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Acute exacerbations of fibrotic interstitial lung disease.  


An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy. PMID:20854464

Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D



Manipulation of acute inflammatory lung disease  

Microsoft Academic Search

Inflammatory lung disease to innocuous antigens or infectious pathogens is a common occurrence and in some cases, life threatening. Often, the inflammatory infiltrate that accompanies these events contributes to pathology by deleterious effects on otherwise healthy tissue and by compromising lung function by consolidating (blocking) the airspaces. A fine balance, therefore, exists between a lung immune response and immune-mediated damage,

E L Wissinger; J Saldana; A Didierlaurent; T Hussell



Distinct macrophage subpopulations characterize acute infection and chronic inflammatory lung disease.  


Although great progress has been made in delineating lung dendritic cell and lymphocyte subpopulations, similar advances in lung macrophages (M?s) have been hampered by their intrinsic autofluorescence, cell plasticity, and the complexities of monocyte-M? compartmentalization. Using spectral scanning, we define alveolar M? autofluorescence characteristics, which has allowed us to develop an alternative flow cytometry method. Using this methodology, we show that mouse lung M?s form distinct subpopulations during acute inflammation after challenge with LPS or influenza virus, and in chronic inflammatory lung disease consequent to SHIP-1 deletion. These subpopulations are distinguished by differential Mac-1 and CD11c integrin expression rather than classical M1 or M2 markers, and display differential gene signatures ex vivo. Whereas the resolution of acute inflammation is characterized by restoration to a homogenous population of CD11c(high)Mac-1(neg/low) M?s reflective of lung homeostasis, chronic inflammatory lung disease associated with SHIP-1 deficiency is accompanied by an additional subpopulation of CD11c(high)Mac-1(pos) M?s that tracks with lung disease in susceptible genetic background SHIP-1(-/-) animals and disease induction in chimeric mice. These findings may help better understand the roles of M? subpopulations in lung homeostasis and disease. PMID:22689883

Duan, Mubing; Li, Waichu C; Vlahos, Ross; Maxwell, Mhairi J; Anderson, Gary P; Hibbs, Margaret L



Defining acute lung disease in children with the oxygenation saturation index  

PubMed Central

Objective To evalute whether a formula could be derived using oxygen saturation (Spo2) to replace Pao2 that would allow identification of children with acute lung injury and acute respiratory distress syndrome. Definitions of acute lung injury and acute respiratory distress syndrome require arterial blood gases to determine the Pao2/Fio2 ratio of 300 (acute lung injury) and 200 (acute respiratory distress syndrome). Design Post hoc data analysis of measurements abstracted from two prospective databases of randomized controlled trials. Setting Academic pediatric intensive care units. Patients A total of 255 children enrolled in two large prospective trials of therapeutic intervention for acute lung disease: calfactant and prone positioning. Interventions Data were abstracted including Pao2, Paco2, pH, Fio2, and mean airway pressure. Repeated-measures analyses, using linear mixed-effects models, were used to build separate prediction equations for the Spo2/Fio2 ratio, oxygenation index [(Fio2 × Mean Airway Pressure)/Pao2], and oxygen saturation index [(Fio2 × Mean Airway Pressure)/Spo2]. A generalization of R2 was used to measure goodness-of-fit. Generalized estimating equations with a logit link were used to calculate the sensitivity and specificity for the cutoffs of Pao2/Fio2 ratio of 200 and 300 and equivalent values of Spo2/Fio2 ratio, oxygenation index, and oxygen saturation index. Measurements and Main Results An Spo2/Fio2 ratio of 253 and 212 would equal criteria for acute lung injury and acute respiratory distress syndrome, respectively. An oxygenation index of 5.3 would equal acute lung injury criteria, and an oxygenation index of 8.1 would qualify for acute respiratory distress syndrome. An oxygen saturation index, which includes the mean airway pressure and the noninvasive measure of oxygenation, of 6.5 would be equivalent to the acute lung injury criteria, and an oxygen saturation index of 7.8 would equal acute respiratory distress syndrome criteria. Conclusions Noninvasive methods of assessing oxygenation may be utilized with reasonable sensitivity and specificity to define acute lung injury and acute respiratory distress syndrome, and, with prospective validation, have the potential to increase the number of children enrolled into clinical trials.

Thomas, Neal J.; Shaffer, Michele L.; Willson, Douglas F.; Shih, Mei-Chiung; Curley, Martha A. Q.



Acute Lung Failure  

PubMed Central

Lung failure is the most common organ failure seen in the intensive care unit. The pathogenesis of acute respiratory failure (ARF) can be classified as (1) neuromuscular in origin, (2) secondary to acute and chronic obstructive airway diseases, (3) alveolar processes such as cardiogenic and noncardiogenic pulmonary edema and pneumonia, and (4) vascular diseases such as acute or chronic pulmonary embolism. This article reviews the more common causes of ARF from each group, including the pathological mechanisms and the principles of critical care management, focusing on the supportive, specific, and adjunctive therapies for each condition.

Mac Sweeney, Rob; McAuley, Daniel F.; Matthay, Michael A.



