Chest
Volume 125, Issue 1, January 2004, Pages 203-211
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Clinical Investigations in Critical Care
Polymorphism in the Surfactant Protein-B Gene, Gender, and the Risk of Direct Pulmonary Injury and ARDS

https://doi.org/10.1378/chest.125.1.203Get rights and content

Study objective

Major risk factors for ARDS have been identified. However, only a minority of patients with such risks develops ARDS. It is likely that, given the same type and degree of insult, there are heritable determinants of susceptibility to ARDS. To investigate the possibility of variable genetic susceptibility to ARDS, we examined the association between ARDS and a polymorphism in intron 4 of the surfactant protein-B (SP-B) gene.

Design

Nested case-control study conducted from September 1999 to March 2001.

Setting

Four adult medical and surgical ICUs at a tertiary academic center.

Patients

One hundred eighty-nine patients meeting study criteria for a defined risk factor for ARDS were enrolled and prospectively followed.

Measurements and results

Seventy-two patients (38%) developed ARDS. After stratification by gender and adjustment for potential confounders, there was a significantly increased odds for women with the variant SP-B gene to develop ARDS compared to women homozygous for the wild-type allele (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.1 to 18.8; p = 0.03). Women with the variant SP-B polymorphism also had significantly increased odds of having a direct pulmonary injury such as aspiration or pneumonia as a risk factor for ARDS as opposed to an indirect pulmonary risk for ARDS (OR, 4.6; 95% CI, 1.1 to 19.9; p = 0.04). No such association with ARDS or direct pulmonary injury was found for men.

Conclusion

The variant polymorphism of the SP-B gene is associated with ARDS and with direct pulmonary injury in women, but not in men. Further study is needed to confirm the association between the variant SP-B gene, and gender, ARDS, and direct pulmonary injury.

Section snippets

Study Population

We conducted a nested case control study in the neurologic, cardiac, medical, and surgical ICUs of the Massachusetts General Hospital (Boston, MA). Every weekday, the research coordinator screens all patients admitted to the ICU in the preceding 24 h for ARDS risk factors, as defined in Table 1. For patients admitted to the ICU with sepsis or severe sepsis, clinical data on the suspected source of infection was collected. Patients were considered to have pneumonia as a source of sepsis if they

Cohort Characteristics

From October 1999 to April 2000 and from June to September 2000, 2,294 consecutive patients admitted to the ICU were screened. A total of 428 patients were admitted to the ICU with one or more of the required risk factors for ARDS. Of those, 188 patients were excluded and 46 patients either refused consent or died before consent could be obtained, resulting in 194 patients being enrolled into the cohort. In addition, nine patients were enrolled as part of the pilot study between January and

Discussion

The limitations of this study should be mentioned. As this was a preliminary report, the study is small. Thus, confirmatory studies on a larger group of patients will need to be performed. The critical presentation of many of the patients and the inability to interview them for clinical history limits the ability to obtain data for certain parameters such as tobacco history, which were missing for 78 patients. To our knowledge, the variant SP-B genotype has not been associated previously with

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    This research was supported by research grants HL60710 and ES00002 from the National Institutes of Health. Dr. Gong was supported by grant K23 HL67197 from the National Heart, Lung, and Blood Institute, and Drs. Xu and Miller were supported by grant T32 ES07069 from the National Institute of Environmental Health Sciences.

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