Type Of Lung Injury Research Articles

Metabolic profiling in human lung injuries by high-resolution nuclear magnetic resonance spectroscopy of bronchoalveolar lavage fluid (BALF)

We present a method for identifying biomarkers in human lung injury. The method is based on high-resolution nuclear magnetic resonance (NMR) spectroscopy applied to bronchoalveolar lavage fluid (BALF) collected from lungs of critically ill patients. This biological fluid can be obtained by bronchoscopic and non-bronchoscopic methods. The type of lung injury in acute respiratory failure presenting as acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), continues to challenge critical care physicians. We characterize different metabolites in BAL fluid by non-bronchoscopic method (mBALF) for better diagnosis and understanding of ALI/ARDS by NMR spectroscopy. NMR spectra of mBALF collected from 30 patients (9 controls, 10 ARDS and 11 ALI) were analyzed for the identification of biomarkers. Statistical methods such as principal components analysis and partial least square discriminant analysis were carried out on 1H NMR spectrum of mBALF to identify biomarker responsible for separation among different lung injuries classes (ALI and ARDS) and normal lungs. The corresponding correlation of biomarkers with metabolic cycle has given insight into metabolism of lung injuries in critically ill patients. Our study shows statistically significant differentiation of various metabolites concentration in mBALF collected from lungs of ALI, ARDS and healthy control patients, making NMR spectroscopy as a possible new method of characterizing human lung injury.

Pathogenesis of Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a common complication of many diseases. Its polyetiological pattern determines the specific features of lung morphological changes and the clinical course of ARDS. Objective: to analyze the pathogenesis of ARDS in the context of the general pathological processes underlying its development. Material and methods. More than 200 lungs from the people who had died from severe concomitant injury or ARDS-complicated pneumonia were investigated. More than 150 rat experiments simulated various types of lung injury: ventilator-induced lung injury with different ventilation parameters; reperfusion injuries (systemic circulation blockade due to 12-minute vascular fascicle ligation, followed by the recovery of cardiac performance and breathing); microcirculatory disorder (injection of a thromboplastin solution into the jugular vein); blood loss; betaine-pepsin aspiration; and closed chest injury. Different parts of the right and left lungs were histologically examined 1 and 3 hours and 1 and 3 days after initiation of the experiment. Lung pieces were fixed in 10% neutral formalin solution and embedded in paraffin. Histological sections were stained with hematoxylin and eosin and using the van Gieson and Weigert procedures; the Schiff test was used. Results. The influence of aggression factors (trauma, blood loss, aspiration, infection, etc.) results in damage to the lung and particularly air-blood barrier structures (endothelium, alveolar epithelium, their basement membrane). In turn the alteration of cellular and extracellular structures is followed by the increased permeability of hemomicrocirculatory bed vessels, leading to the development of non-cardiogenic (interstitial, alveolar) pulmonary edema that is a central component in the pathogenesis of ARDS. Conclusion. The diagnosis of the early manifestations of ARDS must account for the nature of an aggression factor, the signs confirming the alteration of the lung and particularly air-blood barrier structures, pulmonary oxygenizing dysfunction, the development of noncardiogenic pulmonary edema; the absence of left ventricular failure signs. Key words: acute respiratory distress syndrome, pathogenesis.

