Histopathologic and Immunohistochemical Assessment of Acute Respiratory Distress Syndrome (ARDS): Challenges and Complexities of Postmortem Diagnosis.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition due to acute lung injury (ALI), characterized by rapid-onset respiratory failure, leading to the clinical manifestations of poor lung compliance, severe hypoxemia, and dyspnea. ARDS/ALI has many causes, most commonly related to infections (sepsis, pneumonia), traumas, and multiple transfusions. The objective of this study is to assess the performance of postmortem anatomopathological examination in identifying etiological agents associated with ARDS or ALI in deceased patients from the State of São Paulo from 2017 to 2018. A retrospective cross-sectional study was performed based on the final outcome obtained by histopathology, histochemical, and immunohistochemical examination for ARDS/ALI differential diagnosis at the Pathology Center of the Adolfo Lutz Institute in São Paulo, Brazil. Of the 154 patients clinically diagnosed with ARDS or ALI, 57% tested positive for infectious agents, and the most frequent outcome was influenza A/H1N1 virus infection. In 43% of cases, no etiologic agent was identified. The opportunity to establish a diagnosis, identify particular infections, confirm a microbiological diagnosis, and uncover unanticipated etiologies is provided by postmortem pathologic analysis of ARDS. A molecular assessment could improve the diagnosis accuracy and lead to research into host responses and public health measures.

Methyl p­hydroxycinnamate exerts anti­inflammatory effects in mouse models of lipopolysaccharide­induced ARDS.

Methyl p­hydroxycinnamate (MH), an esterified derivative of p­Coumaric acid exerts anti­inflammatory effects on lipopolysaccharide (LPS)­stimulated RAW264.7 macrophages. Based on these effects, the present study investigated the protective role of MH in a mouse model of LPS­induced acute respiratory distress syndrome (ARDS). The results demonstrated that administration of LPS (5 mg/kg intranasally) markedly increased the neutrophil/macrophage numbers and levels of inflammatory molecules (TNF­α, IL­6, IL­1ß and reactive oxygen species) in the bronchoalveolar lavage fluid (BALF) of mice. On histological examination, the presence of inflammatory cells was observed in the lungs of mice administered LPS. LPS also notably upregulated the secretion of monocyte chemoattractant protein­1 and protein content in BALF as well as expression of inducible nitric oxide synthase in the lungs of mice; it also caused activation of p38 mitogen­activated protein kinase (MAPK) and NF­κB signaling. However, MH treatment significantly suppressed LPS­induced upregulation of inflammatory cell recruitment, inflammatory molecule levels and p38MAPK/NF­κB activation, and also led to upregulation of heme oxygenase­1 (HO­1) expression in the lungs of mice. In addition, the ability of MH to induce HO­1 expression was confirmed in RAW264.7 macrophages. Taken together, the findings of the present study indicated that MH may exert protective effects against airway inflammation in ARDS mice by inhibiting inflammatory cell recruitment and the production of inflammatory molecules.

Retrospective evaluation of the prevalence, risk factors, management, outcome, and necropsy findings of acute lung injury and acute respiratory distress syndrome in dogs and cats: 29 cases (2011-2013).

