Lung DiseasesNCT00233285
Factors in Childhood Lung Susceptibility to Pollution
An observational study of Lung Diseases and Asthma, run by National Heart, Lung, and Blood Institute (NHLBI).
Trial summary
To investigate gene-environment interactions that may influence susceptibility to respiratory illness in children living in highly polluted areas in California. Read more about this study
- Who is it for?
- Ages Up to 100 years
- Conditions the study is for
- Lung Diseases, Asthma
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Sep 1999to Mar 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
No eligibility criteria
About this study
To investigate gene-environment interactions that may influence susceptibility to respiratory illness in children living in highly polluted areas in California.
Read the detailed description
BACKGROUND:
Ambient air pollutants and tobacco smoke produce adverse respiratory health effects in children. Differences in susceptibility for these outcomes are likely to involve genetic variation in multiple pathophysiological pathways that modulate responses and subsequent biologic effects following exposure. The study initially investigated the hypothesis that genetic variants in oxidant stress pathways modulate the occurrence of adverse outcomes using a candidate gene approach in the Children's Health Study (CHS), a longitudinal study of children's respiratory health in 12 Southern California communities. The investigators found that variants in GSTM1 (null), GSTP1 (A105G), TNF (- 308), and ICAM-1 (241) were associated with reduced lung function growth, increased asthma occurrence, and increased respiratory illnesses. These variants also showed gene-environment and gene-gene interactions with tobacco smoke and ambient air pollutants. Their findings add to the growing body of evidence that pathways involving glutathione (GSH) play important roles in respiratory health.
DESIGN NARRATIVE:
In the initial grant period, the investigators studied the effects of ambient air pollution and tobacco smoke on children's respiratory health and the role of diet, physical activity and genetic variation on susceptibility to ambient air pollutants and completed each of the specific aims. They noted associations between genotypes studied and reduced lung function growth, increased sensitivity to in utero exposure to maternal smoking, increased the risk of asthma, and risk of respiratory-related school absences, varied by GSTM1 and GSTP1 genotype. They noted that diets low in antioxidant vitamins were associated with deficits in lung function and that low magnesium intake was associated with lung function deficits. Finally, the investigators identified haplotype structure and tag single nucleotide polymorphisms (SNPs) for selected candidate loci and employed a limited version of haplotype analysis for investigation of association of three ICAM-1 variants on childhood asthma.
The investigators will extend their candidate gene association study using existing data from the Children's Health Study (CHS), to examine the role of sequence variation in 38 genes in five glutathione (GSH) pathways including GSH production, transport, and redox cycling, electrophil and oxidation products detoxification, and nitric oxide cell signaling. The exposures of interest are ozone (O3), nitric oxide (NO2), ambient PM2.5, and tobacco smoke. The respiratory health outcomes are lung function growth, asthma, and respiratory absences. Associations of respiratory health outcomes with sequence variants in candidate genes and air pollution will be assessed using haplotypes and functional SNPs. They will test for overall association of a locus with outcomes using functional SNPs and a haplotype-based approach, and gene-gene and gene-environment interaction within and between pathways will also be examined using approaches to minimize multiple comparisons issues. Confounding by admixture will be addressed using SNP-based genome-wide control methods. Finally, hierarchical Bayesian models of these complex pathways incorporate a priori knowledge about biological relationships to efficiently examine interactions within and between pathways.
- Conditions
- Lung Diseases, Asthma
- Medical subject headings
- Lung Diseases, Asthma
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2005 (estimated)
- Study startSep 1999
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Lung DiseasesStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Frank Gilliland, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00233285
- Sponsor's protocol ID
- 1306
- Other IDs
- R01HL061768
- Status last verified
- Apr 2009
- First submitted
- 3 Oct 2005
- Last updated
- 12 Jul 2016
- Results posted
- No
Publications
Gilliland FD, Li YF, Saxon A, Diaz-Sanchez D. Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study. Lancet. 2004 Jan 10;363(9403):119-25. doi: 10.1016/S0140-6736(03)15262-2.
