Surfactant protein-B polymorphisms and mortality in the acute respiratory distress syndrome.

OBJECTIVE: To determine whether polymorphisms of the surfactant protein B gene may be associated with increased mortality in patients with the acute respiratory distress syndrome. DESIGN: A prospective cohort study. SETTING: Four adult intensive care units at a tertiary academic medical center. PATIENTS: Two hundred fourteen white patients who had met criteria for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were genotyped for a variable nuclear tandem repeat polymorphism in intron 4 of the surfactant protein B gene and the surfactant protein B gene +1580 polymorphism. For the variable nuclear tandem repeat surfactant protein B gene polymorphism, patients were found to have either a homozygous wild-type genotype or a variant genotype consisting of either a heterozygous insertion or deletion polymorphism. Logistic regression was performed to analyze the relationship of the polymorphisms to mortality in patients with acute respiratory distress syndrome. In multivariate analysis, the presence of variable nuclear tandem repeat surfactant protein B gene polymorphism was associated with a 3.51 greater odds of death at 60 days in patients with acute respiratory distress syndrome as compared to those patients with the wild-type genotype (95% confidence interval 1.39-8.88, p = 0.008). There was no association found between the +1580 variant and outcome (p = 0.15). CONCLUSIONS: In this study, the variable nuclear tandem repeat surfactant protein B gene polymorphism in intron 4 is associated with an increased 60 day mortality in acute respiratory distress syndrome after adjusting for age, severity of illness, and other potential confounders. Additional studies in other populations are needed to confirm this finding.

Polymorphisms in the mannose binding lectin-2 gene and acute respiratory distress syndrome.

OBJECTIVE: The variant alleles in the mannose binding lectin-2 (MBL-2) gene have been associated with MBL deficiency and increased susceptibility to sepsis. We postulate that the variant MBL-2 genotypes are associated with increased susceptibility to and mortality in acute respiratory distress syndrome (ARDS). DESIGN: Nested case-control study. SETTING: Tertiary academic medical center. PATIENTS: Two hundred and twelve Caucasians with ARDS and 442 controls genotyped for the variant X, D, B, and C alleles of codon -221, 52, 54, and 57, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients homozygous for the variant codon 54B allele (54BB) had worse severity of illness on admission (p = .007), greater likelihood of septic shock (p = .04), and increased odds of ARDS (adjusted odds ratio, 6.7; 95% confidence interval, 1.5-31) when compared with heterozygotes and homozygotes for the wild-type allele. This association with ARDS was especially strong among the 311 patients with septic shock (adjusted odds ratio, 12.0; 95% confidence interval, 1.9-74). Among the patients with ARDS, the 54BB genotype was associated with more daily organ dysfunction (p = .01) and higher mortality (adjusted hazard rate, 4.0; 95% confidence interval, 1.6-10). Development of ARDS and outcomes in ARDS did not vary significantly with variant alleles of codon -221, 52, and 57, but the power to detect an effect was limited secondary to the low allele frequencies. CONCLUSIONS: The MBL-2 codon 54BB genotype may be important in ARDS susceptibility and outcome. Additional studies are needed to confirm these findings in other populations.

Residential exposure to petrochemicals and the risk of leukemia: using geographic information system tools to estimate individual-level residential exposure.

The authors conducted a population-based, case-control study in Kaohsiung, southern Taiwan, Republic of China, to investigate the association between residential petrochemical exposure and leukemia risk among subjects 29 years of age and younger. Between November 1997 and June 2003, 171 cases and 410 controls matched for age and sex were recruited. Since assessment of petrochemical impacts depends on accurate exposure estimates, the authors developed a procedure using geographic information system tools to assign subjects' exposure. The resulting individual-level exposure estimates (the exposure opportunity score) are an integrated exposure measure that accounts for subjects' mobility, length of stay at each residence, distance to petrochemical plant(s), monthly prevailing wind direction, and multiple petrochemical pollution sources. Different conditional logistic regression models were fitted for subjects aged 0-19 and 20-29 years to evaluate separately childhood versus adulthood leukemia. No overall association was observed for the younger age group. However, residential petrochemical exposure was a significant risk factor for leukemia for the older age group. For one unit of increase in the log-transformed exposure opportunity score, the adjusted odds ratio was 1.54 (95 percent confidence interval: 1.14, 2.09). This study illustrates the utility of geographic information system tools for providing refined exposure estimates for residential exposure to petrochemical pollution.

Dietary iron, zinc, and calcium and the risk of lung cancer.