[Acute respiratory distress syndrome caused by tropical eosinophilic lung disease: a case in Gabon].  


The purpose of this report is to describe the case of a 28-year-old woman in whom acute respiratory distress syndrome (ARDS) following cholecystectomy led to the discovery of eosinophilic lung disease. Outcome was favorable after oxygenotherapy and medical treatment using ivermectin and corticosteroids. The case shows that hypereosinophilic syndrome can be the underlying cause of ARDS. PMID:21695880

Chani, M; Iken, M; Eljahiri, Y; Nzenze, J R; Mion, G



Serum biomarker analysis of collagen disease patients with acute-onset diffuse interstitial lung disease  

PubMed Central

Background Interstitial lung disease (ILD) is frequently associated with collagen diseases. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in collagen disease patients is very poor. Here, we investigated serum biomarker profiles of AoDILD to find markers predicting outcome in patients with collagen diseases. Methods A solid-phase antibody array was used for screening 274 biomarkers in pooled sera from collagen disease patients in the AoDILD state and in the stable state. Biomarkers in individual sera were detected without pooling by bead-based immunoassay. Results The serum levels of matrix metalloproteinase (MMP)-1, tissue inhibitor of metalloproteinase (TIMP)-1, osteopontin, interleukin (IL)-2 receptor ? (IL-2R?), and IL-1 receptor antagonist were significantly increased in AoDILD, but TIMP-2, MMP-3, and eotaxin 2 levels were decreased. The MMP-3 to MMP-1 ratio was reduced in AoDILD state. This tendency was also observed in RA patients with AoDILD. Moreover, serum IL-6 level was significantly increased in the AoDILD state in patients with acute exacerbation of ILD (AE-ILD). Serum TIMP-1 and IL-2R? levels were significantly increased in the AoDILD state in patients with drug-induced ILD (DI-ILD), whereas TIMP-2, MMP-3, and eotaxin 2 levels were decreased. The MMP-3 to MMP-1 ratio was reduced in AoDILD state in patients with DI-ILD. The serum TIMP-3, MMP-9, osteopontin, IL-2R?, MMP-1, and MMP-8 levels were significantly increased in the AoDILD state in patients who subsequently died, whereas TIMP-2 and MMP-3 levels were decreased in those who survived. The MMP-3 to MMP-1 ratio was reduced in AoDILD state in patients who died, but not in those who survived. Conclusions Serum biomarker profiles could represent prognosis markers for AoDILD in collagen diseases.



Acute lung injury: cellular mechanisms and derangements  

Microsoft Academic Search

The clinical course of acute lung injury (ALI) is a complex and variable process accompanied by severe lung dysfunction, which persists for a long period of time with variable recovery of pulmonary function. The extent and severity of the lung disease associated with ALI varies with those patients having the most severe manifestations of lung disease being grouped as acute

M. A. Schwarz



Lung Diseases  


When you breathe, your lungs take in oxygen from the air and deliver it to the bloodstream. The cells in your body need oxygen to ... you breathe nearly 25,000 times. People with lung disease have difficulty breathing. Millions of people in ...


[Surgical aspects of non-respiratory activity of the lungs during acute pyonecrotizing diseases].  


The preoperative preparation program based upon the experience of treating 465 patients with acute pyonecrotizing diseases of lungs was developed. This system takes into account the stage of the disease (I--septic, II--stabilization, III--remission), endotoxicosis intensity and non respiratory activity of the affected lung (NRAL). The patients of the first group (I stage of the disease) with long-term subclavian vein catheterization were on the special scheme of NRAL correction, their supurative focuses being treated with electrized hypochlorite sodium solution. The system appeared to be effective in managing patients, in the first group--254 patients of which 202 (79,9%) were successfully treated without operation, as for the second group, there were only 52 (40,6%), in the third--26 (31,3%). By limiting and stabilizing the process, the effect of this preoperative preparation program was also seen in other patients. It allowed to perform less traumatic operations (lung resection) in 109 patients of the 179 operated on, with 8,7% of postoperative complications in 8,7% in the first group vers. 18,4% and 24,6% in the second and third, respectively. Thus the above mentioned results show the proposed system to be effective. PMID:17051711

Karimov, Kh Ia; Babadzhanov, B D; Okhunov, A O; Atakov, S S; Kasymov, U K; Ibragimov, N K; Mukhitdinov, U M; Rikhsibekov, S N; Rakhmatov, A N; Kutlimuratov, Kh


Eosinophilic lung diseases.  


Eosinophilic lung diseases comprise eosinophilic pneumonia, which may present with chronic or acute onset, or as Löffler syndrome. The diagnosis of eosinophilic pneumonia relies on clinical imaging and the demonstration of alveolar eosinophilia. Lung biopsy is generally not necessary. Peripheral blood eosinophilia is common but may be absent at presentation in idiopathic acute eosinophilic pneumonia, which may be misdiagnosed as severe infectious pneumonia. Extra-thoracic manifestations should raise the suspicion of Churg-Strauss syndrome. All possible causes of eosinophilia (especially fungus infection or drug or toxic exposure) must be thoroughly investigated before the diagnosis of idiopathic disease is made. PMID:23102066

Cottin, Vincent; Cordier, Jean-François



Childhood Interstitial Lung Disease  


... page from the NHLBI on Twitter. What Is Childhood Interstitial Lung Disease? Childhood interstitial (in-ter-STISH-al) lung disease, or ... doctors better understand these diseases. Rate This Content: Childhood Interstitial Lung Disease Clinical Trials Clinical trials are ...


Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans.  


Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72h of hyperoxia (FiO2>0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF 2?) (LC-MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2? levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F>M) and VEGF (M>F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. PMID:23792423

Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I; Barrios, Roberto; Moorthy, Bhagavatula



Diffuse disease of the lung  

SciTech Connect

The clinical areas of diffuse diseases of the lung is given a review in this book. Emphasizing diagnostic pathology and radiographic interpretation, this volume acquaints the reader with the techniques, limitations, and indications of diagnosis. Biopsy is also reviewed with comparative views of normal and abnormal histologic views. This interdisciplinary approach includes chronic infiltrative lung, acute lung disease, collagen vascular disease, and much more. Clinical cases demonstrate the application of diagnostic techniques.

Thurlbeck, W.M. (Faculty of Medicine, Univ. of British Columbia, Vancover (CA)); Miller, R.R.; Muller, N.L.; Ostrow, D.N.



Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study  

PubMed Central

Objectives To investigate the risk factors and prognosis associated with acute exacerbation (AE) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Design A retrospective case–control study. Setting A single academic hospital. Participants 51 consecutive patients diagnosed with RA-ILD between 1995 and 2012. All patients fulfilled the diagnostic criteria of the American College of Rheumatology for RA. ILD was diagnosed on the basis of clinical presentation, pulmonary function tests, high-resolution CT (HRCT) findings and lung biopsy findings. Main outcome measures Overall survival and cumulative AE incidence were analysed using Kaplan-Meier method. Cox hazards analysis was used to determine significant variables associated with AE occurrence and survival status. Results A total of 11 patients (22%) developed AE, with an overall 1-year incidence of 2.8%. Univariate analysis revealed that older age at ILD diagnosis (HR 1.11; 95% CI 1.02 to 1.21; p=0.01), usual interstitial pneumonia (UIP) pattern on HRCT (HR 1.95; 95% CI 1.07 to 3.63; p=0.03) and methotrexate usage (HR 3.04; 95% CI 1.62 to 6.02; p=0.001) were associated with AE. Of 11 patients who developed AE during observation period, 7 (64%) died of initial AE. In survival, AE was a prognostic factor for poor outcome (HR 2.47; 95% CI 1.39 to 4.56; p=0.003). Conclusions In patients with RA-ILD, older age at ILD diagnosis, UIP pattern on HRCT and methotrexate usage are associated with the development of AE. Furthermore, AE has a serious impact on their survival.

Hozumi, Hironao; Nakamura, Yutaro; Johkoh, Takeshi; Sumikawa, Hiromitsu; Colby, Thomas V; Kono, Masato; Hashimoto, Dai; Enomoto, Noriyuki; Fujisawa, Tomoyuki; Inui, Naoki; Suda, Takafumi; Chida, Kingo



Skin ulcer is a predictive and prognostic factor of acute or subacute interstitial lung disease in dermatomyositis.  


The aim of this study was to determine whether skin ulcer can be used as a predictive and prognostic factor of acute/subacute interstitial lung disease (ILD) in Japanese patients with dermatomyositis (DM). We reviewed the medical records of 39 consecutive DM patients who were admitted to Tokyo Metropolitan Komagome Hospital from January 2000 to December 2009. The mean follow-up period was 63.9 ± 51.6 months. Fifteen patients had acute/subacute ILD and 11 patients had chronic ILD. Seven out of 15 acute/subacute ILD led to respiratory failure and 3 of them died due to ILD. Skin ulcers were observed in 5 out of 15 patients with acute/subacute ILD (33.3 %) and in 2 out of 24 patients without acute/subacute ILD (8.3 %). The presence of skin ulcers was revealed to be a significant predictive factor for acute/subacute ILD among various parameters by multivariate analysis. In the 15 patients with acute/subacute ILD, the presence of skin ulcers was a significant poor prognostic factor (p = 0.0231) and the cumulative survival rate of patients with skin ulcers was 53.3 % for 12 months. Skin ulcer is a significant predictive and prognostic factor of acute/subacute ILD in patients with DM. PMID:23553518

Ishigaki, Kazuyoshi; Maruyama, Junko; Hagino, Noboru; Murota, Atsuko; Takizawa, Yasunobu; Nakashima, Ran; Mimori, Tsuneyo; Setoguchi, Keigo



Warning Signs of Lung Disease  


... Lungs Warning Signs of Lung Disease Top Stories Lung HelpLine Questions about your lung health? Ask an ... Warning Signs of Lung Disease Warning Signs of Lung Disease WARNING SIGNS If you have any of ...


