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- Study Description
SNP Health Association Resource (SHARe) Asthma Resource project (SHARP) is conducting a genome-wide analysis in adults and children who have participated in National Heart, Lung, and Blood Institute's clinical research trials on asthma. This includes 1041 children with asthma who participated in the Childhood Asthma Management Program (CAMP), 994 children who participated in one or five clinical trials conducted by the Childhood Asthma Research and Education (CARE) network, and 701 adults who participated in one of six clinical trials conducted by the Asthma Clinical Research Network (ACRN).
There are three study types. The longitudinal clinical trials can be subsetted for population-based and/or case-control analyses. Each of the childhood asthma studies has a majority of children participating as part of a parent-child trio. The ACRN (adult) studies are probands alone. Control genotypes will be provided for case-control analyses.
- Authorized Access
- Publicly Available Data (Public ftp)
Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.
- Study Inclusion/Exclusion Criteria
CAMP (Childhood Asthma Management Program):Inclusion Criteria
- Aged 5 to 12 years at time of screening
- Chronic asthma as evidenced by one or more of the following historical findings for at least 6 months in the year prior to interview:
- Asthma symptoms at least two times per week
- At least two usages per week of an inhaled bronchodilator
- Daily asthma medication
- Completion of a screening period (28 days) providing evidence of mild to moderate asthma as defined by criteria (see Table 2)
- Methacholine reactivity: FEV1 PC20 no greater than 12.5 mg/mL
- Consent of parent or guardian
- Assent of child
- Ability to comply with trial for 5 to 6 years
- Severe asthma as evidenced by one or more of the following historical findings:
- Two or more hospitalizations for asthma in the year prior to screening
- Six or more steroid bursts in the year prior to screening
- Intubation for asthma at any time in the past
- Presence of one or more of the following confounding or complicating conditions:
- Other active pulmonary disease
- Pulmonary function suggesting a ventilatory defect or evidence of irreversible lung disease
- Severe chronic sinusitis or nasal polyposis
- Introduction of, or a change in, allergen immunotherapy in the month prior to interview
- Use of more than four sprays of nasal steroids daily (only beclomethasone allowed) at the time of randomization
- Current use of cimetidine, metoclopramide, ranitidine, or other treatment for gastroesophageal reflux
- Participation in another pharmaceutical, immunotherapy, respiratory, or asthma study
- Inability to perform acceptable spirometry
- Inability to complete the methacholine challenge
- Evidence that the patient or family might be noncompliant or might move from the clinic area before completion of follow-up
CARE (Childhood Asthma Research and Education) (Note that in lieu of criteria for all five CARE trials, two representative study, PEAK and PACT, were selected):PEAK (Prevention of Early Asthma in Kids):
- The child may be male or female.
- The child must be between 24-48 months of age at the time of randomization. At least half of all enrolled children should be between 24-35 months.
- The child must have a positive asthma predicted index (API), defined as follows: he/she must have had more than three
exacerbations of wheezing during the previous twelve months. The wheezing episodes should have lasted for more than 24 hours.
At least one exacerbation must have been confirmed by a physician, per parental report. In addition, the child must meet at least
one of the following major conditions or at least 2 of the following minor conditions.
Major Criteria Minor Criteria Parental history of asthma Wheezing unrelated to colds MD-diagnosed atopic dermatitis Eosinophils at least 4% in circulation Allergic sensitization to at least on aeroallergen Allergic sensitization to milk, egg, or peanuts
- The child must have had at least one parent/guardian who can communicate with the study staff to allow assessment of study outcomes.
- The child's parent/guardian must have a working direct contact telephone number.
- The child's parent/guardian has appropriately signed and dated the written consent.
- The child's immunizations are up to date, including varicella (unless the subject has already had clinical varicella). If the subject needs varicella vaccine then this will be arranged with the primary care physician and must be received prior to enrollment.
- The child has a systemic illness (other than allergy or asthma) including (but not limited to) seizures, chronic gastroesophageal reflux (GER) requiring medical treatment, major congenital anomalies, physical and intellectual delay, cerebral palsy, chest surgery, tuberculosis, primary or secondary immunodeficiency, or cardiac disorder (except a hemodynamically insignificant ASD, VSD, or heart murmur).
- The child was born following 35 or less weeks of gestation.
- The child received oxygen for more than 5 days in the neonatal period, or required mechanical ventilation at any time since birth.
- The child has significant developmental delay/failure to thrive, defined as crossing of two major percentile lines during the last year. If a child plots less than the 10th percentile, a growth chart for the previous year will be obtained from the child's primary care provider.
- The child has chronic lung disease of prematurity (CLDP), cystic fibrosis, or any other chronic lung disease.