PubMed 14726165Wenten M, Berhane K, Rappaport EB, Avol E, Tsai WW, Gauderman WJ, McConnell R, Dubeau L, Gilliland FD. TNF-308 modifies the effect of second-hand smoke on respiratory illness-related school absences. Am J Respir Crit Care Med. 2005 Dec 15;172(12):1563-8. doi: 10.1164/rccm.200503-490OC. Epub 2005 Sep 15.
PubMed 16166621Li YF, Tsao YH, Gauderman WJ, Conti DV, Avol E, Dubeau L, Gilliland FD. Intercellular adhesion molecule-1 and childhood asthma. Hum Genet. 2005 Sep;117(5):476-84. doi: 10.1007/s00439-005-1319-7. Epub 2005 Jul 14.
PubMed 16021473Li YF, Langholz B, Salam MT, Gilliland FD. Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest. 2005 Apr;127(4):1232-41. doi: 10.1378/chest.127.4.1232.
PubMed 15821200Salam MT, Li YF, Langholz B, Gilliland FD; Children's Health Study. Early-life environmental risk factors for asthma: findings from the Children's Health Study. Environ Health Perspect. 2004 May;112(6):760-5. doi: 10.1289/ehp.6662.
PubMed 15121522Gilliland FD, Berhane KT, Li YF, Gauderman WJ, McConnell R, Peters J. Children's lung function and antioxidant vitamin, fruit, juice, and vegetable intake. Am J Epidemiol. 2003 Sep 15;158(6):576-84. doi: 10.1093/aje/kwg181.
PubMed 12965883Gilliland FD, Berhane K, Islam T, McConnell R, Gauderman WJ, Gilliland SS, Avol E, Peters JM. Obesity and the risk of newly diagnosed asthma in school-age children. Am J Epidemiol. 2003 Sep 1;158(5):406-15. doi: 10.1093/aje/kwg175.
PubMed 12936895Gilliland FD, Berhane K, Islam T, Wenten M, Rappaport E, Avol E, Gauderman WJ, McConnell R, Peters JM. Environmental tobacco smoke and absenteeism related to respiratory illness in schoolchildren. Am J Epidemiol. 2003 May 15;157(10):861-9. doi: 10.1093/aje/kwg037.
PubMed 12746237Gilliland FD, Berhane K, Li YF, Rappaport EB, Peters JM. Effects of early onset asthma and in utero exposure to maternal smoking on childhood lung function. Am J Respir Crit Care Med. 2003 Mar 15;167(6):917-24. doi: 10.1164/rccm.200206-616OC. Epub 2002 Dec 12.
PubMed 12480608Xie B, Gilliland FD, Li YF, Rockett HR. Effects of ethnicity, family income, and education on dietary intake among adolescents. Prev Med. 2003 Jan;36(1):30-40. doi: 10.1006/pmed.2002.1131.
PubMed 12473422Gilliland FD, Li YF, Dubeau L, Berhane K, Avol E, McConnell R, Gauderman WJ, Peters JM. Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and environmental tobacco smoke on asthma and wheezing in children. Am J Respir Crit Care Med. 2002 Aug 15;166(4):457-63. doi: 10.1164/rccm.2112064.
PubMed 12186820Gilliland FD, Rappaport EB, Berhane K, Islam T, Dubeau L, Gauderman WJ, McConnell R. Effects of glutathione S-transferase P1, M1, and T1 on acute respiratory illness in school children. Am J Respir Crit Care Med. 2002 Aug 1;166(3):346-51. doi: 10.1164/rccm.2111048.
PubMed 12153968Rappaport EB, Gilliland FD, Linn WS, Gauderman WJ. Impact of respiratory illness on expiratory flow rates in normal, asthmatic, and allergic children. Pediatr Pulmonol. 2002 Aug;34(2):112-21. doi: 10.1002/ppul.10142.
