. Kirenga, MBChB, MMed, PhD, Jeremiah Chakaya, MBChB, MMed, Getnet Yimer, MD, PhD, George Nyale, MBChB, MMed, Tewodros Haile, MD, Winters Muttamba, MBChB, MPH, Levicatus Mugenyi, PhD, Winceslaus Katagira, MBChB, MMed, William Worodria, MBChB, MMed, PhD, Hellen Aanyu-Tukamuhebwa, MBChB, MMed, Njira Lugogo, MD, Moses Joloba, MBChB, MS, PhD, Tesfaye B. Mersha, PhD, Amsalu Bekele, MD, Fred Makumbi, PhD, Amha Mekasha, PhD, Cynthia L. Green, PhD, Corina de Jong, PhD, Moses Kamya, MBChB, MMed, MPH, PhD, and Thys van der Molen, MD, PhD

Subjects
Severe asthma, burden of severe asthma, severe asthma determinants, sub-Saharan Africa, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Severe asthma is associated with high morbidity, mortality, and health care utilization, but its burden in Africa is unknown. Objective: We sought to determine the burden (prevalence, mortality, and activity and work impairment) of severe asthma in 3 countries in East Africa: Uganda, Kenya, and Ethiopia. Methods: Using the American Thoracic Society/European Respiratory Society case definition of severe asthma, we analyzed for the prevalence of severe asthma (requiring Global Initiative for Asthma [GINA] steps 4-5 asthma medications for the previous year to achieve control) and severe refractory asthma (remains uncontrolled despite treatment with GINA steps 4-5 asthma medications) in a cohort of 1086 asthma patients who had been in care for 12 months and had received all GINA-recommended medications. Asthma control was assessed by the asthma control questionnaire (ACQ). Results: Overall, the prevalence of severe asthma and severe refractory asthma was 25.6% (95% confidence interval [CI], 23.1-28.3) and 4.6% (95% CI, 3.5-6.0), respectively. Patients with severe asthma were (nonsevere vs severe vs severe refractory) older (39, 42, 45 years, P = .011), had high skin prick test reactivity (67.1%, 76.0%, 76.0%, P = .004), had lower forced expiratory volume in 1 second percentage (81%, 61%, 55.5%, P < .001), had lower quality of life score (129, 127 vs 121, P < .001), and had higher activity impairment (10%, 30%, 50%, P < .001). Factors independently associated with severe asthma were hypertension comorbidity; adjusted odds ratio 2.21 (1.10-4.47), P = .027, high bronchial hyperresponsiveness questionnaire score; adjusted odds ratio 2.16 (1.01-4.61), P = .047 and higher ACQ score at baseline 2.80 (1.55-5.08), P = .001. Conclusion: The prevalence of severe asthma in Africa is high and is associated with high morbidity and poor quality of life.

Published
2024
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2. Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study

Author

Andrew Menzies-Gow, Michael E Wechsler, Christopher E Brightling, Stephanie Korn, Jonathan Corren, Elliot Israel, Geoffrey Chupp, Artur Bednarczyk, Sandhia Ponnarambil, Scott Caveney, Gun Almqvist, Monika Gołąbek, Linda Simonsson, Kaitlyn Lawson, Karin Bowen, Gene Colice, Jorge Lima Hetzel, Jussara Fiterman, Adelmir Souza Machado, Martti Anton Antila, Marina Andrade Lima, Suzana Erico Tanni Minamoto, Daniela Cavalet Blanco, Patricia Gomes de Matos Bezerra, Pierre-Alain Houle, Catherine Lemiere, Lyle S Melenka, Richard Leigh, Patrick Mitchell, Syed Anees, Bonavuth Pek, Guy Chouinard, Amarjit S Cheema, William Ho-Ching Yang, George Philteos, Pascal Chanez, Arnaud Bourdin, Gilles Devouassoux, Camille Taille, Frédéric De Blay, Christophe Leroyer, Antoine Beurnier, Gilles Garcia, Pierre-Olivier Girodet, François-Xavier Blanc, Antoine Magnan, Stéphanie Wanin, Jocelyne Just, Richard Linde, Stefan Zielen, Karin Förster, Christian Geßner, Margret Jandl, Roland Otto Buhl, Marc Oliver Kornmann, Anneliese Linnhoff, Andrea Ludwig-Sengpiel, Martin Ehlers, Tibor Schmoller, Heiner Steffen, Martin Hoffmann, Joachim Kirschner, Olaf Schmidt, Tobias Welte, Hilke Temme, Ori Wand, Amir Bar-Shai, Gabriel Izbicki, Neville Berkman, Gershon Fink, David Shitrit, Yochai Adir, Piotr Kuna, Barbara Rewerska, Ewa Pisarczyk-Bogacka, Oksana Kurbacheva, Sergey L Mikhailov, Maksim Vasilev, Alexander Emelyanov, Siraj Wali, Amr Albanna, Richard van Zyl-Smit, Ismail Abdullah, David Bernhardi, Farzana Hoosen, Elvis Irusen, Ismail Kalla, Deepak Lakha, Essack Mitha, Visvakuren Naidoo, Haylene Nell, Trevenesan Padayachee, Jeevren Reddy, Friedrich Petrick, Eugene van der Walt, Zubar Fazal Ahmed Vawda, Hae-Sim Park, Sang Haak Lee, Mi-Kyeong Kim, Jung-Won Park, You Sook Cho, Byung Jae Lee, Yoon-Seok Chang, Choon-Sik Park, Kwan Ho Lee, Sook Young Lee, HyoungKyu Yoon, Kyoung Hee Sohn, Myung Jae Park, Kyung Hoon Min, Young Joo Cho, Han Ki Park, YongChul Lee, Jaechun Lee, Chau-Chyun Sheu, Chih-Yen Tu, Kang-Yun Lee, Sevim Bavbek, Bilun Gemicioglu, Dane Ediger, Ilkay Koca Kalkan, Nataliia Makieieva, Mykola Ostrovskyy, Yevgeniya Dytyatkovs'ka, Yuriy Mykhaylovych Mostovoy, Kyrylo Lebed, Oleh Yakovenko, Atoya Adams, Timothy Mooring, Louis Torres Jr, Marvin Sexton, Ernest Thompson, Jonathan A Bernstein, Paul Lisi, Christopher M Chappel, Jeremy Cole, Gary I Greenwald, Conigliaro Jones, Ryan Mitchell Klein, David N Pham, Selwyn Spangenthal, Steven F Weinstein, Hugh H Windom, Neil L Kao, Mila A Leong, Vinay Mehta, Wendy C Moore, Saligrama Bhat, Bassil Aish, Steven M Meltzer, Mark H Moss, Edward M Kerwin, John Palsted Delgado, Gregg Hudson Lucksinger, Charles A Thompson, Sady A Alpizar, Sanjay Virgi Vadgama, Zahid Zafar, Joshua S Jacobs, NJira Lugogo, Neal Jain, Lawrence D Sher, Nabil S Andrawis, David Fuentes, Eric Jason Boren, Erika G Gonzalez, Neetu Talreja, Sheharyar Sandy Durrani, Sudhir Sekhsaria, Samuel DeLeon, Mayank Shukla, Martha M Totszollosy Tarpay, Faisal Fakih, Golda Hudes, Jeffrey P Tillinghast, Phillip E Korenblat, Kartik Shenoy, Loretta Que, Shahrukh Ahmad Kureishy, Fred Chukwuemeka Umeh, Vinh Nhu Nguyen, Hanh Thi Chu, and Thuy Thi Dieu Nguyen

Subjects
Pulmonary and Respiratory Medicine
Published
2023
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3. Airway microbiota and immune mediator relationships differ in obesity and asthma

Author

Ariangela J. Kozik, Lesa A. Begley, Njira Lugogo, Alan Baptist, John Erb-Downward, Kristopher Opron, and Yvonne J. Huang

Subjects
Immunology, Immunology and Allergy
Abstract

Asthma and obesity are both complex conditions characterized by chronic inflammation, and obesity-related severe asthma has been associated with differences in the microbiome. However, whether the airway microbiome and microbiota-immune response relationships differ between obese persons with or without non-severe asthma is unestablished.To compare the airway microbiome and microbiota-immune mediator relationships between obese and non-obese subjects, with and without mild-moderate asthma.We performed cross-sectional analyses of the airway (induced sputum) microbiome and cytokine profiles from blood and sputum, employing 16S rRNA gene and ITS region sequencing to profile bacteria and fungi, and multiplex immunoassays. Analysis tools included QIIME2, linear discriminant analysis effect size (LEfSe), Piphillin, and SParse InversE Covariance Estimation for Ecological Association Inference (SPIEC-EASI).Obesity, irrespective of asthma status, was associated with significant differences in sputum bacterial community structure and composition (unweighted Unifrac PERMANOVA, p=0.02), including a higher relative abundance of Prevotella, Gemella, and Streptococcus species. Among asthmatic subjects, additional differences in sputum bacterial composition and fungal richness were identified between obese and non-obese individuals. Correlation network analyses demonstrated differences between obese and non-obese asthma in relationships between cytokine mediators, and these together with specific airway bacteria, involving blood PAI-1, sputum IL1-β, GM-CSF, IL-8, TNF-α, and several Prevotella species.Obesity itself is associated with an altered sputum microbiome, which further differs in those with mild-moderate asthma. The distinct differences in airway microbiota and immune marker relationships in obese asthma suggest potential involvement of airway microbes that may impact mechanisms or outcomes of obese asthma.

Published
2023
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4. SARS-CoV-2 vaccines: a triumph of science and collaboration

Author

Jonathan L. Golob, Njira Lugogo, Adam S. Lauring, and Anna S. Lok

Subjects
Medicine
Abstract

Roughly 1 year after the first case of COVID-19 was identified and less than 1 year after the sequencing of SARS-CoV-2, multiple SARS-CoV-2 vaccines with demonstrated safety and efficacy in phase III clinical trials are available. The most promising vaccines have targeted the surface glycoprotein (S-protein) of SARS-CoV-2 and achieved an approximate 85%–95% reduction in the risk of symptomatic COVID-19, while retaining excellent safety profiles and modest side effects in the phase III clinical trials. The mRNA, replication-incompetent viral vector, and protein subunit vaccine technologies have all been successfully employed. Some novel SARS-CoV-2 variants evade but do not appear to fully overcome the potent immunity induced by these vaccines. Emerging real-world effectiveness data add evidence for protection from severe COVID-19. This is an impressive first demonstration of the effectiveness of the mRNA vaccine and vector vaccine platforms. The success of SARS-CoV-2 vaccine development should be credited to open science, industry partnerships, harmonization of clinical trials, and the altruism of study participants. The manufacturing and distribution of the emergency use–authorized SARS-CoV-2 vaccines are ongoing challenges. What remains now is to ensure broad and equitable global vaccination against COVID-19.

Published
2021
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5. Phenotypic characteristics and asthma severity in an East African cohort of adults and adolescents with asthma: findings from the African severe asthma project

Author

Bruce Kirenga, Corina de Jong, Thys van der Molen, Jeremiah Chakaya, Getnet Yimer, George Nyale, Tewodros Haile, Levicatus Mugenyi, Winceslaus Katagira, William Worodria, Njira Lugogo, Moses Joloba, Amsalu Bekele, Fred Makumbi, Cindy Green, and Moses Kamya

Subjects
Medicine, Diseases of the respiratory system, RC705-779
Abstract

Rationale The relationship between clinical and biomarker characteristics of asthma and its severity in Africa is not well known.Methods Using the Expert Panel Report 3, we assessed for asthma severity and its relationship with key phenotypic characteristics in Uganda, Kenya and Ethiopia. The characteristics included adult onset asthma, family history of asthma, exposures (smoking and biomass), comorbidities (HIV, hypertension, obesity, tuberculosis (TB), rhinosinusitis, gastro-oesophageal disease (GERD) and biomarkers (fractional exhaled nitric oxide (FeNO), skin prick test (SPT) and blood eosinophils). We compared these characteristics on the basis of severity and fitted a multivariable logistic regression model to assess the independent association of these characteristics with asthma severity.Results A total of 1671 patients were enrolled, 70.7% women, with median age of 40 years. The prevalence of intermittent, mild persistent, moderate persistent and severe persistent asthma was 2.9%, 19.9%, 42.6% and 34.6%, respectively. Only 14% were on inhaled corticosteroids (ICS). Patients with severe persistent asthma had a higher rate of adult onset asthma, smoking, HIV, history of TB, FeNO and absolute eosinophil count but lower rates of GERD, rhinosinusitis and SPT positivity. In the multivariate model, Ethiopian site and a history of GERD remained associated with asthma severity.Discussion The majority of patients in this cohort presented with moderate to severe persistent asthma and the use of ICS was very low. Improving access to ICS and other inhaled therapies could greatly reduce asthma morbidity in Africa.

