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Background: Single nucleotide polymorphisms in the myosin light chain kinase (MYLK) gene have been implicated in the risk of sepsis-related acute lung injury and asthma. MYLK encodes protein isoforms involved in multiple components of the inflammatory response, including apoptosis, vascular permeability, and leukocyte diapedesis. We tested the association of MYLK gene variation in the development of acute lung injury in major trauma patients.Methods: We conducted a prospective cohort study of 273 subjects with major trauma (injury severity score > or = 16). All x-rays and clinical data were reviewed by three clinicians for acute lung injury classification. A total of 17 tagging single nucleotide polymorphisms in MYLK were genotyped. Single nucleotide polymorphisms were individually assessed at the genotype level, and multiple logistic regression models were used to adjust for baseline variables. Haplotype analyses of sliding windows including 2-5 single nucleotide polymorphisms were conducted.Results: Ninety-one of the 273 subjects (33%) met criteria for acute lung injury within 5 days of traumatic insult. Three informative MYLK coding single nucleotide polymorphisms were individually associated with acute lung injury, with two informative risk-conferring genotypes His21Pro (CC genotype, odds ratio = 1.87, 95% confidence interval 1.06-3.33; p = 0.022) and Pro147Ser (TT, odds ratio = 2.13, 95% confidence interval 1.14-4.10; p = 0.011) more frequent than the noninformative Thr335Thr CC genotype (odds ratio = 0.42, 95% confidence interval 0.20-0.85; p = 0.010). Each of these genotypic associations was more pronounced in African Americans with trauma. Multivariate analyses demonstrated the association of each MYLK single nucleotide polymorphism with acute lung injury to be independent of age, injury severity score, Acute Physiology and Chronic Health Evaluation III, and the mechanism of trauma. Finally, haplotype analyses revealed strong acute lung injury associations with 2-4 single nucleotide polymorphism haplotypes, all involving His21Pro (p < 0.008).Conclusions: Three MYLK coding single nucleotide polymorphisms previously associated with sepsis-induced acute lung injury and severe asthma in African Americans were associated with acute lung injury development after trauma in African Americans, although effect directions differed. These results confirm our prior studies implicating MYLK as a susceptibility gene in a distinct acute lung injury subset other than sepsis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Both single and bilateral lung transplantation are recognised options for patients who have end-stage chronic obstructive pulmonary disease (COPD); however, which procedure leads to longer survival remains unclear. We aimed to compare survival after each procedure by analysing data from the registry of the International Society for Heart and Lung Transplantation. METHODS: We analysed data for 9883 patients with COPD, 3525 (35.7%) of whom underwent bilateral lung transplantation, and 6358 (64.3%) single lung transplantation, between 1987 and 2006. We accounted for possible selection bias with analysis of covariance, propensity-score risk adjustment, and propensity-based matching. FINDINGS: Median survival after either type of lung transplantation for patients with COPD was 5.0 years (95% CI 4.8-5.2). Survival for patients who had lung transplantation before 1998 was 4.5 years (4.3-4.8), compared with 5.3 years (5.0-5.5) for those who had it after 1998 (p<0.0001). The proportion of patients who had bilateral lung transplantation increased from 101/467 (21.6%) in 1993 to 345/614 (56.2%) in 2006. Median survival time after bilateral lung transplantation was longer than that after single lung transplantation: 6.41 years (6.02-6.88) versus 4.59 years (4.41-4.76) (p<0.0001). Pretransplant characteristics of patients who had single and bilateral lung transplantation differed, but whichever method was used to adjust for baseline differences, bilateral lung transplantation was associated with longer survival than was single lung transplantation; the hazard ratio ranged from 0.83 (0.78-0.92) for analysis of covariance to 0.89 (0.80-0.97) for propensity-based matching. However, bilateral lung transplantation had little benefit compared with single lung transplantation for patients who were 60 years and older (HR 0.95; 0.81-1.13). INTERPRETATION: Bilateral lung transplantation leads to longer survival than single lung transplantation in patients with COPD, especially those who are younger than 60 years. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVES: Sarcoidosis is a granulomatous disorder with heterogeneous clinical manifestations, which are potentially reflective of a syndrome with different etiologies leading to similar histologic findings. We examined the relationship between environmental and occupational exposures, and the clinical phenotype of sarcoidosis. DESIGN: We performed a cross-sectional study of incident sarcoidosis cases that had been identified by A Case Control Etiologic Study of Sarcoidosis. Subjects were categorized into the following two groups: (1) pulmonary-only disease; and (2) systemic disease (with or without pulmonary involvement). Logistic regression was used to examine the associations of candidate exposures with clinical phenotype. SETTING: Ten academic medical centers across the United States. PATIENTS: The current study included 718 subjects in whom sarcoidosis had been diagnosed within 6 months of study enrollment. Patients met the following criteria prior to enrollment: (1) tissue confirmation of noncaseating granulomas on tissue biopsy on one or more organs within 6 months of study enrollment with negative stains for acid-fast bacilli and fungus; (2) clinical signs or symptoms that were consistent with sarcoidosis; (3) no other obvious explanation for the granulomatous disease; and (4) age > 18 years. MEASUREMENTS AND RESULTS: Several exposures were associated with significantly less likelihood of having extrapulmonary disease in multivariate analysis, including agricultural organic dusts and wood burning. The effects of many of these exposures were significantly different in patients of different self-defined race. CONCLUSIONS: The differentiation of sarcoidosis subjects on the basis of clinical phenotypes suggests that these subgroups may have unique environmental exposure associations. Self-defined race may play a role in the determination of the effect of certain exposures on disease phenotypes. [ABSTRACT FROM AUTHOR]

