Anne M Fitzpatrick1, Leonard B Bacharier2, Daniel J Jackson3, Stanley J Szefler4, Avraham Beigelman2, Michael Cabana5, Ronina Covar6, Theresa Guilbert7, Fernando Holguin8, Robert F Lemanske3, Fernando D Martinez9, Wayne Morgan9, Wanda Phipatanakul10, Jacqueline A Pongracic11, Hengameh H Raissy12, Robert S Zeiger13, David T Mauger14. 1. Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga. Electronic address: anne.fitzpatrick@emory.edu. 2. Department of Pediatrics, Washington University and St Louis Children's Hospital, St Louis, Mo. 3. Departments of Pediatrics and Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis. 4. Children's Hospital Colorado and Department of Pediatrics, University of Colorado, Aurora, Colo. 5. Department of Pediatrics, Albert Einstein College of Medicine and Montefiore Health System, Bronx, New York, NY. 6. Department of Pediatrics, National Jewish Health, Denver, Colo. 7. Department of Pediatrics, University of Cincinnati and Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio. 8. Department of Medicine, University of Colorado, Denver, Colo. 9. Department of Pediatrics, The University of Arizona, Tucson, Ariz. 10. Division of Allergy and Immunology, Boston Children's Hospital and Harvard Medical School Department of Pediatrics, Boston, Mass. 11. Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill. 12. Department of Pediatrics, University of New Mexico, Albuquerque, NM. 13. Kaiser Permanente, Southern California Region and Department of Pediatrics, University of California San Diego, San Diego, Calif. 14. Department of Public Health Sciences, Penn State University, Hershey, Pa.
Abstract
BACKGROUND: Compared with adults, phenotypic characterization of children with asthma is still limited and it remains difficult to predict which children with asthma are at highest risk for poor outcomes. OBJECTIVE: To identify latent classes in a large population of treatment-adherent children with mild to moderate asthma enrolled in clinical trials and determine whether latent class assignment predicts future lung function abnormalities and exacerbation rate. METHODS: Latent class analysis was performed on 2593 children with mild to moderate asthma aged 5 18 years, with 19 variables encompassing demographic characteristics, medical history, symptoms, lung function, allergic sensitization, and type 2 inflammation. Outcomes included lung function and the annualized exacerbation rate at 12 months of follow-up. RESULTS: Five latent classes were identified with differing demographic features, asthma control, sensitization, type 2 inflammatory markers, and lung function. Exacerbation rates were 1.30 ± 0.12 for class 1 (multiple sensitization with partially reversible airflow limitation), 0.90 ± 0.05 for class 2 (multiple sensitization with reversible airflow limitation), 0.87 ± 0.08 for class 3 (lesser sensitization with reversible airflow limitation), 0.87 ± 0.05 for class 4 (multiple sensitization with normal lung function), and 0.71 ± 0.06 for class 5 (lesser sensitization with normal lung function). Lung function abnormalities persisted in class 1 at 12 months. CONCLUSIONS: Children with mild to moderate asthma are a heterogeneous group. Allergic sensitization and lung function may be particularly useful in identifying children at the greatest risk for future exacerbation. Additional studies are needed to determine whether latent classes correspond to meaningful phenotypes for the purpose of personalized treatment.
BACKGROUND: Compared with adults, phenotypic characterization of children with asthma is still limited and it remains difficult to predict which children with asthma are at highest risk for poor outcomes. OBJECTIVE: To identify latent classes in a large population of treatment-adherent children with mild to moderate asthma enrolled in clinical trials and determine whether latent class assignment predicts future lung function abnormalities and exacerbation rate. METHODS: Latent class analysis was performed on 2593 children with mild to moderate asthma aged 5 18 years, with 19 variables encompassing demographic characteristics, medical history, symptoms, lung function, allergic sensitization, and type 2 inflammation. Outcomes included lung function and the annualized exacerbation rate at 12 months of follow-up. RESULTS: Five latent classes were identified with differing demographic features, asthma control, sensitization, type 2 inflammatory markers, and lung function. Exacerbation rates were 1.30 ± 0.12 for class 1 (multiple sensitization with partially reversible airflow limitation), 0.90 ± 0.05 for class 2 (multiple sensitization with reversible airflow limitation), 0.87 ± 0.08 for class 3 (lesser sensitization with reversible airflow limitation), 0.87 ± 0.05 for class 4 (multiple sensitization with normal lung function), and 0.71 ± 0.06 for class 5 (lesser sensitization with normal lung function). Lung function abnormalities persisted in class 1 at 12 months. CONCLUSIONS: Children with mild to moderate asthma are a heterogeneous group. Allergic sensitization and lung function may be particularly useful in identifying children at the greatest risk for future exacerbation. Additional studies are needed to determine whether latent classes correspond to meaningful phenotypes for the purpose of personalized treatment.
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