- The child's family expects to relocate out of study area within three years of the initiation of the study, or is unable to or suspected by the study coordinator to be unable to provide good compliance with therapy.
- The child has used inhaled steroids for asthma for greater than or equal to 4 months in the past year.
- The child had 4 courses or more of systemic corticosteroids in the last year.
- The child ever received immunotherapy.
- The child has ever received IV gammaglobulins or immunosuppressants.
- History of a life-threatening asthma exacerbation requiring intubation and mechanical ventilation anytime.
- History of hypoxic seizures during an asthma exacerbation anytime.
- History of current soybean allergy.
- The child has experienced on average more than four days of symptoms per week in the last 28 days.
- The child has required on average more than four days of Albuterol treatment per week over the last 28 days.
- The child has required controller medication (inhaled corticosteroids, systemic corticosteroids, formoterol, theophylline, cromolyn, leukotriene antagonists, or salmeterol) in the last 28 days.
- The child has been hospitalized for asthma in the past 28 days.
- The child has been on any investigational medication in the last 28 days prior to randomization.
- The child or parent demonstrates poor adherence, less than 80% of study medication use during the run-in period.
PACT (Pediatric Asthma Controller Trial):
- Male and female subjects more than 6 and less than 14 years of age at enrollment.
- Able to perform reproducible spirometry according to ATS criteria.
- Mild-moderate persistent asthma, as defined by the presence of self-reported symptoms or inhaled bronchodilator (not including pre-exercise) use an average of at least 4 times per week during the 4 weeks preceding visit 1.
- Mild-moderate persistent asthma, as defined by the presence of diary-reported symptoms or inhaled bronchodilator (not including pre-exercise) use or peak flows in the yellow zone an average of at least 4 times per week during the 2-week run-in. Yellow zone to be determined by reproducible personal best peak flow during the 2-week run-in.
- PC20 methacholine FEV1 ≤12.5 mg/ml at Visit 1.
- History of clinical varicella or varicella vaccine.
- Nonsmoker within the past year. No use of smokeless tobacco products in the past year.
- Ability of parent to provide informed consent, as evidenced by signing a copy of the consent form approved by the Institutional Review Board of the subjects' respective study institution.
- Verbal assent for children less than 7 years of age and written assent for children between 7 and 14 years of age.
- Corticosteroid treatment for any condition within the defined intervals prior to enrollment.
- Oral - Use within one-month period of the screening visit.
- Inhaled oral corticosteroids - Use within one-month period of the screening visit.
- Injectable - Use within one-month period of the screening visit.
- Nasal corticosteroids may be used at any time during this trial at the discretion of the study investigator or primary care physician.
- Use of other asthma controller medication within the defined interval prior to enrollment.
- Leukotriene modifiers (zileuton, zafirlukast, montelukast) - 2 weeks
- Cromolyn/nedocromil - 2 weeks
- Oral beta-adrenergic agents - 2 weeks
- Theophylline products - 2 weeks
- Long-acting beta-agonists (salmeterol, formoterol) - 2 weeks
- Asthma symptoms (night awakenings more than 2 days per week on average) and/or albuterol use (more than 8 puffs per day on average, not including pre-exercise puffs) consistent with severe persistent disease during the 2-week run-in period.
- Current or prior use of medications known to significantly interact with corticosteroid disposition (within a one-month period of Visit 1), including but not limited to carbamazepine, erythromycin or other macrolide antibiotics, phenobarbital, phenytoin, rifampin, and ketoconazole.
- FEV1 <80% predicted at Visit 1.
- Two or more hospitalizations for asthma in the past year.
- Presence of chronic or active lung disease other than asthma.
- Significant medical illness other than asthma, including thyroid disease, diabetes mellitus, Cushing's disease, Addison's disease, hepatic disease, or concurrent medical problems that could require oral corticosteroids during the study.
- A history of cataracts, glaucoma, or any other medical disorder associated with an adverse effect to corticosteroids.
- History of respiratory tract infection within 4 weeks of the screening visit (may be re-screened after resolution of URI).
- History of significant asthma exacerbation within 4 weeks of the screening visit or more than 3 courses of systemic corticosteroids in the past year.
- History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure.
- History of adverse reactions to ICS, LTRA, or LABA preparations or any of their ingredients.
- Receiving hyposensitization therapy other than an established maintenance regimen (continuous regimen for ≥3 months).
- Inability to coordinate use of the study drug delivery systems or to adhere with therapy (>75% of doses) during the 2-week run-in period.
- Pregnancy or lactation.
- If of child bearing potential, failure to practice abstinence or use of an acceptable birth control method.
- Inability to perform study procedures.
ACRN (Asthma Clinical Research Network) (Note that in lieu of criteria for all six ACRN trials, a representative study, IMPACT, was selected):Subjects who appear by their history of symptom frequency and severity, beta-agonist use, and baseline spirometry to have mild persistent asthma will be evaluated in an eight-week run-in period. Only subjects whose symptoms, PEF measurements, "as needed" beta-agonist use and spirometry indicate that they have mild, persistent asthma over the first four weeks will be continued in the study.
- Male and female subjects 18 to 65 years of age. A goal of 50% female and 33% minority subjects will be incorporated in recruitment.
- History of asthma.
- Heightened airway reactivity, shown by reversible airflow obstruction ≥12% and ≥200 ml improvement in FEV1 following 2-4 inhalations of albuterol MDI or by methacholine PC20 ≤8 mg/ml.
- Baseline FEV1 ≥ 80% of predicted, after withholding bronchodilator and restricted medications per Manual of Operations.
- Diary data over four weeks of observation in the run-in period indicating mild, persistent asthma, as defined by the NAEPP guidelines as any of the following: asthma symptoms >2 times per week but <1 time per day; nocturnal wakenings from asthma >2 per month but ≤1 time per week or PEF variability 20-30%.
- Nonsmoker (<10 pack-years and no smoking within the previous year).
- For heterosexually active women of child-bearing age, agreement to use reliable form of contraception (tubal ligation, oral contraceptive, single barrier method, stable partner with vasectomy) for the duration of the study.
- Willingness to provide informed consent, as evidenced by signing a copy of the consent form approved by the Institutional Review Board of the subject's respective study institution.
- Compliance described above.
- Asthma more or less severe than "mild, persistent" asthma, as defined by the NAEPP.
- Presence of lung disease other than asthma.
- Significant medical illness other than asthma in particular, Cushings, Addison's and hepatic disease or concurrent medical problems that could require oral prednisone during the study.
- History of respiratory tract infection within the six weeks prior to screening visit.
- History of a life-threatening asthma exacerbation requiring intubation and/or mechanical ventilation within 10 years.
- Receiving hyposensitization therapy other than an established maintenance (continuous for three months duration or longer) regimen.
- Pregnancy or lactation.
- Inability, in the opinion of the study investigator, to coordinate use of powder or MDI inhalers or to comply with medication regimens or with the procedures of the study.
- Use of inhaled or oral corticosteroids within the previous six weeks.
- Two or more emergency department visits for asthma in the past year.
- Hospitalization for asthma in the past year.
- Molecular Data
Type Source Platform Number of Oligos/SNPs SNP Batch Id Comment Whole Genome Genotyping Affymetrix AFFY_6.0 934940 52074
- Study History
CAMP: The Childhood Asthma Management Program (CAMP) was designed to evaluate whether continuous, long-term treatment (over a period of four to six years) with either an inhaled corticosteroid (budesonide) or an inhaled noncorticosteroid drug (nedocromil) safely produces an improvement in lung growth as compared with treatment for symptoms only (with albuterol and, if necessary, prednisone, administered as needed). The primary outcome in the study was lung growth, as assessed by the change in forced expiratory volume in one second (FEV1, expressed as a percentage of the predicted value) after the administration of a bronchodilator. Secondary outcomes included the degree of airway responsiveness, morbidity, physical growth, and psychological development.
CARE: The Childhood Asthma Research and Education (CARE) Network was established in 1999 by the National Heart, Lung and Blood Institute (NHLBI). Five clinical centers and a data coordinating center were selected to participate in this research network. Since asthma is the most common chronic childhood disease in the U.S., the CARE Network was established to evaluate treatments for children with asthma, conducting studies for children with asthma and sharing their findings with the health care community.
ACRN: The Asthma Clinical Research Network (ACRN) was established in 1993 by the Division of Lung Diseases (DLD), National Heart, Lung and Blood Institute (NHLBI). The objectives of this multi-center program are to conduct multiple well designed clinical trials for rapid evaluation of new and existing therapeutic approaches to asthma and to disseminate laboratory and clinical findings to the health care community. From 1993 to 2003, ACRN consisted of six Clinical Centers and one Data Coordinating Center (DCC). In September 2003, after a national competition, NHLBI re-awarded ACRN for another 5 years with eight Clinical Centers and one DCC to continue pursuit of the same objectives.
- Selected publications
- Diseases Related to Study (MESH terms)
- Primary Phenotype: Asthma
- Links to Other NCBI Resources
- Authorized Data Access Requests
- Study Attribution
Steering Committee Chairs
- James Kiley, PhD. National Institutes of Health, Bethesda, MD, USA
- Scott Weiss, MD, MS. Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- National Institutes of Health, Bethesda, MD, USA
- Steering Committee Chairs