Pattern Of Acute Lung Injury Research Articles

Immune and epithelial determinants of age-related risk and alveolar injury in fatal COVID-19.

Respiratory failure in COVID-19 is characterized by widespread disruption of the lung’s alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18–92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased perialveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there was also progressive loss of T2AE cells with increasing age, which may increase susceptibility to COVID-19–mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that expressed distinctly high levels of T cell activation and costimulation genes and strongly correlated with increased extent of alveolar epithelial cell depletion and CD8+ T cell cytotoxicity. Together, our results show that T2AE cell deficiency may underlie age-related COVID-19 risk and initiate alveolar dysfunction shortly after infection, and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of fatal COVID-19.

ACUTE FIBRINOUS ORGANIZING PNEUMONIA: A NEW ASSOCIATION

TOPIC: Lung Pathology TYPE: Fellow Case Reports INTRODUCTION: Acute Fibrinous and Organizing Pneumonia (AFOP) is a rare histological pattern of acute lung injury of unclear etiology. It can present with severe hypoxemia and characteristic bilateral basilar infiltrates meeting criteria for acute respiratory distress syndrome(ARDS). We present the case of a 48-year-old female with ARDS who was diagnosed with AFOP after an open lung biopsy. CASE PRESENTATION: A 48-year-old female with a past history of schizophrenia, hypertension, type 2 diabetes, osteoarthritis and monoclonal gammopathy of undetermined significance (MGUS) presented with cough and progressive shortness of breath, worsening acutely over three days. Upon arrival, the patient was hypoxic with oxygen saturation of 47%, on room air so she was emergently intubated. Initial chest X-ray revealed bilateral mid to lower zone infiltrates concerning for severe pneumonia (Picture 1). Chest CT-Angiogram ruled out pulmonary embolism. She was admitted to our intensive care unit and started on empiric broad spectrum antibiotics (Vancomycin/Piperacillin-Tazobactam/Levaquin) and ventilated using a lung-protective strategy for ARDS. Over the next 15 days, she remained ventilator dependent with high FiO2/PEEP requirements and eventually had a tracheostomy. Microbiological studies including bronchoscopic samples remained negative. An open lung biopsy was performed which showed lymphocyte and plasma cell infiltration and intra-alveolar fibrin balls with an absence of neutrophil/eosinophil infiltration and hyaline membrane formation typical of other well-recognized patterns of acute lung injury, leading to a diagnosis of AFOP (Picture 2). She was started on high dose steroids (methyprednisolone 60mg IV q8h) with prompt resolution of infiltrates and improvement in her oxygenation. DISCUSSION: (AFOP) is a rare histologic pattern of acute lung injury with multiple clinical associations but unclear etiology. Two clinical patterns have been described: i) an acute fulminant condition with severe hypoxemia and ii) a subacute respiratory illness. Diagnosis requires biopsy revealing intra-alveolar fibrin balls amidst an organizing pneumonia. AFOP has been described in patients with HIV infection, decitabine exposure, amiodarone toxicity, post hematopoietic stem cell transplantation, connective tissue diseases etc. Patients have been treated with corticosteroids, mycophenolate mofetil, cyclophosphamide, and cyclosporine with variable response. [1] CONCLUSIONS: In this case, monoclonal gammopathy of unknown significance (MGUS) represents a new association of AFOP and thus adds to our understanding of the clinical and pathological characteristics of this disease. REFERENCE #1: 1. Acute fibrinous and organizing pneumonia and undifferentiated connective tissue disease: a case report. Valim V, Rocha RH, Couto RB, Paixão TS, Serrano EV. Case Rep Rheumatol. 2012;2012:549298. doi: 10.1155/2012/549298. Epub 2012 Apr 4. DISCLOSURES: No relevant relationships by Sukhmani Boparai, source=Web Response No relevant relationships by Prangthip Charoenpong, source=Web Response No relevant relationships by Deon Ford, source=Web Response

