The University of Arizona

Childhood Asthma Research and Education (CARE) Network

Summary: 

The National Heart, Lung and Blood Institute (NHLBI) initiated the Childhood Asthma Research and Education Network (CARE) in September 1999. The specific aims of the CARE Network were to (1) facilitate evaluation of novel treatment methods and management strategies for asthma and (2) rapidly disseminate the study findings to the health care community. The CARE Network consisted of five Clinical Centers and one Data Coordinating Center:

  • University of Arizona (Tucson, AZ)
  • National Jewish Health (Denver, CO)
  • University of California – San Diego (San Diego, CA)
  • University of Wisconsin (Madison, WI)
  • Washington University (St. Louis, MO)
  • The Pennsylvania State University (Hershey, PA)

The CARE Network completed eight major clinical trials during this 10-year period and published 28 manuscripts. Before implementation, each clinical trial was peer reviewed by the CARENetwork Protocol Review Committee, an independent group of experts in the fields of clinical trial design, biostatistics and pediatric asthma research, which reported directly to the NHLBI. During implementation, each clinical trial was monitored for data quality, study performance and patient safety by the CARE Network Data and Safety Monitoring Board, an independent group of experts in the fields of clinical trial implementation, biostatistics, pediatric asthma research and clinical research ethics, which convened bi-annually and reported directly to the NHLBI. The Data and Safety Monitoring Board also reviewed and approved the major study results and interpretation prior to public presentation and manuscript submission. A link to the synopsis of each clinical trial appears below. The synopsis describes the null hypothesis, the design, the results, and the major publication citation from each clinical trial. A complete list of publications follows this set of one-page synopses.

Studies:
CARE Network Publications:

Strunk RC, Szefler SJ, Phillips BR, Zeiger RS, Chinchilli VM, Larsen G, Hodgdon K, Morgan W, Sorkness CA, Lemanske RF Jr. Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. J. Allergy Clin Immunol (2003); 112:883-892. PMID: 14610474.

Guilbert TW, Morgan WJ, Krawiec M, Lemanske RF Jr, Sorkness C, Szefler SJ, Larsen G, Spahn JD, Zeiger RS, Heldt G, Strunk RC, Bacharier LB, Bloomberg GR, Chinchilli VM, Boehmer SJ, Mauger EA, Mauger DT, Taussig LM, Martinez FD. The Prevention of Early Asthma in Kids study: design, rationale and methods for the Childhood Asthma Research and Education network. Control Clin Trials. (2004); 25:286-310. PMID: 15577824

Bacharier LB, Strunk RC, Mauger D, White D, Lemanske RF Jr, Sorkness CA. Classifying Asthma Severity in Children-Mismatch Between Symptoms, Medication Use and Lung Function. Am J Respir Crit Care Med. (2004); 170:426-432. PMID: 15172893

Guilbert TW, Morgan WJ, Zeiger RS, Bacharier L, Boehmer SJ, Krawiec M, Larsen G, Lemanske RF Jr, Liu A, Mauger DT, Sorkness C, Szefler SJ, Strunk RC, Taussig L, Martinez F. Atopic Characteristics of Children with Recurrent Wheezing at high risk for the development of childhood asthma. J Allergy Clin Immunol (2004); 114:1282-1287. PMID: 15577824

Szefler SJ, Phillips B, Martinez FD, Chinchilli VM, Lemanske RF Jr, Strunk RC, Zeiger RS, Larsen G, Spahn JD, Bacharier LB, Bloomberg GR, Guilbert TW, Heldt G, Morgan WJ, Moss MH, Sorkness CA, Taussig LM. Characterization of Within-Subject Responses to Fluticasone and Montelukast in Childhood Asthma. J Allergy Clin Immunol (2005); 115:233-242. PMID: 15577824

Schmidt JR, Vignati AJ, Pogash RM, Simmons VA, Evans RL. Web-based distributed data management in the Childhood Asthma Research and Education (CARE) Network. Clinical Trials (2005); 2:50-60 Chinchilli VM, Phillips BR, Mauger DT, Szefler, SJ. A General Class of Correlation Coefficients for the 2 X 2 Crossover Design. Biometrical Journal (2005); 47:5:644-653. PMID: 16385905

Zeiger RS, Szefler SJ, Phillips BR, Schatz M, Martinez FD, Chinchilli VM, Lemanske RF Jr, Strunk RC, Larsen G, Spahn JD, Bacharier LB, Bloomberg GR, Guilbert TW, Heldt G, Morgan WJ, Moss MH, Sorkness CA, Taussig LM. Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. J Allergy Clin Immunol (2006); 117:1:45-52. PMID: 16287583