Published
2020
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6. Bacterial biogeography of adult airways in atopic asthma

Author

Juliana Durack, Yvonne J. Huang, Snehal Nariya, Laura S. Christian, K. Mark Ansel, Avraham Beigelman, Mario Castro, Anne-Marie Dyer, Elliot Israel, Monica Kraft, Richard J. Martin, David T. Mauger, Sharon R. Rosenberg, Tonya S. King, Steven R. White, Loren C. Denlinger, Fernando Holguin, Stephen C. Lazarus, Njira Lugogo, Stephen P. Peters, Lewis J. Smith, Michael E. Wechsler, Susan V. Lynch, Homer A. Boushey, and for the National Heart, Lung and Blood Institute’s “AsthmaNet”

Subjects
Adult asthma, Atopy, Upper airways, Lower airways, Bronchial microbiota, Nasal microbiota, Microbial ecology, QR100-130
Abstract

Abstract Background Perturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and mechanisms of these complex associations will require large longitudinal studies, for which bronchoscopy is poorly suited. Studies of samples obtained by sputum induction and nasopharyngeal brushing or lavage have also reported asthma-associated microbiota characteristics. It remains unknown, however, whether the microbiota detected in these less-invasive sample types reflect the composition of bronchial microbiota in asthma. Results Bacterial microbiota in paired protected bronchial brushings (BB; n = 45), induced sputum (IS; n = 45), oral wash (OW; n = 45), and nasal brushings (NB; n = 27) from adults with mild atopic asthma (AA), atopy without asthma (ANA), and healthy controls (HC) were profiled using 16S rRNA gene sequencing. Though microbiota composition varied with sample type (p

Published
2018
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7. Severe asthma exacerbation rates are increased among female, Black, Hispanic, and younger adult patients: results from the US CHRONICLE study

Author

Njira, Lugogo, Elizabeth, Judson, Erin, Haight, Frank, Trudo, Bradley E, Chipps, Jennifer, Trevor, and Christopher S, Ambrose

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Adrenal Cortex Hormones, Pediatrics, Perinatology and Child Health, Quality of Life, Ethnicity, Humans, Immunology and Allergy, Female, Hispanic or Latino, United States, Asthma
Abstract

To describe clinical outcomes in patients with severe asthma (SA) by common sociodemographic determinants of health: sex, race, ethnicity, and age.CHRONICLE is an observational study of subspecialist-treated, United States adults with SA receiving biologic therapy, maintenance systemic corticosteroids, or uncontrolled by high-dosage inhaled corticosteroids with additional controllers. For patients enrolled between February 2018 and February 2020, clinical characteristics and asthma outcomes were assessed by sex, race, ethnicity, age at enrollment, and age at diagnosis. Treating subspecialists reported exacerbations, exacerbation-related emergency department visits, and asthma hospitalizations from 12 months before enrollment through the latest data collection. Patients completed the St. George's Respiratory Questionnaire and the Asthma Control Test at enrollment.Among 1884 enrolled patients, the majority were female (69%), reported White race (75%), non-Hispanic ethnicity (69%), and were diagnosed with asthma as adults (60%). Female, Black, Hispanic, and younger patients experienced higher annualized rates of exacerbations that were statistically significant compared with male, White, non-Hispanic, and older patients, respectively. Black, Hispanic, and younger patients also experienced higher rates of asthma hospitalizations. Female and Black patients exhibited poorer symptom control and poorer health-related quality of life.In this contemporary, real-world cohort of subspecialist-treated adults with SA, female sex, Black race, Hispanic ethnicity, and younger age were important determinants of health, potentially attributable to physiologic and social factors. Knowledge of these disparities in SA disease burden among subspecialist-treated patients may help optimize care for all patients.Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Published
2022
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8. Long-Term Use of Maintenance Systemic Corticosteroids is Associated with Multiple Adverse Conditions in a Large, Real-World Cohort of US Adults with Severe Asthma

Author

Njira Lugogo, Bradley E Chipps, Reynold A Panettieri Jr, Frank Trudo, and Christopher S Ambrose

Subjects
Pulmonary and Respiratory Medicine, Journal of Asthma and Allergy, Immunology and Allergy
Abstract

Njira Lugogo,1 Bradley E Chipps,2 Reynold A Panettieri Jr,3 Frank Trudo,4 Christopher S Ambrose5 1University of Michigan, Ann Arbor, MI, USA; 2Capital Allergy & Respiratory Disease Center, Sacramento, CA, USA; 3Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; 4AstraZeneca, Wilmington, DE, USA; 5AstraZeneca, Gaithersburg, MD, USACorrespondence: Christopher S Ambrose, BioPharmaceuticals Medical, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USA, Tel +1 301-398-4454, Email chris.ambrose@astrazeneca.comAbstract: There is growing recognition of the adverse consequences of maintenance systemic corticosteroid (mSCS) therapy in severe asthma (SA). The objective of this study was to describe the prevalence of potential adverse effects of long-term mSCS therapy in adults with specialist-confirmed SA in the United States (US). CHRONICLE is an ongoing, noninterventional, observational study of US adults with SA treated by allergists/immunologists and pulmonologists. Once enrolled, patients’ duration of mSCS therapy was reported by sites based on medical record review. For patients enrolled between February 2018 and February 2021, the prevalence of SCS-associated conditions was evaluated among those with no reported history of mSCS use, or mSCS use with < 2 years or ≥ 2 years cumulative duration. Prevalence and incidence estimates were adjusted for age and smoking history. Of 2793 patients enrolled, 311 and 231 had mSCS use for < 2 and ≥ 2 years, respectively. In adjusted analyses, adrenal insufficiency, pneumonia, type 2 diabetes, osteoporosis/osteopenia, congestive heart failure, coronary artery disease, hypertension, anxiety, and depression were statistically significantly associated with any mSCS use. By duration, mSCS use ≥ 2 years was associated with osteopenia/osteoporosis, coronary artery disease, adrenal insufficiency, and diabetes-related neuropathy; mSCS use < 2 years was associated with depression and osteopenia/osteoporosis, and diagnoses of depression, anxiety, and hypertension during the 12 months prior to enrollment. Overall, among patients with specialist-confirmed SA, mSCS use was associated with a high prevalence of multiple adverse conditions. Healthcare professionals should employ mSCS-sparing treatment strategies to avoid these negative consequences.Keywords: duration, steroids, diabetes, pneumonia, osteoporosis

Published
2022

9. A Paradigm Shift for Asthma Care

Author

Njira, Lugogo, Neil, Skolnik, and Yihui, Jiang

Subjects
Adrenal Cortex Hormones, Administration, Inhalation, Humans, Drug Therapy, Combination, Anti-Asthmatic Agents, Asthma, Bronchodilator Agents
Abstract

Asthma remains a substantial health burden, despite continued treatment advances. Patients with mild or moderate asthma, even those with intermittent symptoms, are at risk for severe or fatal exacerbations. Use of short-acting beta2-agonist (SABA)-only rescue therapy is associated with an increased risk of exacerbations, beginning at about the second fill annually. Systemic corticosteroids have shortterm and long-term adverse effects, and long-term adverse effects are driven by cumulative lifetime doses starting at 0.5 to 1.0 g. Expert opinion on the use of SABA only for rescue therapy differs, but recent evidence suggests that a fast-acting bronchodilator combined with inhaled corticosteroids (ICS) is more effective at reducing the risk of exacerbations than SABA alone. There is a window of opportunity just prior to an asthma exacerbation during which use of fast-acting bronchodilator + ICS may play a significant role in mitigating the risk of exacerbation. Patients may respond better to a combination inhaler of a fast-acting bronchodilator and an ICS as needed for rescue therapy or as part of a maintenance and rescue therapy paradigm, rather than attempting to use separate inhalers. However, there is currently no fixed-dose, fast-acting bronchodilator + ICS approved in the United States for as-needed use.

Published
2022

12. Biologic use and outcomes among adults with severe asthma treated by US subspecialists

Author

Reynold A. Panettieri, Dennis K. Ledford, Bradley E. Chipps, Weily Soong, Njira Lugogo, Warner Carr, Arjun Mohan, Donna Carstens, Eduardo Genofre, Frank Trudo, and Christopher S. Ambrose

Subjects
Pulmonary and Respiratory Medicine, Adult, Biological Products, Adrenal Cortex Hormones, Immunology, Immunology and Allergy, Humans, Anti-Asthmatic Agents, Omalizumab, Asthma
Abstract

Multiple biologics are now available for severe asthma (SA) treatment and can improve outcomes for patients. However, few available data describe the real-world use and effectiveness of multiple approved biologics, including biologic switching, among subspecialists in the United States.To evaluate biologic use and associated exacerbation outcomes in a large cohort of subspecialist-treated US adults with SA.CHRONICLE is an ongoing, noninterventional study of subspecialist-treated US adults with SA receiving biologics, maintenance systemic corticosteroids, or those persistently uncontrolled by high-dose inhaled corticosteroids with additional controllers. For enrolled patients, sites report asthma exacerbations and medication use starting 12 months before enrollment. For patients enrolled between February 2018 and February 2021, biologic use and exacerbation outcomes before and after biologic initiation are described.Among 2793 enrolled patients, 66% (n = 1832) were receiving biologics. The most used biologic (gt; 1 biologic use per patient allowed) was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), dupilumab (18%), and reslizumab (3%). Overall, 16% of patients had biologic switches, 13% had stops, and 89% had ongoing biologic use. Patients starting and switching biologics experienced a 58% (1.80 vs 0.76 per patient-year) and 49% (1.47 vs 0.75 per patient-year) reduction in exacerbations, respectively (both Plt; .001), with a numerically greater reduction observed among those starting non-anti-immunoglobulin E biologics compared with anti-immunoglobulin E.Real-world starting and switching of biologic therapies for SA were associated with meaningful reductions in exacerbations. With increasing biologic options available, individualized approaches to therapy may improve patient outcomes.ClinicalTrials.gov identifier: NCT03373045.

Published
2022

14. Asthma and coronavirus disease 2019-related outcomes in hospitalized patients: A single-center experience

Author

Amy, Ludwig, Caryn Elizabeth, Brehm, Christopher, Fung, Shijing, Jia, Jonathan P, Troost, Laura, Leuenberger, Rayan, Kaakati, Catherine, Tarantine, Ella, Christoph, Michael W, Sjoding, and Njira, Lugogo

Subjects
Hospitalization, Intensive Care Units, SARS-CoV-2, COVID-19, Humans, Pandemics, Asthma, Retrospective Studies
Abstract

Several chronic conditions have been associated with a higher risk of severe coronavirus disease 2019 (COVID-19), including asthma. However, there are conflicting conclusions regarding risk of severe disease in this population.To understand the impact of asthma on COVID-19 outcomes in a cohort of hospitalized patients and whether there is any association between asthma severity and worse outcomes.We identified hospitalized patients with COVID-19 with confirmatory polymerase chain reaction testing with (n = 183) and without asthma (n = 1319) using International Classification of Diseases, Tenth Revision, codes between March 1 and December 30, 2020. We determined asthma maintenance medications, pulmonary function tests, highest historical absolute eosinophil count, and immunoglobulin E. Primary outcomes included death, mechanical ventilation, intensive care unit (ICU) admission, and ICU and hospital length of stay. Analysis was adjusted for demographics, comorbidities, smoking status, and timing of illness in the pandemic.In unadjusted analyses, we found no difference in our primary outcomes between patients with asthma and patients without asthma. However, in adjusted analyses, patients with asthma were more likely to have mechanical ventilation (odds ratio, 1.58; 95% confidence interval [CI], 1.02-2.44; P = .04), ICU admission (odds ratio, 1.58; 95% CI, 1.09-2.29; P = .02), longer hospital length of stay (risk ratio, 1.30; 95% CI, 1.09-1.55; P.003), and higher mortality (hazard ratio, 1.53; 95% CI, 1.01-2.33; P = .04) compared with the non-asthma cohort. Inhaled corticosteroid use and eosinophilic phenotype were not associated with considerabledifferences. Interestingly, patients with moderate asthma had worse outcomes whereas patients with severe asthma did not.Asthma was associated with severe COVID-19 after controlling for other factors.

