acute pancreatitis is an inflammatory disease characterized by the presence of acute abdominal pain and/or increased levels of serum pancreatic enzymes .
more importantly , takeda et al .   have indicated that the mortality rate was of approximately 20% when acute pancreatitis developed to severe acute pancreatitis ( sap ) .
similarly , several lines of evidence have demonstrated that systemic inflammatory response syndrome ( sirs ) and multiple - organ dysfunction syndrome ( mods ) are the 2 most common causes of death in the early stage ( within approximately 2 weeks ) of patients with sap .
previous research has suggested that acute respiratory distress syndrome ( ards ) , which is a clinical manifestation of lung injury , is one of the earliest manifestations of functional deterioration in human organs and is one of the most common and serious complications of sap .
the most severe clinical manifestations of ards exhibit significant hypoxemia with bilateral pulmonary infiltrates consistent with edema . currently , the criteria for the diagnosis of ards are mainly based on the berlin definition , which includes the original diagnosis of acute lung injury ( ali ) and ards : acute onset of respiratory distress , hypoxemia ( ali : pao2/fio2  300 mmhg , ards : pao2/fio2  200 mmhg ) , bilateral consolidation of chest radiograph , and absence of clinical findings of cardiogenic pulmonary edema . in practice ,
the complexity of multiple - item criteria of ards often causes inconvenience for physicians in the management of patients with sap .
if ards also causes changes in several related bio - markers , similar to the characteristic elevation of troponin in myocardial infarction , this bio - marker might be useful to help diagnose of sap - induced ards .
previous reports indicate that pulmonary surfactant consists principally of various lipids and proteins ( surfactant proteins ) .
furthermore , the major constituent of surfactant proteins is sp - a , and the remainder includes sp - b , sp - c , and sp - d .
recently , a study suggested that sp - a is a large multimeric protein found in the airways and alveoli .
several lines of evidence have shown that sp - a not only mediates the inflammatory response , but also controls vascular permeability , which are considered to be important factors in the development of ards .
a large number of studies   have shown that sp - a levels in bronchoalveolar lavage fluid ( balf ) are significantly lower in patients with bleomycin - induced ards compared with healthy volunteers . in contrast , the serum levels of sp - a were raised in patients with bleomycin - induced ards .
thus , the serum levels of sp - a may be suggested as a sensitive and specific serum marker on the diagnosis of sap - induced ards .
it has been suggested that the presence of qualitatively assessed ( yes or no ) diffuse alveolar damage ( dad ) should be considered the criterion standard for the diagnosis of ards . to improve the early detection and diagnosis of sap - induced ards , determination of serum levels of sp - a in sap - induced ards rats was used . in the present study ,
we therefore evaluated serum sp - a levels according to the criterion standard for the diagnosis of ards to evaluate the qualitative assessment of presence of diffuse alveolar damage ( dad ) in the diagnosis of sap - induced ards in an animal model .
one hundred male wistar rats weighing 250300 g were purchased from cavens laboratory animal company , changzhou , jiangsu , china .
six rats were housed per cage with food and water available ad libitum and maintained on a 12-h light / dark cycle ( lights on at 07:00 am ) .
eighty rats were randomly divided into 2 groups ( n=40 each ) : the sham - operated ( so group ) and the severe acute pancreatitis ( sap group ) and then randomly subdivided into 1-h , 2-h , 3-h , and 4-h subgroups , with 10 rats in each subgroup .
the rats in the 1-h , 2-h , 3-h , and 4-h subgroups of the sap group , a total of 40 rats , were subdivided into a sap - induced ards group ( ards group ) and a sap without ards group ( non - ards group ) according to the diagnosis   of ards for lung tissue , including the presence of dad , qualitatively assessed ( yes or no ) after the operation .
the other 20 rats were regarded as the  baseline  and euthanized without any operation in initial experiments .
intra - peritoneal injection of 1% sodium pentobarbital ( 50 mg / kg ; sigma , st .
louis , mo , usa ) was used for abdominal cavity anesthesia to all rats of the 1-h , 2-h , 3-h , 4-h subgroups .
animal care was in accordance with the national institutes of health guide for the care and use of laboratory animals , and was approved by the animal use and protection committee of soochow university .
the abdominal surgery of the so group ( n=40 ) consisted of opening the abdomen , flipping the pancreas , returning them to their original position , then closing the abdominal cavity with 2 layers of sutures .