Theresa W. Guilbert TW, Morgan YJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, Bacharier LB, Lemanske RF Jr, Strunk RC, Allen DB, Bloomberg GR, Heldt G, Krawiec M, Larsen G, Liu AH, Chinchilli VM, Sorkness CA, Taussig LM. Long-Term Inhaled Corticosteroids in Preschool Children at High Risk for Asthma. NEJM (2006); 354:1985-1997. PMID: 16687711

Bacharier LB, Phillips BR, Bloomberg GR, Zeiger RS, Paul IM, Krawiec M, Guilbert T, Chinchilli VM, Strunk RC, for the Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Severe intermittent wheezing in preschool children: A distinct phenotype. Journal of Allergy and Clinical Immunology (2007); 119: 604-610. PMID: 17336610

Sorkness CA, Lemanske RF Jr, Mauger DT, Boehmer SJ, Chinchilli VM, Martinez FD, Strunk RC, Szefler SJ, Zeiger RS, Bacharier LB, Bloomberg GR, Covar RA, Guilbert TW, Heldt G, Larsen G, Mellon MH, Morgan WJ, Moss MH, Spahn JD, Taussig LM. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: The Pediatric Asthma Controller Trial. J Allergy Clin Immunol (2007); 119:64-72. PMID: 17140647.

Bacharier LB, Phillips BR, Zeiger RS, Szefler SJ, Martinez FD, Lemanske RF Jr, Sorkness CA, Bloomberg GR, Morgan WJ, Paul IM, Guilbert T, Krawiec M, Covar R, Larsen G, Mellon M, Moss MH, Chinchilli VM, Taussig LM, Strunk RC; CARE Network. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol. (2008) Dec;122:6:1127-1135.e8 PMID: 18973936. PMCID: PMC2753208.

Covar RA, Szefler SJ, Zeiger RS, Sorkness CA, Moss MH, Mauger DT, Boehmer SJ, Strunk RC, Martinez FD, Taussig LM for the Childhood Asthma Research and Education Network. Factors associated with asthma exacerbations during a long-term clinical trial of controller medications in children. American Academy of Allergy, Asthma (2008); 122:741-747. PMID: 19014765. PMCID: PMC3024439

Strunk RC. Bacharier LB. Phillips BR. Szefler SJ. Zeiger RS. Chinchilli VM. Martinez FD. Lemanske RF Jr. Taussig LM. Mauger DT. Morgan WJ. Sorkness CA. Paul IM. Guilbert T. Krawiec M. Covar R. Larsen G. CARE Network. Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. Journal of Allergy & Clinical Immunology (2008); 122(6):1138-1144.e4. PMID: 18973936. PMCID: PMC2737448

Knuffman JE, Sorkness CA, Lemanske RF Jr, Mauger DT, Boehmer SJ, Martinez FD, Bacharier LB, Strunk RC, Szefler SJ, Zeiger RS, Taussig LM. Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Phenotypic predictors of long-term response to inhaled corticosteroid and leukotriene modifier therapies in pediatric asthma. Journal of Allergy & Clinical Immunology (2009); 23(2):411-6. PMID: 19121860

Larsen GL. Morgan W. Heldt GP. Mauger DT. Boehmer SJ. Chinchilli VM. Lemanske RF Jr. Martinez F. Strunk RC. Szefler SJ. Zeiger RS. Taussig LM. Bacharier LB. Guilbert TW. Radford S. Sorkness CA. Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Impulse oscillometry versus spirometry in a long-term study of controller therapy for pediatric asthma. Journal of Allergy & Clinical Immunology (2009); 123(4):861-7.e1 PMID: 19070356

Bacharier LB. Guilbert TW. Zeiger RS. Strunk RC. Morgan WJ. Lemanske RF Jr. Moss M. Szefler SJ. Krawiec M. Boehmer S. Mauger D. Taussig LM. Martinez FD. Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Patient characteristics associated with improved outcomes with use of an inhaled corticosteroid in preschool children at risk for asthma. Journal of Allergy & Clinical Immunology (2009); 123(5):1077-82, 1082.e1-5. PMID: 19230959, NIHMSID: 207892. PMCID: PMC2909590

Signs and Symptoms that Precede Wheezing in Children with a Pattern of Moderate-to- Severe Intermittent Wheezing. Kathy Rivera-Spoljaric, Vernon M. Chinchilli, Lindsay J. Camera, Robert S. Zeiger, Ian M. Paul, Brenda R. Phillips, Lynn M. Taussig, Robert C. Strunk, Leonard B. Bacharier, Childhood Asthma Research and Education (CARE) Network. The Journal of Pediatrics (2009); 154(6): 877-881.e4. NIHMSID283244. PMCID: PMC 3086348