Published
2022

15. Respiratory Symptoms Among US Adults

Author

Roy Alton Pleasants, Khosrow Heidari, James F. Donohue, Jill Ohar, Njira Lugogo, Sarojini Kanotra, Monica Kraft, David Mannino, and Charlie Strange

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2022
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18. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study

Author

Michael E Wechsler, Andrew Menzies-Gow, Christopher E Brightling, Piotr Kuna, Stephanie Korn, Tobias Welte, Janet M Griffiths, Kinga Sałapa, Åsa Hellqvist, Gun Almqvist, Harbans Lal, Primal Kaur, Tor Skärby, Gene Colice, Victor H Cambursano, Marcelo J Fernandez, Fernando D Scherbovsky, Anahi Yanez, Alberto J Tolcachier, Ana M Stok, Fernando J B Verra, Karin Forster, Mathias Rolke, Andrea Ludwig-Sengpiel, Tibor Schmoller, Olaf Schmidt, Katrin Milger-Kneidinger, Martin Hoffmann, Hilke Temme, Anneliese Linnhoff, Joachim Kirschner, Barbara Rewerska, Ewa Pisarczyk-Bogacka, Sang Haak Lee, Byung Jae Lee, Heung-Woo Park, Jung-Won Park, Sook Young Lee, You Sook Cho, Kwan Ho Lee, Sevim Bavbek, Bilun Gemicioglu, Dane Ediger, Ilkay Koca Kalkan, Ismail Hanta, Arzu Yorgancioglu, Yevgeniya DytyatkovsKa, Yuriy M Mostovoy, Kyrylo Lebed, Oleh Yakovenko, David I Bernstein, Jeffrey P Tillinghast, Loretta Que, Jan Madison, Todd Rambasek, Kartik Shenoy, Charles A Thompson, Christopher M Chappel, Golda Hudes, Ehab Sorial, Shahrukh A Kureishy, Syed M Rehman, Njira Lugogo, Erika G Gonzalez, Fred C Umeh, Eric J Boren, Jason Sigmon, Hummayun Ismail, Arjun Mohan, Sandeep Bansal, and Thomas D Kaelin

Subjects
Pulmonary and Respiratory Medicine, Adult, Eosinophils, Treatment Outcome, Double-Blind Method, Adrenal Cortex Hormones, Humans, Antibodies, Monoclonal, Humanized, Asthma
Abstract

Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. SOURCE evaluated the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma.We conducted this phase 3, multicentre, randomised, double-blind, placebo-controlled study across 60 sites in seven countries. Participants aged 18-80 years with physician-diagnosed asthma, who had been receiving medium-dose or high-dose inhaled corticosteroids and had at least one asthma exacerbation in the 12 months before screening were eligible. Patients who were receiving medium-dose inhaled corticosteroids must have had their dose increased to a high dose for at least 3 months before screening. After an oral corticosteroid optimisation phase of up to 8 weeks, participants were randomly assigned according to a computer-generated fixed block randomisation sequence to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks during a 48 week treatment period (4 week induction phase, 36 week oral corticosteroid reduction phase, and 8 week maintenance phase). Randomisation was stratified by region. Participants, investigators, and site staff were masked to treatment assignment. The primary endpoint was the categorised percentage reduction from baseline in daily oral corticosteroid dose at week 48 without the loss of asthma control. Efficacy and safety endpoints were assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03406078.Between March 5, 2018, and Sept 27, 2019, 150 participants were randomly assigned to receive tezepelumab 210 mg (n=74) or placebo (n=76). The cumulative odds of achieving a category of greater percentage reduction in an oral corticosteroid dose for daily maintenance at week 48 were similar with tezepelumab or placebo in the overall population (odds ratio [OR] 1·28 [95% CI 0·69-2·35], p=0·43; the primary endpoint was not met). The cumulative odds were higher with tezepelumab than with placebo in participants with baseline blood eosinophil counts of at least 150 cells per μL (2·58 [1·16-5·75]), but not in participants with counts below 150 cells per μL (0·40 [0·14-1·13]). Tezepelumab was well tolerated, with no safety concerns identified. 53 (72%) of 74 tezepelumab-assigned participants and 65 (86%) of 76 placebo-assigned participants reported an adverse event. Serious adverse events were reported in 12 (16%) participants in the tezepelumab group and 16 (21%) participants in the placebo group.We did not observe a significant improvement in oral corticosteroid dose reduction with tezepelumab versus placebo in the overall population of this oral corticosteroid-sparing study, although an improvement was observed in participants with baseline blood eosinophil counts of at least 150 cells per μL.AstraZeneca and Amgen.

Published
2021

19. Asthma exacerbations are associated with a decline in lung function: a longitudinal population-based study

Author

Seyi Soremekun, Liam G Heaney, Derek Skinner, Lakmini Bulathsinhala, Victoria Carter, Isha Chaudhry, Naeimeh Hosseini, Neva Eleangovan, Ruth Murray, Trung N Tran, Benjamin Emmanuel, Esther Garcia Gil, Andrew Menzies-Gow, Matthew Peters, Njira Lugogo, Rupert Jones, and David B Price

Subjects
Pulmonary and Respiratory Medicine, asthma
Abstract

RationaleProgressive lung function (LF) decline in patients with asthma contributes to worse outcomes. Asthma exacerbations are thought to contribute to this decline; however, evidence is limited with mixed results.MethodsThis historical cohort study of a broad asthma patient population in the Optimum Patient Care Research Database, examined asthma patients with 3+eligible post-18th birthday peak expiratory flow rate (PEF) records (primary analysis) or records of forced expiratory flow in 1 s (FEV1) (sensitivity analysis). Adjusted linear growth models tested the association between mean annual exacerbation rate (AER) and LF trajectory.ResultsWe studied 1 09 182 patients with follow-up ranging from 5 to 50 years, of which 75 280 had data for all variables included in the adjusted analyses. For each additional exacerbation, an estimated additional −1.34 L/min PEF per year (95% CI −1.23 to –1.50) were lost. Patients with AERs >2/year and aged 18–24 years at baseline lost an additional −5.95 L/min PEF/year (95% CI −8.63 to –3.28) compared with those with AER 0. These differences in the rate of LF decline between AER groups became progressively smaller as age at baseline increased. The results using FEV1 were consistent with the above.ConclusionTo our knowledge, this study is the largest nationwide cohort of its kind and demonstrates that asthma exacerbations are associated with faster LF decline. This was more prominent in younger patients but was evident in older patients when it was related to lower starting LF, suggesting a persistent deteriorating phenotype that develops in adulthood over time. Earlier intervention with appropriate management in younger patients with asthma could be of value to prevent excessive LF decline.

Published
2022
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21. SARS-CoV-2 vaccines: a triumph of science and collaboration

Author

Njira Lugogo, Anna S. Lok, Jonathan L. Golob, and Adam S. Lauring

Subjects
0301 basic medicine, Open science, medicine.medical_specialty, COVID-19 Vaccines, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Review, Global Health, Public-Private Sector Partnerships, Viral vector, 03 medical and health sciences, 0302 clinical medicine, Immunity, medicine, Global health, Humans, Intensive care medicine, Pandemics, business.industry, SARS-CoV-2, Vaccination, COVID-19, General Medicine, Vector vaccine, Clinical trial, 030104 developmental biology, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Medicine, Safety, business
Abstract

Roughly 1 year after the first case of COVID-19 was identified and less than 1 year after the sequencing of SARS-CoV-2, multiple SARS-CoV-2 vaccines with demonstrated safety and efficacy in phase III clinical trials are available. The most promising vaccines have targeted the surface glycoprotein (S-protein) of SARS-CoV-2 and achieved an approximate 85%–95% reduction in the risk of symptomatic COVID-19, while retaining excellent safety profiles and modest side effects in the phase III clinical trials. The mRNA, replication-incompetent viral vector, and protein subunit vaccine technologies have all been successfully employed. Some novel SARS-CoV-2 variants evade but do not appear to fully overcome the potent immunity induced by these vaccines. Emerging real-world effectiveness data add evidence for protection from severe COVID-19. This is an impressive first demonstration of the effectiveness of the mRNA vaccine and vector vaccine platforms. The success of SARS-CoV-2 vaccine development should be credited to open science, industry partnerships, harmonization of clinical trials, and the altruism of study participants. The manufacturing and distribution of the emergency use–authorized SARS-CoV-2 vaccines are ongoing challenges. What remains now is to ensure broad and equitable global vaccination against COVID-19.

Published
2021

23. Severe asthma exacerbations in the United States:: Incidence, characteristics, predictors, and effects of biologic treatments

Author

Jennifer, Trevor, Njira, Lugogo, Warner, Carr, Wendy C, Moore, Weily, Soong, Reynold A, Panettieri, Pooja, Desai, Frank, Trudo, and Christopher S, Ambrose

Subjects
Adult, Aged, 80 and over, Male, Biological Products, Adolescent, Immunoglobulin E, Middle Aged, Nitric Oxide, Symptom Flare Up, Severity of Illness Index, Asthma, United States, Eosinophils, Hospitalization, Young Adult, Adrenal Cortex Hormones, Eosinophilia, Humans, Female, Anti-Asthmatic Agents, Aged
Abstract

Patients with severe asthma (SA) have a heightened risk of exacerbations including hospitalization. The real-world, specialist-verified incidence and characteristics of exacerbations among patients with SA in the United States have not been described.To describe the real-world incidence, characteristics, and predictors of exacerbations among patients with SA in the United States.The CHRONICLE study is an ongoing observational study of specialist-treated adults with SA in the United States receiving biologic treatment or maintenance systemic corticosteroids or uncontrolled by high-dosage inhaled corticosteroids with additional controllers. For patients enrolled from February 2018 to February 2020, annualized rates and characteristics of exacerbation-related events were summarized by treatment category for 12 months before enrollment and after enrollment through the latest data collection. Results were further analyzed for subgroups of interest.Among 1884 enrolled patients, 53.5% and 12.3% experienced an exacerbation and asthma hospitalization, respectively (0.81 and 0.14 per person-year). Of all exacerbations, 36%, 9%, and 15% required an unscheduled health care provider visit, emergency department visit without hospitalization, and hospitalization, respectively. Among patients not receiving biologics or systemic corticosteroids, higher blood eosinophil count, higher fractional exhaled nitric oxide, and lower total immunoglobulin E level were associated with higher exacerbation rates. Exacerbation rates decreased after starting or switching biologics (n = 1299). Multivariate analyses of enrolled patients revealed previous-year exacerbations or hospitalizations, lack of asthma control, and the geographic region also predicted event risk.In this real-world cohort of specialist-treated adults with SA in the United States, there was a substantial burden of exacerbations and associated health care resource utilization. Patients receiving biologics had a lower exacerbation burden.ClinicalTrials.gov Identifier: NCT03373045.

