exposure to chrysotile asbestos and smoking: a case-control study within a cohort in China. Occup Environ Med 2010;67:867â871. 9. Frost G, Darnton A, ...
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AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
During the study period, mortality also decreased from a baseline of 21.2% to an impressive 8.7%. Despite limitations related to patient selection (exclusion of patients admitted from the floor) and potential ascertainment bias (addition of prospective screening along with retrospective query using International Classification of Diseases, Ninth Revision codes), the mortality figures are substantially lower than previously reported. However, the mortality improvement in patients who were eligible and compliant with the later bundle elements was similar to that in eligible and noncompliant patients. There are still a few unanswered questions. Does educational intervention alone suffice? Which elements in particular among the resuscitation and maintenance bundle are more significant in improving mortality? In their final multivariate model, the authors conclude that compliance with inotropes/packed red cell transfusion, steroid administration, and the use of a lung-protective ventilation strategy were predictors for improved survival; however, compliance with fluid resuscitation and the presence of septic shock versus severe sepsis did not influence mortality. Unfortunately, data are not provided on the number of subjects who reached the CVP goal or the amount of fluids given to the subjects. Does this mean that fluid administration according to CVP goal can be removed as being part of the resuscitation bundle element? The other question that is debated nationally is whether metrics such as assessment of dynamic and static variables provided noninvasively (ultrasound and passive leg raising) can replace CVP. This study was not designed to determine the effectiveness of specific interventions on progression of sepsis and patient outcomes. Although previous studies have clearly shown improved mortality with increased compliance with the resuscitation bundle elements, none of them were able to achieve all-or-none compliance comparable to Miller and colleagues. How did the investigators achieve this impressive compliance in 11 different participating hospitals? Along with early prompt recognition of severe sepsis/septic shock, active ED collaboration seems to be of paramount importance. In this study, the median ED duration of stay for patients with severe sepsis/septic shock was around 3.5 to 3.7 hours, indicating that most of the early part of the resuscitation bundle elements had to be accomplished in the ED. Also, the sepsis onset time was ED admission, emphasizing again the importance of ED collaboration when undertaking any QI project to improve compliance with the sepsis bundle elements. Although not assessed in this study, the same should hold true for hospital wards or referring hospitals, where the majority of patients with sepsis are located until the very late stages prompting ICU admission (particularly in settings with limited ICU resources). Though the authors briefly discuss the education of healthcare providers, and leadership buy-in for corporate initiative, they unfortunately do not discuss barriers encountered during implementation of the QI intervention and the lessons learned that can be applied to other institutions. We need future studies to test simple innovative ideas for QI interventions that will not only help improve compliance with the sepsis bundle elements, but also be applicable to other hospitals and, more importantly, show sustained compliance once achieved. In summary, the study by Miller and colleagues has definitely set a higher standard by achieving greater compliance with best practices, and thereby improving the quality of care delivered to our patients. The study
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clearly emphasizes the need for the concept of early recognition and treatment of critical illness (“golden hour”), a long-standing mantra in trauma and acute coronary syndrome that should be adopted for all potential life threats, including sepsis. In the words of the late Peter Safar, “the most sophisticated intensive care becomes unnecessarily expensive terminal care once the pre ICU system fails” (9, 10). Redesigning hospital (and prehospital) structure and processes to meet the requirements for early recognition and treatment of critical illness is necessary to reduce preventable errors and complications, increase patient safety, and improve outcomes in a sustainable and costeffective manner. Author disclosures are available with the text of this article at www.atsjournals.org.
Kannan Ramar, M.D. Ognjen Gajic, M.D. Division of Pulmonary and Critical Care Medicine Mayo Clinic Rochester, Minnesota
References 1. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med 2013;41:1167–1174. 2. Lagu T, Rothberg MB, Shieh MS, Pekow PS, Steingrub JS, Lindenauer PK. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med 2012;40:754–761. 3. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368–1377. 4. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, et al.; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580–637. 5. Ferrer R, Artigas A, Levy MM, Blanco J, González-Díaz G, GarnachoMontero J, Ibán˜ez J, Palencia E, Quintana M, de la Torre-Prados MV; Edusepsis Study Group. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA 2008;299:2294–2303. 6. Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med 2010;36:222–231. 7. Schramm GE, Kashyap R, Mullon JJ, Gajic O, Afessa B. Septic shock: a multidisciplinary response team and weekly feedback to clinicians improve the process of care and mortality. Crit Care Med 2011;39:252–258. 8. Miller RR III, Dong L, Nelson NC, Brown SM, Kuttler KG, Probst DR, Allen TL, Clemmer TP; Intermountain Healthcare Intensive Medicine Clinical Program. Multicenter implementation of a severe sepsis and septic shock treatment bundle. Am J Respir Crit Care Med 2013;188:77–82. 9. Hillman K, Chen J, Aneman A. Continuum of hospital care: the role of intensive care. Curr Opin Crit Care 2010;16:505–509. 10. Safar P. Critical care medicine: quo vadis? Crit Care Med 1974;2:1–5. Copyright ª 2013 by the American Thoracic Society DOI: 10.1164/rccm.201304-0801ED
Asbestos and Lung Cancer: What We Know Asbestos is an imprecise term for a group of fibrous minerals that have considerable toxicity for humans when inhaled as dust. Multiple epidemiological studies of populations with
occupational and environmental exposures to respirable asbestos fibers have assessed risk for both pulmonary parenchymal fibrosis (asbestosis) and lung cancer (1, 2). Despite these
Editorials
many studies, controversy about several issues continues (3). First, does asbestos exposure in the absence of cigarette smoking increase the risk of lung cancer? Second, is asbestosis a necessary precondition for asbestos-related lung cancer? Finally, what is the nature of the interaction between asbestos exposure and cigarette smoking regarding lung cancer risk? In a seminal article published in 1968, Irving Selikoff and colleagues reported a striking interaction between occupational exposure to asbestos and cigarette smoking among 370 insulators in the New York metropolitan area (4). They estimated that insulators with a history of both exposures had in excess of a 90-fold increased risk of death due to lung cancer compared with never-smokers in the general U.S. population not occupationally exposed to asbestos. Dr. Selikoff’s group at the Mount Sinai School of Medicine went on to study the mortality experience of the entire North American insulation workers union. In 1979, they reported that among 17,800 insulators followed from 1967 through 1976, there were at least 429 deaths due to lung cancer, with a greater than fourfold increased risk (5). In 1991, these investigators reported on follow-up of this cohort through 1986, with at this point over 1,000 deaths due to lung cancer, a continued fourfold increased risk for the group as a whole, and increasing risk with age (6). These studies were subject to multiple criticisms, including comparison with the mortality experience of the U.S. general population and the lack of adjustment for smoking. In this issue of the Journal, several members of Dr. Selikoff’s team at Mount Sinai (pp. 90–96) have provided further followup of a subgroup of the asbestos insulators cohort (n ¼ 2,377) for whom chest X-ray, spirometric, occupational, and smoking data were available from 1981 to 1983 (7). In addition, Markowitz and colleagues used a comparison group of 54,237 non– asbestos-exposed blue-collar workers from an American Cancer Society cohort study for whom occupational and smoking data were available. By including individual smoking data and an appropriate comparison group, this latest insulator study was designed to address the criticisms noted above. The results of Markowitz and colleagues’ study (7) provide strong confirmation of the findings previously reported by Selikoff and colleagues (3–5). Specifically, from 1981 to 2008, there were 18 deaths due to lung cancer among 468 nonsmoking asbestos-exposed workers, representing a 3.6-fold increased risk compared with nonsmokers in the American Cancer Society cohort. Combined exposure to asbestos and cigarette smoking was associated with an additive effect on lung cancer mortality, with a 14-fold increased risk. The presence of parenchymal asbestosis doubled the risk of lung cancer among nonsmoking insulators and led to a supraadditive 37-fold increase among smoking insulators. The magnitude of the observed asbestos– smoking interaction regarding lung cancer risk is consistent with results from two other reports, greater than additive but less than multiplicative (8, 9). The late Irving Selikoff (1915–1992) has been attacked for misrepresenting his credentials as a physician and being more of an advocate than a scientist (10). The results of this latest insulator mortality study, however, demonstrate that he was essentially right about what he published. By today’s standards, his epidemiological methods were crude, but the insulator mortality data stand undiminished by the test of time. I would argue that time has in fact shown Selikoff to be one of the true public health heroes of the late 20th century. His tenacious voice called public attention to the hazard of asbestos and led the U.S. Occupational Safety and Health Administration to regulate workplace exposure to asbestos, which has saved countless lives. Less
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well known are his vigorous efforts to counsel asbestos insulators to stop smoking. As shown in Markowitz and colleagues’ article (7), this saved lives as well. Moreover, asbestos was not the only hazard that Dr. Selikoff battled. Of particular interest to pulmonary clinicians, he conducted the first clinical trial of isoniazid as an antituberculosis therapy, for which he received a Lasker Award in 1955. Policies to protect workers and the public from harm should be based on data. Reasonable skepticism about the veracity of published data is a feature of the scientific process. This may be especially applicable to observational epidemiological studies. There comes a point, however, when the evidence is sufficient to say that we have achieved knowledge about what the data show. It is the carefully considered opinion of this observer that the results of Markowitz and colleagues’ study, taken together with those of recent and past studies (2, 7–9), allow us to state that we know the following: (1) asbestos exposure alone is capable of causing lung cancer, (2) asbestos exposure and smoking together are associated with an at least additive increased risk; (3) asbestosis further increases the risk in both nonsmoking and smoking asbestos-exposed workers, and (4) smoking cessation substantially decreases the lung cancer risk associated with asbestos exposure. Author disclosures are available with the text of this article at www.atsjournals.org.
John R. Balmes, M.D. Human Exposure Laboratory UCSF Lung Biology Center San Francisco, California
References 1. Guidotti T, Miller A, Christiani D, Wagner G, Balmes J, Harber P, Brodkin CA, Rom W, Hillerdahl G, Harbut M, et al.; American Thoracic Society. Diagnosis and initial management of nonmalignant diseases related to asbestos. Am J Respir Crit Care Med 2004;170:691– 715. 2. Lenters V, Vermeulen R, Dogger S, Stayner L, Portengen L, Burdorf A, Heederik D. A meta-analysis of asbestos and lung cancer: is better quality exposure assessment associated with steeper slopes of the exposure-response relationships? Environ Health Perspect 2011;119: 1547–1555. 3. Mossman BT, Lippmann M, Hesterberg TW, Kelsey KT, Barchowsky A, Bonner JC. Pulmonary endpoints (lung carcinomas and asbestosis) following inhalation exposure to asbestos. J Toxicol Environ Health B Crit Rev 2011;14:76–121. 4. Selikoff IJ, Hammond EC, Churg J. Asbestos exposure, smoking, and neoplasia. JAMA 1968;204:106–112. 5. Selikoff IJ, Hammond EC, Seidman H. Mortality experience of insulation workers in the United States and Canada, 1943–1976. Ann N Y Acad Sci 1979;330:91–116. 6. Selikoff IJ, Seidman H. Asbestos-associated deaths among insulation workers in the United States and Canada, 1967-1987. Ann N Y Acad Sci 1991;643:1–14. 7. Markowitz SB, Levin SM, Miller A, Morabia A. Asbestos, asbestosis, smoking and lung cancer: new findings from the North American insulator cohort. Am J Respir Crit Care Med 2013;188:90–96. 8. Yano E, Wang X, Wang M, Qiu H, Wang Z. Lung cancer mortality from exposure to chrysotile asbestos and smoking: a case-control study within a cohort in China. Occup Environ Med 2010;67:867–871. 9. Frost G, Darnton A, Harding AH. The effect of smoking on the risk of lung cancer mortality for asbestos workers in Great Britain (19712005). Ann Occup Hyg 2011;55:239–247. 10. Seaton A. The strange case of Irving Selikoff. Occup Med (Lond) 2010; 60:53. Copyright ª 2013 by the American Thoracic Society DOI: 10.1164/rccm.201305-0885ED
