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      The genetics of acute lung injury: looking back and pointing the way forward

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      Author(s): 1 ,
      Publication date (Electronic):
      Journal: Critical Care
      Publisher: BioMed Central

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          Abstract

          Individual genetic factors have long been suspected of playing a major role in susceptibility to acute lung injury and acute respiratory distress syndrome. Flores and colleagues evaluate the quality of published studies testing the relationships between variation in candidate genes and susceptibility to lung injury syndromes or worsened outcome in patients with these conditions. Their results demonstrate that while important advances have been made in this area, attention should be paid to improving the methodology of future studies in order to minimize the chances of publishing false-positive results.

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          A comprehensive review of genetic association studies.

          Joel Hirschhorn, Kirk Lohmueller, Edward Byrne … (2015)
          Most common diseases are complex genetic traits, with multiple genetic and environmental components contributing to susceptibility. It has been proposed that common genetic variants, including single nucleotide polymorphisms (SNPs), influence susceptibility to common disease. This proposal has begun to be tested in numerous studies of association between genetic variation at these common DNA polymorphisms and variation in disease susceptibility. We have performed an extensive review of such association studies. We find that over 600 positive associations between common gene variants and disease have been reported; these associations, if correct, would have tremendous importance for the prevention, prediction, and treatment of most common diseases. However, most reported associations are not robust: of the 166 putative associations which have been studied three or more times, only 6 have been consistently replicated. Interestingly, of the remaining 160 associations, well over half were observed again one or more times. We discuss the possible reasons for this irreproducibility and suggest guidelines for performing and interpreting genetic association studies. In particular, we emphasize the need for caution in drawing conclusions from a single report of an association between a genetic variant and disease susceptibility.
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            Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion.

            B Taylor Thompson, David Christiani, P Boyce … (2005)
            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. Observational prospective cohort. Intensive care unit of Massachusetts General Hospital. We studied 688 patients with sepsis, trauma, aspiration, and hypertransfusion. None. 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
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              Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis

              José Garnacho-Montero, Teresa Aldabo-Pallas, Carmen Garnacho-Montero … (2006)
              Introduction Genetic variations may influence clinical outcomes in patients with sepsis. The present study was conducted to evaluate the impact on mortality of three polymorphisms after adjusting for confounding variables, and to assess the factors involved in progression of the inflammatory response in septic patients. Method The inception cohort study included all Caucasian adults admitted to the hospital with sepsis. Sepsis severity, microbiological information and clinical variables were recorded. Three polymorphisms were identified in all patients by PCR: the tumour necrosis factor (TNF)-α 308 promoter polymorphism; the polymorphism in the first intron of the TNF-β gene; and the IL-10-1082 promoter polymorphism. Patients included in the study were followed up for 90 days after hospital admission. Results A group of 224 patients was enrolled in the present study. We did not find a significant association among any of the three polymorphisms and mortality or worsening inflammatory response. By multivariate logistic regression analysis, only two factors were independently associated with mortality, namely Acute Physiology and Chronic Health Evaluation (APACHE) II score and delayed initiation of adequate antibiotic therapy. In septic shock patients (n = 114), the delay in initiation of adequate antibiotic therapy was the only independent predictor of mortality. Risk factors for impairment in inflammatory response were APACHE II score, positive blood culture and delayed initiation of adequate antibiotic therapy. Conclusion This study emphasizes that prompt and adequate antibiotic therapy is the cornerstone of therapy in sepsis. The three polymorphisms evaluated in the present study appear not to influence the outcome of patients admitted to the hospital with sepsis.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Crit Care
                Title: Critical Care
                Publisher: BioMed Central
                ISSN (Print): 1364-8535
                ISSN (Electronic): 1466-609X
                Publication date (Print): 2009
                Publication date (Electronic): 12 January 2009
                Volume: 13
                Issue: 1
                Page: 108
                Affiliations
                [1 ]Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Bulfinch 148, 55 Fruit Street, Boston, MA 02114, USA
                Article
                Publisher ID: cc7132
                DOI: 10.1186/cc7132
                PMC ID: 2688096
                PubMed ID: 19183434
                SO-VID: eb5677b3-b0a8-419e-8e5e-85240abf9bb9
                Copyright © Copyright © 2009 BioMed Central Ltd
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                Subject: Commentary

                ScienceOpen disciplines: Emergency medicine & Trauma
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                ScienceOpen disciplines: Emergency medicine & Trauma

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