Published
2021

24. Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial

Author

Harrison, Tim W, Chanez, Pascal, Menzella, Francesco, Canonica, Giorgio Walter, Louis, Renaud, Cosio, Borja G, Lugogo, Njira L, Mohan, Arjun, Burden, Annie, McDermott, Lawrence, Garcia Gil, Esther, Zangrilli, James G, Wolfgang Pohl, Robert Voves, Maud Deschampheleire, Renaud Louis, Jean-Benoit Martinot, Rudi Peché, Kenneth Chapman, Amarjit Cheema, Delbert Dorscheid, J Mark FitzGerald, Remi Gagnon, William Patrick Killorn, Ronald Olivenstein, George Philteos, Clare Ramsey, J Douglass Rolf, Brandie Walker, Ole Hilberg, Tina Skjold, Ingrid Titlestad, Auli Hakulinen, Maritta Kilpeläinen, Michèle Ben Hayoun, Philippe Bonniaud, Arnaud Bourdin, Pascal Chanez, Frédéric De Blay, Gaëtan Deslee, Gilles Devouassoux, Alain Didier, Youcef Douadi, Stéphanie Fry, Gilles Garcia, Pierre-Olivier Girodet, Christophe Leroyer, Antoine Magnan, Guillaume Mahay, Cécilia Nocent, Christophe Pison, Pauline-Marie Roux, Camille Taillé, Juliana-Angelica Tiotiu, Ekkehard Beck, Margret Jandl, Christian Kaehler, Frank Kässner, Frank Koesters, Juliane Kronsbein, Thomas Schaum, Christian Schulz, Dirk Skowasch, Christian Taube, Tobias Welte, Andrés de Roux, Bianca Beghé, Francesco Blasi, Giorgio Walter Canonica, Giovanna Carpagnano, Cristiano Caruso, Angelo Guido Corsico, Elio Constantino, Nunzio Crimi, Piero Maestrelli, Francesco Menzella, Manlio Milanese, Alberto Papi, Girolamo Pelaia, Laura Pini, Pierachille Santus, Eleonora Savi, Nicola Scichilone, Gianenrico Senna, Giuseppe Spadaro, Adriano Vaghi, Steven Gans, Jurgen Hölters, B Langeveld, Willem Pieters, G H A Staaks, Ilonka van Veen, J W K van den Berg, Gunnar Einvik, Sverre Lehmann, Ismael Ali García, Carlos Almonacid, Irina Bobolea, Paloma Campo Mozo, Gustavo de Luiz, Christian Domingo Ribas, José María Echave-Sustaeta María-Tomé, Juan Luis García Rivero, Borja García-Cosío Piqueras, Ana Gómez-Bastero Fernández, Ruperto González Pérez, Aythamy Henríquez Santa, Carlos Martínez Rivera, Xavier Muñoz Gall, Jacinto Ramos, Jose Gregorio Soto Campos, Carmen Vidal Pan, Nikolai Stenfors, Alf Tunsäter, Ines Vinge, Rekha Chaudhuri, Timothy Harrison, Adel Mansur, Shuaib Nasser, Monica Nordstrom, Paul Pfeffer, Dinesh Saralaya, Philip Short, Arun Adlakha, Oral Alpan, Francis Averill, Anil Badhwar, Jose Bardelas, Barbara Baxter, George Bensch, William Berger, Jonathan Bernstein, Tracy Bridges, Ryan Brimeyer, William Calhoun, Edward Campbell, William Brett Cherry, Geoffrey Chupp, Lee Clore, John Cohn, Jeremy Cole, John Condemi, James Cury, Benjamin Davis, Samuel DeLeon, Luis Delacruz, Joseph Diaz, David Erb, Emeka Eziri, Faisal Fakih, Douglas Fiedler, David Fost, Stephen Fritz, Erika Gonzalez, Brad Goodman, Peter Gottlieb, Gregory Gottschlich, Richard Gower, Rizan Hajal, James Harris, Hengameh Heidarian-Raissy, Albrecht Heyder, David Hill, Fernando Holguin, Iftikhar Hussain, Jonathan Illowite, Joshua Jacobs, Mikell Jarratt, Harold Kaiser, Neil Kao, Ravindra Kashyap, David Kaufman, Edward Kent, Kenneth Kim, Ryan Klein, Monica Kraft, Ritsu Kono, Shahrukh Kureishy, Jeffrey Leflein, Mila Leong, Huamin Li, Robert Lin, Njira Lugogo, Michael Marcus, Diego Jose Maselli Caceres, Vinay Mehta, Curtis Mello, Mark Millard, Aaron Milstone, Arjun Mohan, Wendy Moore, Mark Moss, Nayla Mumneh, Thomas O'Brien, David Ostransky, Michael Palumbo, Purvi Parikh, Sudhir Parikh, Amit Patel, Guido Perez, Warren Pleskow, Bruce Prenner, Dileep Puppala, John Ramey, Joan Reibman, Ramon Reyes, Emory Robinette, Ileana Rodicio, Stephen Ryan, Sudhir Sekhsaria, Barry Sigal, Vinay Sikand, Weily Soong, Selwyn Spangenthal, Roy St John, Gary Steven, Vijay Subramaniam, Kaharu Sumino, Eric Sztejman, Ricardo A Tan, Tonny Tanus, Charles Thompson, Carl Thornblade, Manuel Villareal, Sally Wenzel, Heidi Zafra, Tomasz Ziedalski, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Tim W, Harrison, Pascal, Chanez, Francesco, Menzella, Giorgio Walter, Canonica, Renaud, Loui, Borja G, Cosio, Njira L, Lugogo, Arjun, Mohan, Annie, Burden, Lawrence, Mcdermott, Esther, Garcia Gil, Zangrilli, G, Jame, Pohl, Wolfgang, Voves, Robert, Deschampheleire, Maud, Louis, Renaud, Martinot, Jean-Benoit, Peché, Rudi, Chapman, Kenneth, Cheema, Amarjit, Dorscheid, Delbert, Mark FitzGerald, J, Gagnon, Remi, Patrick Killorn, William, Olivenstein, Ronald, Philteos, George, Ramsey, Clare, Douglass Rolf, J, Walker, Brandie, Hilberg, Ole, Skjold, Tina, Titlestad, Ingrid, Hakulinen, Auli, Kilpeläinen, Maritta, Ben Hayoun, Michèle, Bonniaud, Philippe, Bourdin, Arnaud, Chanez, Pascal, De Blay, Frédéric, Deslee, Gaëtan, Devouassoux, Gille, Didier, Alain, Douadi, Youcef, Fry, Stéphanie, Garcia, Gille, Girodet, Pierre-Olivier, Leroyer, Christophe, Magnan, Antoine, Mahay, Guillaume, Nocent, Cécilia, Pison, Christophe, Roux, Pauline-Marie, Taillé, Camille, Tiotiu, Juliana-Angelica, Beck, Ekkehard, Jandl, Margret, Kaehler, Christian, Kässner, Frank, Koesters, Frank, Kronsbein, Juliane, Schaum, Thoma, Schulz, Christian, Skowasch, Dirk, Taube, Christian, Welte, Tobia, de Roux, André, Beghé, Bianca, Blasi, Francesco, Walter Canonica, Giorgio, Carpagnano, Giovanna, Caruso, Cristiano, Guido Corsico, Angelo, Constantino, Elio, Crimi, Nunzio, Maestrelli, Piero, Menzella, Francesco, Milanese, Manlio, Papi, Alberto, Pelaia, Girolamo, Pini, Laura, Santus, Pierachille, Savi, Eleonora, Scichilone, Nicola, Senna, Gianenrico, Spadaro, Giuseppe, Vaghi, Adriano, Gans, Steven, Hölters, Jurgen, Langeveld, B, Pieters, Willem, A Staaks, G H, van Veen, Ilonka, K van den Berg, J W, Einvik, Gunnar, Lehmann, Sverre, Ali García, Ismael, Almonacid, Carlo, Bobolea, Irina, Campo Mozo, Paloma, de Luiz, Gustavo, Domingo Ribas, Christian, María Echave-Sustaeta María-Tomé, José, Luis García Rivero, Juan, García-Cosío Piqueras, Borja, Gómez-Bastero Fernández, Ana, González Pérez, Ruperto, Henríquez Santa, Aythamy, Martínez Rivera, Carlo, Muñoz Gall, Xavier, Ramos, Jacinto, Gregorio Soto Campos, Jose, Vidal Pan, Carmen, Stenfors, Nikolai, Tunsäter, Alf, Vinge, Ine, Chaudhuri, Rekha, Harrison, Timothy, Mansur, Adel, Nasser, Shuaib, Nordstrom, Monica, Pfeffer, Paul, Saralaya, Dinesh, Short, Philip, Adlakha, Arun, Alpan, Oral, Averill, Franci, Badhwar, Anil, Bardelas, Jose, Baxter, Barbara, Bensch, George, Berger, William, Bernstein, Jonathan, Bridges, Tracy, Brimeyer, Ryan, Calhoun, William, Campbell, Edward, Brett Cherry, William, Chupp, Geoffrey, Clore, Lee, Cohn, John, Cole, Jeremy, Condemi, John, Cury, Jame, Davis, Benjamin, Deleon, Samuel, Delacruz, Lui, Diaz, Joseph, Erb, David, Eziri, Emeka, Fakih, Faisal, Fiedler, Dougla, Fost, David, Fritz, Stephen, Gonzalez, Erika, Goodman, Brad, Gottlieb, Peter, Gottschlich, Gregory, Gower, Richard, Hajal, Rizan, Harris, Jame, Heidarian-Raissy, Hengameh, Heyder, Albrecht, Hill, DAVID STANLEY, Holguin, Fernando, Hussain, Iftikhar, Illowite, Jonathan, Jacobs, Joshua, Jarratt, Mikell, Kaiser, Harold, Kao, Neil, Kashyap, Ravindra, Kaufman, David, Kent, Edward, Kim, Kenneth, Klein, Ryan, Kraft, Monica, Kono, Ritsu, Kureishy, Shahrukh, Leflein, Jeffrey, Leong, Mila, Li, Huamin, Lin, Robert, Lugogo, Njira, Marcus, Michael, Jose Maselli Caceres, Diego, Mehta, Vinay, Mello, Curti, Millard, Mark, Milstone, Aaron, Mohan, Arjun, Moore, Wendy, Moss, Mark, Mumneh, Nayla, O'Brien, Thoma, Ostransky, David, Palumbo, Michael, Parikh, Purvi, Parikh, Sudhir, Patel, Amit, Perez, Guido, Pleskow, Warren, Prenner, Bruce, Puppala, Dileep, Ramey, John, Reibman, Joan, Reyes, Ramon, Robinette, Emory, Rodicio, Ileana, Ryan, Stephen, Sekhsaria, Sudhir, Sigal, Barry, Sikand, Vinay, Soong, Weily, Spangenthal, Selwyn, St John, Roy, Gary, Steven, Subramaniam, Vijay, Sumino, Kaharu, Sztejman, Eric, A Tan, Ricardo, Tanus, Tonny, Thompson, Charle, Thornblade, Carl, Villareal, Manuel, Wenzel, Sally, Zafra, Heidi, Ziedalski, Tomasz, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pneumologie, Harrison T.W., Chanez P., Menzella F., Canonica G.W., Louis R., Cosio B.G., Lugogo N.L., Mohan A., Burden A., McDermott L., Garcia Gil E., Zangrilli J.G., Pohl W., Voves R., Deschampheleire M., Martinot J.-B., Peche R., Chapman K., Cheema A., Dorscheid D., FitzGerald J.M., Gagnon R., Killorn W.P., Olivenstein R., Philteos G., Ramsey C., Rolf J.D., Walker B., Hilberg O., Skjold T., Titlestad I., Hakulinen A., Kilpelainen M., Ben Hayoun M., Bonniaud P., Bourdin A., De Blay F., Deslee G., Devouassoux G., Didier A., Douadi Y., Fry S., Garcia G., Girodet P.-O., Leroyer C., Magnan A., Mahay G., Nocent C., Pison C., Roux P.-M., Taille C., Tiotiu J.-A., Beck E., Jandl M., Kaehler C., Kassner F., Koesters F., Kronsbein J., Schaum T., Schulz C., Skowasch D., Taube C., Welte T., de Roux A., Beghe B., Blasi F., Carpagnano G., Caruso C., Corsico A.G., Constantino E., Crimi N., Maestrelli P., Milanese M., Papi A., Pelaia G., Pini L., Santus P., Savi E., Scichilone N., Senna G., Spadaro G., Vaghi A., Gans S., Holters J., Langeveld B., Pieters W., Staaks G.H.A., van Veen I., van den Berg J.W.K., Einvik G., Lehmann S., Ali Garcia I., Almonacid C., Bobolea I., Campo Mozo P., de Luiz G., Domingo Ribas C., Echave-Sustaeta Maria-Tome J.M., Garcia Rivero J.L., Garcia-Cosio Piqueras B., Gomez-Bastero Fernandez A., Gonzalez Perez R., Henriquez Santa A., Martinez Rivera C., Munoz Gall X., Ramos J., Gregorio Soto Campos J., Vidal Pan C., Stenfors N., Tunsater A., Vinge I., Chaudhuri R., Harrison T., Mansur A., Nasser S., Nordstrom M., Pfeffer P., Saralaya D., Short P., Adlakha A., Alpan O., Averill F., Badhwar A., Bardelas J., Baxter B., Bensch G., Berger W., Bernstein J., Bridges T., Brimeyer R., Calhoun W., Campbell E., Cherry W.B., Chupp G., Clore L., Cohn J., Cole J., Condemi J., Cury J., Davis B., DeLeon S., Delacruz L., Diaz J., Erb D., Eziri E., Fakih F., Fiedler D., Fost D., Fritz S., Gonzalez E., Goodman B., Gottlieb P., Gottschlich G., Gower R., Hajal R., Harris J., Heidarian-Raissy H., Heyder A., Hill D., Holguin F., Hussain I., Illowite J., Jacobs J., Jarratt M., Kaiser H., Kao N., Kashyap R., Kaufman D., Kent E., Kim K., Klein R., Kraft M., Kono R., Kureishy S., Leflein J., Leong M., Li H., Lin R., Lugogo N., Marcus M., Maselli Caceres D.J., Mehta V., Mello C., Millard M., Milstone A., Moore W., Moss M., Mumneh N., O'Brien T., Ostransky D., Palumbo M., Parikh P., Parikh S., Patel A., Perez G., Pleskow W., Prenner B., Puppala D., Ramey J., Reibman J., Reyes R., Robinette E., Rodicio I., Ryan S., Sekhsaria S., Sigal B., Sikand V., Soong W., Spangenthal S., St. John R., Steven G., Subramaniam V., Sumino K., Sztejman E., Tan R.A., Tanus T., Thompson C., Thornblade C., Villareal M., Wenzel S., Zafra H., Ziedalski T., and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pulmonary and Respiratory Medicine, Spirometry, Adult, Male, medicine.medical_specialty, Exacerbation, [SDV]Life Sciences [q-bio], Population, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Placebo, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Internal medicine, medicine, Humans, 030212 general & internal medicine, Anti-Asthmatic Agents, Patient Reported Outcome Measures, education, Sinusitis, Asthma, education.field_of_study, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, Benralizumab, 3. Good health, Eosinophils, 030228 respiratory system, chemistry, Asthma Control Questionnaire, Disease Progression, Quality of Life, Female, business
Abstract

Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.