PubMed 12112777Gilliland FD, Berhane KT, Li YF, Kim DH, Margolis HG. Dietary magnesium, potassium, sodium, and children's lung function. Am J Epidemiol. 2002 Jan 15;155(2):125-31. doi: 10.1093/aje/155.2.125.
PubMed 11790675Gilliland FD, Li YF, Peters JM. Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children. Am J Respir Crit Care Med. 2001 Feb;163(2):429-36. doi: 10.1164/ajrccm.163.2.2006009.
PubMed 11179118
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Factors in Childhood Lung Susceptibility to Pollution
- ClinicalTrials.gov ID
- NCT00233285
- Acronym / sponsor ID
- 1306
- Conditions
- Lung Diseases, Asthma
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Sep 1999
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 5 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate gene-environment interactions that may influence susceptibility to respiratory illness in children living in highly polluted areas in California.
Detailed description
BACKGROUND:
Ambient air pollutants and tobacco smoke produce adverse respiratory health effects in children. Differences in susceptibility for these outcomes are likely to involve genetic variation in multiple pathophysiological pathways that modulate responses and subsequent biologic effects following exposure. The study initially investigated the hypothesis that genetic variants in oxidant stress pathways modulate the occurrence of adverse outcomes using a candidate gene approach in the Children's Health Study (CHS), a longitudinal study of children's respiratory health in 12 Southern California communities. The investigators found that variants in GSTM1 (null), GSTP1 (A105G), TNF (- 308), and ICAM-1 (241) were associated with reduced lung function growth, increased asthma occurrence, and increased respiratory illnesses. These variants also showed gene-environment and gene-gene interactions with tobacco smoke and ambient air pollutants. Their findings add to the growing body of evidence that pathways involving glutathione (GSH) play important roles in respiratory health.
DESIGN NARRATIVE:
In the initial grant period, the investigators studied the effects of ambient air pollution and tobacco smoke on children's respiratory health and the role of diet, physical activity and genetic variation on susceptibility to ambient air pollutants and completed each of the specific aims. They noted associations between genotypes studied and reduced lung function growth, increased sensitivity to in utero exposure to maternal smoking, increased the risk of asthma, and risk of respiratory-related school absences, varied by GSTM1 and GSTP1 genotype. They noted that diets low in antioxidant vitamins were associated with deficits in lung function and that low magnesium intake was associated with lung function deficits. Finally, the investigators identified haplotype structure and tag single nucleotide polymorphisms (SNPs) for selected candidate loci and employed a limited version of haplotype analysis for investigation of association of three ICAM-1 variants on childhood asthma.
The investigators will extend their candidate gene association study using existing data from the Children's Health Study (CHS), to examine the role of sequence variation in 38 genes in five glutathione (GSH) pathways including GSH production, transport, and redox cycling, electrophil and oxidation products detoxification, and nitric oxide cell signaling. The exposures of interest are ozone (O3), nitric oxide (NO2), ambient PM2.5, and tobacco smoke. The respiratory health outcomes are lung function growth, asthma, and respiratory absences. Associations of respiratory health outcomes with sequence variants in candidate genes and air pollution will be assessed using haplotypes and functional SNPs. They will test for overall association of a locus with outcomes using functional SNPs and a haplotype-based approach, and gene-gene and gene-environment interaction within and between pathways will also be examined using approaches to minimize multiple comparisons issues. Confounding by admixture will be addressed using SNP-based genome-wide control methods. Finally, hierarchical Bayesian models of these complex pathways incorporate a priori knowledge about biological relationships to efficiently examine interactions within and between pathways.
Study design
Who may qualify
- Ages
- Up to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2016.
- Background: PubMed 14726165Gilliland FD, Li YF, Saxon A, Diaz-Sanchez D. Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study. Lancet. 2004 Jan 10;363(9403):119-25. doi: 10.1016/S0140-6736(03)15262-2.
