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2. Wheeze is an unreliable endpoint for bronchial methacholine challenges in preschool children

Author

Lora Stewart, Naomi Miyazawa, Ronina Covar, Christopher Mjaanes, Reed Shimamoto, Melanie Gleason, Diego Peroni, Joseph D. Spahn, and Pasquale Comberiati

Subjects
preschool children, wheezing, Immunology, bronchial hyper-responsiveness, spirometry, lung function, asthma, Bronchial Provocation Tests, methacholine challenge, Child, Child, Preschool, Humans, Methacholine Chloride, Spirometry, Asthma, Respiratory Sounds, Pediatrics, Perinatology and Child Health, Immunology and Allergy, Preschool
Abstract

Onset of wheeze is the endpoint often used in the determination of a positive bronchial challenge test (BCT) in young children who cannot perform spirometry. We sought to assess several clinical endpoints at the time of a positive BCT in young children with recurrent wheeze compared to findings in school-aged children with asthma.Positive BCT was defined in: (1) preschool children (n = 22) as either persistent cough, wheeze, fall in oxygen saturation (SpOAll preschool children (mean age 3.4 years) had a positive BCT (median provocative MCh concentration 1.25 mg/ml [IQR, 0.62, 1.25]). Twenty (91%) school-aged children (mean age 11.3 years) had a positive BCT (median PCThe use of wheeze as an endpoint for BCT in preschool children is unreliable, as it rarely occurs. The use of clinical endpoints, such as ≥25% increase in RR or fall in SpO

Published
2022

3. Pharmacogenetic studies of long-acting beta agonist and inhaled corticosteroid responsiveness in randomised controlled trials of individuals of African descent with asthma

Author

Loren C. Denlinger, Jerry A. Krishnan, Maria Pino-Yanes, Hengameh Raissy, Wayne J. Morgan, Manuela Cernadas, Michael D. Cabana, Daniel J. Jackson, J. Tod Olin, David Kantor, Julian Solway, Nicole Grossman, Elizabeth J. Ampleford, Jonathan M. Gaffin, Ronina Covar, Corey Cox, Michael E. Wechsler, James F. Chmiel, Elliot Israel, Kathleen C. Barnes, Steven R. White, Lisa Sullivan-Vedder, Stephen C. Lazarus, Fernando Holguin, Gregory A. Hawkins, Anne M. Fitzpatrick, Jason E. Lang, Vernon M. Chinchilli, Harsha Kumar, Jacqueline A. Pongracic, Max A. Seibold, Njira L Lugogo, Esteban G. Burchard, Angel C.Y. Mak, Fernando D. Martinez, Esther Herrera-Luis, Stephen P. Peters, James N. Moy, Lewis J. Smith, Victor E. Ortega, Sachin Baxi, Craig F. LaForce, Perdita Permaul, Marissa Hautpman, John J. Lima, Wanda Phipatanakul, Tarig Ali-Dinar, Michelle Daya, Juan Carlos Cardet, Kristie Ross, Nizar N. Jarjour, Christine A. Sorkness, Celeste Eng, Robert F. Lemanske, Susan J. Kunselman, Monica Kraft, Rachel G. Robison, Stanley J. Szefler, Deborah A. Meyers, Deborah Gentile, Mario Castro, Satria P Sajuthi, Dayna Long, Dave Mauger, Margee Louisias, Elizabeth Burke-Roberts, Donglei Hu, Ross E. Myers, Sally E. Wenzel, Kathryn V. Blake, Avraham Beigelman, Lakeia Wright, Mindy Benson, Leonard B. Bacharier, Eugene R. Bleecker, Wendy C. Moore, Emily DiMango, Loretta Que, Edward T. Naureckas, Lisa Bartnikas, and William Sheehan