Noninfectious Lung Disease in the Immunocompromised Host  

Microsoft Academic Search

Patients with compromised immune function suffer a wide variety of lung insults. Infections are the most common causes of both acute and chronic lung diseases, but many noninfectious conditions affect the lungs. The clinical presentation of these noninfectious conditions often mimic infections, thus causing diagnostic dilemmas. The spectrum of noninfectious lung injury and response in the immunosuppressed host includes interstitial

Stephen W. Crawford



Lung Diseases  


... Environmental Health (259KB) A Human Health Perspective on Climate Change (Full Report) (4MB) Certain Glass Wool Fibers (Inhalable) ( ... Environmental Public Health (PEPH) (357KB) Programs and Initiatives: Climate Change and Human Health Respiratory Disease and the Environment ( ...


Reflux and Lung Disease  


... Nutrition Reflux and Lung Disease Back-to-School Nutrition Tips Proper Hydration Sodium Dangers Plant-Based Diets Make an appointment Ask a Question Refer a Patient 1.877.CALL NJH ( 877.225.5654 ) You are ... > Health Information > Healthy Lifestyle > Nutrition > Reflux and Lung Disease Reflux and Lung Disease ...


Particles causing lung disease  

SciTech Connect

The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. 164 references, 1 figure, 2 tables.

Kilburn, K.H.



Interstitial Lung Disease  


... radiation treatments to your chest or using some chemotherapy drugs makes it more likely that you'll develop lung disease. Oxygen. Continually inhaling very high levels of therapeutic oxygen for more than 48 hours can harm the lungs. Complications Interstitial lung disease can lead to a series ...


Lung Diseases and Conditions  


... Search Form Advanced Search Search the NHLBI, use radio buttons below to select whole site or Disease and Conditions Index only NHLBI Entire ... Information for the Public » Health Topics » How the Lungs Work » Lung Diseases & Conditions How the Lungs Work Explore ...


Interstitial lung disease.  


This article reviews the most important articles published in interstitial lung disease, as reviewed during the Clinical Year in Review session at the 2012 annual European Respiratory Society Congress in Vienna, Austria. Since the recent international guidelines for the management of idiopathic pulmonary fibrosis (IPF), important new evidence is available. The anti-fibrotic drug pirfenidone has been recently approved in Europe. Other pharmacological agents, especially nintedanib, are still being tested. The so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended as treatment. Although the clinical course of IPF is highly variable, novel tools have been developed for individual prediction of prognosis. Acute exacerbations of IPF are associated with increased mortality and may occur with higher frequency in IPF patients with associated pulmonary hypertension. Interstitial lung disease associated with connective tissue disease has been definitely established to have a better long-term survival than IPF. A subset of patients present with symptoms and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given autoimmune disease; this condition is associated with a higher prevalence of nonspecific interstitial pneumonia pattern, female sex and younger age, although survival relevance is unclear. PMID:23457161

Cottin, Vincent



Interstitial Lung Diseases  


Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and scarring make it hard to get enough oxygen. The scarring is called pulmonary fibrosis. Breathing in dust or other particles in ...


Role of Extracellular Adenosine in Acute Lung Injury  

NSDL National Science Digital Library

Acute lung injury (ALI) is a lung disease characterized by pulmonary edema and severe hypoxia. The past decade hosted a search for endogenous mechanisms controlling lung inflammation and pulmonary edema during ALI. As such, recent evidence indicates extracellular adenosine in orchestrating the resolution of pulmonary edema and inflammation during ALI.

Tobias Eckle (University of Colorado Denver Anesthesiology, Mucosal Inflammation Program); Michael Koeppen (University of Colorado Denver Anesthesiology); Holger K. Eltzschig (University of Colorado Denver Anesthesiology)



Diffuse lung diseases in cigarette smokers.  


Cigarette smoking is a recognized causative agent or precipitant of specific diffuse lung diseases characterized by bronchiolar and interstitial lung inflammation. Respiratory bronchiolitis-associated interstitial lung disease and pulmonary Langerhans cell histiocytosis are now considered smoking-induced diffuse lung diseases. Desquamative interstitial pneumonia is also recognized as a smoking-induced interstitial pneumonia in most cases. These disorders affect relatively young adult smokers and may be progressive. Although distinguishable by histopathological and radiographic features, significant overlap occurs in many cases with chest radiography and lung histology showing overlapping features of smoking-related bronchiolar and interstitial lung injury. Cigarette smoking is also recognized as an important precipitant of many acute eosinophilic pneumonia cases. Smokers are at higher risk of developing fibrotic interstitial lung diseases such as idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial lung disease. Certain smokers also develop combined emphysema and lung fibrosis. The avoidance of primary and second-hand cigarette smoke is a critical component of management for patients afflicted with these smoking-induced diffuse lung diseases. The role of corticosteroids and other immunosuppressive treatments in the management of smoking-related interstitial lung diseases remains poorly defined and should be reserved for individuals with progressive disease despite smoking cessation. Understanding mechanisms by which tobacco induces diffuse lung pathology is critical in the pursuit of novel therapeutic approaches for these diseases. PMID:23001806

Vassallo, Robert



Role of endothelin-1 in lung disease  

PubMed Central

Endothelin-1 (ET-1) is a 21 amino acid peptide with diverse biological activity that has been implicated in numerous diseases. ET-1 is a potent mitogen regulator of smooth muscle tone, and inflammatory mediator that may play a key role in diseases of the airways, pulmonary circulation, and inflammatory lung diseases, both acute and chronic. This review will focus on the biology of ET-1 and its role in lung disease.