louis , mo , usa ) was administered into the common biliopancreatic duct of the sap group ( n=40 ) by retrograde injection .
we identified the duodenal papilla inside the duodenum duct wall , and then used a no .
a segmental epidural catheter was inserted into the duodenum cavity through the hole , and inserted retrogradely into the biliary - pancreatic duct through the papilla .
this was followed by retrograde transfusion of 4.5% sodium taurocholate solution ( 4.5% ; 0.1 ml/100 g ) by a microinjection pump at 0.1 ml / min .
all rats of the 2 groups were injected with normal saline ( 20 ml / kg ) through the vena caudalis to compensate for loss of fluid during surgery .
the rats in all groups were euthanized at 1 , 2 , 3 and 4 hours , according to the subgroup , after the operation .
blood samples ( 5 ml ) were collected from the heart , and were mixed with edta anticoagulative liquor , then were centrifuged at 3000
sera of their blood samples were collected and maintained at 4c for the detection of sp - a .
serum levels of sp - a were determined by the elisa method by using the  rat sp - a elisa kit  purchased from mybiosource ( san diego , california , usa ) .
the antigens were measured by elisa inhibition assays using antibodies raised against alveolar proteinosis - derived sp - a .
briefly , in order to free the sp - a from any associated plasma or surfactant components , aliquots were first treated with edta , sds , and triton x-100 .
serial dilutions of the samples in pbst containing 0.25% bsa ( w / v ) were incubated in an elisa plate with aliquots of the respective antibody .
free antibody was captured using a second elisa plate coated with purified sp - a ( 1 g / ml ) and the amount measured using alkaline phosphatase conjugated igg against rabbit immunoglobulins and 15 mm disodium p - nitrophenyl phosphate in 1.0 m diethanolamine and 0.5 mm mgcl 2 as a substrate .
after 1 h , the absorbance of the substrate was measured at 405 nm using a dynatech mr5000 reader ( dynatech laboratories , chantilly , va , usa ) . the assayzap program (
biosoft , ferguson , mo , usa ) was used to generate a standard curve and to compute the concentration of sp - a in each sample .
standards , assayed in quadruplicate , were included in each elisa plate at 8 serial dilutions ( range 1.95250 ng / ml for sp - a , r>0.99 ) .
the antibodies used do not react with any other known antigens and the assays have coefficients of variance of ~6% .
rat pancreatic and lung tissues were collected , fixed in 10% formalin , embedded in paraffin , and sectioned into 4- sections , after which they were stained by hematoxylin and eosin ( h&e ) staining for histopathological observation .
histopathology of the pancreas and lungs was scored and classified by 2 professional pathologists using a double - blind method .
each group randomly selected 3 slices ; for each slice , 10 high - power fields of vision were again randomly selected , and finally the extent of pancreatic tissue damage by edema , infection , hemorrhage , and necrosis were evaluated . the pathological score for pancreatic tissue was calculated according to rongiones standards   as a reference , with a minimum score of 0 and the highest score of 4 .
the pathological grade for lung tissue was according to lei   as a reference , with a minimum grade of 0 and the highest grade of iii .
criteria for the diagnosis of ards for lung tissue included the presence of diffuse alveolar damage ( dad ) , qualitatively assessed ( yes / positive result or no / negative result ) as : intra - alveolar edema , alveolar type i cell necrosis , alveolar type ii cell ( cuboidal cells ) proliferation progressively covering the denuded alveolar - capillary membrane , interstitial proliferation of fibroblasts and myofibroblasts , or organizing interstitial fibrosis .
values of sp - a for ards were determined by the receiver operating characteristic curve ( roc ) .
the comparison among multiple groups was analyzed with 1-dimensional analysis of variance after data conversion .
ards group and so group + non - ards group  was tested with nonparametric rank sum test .
true- positive ( tp ) was defined as sp - a values higher than the cut - off value in rats with sap induced - ards groups ( ards group ) .
false - negative ( fn ) included rats with ards but who scored negative . sensitivity and specificity
formulas for calculation were : sensitivity = tp/(tp+fn)100% , specificity = tn/(tn+fp)100% , diagnostic accuracy=(tp+tn)/(tp+fp+tn+fn)100% , positive predictive value = tp/(tp+fp ) 100% , and negative predictive value = tn/(tn+fn)100% .