BACKGROUND: Iron, zinc, and calcium are all involved in the metabolism of reactive oxygen species and may compete with each other for similar binding sites. Dietary intakes of these micronutrients have been associated with altered risks of colorectal, breast, and prostate cancers. METHODS: In this Massachusetts hospital-based case-control study of 923 patients with lung cancer and 1125 healthy controls, we studied the associations between dietary iron, zinc, and calcium intake and the risk of lung cancer. Dietary intake was assessed at the time of recruitment (1992 to 2000) with the use of a 126-item semiquantitative food-frequency questionnaire. We analyzed the data using multiple logistic regression models adjusting for smoking history and other potential risk factors. RESULTS: The adjusted odds ratios of dietary iron, zinc, and calcium from food sources were 1.45 (95% confidence interval=1.03-2.06), 0.71 (0.50-0.99), and 1.64 (1.17-2.29), respectively, for the highest quintile versus the lowest quintile of each micronutrient. Stronger associations between micronutrients and lung cancer risk were found when iron, zinc, and calcium were included together in the same model. The associations between dietary micronutrients intake and lung cancer risk were stronger among current smokers than among former smokers. When we examined intake from supplements as well as diet, associations were similar to those for diet alone. CONCLUSIONS: Dietary iron, zinc, and calcium may play an important role in the development of lung cancer, especially among current smokers. These results need to be confirmed in large prospective studies.

Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion.

OBJECTIVE: Clinical predictors for acute respiratory distress syndrome (ARDS) have been studied in few prospective studies. Although transfusions are common in the intensive care unit, the role of submassive transfusion in non-trauma-related ARDS has not been studied. We describe here the clinical predictors of ARDS risk and mortality including the role of red cell transfusion. DESIGN: Observational prospective cohort. SETTING: Intensive care unit of Massachusetts General Hospital. PATIENTS: We studied 688 patients with sepsis, trauma, aspiration, and hypertransfusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred twenty-one (32%) subjects developed ARDS with a 60-day mortality rate of 46%. Significant predictors for ARDS on multivariate analyses included trauma (adjusted odds ratio [ORadj] 0.22, 95% confidence interval [CI] 0.09-0.53), diabetes (ORadj 0.58, 95% CI 0.36-0.92), direct pulmonary injury (ORadj 3.78, 95% CI 2.45-5.81), hematologic failure (ORadj 1.84, 95% CI 1.05-3.21), transfer from another hospital (ORadj 2.08, 95% CI 1.33-3.25), respiratory rate >33 breaths/min (ORadj 2.39, 95% CI 1.51-3.78), hematocrit >37.5% (ORadj 1.77, 95% CI 1.14-2.77), arterial pH <7.33 (ORadj 2.00, 95% CI 1.31-3.05), and albumin

The relationship between human semen parameters and environmental exposure to polychlorinated biphenyls and p,p'-DDE.

Scientific and public concern exists about potential reproductive health effects of persistent chlorinated organic chemicals, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE, the most stable daughter compound of DDT). To explore the hypothesis that environmental exposures to PCBs and DDE are associated with altered semen parameters, we conducted a cross-sectional study of 212 male partners of subfertile couples who presented to the Massachusetts General Hospital Andrology Laboratory. Semen parameters were analyzed as both a continuous measure and dichotomized based on World Health Organization reference values for sperm concentration (< 20 million/mL), motility (< 50% motile), and Kruger strict criteria for morphology (< 4% normal). The comparison group for the dichotomized analysis was men with all three semen parameters above the reference values. In serum, 57 PCB congeners and p,p -DDE were measured by congener-specific analysis using gas chromatography with electron capture detection. There were dose-response relationships among PCB-138 and sperm motility (odds ratio per tertile, adjusted for age, abstinence, and smoking, and p-value for trend were, respectively, 1.00, 1.68, 2.35, and p-value = 0.03) and morphology (1.00, 1.36, 2.53, p-value = 0.04). There was limited evidence of an inverse relationship between sum of PCBs, as well as those PCBs classified as cytochrome P450 enzyme inducers, with sperm motility and sperm morphology, as well as limited evidence of an inverse association between p,p -DDE and sperm motility. The lack of a consistent relationship among semen parameters and other individual PCB congeners and groupings of congeners may indicate a difference in spermatotoxicity between congeners.

Spirometric abnormalities associated with chronic bronchitis, asthma, and airway hyperresponsiveness among boilermaker construction workers.

STUDY OBJECTIVES: In a 2-year longitudinal study of boilermaker construction workers, we found a significant association between working at oil-fired, coal-fired, and gas-fired industries during the past year and reduced lung function. In the present study, we investigated whether chronic bronchitis, asthma, or baseline methacholine airway responsiveness can explain the heterogeneity in lung function response to boilermaker work. DESIGN: This study is part of an ongoing prospective cohort study of boilermakers. Exposure was assessed with a work history questionnaire. Spirometry was performed annually to assess lung function. A generalized estimating equation approach was used to account for the repeated-measures design. SETTING: Boilermaker union members. PARTICIPANTS: One hundred eighteen boilermakers participated in the study. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Self-reported history of chronic bronchitis and asthma were associated with a larger FEV1 reduction in response to workplace exposure at coal-fired and gas-fired industries. Although we found a high prevalence (39%) of airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEV1 of < 8 mg/mL) among boilermakers, we did not find a consistent pattern of effect modification by airway responsiveness. CONCLUSIONS: Although chronic bronchitis and asthma were associated with a greater loss in lung function in response to hours worked as a boilermaker, and therefore they acted as effect modifiers of the exposure-lung function relationship, airway hyperresponsiveness did not. However, the high prevalence of airway hyperresponsiveness found in the cohort may be a primary consequence of long-term workplace exposure among boilermakers.