BULLOUS LUNG DISEASE COMPLICATING COVID-19 PNEUMONIA

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: The long-term pulmonary sequelae and mechanism of lung injury seen in COVID-19 pneumonia are still under investigation, but have consistently been characterized by tissue destruction due to a hyperinflammatory state [1]. We discuss a case of bullous disease as a consequence of severe COVID 19 infection. CASE PRESENTATION: 71-year-old never smoker male presented with dyspnea, fevers and myalgias diagnosed with COVID-19 infection and admitted to the intensive care unit for acute hypoxemic respiratory failure due to acute respiratory distress syndrome (ARDS). On examination, he was noted to be in respiratory distress, with decreased breath sounds and crackles noted at the lung bases. Commuted Tomography (CT) chest revealed ground glass opacities (GGO), peripheral consolidative opacities affecting all five lobes, intralobular septal thickening in upper lobes, and traction bronchiectasis (Figure 1). His inflammatory markers were significantly elevated: C-reactive protein 384.8 mg/L, ferritin 2803 ng/mL, and D-dimer >20,000 ng/mL. His persistent hypoxemia due to COVID-19 infection was managed with high flow nasal cannula, prolonged course of corticosteroids, convalescent plasma and remdesivir. Follow up CT chest without IV contrast one month after hospitalization showed a new 8 cm bulla at the apex of the right lung with new focal emphysematous-type changes in the upper lobes, improved GGOs, traction bronchiectasis and subpleural fibrosis (Figure 2). Unfortunately, his recovery was complicated by readmission to the hospital for large right sided pneumothorax which required definitive management with surgical pleurodesis. DISCUSSION: Biopsies of lung tissue affected by severe COVID-19 pneumonia have shown interstitial inflammatory infiltrates and predominant findings consistent with diffuse alveolar damage, which is the primary histopathology of acute respiratory distress syndrome [2]. The formation of bullae after disruption of normal lung morphology is an established complication of ARDS and this underlying pattern of acute lung injury [3]. This case is unique in its description of development and recognition of significant bullous disease in a patient with COVID-19 infection without prior history of lung disease. To our knowledge, this is only the second reported case of bulla formation prior to observed pneumothorax in COVID-19 infection. There are otherwise an increasing number of cases reporting incidental bullous lung disease seen on CT imaging after readmission for spontaneous pneumothorax following index hospitalization for COVID-19 pneumonia. CONCLUSIONS: Although the precise etiologic mechanism is unclear, development of bullous lung disease as a consequence of COVID-19 infection is important to recognize and could represent an interval finding prior to presentation with spontaneous pneumothorax. REFERENCE #1: Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020;383(23):2255-2273. REFERENCE #2: Hariri LP, North CM, Shih AR, et al. Lung Histopathology in Coronavirus Disease 2019 as Compared With Severe Acute Respiratory Sydrome and H1N1 Influenza: A Systematic Review. Chest. 2021;159(1):73-84. REFERENCE #3: Gattinoni L, Caironi P, Pelosi P, Goodman LR. What has computed tomography taught us about the acute respiratory distress syndrome?. Am J Respir Crit Care Med. 2001;164(9):1701-1711. DISCLOSURES: No relevant relationships by Raymond Foley, source=Web Response No relevant relationships by Ashita Mittal, source=Web Response No relevant relationships by Simrina Sabharwal, source=Web Response