H1N1-infected patients in ICU and their clinical outcome

Background:The swine flu (H1N1) with rapid spread and panic in population is truly global pandemic, affected mainly younger population. There is need to accumulate evidence regarding patient's intensive care parameters for effective management of newer strains of influenza viral infections. Hence an observed retrospective record analysis of confirmed H1N1 patients admitted to intensive care unit (ICU) of a tertiary care centre is done.Aims:The study was designed to study the profile and pattern of H1N1 patients admitted to ICU and to study the distribution and associated factors with treatment outcomes.Materials and Methods:The demographic, clinical, and laboratory data of 32 (RT-PCR confirmed) H1N1cases were collected and analyzed using Fischer's exact test/paired t test between survivors and nonsurvivors to know their significance. This data included criteria for admission to ICU, type of lung injury, mode of oxygenation, antiviral, and other drugs used.Results:There were 11 males and 21 female. Age ranged from 19 to 72 years. Age group of 15–45 years had most cases (78%) and mortality (60%). Most common symptoms were fever and breathlessness (100%). The mean duration of breathlessness was statistically significant (P = 0.037) between two groups. Most common signs were tachycardia and tachypnea. The 75% cases developed acute respiratory distress syndrome (ARDS), of this 16% survived. Among these fatal cases nine were positive for procalcitonin (PCT) (P = 0.006). The rest of 25% developed acute lung injury (ALI) and recovered completely (P = 0.0001).Conclusion:Fever and breathlessness were the main presenting complaints. Tachypnea and tachycardia as clinical signs predict development of respiratory complications. Arterial blood gas analysis (ABG) and PaO2/FiO2 were important in deciding severity of lung injury and mode of ventilation. ARDS was observed to be the main cause of mortality in this study. Serum PCT level estimation is useful in determining outcome.

Manejo higiênico-sanitário e lesões pulmonares em suínos na Região Metropolitana de Recife e Zona da Mata de Pernambuco, Brasil

The objective of the present study was to determine the main lesions found during the sanitary inspection of the lungs of slaughtered pigs. The study was carried out at three slaughterhouses registered with the Pernambuco State Inspection System located in metropolitan Recife and the coastal zone of the state of Pernambuco, Brazil. A total of 715 pig lungs were inspected from July 2008 to May 2009. Pulmonary lesions were detected in all herds studied. Among the total number of animals evaluated, 43.8% (313/715) had some type of lung injury. Pneumonia was the most common finding, recorded in 93.0% (291/313) of damaged lungs, followed by petechial hemorrhaging (6.7%; 21/313) and blood aspiration (3.5%; 11/313). Among the lungs submitted to histopathology, the most frequent microscopic finding was granulomatous pneumonia with 32.2% (49/152), followed by 21.7% (33/152) of interstitial pneumonia and 3.2% (14/152) fibrinous bronchopneumonia. There was a significant association between the occurrence of lung lesions and all variables related to the environment in which the animals were raised as well as the type of operation and nutritional status.

Paracrine Factors of Multipotent Stromal Cells Ameliorate Lung Injury in an Elastase-induced Emphysema Model

Multipotent stromal cells (MSCs) ameliorate several types of lung injury. The differentiation of MSCs into specific cells at the injury site has been considered as the important process in the MSC effect. However, although MSCs reduce destruction in an elastase-induced lung emphysema model, MSC differentiation is relatively rare, suggesting that MSC differentiation into specific cells does not adequately explain the recuperation observed. Humoral factors secreted by MSCs may also play an important role in ameliorating emphysema. To confirm this hypothesis, emphysema was induced in the lungs of C57BL/6 mice by intratracheal elastase injection 14 days before intratracheal MSC or phosphate-buffered saline (PBS) administration. Thereafter, lungs were collected at several time points and evaluated. Our results showed that MSCs reduced the destruction in elastase-induced emphysema. Furthermore, double immunofluorescence staining revealed infrequent MSC engraftment and differentiation into epithelial cells. Real-time PCR showed increased levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF). Real-time PCR and western blotting showed enhanced production of secretory leukocyte protease inhibitor (SLPI) in the lung. In-vitro coculture studies confirmed the in vivo observations. Our findings suggest that paracrine factors derived from MSCs is the main mechanism for the protection of lung tissues from elastase injury.

Lung protective strategies in anaesthesia

SummaryPatients are at risk for several types of lung injury in the perioperative period including atelectasis, pneumonia, pneumothorax, acute lung injury, and acute respiratory distress syndrome. Anaesthetic management can cause, exacerbate, or ameliorate these injuries. This review examines the effects of perioperative mechanical ventilation and its role in ventilator-induced lung injury. Lung protective ventilatory strategies to specific clinical situations such as cardiopulmonary bypass and one-lung ventilation along with newer novel lung protective strategies are discussed.