one hundred male wistar rats weighing 250300 g were purchased from cavens laboratory animal company , changzhou , jiangsu , china .
six rats were housed per cage with food and water available ad libitum and maintained on a 12-h light / dark cycle ( lights on at 07:00 am ) .
eighty rats were randomly divided into 2 groups ( n=40 each ) : the sham - operated ( so group ) and the severe acute pancreatitis ( sap group ) and then randomly subdivided into 1-h , 2-h , 3-h , and 4-h subgroups , with 10 rats in each subgroup .
the rats in the 1-h , 2-h , 3-h , and 4-h subgroups of the sap group , a total of 40 rats , were subdivided into a sap - induced ards group ( ards group ) and a sap without ards group ( non - ards group ) according to the diagnosis   of ards for lung tissue , including the presence of dad , qualitatively assessed ( yes or no ) after the operation .
the other 20 rats were regarded as the  baseline  and euthanized without any operation in initial experiments .
intra - peritoneal injection of 1% sodium pentobarbital ( 50 mg / kg ; sigma , st .
louis , mo , usa ) was used for abdominal cavity anesthesia to all rats of the 1-h , 2-h , 3-h , 4-h subgroups .
animal care was in accordance with the national institutes of health guide for the care and use of laboratory animals , and was approved by the animal use and protection committee of soochow university .
the abdominal surgery of the so group ( n=40 ) consisted of opening the abdomen , flipping the pancreas , returning them to their original position , then closing the abdominal cavity with 2 layers of sutures .
louis , mo , usa ) was administered into the common biliopancreatic duct of the sap group ( n=40 ) by retrograde injection .
we identified the duodenal papilla inside the duodenum duct wall , and then used a no .
a segmental epidural catheter was inserted into the duodenum cavity through the hole , and inserted retrogradely into the biliary - pancreatic duct through the papilla .
this was followed by retrograde transfusion of 4.5% sodium taurocholate solution ( 4.5% ; 0.1 ml/100 g ) by a microinjection pump at 0.1 ml / min .
all rats of the 2 groups were injected with normal saline ( 20 ml / kg ) through the vena caudalis to compensate for loss of fluid during surgery .
the rats in all groups were euthanized at 1 , 2 , 3 and 4 hours , according to the subgroup , after the operation .
blood samples ( 5 ml ) were collected from the heart , and were mixed with edta anticoagulative liquor , then were centrifuged at 3000
sera of their blood samples were collected and maintained at 4c for the detection of sp - a .
serum levels of sp - a were determined by the elisa method by using the  rat sp - a elisa kit  purchased from mybiosource ( san diego , california , usa ) .
the antigens were measured by elisa inhibition assays using antibodies raised against alveolar proteinosis - derived sp - a .
briefly , in order to free the sp - a from any associated plasma or surfactant components , aliquots were first treated with edta , sds , and triton x-100 .
serial dilutions of the samples in pbst containing 0.25% bsa ( w / v ) were incubated in an elisa plate with aliquots of the respective antibody .
free antibody was captured using a second elisa plate coated with purified sp - a ( 1 g / ml ) and the amount measured using alkaline phosphatase conjugated igg against rabbit immunoglobulins and 15 mm disodium p - nitrophenyl phosphate in 1.0 m diethanolamine and 0.5 mm mgcl 2 as a substrate .
after 1 h , the absorbance of the substrate was measured at 405 nm using a dynatech mr5000 reader ( dynatech laboratories , chantilly , va , usa ) . the assayzap program (
biosoft , ferguson , mo , usa ) was used to generate a standard curve and to compute the concentration of sp - a in each sample .
standards , assayed in quadruplicate , were included in each elisa plate at 8 serial dilutions ( range 1.95250 ng / ml for sp - a , r>0.99 ) .
the antibodies used do not react with any other known antigens and the assays have coefficients of variance of ~6% .
rat pancreatic and lung tissues were collected , fixed in 10% formalin , embedded in paraffin , and sectioned into 4- sections , after which they were stained by hematoxylin and eosin ( h&e ) staining for histopathological observation .
histopathology of the pancreas and lungs was scored and classified by 2 professional pathologists using a double - blind method .
