A novel large animal model of smoke inhalation-induced acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS. METHODS: Animals (n = 21) were exposed to smoke under general anesthesia for 1 to 2 h (median smoke exposure = 0.5 to 1 L of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO2), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48 h after smoke inhalation. RESULTS: Animals developed ARDS 48 h after smoke inhalation as reflected by a decrease in SpO2 by approximately 31%, PaO2/FiO2 ratio by approximately 208 (50%), and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet/dry ratio, as well as changes in other arterial blood gas (ABG) parameters. CONCLUSIONS: This study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.

Automatic proximal airway volume segmentation using optical coherence tomography for assessment of inhalation injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury with a mortality rate of up to 40%. Early management of ARDS has been difficult due to the lack of sensitive imaging tools and robust analysis software. We previously designed an optical coherence tomography (OCT) system to evaluate mucosa thickness (MT) after smoke inhalation, but the analysis relied on manual segmentation. The aim of this study is to assess in vivo proximal airway volume (PAV) after inhalation injury using automated OCT segmentation and correlate the PAV to lung function for rapid indication of ARDS. METHODS: Anesthetized female Yorkshire pigs (n = 14) received smoke inhalation injury (SII) and 40% total body surface area thermal burns. Measurements of PaO2-to-FiO2 ratio (PFR), peak inspiratory pressure (PIP), dynamic compliance, airway resistance, and OCT bronchoscopy were performed at baseline, postinjury, 24 hours, 48 hours, 72 hours after injury. A tissue segmentation algorithm based on graph theory was used to reconstruct a three-dimensional (3D) model of lower respiratory tract and estimate PAV. Proximal airway volume was correlated with PFR, PIP, compliance, resistance, and MT measurement using a linear regression model. RESULTS: Proximal airway volume decreased after the SII: the group mean of proximal airway volume at baseline, postinjury, 24 hours, 48 hours, 72 hours were 20.86 cm (±1.39 cm), 17.61 cm (±0.99 cm), 14.83 cm (±1.20 cm), 14.88 cm (±1.21 cm), and 13.11 cm (±1.59 cm), respectively. The decrease in the PAV was more prominent in the animals that developed ARDS after 24 hours after the injury. PAV was significantly correlated with PIP (r = 0.48, p < 0.001), compliance (r = 0.55, p < 0.001), resistance (r = 0.35, p < 0.01), MT (r = 0.60, p < 0.001), and PFR (r = 0.34, p < 0.01). CONCLUSION: Optical coherence tomography is a useful tool to quantify changes in MT and PAV after SII and burns, which can be used as predictors of developing ARDS at an early stage. LEVEL OF EVIDENCE: Prognostic, level III.

Association of Obesity with Quantitative Chest CT Measured Airway Wall Thickness in WTC Workers with Lower Airway Disease.

BACKGROUND: We previously reported that wall area percent (WAP), a quantitative CT (QCT) indicator of airway wall thickness and, presumably, inflammation, is associated with adverse longitudinal expiratory flow trajectories in WTC workers, but that obesity and weight gain also seemed to be independently predictive of the latter. Previous studies have reported no association between WAP and obesity, so we investigated that association in nonsmoking WTC-exposed individuals and healthy unexposed controls. METHODS: We assessed WAP using the Chest Imaging Platform QCT system in a segmental bronchus in 118 former WTC workers, and 89 COPDGene® WTC-unexposed and asymptomatic subjects. We used multiple regression to model WAP vs. body mass index (BMI) in the two groups, adjusting for important subject and CT image characteristics. RESULTS: Unadjusted analyses revealed significant differences between the two groups with regards to WAP, age, gender, scan pixel spacing and slice interval, but not BMI or total lung capacity. In adjusted analysis, there was a significant interaction between BMI and WTC exposure on WAP. BMI was significantly and positively associated with WAP in the WTC group, but not in the COPDGene® group, but stratified analyses revealed that the effect was significant in WTC subjects with clinical evidence of lower airway disease (LAD). DISCUSSION: Unlike non-diseased subjects, BMI was significantly associated with WAP in WTC workers and, in stratified analyses, the association was significant only among those with LAD. Our findings suggest that this adverse effect of obesity on airway structure and inflammation may be confined to already diseased individuals.

Point-of-care endoscopic optical coherence tomography detects changes in mucosal thickness in ARDS due to smoke inhalation and burns.

BACKGROUND: The prevalence of acute respiratory distress syndrome (ARDS) in mechanically ventilated burn patients is 33%, with mortality varying from 11-46% depending on ARDS severity. Despite the new Berlin definition for ARDS, prompt bedside diagnosis is lacking. We developed and tested a bedside technique of fiberoptic-bronchoscopy-based optical coherence tomography (OCT) measurement of airway mucosal thickness (MT) for diagnosis of ARDS following smoke inhalation injury (SII) and burns. METHODS: 16 female Yorkshire pigs received SII and 40% thermal burns. OCT MT and PaO2-to-FiO2 ratio (PFR) measurements were taken at baseline, after injury, and at 24, 48, and 72h after injury. RESULTS: Injury led to thickening of MT which was sustained in animals that developed ARDS. Significant correlations were found between MT, PFR, peak inspiratory pressure (PIP), and total infused fluid volume. CONCLUSIONS: OCT is a useful tool to quantify MT changes in the airway following SII and burns. OCT may be effective as a diagnostic tool in the early stages of SII-induced ARDS and should be tested in humans.

[Dynamic variation trend and prognostic value of bronchial wall thickness in severely burned patients combined with inhalation injury].

Objective: To explore the dynamic variation trend of bronchial wall thickness (BWT) in severely burned patients combined with inhalation injury, and to determine the value of BWT to prognosis of patients. Methods: Forty-three severely burned patients with inhalation injury hospitalized in Intensive Burn Department of the Affiliated Hospital of Nankai University (Tianjin No.4 Hospital) from July to November 2016, conforming to the study criteria, were divided into survival group (n=27) and death group (n=16) according to the prognosis of patients within 14 days after admission. All patients underwent fiberoptic bronchoscopy and inhalation injury rating based on abbreviated injury scale at admission. High resolution CT examination was performed in patients of two groups at admission and 24 h post admission, 3, 7, and 14 d post admission to measure the BWT of right superior lobar bronchus trunk opening. Receiver operating characteristic curves of rating of inhalation damage at admission and BWT at admission were drawn to evaluate the predictive value for death of 43 patients. Data were processed with chi-square test, independent sample t test, Wilcoxon rank sum test, analysis of variance for repeated measurement and least-significant difference-t test. Results: (1) The numbers of patients rated as 0, 1, 2, 3, and 4 grade for inhalation injury in survival group and death group were 0, 19, 6, 2, and 0, and 0, 2, 7, 7, and 0, respectively. There were statistically significant differences between the two groups (Z=-3.79, P<0.01). (2) BWT of patients in death group at admission and 24 h post admission, 3, 7, and 14 d post admission was respectively (2.72±0.26), (3.18±0.22), (2.98±0.18), (2.29±0.17), and (1.45±0.21) mm, which was significantly larger than (2.24±0.15), (2.49±0.15), (1.51±0.17), (1.04±0.16), and (1.01±0.13) mm in survival group (t=7.55, 12.14, 27.11, 19.99, 7.11, P<0.01). BWT of patients in survival group and death group at 24 h post admission, 3, 7, and 14 d post admission showed statistically significant difference when compared with that at admission within the corresponding group (t=5.97, 16.63, 28.21, 38.57, 5.34, 3.31, 4.39, 6.48, P<0.01). BWT of patients in survival group and death group on 3, 7, and 14 d post admission was significantly smaller than that at 24 h post admission within the corresponding group (t=22.27, 34.02, 45.03, 2.77, 10.53, 10.59, P<0.01). BWT of patients in survival group and death group on 7 and 14 d post admission was significantly smaller than that on 3 d post admission within the corresponding group (t=10.49, 18.26, 9.57, 11.44, P<0.01). BWT of patients in survival group and death group on 14 d post admission was significantly smaller than that on 7 d post admission within the corresponding group (t=6.97, 6.15, P<0.01). (3) The total areas under ROC curves of inhalation injury rating at admission and BWT at admission for predicting death of 43 patients were 0.880 and 0.956, respectively (with 95% confidence intervals 0.768-0.991, 0.882-1.000, P<0.05). Grade 1.5 and 2.75 mm were respectively chosen as the optimal threshold values of inhalation injury rating at admission and BWT at admission, with sensitivity of 87.50%, 83.33% and specificity of 77.78%, 96.00%, respectively. Conclusions: The BWT of survived and dead patients with severe burn and inhalation injury increases significantly post burn, while the BWT of survived patients restores to normal level faster. BWT can be used to assess the severity of inhalation injury and to predict death in severely burned patients combined with inhalation injury.

A model of recovery from inhalation injury and cutaneous burn in ambulatory swine.

Inhalation injury commonly accompanies thermal injury, increasing the likelihood of mortality and multiple organ dysfunction (MOD). Large animal models have given important insight into the pathophysiology of this injury; however recapitulating late MOD has remained difficult. The current report describes experiments using a smoke inhalation and burn model, with follow-up of ambulatory swine for 14days with bronchoscopy, CT scanning, and bronchoalveolar lavage fluid (BALF)/blood collection. Clinically, animals cleared airway damage in the first several days after-injury. This was mirrored with erythematous airways on day 2 after-injury, which resolved by the end of the experiment, as did parenchymal damage seen on CT. An initial rise in the protein content of BALF immediately after-injury was followed by a dramatic increase in the concentration of leukocytes. Circulating neutrophils increased while lymphocytes decreased; both correlated with cell counts in BALF. IL8 levels in BALF increased 30-fold and remained elevated throughout the experiment. IL1ra increased circulation immediately after-injury, and afterwards in BALF. Other cytokines (TNFα, IL12) transiently increased in BALF (and decreased in circulation) on day 2. Taken together, these results display a remarkable capability for the lungs to recover in the absence of intubation, with further evidence of the role of cytokines such as IL8 and IL1ra. The possible exacerbating effects of clinical practices such as ventilation and bronchoscopies should be considered.

Use of Nebulized Heparin, Nebulized N-Acetylcysteine, and Nebulized Epoprostenol in a Patient With Smoke Inhalational Injury and Acute Respiratory Distress Syndrome.

Smoke inhalation injury (SIJ) is associated with an increase in morbidity and mortality in patients with burns. SIJ causes airway damage, inflammation, and bronchial obstruction, resulting in decreased oxygenation and perfusion status in these patients. Retrospective studies have compared the use of nebulized heparin (NH) plus nebulized N-acetylcysteine (NAC) and albuterol in patients with SIJ to those who received standard ventilator support with bronchodilator therapy. These studies are associated with a decrease in mortality when NH and nebulized NAC are administered to patients with SIJ. Approximately 20% of patients who develop SIJ will also develop acute respiratory distress syndrome (ARDS). Epoprostenol, a selective pulmonary vasodilator, has been utilized in the treatment of ARDS with mixed results for improving gas exchange. To our knowledge, this is the first case report of the concomitant administration of NH, nebulized NAC, and nebulized epoprostenol following SIJ in a burn patient with ARDS.

[Damage of the lungs after exposure to obscurant smoke - a case report]. / Uszkodzenie pluc po narazeniu na dzialanie swiecy dymnej - opis przypadku.

Firing smoke candle, on reaction of pyrotechnic mixture of zinc oxide and hexachloroethane, releases of white smoke, which can damage the pulmonary parenchyma. Presented case illustrates the effects of such an inhalation injury that has led to acute respiratory distress syndrome (ARDS). The use of mechanical ventilation and administration of antibiotics and corticosteroids give the possibility to obtain clinical improvement. The resulting changes in the lung parenchyma shown on imaging studies resulted in significant impairment of breathing.

Computed tomographic assessment of airflow obstruction in smoke inhalation injury: Relationship with the development of pneumonia and injury severity.

PURPOSE: The prediction of pulmonary deterioration in patients with smoke inhalation injury is important because this influences the strategy for patient management. We hypothesized that narrowing of the luminal bronchus due to bronchial wall thickening correlates to respiratory deterioration in smoke inhalation injury patients. METHODS: In a prospective observational study, all patients were enrolled at a single tertiary trauma and critical care center. In 40 patients, chest computed tomographic images were obtained within a few hours after smoke inhalation injury. We assessed bronchial wall thickness and luminal area % on chest computed tomographic images. Airway wall thickness to total bronchial diameter (T/D) ratio, percentage of luminal area, and clinical indices were compared between patients with smoke inhalation injury and control patients. RESULTS: The T/D ratio of patients with smoke inhalation was significantly higher than that of control patients (p<0.001), and the luminal area of these patients was significantly smaller than that of control patients (p<0.001). The number of mechanical ventilation days correlated with the initial infusion volume, T/D ratio, and luminal area %. ROC analysis showed a cut-off value of 0.26 for the T/D ratio, with a sensitivity of 79.0% and specificity of 73.7%, and a value of 23.4% for luminal area %, with a sensitivity of 68.4% and specificity of 84.2%. CONCLUSIONS: These data revealed the utility of computed tomography scanning on admission to show that the patients with smoke inhalation injury had airway wall thickening compared to control patients without smoke inhalation injury. Airflow narrowing due to airway wall thickening was related to the development of pneumonia and the number of mechanical ventilation days in patients with smoke inhalation injury. Airflow narrowing is one important factor of respiratory deterioration in smoke inhalation injury.

Comparison of virtual bronchoscopy to fiber-optic bronchoscopy for assessment of inhalation injury severity.

PURPOSE: Compare virtual bronchoscopy (VB) to fiberoptic bronchoscopy (FOB) for scoring smoke inhalation injury (SII). METHODS: Swine underwent computerized tomography (CT) with VB and FOB before (0) and 24 and 48 h after SII. VB and FOB images were scored by 5 providers off line. RESULTS: FOB and VB scores increased over time (p<0.001) with FOB scoring higher than VB at 0 (0.30±0.79 vs. 0.03±0.17), 24 h (4.21±1.68 vs. 2.47±1.50), and 48h (4.55±1.83 vs. 1.94±1.29). FOB and VB showed association with PaO2-to-FiO2 ratios (PFR) with areas under receiver operating characteristic curves (ROC): for PFR≤300, VB 0.830, FOB 0.863; for PFR≤200, VB 0.794, FOB 0.825; for PFR≤100, VB 0.747, FOB 0.777 (all p<0.001). FOB showed 80.3% specificity, 77% sensitivity, 88.8% negative-predictive value (NPV), and 62.3% positive-predictive value (PPV) for PFR≤300 and VB showed 67.2% specificity, 85.5% sensitivity, 91.3% NPV, and 53.4% PPV. CONCLUSIONS: VB provided similar injury severity scores to FOB, correlated with PFR, and reliably detected airway narrowing. VB performed during admission CT may be a useful screening tool specifically to demonstrate airway narrowing induced by SII.

Chest computed tomography performed on admission helps predict the severity of smoke-inhalation injury.

INTRODUCTION: Smoke-inhalation injury is a major cause of mortality in burn patients, and therefore, it is important to determine accurately the severity of such injuries in these patients. The objective of this study was to evaluate whether chest computed tomography (CT) can be used for detecting early predictors of severity and complications of smoke-inhalation injury. METHODS: We evaluated 37 patients who had sustained smoke-inhalation injuries and had undergone chest CT within a few hours of admission to a hospital. Bronchoscopy was performed according to a standardized protocol within 12 hours of admission in all smoke-inhalation injury patients. Bronchial-wall thickness (BWT) was measured 2 cm distal from the tracheal bifurcation with CT images, and the following data were collected: total number of ventilator days, duration of intensive care unit (ICU) stay, pneumonia development, and patient outcome. RESULTS: The mean age of the patients was 63±18 years (range, 22 to 87 years), 31 (83.8%) of the patients were men, and the mortality rate was 10.8%. The causes of death in these patients were smoke inhalation (n=1), hemorrhage (n=1), and other factors resulting in sepsis (n=2). The initial carboxyhemoglobin level was 13%±14% (range, 1% to 50%). No significant correlation was found between bronchoscopic scoring and clinical factors. However, significant correlations were noted between admission BWT and development of pneumonia (R2=0.41; P<0.0001) and total number of ventilator days (R2=0.56; P<0.0001) and ICU-stay days (R2=0.17; P=0.01). Receiver operating characteristic curve analysis showed that an admission BWT cutoff value of >3.0 mm predicted pneumonia development with a sensitivity of 79%, specificity of 96%, positive predictive value of 91%, and negative predictive value of 88%. CONCLUSION: BWT measured by using the chest CT scans obtained within a few hours of admission was predictive of the total number of ventilator days and ICU-stay days and the development of pneumonia in patients with smoke-inhalation injuries.

Progressive neuropsychiatric and brain abnormalities after smoke inhalation.

A 46-year-old man inhaled combustible smoke of unknown chemical composition for 15-20 min in an automobile body shop. Within 1 month, he noted headache, sadness, anergia, anhedonia, agitation, poor sleep and impairment of concentration, attention and learning skills. Three years later, mental status examination showed major depression and cognitive disorder manifested by apprehension, continuous sadness, agitation, exhaustion, difficulty with word finding, bradyphrenia, short-term and long-term memory impairment, and judgement impaired by impulsive and affect-laden reactions without reflection. Impairments were noted on neuropsychiatric tests, and positron emission tomography (PET) scan of the brain with (18)F-fluorodeoxyglucose showed globally decreased and heterogeneous metabolic activity in the entire brain. Treatment included sertraline, methylphenidate, valproic acid and topiramate. At 14 years after smoke inhalation injury, he had persistent cognitive impairment. Repeat brain PET scan showed areas of improvement and deterioration. This case shows long-term brain and psychiatric dysfunction resulting after toxic smoke inhalation, with some areas of the brain having progressive deterioration between years 3 and 14 after smoke inhalation.

Admission chest CT complements fiberoptic bronchoscopy in prediction of adverse outcomes in thermally injured patients.

In burned patients, inhalation injury can result in progressive pulmonary dysfunction, infection, and death. Although bronchoscopy is the standard for diagnosis, it only assesses the proximal airway and does not provide a comprehensive analysis of pulmonary insult. Chest radiographs have not been proven helpful in diagnosis of inhalation injury. Our hypothesis is that a CT scan alone or in conjunction with bronchoscopy can be used as a prognostic tool for critically ill burn patients, especially those with inhalation injury. The authors performed a retrospective study of all patients admitted to the U.S. Army Institute of Surgical Research Burn Center between 2002 and 2008 with chest CT within 24 hours of admission. They divided subjects into two groups, those with evidence of inhalation injury on bronchoscopy and those without. They used a radiologist's score to assess the degree of damage to the pulmonary parenchyma. The primary endpoint was a composite of pneumonia, acute lung injury/acute respiratory distress syndrome, and death. The inhalation injury group consisted of 25 patients and the noninhalation injury group of 19 patients. Groups were not different in age, TBSA burned, and percentage full-thickness burn. By multiple logistic regression, detection of inhalation injury on bronchoscopy was associated with an 8.3-fold increase in the composite endpoint. The combination of inhalation injury on bronchoscopy and a high radiologist's score was associated with a 12.7-fold increase in the incidence of the composite endpoint. Admission CT assists in predicting future lung dysfunction in burn patients.

Selective thromboxane A2 synthase inhibition by OKY-046 prevents cardiopulmonary dysfunction after ovine smoke inhalation injury.

BACKGROUND: Because thromboxane A2 is implicated in the pathophysiology of acute lung injury, the aim of this study was to evaluate the effects of selective thromboxane A2 synthase inhibition on cardiopulmonary function in the experimental setting of severe smoke inhalation injury. METHODS: Sixteen adult sheep were operatively instrumented for chronic study. The injured intervention group was treated with the selective thromboxane A2 synthase inhibitor OKY-046, whereas the injured control group received only the vehicle (n = 8 each). RESULTS: The progressive increase in thromboxane B2 lung lymph concentrations in control animals was associated with increased transvascular fluid flux, augmented resistances in the pulmonary and systemic circulation, and a reciprocal decrease in cardiac output. In addition, end-systolic pressure-diameter relation and maximum +dp/dt were markedly depressed as compared with baseline (24 h: 14.3 +/- 0.9 vs. 8.9 +/- 0.5 mmHg/mm and 2,120 +/- 50 vs. 1,915 +/- 40 mmHg/s, respectively; each P < 0.05). Infusion of OKY-046 significantly inhibited pulmonary thromboxane B2 delivery, attenuated the early increase in pulmonary vascular resistance, and blocked the increase in systemic vascular resistance. In addition, OKY-046 blunted and delayed the decrease in cardiac output and maintained end-systolic pressure-diameter relation, +dp/dt, and lung lymph flow at baseline values. CONCLUSIONS: These findings suggest that selective thromboxane A2 synthase inhibition may represent a goal-directed therapeutic approach to alleviate cardiovascular and pulmonary dysfunction in the setting of smoke inhalation injury.

Usefulness of technetium-99m hexamethylpropylene amine oxime lung scan to detect inhalation lung injury of patients with pulmonary symptoms/signs but negative chest radiograph and pulmonary function test findings after a fire accident--a preliminary report.

OBJECTIVE: In this study, we employed technetium-99m hexamethylpropylene amine oxime (99mTc HMPAO) lung scan to detect inhalation lung injury of patients after a fire accident. METHODS: Ten healthy men for controls and 10 male patients with pulmonary symptoms/signs from a fire accident were enrolled in this study for comparison. 99mTc HMPAO lung scan was performed in each control and patient, as well as the degree of pulmonary vascular endothelium damage was represented as lung/liver uptake ratios (L/L ratio). All of the controls and patients had no smoking histories. None of the controls and patients had positive findings of plain chest radiograph (CXR) and pulmonary function test (PFT). RESULTS: The results showed that significantly higher L/L ratio in the 10 patients (0.53 +/- 0.07) than in the 10 controls (0.30 +/- 0.07) (the p value < 0.05). Using a cut-off value of 0.40, all of the 10 patients had abnormally increased L/L ratios. CONCLUSIONS: We conclude that 99mTc HMPAO lung scan has the potential to be a sensitive, objective and noninvasive method to detect inhalation lung injury of patients with pulmonary symptoms/signs but negative CXR and PFT findings after a fire accident.