OBJECTIVE: To determine the prevalence and risk factors for veterinary acute lung injury (VetALI) and veterinary acute respiratory distress syndrome (VetARDS), assess mechanical ventilation settings and patient outcomes, and to evaluate the relationship of clinical diagnoses with necropsy findings. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: Twenty-four dogs and 5 cats with a clinical diagnosis of VetALI or VetARDS. Control population includes 24 dogs and 5 cats with a clinical diagnosis of respiratory disease other than VetALI or VetARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: VetALI and VetARDS were diagnosed in 3.2% of dogs and 1.3% of cats presenting to the ICU. Systemic inflammatory response syndrome was the most common inciting condition (16/24 dogs, 2/5 cats), followed by vomiting and subsequent aspiration of gastric contents (9/24 dogs), sepsis (5/24 dogs, 3/5 cats), multiple transfusions (4/24 dogs), trauma (3/24 dogs), and adverse drug reactions (1/24 dogs, 1/5 cats).  None of these conditions were found to be significantly associated with a risk of development of VetALI or VetARDS when compared to controls. Twelve dogs (50%) and 4 cats (80%) underwent mechanical ventilation for a median duration of 18 hours in dogs (range: 6-174 h) and 15.5 hours in cats (range: 6-91 h). Overall, 3/29 patients survived to discharge including 2/24 dogs and 1/5 cats. Necropsy results were available for 8/22 dogs and 3/4 cats. A total of 6/8 dogs (75%) dogs and 3/3 (100%) cats met the histopathologic criteria for diagnosis of VetALI or VetARDS. CONCLUSIONS: VetALI and VetARDS can cause life-threatening respiratory distress in dogs and cats necessitating mechanical ventilation in 50% of dogs and 80% of cats in this study. These diseases are associated with a poor clinical outcome and a high rate of humane euthanasia.

Performance of Multiple Risk Assessment Tools to Predict Mortality for Adult Respiratory Distress Syndrome with Extracorporeal Membrane Oxygenation Therapy: An External Validation Study Based on Chinese Single-center Data.

BACKGROUND: There has been no external validation of survival prediction models for severe adult respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO) therapy in China. The aim of study was to compare the performance of multiple models recently developed for patients with ARDS undergoing ECMO based on Chinese single-center data. METHODS: A retrospective case study was performed, including twenty-three severe ARDS patients who received ECMO from January 2009 to July 2015. The PRESERVE (Predicting death for severe ARDS on VV-ECMO), ECMOnet, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score, a center-specific model developed for inter-hospital transfers receiving ECMO, and the classical risk-prediction scores of Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) were calculated. In-hospital and six-month mortality were regarded as the endpoints and model performance was evaluated by comparing the area under the receiver operating characteristic curve (AUC). RESULTS: The RESP and APACHE II scores showed excellent discriminate performance in predicting survival with AUC of 0.835 (95% confidence interval [CI], 0.659-1.010, P = 0.007) and 0.762 (95% CI, 0.558-0.965, P = 0.035), respectively. The optimal cutoff values were risk class 3.5 for RESP and 35.5 for APACHE II score, and both showed 70.0% sensitivity and 84.6% specificity. The excellent performance of these models was also evident for the pneumonia etiological subgroup, for which the SOFA score was also shown to be predictive, with an AUC of 0.790 (95% CI, 0.571-1.009, P = 0.038). However, the ECMOnet and the score developed for externally retrieved ECMO patients failed to demonstrate significant discriminate power for the overall cohort. The PRESERVE model was unable to be evaluated fully since only one patient died six months postdischarge. CONCLUSIONS: The RESP, APCHAE II, and SOFA scorings systems show good predictive value for intra-hospital survival of ARDS patients treated with ECMO in our single-center evaluation. Future validation should include a larger study with either more patients' data at single-center or by integration of domestic multi-center data. Development of a scoring system with national characteristics might be warranted.

Sequential oxygenation index and organ dysfunction assessment within the first 3 days of mechanical ventilation predict the outcome of adult patients with severe acute respiratory failure.

OBJECTIVE: To determine early predictors of outcomes of adult patients with severe acute respiratory failure. METHOD: 100 consecutive adult patients with severe acute respiratory failure were evaluated in this retrospective study. Data including comorbidities, Sequential Organ Failure Assessment (SOFA) score, Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) score, PaO2, FiO2, PaO2/FiO2, PEEP, mean airway pressure (mPaw), and oxygenation index (OI) on the 1st and the 3rd day of mechanical ventilation, and change in OI within 3 days were recorded. Primary outcome was hospital mortality; secondary outcome measure was ventilator weaning failure. RESULTS: 38 out of 100 (38%) patients died within the study period. 48 patients (48%) failed to wean from ventilator. Multivariate analysis showed day 3 OI (P=0.004) and SOFA (P=0.02) score were independent predictors of hospital mortality. Preexisting cerebrovascular accident (CVA) (P=0.002) was the predictor of weaning failure. Results from Kaplan-Meier method demonstrated that higher day 3 OI was associated with shorter survival time (log-Rank test, P<0.001). CONCLUSION: Early OI (within 3 days) and SOFA score were predictors of mortality in severe acute respiratory failure. In the future, prospective studies measuring serial OIs in a larger scale of study cohort is required to further consolidate our findings.