Published
2021
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25. Benralizumab for the Prevention of COPD Exacerbations

Author

Criner, G. J., Celli, B. R., Brightling, C. E., Agusti, A., Papi, A., Singh, D., Sin, D. D., Vogelmeier, C. F., Sciurba, F. C., Bafadhel, M., Backer, V., Kato, M., Ramirez-Venegas, A., Wei, Y. -F., Bjermer, L., Shih, V. H., Jison, M., O'Quinn, S., Makulova, N., Newbold, P., Goldman, M., Martin, U. J., GALATHEA Study Investigators, TERRANOVA Study Investigators, Otto, Burghuber, Bernhard, Forstner, Gerhard, Köberl, Bernd, Lamprecht, Judith, Löffler-Ragg, Horst, Olschewski, Michael, Studnicka, Francois, Beaucage, Guy, Chouinard, Anthony, Dechant, Anthony, Dowell, Jacques, Hebert, Sohail, Khattak, Kieran, Killian, William, Killorn, Andy, Lam, Francois, Maltais, Darcy, Marciniuk, Lyle, Melenka, Bonavuth, Pek, Jeremy, Road, Donald, Sin, Alain, Vaugeois, Brandie, Walker, Tomas, Dvorak, Stanislav, Holub, Otakar, Hokynar, Vitezslav, Kolek, Daniela, Kopecka, Jan, Krepelka, Jaroslav, Mares, Josef, Veverka, Vladimir, Zindr, Sabine, Ballenberger, Rolf, Dichmann, Christian, Geßner, Margret, Jandl, Claus, Keller, Joachim, Kirschner, Marc, Kornmann, Petra, Mikloweit, Ingomar, Naudts, Axel, Overlack, Isabelle, Schenkenberger, Volker, Schlegel, Lutz Von Versen, Claus Franz Vogelmeier, Stefan, Zielen, István, Albert, Beatrix, Bálint, Mária Csilla Hangonyi, Teréz, Kecskés, Anikó, Kurucz, Balázs, Medgyasszay, Lajos, Molnár, János, Mucsi, Márta, Papp, Magdolna, Póczi, Éva, Radeczky, Zsolt Pápai Székely, Csilla, Szabó, Gyöngyi, Szabó, Melinda, Szabó, Alfredo Antonio Chetta, Giuseppe Di Maria, Giulio, Donazzan, Federica, Meloni, Elisabetta, Pace, Pierluigi, Paggiaro, Alberto, Papi, Ricciardolo, Fabio Luigi Massimo, Antonio, Spanevello, Fumiaki, Aoki, Ryosuke, Eda, Takeo, Endo, Yasushi, Fukushima, Kenichi, Gemba, Naoki, Hagimoto, Hiromasa, Harada, Yasuko, Harada, Norihiko, Hata, Osamu, Hataji, Nobuo, Hatakeyama, Takahiko, Horiguchi, Gen, Ideura, Motoyasu, Iikura, Azusa, Ikegami, Shirou, Imokawa, Yoshikazu, Inoue, Takeshi, Isobe, Ryoji, Ito, Susumu, Iwata, Tadashi, Kamei, Motokazu, Kato, Hideki, Katsura, Yuji, Kawarada, Norio, Kihara, Masaharu, Kinoshita, Takashi, Kinoshita, Tomoo, Kishaba, Hideo, Kita, Arihiro, Kiyosue, Shigeru, Komatsu, Kazuki, Konishi, Sekiya, Koyama, Makoto, Kudo, Kazuhiko, Machida, Hironi, Makita, Hiroto, Matsuse, Naoki, Miyazawa, Hiroyuki, Nakamura, Yuji, Nakatani, Kazuyuki, Nishimura, Takashi, Nishimura, Junichi, Ogawa, Hiroyuki, Ohbayashi, Tetsuro, Ohdaira, Tsukasa, Ohnishi, Kazuhiko, Oki, Masahiko, Saito, Kenji, Sakamoto, Osamu, Sakamoto, Hisakuni, Sekino, Noriharu, Shijubo, Masaharu, Shinkai, Hideo, Soto, Yoshitaka, Sugawara, Noriaki, Suko, Hisaho, Takahashi, Masamitsu, Takahashi, Tsuneyuki, Takahashi, Hiroshi, Tanaka, Hiroyuki, Taniguchi, Tadayuki, Terada, Takao, Tochigi, Kazuyo, Tohyama, Hirokazu, Tokuyasu, Keisuke, Tomii, Tomomasa, Tsuboi, Mitsuyoshi, Utsugi, Katsumaru, Yamamoto, Michiko, Yamamoto, Shuichi, Yano, Makoto, Yoshida, Frank, Custers, Richard, Dekhuijzen, Remco, Djamin, Jan Willem Van Dan Berg, Lowie, Vanfleteren, Pascal, Wielders, Bogusława, Cimoszko, Anna, Doboszyńska, Andrzej, Dyczek, Andrzej, Fal, Krystyna, Folcik, Łukasz, Goliński, Marek, Jutel, Andrzej, Kolczyński, Piotr, Kuna, Ewa, Łączyńska, Wojciech, Machowiak, Maciej, Marczak, Joanna, Markiewicz, Janusz, Milanowski, Grzegorz, Mincewicz, Maria, Nittner-Marszalska, Wojciech, Papiewski, Małgorzata, Pawlukiewicz, Witold, Pomiećko, Barbara, Rewerska, Cezary, Rybacki, Wojciech, Skucha, Ewa, Trębas-Pietraś, Ewa, Uhryn, Małgorzata, Żurowska-Gębala, Laurentia, Andrei, Traian, Mihaescu, Stefan, Mihaicuta, Eniko Vera Pall, Ioan, Petrui, Angelica, Savu, Claudia, Toma, Ana, Trailescu, Vladimir, Abrosimov, Nataliya, Astafyeva, Evgenyi, Bazdyrev, Nadezhda, Berdnikova, Laura, Bolieva, Ekaterina, Bukreeva, Valery, Chistyakov, Anna, Galustyan, Halida, Gantseva, Svetlana, Goncharova, Sergey, Grigoriev, Galina, Ignatova, Inna, Ilyashevich, Nadezhda, Izmozherova, Magomed, Kamalov, Yaroslava, Khovaeva, Natalia, Kuzubova, Lyudmila, Kvitkova, Liudmila, Lenskaya, Igor, Leshchenko, Olga, Magnitskaya, Boris, Molotilov, Artem, Molotkov, Svetlana, Myasoedova, Sergey, Nedogoda, Vladimir, Nosov, Marina, Osipenko, Andrey, Peskov, Veronika, Popova, Oksana, Ratushnay, Irina, Ryzhova, Olga, Shangina, Natalia, Shaporova, Evgeny, Shmelev, Lybov, Shpagina, 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Patel, Allan, Reid, Dinesh, Saralaya, Tariq, Sethi, Sukh Dave Singh, Anthony, G de Soyza, Tom, Wilkinson, Alice, Turner, Helen, Ward, Chandar, Abboy, Ivan, Ackerman, Idalia, Acosta, Arun, Adlakha, Bassil, Aish, Mohamed, Ali, Charles, Andrews, Robby, Ayoub, Anil, Badhwar, Dennis, Bassetti, Sherif El Bayadi, Richard, Beasley, Shashi, Bellam, Jonathan, Bernstein, Maria, Blahey, Scott, Bloom, Eugene, Bleecker, Wesley, Bray, Johnathan, Brewer, Robert, Buynak, William, Calhoun, Edward, Campbell, Anthony, Captain, Birjis, Chinoy, Kenneth, Chinsky, Geoffrey, Chupp, Arsenio, Columbie, Clinton, Corder, Gerard, Criner, Humberto, Cruz, Edward, Cullen, Kevin, Deboer, Michael, Denenberg, Mark, Dransfield, Leonard, Dunn, Miles, Elmore, David, Erb, Faisal, Fakih, Gary, Ferguson, Charles, Fogarty, Mark, Freed, Stephen, Fritz, David, Fuentes, Shariar, Cohen-Gadol, Robert, Garver, John, Given, Luis Ramos Gonez, Raul Ebran Gonzalez, Robert, Gordon, Gregory, Gottschlich, Donald, Graham, David, Grant, Gary, 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Fernando Rodriguez Chariarse, Pedro Elias, Marcelo Fernández, Ana Lopez, Andrea Medina, María Otaola, Maria Salazan Saez, Maria De Salvo, Fernando Scherbovsky, Ana Stok, Jorge Taborda, Alberto Tolcachier, Fernando Verra, Carlos Victorio, Rita Gisela Delgado Vizcarra, Philip Bardin, Peter Bremner, Martin Phillips, John Upham, Peter Wark, Antoine Bolly, Alain Delobbe, Peter Driesen, Eduard Janssens, Wim Janssens, Olivier Michel, Bernard Vandooren, Martti Antila, Jussara Fiterman, Carlos Fritscher, Jorge Hetzel, Jose Jardim, Waldo De Mattos, Rafael Martins, Maria Eunice De Oliveira, Andreia Pez, Maria Sales, Rafael Stelmach, Priscila Wolff, Svetla Andreeva, Reneta Antonova, Ana Dancheva, Yuliya Ivanova, Slavcho Ivanov, Hristo Metev, Iveta Naydenova, Tatyana Petkova, Galina Petrova, Kostadinka Sotirova, Mariyana Stoyanova, Rumen Tiholov, Iliyana Valkanova, Oleg Yakov, Rosa Feijoo, Juana Pavie, Patricia Schönffeldt, Absalon Silva, Victor Martinez, David Espinosa, Alejandro Londono, Dora Molina, Gonzalo Prada, Andrés Rico, Gregorio Sanchez Vallejo, Alvaro Urbina, Ana Vanegas, Maria Villegas, Josip Aralica, Gordana Stjepanovic, Vibeke Backer, Uffe Bødtger, Christian Meyer, Læge Sven Nielsen, Anders Loekke Ottesen, Ingrid Titlestad, Nathalie Bautin, Arnaud Bourdin, Pascal Chanez, Francis Couturaud, Antoine Cuvelier, Gilles Devouassoux, Pierre-Olivier Girodet, Jean-François Muir, Jean-Louis Pépin, Alain Proust, Azzedine Yaici, Yochai Adir, Gershon Fink, Zvi Fridlender, Gabriel Izbicki, Mordechai Kramer, Yehuda Schwartz, Juan Moreno Hoyos Abril, Ricardo Campos Cerda, Efraín Montaño Gonzalez, Ricardo Ramirez Terrones, Rodolfo Posadas Valay, Alejandra Ramirez-Venegas, Paul Dawkins, Syed Hussain, Benedict Brockway, John Richmond, Colin Helm, Catherina Chang, Jørn Ahlqvist, Terje Tollåli, Tadeusz Tomala, Socorro Castro, William Chavez, Octavio Cubas, Rolando Estrella, Efrain Felix, Ronal Gamarra, Alfredo Guerreros, Alberto Matsuno, Danilo Salazar, Miguel Tsukayama, Albert Albay Jr, Teresita Aquino, Tito Atienza, Joven Roque Gonong, Ronnie Samoro, Joel Santiaguel, Beata Asankowicz-Bargiel, Ewa Pisarczyk-Bogacka, Renata Bijata-Bronisz, Marta Chełmińska, Małgorzata Dobryniewska, Anna Olech-Cudzik, Tomasz Fijołek, Krzysztof Filipek, Agata Kot, Bożena Kucińska, Krzysztof Lis, Elżbieta Rybicka-Liszewska, Marzenna Tarnowska-Matusiak, Robert Mróz, Piotr Napora, Wojciech Naumnik, Artur Niemiec, Władysław Pierzchała, Grzegorz Przybylski, Katarzyna Styka, Danuta Wrońska, Branislava Milenkovic, Dobrivoje Novkovic, Matijaz Flezar, Niksa Segota, Snezana Ulcar Kostic, Albert Klobucar, Leif Bjermer, Dan Curiac, Christer Janson, Pekka Koskinen, Bo Lundback, Åke Olsson, Shih-Lung Cheng, Ming-Lin Ho, Jeng-Yuan Hsu, Wu-Huei Hsu, Ping-Hung Kuo, Chin-Chou Wang, Yu-Feng Wei, Kuang-Yao Yang, Watchara Boonsawat, Somchai Chantarothorn, Warangkana Keeratichananont, Kittipong Maneechotesuwan, Kanok Pipatvech, Piamlarp Sangsayunh, Sibel Arinc, Sermin Borekci, Arzu Kaner Erturk, Filiz Kosar, Hakan Gunen, Ismail Hanta, Pinar Akin Kabalak, Tunc Alp Demir, Sibel Nayci, Serir Aktogu Ozkan, Abdullah Sayiner, Esra Uzaslan, Viktor Blazhko, Volodymyr Gavrysyuk, Olena Golub, Liudmyla Iashyna, Tetiana Ilashchuk, Volodymyr Koshlia, Olena Krakhmalova, Vitali Kryvenko, Lesia Kuryk, Olena Levchenko, Yuriy Mostovoy, Mykola Ostrovskyy, Tetyana Pertseva, Olena Piura, Nadiya Rudnytska, Ganna Stupnytska, Nataliia Velychko, Oleh Yakovenko, Lilia Rodriguez Ables, Roger Abrahams, Bassil Aish, Jose Alvarez, Fernando Arencibia, Chander Arora, Samir Arora, Francis Averill, Kwabena Ayesu, Stephen Basheda, Steven Bauer, Jose Bautista, Matthew Beacom, Richard Beasley, Hernando Bernal, Subodh Bhuchar, J'Cinda Bitters, John Burk, Elizabeth Burkett, James Cain, Robert Call, Christopher Chappel, Bartolome Celli, Tom Christensen, Jeremy Cole, Jerome Daniel, Nguyen Dang, Enrique Davis, Samuel Deleon, Robert DeLuca, Ernesto Diaz, Anthony DiMarco, Calvin Dixon, Ankur Doshi, Hugh Durrence, Alain Eid, John Elsen, Herbon Fleming, May Flores, Charles Fogarty, Scott Franczek, Stephen Fritz, Gregory Funk, Stuart Garay, Bernard Garcia, Luis Ramos Gonez, Gregory Gottschlich, Joseph Graif, Carl Griffin, Yamirka Duardo Guerra, David Headley, Mitzie Hewitt, Susan Hole, Robert Holladay, Ira Horowitz, Yu-Luen Hsu, Jonathan Ilowite, Stephen Jones, Ravindra Kashyap, Edward Kerwin, Ahtaram Khan, Nicole Kimzey, James Krainson, Flory Kreutter, Kannappan Krishnaswamy, Shahrukh Kureishy, Albert Lai, Alex Lechin, Daria Lee, Marcus Lee, Williams Leeds, Joseph Lillo, Edward Lisberg, Lawrence Madoff, Narendra Maheskwari, Mujibur Majumder, Sashi Makam, Douglas Mapel, Matthew Mardiney, Jennifer Martin, David Maybee, Isaac Melamed, Elvin Mendez, Stuart Millstone, Joseph Montes, Lee Morrow, Frank Murphy, Dany Obeid, France Occy, Godson Oguchi, Juan Ortiz, Francisco Padron, Ward Paine, James Pearle, Enrique Pelayo, Vandely Perez, David Pham, Carlos Piniella, Kevin Pritchett, Padmashri Rastogi, Stephen Ryan, Syed Rehman, Jackson Rhudy, Eustace Riley, James Riser, Clifford Risk, Emory Robinette, Christopher Roney, Gary Ruoff, David Russian, Mercedes Samson, Jay Sandberg, Jose Santiago, William Sargeant, Alan Schecter, Frank Sciurba, Jeffrey Scott, Ilia Segal, Sudhir Sehgal, Frederic Seifer, Sudhir Sekhsaria, Richard Sellman, Paul Shapero, Jeffrey Shea, Lawrence Sher, John Sibille, Jawed Siddiqui, William Sims, Toniya Singh, Deren Sinkowitz, Denise Smyth, Daniel Soteres, Daniel Sousa, Ralph Steele, Thomas Stern, Jose Suarez, Sever Surdulescu, Ricardo Tan, Tonny Tanus, Raymond Tidman, Aurelio Torres-Consuegra, Barry Troyan, John Updegrove, Sanjay Vadgama, Armando Pineda-Velez, Eduardo Viera, Andrew Wachtel, Ralph Wade, Jimin Wang, Dave Webster, Paul Weinberg, Terry Wells, Jeffrey White, Bram Wieskopf, Hugh Windom, Patrick Wright, David Wyatt, Bassam Yousef, Zahid Zafar, Chau Ngo, Huong Le, Lan Nguyen, Thanh Nguyen, Nhung Nguyen