A SINGLE ODDITY: EVALI OF THE UNILATERAL LUNG

TOPIC: Tobacco Cessation and Prevention TYPE: Medical Student/Resident Case Reports INTRODUCTION: The United States is in an epidemic of electronic cigarette or vaping product use-associated lung injury (EVALI) which is characterized by a combination of respiratory, constitutional and gastrointestinal symptoms1. The most common presenting signs and symptoms include dyspnea, cough, fever, tachypnea, tachycardia, hypoxia, malaise, and emesis2. Two predominant patterns of acute lung injury have been recognized in EVALI: Diffuse Alveolar Damage and Organizing Pneumonia. Radiographic findings in the literature for patients diagnosed with EVALI include a pattern of bilateral and symmetric ground glass opacities with subpleural and areas of lobular sparing3. We present a unique case of severe EVALI isolated to a single lung that has not been documented in the literature and was managed conservatively. CASE PRESENTATION: A 36-year-old male with a history of vaping nicotine products presented with acute onset of dyspnea, hypoxia and tachycardia. Prior to switching to vaping, he admitted to a 7 pack-year smoking history of cigarettes. He endorsed using a Juul© vaping device for two years before switching to another product, Fume©, for 2 months prior to presentation. On physical exam, the patient was tachypneic and in severe respiratory distress with crackles in the right lung. Vital signs were significant for a heart rate of 129 and oxygen saturation of 90% on ambient air. COVID PCR and viral respiratory panel testing were negative. CT of the chest showed diffuse right sided nonspecific reticulonodular pattern with some bronchiectatic changes. Our patient requested conservative management due to financial concerns. Thus we elected to treat without antibiotics and systemic steroids. Supportive treatment included bronchodilators and supplemental oxygen. He improved clinically over the next five days despite our unusual conservative approach. A repeat CT of the chest at that time showed marked interval resolution of radiographic findings. DISCUSSION: Our case highlights that clinicians must be able to recognize that unilateral organizing pneumonia in the setting of recent vaping can be a manifestation of EVALI. Anecdotal literature supports the use of systemic glucocorticoids but an exact treatment of EVALI is not yet known1. The approach in our patient with significant hypoxia and radiographic lung involvement reinforces that supportive treatment of EVALI, as opposed to aggressive measures with empiric antibiotics and systemic glucocorticoids, can lead to similar outcomes without the risk of adverse effects of those medications. CONCLUSIONS: A conservative approach can likely decrease financial burdens for patients and medical institutions and still yield positive medical results. Further longitudinal research is required to determine the benefit of empiric treatment of EVALI and radiographic studies to database future unilateral presentations of EVALI. REFERENCE #1: Werner AK, Koumans EH, Chatham-Stephens K, et al. Hospitalizations and Deaths Associated with EVALI. The New England Journal of Medicine 2020;382;1589-98. REFERENCE #2: Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin - preliminary report. N Engl J Med 2019;382:903-916. REFERENCE #3: Kligerman S, Raptis C, Larsen B, et al. Radiologic, Pathologic, Clinical and Physiologic Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions. Radiology 2020;294: 491-505 DISCLOSURES: No relevant relationships by MARIA CANIZARES-OTERO, source=Web Response No relevant relationships by Benjamin Carmel, source=Web Response No relevant relationships by Vijay Srinivasan, source=Web Response No relevant relationships by Hector Vazquez Saad, source=Web Response

LIPID LADEN MACROPHAGES IN E-CIGARETTE OR VAPING PRODUCT USE-ASSOCIATED LUNG INJURY

SESSION TITLE: Medical Student/Resident Tobacco Cessation and Prevention Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Electronic-cigarette or vaping, product use-associated lung injury (EVALI) was first reported to the CDC in August 2019 and has to lead to a significant number of hospitalizations and deaths [1]. Various patterns of acute lung injury including diffuse alveolar damage, acute fibrinous pneumonitis, and organizing pneumonia have been described in association with EVALI [2]. However, the presence of lipid-laden macrophages in BAL has been consistently noted in some series of EVALI [3]. Here, we present a unique case of EVALI in which a very high number of lipid-laden macrophages were noted. CASE PRESENTATION: A 44-year-old man who had been vaping nicotine and THC regularly presented with progressively worsening dyspnea. He was febrile, tachycardic, tachypneic and hypoxemic upon presentation. Computed tomography of the chest revealed multi-focal bilateral hazy ground-glass opacities with subpleural sparing and inter-lobular septal thickening. He underwent flexible bronchoscopy for further evaluation. Bronchoalveolar lavage (BAL) showed a high number of lipid-laden macrophages on the oil-red-O stain with a Colombo count over 200. He was started on systemic corticosteroids for presumed EVALI resulting in significant improvement of his condition. He was discharged home in stable condition on day 6 of admission. DISCUSSION: A total of 2,807 hospitalized EVALI cases with 68 reported deaths have been confirmed by the Centers for Disease Control and Prevention in the United States with a majority of cases being associated with tetrahydrocannabinol containing products. Radiographic abnormalities of interlobular septal thickening along with bilateral hazy ground-glass opacities have been described with this condition and histopathological features include acute fibrinous pneumonitis, diffuse alveolar damage, lipoid pneumonia and organizing pneumonia. Lipid-laden macrophages in BAL fluid have been noted in many patients with EVALI but the significance of lipid-laden macrophages in diagnosing this condition remains unclear. However, the presence of lipid-laden macrophages in a patient with a history of electronic-cigarette or vaping product use and no evidence of infection should strongly suggest a diagnosis of EVALI. To our knowledge, no previous case with such a high number of lipid-laden macrophages has been reported. CONCLUSIONS: A rapid identification tool for EVALI is required given the current outbreak. The presence of lipid-laden macrophages in the BAL fluid may serve as such a marker in the appropriate clinical setting. Prompt treatment with systemic corticosteroids should be considered once lipid-laden macrophages are identified in patients with a history of vaping. Reference #1: Perrine CG, Pickens CM, Boehmer TK, et al. Characteristics of a Multistate Outbreak of Lung Injury Associated with E-cigarette Use, or Vaping - United States, 2019 [published correction appears in MMWR Morb Mortal Wkly Rep. 2019 Oct 11;68(40):900]. MMWR Morb Mortal Wkly Rep. 2019;68(39):860-864. Published 2019 Oct 4. doi:10.15585/mmwr.mm6839e1 Reference #2: Butt YM, Smith ML, Tazelaar HD, et al. Pathology of Vaping-Associated Lung Injury. N Engl J Med. 2019;381(18):1780-1781. doi:10.1056/NEJMc1913069 Reference #3: Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary Lipid-Laden Macrophages and Vaping. N Engl J Med. 2019;381(15):1488-1489. doi:10.1056/NEJMc1912038 DISCLOSURES: No relevant relationships by Moeezullah Beg, source=Web Response No relevant relationships by Mahnoor Mir, source=Web Response No relevant relationships by Jay Peters, source=Web Response