Fagan, Karen A; McMurtry, Ivan F; Rodman, David M



Treatment of acute silicoproteinosis by whole-lung lavage.  


Acute silicoproteinosis is a rare disease that occurs following a heavy inhalational exposure to silica dusts. Clinically, it resembles pulmonary alveolar proteinosis (PAP); silica exposure is thought to be a cause of secondary PAP. We describe a patient with biopsy-confirmed acute silicoproteinosis whose course was complicated by acute hypoxemic respiratory failure requiring mechanical ventilation. Without clinical improvement despite antibiotic and steroid treatment, the patient was scheduled for whole-lung lavage under general anesthesia. Anesthetic challenges included double-lumen tube placement and single-lung ventilation in a hypoxic patient, facilitating lung lavage, and protecting the contralateral lung from catastrophic spillage. PMID:23632425

Stafford, Marshall; Cappa, Anthony; Weyant, Michael; Lara, Abigail; Ellis, James; Weitzel, Nathaen S; Puskas, Ferenc



Diffuse interstitial lung disease  


... to the chest Working with or around asbestos, coal dust, cotton dust, and silica dust (called occupational ... routinely screened for lung disease. These jobs include coal mining, sand blasting, and working on a ship.


Indium Lung Disease  

PubMed Central

Background: Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. Methods: To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. Results: Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Conclusions: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies.

Nakano, Makiko; Omae, Kazuyuki; Takeuchi, Koichiro; Chonan, Tatsuya; Xiao, Yong-long; Harley, Russell A.; Roggli, Victor L.; Hebisawa, Akira; Tallaksen, Robert J.; Trapnell, Bruce C.; Day, Gregory A.; Saito, Rena; Stanton, Marcia L.; Suarthana, Eva; Kreiss, Kathleen



Efferocytosis and lung disease.  


In healthy individuals, billions of cells die by apoptosis each day. Clearance of these apoptotic cells, termed "efferocytosis," must be efficient to prevent secondary necrosis and the release of proinflammatory cell contents that disrupt tissue homeostasis and potentially foster autoimmunity. During inflammation, most apoptotic cells are cleared by macrophages; the efferocytic process actively induces a macrophage phenotype that favors tissue repair and suppression of inflammation. Several chronic lung diseases, particularly airways diseases such as chronic obstructive lung disease, asthma, and cystic fibrosis, are characterized by an increased lung burden of uningested apoptotic cells. Alveolar macrophages from individuals with these chronic airways diseases have decreased efferocytosis relative to alveolar macrophages from healthy subjects. These two findings have led to the hypothesis that impaired apoptotic cell clearance may contribute causally to sustained lung inflammation and that therapies to enhance efferocytosis might be beneficial. This review of the English-language scientific literature (2006 to mid-2012) explains how such existing therapies as corticosteroids, statins, and macrolides may act in part by augmenting apoptotic cell clearance. However, efferocytosis can also impede host defenses against lung infection. Thus, determining whether novel therapies to augment efferocytosis should be developed and in whom they should be used lies at the heart of efforts to differentiate specific phenotypes within complex chronic lung diseases to provide appropriately personalized therapies. PMID:23732585

McCubbrey, Alexandra L; Curtis, Jeffrey L



Miscellaneous Occupational Lung Diseases  

Microsoft Academic Search

A case is presented of a rare occupational lung disease for which the workplace etiology may have been overlooked. The authors review 4 such diseases, which are important to recognize not only because cessation of exposure can lead to clinical improvement, but also because other cases of these conditions may be identified in the workplace.

M. Sarper Erdogan; Christopher J. Martin



Predicting occupational lung diseases  

Microsoft Academic Search

This thesis aims at demonstrating the development, validation, and application of prediction models for occupational lung diseases. Prediction models are developed to estimate an individual’s probability of the presence or future likelihood of occurrence of an outcome (i.e. disease of interest or its related condition). These models are used to assist clinical decision making for individuals, or to stratify individuals

E. Suarthana



Vitamin D deficiency and acute lung injury.  


Acute Lung Injury (ALI) and the more severe form Acute Respiratory Distress Syndrome (ARDS) remain a significant cause of morbidity and mortality in the critically ill patient. It is characterised by a severe inflammatory process resulting in diffuse alveolar damage, influx of neutrophils, macrophages and a protein rich exudate in the alveolar spaces caused by endothelial and epithelial injury. Improvements in outcomes are in part due to restrictive fluid management and protective lung ventilation however successful therapeutic strategies remain elusive with promising therapies failing to translate positively in human studies. The evidence for the role of vitamin D in lung disease is growing - deficiency has been associated with impaired pulmonary function, increased incidence of viral and bacterial infections and inflammatory disease including asthma and COPD. Studies have also reported a high prevalence of vitamin D deficiency in the critically ill and an association with adverse outcomes. Although exact mechanisms are yet to be discerned, vitamin D appears to impact on a variety of inflammatory and structural cells within the lung including macrophages, lymphocytes and epithelial cells. To date there are few directly supportive clinical studies in ALI; this review explores the compelling evidence suggesting arole for vitamin D in ALI and the mechanisms by which it could contribute to pathogenesis. PMID:23782208

Parekh, Dhruv; Thickett, David R; Turner, Alice M



Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome  

PubMed Central

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Mortality from ALI/ARDS is substantial, and current therapy primarily emphasizes mechanical ventilation and judicial fluid management plus standard treatment of the initiating insult and any known underlying disease. Current pharmacotherapy for ALI/ARDS is not optimal, and there is a significant need for more effective medicinal chemical agents for use in these severe and lethal lung injury syndromes. To facilitate future chemical-based drug discovery research on new agent development, this paper reviews present pharmacotherapy for ALI/ARDS in the context of biological and biochemical drug activities. The complex lung injury pathophysiology of ALI/ARDS offers an array of possible targets for drug therapy, including inflammation, cell and tissue injury, vascular dysfunction, surfactant dysfunction, and oxidant injury. Added targets for pharmacotherapy outside the lungs may also be present, since multiorgan or systemic pathology is common in ALI/ARDS. The biological and physiological complexity of ALI/ARDS requires the consideration of combined-agent treatments in addition to single-agent therapies. A number of pharmacologic agents have been studied individually in ALI/ARDS, with limited or minimal success in improving survival. However, many of these agents have complementary biological/biochemical activities with the potential for synergy or additivity in combination therapy as discussed in this article.

Raghavendran, Krishnan; Pryhuber, Gloria S.; Chess, Patricia R.; Davidson, Bruce A.; Knight, Paul R.; Notter, Robert H.



Incidence and Outcomes of Acute Lung Injury  

Microsoft Academic Search

background Acute lung injury is a critical illness syndrome consisting of acute hypoxemic respira- tory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hy- pertension. Despite recent advances in our understanding of the mechanism and treat- ment of acute lung injury, its incidence and outcomes in the United States have been unclear. methods We conducted a

Gordon D. Rubenfeld; Ellen Caldwell; Eve Peabody; Jim Weaver; Diane P. Martin; Margaret Neff; Eric J. Stern; Leonard D. Hudson



Lung development and adult lung diseases.  


Adult respiratory diseases are caused by many factors, including genetic-environmental interaction. Genetic abnormalities can impact early fetal lung development, postnatal lung maturation, as well as adult lung injury and repair. Studies suggest that abnormally developed lung structure and function may contribute as a susceptibility factor for several adult lung diseases. This review focuses on the relationship between lung development and pathogenesis of several lung diseases including COPD, cystic fibrosis (CF), and asthma. COPD with emphysema has been considered to be an accelerated involutional disease of aging smokers. However, since only a proportion (approximately 15%) of smokers get COPD with emphysema, clearly genetic susceptibility must play a significant part in determining both the age of onset and the rapidity of decline in lung function. In mice, interference with key genes either by null mutation, hypomorphism, or gain or loss of function results in phenotypes comprising either neonatal lethal respiratory distress if the structural effect is severe, or reduced alveolarization and/or early onset emphysema if the effect is milder. Reported susceptibility candidate genes are therefore discussed in some detail, including elastin, lysyl oxidase, fibrillin, the transforming growth factor-beta-Smad3 pathway, as well as extracellular matrix proteases. In the case of CF, the Cftr gene has been shown to regulate fetal lung epithelial cell differentiation and maturation. Subtle abnormalities of lung structure and function are found in clinically asymptomatic CF infants. Finally, airway remodeling due to chronic inflammation is important in infants who later acquire asthma. PMID:17699136

Shi, Wei; Bellusci, Saverio; Warburton, David



Extracorporeal Perfusion for Acute Respiratory Failure. Membrane Lung Perfusion for Acute Respiratory Failure.  

National Technical Information Service (NTIS)

The overall long term extracorporeal perfusion (ECMO) therapy in the treatment of severe acute respiratory distress syndrome (ARDS). Efforts were directed at four components of the overall goal: (1) Which lung diseases improve during ECMO or control thera...

W. M. Zapol



Lung injury following acute kidney injury: kidney–lung crosstalk  

Microsoft Academic Search

The mortality of acute kidney injury (AKI) remains unacceptably high, especially associated with acute respiratory failure.\\u000a Lung injury complicated with AKI was previously considered as “uremic lung”, which is characterized by volume overload and\\u000a increased vascular permeability. New experimental data using rodent models of renal ischemia–reperfusion and bilateral nephrectomy\\u000a have emerged recently focusing on kidney–lung crosstalk in AKI, and have

Kent Doi; Tomoko Ishizu; Toshiro Fujita; Eisei Noiri


Cystic lung disease.  