The Plasminogen Activation System in Lung Disease

The importance of the plasminogen activator (PA) system in multiple pulmonary disorders has become increasingly apparent as methods to analyze its components have improved. Early investigations discovered that the pulmonary alveolar space is normally a pro-fibrinolytic environment that is diminished in a variety of lung diseases. Interest in these observations was greatly increased when animal experiments revealed that manipulations of the PA system significantly modulated the tissue fibrosis that follows many types of lung injury. In particular, enhancement of PA activity was found to consistently decrease the extent of scarring induced by lung damage. Based upon these early observations, it was hypothesized that fibrin was necessary for the pathogenesis of lung fibrosis, and that an increase in PA activity would reduce collagen accumulation by accelerating the clearance of fibrin from the provisional matrix. However, as is often the case with simple hypotheses, subsequent studies revealed that the actual role of the PA system in pulmonary disease is much more complex. Possible mechanisms beyond fibrinolysis include degradation of other matrix proteins, activation of protease cascades including those involving matrix metalloproteinases, activation and release of growth factors from sites of production and sequestration, and modulation of cell adhesion and motility. In each of these processes, the serpin plasminogen activator inhibitor-1 (PAI-1) plays a central role. For these reasons, it has become apparent that PAI-1 presents an attractive target to influence multiple disease processes within the lung, particularly those that lead to lung fibrosis.

Alveolar epithelial cells: differentiation and lung injury

Re-epithelialization of alveolar epithelial cells is one of the important repair processes in many types of lung injury. The major functions of alveolar type II cells are synthesis and secretion of surfactant, hyperplasia in reaction to alveolar epithelial injury, and serving as progenitor cells for alveolar type I cells. The authors have examined the effects of several soluble factors on cultured alveolar type II cells in vitro, and also examined the histopathology and gene expression of surfactant proteins in the rat lungs with LPS, bleomycin and/or treated with keratinocyte growth factor. The authors next examined the effects of bone marrow stromal cells (BMSC) implanted transvenously into bleomycin-induced lungs. The authors found that keratinocyte growth factor (KGF) is a strong growth factor for alveolar type II cells, and that KGF instillation prevents bleomycin-induced lung injury. Furthermore, the authors showed the possibility of differentiation of implanted BMSC into alveolar epithelial cells. KGF and BMSC may play an important role in maintaining the alveolar epithelium and repairing the damaged epithelium after injury, and may well provide potential therapeutic alternatives.

Role for platelet-endothelial cell adhesion molecule-1 in macrophage Fcgamma receptor function.

Platelet-endothelial cell adhesion molecule-1 (PECAM-1) (CD31), a 130-kD transmembrane glycoprotein that functions in adhesion and signaling, is thought to play a role in some forms of leukocyte transmigration. In the lung, PECAM-1 is highly expressed, yet there have been few studies examining its role in pulmonary pathology. We therefore examined the inflammatory response (measured by bronchoalveolar lavage cell counts and protein content) after several types of lung injury in wild-type and PECAM-1 knockout mice. Consistent with studies in other organs, instillation of an endothelial stimulant (interleukin-1) was PECAM-1-dependent. In contrast, we noted that three other forms of acute lung injury (acid aspiration, adenoviral instillation, and tumor necrosis factor instillation) were completely PECAM-1-independent. Interestingly, in situ immune complex deposition injury, another complex lung disease, was also PECAM-1-dependent. This surprising finding was investigated in more detail and found to be due to a defect in macrophage activation, and not to a blockade of leukocyte transmigration. Experiments in bone marrow chimeric mice as well as ex vivo data demonstrated that Fcgamma receptor-dependent phagocytosis and tumor necrosis factor release were significantly reduced in macrophages derived from PECAM-1 knockout mice. Although PECAM-1 may not be required for transmigration of leukocytes into the alveolar space in many forms of complex lung inflammation, it is important in the function of Fcgamma receptors on alveolar macrophages.