Pulmonary Injury Resulting from Vaping or e-Cigarette Use: Imaging Appearances at Presentation and Follow-up.

Electronic cigarette or vaping product use-associated lung injury most frequently presents with an acute lung injury pattern at CT, manifesting as multifocal ground-glass opacity and/or consolidation, typically multifocal and multilobar, possibly with subpleural sparing. Areas of organization, manifesting as contracting consolidation, mild architectural distortion, intralobular lines, lobular distortion, and traction bronchiectasis may occur as the illness evolves. A CT appearance resembling hypersensitivity pneumonitis, reflecting the exquisitely bronchiolocentric micronodular lesions of organizing pneumonia and acute lung injury seen at histopathologic findings in these patients, may be encountered. Less common CT appearances include organizing pneumonia or acute eosinophilic pneumonia patterns, the latter consisting of multifocal opacity and smooth interlobular septal thickening, possibly with small effusions, but without clinical evidence of volume overload. Patients may present with pneumothorax or pneumomediastinum, or these conditions may develop during their illness course. Most patients improve clinically and at imaging on follow-up, particularly following exposure cessation and corticosteroid therapy, but the time course to improvement is variable and most likely related to the severity of the lung injury. Radiologists should be familiar with the imaging manifestations of vaping-associated pulmonary injury, and the possibility of this condition should be considered when the imaging findings reviewed in this article are encountered. © RSNA, 2020.

Radiologic, Pathologic, Clinical, and Physiologic Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions.

Proposed as a safer alternative to smoking, the use of electronic cigarettes has not proven to be innocuous. With numerous deaths, there is an increasing degree of public interest in understanding the symptoms, imaging appearances, causes of, and treatment of electronic cigarette or vaping product use-associated lung injury (EVALI). Patients with EVALI typically have a nonspecific clinical presentation characterized by a combination of respiratory, gastrointestinal, and constitutional symptoms. EVALI is a diagnosis of exclusion; the patient must elicit a history of recent vaping within 90 days, other etiologies must be eliminated, and chest imaging findings must be abnormal. Chest CT findings in EVALI most commonly show a pattern of acute lung injury on the spectrum of organizing pneumonia and diffuse alveolar damage. The pathologic pattern found depends on when in the evolution of the disease process the biopsy sample is taken. Other less common forms of lung injury, including acute eosinophilic pneumonia and diffuse alveolar hemorrhage, have also been reported. Radiologists and pathologists help play an important role in the evaluation of patients suspected of having EVALI. Accurate and rapid identification may decrease morbidity and mortality by allowing for aggressive clinical management and glucocorticoid administration, which have been shown to decrease the severity of lung injury in some patients. In this review, the authors summarize the current state of the art for the imaging and pathologic findings of this disorder and outline a few of the major questions that remain to be answered.