Background: Patients at the Philadelphia Veterans Affairs Medical Center frequently voice concern that air exposure during lung cancer surgery might cause tumor spread. Several African-American patients asserted that this belief was common in the African-American community.Objective: To assess the prevalence of the belief that air exposure during lung cancer surgery might cause tumor spread and gauge the influence of this belief on the willingness of African-American and white patients to have lung cancer surgery.Design: Prospective questionnaire survey.Setting: Philadelphia Veterans Affairs Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Los Angeles Veterans Affairs Medical Center, Los Angeles, California; and Medical University of South Carolina, Charleston, South Carolina.Patients: 626 consecutive patients in pulmonary and lung cancer clinics.Measurements: None.Results: 38% of patients (61% of whom were African American and 29% of whom were white) stated that they believe air exposure at surgery causes tumor spread. The most significant predictor of belief was African-American race (odds ratio, 3.5 [95% CI, 1.9 to 6.5]), even after controlling for other relevant variables in a multivariable analysis. Nineteen percent of African Americans stated that this belief was a reason for opposing surgery, and 14% would not accept their physicians' assertion that the belief is false. These rates were also statistically significantly higher among African-American than white patients.Conclusions: Belief in accelerated tumor spread at surgery is prevalent among general pulmonary outpatients and lung cancer clinic patients facing lung surgery, particularly among African-American patients. Our findings may pertain to key racial disparities in lung cancer surgery and survival rates and suggest that culturally sensitive physician training or outreach programs directed at disparate beliefs and attitudes may help to address racial discrepancies in health care outcomes. [ABSTRACT FROM AUTHOR]

Background: Warfarin is the primary therapy to prevent stroke and venous thromboembolism. Significant periods of nonadherence frequently go unreported by patients and undetected by providers. Currently, no comprehensive screening tool exists to help providers assess the risk of nonadherence at the time of initiation of warfarin therapy.Methods: This article reports on a prospective cohort study of adults initiating warfarin therapy at two anticoagulation clinics (university- and Veterans Affairs-affiliated). Nonadherence, defined by failure to record a correct daily pill bottle opening, was measured daily by electronic pill cap monitoring. A multivariable logistic regression model was used to develop a point system to predict daily nonadherence to warfarin.Results: We followed 114 subjects for a median of 141 days. Median nonadherence of the participants was 14.4% (interquartile range [IQR], 5.8-33.8). A point system, based on nine demographic, clinical, and psychosocial factors, distinguished those demonstrating low vs high levels of nonadherence: four points or fewer, median nonadherence 5.8% (IQR, 2.3-14.1); five points, 9.1% (IQR, 5.9-28.6); six points, 14.5% (IQR, 7.1-24.1); seven points, 14.7% (IQR, 7.0-34.7); and eight points or more, 29.3% (IQR, 15.5-41.9). The model produces a c-statistic of 0.66 (95% CI, 0.61-0.71), suggesting modest discriminating ability to predict day-level warfarin nonadherence.Conclusions: Poor adherence to warfarin is common. A screening tool based on nine demographic, clinical, and psychosocial factors, if further validated in other patient populations, may help to identify groups of patients at lower risk for nonadherence so that intensified efforts at increased monitoring and intervention can be focused on higher-risk patients. [ABSTRACT FROM AUTHOR]

Background: Evidence that continuous positive airway pressure (CPAP) reduces cardiovascular morbidity comes largely from observational studies. This association may be confounded if CPAP adherents are healthier in ways not measured by investigators. We assessed whether patients adhering to lipid-lowering medications were more adherent to CPAP.Methods: This was a retrospective cohort study undertaken at the Philadelphia Veterans Affairs (VA) Medical Center (2005-2006) of consecutive patients on lipid-lowering therapy newly initiating CPAP for obstructive sleep apnea. Adherence to medications dispensed via the VA closed-pharmacy system was measured as the proportion of days covered (>/=80% vs < 80%) in the year prior to CPAP initiation. CPAP adherence was defined as >/= 4 h/d of "mask-on" time, measured electronically daily during the first week of CPAP. We examined the association between medication adherence and CPAP adherence using multivariable logistic regression.Results: Complete data were available for 117 of 142 (81.5%) subjects. After adjustment for age, race, medical comorbidity, and sleep apnea-related clinical factors, subjects with low medication adherence demonstrated a 40.1% (95% CI, 30.0-51.0) probability of using CPAP >/= 4 h/d compared with 55.2% (95% CI, 46.9-63.1) for subjects with adequate (>/=80%) medication adherence (adjusted for comparison, odds ratio (OR) = 1.8 [95% CI, 1.0-3.3], P = .04). Married patients were more adherent to medications and CPAP; inclusion of this factor reduced to nonsignificance the association of medication and CPAP adherence (OR = 1.6 [95% CI, 0.9-2.8], P = .12).Conclusion: Patients consistently refilling lipid-lowering medications were more adherent to CPAP, suggesting that differences in medication adherence or other health-promoting behaviors should be investigated in future nonrandomized, observational studies linking CPAP adherence and cardiovascular outcomes. [ABSTRACT FROM AUTHOR]