An assessment of H1N1 influenza-associated acute respiratory distress syndrome severity after adjustment for treatment characteristics.

Pandemic influenza caused significant increases in healthcare utilization across several continents including the use of high-intensity rescue therapies like extracorporeal membrane oxygenation (ECMO) or high-frequency oscillatory ventilation (HFOV). The severity of illness observed with pandemic influenza in 2009 strained healthcare resources. Because lung injury in ARDS can be influenced by daily management and multiple organ failure, we performed a retrospective cohort study to understand the severity of H1N1 associated ARDS after adjustment for treatment. Sixty subjects were identified in our hospital with ARDS from "direct injury" within 24 hours of ICU admission over a three month period. Twenty-three subjects (38.3%) were positive for H1N1 within 72 hours of hospitalization. These cases of H1N1-associated ARDS were compared to non-H1N1 associated ARDS patients. Subjects with H1N1-associated ARDS were younger and more likely to have a higher body mass index (BMI), present more rapidly and have worse oxygenation. Severity of illness (SOFA score) was directly related to worse oxygenation. Management was similar between the two groups on the day of admission and subsequent five days with respect to tidal volumes used, fluid balance and transfusion practices. There was, however, more frequent use of "rescue" therapy like prone ventilation, HFOV or ECMO in H1N1 patients. First morning set tidal volumes and BMI were significantly associated with increased severity of lung injury (Lung injury score, LIS) at presentation and over time while prior prescription of statins was protective. After assessment of the effect of these co-interventions LIS was significantly higher in H1N1 patients. Patients with pandemic influenza-associated ARDS had higher LIS both at presentation and over the course of the first six days of treatment when compared to non-H1N1 associated ARDS controls. The difference in LIS persisted over the duration of observation in patients with H1N1 possibly explaining the increased duration of mechanical ventilation.

Prognostic utility of changes in N-terminal pro-brain natriuretic Peptide combined with sequential organ failure assessment scores in patients with acute lung injury/acute respiratory distress syndrome concomitant with septic shock.

We investigated the prognostic utility of changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with Sequential Organ Failure Assessment (SOFA) score in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) concomitant with septic shock. Forty-nine mechanically ventilated patients with ALI/ARDS concomitant with septic shock were studied. N-terminal pro-brain natriuretic peptide levels were measured on the first 3 days (days 0, 1, and 2) in the intensive care unit. The median NT-proBNP levels in survivors and nonsurvivors were 3,999 vs. 2,819 pg/mL on day 0 (P = 0.719); 4,495 vs. 5,397 pg/mL on day 1 (P = 0.543); and 2,325 vs. 14,173 pg/mL on day 2 (P = 0.028). N-terminal pro-brain natriuretic peptide levels increased significantly from baseline values in nonsurvivors only. We observed a monotonic increase in 28-day mortality associated with increasing quartiles of percent change in NT-proBNP on day 2 (P < 0.0001). Kaplan-Meier survival analysis revealed that mortality was significantly higher in patients with a change in NT-proBNP of 30% or more (log-rank P < 0.0001). On day 2, areas under the receiver operating characteristic curves for predicting 28-day mortality were 0.74 for SOFA alone and 0.85 (P = 0.028) for SOFA combined with percent change in NT-proBNP. In conclusion, in patients with ALI/ARDS concomitant with septic shock, a rising trend (high percent change) in NT-proBNP levels had better prognostic utility than absolute levels. The combination of percent change in NT-proBNP with SOFA may provide superior prognostic accuracy to SOFA alone.

