Molecular Epidemiology of ARDS

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

To examine the possible relationship between genetic factors and the acute respiratory distress syndrome (ARDS).

Condition or disease
Acute Respiratory Distress Syndrome; Lung Diseases

Detailed Description:

BACKGROUND:

The acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality around the world. In the United States alone there are 150,000 cases per year. Although there have been significant scientific advances in understanding the clinical and pathophysical aspects of the syndrome, there is as yet no specific therapy for ARDS. Moreover, although major risk factors for the development of ARDS include sepsis, aspiration, and multiple trauma, only a minority of patients with these risk factors develop ARDS. Individual differences in susceptibility to chronic disease have been a subject of active molecular epidemiologic investigations for the past decade. In particular, risk factors for cancer conferred by heritable polymorphisms and various metabolic functions have been reported. More recently, a polymorphism of endothelial nitrate oxide synthase has been associated with an increased susceptibility to coronary-artery disease, and polymorphisms in GSTM1 have been associated with an increased risk of developing asbestosis. A recent study of tumor necrosis factor (TNF) polymorphisms has been associated with poor outcome in ARDS.

DESIGN NARRATIVE:

The case-control study examined the association between specific polymorphisms in several genes coding for specific inflammatory responses and for surfactant protein and their potential association with increased susceptibility to ARDS. The first objective was to assess the role of candidate-gene polymorphisms as risk factors for ARDS in a case-control study. The second objective was to assess the relationship between genotype and phenotype for candidate markers in cases and controls. The third objective was to assess the role of these polymorphisms in clinical outcome (survival, recovery) using patients from both the proposed case-control study and the multicenter case series and clinical trial sponsored by the NHLBI ARDS network. By combining both a large case-control study and case series from the network, the study had the advantages of sufficient case ascertainment, statistical power, diagnostic standardization, uniform outcome criteria and study efficiency. Overall, the results of this study should provide new insights into the epidemiology of ARDS and allow for possible preventive strategies as well as possible modifications of therapeutic interventions for the Network Phase III trials.

The investigators test the hypothesis that there is an increased risk of ARDS in patients with heritable traits relating to inflammatory cytokines and surfactant. They are examining risk and prognosis, and examining case and control genetics in relation to cytokine levels. They also plan to do a case-series analysis from a separate study of the ARDS network. They will examine TNF alpha and beta, interleukin-1 receptor antagonist, surfactant protein B and interleukin-10 (IL-10).

Study Design

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Study Type :	Observational
Estimated Enrollment :	4000 participants
Observational Model:	Case-Control
Time Perspective:	Prospective
Official Title:	Molecular Epidemiology of Acute Respiratory Distress Syndrome
Study Start Date :	February 2000
Estimated Primary Completion Date :	August 2019
Estimated Study Completion Date :	December 2019

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Risk of ARDS [ Time Frame: From admission to ICU ]

Secondary Outcome Measures :

1. Mortality [ Time Frame: From admission to ICU to 60 days ]

Other Outcome Measures:

1. Multi-organ Failure [ Time Frame: From admission to ICU ]

Biospecimen Retention:   Samples With DNA

Blood will be collected for DNA extraction and plasma cytokine measurements

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

All patients admitted to ICU with risk factors for ARDS

Criteria

Eligibility Criteria:

All those with risk factors for ARDS - eg, pneumonia, trauma, sepsis.

Vulnerable populations (incarcerated, pregnant, etc.) will be excluded from enrollment. The following medical conditions will also exclude from study:

1. immunocompromised patients
2. patients with chronic lung disease that may appear like ARDS
3. pulmonary vasculitis patients
4. patients with diffuse alveolar hemorrhage
5. patients treated with immune-modulating agents within 3 weeks of admission
6. patients unable to intubate because of DNI order or patient is placed on comfort measures only

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: David C Christiani, MD, MPH	617-726-9274	dchristiani@partners.org
Contact: Andrea Shafer, MPH	617-726-9274	ashafer@partners.org

Locations

United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Andrea Shafer, MPH 617-726-9274 ashafer@partners.org
Contact: Ednan Bajwa, MD 617-726-9274 ebajwa@partners.org
Principal Investigator: David C Christiani, MD.MPH

Sponsors and Collaborators

Massachusetts General Hospital

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	David Christiani, MD	Harvard University School of Public Health

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Gong MN, Wei Z, Xu LL, Miller DP, Thompson BT, Christiani DC. Polymorphism in the surfactant protein-B gene, gender, and the risk of direct pulmonary injury and ARDS. Chest. 2004 Jan;125(1):203-11.

Gong MN, Thompson BT, Williams P, Pothier L, Boyce PD, Christiani DC. Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion. Crit Care Med. 2005 Jun;33(6):1191-8.

Responsible Party:	David Christopher Christiani, Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00006496 History of Changes
Other Study ID Numbers:	937; R01HL060710 ( U.S. NIH Grant/Contract )
First Posted:	November 17, 2000
Last Update Posted:	March 27, 2018
Last Verified:	March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Additional relevant MeSH terms:

Syndrome; Lung Diseases; Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome, Adult; Acute Lung Injury; Disease	Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury