Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome. 2016

David S Y Ong, and Cristian Spitoni, and Peter M C Klein Klouwenberg, and Frans M Verduyn Lunel, and Jos F Frencken, and Marcus J Schultz, and Tom van der Poll, and Jozef Kesecioglu, and Marc J M Bonten, and Olaf L Cremer
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. davidsyong@gmail.com.

OBJECTIVE Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate the attributable effect of CMV reactivation on mortality in immunocompetent ARDS patients. METHODS We prospectively studied immunocompetent ARDS patients who tested seropositive for CMV and remained mechanically ventilated beyond day 4 in two tertiary intensive care units in the Netherlands from 2011 to 2013. CMV loads were determined in plasma weekly. Competing risks Cox regression was used with CMV reactivation status as a time-dependent exposure variable. Subsequently, in sensitivity analyses we adjusted for the evolution of disease severity until onset of reactivation using marginal structural modeling. RESULTS Of 399 ARDS patients, 271 (68%) were CMV seropositive and reactivation occurred in 74 (27%) of them. After adjustment for confounding and competing risks, CMV reactivation was associated with overall increased ICU mortality (adjusted subdistribution hazard ratio (SHR) 2.74, 95% CI 1.51-4.97), which resulted from the joint action of trends toward an increased mortality rate (direct effect; cause specific hazard ratio (HR) 1.58, 95% CI 0.86-2.90) and a reduced successful weaning rate (indirect effect; cause specific HR 0.83, 95% CI 0.58-1.18). These associations remained in sensitivity analyses. The population-attributable fraction of ICU mortality was 23% (95% CI 6-41) by day 30 (risk difference 4.4, 95% CI 1.1-7.9). CONCLUSIONS CMV reactivation is independently associated with increased case fatality in immunocompetent ARDS patients who are CMV seropositive.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009426 Netherlands Country located in EUROPE. It is bordered by the NORTH SEA, BELGIUM, and GERMANY. Constituent areas are Aruba, Curacao, and Sint Maarten, formerly included in the NETHERLANDS ANTILLES. Holland,Kingdom of the Netherlands
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D012121 Respiration, Artificial Any method of artificial breathing that employs mechanical or non-mechanical means to force the air into and out of the lungs. Artificial respiration or ventilation is used in individuals who have stopped breathing or have RESPIRATORY INSUFFICIENCY to increase their intake of oxygen (O2) and excretion of carbon dioxide (CO2). Ventilation, Mechanical,Mechanical Ventilation,Artificial Respiration,Artificial Respirations,Mechanical Ventilations,Respirations, Artificial,Ventilations, Mechanical
D012128 Respiratory Distress Syndrome A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA. ARDS, Human,Acute Respiratory Distress Syndrome,Adult Respiratory Distress Syndrome,Pediatric Respiratory Distress Syndrome,Respiratory Distress Syndrome, Acute,Respiratory Distress Syndrome, Adult,Respiratory Distress Syndrome, Pediatric,Shock Lung,Distress Syndrome, Respiratory,Distress Syndromes, Respiratory,Human ARDS,Lung, Shock,Respiratory Distress Syndromes,Syndrome, Respiratory Distress
D003586 Cytomegalovirus Infections Infection with CYTOMEGALOVIRUS, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. CMV Inclusion,CMV Inclusions,Congenital CMV Infection,Congenital Cytomegalovirus Infection,Cytomegalic Inclusion Disease,Cytomegalovirus Colitis,Cytomegalovirus Inclusion,Cytomegalovirus Inclusion Disease,Cytomegalovirus Inclusions,Inclusion Disease,Perinatal CMV Infection,Perinatal Cytomegalovirus Infection,Renal Tubular Cytomegalovirus Inclusion,Renal Tubular Cytomegalovirus Inclusions,Salivary Gland Virus Disease,Severe Cytomegalovirus Infection,Severe Cytomegalovirus Infections,Infections, Cytomegalovirus,CMV Infection, Congenital,CMV Infection, Perinatal,Colitis, Cytomegalovirus,Congenital CMV Infections,Congenital Cytomegalovirus Infections,Cytomegalic Inclusion Diseases,Cytomegalovirus Colitides,Cytomegalovirus Inclusion Diseases,Cytomegalovirus Infection,Cytomegalovirus Infection, Congenital,Cytomegalovirus Infection, Perinatal,Cytomegalovirus Infection, Severe,Cytomegalovirus Infections, Severe,Disease, Cytomegalic Inclusion,Disease, Cytomegalovirus Inclusion,Diseases, Cytomegalovirus Inclusion,Inclusion Disease, Cytomegalic,Inclusion Disease, Cytomegalovirus,Inclusion Diseases,Inclusion Diseases, Cytomegalovirus,Inclusion, CMV,Inclusion, Cytomegalovirus,Infection, Congenital CMV,Infection, Congenital Cytomegalovirus,Infection, Cytomegalovirus,Infection, Perinatal CMV,Infection, Perinatal Cytomegalovirus,Infection, Severe Cytomegalovirus,Perinatal CMV Infections,Perinatal Cytomegalovirus Infections
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly

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