Estimated right ventricular systolic time intervals for the assessment of right ventricular function in acute respiratory distress syndrome.

Right ventricular (RV) systolic time intervals (STIs) have been shown to accurately reflect RV function in patients with acute respiratory distress syndrome (ARDS). The measurement of RVSTIs requires phonocardiography to define the time of RV end systole. If RV end-systolic pressure (RVESP) can be derived from peak pulmonary artery (PA) systolic pressure, then the time of RV end systole, and hence, RVSTIs can be deduced without phonocardiography. We tested this possibility. In 34 patients with ARDS, RVESP was determined on the PAP curve at RV end systole, which was defined by phonocardiography. The ratios of RVESP/peak PA systolic pressure were obtained in each patient, the mean of which was 0.90 +/- 0.006. With an application of this value, the estimated RVSTIs were determined in other groups of patients. Right ventricular end-systolic pressure was estimated from the peak PA systolic pressure by multiplying 0.9. Then the point of RV end systole was determined on the electrocardiographic tracing that coincided with the point of RVESP on the PAP curve by simultaneous display of electrocardiograph and PAP curve. Total electromechanical systole was measured from the onset of the QRS complex to the point of RV end systole on the electrocardiograph. The onset of RV ejection was defined by PAP curve. The validity of this estimated RVSTIs was tested by comparing with the measured RVSTIs. By Bland-Altman analysis, the mean difference in RVSTIs between the two methods was 0.007, and bias was 0.0036, suggesting close agreement. The estimated RVSTIs can be used to accurately assess RV function.

Accuracy of clinical diagnosis of acute respiratory distress syndrome in comparison with autopsy findings.

OBJECTIVE: To compare the American-European Consensus Conference (AECC) definition of acute respiratory distress syndrome (ARDS) to autopsy findings. METHODS: All patients who died in the intensive care unit of the Federal University of Juiz de Fora University Hospital between 1995 and 2003 and were submitted to autopsy were included in the study. Patient clinical charts were reviewed to establish whether cases met the AECC criteria for a diagnosis of ARDS, histologically defined as the presence of diffuse alveolar damage (DAD). RESULTS: During the study period, 592 patients died, and 22 were submitted to autopsy. Of those 22 patients, 10 (45%) met the AECC criteria, and 7 (32%) met the histopathological criteria for DAD. The AECC clinical criteria presented a sensitivity of 71% (95%CI: 36-92%) and a specificity of 67% (95%CI: 42-85%). The positive and negative predictive values were, respectively, 50 and 83%, whereas the positive and negative likelihood ratios were, respectively, 2.33 and 0.47. The histopathological findings in the 5 patients who met AECC criteria but did not present DAD were pneumonia (n = 2), pulmonary embolism (n = 1), tuberculosis (n = 1), and cryptococcosis (n = 1). CONCLUSION: The accuracy of the AECC definition of ARDS was godless than satisfactory. Due to the low positive predictive value and the low positive likelihood ratio, other hypotheses must be considered when ARDS is suspected.

Precisão do diagnóstico clínico da síndrome do desconforto respiratório agudo quando comparado a achados de necropsia / Accuracy of clinical diagnosis of acute respiratory distress syndrome in comparison with autopsy findings

OBJETIVO: Comparar a definição de síndrome do desconforto respiratório agudo (SDRA) estabelecida pela American-European Consensus Conference (AECC, Conferência Americano-Européia) com achados de necropsia. MÉTODOS: Avaliaram-se todos os pacientes que morreram na unidade de terapia intensiva do Hospital Universitário da Universidade Federal de Juiz de Fora entre 1995 e 2003 e que foram submetidos à necropsia. Seus prontuários foram revisados para estabelecer a presença ou não dos critérios clínicos de SDRA, cujo diagnóstico histológico foi definido pela presença de dano alveolar difuso (DAD). RESULTADOS: No período, 592 pacientes faleceram e 22 foram submetidos à necropsia. Destes, 10 pacientes (45 por cento) preencheram os critérios de SDRA pela AECC e sete (32 por cento) preencheram os critérios histopatológicos de DAD. A sensibilidade da definição clínica foi de 71 por cento (IC95 por cento: 36-92 por cento) e a especificidade foi de 67 por cento (IC95 por cento: 42-85 por cento). Os valores preditivos positivo e negativo foram, respectivamente, 50 e 83 por cento; e as razões de verossimilhança positiva e negativa foram, respectivamente, 2,33 e 0,47. Os achados histopatológicos nos cinco pacientes que preencheram os critérios clínicos de SDRA, mas não apresentavam DAD, foram pneumonia (n = 2), embolia pulmonar (n = 1), tuberculose (n = 1) e criptococose (n = 1). CONCLUSÃO: A precisão dos critérios da AECC para diagnóstico de SDRA não é tão boa. Em função do baixo valor preditivo positivo e da baixa razão de verossimilhança positiva do diagnóstico clínico, outras hipóteses devem ser consideradas quando há suspeita de SDRA.

OBJECTIVE: To compare the American-European Consensus Conference (AECC) definition of acute respiratory distress syndrome (ARDS) to autopsy findings. METHODS: All patients who died in the intensive care unit of the Federal University of Juiz de Fora University Hospital between 1995 and 2003 and were submitted to autopsy were included in the study. Patient clinical charts were reviewed to establish whether cases met the AECC criteria for a diagnosis of ARDS, histologically defined as the presence of diffuse alveolar damage (DAD). RESULTS: During the study period, 592 patients died, and 22 were submitted to autopsy. Of those 22 patients, 10 (45 percent) met the AECC criteria, and 7 (32 percent) met the histopathological criteria for DAD. The AECC clinical criteria presented a sensitivity of 71 percent (95 percentCI: 36-92 percent) and a specificity of 67 percent (95 percentCI: 42-85 percent). The positive and negative predictive values were, respectively, 50 and 83 percent, whereas the positive and negative likelihood ratios were, respectively, 2.33 and 0.47. The histopathological findings in the 5 patients who met AECC criteria but did not present DAD were pneumonia (n = 2), pulmonary embolism (n = 1), tuberculosis (n = 1), and cryptococcosis (n = 1). CONCLUSION: The accuracy of the AECC definition of ARDS was godless than satisfactory. Due to the low positive predictive value and the low positive likelihood ratio, other hypotheses must be considered when ARDS is suspected.

Assessment of inflammatory response and sequestration of blood iron transferrin complexes in a rat model of lung injury resulting from exposure to low-frequency shock waves.