Subjects
Male, Pharmacogenetic Study, Adrenal Cortex Hormones, Developmental and Educational Psychology, Anti-Asthmatic Agents, Child, Salmeterol Xinafoate, Lung, Fluticasone, Pediatric, Middle Aged, Bronchodilator Agents, NHLBI AsthmaNet, Inhalation, 6.1 Pharmaceuticals, Combination, Administration, Respiratory, Drug Therapy, Combination, Female, Salmeterol, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Clinical Trials and Supportive Activities, Black People, Fluticasone propionate, Article, Young Adult, Drug Therapy, Clinical Research, Internal medicine, Administration, Inhalation, medicine, Genetics, Humans, Asthma, business.industry, Human Genome, Evaluation of treatments and therapeutic interventions, Odds ratio, medicine.disease, United States, Pharmacogenomic Testing, Clinical trial, Pharmacogenetics, Pediatrics, Perinatology and Child Health, business
Abstract

BACKGROUND Pharmacogenetic studies in asthma cohorts, primarily made up of White people of European descent, have identified loci associated with response to inhaled beta agonists and corticosteroids (ICSs). Differences exist in how individuals from different ancestral backgrounds respond to long-acting beta agonist (LABA) and ICSs. Therefore, we sought to understand the pharmacogenetic mechanisms regulating therapeutic responsiveness in individuals of African descent. METHODS We did ancestry-based pharmacogenetic studies of children (aged 5-11 years) and adolescents and adults (aged 12-69 years) from the Best African Response to Drug (BARD) trials, in which participants with asthma uncontrolled with low-dose ICS (fluticasone propionate 50 μg in children, 100 μg in adolescents and adults) received different step-up combination therapies. The hierarchal composite outcome of pairwise superior responsiveness in BARD was based on asthma exacerbations, a 31-day difference in annualised asthma-control days, or a 5% difference in percentage predicted FEV1. We did whole-genome admixture mapping of 15 159 ancestral segments within 312 independent regions, stratified by the two age groups. The two co-primary outcome comparisons were the step up from low-dose ICS to the quintuple dose of ICS (5 × ICS: 250 μg twice daily in children and 500 μg twice daily in adolescents and adults) versus double dose (2-2·5 × ICS: 100 μg twice daily in children, 250 μg twice daily in adolescents and adults), and 5 × ICS versus 100 μg fluticasone plus a LABA (salmeterol 50 μg twice daily). We used a genome-wide significance threshold of p

Published
2021

4. Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations

Author

Daniel J, Jackson, Leonard B, Bacharier, David T, Mauger, Susan, Boehmer, Avraham, Beigelman, James F, Chmiel, Anne M, Fitzpatrick, Jonathan M, Gaffin, Wayne J, Morgan, Stephen P, Peters, Wanda, Phipatanakul, William J, Sheehan, Michael D, Cabana, Fernando, Holguin, Fernando D, Martinez, Jacqueline A, Pongracic, Sachin N, Baxi, Mindy, Benson, Kathryn, Blake, Ronina, Covar, Deborah A, Gentile, Elliot, Israel, Jerry A, Krishnan, Harsha V, Kumar, Jason E, Lang, Stephen C, Lazarus, John J, Lima, Dayna, Long, Ngoc, Ly, Jyothi, Marbin, James N, Moy, Ross E, Myers, J Tod, Olin, Hengameh H, Raissy, Rachel G, Robison, Kristie, Ross, Christine A, Sorkness, Robert F, Lemanske, and Lindsay, Texter

Subjects
Male, Pediatrics, Peak Expiratory Flow Rate, Growth, Anti-asthmatic Agent, Medical and Health Sciences, law.invention, 0302 clinical medicine, Randomized controlled trial, law, 030212 general & internal medicine, Anti-Asthmatic Agents, Child, Lung, Fluticasone, media_common, Pediatric, Inhalation, General Medicine, medicine.anatomical_structure, 6.1 Pharmaceuticals, Child, Preschool, Administration, Respiratory, Female, Drug, medicine.drug, medicine.medical_specialty, media_common.quotation_subject, Clinical Trials and Supportive Activities, Fluticasone propionate, Article, Dose-Response Relationship, 03 medical and health sciences, Double-Blind Method, Clinical Research, General & Internal Medicine, Administration, Inhalation, medicine, and Blood Institute AsthmaNet, Humans, Albuterol, Preschool, Asthma, Dose-Response Relationship, Drug, business.industry, Evaluation of treatments and therapeutic interventions, National Heart, medicine.disease, 030228 respiratory system, business
Abstract

BackgroundAsthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited.MethodsWe studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids.ResultsThe rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06).ConclusionsIn children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

Published
2018

5. Challenges in assessing the efficacy of systemic corticosteroids for severe wheezing episodes in preschool children

Author

Theresa W. Guilbert, Leonard B. Bacharier, David T. Mauger, Wanda Phipatanakul, Stanley J. Szefler, Susan Boehmer, Avraham Beigelman, Anne M. Fitzpatrick, Daniel J. Jackson, Sachin N. Baxi, Mindy Benson, Carey-Ann D. Burnham, Michael D. Cabana, Mario Castro, James F. Chmiel, Ronina Covar, Michael Daines, Jonathan M. Gaffin, Deborah A. Gentile, Fernando Holguin, Elliot Israel, H. William Kelly, Stephen C. Lazarus, Robert F. Lemanske, Ngoc Ly, Kelley Meade, Wayne Morgan, James Moy, J. Tod Olin, Stephen P. Peters, Jacqueline A. Pongracic, Hengameh H. Raissy, Kristie Ross, William J. Sheehan, Christine Sorkness, W. Gerald Teague, Shannon Thyne, Fernando D. Martinez, Lisa Bartnikas, Alisha Bouzaher, Christopher Burke, Matthew Cavanaugh, Julia Chen, Elizabeth Cunningham, Amparito Cunningham, James Friedlander, Enal Hindi, David Kantor, Perdita Permaul, Devako Rao, Melinda Rossi, Doris Schierembergg, Kynda Schneider, Jennifer Troung, Dale Umetsu, Joseph Zhou, Jill Chmielewski, Anna Fishbein, Iliana Flexas, Ramsay Fuleihan, Rajesh Kumar, James Lane, Melanie Makhija, Louis Martos, Brandon Parker, Benjamin Prince, Nashmia Qamar, Mary Riordan, Rachel Robinson, Waheeda Samady, Christine Szychlinski, Daniel Tsang, Christopher Codispoti, Juan Fu, Grace Li, Diana Munoz-Mendoza, Benjamin Thompson, Melanie Gleason, Sakari Graves, Jonathan Malka, Melanie Phillips, Gayle Spears, D. Sundstrom, Michael White, Christina Batson, Lea Davies, Franceska Kelly, Esmeralda Morales, Abby Redway, Mary Spicher, Lauren Kaminski, Megan R. Knutson, Kelly Miller, Jennifer Promer, Sheila Turcsanyi, Tanya Watson, Shean Aujla, John Broyles, Hey Chong, Patricia Dubin, Jonathan Finder, Todd D. Green, Lori Holt, Adam Kufen, Geoffrey Kurland, Rose Lanzo, David Nash, Julianne Parente, Catherine Smith, Jonathan Spahr, Daniel J. Weiner, Daniel Craven, Danielle Goetz, Meeghan Hart, Leigh A. Kerns, Laurie Logan, Ross Myers, Laura Veri, Erica Butler, Jennifer Maiolo, Sara Misplay, David Skoner, Glennys Smith, Wanda Caldwell, Courtney Dula, Alysa Ellis, Caroline Horner, Lila Kertz, Tina Norris, Katherine Rivera-Spoljaric, Oscar Rodriguez, Robert Strunk, Jessica Bowman, Vicky Bowyer, Judy Gonzales-Vargas, Sara Hawkey, Susannah McCormick, Michelle McKean, Dan Shapiro, Katherine Tom, Jason Decker, Keonna Harrison, Dayna Long, Jyothi Marbin, Robert Mok, Cindy Nelson-Purdy, Dennis Ren, Hollie Stessel, Deb Green, Denise Thompson-Batt, Kristin Wavell, Donna Wolf, Timothy Beaty, Alice C. Bruce, Karen DeMuth, Jennifer Dodds, Shaneka Douglas, Dawn M. Simon, Denise Whitlock, Shanae Brown, Matthew Bowman, Loretta Doty, Linda Ferrari, Beth Gern, Dave Mauger, Aimee Merchlinski, James Schmidt, Daniel Tekely, Lindsay Texter, Angela Updegrave, and Ronald Zimmerman