Acute Fibrinous and Organizing Pneumonia Associated With Allogenic Hematopoietic Stem Cell Transplant Successfully Treated With Corticosteroids: A Two-Patient Case Series.

Acute fibrinous and organizing pneumonia (AFOP) is an extremely rare, relatively new, and distinct histological pattern of acute lung injury characterized predominately by the presence of intra-alveolar fibrin and associated organizing pneumonia. AFOP may be idiopathic or associated with a wide spectrum of clinical conditions. It has a variable clinical presentation from mild respiratory symptoms to that similar to the acute respiratory distress syndrome. Currently there is no consensus on treatment, and corticosteroids previously were of unclear benefit. To date, there are less than 40 cases of AFOP reported in the literature and only one has been linked to hematopoietic stem cell transplantation. Here we report the first case series of 2 patients who developed AFOP following allogenic stem cell transplant that were successfully treated with high-dose corticosteroids.

(292) - Acute Fibrinous and Organizing Pneumonia is a Common Histological Pattern of Acute Lung Injury in Patients Developing Restrictive Allograft Syndrome

identify the histologic features of AMR in allograft biopsies and correlate them with the presence of serologic alloantibodies in lung transplant patients. Methods: We reviewed a consecutive series of lung allograft biopsies stained with hematoxylin-eosin, anti-CD68, and anti-C4d, blinded to serologic data. Findings of ACR were classified by ISHLT criteria. Complement deposition was considered positive if there was capillary endothelial positivity, excluding stromal and larger vessel staining. Macrophages were considered increased if there was linear granular staining in capillary septa. Results: There were 628 biopsies from 111 patients. Panel reactive alloantibodies (PRA) and donor specific antibodies (DSA) were available in 103 and 100 patients, respectively. There were 73 men (64 ± 13 years) and 38 women (60 ± 12 years). PRA was positive in 38% of patients, and DSA in 30%. 24 patients had ≥ 1 biopsy with positive complement staining and 26 patients had increased macrophage density. 65 patients had ≥ 1 episode of ACR (31 A only, 25 AB, and 6 B; all were grade 1 or 2). There was a positive correlation between ACR and PRA to type II HLA antigens (p= .02), any DSA (p= .0016), the number of DSA (p= .0008) as well as the presence of DSA to type II HLA antigens (p= .003). Additionally, there was a positive correlation between increased macrophages and PRA to type II HLA antigens (p= .04), presence of DSA (p= .009) and the number of DSA type II HLA antibodies (p= .02). There was a positive correlation between complement staining and the presence of any DSA (p= .05). Other correlations were not significant. Conclusion: There is a correlation between multiple histologic findings suggestive of rejection and the serologic presence of donor specific alloantibodies, specifically against type II HLA antigens. The correlation is strongest for ACR, followed by the presence of increased capillary septal macrophages, and weakest for complement staining for C4d.

A cluster of lung injury associated with home humidifier use: clinical, radiological and pathological description of a new syndrome

BackgroundOver a few months in the spring of 2011, a cluster of patients with severe respiratory distress were admitted to our intensive care unit (ICU). Household clustering was also observed....

Histologic Patterns of Acute Lung Injury and Issues in Forensic Medicine

Context Acute lung injury and acute respiratory distress syndrome are significant causes of pulmonary morbidity and are frequently fatal. These two entities have precise definitions from a clinical standpoint. Histologically, cases from patients with clinical acute lung injury typically exhibit diffuse alveolar damage, but other histologic patterns may occasionally be encountered such as acute fibrinous and organizing pneumonia, acute eosinophilic pneumonia, and diffuse hemorrhage with capillaritis. Objective To review the diagnostic criteria for various histologic patterns associated with a clinical presentation of acute lung injury and to provide diagnostic aids and discuss the differential diagnosis. Data Sources The review is drawn from pertinent peer-reviewed literature and the author's personal experience. Conclusions Acute lung injury remains a significant cause of morbidity and mortality. The pathologist should be aware of histologic patterns of lung disease other than diffuse alveolar damage which are associated with a clinical presentation of acute lung injury. Identification of these alternate histologic findings as well as identification of potential etiologic agents, especially infection, may impact patient treatment and disease outcome.