- Background: PubMed 16166621Wenten M, Berhane K, Rappaport EB, Avol E, Tsai WW, Gauderman WJ, McConnell R, Dubeau L, Gilliland FD. TNF-308 modifies the effect of second-hand smoke on respiratory illness-related school absences. Am J Respir Crit Care Med. 2005 Dec 15;172(12):1563-8. doi: 10.1164/rccm.200503-490OC. Epub 2005 Sep 15.
- Background: PubMed 16021473Li YF, Tsao YH, Gauderman WJ, Conti DV, Avol E, Dubeau L, Gilliland FD. Intercellular adhesion molecule-1 and childhood asthma. Hum Genet. 2005 Sep;117(5):476-84. doi: 10.1007/s00439-005-1319-7. Epub 2005 Jul 14.
- Background: PubMed 15821200Li YF, Langholz B, Salam MT, Gilliland FD. Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest. 2005 Apr;127(4):1232-41. doi: 10.1378/chest.127.4.1232.
- Background: PubMed 15121522Salam MT, Li YF, Langholz B, Gilliland FD; Children's Health Study. Early-life environmental risk factors for asthma: findings from the Children's Health Study. Environ Health Perspect. 2004 May;112(6):760-5. doi: 10.1289/ehp.6662.
- Background: PubMed 12965883Gilliland FD, Berhane KT, Li YF, Gauderman WJ, McConnell R, Peters J. Children's lung function and antioxidant vitamin, fruit, juice, and vegetable intake. Am J Epidemiol. 2003 Sep 15;158(6):576-84. doi: 10.1093/aje/kwg181.
- Background: PubMed 12936895Gilliland FD, Berhane K, Islam T, McConnell R, Gauderman WJ, Gilliland SS, Avol E, Peters JM. Obesity and the risk of newly diagnosed asthma in school-age children. Am J Epidemiol. 2003 Sep 1;158(5):406-15. doi: 10.1093/aje/kwg175.
- Background: PubMed 12746237Gilliland FD, Berhane K, Islam T, Wenten M, Rappaport E, Avol E, Gauderman WJ, McConnell R, Peters JM. Environmental tobacco smoke and absenteeism related to respiratory illness in schoolchildren. Am J Epidemiol. 2003 May 15;157(10):861-9. doi: 10.1093/aje/kwg037.
- Background: PubMed 12480608Gilliland FD, Berhane K, Li YF, Rappaport EB, Peters JM. Effects of early onset asthma and in utero exposure to maternal smoking on childhood lung function. Am J Respir Crit Care Med. 2003 Mar 15;167(6):917-24. doi: 10.1164/rccm.200206-616OC. Epub 2002 Dec 12.
- Background: PubMed 12473422Xie B, Gilliland FD, Li YF, Rockett HR. Effects of ethnicity, family income, and education on dietary intake among adolescents. Prev Med. 2003 Jan;36(1):30-40. doi: 10.1006/pmed.2002.1131.
- Background: PubMed 12186820Gilliland FD, Li YF, Dubeau L, Berhane K, Avol E, McConnell R, Gauderman WJ, Peters JM. Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and environmental tobacco smoke on asthma and wheezing in children. Am J Respir Crit Care Med. 2002 Aug 15;166(4):457-63. doi: 10.1164/rccm.2112064.
- Background: PubMed 12153968Gilliland FD, Rappaport EB, Berhane K, Islam T, Dubeau L, Gauderman WJ, McConnell R. Effects of glutathione S-transferase P1, M1, and T1 on acute respiratory illness in school children. Am J Respir Crit Care Med. 2002 Aug 1;166(3):346-51. doi: 10.1164/rccm.2111048.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Gilliland
University of Southern California
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Diseases and Asthma, run by National Heart, Lung, and Blood Institute (NHLBI).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00233285, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2016.