Subjects
Pediatrics, medicine.medical_specialty, Allergy, Adrenal cortex hormones, Immunology, education, MEDLINE, Article, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, 030225 pediatrics, Administration, Inhalation, and Blood Institute's AsthmaNet, medicine, Immunology and Allergy, Humans, Respiratory sounds, Child, Preschool, Lung, Asthma, Respiratory Sounds, medicine.diagnostic_test, Inhalation, business.industry, National Heart, medicine.disease, Clinical trial, medicine.anatomical_structure, 030228 respiratory system, Child, Preschool, Administration, business
Abstract

Summary This letter addresses the controversial issue of the use of oral corticosteroids during wheezing exacerbations in preschool-aged children by demonstrating findings of a prematurely terminated multi-center clinical trial, discussing lessons learned, and suggesting future directions.

Published
2018

6. Airway obstruction worsens in young adults with asthma who become obese

Author

Robert C. Strunk, Ryan Colvin, Leonard B. Bacharier, Anne Fuhlbrigge, Erick Forno, Ana Maria Arbelaez, Kelan G. Tantisira, Paul Williams, Mary V. Lasley, Tamara Chinn, Michele Hinatsu, Clifton T. Furukawa, Leonard C. Altman, Frank S. Virant, Michael S. Kennedy, Stephen Tilles, Jonathan W. Becker, C. Warren Bierman, Dan Crawford, Thomas DuHamel, Heather Eliassen, Babi Hammond, Miranda MacLaren, Dominick A. Minotti, Chris Reagan, Gail Shapiro, Marian Sharpe, Ashley Tatum, Grace White, Timothy G. Wighton, Anne Plunkett, Nancy Madden, Susan Anderson, Mark Boehnert, Anita Feins, Amanda Gentile, Natalia Kandror, Kelly MacAulay, Ernestina Sampong, Scott Weiss, Walter Torda, Martha Tata, Sally Babigian, Peter Barrant, Linda Benson, Jose Caicedo, Tatum Calder, Christine Darcy, Anthony DeFilippo, Cindy Dorsainvil, Julie Erickson, Phoebe Fulton, Mary Grace, Jennifer Gilbert, Dirk Greineder, Stephanie Haynes, Margaret Higham, Deborah Jakubowski, Susan Kelleher, Jay Koslof, Dana Mandel, Patricia Martin, Agnes Martinez, Jean McAuliffe, Erika Nakamoto, Paola Pacella, Paula Parks, Johanna Sagarin, Kay Seligsohn, Susan Swords, Meghan Syring, June Traylor, Melissa Van Horn, Carolyn Wells, Ann Whitman, Hartmut Grasemann, Melody Miki, Melinda Solomon, Padmaja Subbarao, Ian MacLusky, Joe Reisman, Henry Levison, Anita Hall, Yola Benedet, Susan Carpenter, Jennifer Chay, Michelle Collinson, Jane Finlayson-Kulchin, Kenneth Gore, Nina Hipolito, Noreen Holmes, Erica Hoorntje, Sharon Klassen, Joseé Quenneville, Renée Sananes, Christine Wasson, Margaret Wilson, N. Franklin Adkinson, Deborah Bull, Stephanie Philips, Peyton Eggleston, Karen Huss, Leslie Plotnick, Margaret Pulsifer, Cynthia Rand, Elizabeth Aylward, Nancy Bollers, Kathy Pessaro, Barbara Wheeler, Stanley Szefler, Ronina Covar, Harold