Histologic findings in lung biopsies in patients with suspected graft-versus-host disease

The histopathologic features of pulmonary graft-versus-host disease (GVHD) status post-bone marrow transplant are not well described. Lung biopsies from patients with clinically suspected GVHD were studied. There were 17 biopsies from 9 men and 5 women. Alveolar changes were classified as acute lung injury with intra-alveolar fibrin, organizing pneumonia (OP), and chronic interstitial pneumonia (CIP). Intraepithelial bronchiolar T cells were increased in 16 of 17 biopsies within bronchiolar mucosa (56 ± 30 per 100 epithelial cells). Atypical pneumocytes were present in 10 biopsies, and atypia was marked in 2 biopsies. Reactive bronchiolar cells were also seen in all 3 groups and showed mild atypia in 5 and marked atypia in 1, mimicking viral cytopathic effect. Apoptosis of bronchiolar epithelium and interstitium was seen in all but 1 case and was most marked in the acute injury and OP patterns. Perivenular cuffing was present in 11 of 17 biopsies. All 3 patients with acute injury died of acute respiratory distress syndrome; 1 patient with OP died of systemic GVHD; and 1 patient with CIP pattern died of opportunistic infection. Obstructive lung disease with obliterative bronchiolitis developed in 3 patients, all of whom stabilized with treatment and were alive at last follow-up (mean, 25 months). All 3 histologic patterns of pulmonary GVHD are characterized by intrabronchiolar T cells, apoptosis, and perivenulitis, which help to distinguish GVHD from infections. The acute lung injury pattern has a poor prognosis, and bronchiolitis obliterans syndrome develops in a subset of patients with CIP histologic pattern.

Rheumatoid Lung Disease, Organizing Pneumonia, and the Pathology of Pulmonary Drug Toxicity

We report histologic findings on open lung biopsies from 2 patients with acute lung symptoms and a long-standing history of rheumatoid arthritis. The findings in 1 patient, who had been treated with methotrexate, include organizing pneumonia and rheumatoid (necrotic) nodules superimposed on underlying interstitial fibrosis with focal honeycombing, consistent with rheumatoid lung disease. The clinical differential diagnosis in this patient includes drug (methotrexate) toxicity. The second patient’s biopsy results had features of capillaritis with superimposed diffuse alveolar damage—2 patterns of acute lung injury that occur in rheumatologic disorders and have a relatively poor prognosis. Although organizing pneumonia is often considered characteristic of rheumatoid lung disease, a variety of other patterns are more common. The clinical differential diagnosis of rheumatoid lung includes infection and drug toxicity, especially when it is in an acute stage.

Critical care considerations in the management of the trauma patient following initial resuscitation

BackgroundCare of the polytrauma patient does not end in the operating room or resuscitation bay. The patient presenting to the intensive care unit following initial resuscitation and damage control surgery may be far from stable with ongoing hemorrhage, resuscitation needs, and injuries still requiring definitive repair. The intensive care physician must understand the respiratory, cardiovascular, metabolic, and immunologic consequences of trauma resuscitation and massive transfusion in order to evaluate and adjust the ongoing resuscitative needs of the patient and address potential complications. In this review, we address ongoing resuscitation in the intensive care unit along with potential complications in the trauma patient after initial resuscitation. Complications such as abdominal compartment syndrome, transfusion related patterns of acute lung injury and metabolic consequences subsequent to post-trauma resuscitation are presented.MethodsA non-systematic literature search was conducted using PubMed and the Cochrane Database of Systematic Reviews up to May 2012.Results and conclusionPolytrauma patients with severe shock from hemorrhage and massive tissue injury present major challenges for management and resuscitation in the intensive care setting. Many of the current recommendations for “damage control resuscitation” including the use of fixed ratios in the treatment of trauma induced coagulopathy remain controversial. A lack of large, randomized, controlled trials leaves most recommendations at the level of consensus, expert opinion. Ongoing trials and improvements in monitoring and resuscitation technologies will further influence how we manage these complex and challenging patients.