each group randomly selected 3 slices ; for each slice , 10 high - power fields of vision were again randomly selected , and finally the extent of pancreatic tissue damage by edema , infection , hemorrhage , and necrosis were evaluated .
the pathological score for pancreatic tissue was calculated according to rongiones standards   as a reference , with a minimum score of 0 and the highest score of 4 . the pathological grade for lung tissue was according to lei   as a reference , with a minimum grade of 0 and the highest grade of iii .
criteria for the diagnosis of ards for lung tissue included the presence of diffuse alveolar damage ( dad ) , qualitatively assessed ( yes / positive result or no / negative result ) as : intra - alveolar edema , alveolar type i cell necrosis , alveolar type ii cell ( cuboidal cells ) proliferation progressively covering the denuded alveolar - capillary membrane , interstitial proliferation of fibroblasts and myofibroblasts , or organizing interstitial fibrosis .
values of sp - a for ards were determined by the receiver operating characteristic curve ( roc ) .
the comparison among multiple groups was analyzed with 1-dimensional analysis of variance after data conversion .
ards group and so group + non - ards group  was tested with nonparametric rank sum test .
true- positive ( tp ) was defined as sp - a values higher than the cut - off value in rats with sap induced - ards groups ( ards group ) .
false - negative ( fn ) included rats with ards but who scored negative . sensitivity and specificity
formulas for calculation were : sensitivity = tp/(tp+fn)100% , specificity = tn/(tn+fp)100% , diagnostic accuracy=(tp+tn)/(tp+fp+tn+fn)100% , positive predictive value = tp/(tp+fp ) 100% , and negative predictive value = tn/(tn+fn)100% .
the glandular architecture of the pancreas in the so group was entirely normal ( h&e ) ( figure 1 ) .
the architecture of the lung in the so group was entirely normal ( h&e ) ( figure 2 ) .
histopathologic features of the pancreas in the sap group included various degrees of edema , minimal necrosis , and inflammatory infiltration ( h&e ) ( figure 3 ) . according to the criteria for the diagnosis of ards ,
the presence of dad was qualitatively assessed ( yes or no ) ; in the 1-h , 2-h , 3-h , and 4-h subgroups we found 1 , 5 , 9 , and 10 cases of ards , respectively .
therefore , the sap group was then subdivided into the ards group ( 25 rats ) and non - ards group ( 15 rats ) according to the criteria for the diagnosis of ards .
histopathologic features of lung in the ards group included the presence of dad , intra - alveolar edema , and organizing interstitial fibrosis ( h&e ) ( figure 4 ) .
serum sp - a levels ( means sd ) in the baseline , so , and sap groups were 43.1514.29 , 51.9116.99 , and 193.435.37
. there was no statistical difference between so group and baseline in serum sp - a levels ( p>0.05 ) .
serum sp - a levels of the sap group were significantly increased compared to baseline and so group ( * p<0.05 , p<0.05 ) ( figure 5 ) .
serum sp - a levels ( means sd ) in the so group , ards group , and non - ards group were 51.9116.99 , 198.029.73 , and 185.743.21 ug / ml , respectively .
serum sp - a levels were significantly increased from the ards group to the so group ( * p<0.05 ) and from the non - ards group to the so group ( p<0.05 ) .
there was no statistical difference between the ards group and non - ards group in serum sp - a levels ( p>0.05 ) ( figure 6 ) . according to the analysis of roc curves ,
the best cut - off value for the serum sp - a level for the diagnosis of sap - induced ards was 150 ug / ml . in analysis of all sap - induced ards rats , the area under the roc curve of sp - a was 0.88 ( figure 7 ) . the sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of sp - a in the diagnosis of sap - induced ards were 100.0% , 81.8% , 71.4% , 100.0% , and 87.5% , respectively ( table 1 ) .
the glandular architecture of the pancreas in the so group was entirely normal ( h&e ) ( figure 1 ) .
the architecture of the lung in the so group was entirely normal ( h&e ) ( figure 2 ) .
histopathologic features of the pancreas in the sap group included various degrees of edema , minimal necrosis , and inflammatory infiltration ( h&e ) ( figure 3 ) . according to the criteria for the diagnosis of ards ,
the presence of dad was qualitatively assessed ( yes or no ) ; in the 1-h , 2-h , 3-h , and 4-h subgroups we found 1 , 5 , 9 , and 10 cases of ards , respectively .