S. Nelson, Bruce Bender, Andrew Liu, D. Sundström, Melanie Phillips, Michael P. White, Melanie Gleason, Kristin Brelsford, Jessyca Bridges, Jody Ciacco, Michael Eltz, Jeryl Feeley, Michael Flynn, Tara Junk-Blanchard, Joseph Hassell, Marcia Hefner, Caroline Hendrickson, Daniel Hettleman, Charles G. Irvin, Alan Kamada, Marzena Krawiec, Gary Larsen, Sai Nimmagadda, Kendra Sandoval, Jessica Sheridan, Joseph Spahn, Gayle Spears, Trella Washington, Eric Willcutt, Ivan Cardona, Kirstin Carel, Jayna Doshi, Rich Hendershot, Jeffrey Jacobs, Neal Jain, June-ku Brian Kang, Tracy Kruzick, Harvey Leo, Beth Macomber, Jonathan Malka, Chris Mjaanes, John Prpich, Lora Stewart, Ben Song, Grace Tamesis, Robert S. Zeiger, Noah Friedman, Michael H. Mellon, Michael Schatz, Terrie Long, Travis Macaraeg, Sandra Christensen, James G. Easton, M. Feinberg, Linda L. Galbreath, Jennifer Gulczynski, Kathleen Harden, Ellen Hansen, Al Jalowayski, Elaine Jenson, Alan Lincoln, Jennie Kaufman, Shirley King, Brian Lopez, Michaela Magiari-Ene, Kathleen Mostafa, Avraham Moscona, Catherine A. Nelle, Jennifer Powers, Elsa Rodriguez, Eva Rodriguez, Karen Sandoval, Nevin W. Wilson, Hengameh H. Raissy, Aaron Jacobs, H. William Kelly, Mary Spicher, Christina Batson, Michelle Harkings, Katie McCallum, Robert Annett, Teresa Archibeque, Naim Bashir, H. Selda Bereket, Marisa Braun, Carrie Bush, Shannon C. Bush, Michael Clayton, Angel Colon-Semidey, Sara Devault, Anna Esparham, Roni Grad, David Hunt, Jeanne Larsson, Sandra McClelland, Bennie McWilliams, Elisha Montoya, Margaret Moreshead, Shirley Murphy, Barbara Ortega, David Weers, Jose Zayas, Leonard Bacharier, Denise Rodgers, Ellen Albers, Gregg Belle, Gordon R. Bloomberg, W. Patrick Buchanan, Mary Caesar, James M. Corry, Karen DeMuth, Marisa Dolinsky, Edwin B. Fisher, Stephen J. Gaioni, Emily Glynn, Bernadette D. Heckman, Debra Kemp, Lila Kertz, Claire Lawhon, Valerie Morgan, Cynthia Moseid, Tina Oliver-Welker, Diana Richardson, Elizabeth Ryan, Sharon Sagal, Thomas F. Smith, Susan Sylvia, Carl Turner, Deborah K. White, James Tonascia, Patricia Belt, Karen Collins, Betty Collison, John Dodge, Michele Donithan, Cathleen Ewing, Rosetta Jackson, Patrick May, Jill Meinert, Girlie Reyes, Michael Smith, Alice L. Sternberg, Mark L. Van Natta, Annette Wagoner, Laura Wilson, Robert Wise, Katherine Yates, Virginia Taggart, Lois Eggers, James Kiley, Howard Moore, Gang Zheng, Paul Albert, Suzanne Hurd, Sydney Parker, Pamela Randall, Margaret Wu, Michelle Cloutier, John Connett, Leona Cuttler, Frank Gilliland, Clarence E. Davis, Howard Eigen, David Evans, Meyer Kattan, Rogelio Menendez, F. Estelle R. Simons, Sanford Leikin, Robert Strunk, Reuben Cherniack, Thomas R. DuHamel, Curtis L. Meinert, Gail G. Shapiro, and Robert Zeiger