Surfactant therapy for acute lung injury/acute respiratory distress syndrome.

Currently, three phase III surfactant replacement trials for acute lung injury (ALI)/acute respiratory distress syndromes (ARDS) patients are underway. Although the efficacy of surfactant replacement therapy will first have to be proved in these phase III trials, recent reports indicate some enticing possibilities for the future of surfactant therapy. Patients requiring mechanical ventilation show alterations in their endogenous surfactant composition. Depending on the type of lung injury or the elapsed time, modifications to surfactant preparations could enhance the efficacy of these preparations. Surfactants that closely resemble natural surfactant, especially those containing surfactant proteins (SP-B/C) and nonphospholipids (cholesterol), are able to restore normal surfactant physiology. Furthermore, lipids that are able to withstand degradation by lipases could further enhance surfactant therapy. If surfactant therapy fulfills the promises expected from the ongoing phase III trials, future surfactant preparations may even enhance therapy efficacy and restore the altered endogenous surfactant pool as soon as possible.

Altered surfactant protein A gene expression and protein metabolism associated with repeat exposure to inhaled endotoxin.

Chronically inhaled endotoxin, which is ubiquitous in many occupational and domestic environments, can adversely affect the respiratory system resulting in an inflammatory response and decreased lung function. Surfactant-associated protein A (SP-A) is part of the lung innate immune system and may attenuate the inflammatory response in various types of lung injury. Using a murine model to mimic occupational exposures to endotoxin, we hypothesized that SP-A gene expression and protein would be elevated in response to repeat exposure to inhaled grain dust and to purified lipopolysaccharide (LPS). Our results demonstrate that repeat exposure to inhaled endotoxin, either in the form of grain dust or purified LPS, results in increased whole lung SP-A gene expression and type II alveolar epithelial cell hyperplasia, whereas SP-A protein levels in lung lavage fluid are decreased. Furthermore, these alterations in SP-A gene activity and protein metabolism are dependent on an intact endotoxin signaling system.

Mechanical stretch induces MMP-2 release and activation in lung endothelium: role of EMMPRIN.

High-volume mechanical ventilation leads to ventilator-induced lung injury. This type of lung injury is accompanied by an increased release and activation of matrix metalloproteinases (MMPs). To investigate the mechanism leading to the increased MMP release, we systematically studied the effect of mechanical stretch on human microvascular endothelial cells isolated from the lung. We exposed cells grown on collagen 1 BioFlex plates to sinusoidal cyclic stretch at 0.5 Hz using the Flexercell system with 17-18% elongation of cells. After 4 days of cell stretching, conditioned media and cell lysate were collected and analyzed by gelatin, casein, and reverse zymograms as well as Western blotting. RT-PCR of mRNA extracted from stretched cells was performed. Our results show that 1) cyclic stretch led to increased release and activation of MMP-2 and MMP-1; 2) the activation of MMP-2 was accompanied by an increase in membrane type-1 MMP (MT1-MMP) and inhibited by a hydroxamic acid-derived inhibitor of MMPs (Prinomastat, AG3340); and 3) the MMP-2 release and activation were preceded by an increase in production of extracellular MMP inducer (EMMPRIN). These results suggest that cyclic mechanical stretch leads to MMP-2 activation through an MT1-MMP mechanism. EMMPRIN may play an important role in the release and activation of MMPs during lung injury.

An unexplained death: Hannah Greener and chloroform.

An unexplained death: Hannah Greener and chloroform.