This review addresses the pathology of lung disease in which the predominant finding is diffuse cystic change. Although cysts may be found radiologically in a wide variety of disease states, the entities discussed are those most likely to be encountered in biopsies where the underlying aetiology is unclear. These include Langerhans cell histiocytosis, lymphangioleiomyomatosis and Birt-Hogg-Dubé syndrome, and recent advances in the molecular pathology of these entities are reviewed. Conditions in which cyst formation may occur but does not represent the predominant pathology are also considered, including alveolar septal amyloidosis, light chain disease, follicular bronchiolitis and lymphocytic interstitial pneumonia. Cystic metastases may present a differential diagnostic dilemma. PMID:23729207

Clarke, Belinda E



Congenital Cystic Lung Diseases  

PubMed Central

Congenital cystic diseases of the lung are a rare but significant cause of morbidity in children and young adults presenting with respiratory distress and repeated chest infections. They consist of cystic adenomatoid malformation, bronchogenic cyst, pulmonary sequestration, and congenital lobar emphysema. Surgical treatment is a safe and an effective method of treatment. Chest X-ray and computed tomography are the key imaging modalities used for diagnosis.

Jain, Aditi; Anand, K; Singla, Saurabh; Kumar, Ashok



Epidemiology and outcomes of acute lung injury.  


Acute lung injury (ALI) and its presentation with more severe hypoxemia, the ARDS, is a challenging entity for clinical investigation because, like many critical illness syndromes, it lacks an accepted diagnostic test and relies on a constellation of clinical findings for diagnosis. Despite these barriers, there have been important advances in the clinical and population epidemiology of ALI. This article will review recent studies of the incidence, diagnosis, etiologic and prognostic factors, relevant disease subsets, mortality, and long-term outcomes of ALI. A detailed understanding of the epidemiology and outcomes of ALI is essential for future research on mechanisms of both the acute presentation and long-term sequelae, for designing studies to identify genetic risk factors for developing ALI, and to develop strategies to treat or prevent the morbidity encountered by survivors. PMID:17296661

Rubenfeld, Gordon D; Herridge, Margaret S



Intravascular laser therapy in different forms of lung diseases  

NASA Astrophysics Data System (ADS)

The potentions of laser intravascular therapy in elimination of pyogenic and inflammatory intoxication in cases of acute pneumonia, pyo-destructive diseases (including posttraumatic diseases) of the lungs are studied clinically.

Kirillov, M. N.; Reshetnikov, V. A.; Kazhekin, O. A.; Shepelenko, A. F.



Asbestos-related lung disease  

SciTech Connect

Asbestos is a versatile fibrous mineral that can cause lung disease and death. Asbestosis, benign pleural disease, lung cancer, and mesothelioma can all result from inhaling asbestos. The history of disease and exposure risks are discussed. The difficult assessment of risk and the long latency period for development of disease demand evaluation and regular surveillance of asbestos-exposed workers.22 references.

Westerfield, B.T. (Commonwealth Respiratory Consultants, Lexington, KY (United States))



Advances in therapy for acute lung injury.  


Despite advances in the therapy for acute lung injury and adult respiratory distress syndrome, mortality remains high. The iatrogenic risk of ventilator-induced lung injury might contribute to this high mortality because the lungs are hyperinflated. Low tidal volume and inspiratory pressure are surrogates for the stress and strain concept; but lung compliance, transpulmonary pressure, and chest wall elastance might differ in individual patients. In previous published studies, an increasing number of patients were treated successfully with extracorporeal support. Extracorporeal membrane oxygenation and interventional lung assist allow ultraprotective ventilation strategies. However, these assists have different technical aspects and different indications. PMID:23089499

von Dossow-Hanfstingl, Vera



Metal-Induced Lung Disease. Lessons from Japan's Experience  

Microsoft Academic Search

Abstract: Metal-Induced Lung Disease: Lessons from Japan’s Experience: Yukinori K USAKA, et al. Department of Environmental Health, School of Medicine, Fukui Medical University— Metals inducing occupational respiratory diseases, e.g. metal fever, acute and chronic pneumonia, asthma, bronchitis, chronic obstructive lung disease, pulmonary fibrosis and lung cancer are described. The metals mentioned are the following: aluminum, antimony, arsenic, barium, beryllium, cadmium,

Yukinori KUSAKA; Kazuhiro SATO; Narufumi SUGANUMA; Yutaka HOSODA



Acute respiratory distress syndrome and acute lung injury  

Microsoft Academic Search

Acute respiratory distress syndrome (ARDS) is a life threatening respiratory failure due to lung injury from a variety of precipitants. Pathologically ARDS is characterised by diffuse alveolar damage, alveolar capillary leakage, and protein rich pulmonary oedema leading to the clinical manifestation of poor lung compliance, severe hypoxaemia, and bilateral infiltrates on chest radiograph. Several aetiological factors associated with the development

A Dushianthan; M P W Grocott; A D Postle; R Cusack



Pathogenesis of occupational lung disease  

Microsoft Academic Search

Conclusion  Many immunologic and nonimmunologic mechanisms are responsible for producing occupational lung disease. Host factors such\\u000a as atopic status, smoking history, and hyperreactivity of the lung all influence how a worker will respond to toxic and antigenic\\u000a substances in the workplace. Particle factors such as size, shape, and solubility influence the site of lung disease that\\u000a develops. Asthma in the workplace