Subjects
Male, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Anti-asthmatic Agent, law.invention, Pulmonary Disease, Chronic Obstructive, Leukocyte Count, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Monoclonal, Receptors, Medicine, Anti-Asthmatic Agents, 030212 general & internal medicine, Humanized, COPD Exacerbations, benralizumab, clinical trials, COPD, Subcutaneous, General Medicine, Middle Aged, anti–IL-5Rα, Benralizumab, Pulmonary Disease, Chronic Obstructive/drug therapy, [SDV] Life Sciences [q-bio], Female, Antibodies, Monoclonal, Humanized/administration & dosage, Chronic Obstructive, Benralizumab COPD exacerbations, Injections, Subcutaneous, Socio-culturale, Aged, Antibodies, Monoclonal, Humanized, Double-Blind Method, Eosinophils, Humans, Patient Acuity, Receptors, Interleukin-5, Antibodies, chronic obstructive pulmonary disease, Injections, Pulmonary Disease, 03 medical and health sciences, Phase III, Anti-Asthmatic Agents/administration & dosage, In patient, business.industry, Eosinophils/metabolism, medicine.disease, Clinical trial, Receptors, Interleukin-5/antagonists & inhibitors, chemistry, Multicenter study, randomized controlled trial, Immunology, Interleukin-5, business
Abstract

BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

Published
2019
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26. Clinical Phenotypes of Atopy and Asthma in COPD: A Meta-analysis of SPIROMICS and COPDGene

Author

Nirupama, Putcha, Ashraf, Fawzy, Elizabeth C, Matsui, Mark C, Liu, Russ P, Bowler, Prescott G, Woodruff, Wanda K, O'Neal, Alejandro P, Comellas, MeiLan K, Han, Mark T, Dransfield, J Michael, Wells, Njira, Lugogo, Li, Gao, C Conover, Talbot, Eric A, Hoffman, Christopher B, Cooper, Laura M, Paulin, Richard E, Kanner, Gerard, Criner, Victor E, Ortega, R Graham, Barr, Jerry A, Krishnan, Fernando J, Martinez, M Bradley, Drummond, Robert A, Wise, Gregory B, Diette, Craig P, Hersh, and Nadia N, Hansel

Subjects
Hypersensitivity, Immediate, Male, Chronic Obstructive, Immediate, Chronic Obstructive Pulmonary Disease, Status Asthmaticus, Population, Clinical Sciences, Respiratory System, atopy, Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome, Pulmonary Disease, asthma COPD overlap, Pulmonary Disease, Chronic Obstructive, Risk Factors, Clinical Research, Tobacco, Hypersensitivity, Prevalence, Humans, COPD, Lung, Molecular Epidemiology, Tobacco Smoke and Health, Smoking, Disease Management, Biological Variation, Immunoglobulin E, Middle Aged, Asthma, Biological Variation, Population, Respiratory, Female
Abstract

BackgroundLittle is known about the concordance of atopy with asthma COPD overlap. Among individuals with COPD, a better understanding of the phenotypes characterized by asthma overlap and atopy is needed to better target therapies.Research questionWhat is the overlap between atopy and asthma status among individuals with COPD, and how are categories defined by the presence of atopy and asthma status associated with clinical and radiologic phenotypes and outcomes in the Genetic Epidemiology of COPD Study (COPDGene) and Subpopulation and Intermediate Outcome Measures in COPD Study (SPIROMICS)?Study design and methodsFour hundred three individuals with COPD from SPIROMICS and 696 individuals from COPDGene with data about specific IgEs to 10 common allergens and mixes (simultaneous assessment of combination of allergens in similar category) were included. Comparison groups were defined by atopic and asthma status (neither, atopy alone, atopic asthma, nonatopic asthma, with atopy defined as any positive specific IgE (≥0.35 KU/L) to any of the 10 allergens or mixes and asthma defined as self-report of doctor-diagnosed current asthma). Multivariable regression analyses (linear, logistic, and zero inflated negative binomial where appropriate) adjusted for age, sex, race, lung function, smoking status, pack-years smoked, and use of inhaled corticosteroids were used to determine characteristics of groups and relationship with outcomes (exacerbations, clinical outcomes, CT metrics) separately in COPDGene and SPIROMICS, and then adjusted results were combined using meta-analysis.ResultsThe prevalence of atopy was 35%and 36%in COPD subjects from SPIROMICS and COPDGene, respectively, and less than 50%overlap was seen between atopic status with asthma in both cohorts. In meta-analysis, individuals with nonatopic asthma had the most impaired symptom scores (effect size for St. George's Respiratory Questionnaire total score, 4.2; 95%CI, 0.4-7.9; effect size for COPD Assessment Test score, 2.8; 95%CI, 0.089-5.4), highest risk for exacerbations (incidence rate ratio, 1.41; 95%CI, 1.05-1.88) compared with the group without atopy or asthma. Those with atopy and atopic asthma were not at increased risk for adverse outcomes.InterpretationAsthma and atopy had incomplete overlap among former and current smokers with COPD in COPDGene and SPIROMICS. Nonatopic asthma was associated with adverse outcomes and exacerbation risk in COPD, whereas groups having atopy alone and atopic asthma had less risk.

Published
2020

27. Real-world patterns and implications of short-acting β

Author

Njira, Lugogo, Ileen, Gilbert, Joseph, Tkacz, Hitesh, Gandhi, Nadia, Goshi, and Miguel J, Lanz

Subjects
Adult, Male, Middle Aged, Drug Prescriptions, Severity of Illness Index, Asthma, United States, Medication Adherence, Hospitalization, Young Adult, Disease Progression, Humans, Female, Anti-Asthmatic Agents, Adrenergic beta-2 Receptor Agonists, Retrospective Studies
Abstract

Short-acting βTo evaluate the associations between real-world SABA use and severe asthma exacerbations in the United States.Patients with asthma 12 years of age or older receiving SABA in the IBM MarketScan research databases of US administrative claims from September 30, 2014, to September 30, 2016, were evaluated. Patients with 12 months' continuous eligibility before and after their first SABA claim (index SABA), an asthma diagnosis before through 60 days postindex, and either one additional SABA or at least 1 maintenance fill(s) were included. SABA claims postindex (including index fill) were grouped as follows: low: index only; medium: 2 to 3 canisters per year; and high: 4 or more canisters per year. Differences in SABA exposure with respect to disease severity groups and severe asthma exacerbations (hospitalizations, emergency visits, or outpatient systemic corticosteroids) were analyzed by analysis of variance and χA total of 135,540 patients were included: 62.8% women; mean (SD) age, 40.9 (18.3) years; SABA fills per 12-months postindex: 3.0(2.7). Furthermore, 28% of patients filled 1 SABA, 47% 2 to 3, and 25% 4 or more canisters per year. Despite higher maintenance medication possession ratio with increasing SABA (low, 0.53 (0.37); medium, 0.59 (0.35); high, 0.66 (0.32)), annual exacerbation rate per person per year and percent of patients within each SABA group having at least 1 exacerbation rose as SABA fills increased (low, 1.00 (1.45), 45.8%; medium, 1.20 (1.62), 54.3%; high, 1.50 (1.94), 58.7%). Mean SABA fills differed between patients with 0 exacerbation, 2.8 (2.6); 1 exacerbation, 2.9 (2.5); and 2 or more exacerbations, 3.3 (2.9).Exacerbation risk increased with increasing SABA fills. Management strategies ensuring adequate anti-inflammatory therapy delivered to the airways when symptoms occur may be needed to mitigate asthma morbidity.

Published
2020

28. Defining a severe asthma super-responder: findings from a Delphi process

Author

Delphi panel: Adel Mansur, Aikaterini, Detoraki, Alan, Altraja, Alan, James, Alexandra, Nanzer-Kelly, Andréanne, Côté, Andrew, Menzies-Gow, Andriana, Papaioannou, Anne-Maree, Cheffins, Arnaud, Bourdin, Bassam, Mahboub, Brian, Lipworth, Carlos Andrés Celis-Preciado, Carlos, Torres-Duque, Caterina, Bucca, Celeste, Porsbjerg, Charlotte, Ulrik, Chris, Corrigan, Christian, Taube, Claude, Farah, Constance, Katelaris, David, Langton, Dermot, Ryan, Désirée, Larenas-Linnemann, Eleftherios, Zervas, Enrico, Heffler, Flavia, Hoyte, Francesca, Puggioni, George, Christoff, Giorgio Walter Canonica, Giovanna Elisiana Carpagnano, Giuseppe, Guida, Gregory, Katsoulotos, Guy, Brusselle, Hitashi, Rupani, Hubertus, Jersmann, Ian, Clifton, Jaideep, Dhariwal, James, Fingleton, Jane, Duke, Janet, Rimmer, Douglass, Jo, João, Fonseca, Job van Boven, John, Corless, John, Harrington, Jorge, Maspero, José Luis Miguel, Kanok, Pipatvech, Karrinda, Kenny, Kenneth, Chapman, Konstantinos, Kostikas, Lauri, Lehtimäki, Li Ping Chung, Liam, Heaney, Liang-Wen, Hang, Louis-Philippe, Boulet, Luis, Perez-de-Llano, Ricciardi, Luisa, Majdy, Idrees, Manlio, Milanese, Maria Elisabetta Conte, Maria Teresa Costantino, Mariko Koh Siyue, Mark, Fitzgerald, Mark, Hew, Matthew, Peters, Ming-Ju, Tsai, Mitesh, Patel, Mohammad Hashim Khan, Mohsen, Sadatsafavi, Mona, Al-Ahmad, Mona-Rita, Yacoub, Mónica De Gennaro, Naghmeh, Radhakrishna, Nicola Alexander Hanania, Nikolaos, Papadopoulos, Njira, Lugogo, Norma, Linaker, Nunzio, Crimi, Paddy, Dennison, Parameswaran, Nair, Patrick David Mitchell, Paul, O’Byrne, Paul, Pfeffer, Paula, Kauppi, Pauline, Hughes, Peter, Middleton, Peter, Wark, Philip, Bardin, Pin-Kuei, Fu, Praveen, Akuthota, Rekha, Chaudhuri, Ricardo, Campos, Riyard, Al-Lehebi, Roberta, Parente, Rovira, Francisco, Sally, Wenzel, Santus, Pierachille, Shrikant, Pawar, Stelios, Loukides, Stephen, Fowler, Tara, Mackenzie, Thomas, Brown, Tze Lee Tan, Unnur, Björnsdóttir, Vanessa, Mcdonald, Veronica, Lawriwskyj, Vibeke, Backer, Violina, Vasileva, Ying-Chun, Chien, and Zinta, Harrington.