Neutrophil Proteinases in Hydrochloric Acid- and Endotoxin-Induced Acute Lung Injury: Evaluation of Interstitial Protease Activity by in situ Zymography

We investigated the role of polymorphonuclear neutrophil (PMN) proteinases, elastase, and gelatinase B in rat models of acute lung injury. Three groups of rats were studied 6 hours after unilateral instillation of hydrochloric acid (HCl; 0.1 N), lipopolysaccharide (LPS) (4 μg), or saline. The results demonstrated that HCl-induced lung injury, as compared with LPS-induced lung injury, was associated with an increase in permeability (wet/dry weight ratio and proteins in bronchoalveolar lavage fluid). In contrast, there was similar PMN recruitment (in bronchoalveolar lavage fluid and myeloperoxidase activity in lung homogenates) and similar proteinase exocytosis (residual alveolar PMN content of elastase and gelatinase B) in both types of lung injury. in situ zymography, evaluating interstitial protease/inhibitor balance, demonstrated a decrease in gelatinolytic activity in both HCl- and LPS-injured lungs compared with normal lung. The increase in interleukin 6 concentration in lung homogenates, which is observed after both injuries compared with saline-instilled animals, could be involved in up-regulation of tissue inhibitor of matrix metalloproteinase-1, shown by immunocytochemistry to participate in antiproteinase excess. Neither inhibition of alveolar neutrophil influx using a leukocyte elastase inhibitor (EPI-hNE-4) nor inhibition of gelatinase activities by recombinant adenovirus for the human tissue inhibitor of matrix metalloproteinase 1 gene transfer decreased lung edema in HCl-induced injury. These data suggest that PMN proteinases do not contribute to HCl-induced acute lung injury in rats.

Magnetic resonance behavior of normal and diseased lungs: spherical shell model simulations.

The alveolar air-tissue interface affects the lung NMR signal, because it results in a susceptibility-induced magnetic field inhomogeneity. The air-tissue interface effect can be detected and quantified by measuring the difference signal (Delta) from a pair of NMR images obtained using temporally symmetric and asymmetric spin-echo sequences. The present study describes a multicompartment alveolar model (consisting of a collection of noninteracting spherical water shells) that simulates the behavior of Delta as a function of the level of lung inflation and can be used to predict the NMR response to various types of lung injury. The model was used to predict Delta as a function of the inflation level (with the assumption of sequential alveolar recruitment, partly parallel to distension) and to simulate pulmonary edema by deriving equations that describe Delta for a collection of spherical shells representing combinations of collapsed, flooded, and inflated alveoli. Our theoretical data were compared with those provided by other models and with experimental data obtained from the literature. Our results suggest that NMR Delta measurements can be used to study the mechanisms underlying the lung pressure-volume behavior, to characterize lung injury, and to assess the contributions of alveolar recruitment and distension to the lung volume changes in response to the application of positive airway pressure (e.g., positive end-expiratory pressure).

Effects of Gabexate Mesilate (FOY) on Ischemia–Reperfusion-Induced Acute Lung Injury in Dogs

