Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity

Mehta, Reena; Scheffler, Margaret; Tapia, Lorena; Aideyan, Letisha; Patel, Kirtida D; Jewell, Alan M; Avadhanula, Vasanthi; Mei, Minghua; Garofalo, Roberto P; Piedra, Pedro A

As has been demonstrated previously, 13 there was a strong correlation (r = 0Á77, P ≤ 0Á0001) between NW-LDH and NW-caspase 3/7 activity, illustrated in Figure 3 . Interestingly, NW-caspase 3/7 activity differences among the disposition groups were not significant (P = 0Á4). However, NW-caspase 3/7 activity varied significantly by virus type (RSV only, RV only, RSV + RV or others, P = 0Á004), as seen in Figure 2B . Those patients infected with RSV only had the highest caspase level in their nasal washes (mean AE SD, 4Á48 AE 0Á58), compared with those co-infected with both RSV and RV (4Á21 AE 0Á54), RV only (4Á17 AE 0Á52) or other types of viruses (3Á91 AE 0Á88). In addition, the NW-LDH/ NW-caspase 3/7 ratio difference between the disposition groups did not achieve statistical significance (P = 0Á07). However, when the children were divided into two disposition groups, hospitalized or not, the NW-LDH to NWcaspase 3/7 ratio in the hospitalized group was significantly higher (mean AE SD, 1Á15 AE 0Á48, median, 1Á15) than those children not hospitalized (1Á01 AE 0Á39, median 0Á98, P = 0Á03). Multivariable logistic regression analyses were conducted using disposition of the patients (home, ACU, and ICU) as the primary outcome to identify demographic and biomarker variables that contributed to disposition. The analysis demonstrated that (i) Children younger than 3 months were more likely to be admitted to the ACU (OR: 3Á87, 95% CI: 1Á11-13Á50) versus being sent home compared to children older than 12 months; (ii) Compared with children who presented on day 6 of illness or later, children presenting on days 3-5 of symptoms were significantly more likely to be admitted to either the ACU (OR: 4Á07, 95% CI: 1Á34-12Á36) or ICU (OR 3Á69, 95% CI: 1Á14-11Á90); (iii) A one-unit increase in NW-LDH (log10, mU/l) was associated with an increased likelihood of admission to either the ACU (OR: 6Á68, 95% CI: 1Á53-29Á29) or ICU (OR 6Á10, 95% CI: 1Á28-28Á99); (iv) By contrast, a one-unit increase in NW-caspase 3/7 activity (log10, U/l) was associated with a decreased likelihood to be admitted to the ACU (OR: 0Á33, 95% CI: 0Á11-0Á96). Three multiple linear regression models were constructed to evaluate the demographic, clinical and virologic variables impacting our biomarkers of interest ( Table 3 ). The independent variables and interaction terms providing the best Rsquare value were used to construct the models. R-squared values indicate that the models explained 73Á2%, 72Á2%, and 32Á0% of the variation for NW-LDH, NW-caspase, and NW-LDH/caspase ratio, respectively. The b coefficient and standard error are shown for each of the independent variables; an asterisk indicates significant variables. The results indicate male children had higher NW-LDH compared with females; Hispanic children had lower NW-LDH and NW-LDH/caspase 3/7 ratio compared to non-Hispanic children; higher NW-LDH and NW-LDH/NW-caspase 3/7 ratio was significantly associated with ACU admission; NWcaspase 3/7 activity was inversely associated with ACU admission; NW-LDH was significantly lower, and NWcaspase 3/7 significantly higher, in children with an identifiable pathogen; and NW-LDH was highly associated with NW-caspase 3/7.