Published
2020

33. Reply

Author

Juan Carlos Cardet, Xiaofeng Jiang, Quan Lu, Norma Gerard, Kristen McIntire, Homer A. Boushey, Mario Castro, Vernon M. Chinchilli, Christopher D. Codispoti, Anne-Marie Dyer, Fernando Holguin, Monica Kraft, Stephen Lazarus, Robert F. Lemanske, Njira Lugogo, Dave Mauger, Wendy C. Moore, James Moy, Victor E. Ortega, Stephen P. Peters, Lewis J. Smith, Julian Solway, Christine A. Sorkness, Kaharu Sumino, Michael E. Wechsler, Sally Wenzel, and Elliot Israel

Subjects
Alendronate, Immunology, Adrenergic beta-Antagonists, Immunology and Allergy, Lung, Bronchodilator Agents
Published
2019

34. Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate

Author

Juan Carlos Cardet, Xiaofeng Jiang, Quan Lu, Norma Gerard, Kristen McIntire, Homer A. Boushey, Mario Castro, Vernon M. Chinchilli, Christopher D. Codispoti, Anne-Marie Dyer, Fernando Holguin, Monica Kraft, Stephen Lazarus, Robert F. Lemanske, Njira Lugogo, Dave Mauger, Wendy C. Moore, James Moy, Victor E. Ortega, Stephen P. Peters, Lewis J. Smith, Julian Solway, Christine A. Sorkness, Kaharu Sumino, Michael E. Wechsler, Sally Wenzel, and Elliot Israel

Subjects
0301 basic medicine, medicine.medical_specialty, Randomization, medicine.drug_class, business.industry, medicine.medical_treatment, Immunology, Bisphosphonate, Placebo, Gastroenterology, Article, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Concomitant, Internal medicine, medicine, Immunology and Allergy, Corticosteroid, Methacholine, 030212 general & internal medicine, Salmeterol, business, Fluticasone, medicine.drug
Abstract

Background Loss of bronchoprotection (LOBP) with a regularly used long-acting β2-adrenergic receptor agonist (LABA) is well documented. LOBP has been attributed to β2-adrenergic receptor (B2AR) downregulation, a process requiring farnesylation, which is inhibited by alendronate. Objective We sought to determine whether alendronate can reduce LABA-associated LOBP in inhaled corticosteroid (ICS)–treated patients. Methods We conducted a randomized, double-blind, placebo-controlled, parallel-design, proof-of-concept trial. Seventy-eight participants with persistent asthma receiving 250 μg of fluticasone twice daily for 2 weeks were randomized to receive alendronate or placebo while initiating salmeterol for 8 weeks. Salmeterol-protected methacholine challenges (SPMChs) and PBMC B2AR numbers (radioligand binding assay) and signaling (cyclic AMP ELISA) were assessed before randomization and after 8 weeks of ICS plus LABA treatment. LOBP was defined as a more than 1 doubling dose reduction in SPMCh PC20 value. Results The mean doubling dose reduction in SPMCh PC20 value was 0.50 and 0.27 with alendronate and placebo, respectively (P = .62). Thirty-eight percent of participants receiving alendronate and 33% receiving placebo had LOBP (P = .81). The after/before ICS plus LABA treatment ratio of B2AR number was 1.0 for alendronate (P = .86) and 0.8 for placebo (P = .15; P = .31 for difference between treatments). The B2AR signaling ratio was 0.89 for alendronate (P = .43) and 1.02 for placebo (P = .84; P = .44 for difference). Changes in lung function and B2AR number and signaling were similar between those who did and did not experience LOBP. Conclusion This study did not find evidence that alendronate reduces LABA-associated LOBP, which relates to the occurrence of LOBP in only one third of participants. LOBP appears to be less common than presumed in concomitant ICS plus LABA–treated asthmatic patients. B2AR downregulation measured in PBMCs does not appear to reflect LOBP.

Published
2019

35. Inhibition of GATA3 and Th2 cytokines expression in type 2 high asthmatics by a small molecule targeting RNA-binding protein HuR

Author

Fatemeh Fattahi, Jason S Ellis, Michael Sylvester, Kristin Bahelda, Sam Hietanen, Luis O Correa, Njira Lugogo, and Ulus Atasoy

Subjects
Immunology, Immunology and Allergy
Abstract

RNA-binding protein human antigen R (HuR) is a master regulator of gene expression in human pathophysiology. Our animal studies in the past showed multiple critical roles for HuR in regulating proinflammatory markers in CD4+ T cells. We hypothesized HuR plays an important role in expression of GATA3 and Th2 cytokines in type 2 high asthma and its inhibition impairs these Th2 inflammatory responses. Peripheral CD4+ T cells were isolated from 26 healthy controls and 32 type 2 high asthmatics (blood eosinophil ≥300 cells/μl or FeNO levels ≥25ppb) and stimulated with anti-CD3/CD28 for 4 days, followed by determination of GATA3 and cytokines expression by flow cytometry and LEGENDplex. HuR levels were quantitated by Western blot, flow cytometry, and qPCR. Inhibition of inflammatory responses was evaluated using a cumarin-derived small molecule named CMLD-2 (a HuR-specific inhibitor). Actinomycin D treatment was used to measure mRNA decay rates of targeted HuR mRNAs. HuR protein levels in CD4+ T cells was significantly higher in type 2 high asthmatics compared to healthy controls. The expression and secretion of Th2 cytokines were significantly higher in asthmatics compared to controls. Our further mRNA and protein studies in type 2 high asthmatics showed reduced expression of GATA3 and Th2 cytokines after CMLD-2 treatment. There was also a significant reduction in gata3 mRNA stability with CMLD-2 treatment, compared with vehicle in the asthmatics. Our study is the first to demonstrate the role of RNA-binding protein HuR in type 2 high asthmatics and that interfering with HuR action using CMLD-2 ameliorates GATA3 and Th2 cytokines production. This data suggests HuR may serve as a novel and powerful therapeutic target to treat type 2 high asthmatics.

Published
2021
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36. Additional file 1: of Bacterial biogeography of adult airways in atopic asthma

Author

Durack, Juliana, Huang, Yvonne, Snehal Nariya, Christian, Laura, K. Mark Ansel, Beigelman, Avraham, Castro, Mario, Dyer, Anne-Marie, Israel, Elliot, Kraft, Monica, Martin, Richard, Mauger, David, Rosenberg, Sharon, King, Tonya, White, Steven, Denlinger, Loren, Holguin, Fernando, Lazarus, Stephen, Njira Lugogo, Peters, Stephen, Smith, Lewis, Wechsler, Michael, Lynch, Susan, and Boushey, Homer

Abstract

Supplemental information includes Figures S1-7 and Tables S1-8. (DOCX 10754 kb)

Published
2018
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37. Bacterial biogeography of adult airways in atopic asthma

Author

Juliana Durack, Yvonne J. Huang, Snehal Nariya, Laura S. Christian, K. Mark Ansel, Avraham Beigelman, Mario Castro, Anne-Marie Dyer, Elliot Israel, Monica Kraft, Richard J. Martin, David T. Mauger, Sharon R. Rosenberg, Tonya S. King, Steven R. White, Loren C. Denlinger, Fernando Holguin, Stephen C. Lazarus, Njira Lugogo, Stephen P. Peters, Lewis J. Smith, Michael E. Wechsler, Susan V. Lynch, Homer A. Boushey, and for the National Heart, Lung and Blood Institute’s 'AsthmaNet'

Subjects
0301 basic medicine, Male, Pathophysiology of asthma, Corynebacterium, Atopy, Induced sputum microbiota, Medical microbiology, RNA, Ribosomal, 16S, 2.1 Biological and endogenous factors, Aetiology, Lung, biology, Ecology, Nasal microbiota, Microbiota, Lung and Blood Institute’s “AsthmaNet”, Middle Aged, Bronchial microbiota, Medical Microbiology, Respiratory, lcsh:QR100-130, Female, medicine.symptom, Lower airways, Microbiology (medical), Adult, medicine.medical_specialty, 16S, Bronchi, Nose, Microbiology, lcsh:Microbial ecology, 03 medical and health sciences, Clinical Research, medicine, Humans, Moraxella, Adult asthma, Asthma, Ribosomal, Inflammation, Upper airways, Mouth Mucosa, Sputum, National Heart, biology.organism_classification, medicine.disease, Eosinophilic inflammation, respiratory tract diseases, Eosinophils, 030104 developmental biology, Oral microbiota, Immunology, RNA, Bacteria
Abstract

Background Perturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and mechanisms of these complex associations will require large longitudinal studies, for which bronchoscopy is poorly suited. Studies of samples obtained by sputum induction and nasopharyngeal brushing or lavage have also reported asthma-associated microbiota characteristics. It remains unknown, however, whether the microbiota detected in these less-invasive sample types reflect the composition of bronchial microbiota in asthma. Results Bacterial microbiota in paired protected bronchial brushings (BB; n = 45), induced sputum (IS; n = 45), oral wash (OW; n = 45), and nasal brushings (NB; n = 27) from adults with mild atopic asthma (AA), atopy without asthma (ANA), and healthy controls (HC) were profiled using 16S rRNA gene sequencing. Though microbiota composition varied with sample type (p

Published
2017

38. Income is an independent risk factor for worse asthma outcomes

Author

Juan Carlos Cardet, Margee Louisias, Tonya S. King, Mario Castro, Christopher D. Codispoti, Ryan Dunn, Linda Engle, B. Louise Giles, Fernando Holguin, John J. Lima, Dayna Long, Njira Lugogo, Sharmilee Nyenhuis, Victor E. Ortega, Sima Ramratnam, Michael E. Wechsler, Elliot Israel, and Wanda Phipatanakul

Subjects
Adult, Male, medicine.medical_specialty, Immunology, Perceived Stress Scale, Context (language use), Rate ratio, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Risk Factors, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Risk factor, Socioeconomic status, Asthma, business.industry, Middle Aged, medicine.disease, 030228 respiratory system, Socioeconomic Factors, Physical therapy, Income, Household income, Female, business, Demography
Abstract

Socioeconomic status (SES) is associated with asthma morbidity in observational studies, but the factors underlying this association are uncertain.We investigated whether 3 SES correlates-low income, low education, and high perceived stress-were independent risk factors for treatment failure and asthma exacerbations in the context of a randomized controlled trial.The effect of low SES (household income of$50,000/y and household educational level of less than a Bachelor's degree) and high perceived stress (defined as a score of20 on a perceived stress scale) on asthma morbidity was analyzed in 381 participants by using Poisson regression models. The primary outcome was treatment failure (defined in the trial protocol as a significant clinical or airflow deterioration), and the secondary outcome was asthma exacerbations requiring systemic corticosteroids.Fifty-four percent of participants had a low income, 40% had a low educational level, and 17% had high perceived stress levels. Even after adjusting for race and other important confounders, participants with lower income had higher rates of both treatment failures (rate ratio, 1.6; 95% CI, 1.1-2.3; P = .03) and exacerbations (rate ratio, 1.9; 95% CI, 1.1-3.3; P = .02). Adherence with inhaled corticosteroids was similarly high for both income categories. Education and perceived stress were not significantly associated with either outcome.In the context of a randomized controlled trial, participants with lower income were more likely to experience adverse asthma outcomes independent of education, perceived stress, race, and medication adherence.