therefore , the sap group was then subdivided into the ards group ( 25 rats ) and non - ards group ( 15 rats ) according to the criteria for the diagnosis of ards .
histopathologic features of lung in the ards group included the presence of dad , intra - alveolar edema , and organizing interstitial fibrosis ( h&e ) ( figure 4 ) .
serum sp - a levels ( means sd ) in the baseline , so , and sap groups were 43.1514.29 , 51.9116.99 , and 193.435.37 ug / ml , respectively .
there was no statistical difference between so group and baseline in serum sp - a levels ( p>0.05 ) .
serum sp - a levels of the sap group were significantly increased compared to baseline and so group ( * p<0.05 , p<0.05 ) ( figure 5 ) .
serum sp - a levels ( means sd ) in the so group , ards group , and non - ards group were 51.9116.99 , 198.029.73 , and 185.743.21 ug / ml , respectively .
serum sp - a levels were significantly increased from the ards group to the so group ( * p<0.05 ) and from the non - ards group to the so group ( p<0.05 ) .
there was no statistical difference between the ards group and non - ards group in serum sp - a levels ( p>0.05 ) ( figure 6 ) .
according to the analysis of roc curves , the best cut - off value for the serum sp - a level for the diagnosis of sap - induced ards was 150 ug / ml . in analysis of all sap - induced ards rats , the area under the roc curve of sp - a was 0.88 ( figure 7 ) . the sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of sp - a in the diagnosis of sap - induced ards were 100.0% , 81.8% , 71.4% , 100.0% , and 87.5% , respectively ( table 1 ) .
in the present study , we evaluated serum sp - a levels for the diagnosis of sap - induced ards in a rat model .
importantly , the sap - induced ards rat model is mostly suitable for investigating the effectiveness and specificity of a particular therapeutic approach .
the model that we chose had to be similar to the etiology and convenient for the experimental operations .
some models focus on etiology , such as the duct ligation model and the taurocholate - induced pancreatitis model .
but the latter is more simple , and less damaging to the animals , which mimic biliary pancreatitis in the clinical setting better than the duct ligation model .
several lines of evidence have indicated that the taurocholate - induced pancreatitis model induced by ards was successfully 34 h after the operation .
thus , we constructed this model by using sodium taurocholate solution injected into the common biliopancreatic duct . according to the criteria for the diagnosis of ards , 1 , 5 , 9 , and 10 cases of ards
were determined as positive results in the 1-h , 2-h , 3-h , and 4-h subgroups , respectively .
the results of the present study are consistent with previous findings that sap leading to a systemic inflammatory response was characterized by widespread leukocyte activation and distant organ injury ( e.g. , ards ) [ 2628 ] .
our previous study showed that a definite correlation exists between pathological changes ( pancreas and lung ) and progression of sap . in the present study
, we found that the glandular architecture of the pancreas and the architecture of the lung in the so group were entirely normal ( h&e ) ( figures 1 and 2 ) .
furthermore , histopathologic features of the pancreas , various degrees of edema , minimal necrosis , and inflammatory infiltration ( h&e ) were detected in glandular architecture of the pancreas in the sap group ( figure 3 ) .
the sap group was subdivided into the ards group ( 25 rats ) and non - ards group ( 15 rats ) according to criteria including presence of dad , intra - alveolar edema , and organizing interstitial fibrosis ( h&e ) ( figure 4 ) .
these results are similar to findings of the present study , suggested that the cases of positive results , which included the presence of dad , was qualitatively assessed ( yes or no ) , showing an increasing trend associated with longer time in the preceding 4 h in the rat model of sap - induced ards .
this gap in serum levels of sp - a has previously been reported in many studies , with the results being similar to those in the present study  baseline , 43.1514.29 ug / ml vs. so group 51.9116.99 ug / ml vs. sap group 193.435.37 ug / ml ( figure 5 ) ; so group , 51.9116.99 ug / ml vs. ards group 198.029.73 ug / ml vs. non - ards group 185.743.21 ug / ml ( figure 6 ) .
these findings demonstrated that ards , the most common and serious complications of sap , was induced in the sap group and contributed to an elevation of sp - a in serum in this study .
however , the underlying mechanism has not yet been fully elucidated and may be related to multiple factors .