Beigelman A, Bacharier LB, Mauger DT, Phillips BR, Zeiger RS, Taussig LM, Strunk RC. Elevated Exhaled Nitric oxide Levels Increase Risk of Respiratory Tract Illness in Preschool Children with Moderate to Severe Intermittent Wheezing. Annals of Allergy, Asthma, & Immunology (2009); 103(2): 108-113. NIHMSID: 283242. Paul IM, Camera L, Zeiger RS, Guilbert TW, Bacharier LB, Taussig LM, Morgan WJ, Covar RA, Krawiec M, Bloomberg GR, Mauger DT. Relationship Between Infant Weight Gain and Later Asthma. Pediatric Allergy and Immunology (2010); 21: 82-89. PMID: 19725894. NIHMSID: 205471. PMCID: PMC2887600

Lemanske RF Jr. Mauger DT. Sorkness CA. Jackson DJ. Boehmer SJ. Martinez FD. Strunk RC. Szefler SJ. Zeiger RS. Bacharier LB. Covar RA. Guilbert TW. Larsen G. Morgan WJ. Moss MH. Spahn JD. Taussig LM. Childhood Asthma Research and Education (CARE) Network of the National Heart, Lung, and Blood Institute. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. New England Journal of Medicine (2010); 362(11):975-85. PMID: 20197425. NIHMSID:241175. PMCID:PMC2989902.

Simon MR, Chinchilli VM, Phillips BR, Sorkness CA, Lemanske RF Jr, Szefler SJ, Taussig LM, Bacharier LB, Morgan WJ for the Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Forced expiratory flow between 25% and 75% of vital capacity and FEV1/forced vital capacity ratio in relation to Clinical and physiologic parameters in asthmatic children with normal FEV1 Values. The Journal of Allergy and Clinical Immunology (2010); 126(3): 527-534.e8. Rabinovitch N, Graber NJ, Chinchilli VM, Sorkness CA, Zeiger RS, Strunk RC, Bacharier LB, Martinez FD, Szefler SJ for the Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Urinary Leukotriene E4/Exhaled Nitric Oxide Ratio and Montelukast Response in Childhood Asthma. The Journal of Allergy and Clinical Immunology (2010); 126(3): 545-551,e4.7/8/10. PMID: 20816189. PMCID: PMC2935914.

Wang L. Hollenbeak CS. Mauger DT. Zeiger RS. Paul IM. Sorkness CA. Lemanske RF Jr. Martinez FD. Strunk RC. Szefler SJ. Taussig LM. Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Cost-effectiveness analysis of fluticasone versus montelukast in children with mild-to-moderate persistent asthma in the Pediatric Asthma Controller Trial. Journal of Allergy & Clinical Immunology 2011; 127(1):161-6, 166.e1. PMID: 21211651 PMCID: PMC3061816

Martinez FD, Chinchilli VM. Morgan WJ. Boehmer SJ. Lemanske RF Jr. Mauger DT. Strunk RC. Szefler SJ, Zeiger RS. Bacharier LB. Bade E. Covar RA. Friedman NJ. Guilbert TW. Heidarian-Raissy H. Kelly HW. Malka-Rais J. Mellon MH. Sorkness CA. Taussig L. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. The Lancet (2011); 377(9766):650-7. PMID: 21324520

Guilbert TW, Mauger DT, Allen DB, Zeiger RS, Lemanske RF Jr, Szefler SJ, Strunk RC, Bacharier LB, Covar RA, Sorkness CA, Taussig LM, Martinez FD for the Childhood Asthma Research and Education (CARE) Network of the National Heart, Lung, and Blood Institute. Growth of preschool children at high risk for asthma two years after discontinuation of fluticasone. The Journal of Allergy and Clinical Immunology (2011); 128(5): 956-963. PMID: 21820163 PMCID: PMC3224818

Horner C, Mauger DT, Strunk RC, Lemanske RF Jr, Sorkness CA, Szefler SJ, Zeiger RS, Taussig LM, Bacharier LB for the Childhood Asthma Research and Education (CARE) Network of the National Heart, Lung, and Blood Institute. Most Nocturnal Asthma Symptoms Occur Outside of Exacerbations and Associate With Morbidity. The Journal of Allergy and Clinical Immunology (2011); 128(5): 977-982. PMID: 21855126.

Zeiger RS, Mauger D, Bacharier LB, Guilbert T, Martinez FD, Lemanske RF Jr, Strunk RC, Covar R, Szefler SJ, Boehmer S, Jackson DJ, Sorkness CA, Gern J, Kelly HW, Friedman NJ, Mellon MH, Schatz M, Morgan WJ, Chinchilli VM, Raissy HH, Bade E, Malka-Raise J, Beigelman A, Taussig LM for the Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Daily or Intermittent Budesonide in Preschool Children with Recurrent Wheezing. NEJM (2011); 365(20): 1990-2001. PMID: 22111718 PMCID: PMC3247621.



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