Severe Acute Fibrinous and Organizing Pneumonia with Acute Respiratory Distress Syndrome

Acute fibrinous and organizing pneumonia is a newly recognized pattern of acute lung injury. A 49-year-old female presented with a cough and worsening dyspnea on exertion. She had no history of smoking and no specific past medical history except exposure of home humidifier containing sterilizer. A chest computed tomography scan showed patchy consolidation with fibrosis in the right lower lobe and ill-defined centrilobular ground glass opacity in both lungs. The pathological findings were patchy areas of lung parenchyma with fibrin deposits in the alveolar ducts and alveoli, and fibrin balls with hemosiderin deposition in the alveolar spaces. The histological pattern of our case is differentiated from diffuse alveolar damage by the absence of hyaline membranes, and from eosinophilic pneumonia by the lack of eosinophils. In our case, the patient was treated with corticosteroid pulse therapy. However, the clinical course became aggravated and she died within two weeks.

Transfusion related lung injury. TRALI

Transfusion related lung injury is almost certainly related to the administration of blood products containing antibodies in the plasma. Those antibodies may have developed during pregnancy or following blood transfusion. They react with specific ‘cognate’ antigens in the recipient and in some patients, but not all, this results in an acute lung injury pattern. The problem resides in the plasma, so the incidence with FFP is far higher than with red cells. Blood transfusion services have adopted several ways of reducing risk such as using untransfused male donors. Leucodepletion may also have a benefit. Diagnosis is an issue as it is easily confused with transfusion associated circulatory overload TACO and often the right preconditions exist for both. Although most sources agree that the condition usually occurs within 6 h of transfusion some new information from critically ill patients has suggested that a condition called ‘delayed TRALI’ may exist, but this is currently contentious. The natural history of the condition is extremely variable and there is an associated mortality, 5–10%. Most patients do require ventilation but most do well.

Acute Exacerbation (Acute Lung Injury of Unknown Cause) in UIP and Other Forms of Fibrotic Interstitial Pneumonias

Acute exacerbation of usual interstitial pneumonia (UIP) is a condition in which patients with UIP, and occasionally other forms of fibrotic interstitial lung disease, develop rapid respiratory failure, accompanied by extensive radiologic infiltrates. The pathologic features of this condition are ill-defined in the literature and the outcome is unclear. We report 12 such patients, 9 with underlying UIP, 2 with underlying fibrotic nonspecific interstitial pneumonia, and 1 with underlying chronic hypersensitivity pneumonitis, who underwent surgical lung biopsy for diagnosis. High-resolution computed tomography data were available in 11 cases and showed the presence of extensive bilateral ground-glass opacities, sometimes accompanied by focal consolidation, superimposed on underlying fibrosis. Three microscopic patterns of acute lung injury were seen: diffuse alveolar damage (DAD), organizing pneumonia (OP), and a pattern of numerous very large fibroblast foci superimposed on underlying fibrosis. After the biopsy, all patients were treated with steroids, in some instances accompanied by cyclophosphamide or azathioprine. Ten patients survived the acute episode and were discharged with survival times of 1 to 11 months; of these cases, 6 showed a pattern of OP or OP plus extensive fibroblast foci; 2 a pattern of extensive fibroblast foci only; and 2 a pattern of DAD. Both patients who died had histologic DAD. We conclude that acute exacerbation of UIP and other fibrotic lung diseases produces a variety of pathologic patterns on biopsy, and that patients with OP or extensive fibroblast foci as the acute pattern seem to do better than those with DAD. Our data also imply that survival (of the acute episode) may be better than the literature suggests.

Quantifying Mechanical Heterogeneity in Canine Acute Lung Injury

The heterogeneous pattern of acute lung injury (ALI) predisposes patients to ventilator-associated lung injury. Currently, there is no simple technique that can reliably quantify lung heterogeneity during the dynamic conditions of mechanical ventilation. Such a technique may be of use in optimizing mechanical ventilatory parameters such as rate, tidal volume, or positive end-expiratory pressure. To determine the impact of heterogeneity on respiratory mechanics, the authors measured respiratory impedance (Zrs), expressed as respiratory resistance (Rrs) and elastance (Ers), in 11 anesthetized dogs from 0.078 to 8.9 Hz using broadband pressure and flow excitations under baseline conditions and after ALI produced by infusion of 0.08 ml/kg oleic acid into the right atrium. Data were obtained at mean airway pressures (Pao) of 5, 10, 15, and 20 cm H2O. The Zrs spectra were fit by various models of the respiratory system incorporating different distributions of parallel viscoelastic tissue properties. Under baseline conditions, both Rrs and Ers exhibited dependence on oscillation frequency, reflecting viscoelastic behavior. The Ers demonstrated significant dependence on Pao. After ALI, both the level and frequency dependence of Rrs and Ers increased, as well as the apparent heterogeneity of tissue properties. Both Rrs and Ers as well as heterogeneity decreased with increasing Pao, approaching baseline levels at the highest levels of Pao. These data demonstrate that Zrs can provide specific information regarding the mechanical heterogeneity of injured lungs at different levels of Pao. Moderate increases in Pao seem to be beneficial in ALI by reducing heterogeneity and recruiting lung units. These noninvasive measurements of lung heterogeneity may ultimately allow for the development of better ventilation protocols that optimize regional lung mechanics in patients with ALI.