we propose that the possible mechanisms include epithelial injury and leak  increased secretion of sp - a per type ii cell , increased leakage from the airspace to the interstitium , an increase in total number of type ii cells per lung due to diffuse hyperplasia , and decreased clearance from the vascular compartment .
in addition , the degree of lung injury and sp - a levels leaked from the airspace to the serum was similar in the ards group and non - ards group .
moreover , the presence of dad was not observed in the non - ards group because of multiple factors , such as the time of lung injury , individual differences , and the degree of lung injury , rather than the absence of lung injury .
found that serum sp - a levels are upregulated by an acute inflammatory stress ; therefore , we used determination of serum levels of sp - a to diagnose sap - induced ards in the rat model .
our data analysis showed that sp - a>150 ug / ml statistically discriminates between sap - induced ards and other groups ( so group and non - ards group ) with 100.0% sensitivity and 81.8% specificity . at this cut - off value ,
the diagnostic accuracy was the highest , and the area under the roc curve of sp - a was 0.88 ( figure 7 ) .
furthermore , sp - a>150 ug / ml was diagnosed as sap - induced ards with 71.4% positive predictive value , 100.0% negative predictive value , and 87.5% accuracy in this study .
these data demonstrated that the accuracy of diagnosis of sp - a for sap - induced ards is relatively high .
therefore , the sp - a , as lung - specific bioactive surface proteins , are valuable parameters for the prediction of sap - induced ards .
interestingly , because it is impossible to collect the human pancreatic and lung tissues in the clinical course of treatment , there is little data on this value .
we , therefore consider that our findings can be extrapolated to other animals and to humans .
although further clinical studies are required to confirm this , rats with sp - a greater than 150 ug / ml and high pulmonary vascular permeability index may be typical for sap - induced ards .
in addition , ellsa can detect small changes in sp - a content and serum sp - a level can be easily , quickly , and repeatedly measured at the bedside .
serum sp - a level correlates with the progression of lung injury and predicts progression to ards in patients with increased risk .
thus , serum sp - a was chosen in this study as the first validated quantitative measure for sap - induced ards and we believe that monitoring serum sp - a level in peripheral blood of sap patients is helpful to evaluate whether sap induces ards .
the serum levels of sp - a may be useful as a sensitive and specific serum marker for the diagnosis of sap - induced ards , as confirmed in the present study .
however , a great limitation of the present study is that we did not observe the long - term clinical significance , and future studies are required to investigate this .
 backgroundthe complexity of multiple - item criteria in acute respiratory distress syndrome ( ards ) often causes inconvenience for physicians in the management of patients with severe acute pancreatitis ( sap ) . 
 we evaluated whether serum sp - a levels in the presence of diffuse alveolar damage ( dad ) can be qualitatively assessed for diagnosis of sap - induced ards.material/methodseighty rats were randomly divided into 2 groups ( n=40 each )  the sham - operated ( so ) group and the sap group  and then randomly subdivided into 4 subgroups in a time - course manner . 
 furthermore , rats in the sap group were subdivided into the sap induced - ards group ( ards group ) and the sap without ards group ( non - ards group ) according to the diagnostic standard of ards . the diagnostic cut - off 
 values of sp - a for sap - induced ards were determined by the receiver operating characteristic curve ( roc).resultsserum sp - a levels in baseline , so group , sap group , ards group , and non - ards group were 43.1514.29 , 51.9116.99 , 193.435.37 , 198.0 + 29.73 , and 185.743.21 ug / ml , respectively . 
 the best cut - off value for the serum sp - a level for the diagnosis of sap - induced ards was 150 ug / ml and the area under the roc curve of sp - a was 0.88 . the sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of sp - a in the diagnosis of sap - induced ards were 100.0% , 81.8% , 71.4% , 100.0% , and 87.5% , respectively.conclusionsserum sp - a levels may allow the detection of sap - induced ards and may help to support the clinical diagnosis of ards . the optimal serum sp - a cut - off value to discriminate sap - induced ards and other groups ( so group and non - ards group ) is around 150 ug / ml . 
Background
Material and Methods
Animals and groups
SAP and ARDS induction
Determination of serum SP-A levels
Pathologic criteria for pancreas and lung tissues
Statistical analysis
Results
Expression of pathology in pancreas and lung tissues
Expression of Serum SP-A levels
Diagnosis of SP-A according to ROC curves
Discussion
Conclusions