Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations
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 Jr, National Heart, Lung, and Blood Institute AsthmaNet, Juan Carlos Cardet, Elizabeth Burke-Roberts, Marissa Hauptman, Bridget Hron, Lianne Kopel, Stavroula Osganian, Perdita Permaul, Lakiea Wright, Christopher Burke, Matthew Cavanaugh, Amparito Cunningham, Amanda Dimas, Alana Gerald, Latasha Nisbett, Benjamin Peterson, Daila Regos, Timothy Ryan, Doris Schierembergg, Brian Volonte, Rajesh Kumar, Melanie Makhija, Christine Szychlinski, Iliana Flexas, Kristen Koridek-Phillips, James Lane, Christopher Codispoti, Byung Yu, AnnaMaria Kayaloglou, Grace Li, Shannon Stevens, Samantha Zitzer, Sharmilee Nyenhuis, Vanessa Gonzalez, Melissa Morales-Perez, Victoria Morken, Gayle Spears, Stanley Szefler, Michael E Wechsler, Lea Davies, Stephanie Jump, Joseph Ruybal, D Sundstrom, Michael White, Laura Caffey, Christina Batson, Franceska Kelly, Abby Redway, Sima Ramratnam, Megan Knutson, Shelly Olson, Valerie Schend, Tanya Watson, Loren Denlinger, Julia Bach, Juan Celedon, Hey Chong, Erick Forno, Todd Green, Geoggrey Kurland, Allyson Larkin, Jonathan Spahr, Daniel Weiner, Cindy Granny, Erinn Kasubinski, Adam Kufen, Rose Lanzo, Susan Richey, Megan Hart, Adam Gluvna, Laurie Logan, Laura Veri, David Skoner, Erica Butler, Sara Misplay, Nicole Sossong, Andrea Coverstone, Alysa Ellis, Caroline Horner, Lila Kertz, Katherine Rivera-Spoljaric, Robert Strunk, Melissa Navin, Tina Norris, Molly Siegel, Wanda Caldwell, Michael Bentz, Nancy Carmona, Judy Gonzalez-Vargas, Ariel Herm, Alyssa Sparatta, Javay Ross, Rigoberto DelToro, Cherri Harris, Robert Mok, Cindy Nelson-Purdy, Hollie Stessel, Perla Aguilar, Tara Carr, Cori Daines, Michael Daines, Lynn Gerald, Mark Goforth, Jamie Goodwin, Roni Grad, Anunya Hiranratta, Ashish Mathur, Argelia Benavides, Valeria Bloss, Samantha Castro, Czarina Cooper, Sarah David, Silvia Lopez, Patricia Oremelendez, Marisol Posada, Martha Preciado, Janette Priefert, Natalie Provencio, Elizabeth Ryan, Ron Schunk, Faryal Shareef, Ian Thomas, Monica Vasquez, Jesus Wences, William Gower, Victor Ortega, Cheryl Wilmoth, Alice Bruce, Jennifer Dodds, David Schaeffer, Jenny Batalla, Kathleen Joyce, Greta LaFave, Michelle Littlefield, Kimberly Ponthieux, Brooke Riber, Sally Rutledge, Tarig Ali-Dinar, Floyd Livingston, Shanae Brown, Omar Oquendo, Mariela Pena-Rufino, Karen Walker, Vernon Chinchilli, Timothy Craig, Tonya King, Ian Paul, Ann-Marie Dyer, Susan Kunselman, Aimee Merchlinski, Angela Updegrave, Jonathan Nelson, Kelly Nye, Kendall Baab, Ronald Zimmerman, Linda Ferrari, Lindsay Texter, 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 Jr, National Heart, Lung, and Blood Institute AsthmaNet, Juan Carlos Cardet, Elizabeth Burke-Roberts, Marissa Hauptman, Bridget Hron, Lianne Kopel, Stavroula Osganian, Perdita Permaul, Lakiea Wright, Christopher Burke, Matthew Cavanaugh, Amparito Cunningham, Amanda Dimas, Alana Gerald, Latasha Nisbett, Benjamin Peterson, Daila Regos, Timothy Ryan, Doris Schierembergg, Brian Volonte, Rajesh Kumar, Melanie Makhija, Christine Szychlinski, Iliana Flexas, Kristen Koridek-Phillips, James Lane, Christopher Codispoti, Byung Yu, AnnaMaria Kayaloglou, Grace Li, Shannon Stevens, Samantha Zitzer, Sharmilee Nyenhuis, Vanessa Gonzalez, Melissa Morales-Perez, Victoria Morken, Gayle Spears, Stanley Szefler, Michael E Wechsler, Lea Davies, Stephanie Jump, Joseph Ruybal, D Sundstrom, Michael White, Laura Caffey, Christina Batson, Franceska Kelly, Abby Redway, Sima Ramratnam, Megan Knutson, Shelly Olson, Valerie Schend, Tanya Watson, Loren Denlinger, Julia Bach, Juan Celedon, Hey Chong, Erick Forno, Todd Green, Geoggrey Kurland, Allyson Larkin, Jonathan Spahr, Daniel Weiner, Cindy Granny, Erinn Kasubinski, Adam Kufen, Rose Lanzo, Susan Richey, Megan Hart, Adam Gluvna, Laurie Logan, Laura Veri, David Skoner, Erica Butler, Sara Misplay, Nicole Sossong, Andrea Coverstone, Alysa Ellis, Caroline Horner, Lila Kertz, Katherine Rivera-Spoljaric, Robert Strunk, Melissa Navin, Tina Norris, Molly Siegel, Wanda Caldwell, Michael Bentz, Nancy Carmona, Judy Gonzalez-Vargas, Ariel Herm, Alyssa Sparatta, Javay Ross, Rigoberto DelToro, Cherri Harris, Robert Mok, Cindy Nelson-Purdy, Hollie Stessel, Perla Aguilar, Tara Carr, Cori Daines, Michael Daines, Lynn Gerald, Mark Goforth, Jamie Goodwin, Roni Grad, Anunya Hiranratta, Ashish Mathur, Argelia Benavides, Valeria Bloss, Samantha Castro, Czarina Cooper, Sarah David, Silvia Lopez, Patricia Oremelendez, Marisol Posada, Martha Preciado, Janette Priefert, Natalie Provencio, Elizabeth Ryan, Ron Schunk, Faryal Shareef, Ian Thomas, Monica Vasquez, Jesus Wences, William Gower, Victor Ortega, Cheryl Wilmoth, Alice Bruce, Jennifer Dodds, David Schaeffer, Jenny Batalla, Kathleen Joyce, Greta LaFave, Michelle Littlefield, Kimberly Ponthieux, Brooke Riber, Sally Rutledge, Tarig Ali-Dinar, Floyd Livingston, Shanae Brown, Omar Oquendo, Mariela Pena-Rufino, Karen Walker, Vernon Chinchilli, Timothy Craig, Tonya King, Ian Paul, Ann-Marie Dyer, Susan Kunselman, Aimee Merchlinski, Angela Updegrave, Jonathan Nelson, Kelly Nye, Kendall Baab, Ronald Zimmerman, Linda Ferrari, Lindsay Texter
Abstract
Background: Asthma 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.
Methods: We 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.
Results: The 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).
Conclusions: In 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 .).
Conflict of interest statement
No other potential conflict of interest relevant to this article was reported.
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Source: PubMed