Background. To assess the effects of gabexate mesilate (FOY), a protease inhibitor, on a canine model of pulmonary ischemia–reperfusion injury. FOY has been applied clinically to treat acute pancreatitis and disseminated intravascular coagulation (DIC) and has been found to suppress some leukocyte-mediated tissue injuries in both in vitro and in vivo studies.Materials and methods. Design: Comparison of four experimental groups: group 1 (untreated control, n = 8), unilateral (left) pulmonary ischemia due to perfusion and ventilation obstruction followed by reperfusion, without receiving any specific treatment; group 2 (negative control, sham operation, n = 8), left pulmonary hilar dissection without ischemia; group 3 (FOY posttreatment, n = 8), FOY treatment during the reperfusion stage only; and group 4 (FOY pretreatment, n = 8), FOY treatment before ischemia and then continued during reperfusion. Setting: University animal laboratory. Subjects: Heart-worm-free mongrel dogs (12 to 15 kg body wt) were anesthetized with pentobarbital and mechanically ventilated. Investigations: Lung ischemia was made by snaring the left pulmonary artery and veins and clamping the bronchus with peribronchial tissue for 90 min followed by reperfusion for 18 h. Animals of the two treatment groups received a 1 mg/kg bolus of FOY at the beginning of reperfusion, with infusion of 2 mg/kg/h of FOY continuously starting 30 min before ischemia (group 4) or after reperfusion (group 3). During this study the following were measured: hemodynamics and aerodynamics, blood gas, bronchoalveolar lavage (BAL) fluid neutrophil percentage and protein concentration, lung wet to dry weight ratio (W/D ratio), myeloperoxidase (MPO) activity of the lung tissue, alveolar neutrophil infiltration, and degree of injury.Results. This model of lung ischemia–reperfusion induced significant pulmonary hypertension, increased pulmonary vascular resistance, decreased pulmonary dynamic compliance and arterial hypoxemia, increased BAL fluid total protein amount and neutrophil percentage, and increased alveolar neutrophil infiltration, histological injury score, and lung tissue MPO assay (group 1). Animals of the sham operation (negative control, group 2) showed only minimal changes in the above parameters. Treatment with FOY significantly attenuated the injury by decreasing the lung W/D ratio, alveolar neutrophil infiltration, histological injury score, lung tissue MPO assay, BAL fluid neutrophil percentage, and protein amount. Pretreatment with FOY (group 4) attenuated the injury to a significantly greater degree than it did when administered at the reperfusion stage only (group 3), which was reflected by the above-mentioned parameters, and as well significantly improved gas exchange function. FOY treatment was found to have little effect in altering hemodynamics and aerodynamics at most time points in this model of lung injury.Conclusions. FOY can attenuate the ischemia–reperfusion-induced acute lung injury in dogs by ameliorating the degree of alveolar membrane permeability change, neutrophil aggregation, and activation. FOY treatment starting before ischemia attenuated this injury to a significantly higher degree than its use after ischemia. However, the effect of FOY may be partial because it cannot alter the hemodynamics or aerodynamics as prominently as other parameters in this type of lung injury. Concomitant use of FOY with other agents will have additive or synergic effects in preventing lung ischemia–reperfusion injury.

Macrophage Elastase Prevents Gemella morbillorum Infection and Improves Outcome Following Murine Bone Marrow Transplantation

Lung injury after bone marrow transplant (BMT) is a major cause of morbidity and mortality limiting the benefits of this procedure. One type of lung injury, idiopathic pneumonia syndrome, has been found to contain abundant expression of a macrophage-derived metalloproteinase, macrophage elastase (ME), in human lung biopsy specimens. To determine the role of ME in post-BMT lung injury, we developed a murine BMT model using wild-type (MME+/+) and mice deficient in ME (MME−/−), generated by gene targeting. Allogeneic single major histocompatibility complex mismatched BMTs were performed to replicate conditions that lead to lung injury.

Lysophosphatidic acid enhances contractility of isolated airway smooth muscle.

The effects of the simple phospholipid mediator lysophosphatidic acid (LPA) on the contractile responsiveness of isolated tracheal rings from rabbits and cats were assessed. In both species, LPA increased the contractile response to the muscarinic agonist methacholine, but LPA did not induce contraction on its own. Conversely, LPA decreased the relaxation response to the beta-adrenergic-agonist isoproterenol in both species. Concentrations of LPA as low as 10(-8) M were effective, and the effects of LPA were rapidly reversed on washing. Phosphatidic acid was much less effective, requiring higher concentrations and producing only a minimal effect. Contractions induced by serotonin and by substance P also were enhanced by LPA, but KCl-induced contractions were unaffected. LPA inhibited the isoproterenol-induced relaxation of KCl-precontracted rings, similar to its effects on methacholine-precontracted rings, and relaxation induced by the direct adenylyl cyclase activator forskolin was inhibited in a manner similar to that induced by isoproterenol. Epithelium removal did not alter the contraction-enhancing effect of LPA. The ability of LPA to both enhance contraction and inhibit relaxation of airway smooth muscle suggests that LPA could contribute to airway hypercontractility in asthma, airway inflammation, or other types of lung injury.

Organizing pneumonia. Features and prognosis of cryptogenic, secondary, and focal variants.

Organizing pneumonia (OP) is a non-specific response to many types of lung injury. Clinicians frequently encounter pathology reports of OP in patients with no underlying condition (cryptogenic OP, also known as BOOP or bronchiolitis obliterans OP) or in association with drugs or nonpulmonary disease. The goals of this study are to describe the clinical course and outcomes in patients with 3 clinical variants of OP. A retrospective study of patients with OP seen at the Mayo Clinic, Rochester, Minn, from January 1, 1984, through June 30, 1994, was conducted. Initial features were obtained from medical records. Chest radiographs and pathology specimens were reviewed for this study. Resolution, relapse, and survival were obtained from medical records and a follow-up patient questionnaire. Seventy-four patients had pathologically confirmed OP. Organizing pneumonia was classified into 3 clinical groups: symptomatic cryptogenic OP; symptomatic OP related to underlying hematologic malignant neoplasm, collagen vascular disease, or drugs (secondary OP); and asymptomatic OP presenting as a focal nodule (focal OP). Thirty-seven patients (50%) had cryptogenic OP and 27 patients (36%) had secondary OP. No difference was found between cryptogenic and secondary OP in type or severity of symptoms, signs, laboratory and pulmonary function tests, or radiologic or pathologic findings. Corticosteroids were given at a similar initial dose (prednisone, about 50 mg/d). Resolution of symptoms was more frequent in patients with cryptogenic OP than those with secondary OP. Relapse was infrequent in both of these groups. Five-year survival was higher in patients with cryptogenic OP (73%) than in secondary OP (44%), and respiratory-related deaths were more frequent in patients with secondary OP. Organizing pneumonia was an asymptomatic focal rounded opacity in 10 patients (14%), most often detected on chest radiograph and diagnosed on lung biopsy done for suspicion of lung cancer. Patients with focal OP required no treatment and had no relapse or respiratory-related deaths. Clinical classification of OP is useful to predict clinical course and outcome. Cryptogenic OP most often was a symptomatic bilateral lung process that had an overall favorable prognosis with prolonged corticosteroid therapy. Patients with secondary OP had a high mortality rate when the disease was associated with predisposing conditions or drugs. Patients with asymptomatic focal OP had an excellent prognosis.

Potential utility of p53 immunopositivity in differentiation of adenocarcinomas from reactive epithelial atypias of the lung

Reactive atypia of alveolar epithelium occurs in many types of lung injury and may sometimes raise suspicions of adenocarcinoma or bronchioloalveolar carcinoma. To assess whether there is sufficient difference in the frequency of p53 protein immunopositivity in these lesions to provide a practical basis for differentiating malignancy from reactive atypia, we immunostained 110 malignant and inflammatory/fibrotic lung specimens for p53 protein. Paraffin-embedded sections were immunostained with p53 protein antibody (clone BP53-12; BioGenex, San Ramon, CA) and standard capillary gap (Microprobe; Fisher Scientific, Fairlawn, NJ) avidin-biotin complex technique with antigen retrieval solution. Percent of immunopositive cells was semiquantitatively categorized as follows: 0%, less than 1%, 1% to 10%, 10% to 50%, more than 50%. Of reactive atypias, 94% are negative or show p53 immunopositivity in less than 10% of cells. Of p53 positive malignancies, 86% are positive in more than 10% of cells. When p53 immunopositivity occurs in more than 10% of atypical cells, the lesion is usually a malignancy, primarily adenocarcinoma. Most reactive atypias are immunopositive in less than 10% of atypical cells. Important caveats were noted. Rare reactive atypias are p53 immunopositive in greater than 10% of cells. Bronchioloalveolar carcinomas are infrequently p53 immunopositive. Therefore, this approach would be less useful in their differentiation from reactive atypias.