Subjects
Adult, Male, Risk, Vital capacity, Pediatrics, medicine.medical_specialty, Adolescent, Childhood obesity, Article, Pulmonary function testing, Body Mass Index, FEV1/FVC ratio, Young Adult, Nedocromil, medicine, Immunology and Allergy, Humans, Obesity, Young adult, Budesonide, Child, Asthma, business.industry, Airway obstruction, medicine.disease, respiratory tract diseases, Respiratory Function Tests, Airway Obstruction, Child, Preschool, Physical therapy, Disease Progression, Female, business, Body mass index, Follow-Up Studies
Abstract

Few studies have examined how developing obesity in early adulthood affects the course of asthma.We analyzed lung function and asthma impairment and risk among nonobese children with asthma, comparing those who were obese in young adulthood with those who remained nonobese.We carried out the post hoc analysis of 771 subjects with mild to moderate asthma who were not obese (pediatric definition, body mass index [BMI]95th percentile) when enrolled in the Childhood Asthma Management Program at ages 5-12 years. The subjects were then followed to age 20 years or more. For visits at ages 20 years or more, spirometry values as percent predicted and recent asthma symptom scores and prednisone exposure were compared between 579 subjects who were nonobese at all visits and 151 who were obese (adult definition of BMI ≥ 30 kg/m(2)) on at least 1 visit (median number of visits when obese = 4, IQR 2-7).Compared with participants who were nonobese (BMI 23.4 ± 2.6 kg/m(2)), those who became obese (BMI 31.5 ± 3.8 kg/m(2)) had significant decreases in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) (P.0003) and FEV1 (P = .001), without differences in FVC (P = .15) during visits at ages 20 years or more. For each unit increase of BMI, FEV1 percent predicted decreased by 0.29 (P = .0009). The relationship between BMI and lung function was not confounded by sex or BMI at baseline. Asthma impairment (symptom scores) and risk (prednisone use) did not differ between the 2 groups.Becoming obese in early adulthood was associated with increased airway obstruction, without impact on asthma impairment or risk.

Published
2015

7. Histopathology of severe childhood asthma: a case series

Author

Henry A, Jenkins, Carlyne, Cool, Stanley J, Szefler, Ronina, Covar, Susan, Brugman, Erwin W, Gelfand, and Joseph D, Spahn

Subjects
Inflammation, Male, Adolescent, Biopsy, Bronchi, Muscle, Smooth, Asthma, Basement Membrane, Respiratory Function Tests, Forced Expiratory Volume, Bronchoscopy, Humans, Female, Child
Abstract

To date, little has been published describing the pathology of severe childhood asthma. The currently accepted model of asthma holds that persistent airway inflammation leads to various symptoms of asthma, airway hyperresponsiveness, and airway remodeling that ultimately results in permanent loss of lung function.Evaluation of six children referred to the National Jewish Medical and Research Center with difficult-to-control asthma, despite aggressive anti-inflammatory therapy, who underwent bronchoscopy with endobronchial biopsy to better characterize their disease.In every case, endobronchial biopsies revealed changes consistent with airway remodeling characterized by thickening of the basement membrane, smooth-muscle hypertrophy, with varying degrees of goblet-cell and submucous gland hyperplasia. The degree of subbasement membrane thickening did not appear to correlate with baseline FEV(1), ultimate FEV(1) following aggressive therapy, or lability in lung function. In five of six cases, there was minimal to no histologic evidence for airway inflammation with mild and patchy submucosal lymphocytic infiltration noted; eosinophils and neutrophils were not present. Further, the majority of the patients achieved normal FEV(1) values despite significant subbasement membrane thickening, counter to the current beliefs regarding airway remodeling and irreversible loss of lung function.This case report highlights some of the shortcomings of the current inflammatory paradigm for severe asthma. Despite little evidence of ongoing airway inflammation, many of the subjects displayed significant lung function lability. The lack of inflammation argues against steroid resistance at a cellular level, although it could be argued that inflammation may have been distal to the site sampled. Additionally, normal to nearly normal lung function was achieved despite the presence of significant remodeling. These findings suggest the need to look beyond inflammation to fully treat severe asthma and ultimately alter its progression.

Published
2003

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