OBJECTIVE: Impact of air blast overpressure waves (OPW), or shock wave, with the body wall or body armor produces two types of energy waves: high-frequency low-amplitude stress waves and long-duration low-frequency share waves. These types of energy waves are characterized by different mechanisms of primary tissue injury that mostly affect lung. Systemic inflammation and resultant acute respiratory distress syndrome are known major secondary causative agents of delayed multiple organ failure and subsequent death after OPW exposure. However, association of each pattern of the blast OPW-produced energy waves with postexposure inflammatory events has not yet been delineated. The objectives of the present research were a) establishment of a rat model for assessment of the inflammatory response following lung injury produced by exposure to medium-amplitude (approximately 120 kPa) low-frequency (260+/-5 Hz) OPWs; and b) assessment of the dynamics of alteration in polymorphonuclear leukocyte counts and expression of CD11b adhesion molecules on the surface of polymorphonuclear leukocytes and status of iron-transferrin complexes in peripheral blood after OPW exposure. DESIGN: This study focused on the OPW effects at different time periods, using a sequential approach to postexposure events. Lung injury in rat was induced by OPW generated in a laboratory shock tube. Animals were exposed to OPW (at peak overpressure of 118+/-7 kPa) that produced "moderate" lung injury. SETTING: Military research institute. SUBJECTS: Twenty-seven CVF Sprague-Dawley rats were subjected to OPW exposures, and 17 sham-treated animals were used as control. INTERVENTIONS: Lung tissue and blood samples were collected at 1, 3, 6, 12, and 24 hrs following OPW exposures and compared with samples collected from nonexposed animals. MEASUREMENTS AND MAIN RESULTS: OPW-induced lung injury caused a 2.7-fold increase in the number of circulatory polymorphonuclear leukocytes as early as 1 hr postexposure, which is indicative of mobilization of the pool of marginated polymorphonuclear leukocytes into the free circulation. Polymorphonuclear leukocyte counts increased through the following 3- and 6-hr periods, when they were, respectively, 5-fold and 3.5-fold higher than in controls. These effects were accompanied by a pronounced expression of CD11b in polymorphonuclear leukocytes and tissue sequestration of blood iron-transferrin complexes during the entire 24-hr period of observations. The increase in circulatory polymorphonuclear leukocytes was accompanied by a decrease in iron-transferrin complex concentrations that apparently reflected implication of blood plasma iron in the inflammatory cell response to OPW-induced injury. CONCLUSIONS: The observed dynamics in polymorphonuclear leukocyte alterations in peripheral blood after OPW exposure were similar to those found recently in clinical observations of nonpenetrating injury and in animal models of infectious insults. Therefore, our data suggest that the main pattern of proinflammatory alterations in the rat model of lung injury induced by exposure to long-duration shock wave is similar to patterns that are characteristic of major trauma. The data further suggest that the expression of polymorphonuclear leukocyte CD11b and the response of iron-transferrin complex can be considered as potential surrogate markers in blood for systemic alterations following OPW-induced injury and, therefore, warrant further investigation in a human pilot study.

Pulmonary surfactant-associated protein A as a marker of respiratory distress in forensic pathology: assessment of the immunohistochemical and biochemical findings.

The aim of the present study was to review the immunohistochemical and biochemical findings with reference to the causes of death in routine casework (total, n=492). In the immunohistochemistry (n=283), an increase in intra-alveolar granular SP-A (SP-A score) was often observed in asphyxiation (n=21/34, 61.8%) and freshwater drowning (n=15/24, 62.5%), and also in fire and methamphetamine (MA) fatalities (n=22/76, 28.9% and n=5/16, 31.3%). Serum SP-A level (n=134) was elevated in acute respiratory distress syndrome and in some cases of drowning, fire and MA fatalities, hyperthermia and chest traumas. A quantitative analysis of SP-A subclass-gene expression (SP-A1/A2 mRNA) in the lung tissue specimens (n=126) revealed an increase in the SP-A1/A2 mRNA ratio in asphyxiation (n=17/21, 80.9%), freshwater drowning (n=7/9, 77.7%), fire and MA fatalities (n=20/35, 57.1% and n=8/10, 80.0%). These findings suggested the usefulness of SP-A as a marker of asphyxiation, respiratory distress and alveolar injury.

ADAR1 is involved in the development of microvascular lung injury.

Deamination of adenosine on pre-mRNA to inosine is a recently discovered process of posttranscription modification of pre-mRNA, termed A-to-I RNA editing, which results in the production of proteins not inherent in the genome. The present study aimed to identify a role for A-to-I RNA editing in the development of microvascular lung injury. To that end, the pulmonary expression and activity of the RNA editase ADAR1 were evaluated in a mouse model of endotoxin (15 mg/kg IP)-induced microvascular lung injury (n=5) as well as in cultured alveolar macrophages stimulated with endotoxin, live bacteria, or interferon. ADAR1 expression and activity were identified in sham lungs that were upregulated in lungs from endotoxin-treated mice (at 2 hours). Expression was localized to polymorphonuclear and monocytic cells. These events preceded the development of pulmonary edema and leukocyte accumulation in lung tissue and followed the local production of interferon-gamma, a known inducer of ADAR1 in other cell systems. ADAR1 was found to be upregulated in alveolar macrophages (MH-S cells) stimulated with endotoxin (1 to 100 microg/mL), live Escherichia coli (5x10(7) colony-forming units), or interferon-gamma (1000 U/mL). Taken together, these data suggest that ADAR1 may play a role in the pathogenesis of microvascular lung injury possibly through induction by interferon.