Published
2017

39. Contributors

Author

Lewis Adams, Dan Elie Adler, Alvar Agusti, Evangelia Akoumianaki, Anthony J. Alberg, Kurt H. Albertine, Barbara D. Alexander, Paul H. Alfille, Devanand Anantham, Douglas A. Arenberg, Najib T. Ayas, Aranya Bagchi, John Randolph Balmes, Niaz Banaei, Christopher F. Barnett, Robert P. Baughman, Margaret R. Becklake, Joshua O. Benditt, Neal L. Benowitz, Nirav R. Bhakta, Anant D. Bhave, Paul D. Blanc, Eugene R. Bleecker, Alfred A. Bove, T. Douglas Bradley, Elisabeth Brambilla, V. Courtney Broaddus, Laurent Brochard, Malcolm V. Brock, Kevin K. Brown, Paul G. Brunetta, Jacques Cadranel, Bartolome Celli, Edward D. Chan, Richard N. Channick, Jean Chastre, Guang-Shing Cheng, Kelly Chin, Kian Fan Chung, Christine Clerici, Thomas V. Colby, Harold R. Collard, Carlyne D. Cool, Jean-François Cordier, Ricardo Luiz Cordioli, Tamera J. Corte, Vincent Cottin, Mark S. Courey, Robert L. Cowie, Kristina Crothers, Gerard F. Curley, Charles L. Daley, J. Lucian Davis, Teresa De Marco, Stanley C. Deresinski, Christophe Deroose, Leland G. Dobbs, Christophe Dooms, Gregory P. Downey, Roland M. du Bois, Megan M. Dulohery, Richard M. Effros, Mark D. Eisner, Brett M. Elicker, Armin Ernst, Joel D. Ernst, John V. Fahy, Peter F. Fedullo, David Feller-Kopman, Brett E. Fenster, Tasha E. Fingerlin, Andrew P. Fontenot, Stephen K. Frankel, Joe G.N. Garcia, G.F. Gebhart, Daniel Lee Gilstrap, Nicolas Girard, Mark T. Gladwin, Robb W. Glenny, Warren M. Gold, Michael B. Gotway, Giacomo Grasselli, James M. Greenberg, David E. Griffith, James F. Gruden, MeiLan King Han, William Henderson, Nicholas S. Hill, Wynton Hoover, Philip C. Hopewell, Jennifer L. Horan-Saullo, Richard L. Horner, Laurence Huang, Gérard Huchon, Yoshikazu Inoue, Michael D. Iseman, James E. Jackson, Claudia V. Jakubzick, Julius P. Janssen, James R. Jett, Kirk Jones, Marc A. Judson, Midori Kato-Maeda, Brian P. Kavanagh, Shaf Keshavjee, Kami Kim, R. John Kimoff, Talmadge E. King, Jeffrey S. Klein, Laura L. Koth, Robert M. Kotloff, Monica Kraft, Elif Küpeli, John G. Laffey, Stephen E. Lapinsky, Stephen C. Lazarus, Frances Eun-Hyung Lee, Jarone Lee, Y.C. Gary Lee, Warren L. Lee, Teofilo L. Lee-Chiong, Catherine Lemière, Richard W. Light, Andrew H. Limper, Robert Loddenkemper, Njira Lugogo, Maurizio Luisetti, Andrew M. Luks, Charles-Edouard Luyt, Roberto F. Machado, Neil R. MacIntyre, William MacNee, David K. Madtes, Lisa A. Maier, Fabien Maldonado, Atul Malhotra, Thomas R. Martin, Nick A. Maskell, Robert J. Mason, Pierre P. Massion, Michael A. Matthay, Richard A. Matthay, Annyce S. Mayer, Stuart B. Mazzone, F. Dennis McCool, Francis Xavier McCormack, Atul C. Mehta, Rosario Menéndez, Adam S. Morgenthau, Alison Morris, Timothy A. Morris, Aaron R. Muncey, John F. Murray, Jeffrey L. Myers, Jay A. Nadel, Catherine Nelson-Piercy, Tom S. Neuman, Joshua D. Nosanchuk, Thomas G. O'Riordan, Victor Enrique Ortega, Prasad M. Panse, William Pao, Peter A. Paré, David R. Park, Nicholas J. Pastis, Nicolò Patroniti, Karen C. Patterson, Antonio Pesenti, Allan Pickens, Benjamin A. Pinsky, Steven D. Pletcher, Frank L. Powell, Loretta G. Que, Elizabeth F. Redente, David W.H. Riches, Bruce W.S. Robinson, Roberto Rodriguez-Roisin, Cecile S. Rose, John M. Routes, Steven M. Rowe, Clodagh M. Ryan, Jay H. Ryu, Jonathan M. Samet, Christian E. Sandrock, Robert B. Schoene, David A. Schwartz, Richard M. Schwartzstein, Marvin I. Schwarz, Moisés Selman, Lecia V. Sequist, John M. Shannon, Claire L. Shovlin, Gerard A. Silvestri, Philip L. Simonian, Jonathan P. Singer, Arthur S. Slutsky, Gerald C. Smaldone, George M. Solomon, Eric J. Sorscher, Erik R. Swenson, Nichole T. Tanner, Herbert B. Tanowitz, Antoni Torres, Bruce C. Trapnell, William David Travis, John J. Treanor, George E. Tzelepis, Olivier Vandenplas, Johan F. Vansteenkiste, Thomas K. Varghese, Jørgen Vestbo, Peter D. Wagner, Momen M. Wahidi, W. Dean Wallace, Louis M. Weiss, Scott T. Weiss, Athol U. Wells, John B. West, Douglas B. White, Jeanine P. Wiener-Kronish, Kathryn A. Wikenheiser-Brokamp, Prescott G. Woodruff, Richard G. Wunderink, D. Dante Yeh, Rachel L. Zemans, Leslie Zimmerman, and Richard L. Zuwallack

Published
2016
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40. Income Is an Independent Risk Factor for Worse Asthma Outcomes

Author

Juan Carlos Cardet, Tonya S. King, Margee Louisias, Mario Castro, Christopher D. Codispoti, Ryan Dunn, Brenda L. Giles, Fernando Holguin, John Lima, Dayna Long, Njira Lugogo, Sharmilee M. Nyenhuis, Victor E. Ortega, Sima Ramratnam, Michael E. Wechsler, Elliot Israel, and Wanda Phipatanakul

Subjects
Immunology, Immunology and Allergy
Published
2016
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41. Asthma

Author

Njira Lugogo, Loretta G. Que, Daniel Fertel, and Monica Kraft

Published
2010
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42. Contributors

Author

Lewis Adams, Anthony J. Alberg, Richard K. Albert, Kurt H. Albertine, Devanand Anantham, Douglas Arenberg, Najib T. Ayas, Ronald C. Balkissoon, John R. Balmes, Srinivas R. Bapoje, Joan Albert Barberà, Peter J. Barnes, Fuad M. Baroody, Margaret R. Becklake, Joshua O. Benditt, Neal L. Benowitz, Paul D. Blanc, Richard C. Boucher, Alfred A. Bove, Elisabeth Brambilla, V. Courtney Broaddus, Kevin K. Brown, Paul G. Brunetta, Jacques Cadranel, David P. Carbone, Bartolome R. Celli, Edward D. Chan, Moira Chan-Yeung, Richard N. Channick, Jean Chastre, Kian Fan Chung, Maria Cirino-Marcano, R. Edward Coleman, Harold R. Collard, Carlyne D. Cool, Jean-François Cordier, Tamera J. Corte, Vincent Cottin, Robert L. Cowie, Robert O. Crapo, Kristina Crothers, Charles L. Daley, Scott F. Davies, Teresa De Marco, Lorenzo Del Sorbo, Gregory P. Downey, Wonder Drake, Roland M. du Bois, James Duffin, Richard M. Effros, Mark D. Eisner, Brett M. Elicker, Armin Ernst, Peter F. Fedullo, Matthew J. Fenton, Daniel Fertel, Hans G. Folkesson, Rodney J. Folz, Andrew P. Fontenot, Joe G.N. Garcia, Gerald F. Gebhart, Thomas J. Giordano, Nicolas Girard, Mark T. Gladwin, Michael B. Gotway, James M. Greenberg, David E. Griffith, Stephen Groshong, Matthew J. Hegewald, Peter M. Henson, Nicholas S. Hill, Philip C. Hopewell, Laurence Huang, Yoshikazu Inoue, Michael D. Iseman, James E. Jackson, Jeffrey R. Jacobson, James R. Jett, Demet Karnak, Midori Kato-Maeda, Mani S. Kavuru, Talmadge E. King, Michael R. Knowles, Kenneth S. Knox, Robert M. Kotloff, Monica Kraft, Elif Kupeli, Stephen E. Lapinsky, Abigail R. Lara, Stephen C. Lazarus, F. Eun-Hyung Lee, Warren L. Lee, Y.C. Gary Lee, Teofilo Lee-Chiong, James F. Lewis, Richard W. Light, Andrew H. Limper, Robert Loddenkemper, John M. Luce, Njira Lugogo, Andrew M. Luks, Charles-Edouard Luyt, Roberto F. Machado, Neil R. MacIntyre, Lisa A. Maier, Fabien Maldonado, Jean-Luc Malo, Erica L. Martin, Thomas R. Martin, Robert J. Mason, Pierre P. Massion, Michael A. Matthay, Richard A. Matthay, Annyce S. Mayer, James McCarthy, F. Dennis McCool, Francis X. McCormack, Dana McGlothlin, Atul C. Mehta, Rosario Menéndez, Alison Morris, Timothy A. Morris, Lake D. Morrison, Marc Moss, Jill Murray, John F. Murray, Jeffrey L. Myers, Jay A. Nadel, Koh Nakata, Thomas S. Neuman, Lee S. Newman, Paul W. Noble, Marc Noppen, Thomas B. Nutman, Thomas G. O’Riordan, Allan I. Pack, Peter D. Paré, David R. Park, Edward F. Patz, Eliot A. Phillipson, Allan Pickens, Grace W. Pien, Frank L. Powell, Bobbi S. Pritt, Loretta G. Que, V. Marco Ranieri, John J. Reilly, Stephen I. Rennard, Susan D. Reynolds, David W.H. Riches, Norman W. Rizk, Bruce W.S. Robinson, Roberto Rodriguez-Roisin, Cecile S. Rose, Charis Roussos, John M. Routes, Lewis J. Rubin, Jonathan M. Samet, Christian Sandrock, George A. Sarosi, Richard T. Sawyer, Gregory A. Schmidt, Robert B. Schoene, Dean E. Schraufnagel, David A. Schwartz, Richard M. Schwartzstein, Marvin I. Schwarz, Moises Selman, John M. Shannon, Steven D. Shapiro, Kenneth E. Shepherd, Claire L. Shovlin, Kathy E. Sietsema, Gerard A. Silvestri, Philip L. Simonian, Arthur S. Slutsky, Gerald C. Smaldone, Eugene J. Sullivan, Erik R. Swenson, Alkis Togias, Antoni Torres, Bruce C. Trapnell, John Treanor, Rubin M. Tuder, George E. Tzelepis, Eric Vallières, Peter D. Wagner, Scott T. Weiss, Athol U. Wells, John B. West, Douglas B. White, John G. Widdicombe, Jeanine P. Wiener-Kronish, Richard Wunderink, James R. Yankaskas, Joseph D.C. Yao, Spyros G. Zakynthinos, Leslie Zimmerman, and Richard L. ZuWallack

Published
2010
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44. Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study

Author

Steven W. Yancey, Martyn J. Gilson, Pascal Chanez, Christian Domingo, Robert Price, Richard Leigh, Hector Ortega, and Njira Lugogo

Subjects
Male, safety, medicine.medical_specialty, Exacerbation, medicine.drug_class, Injections, Subcutaneous, Antibodies, Monoclonal, Humanized, Placebo, Drug Administration Schedule, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, exacerbations, Adrenal Cortex Hormones, Internal medicine, Eosinophilia, medicine, Humans, Pharmacology (medical), Anti-Asthmatic Agents, 030212 general & internal medicine, Dosing, Adverse effect, Glucocorticoids, Asthma, Pharmacology, business.industry, mepolizumab, Middle Aged, medicine.disease, severe eosinophilic asthma, Surgery, 030228 respiratory system, Corticosteroid, durability, Administration, Intravenous, Female, business, Mepolizumab, Anaphylaxis, medicine.drug
Abstract

Purpose Patients with severe eosinophilic asthma often experience recurrent asthma exacerbations despite intensive inhaled corticosteroid therapy. In 2 previous double-blind studies (MENSA [NCT01691521] and SIRIUS [NCT01691508]), treatment with intravenous or subcutaneous mepolizumab was associated with significantly reduced annualized exacerbation rates and oral corticosteroid (OCS) requirements compared with placebo. The purpose of this study was to assess the long-term safety and efficacy of subcutaneous mepolizumab treatment in patients with severe eosinophilic asthma. Methods COSMOS was a 52-week, open-label extension study in patients who received mepolizumab or placebo in MENSA or SIRIUS. Patients received subcutaneous mepolizumab regardless of prior treatment allocation and continued to receive appropriate standard-of-care asthma therapy throughout. The primary objective was to assess the long-term safety of mepolizumab; end points included adverse events (AEs) and serious AEs (SAEs). Efficacy assessments included the annualized exacerbation rate and durability of response (defined as the exacerbation rate and OCS dose reduction when combined with MENSA and SIRIUS data, respectively). Findings In total, 558 (86%; previous mepolizumab: 358; previous placebo: 200) and 94 (14%; previous mepolizumab: 58, previous placebo: 36) patients experienced on-treatment AEs and SAEs, respectively. No fatal AEs were reported. Totals of 13 (2%) and 29 (4%) patients experienced systemic and local site reactions, respectively. There were no reports of mepolizumab-related anaphylaxis. Mepolizumab treatment was shown to exert a durable response, with patients who previously received mepolizumab in MENSA or SIRIUS maintaining reductions in exacerbation rate and OCS dosing throughout COSMOS. Patients who previously received placebo in MENSA or SIRIUS demonstrated improvements in these end points following treatment with mepolizumab in COSMOS. Implications These data demonstrate a favorable safety profile of mepolizumab and indicate a durable and stable effect over time, supporting long-term treatment in patients with severe eosinophilic asthma. ClinicalTrials.gov identifier: NCT01842607.

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45. A Paradigm Shift for Asthma Care.

Author

Lugogo N, Skolnik N, and Jiang Y

Subjects
Administration, Inhalation, Adrenal Cortex Hormones therapeutic use, Bronchodilator Agents therapeutic use, Drug Therapy, Combination, Humans, Anti-Asthmatic Agents therapeutic use, Asthma drug therapy
Abstract

Key Takeaways: Asthma remains a substantial health burden, despite continued treatment advances. Patients with mild or moderate asthma, even those with intermittent symptoms, are at risk for severe or fatal exacerbations. Use of short-acting beta2-agonist (SABA)-only rescue therapy is associated with an increased risk of exacerbations, beginning at about the second fill annually. Systemic corticosteroids have shortterm and long-term adverse effects, and long-term adverse effects are driven by cumulative lifetime doses starting at 0.5 to 1.0 g. Expert opinion on the use of SABA only for rescue therapy differs, but recent evidence suggests that a fast-acting bronchodilator combined with inhaled corticosteroids (ICS) is more effective at reducing the risk of exacerbations than SABA alone. There is a window of opportunity just prior to an asthma exacerbation during which use of fast-acting bronchodilator + ICS may play a significant role in mitigating the risk of exacerbation. Patients may respond better to a combination inhaler of a fast-acting bronchodilator and an ICS as needed for rescue therapy or as part of a maintenance and rescue therapy paradigm, rather than attempting to use separate inhalers. However, there is currently no fixed-dose, fast-acting bronchodilator + ICS approved in the United States for as-needed use.

Published
2022
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