BOSTON – Higher levels of nasopharyngeal lactate dehydrogenase were associated with decreased odds of hospitalization in a prospective, observational, multicenter cohort study of samples from 277 children under 2 years of age who presented to the emergency department with bronchiolitis.
"Despite identified risk factors for severe disease, the difficulty and uncertainty of determining the appropriate level of supportive care for children with bronchiolitis is well documented by the large variability in hospital admission practices. Admission rates for infants with bronchiolitis are significantly different between pediatric and general EDs and even among pediatric ED attending physicians. There is also wide variation in thresholds for pediatric intensive care unit admission and intubation," said Dr. Jonathan M. Mansbach, a hospitalist physician at Children’s Hospital Boston at the annual meeting of the Society for Academic Emergency Medicine.
Recent studies suggest that lactate dehydrogenase (LDH), a membrane-associated protein released from injured cells that is a marker of inflammatory response, correlates with innate immunity and could therefore be used as a predictor of disease severity. In one recent single-center study of 98 children aged less than 2 years presenting to the ED with bronchiolitis, serum LDH was not predictive of admission, but higher levels of nasopharyngeal LDH were associated with an 81% reduced risk of hospital admission (Pediatrics 2010;125:e225-33).
The current study is part of the larger Multicenter Airway Research Collaboration (MARC), a program of the Emergency Medicine Network. The primary aim of the MARC-25 Virology Study is to describe virology of children presenting to the ED with bronchiolitis using nasopharyngeal aspirate (NPA) samples (Acad. Emerg. Med. 2008;15:111-8).
Nasopharyngeal aspirate samples were collected between December 2005 and March 2006 at 14 centers in 10 states. The 277 children had a median age of 6 months. More than half (61%) were boys; 37% were Hispanic, 31% white, 28% black, and 4% other. The median value of NPA LDH was 7 U/mL but the range was wide, 0-8,400 U/mL. "Nasopharyngeal LDH is a new test. Therefore, when considering the actual values for LDH, please remember that there are no known standards," Dr. Mansbach commented.
Of the study cohort, 45% (125 children) were admitted to the hospital, and of those, 74% (93) were admitted for longer than 24 hours. For the entire 0-8,400 U/mL range, higher LDH values were associated with a lower rate of admission for 24 hours or longer. However, there were two outlier patients. With those two removed, the LDH range dropped to 0-1,000 and the inverse relationship between LDH and admission remained, but there was a blunting of the association at higher levels of LDH.
The rest of the analysis was limited to patients with the two most common viral etiologies, respiratory syncytial virus (64%) and rhinovirus (16%). The low frequency of infections with human metapneumovirus and influenza did not affect the results, he noted.
In the 176 children with RSV, the median LDH values were higher but not significantly higher than in the 101 children without RSV, 8 vs. 4 U/mL (P = .53). However, in the 44 children with rhinovirus, median LDH values were significantly higher than in children without rhinovirus, 14 vs. 5 U/mL (P = .03).
Moving from the first to the third LDH quartile after adjustment for common variables associated with illness severity (age less than 2 months, sex, history of intubation, retractions, oxygen saturation 94% or below), there was a fairly linear drop in the odds of admission. With the quartile of 1.33 U/mL and below as the referent 1.0, those with LDH levels 1.34-6.6 U/mL had an adjusted odds ratio of admission of 0.58 (P = .23, confidence interval 0.24-1.4), while the adjusted odds ratio for those with LDH 6.7-43.2 U/mL was 0.23 (P = .002, confidence interval 0.09-0.58). The difference was no longer significant for LDH of 43.3 U/mL or above (P = .33, 0.28-1.5). Stratification by virus or site did not change the outcomes, Dr. Mansbach added.
"We do not know why the association is blunted at the highest level of LDH, and more research will be needed to sort through this aspect of our findings. Remember that the test still shows that higher levels of LDH are associated with fewer admissions. It was just blunted, with slightly lower magnitude, so it could still be clinically useful," he said in an interview.
Dr. Mansbach stated that he has no conflicts of interest.