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.

Urinary 8-isoprostane and 8-OHdG concentrations in boilermakers with welding exposure.

OBJECTIVE: To investigate the association of exposure to fine particulate matter (PM2.5) with DNA damage and oxidative stress in boilermakers exposed to welding fumes. METHODS: Forty-one workers were monitored over 24 hours during which baseline, postshift, bedtime, and next morning measurements were collected. Twenty-two workers participated as controls. RESULTS: Linear regression was used to model pairwise change in u-8-isoprostane and u-8-OHdG: pre- to postshift, preshift to bedtime, postshift to bedtime, and postshift to next morning. In the models, pre- to postshift change in 8-OHdG was statistically significant, whereas postshift to bedtime change in 8-isoprostane showed an unexpected inverse relationship with PM2.5. CONCLUSIONS: Acute welding exposure is associated with a postshift blunting of systemic inflammation in chronically exposed boilermakers, as measured by 8-isoprostane. The level of oxidative DNA damage as measured by 8-OHdG is less clear.

Biomarker evidence of myocardial cell injury is associated with mortality in acute respiratory distress syndrome.

OBJECTIVE: Although a number of studies have reported elevated levels of markers of myocardial necrosis among critically ill patients, the association between these markers and outcome remains poorly studied in patients with lung injury. We investigated the association of elevated troponin and creatine phosphokinase isoenzyme levels with mortality and organ failure in subjects with acute respiratory distress syndrome. DESIGN: Retrospective study. SETTING: Tertiary academic medical center. PATIENTS: A total of 305 subjects with acute respiratory distress syndrome enrolled in a prospective intensive care unit cohort. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Cardiac biomarker data were available on 248 of 305 patients with acute respiratory distress syndrome (81%), of which 89 patients had at least one elevated cardiac marker level (35%). The presence of an elevated cardiac marker was associated with significantly higher mortality (p = .01) and was an independent predictor of mortality (p = .02) among patients with lower severity of illness (Acute Physiology and Chronic Health Evaluation III, <79). Patients with at least one elevated cardiac marker also had significantly more organ system derangement, including noncardiovascular organ system failures (p = .02). CONCLUSIONS: Patients with acute respiratory distress syndrome have a high prevalence of elevated cardiac markers. The presence of elevated cardiac markers is independently associated with increased 60-day mortality and increased organ failure. This association is most pronounced among patients with lower severity of illness. These results indicate that occult myocardial injury may be an important factor in acute respiratory distress syndrome morbidity and mortality. Further study of the relevant causal relationships and mechanisms is warranted.

pH increase observed in exhaled breath condensate from welding fume exposure.

OBJECTIVES: We sought to investigate changes in exhaled breath condensate (EBC) pH in healthy workers exposed to welding fumes. METHODS: Fourteen exposed participants (median age 39 years, 5 smokers) and 8 nonexposed controls (median age 44 years, 1 smoker) were monitored at an apprentice welding school. Exposure to fine particulate matter less than 2.5 microm (PM2.5) was assessed using cyclone samplers. EBC samples were collected at baseline and at the end of the work shift. EBC samples were deaerated using argon and pH values were measured using standard pH microelectrodes. RESULTS: Mean +/- SEM PM2.5 levels were 1.17 +/- 0.18 mg/m for exposed subjects and 0.03 +/- 0.01 mg/m for controls. Baseline median (range) EBC pH values for the control and exposed group were similar (P = 0.86), 7.21 (4.91 to 8.26), and 7.39 (4.85 to 7.79), respectively. The exposed subjects had a small-but-marginally significant (P = 0.07) pre- to post-work shift increase in pH of 0.28, whereas the control group showed a minimal increase of only 0.03 (P = 0.56). Compared with the control group, the exposed group had a median cross-shift pH increase of 0.25 (P = 0.49). CONCLUSIONS: The aerosolized fine particulate matter contained in metal fumes may be associated with an acute increase in EBC pH values. Further study is necessary to investigate the acute rise in EBC pH after acute exposure to welding fume.

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

Pulmonary hypertension: work in progress.

Pulmonary arterial hypertension is a rare disorder defined by mean pulmonary artery pressures that exceed 25 mm Hg at rest or are greater than 30 mm Hg with exercise. The mortality rate is high for untreated patients, mainly as a result of progressive right heart dysfunction. Pulmonary arterial hypertension has been historically classified as primary pulmonary hypertension or pulmonary hypertension resulting from an underlying disease process. Ongoing research in the nuclear medicine field holds great promise for understanding the pathophysiologic pathways for this condition, as well as the monitoring of the continually evolving therapeutic options.