Novel assessment of acute lung injury by in vivo near-infrared spectroscopy.

We investigated the feasibility and validity of near-infrared (NIR) spectroscopy for evaluation of acute lung injury (ALI). In an in vitro model simulating the spectrophotometric characteristics of the lung, NIR spectroscopy could precisely detect changes in water volume, suggesting its ability to assess the extent of pulmonary edema caused by ALI. The different grades of ALI were induced in rats by administering oleic acid and varying the pulmonary ventilation conditions, and NIR spectroscopy was employed to determine lung water content and hemoglobin (Hb) oxygenation of the lungs. NIR spectroscopy detected increased water content even in histologically mild ALI. The changes in lung water content measured by NIR spectroscopy were significantly correlated with gravimetric lung water content (r = 0.877, p < 0.0001). Deoxy-Hb measured by NIR spectroscopy consistently reflected the histological changes in the lungs, and the deoxy-Hb levels correlated with changes in SaO2 (r = -0.798, p < 0.0001). These findings demonstrate that NIR spectroscopy can evaluate lung water content and Hb oxygenation quantitatively, and may be a useful tool for assessing pathological status in ALI.

An improved mathematical approach for the assessment of the medial thickness of pulmonary arteries.

Medial hypertrophy of pulmonary arteries is caused by different acute and chronic diseases complicated by pulmonary hypertension and malformations of the lung. Thus the precise assessment of external radius and relative medial thickness are of importance for clinical and experimental pathology. Different concepts have been proposed to solve this problem. Wall thickness methods which can be applied to obliquely cut arteries suffer from the disadvantage that they require prior injection of vessels. Planimetric methods can be applied to not injected vessels but they fail in assessing the medial thickness of obliquely cut arteries. We describe a mathematical approach which renders even obliquely cut and simultaneously not injected pulmonary arteries able to be assessed accurately for medial thickness and external vessel radius. This method combines the advantages of wall thickness and planimetric methods. This new method and the established wall thickness and planimetric methods were applied to 178 rat pulmonary arteries and 412 injected and 401 not injected human pulmonary arteries. The statistical analysis revealed a satisfying reproducibility (Coefficient of correlation: 0.70-0.90) of the new method. The data assessed by the new method are similar to those of the established methods. We conclude our new method to be a significant tool for the assessment of vessel parameters even in small specimens including only few not injected vessels.

[Assessment of bleomycin-induced pulmonary fibrosis by bronchoalveolar lavage].

To elucidate the pathogenesis of adult respiratory distress syndrome (ARDS), bleomycin is often used to induce lung injury because of is acute inflammatory and late fibrogenic effects on the lung. This study was undertaken to determine if fibroblast growth factors or suppressive factors might exist in bronchoalveolar lavage fluid (BALF) when acute lung injury is induced by bleomycin in rats. In the experimental group, 1.5 U of bleomycin was administered intratracheally, whereas in the control group, saline solution was given. In both groups, rats were sacrificed serially up to 4 wks. In each rat, bronchoalveolar lavage was done three times using an aliquot of 5 ml saline solution. BALF was centrifuged to obtain cells and supernatants which were further fractionated by gel-filtration. Fibroblast stimulatory and inhibitory activities were evaluated by [3H]-thymidine incorporation by fibroblasts. In the experimental group, the recovered cell count increased threefold compared with the control group and most of the increase was attributed to the increase of neutrophil. The fraction whose molecular weight is about 20,000 potentiated the [3H]-thymidine incorporation by fibroblast and its peak activity was found on the 5th day after BLM administration. On the other hand, the fraction of small molecular weight (less than 1,000) showed inhibitory activity which did not change throughout the study period. These results suggest that the imbalance between the fibroblast stimulatory and inhibitory activities after the acute lung injury may have a key role to develop pulmonary fibrosis.