Pulmonary pathology of severe acute respiratory syndrome in Toronto

The severe acute respiratory syndrome (SARS) pandemic in Toronto resulted in a large number of autopsies on its victims. We describe the pulmonary pathology of patients who died in the 2003 Toronto outbreak. Autopsy material from the lungs of 20 patients who died between March and July 2003 were characterized by histology, molecular biology, and immunohistochemistry for cytokeratins, thyroid transcription factor-1, CD68, Epstein–Barr virus, cytomegalovirus, and human herpes simplex viruses. Matched controls were obtained from patients who died of other causes over the same interval. The mean duration of illness was 27 days (range 5–108 days). Post-mortem lung tissues from 19 of 20 patients with probable SARS were positive for SARS-associated coronavirus by RT-PCR. Histologically, all patients showed varying degrees of exudative and proliferative phase acute lung injury, evidenced in conventional and immunohistochemical stains by edema, inflammatory infiltrate, pneumocyte hyperplasia, fibrinous exudates, and organization. Eight of 20 patients showed predominantly a diffuse alveolar damage pattern of acute lung injury, six showed predominantly an acute fibrinous and organizing pneumonia pattern, and the remainder showed an admixture of the two patterns. Squamous metaplasia and scattered multinucleate giant cells were present in most cases. Vascular fibrin thrombi were a common finding and were often associated with pulmonary infarcts. Special stains demonstrated vascular endothelial damage of both small- and mid-sized pulmonary vessels. Two cases were complicated by invasive fungal disease consistent with Aspergillosis, and another by coinfection with cytomegalovirus. Our findings indicate that the lungs of patients who die of SARS are almost always positive for the SARS-associated coronavirus by RT-PCR, and may show features of both diffuse alveolar damage and acute fibrinous and organizing pneumonia patterns of acute injury. Cases of SARS may be complicated by coexistent infections and therapy-related lung injury.

The oxidants hypochlorite and hydrogen peroxide induce distinct patterns of acute lung injury

Oxidative stress due to activated neutrophils, macrophages and endothelial cells plays a crucial role in acute lung injury. This study compares the effects of the nonradical oxidants hypochlorite (HOCl) and hydrogen peroxide (H2O2) on pulmonary artery pressure [PAPtorr], capillary filtration coefficient (Kf,c), tissue lipid peroxidation (LPO) and reduced glutathione (GSH) depletion. HOCl, H2O2 (1000 nmol min(-1)) or buffer (control) is infused into isolated rabbit lungs. PAP, K(f,c) and lung weight were measured. Experiments were terminated after 105 min or when fluid retention exceeded 50 g. Lung tissue was analyzed for LPO products and GSH. The oxidants induced comparable maximum effects. However, the patterns of lung injury were distinct: H2O2 infusion evoked an early biphasic pressure response (DeltaPAPmax 2.8+/-0.22/4.2+/-0.37 after 5.7+/-1.4/39+/-4.0 min) and a sixfold increase in Kf,c after 90 min. HOCl application caused a late pressure response (DeltaPAPmax 7.6+/-1.7 after 50.6+/-3.7 min) and a sevenfold increase in Kf,c after 60 min. H2O2-induced effects were attenuated by desferal. This may suggest an involvement of transition metal catalysed hydroxyl radical formation. Different oxidants induced distinct patterns of changes in PAP and Kf,c , which are accompanied by a comparable accumulation of LPO products and by a distinct degree of GSH depletion.