Bruce F. Paterson; Roy Patterson; Leslie C. Grammer



Genomic Medicine and Lung Diseases  

PubMed Central

The recent explosion of genomic data and technology points to opportunities to redefine lung diseases at the molecular level; to apply integrated genomic approaches to elucidate mechanisms of lung pathophysiology; and to improve early detection, diagnosis, and treatment of lung diseases. Research is needed to translate genomic discoveries into clinical applications, such as detecting preclinical disease, predicting patient outcomes, guiding treatment choices, and most of all identifying potential therapeutic targets for lung diseases. The Division of Lung Diseases in the National Heart, Lung, and Blood Institute convened a workshop, “Genomic Medicine and Lung Diseases,” to discuss the potential for integrated genomics and systems approaches to advance 21st century pulmonary medicine and to evaluate the most promising opportunities for this next phase of genomics research to yield clinical benefit. Workshop sessions included (1) molecular phenotypes, molecular biomarkers, and therapeutics; (2) new technology and opportunity; (3) integrative genomics; (4) molecular anatomy of the lung; (5) novel data and information platforms; and (6) recommendations for exceptional research opportunities in lung genomics research.

Center, David M.; Schwartz, David A.; Solway, Julian; Gail, Dorothy; Laposky, Aaron D.



Occupational Lung Diseases: Prevention and Control.  

National Technical Information Service (NTIS)

Contents: Occupational Lung Diseases: Magnitude of the Problem; Air Pollutants at the Workplace and Their Effects on the Respiratory System; Approaches to the Prevention and Control of Occupational Lung Diseases; Occupational Lung Diseases: Their Causes a...



Claudins in lung diseases  

PubMed Central

Tight junctions are the most apically localized part of the epithelial junctional complex. They regulate the permeability and polarity of cell layers and create compartments in cell membranes. Claudins are structural molecules of tight junctions. There are 27 claudins known, and expression of different claudins is responsible for changes in the electrolyte and solute permeability in cells layers. Studies have shown that claudins and tight junctions also protect multicellular organisms from infections and that some infectious agents may use claudins as targets to invade and weaken the host's defense. In neoplastic diseases, claudin expression may be up- or downregulated. Since their expression is associated with specific tumor types or with specific locations of tumors to a certain degree, they can, in a restricted sense, also be used as tumor markers. However, the regulation of claudin expression is complex involving growth factors and integrins, protein kinases, proto-oncogens and transcription factors. In this review, the significance of claudins is discussed in lung disease and development.



International Union Against Tuberculosis and Lung Disease (IUATLD): Initiatives in non-tuberculous lung disease  

Microsoft Academic Search

IUATLD initiatives in non-tuberculous lung disease developed in the late 1970s, coincident with improving tuberculosis control, and have targeted acute respiratory infections in children and chronic airways disease in adults and in children.The focus has been on methodology and the tools required to document the distribution and determinants of disease, and is illustrated in data gathered in African populations. Instruments

M. R. Becklake



Animal models of acute lung injury  

PubMed Central

Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.

Matute-Bello, Gustavo; Frevert, Charles W.; Martin, Thomas R.



Plasmacytoid Dendritic Cells Control Lung Inflammation and Monocyte Recruitment in Indirect Acute Lung Injury in Mice  

PubMed Central

Indirect acute lung injury (ALI, not caused by a direct insult to the lung) represents the first organ dysfunction in trauma patients, with nonpulmonary sepsis being the most common cause of indirect ALI. Dendritic cells (DCs) are thought to participate in a number of inflammatory lung diseases; however, their role in indirect ALI is currently not established. Using a clinically relevant model of indirect ALI induced in mice by hemorrhagic shock followed 24 hours later by polymicrobial septic challenge, we report that mature DC numbers were markedly increased in the lung during indirect ALI. DC depletion induced a significant increase in indirect ALI severity, which was associated with enhanced lung and plasma proinflammatory cytokine concentration and recruitment of proinflammatory CD115+ monocytes in response to increased lung monocyte chemotactic protein-1 production. Among the different DC subpopulations, plasmacytoid DCs, which were induced and activated in the lung during indirect ALI, were responsible for this effect because their specific depletion reproduced the observations made in DC-depleted mice. As the recruitment of monocytes to the lung plays a central deleterious role in the pathophysiology of indirect ALI, our data therefore position plasmacytoid DCs as important regulators of acute lung inflammation.

Venet, Fabienne; Huang, Xin; Chung, Chun-Shiang; Chen, Yaping; Ayala, Alfred



Carbon monoxide in acute lung injury.  


Despite modern clinical practice in critical care medicine, acute lung injury still causes unacceptably high rates of morbidity and mortality. Therefore, the challenge today is to identify new and effective strategies in order to improve the outcome of these patients. Carbon monoxide, endogenously produced by the heme oxygenase enzyme system, has emerged as promising gaseous therapeutic that exerts protective effects against inflammation, oxidative and mechanical stress, and apoptosis, thus potentially limiting acute lung injury. In this review we discuss the effects of inhaled carbon monoxide on acute lung injury that results from ischemia-reperfusion, transplantation, sepsis, hyperoxia, or mechanical ventilation, the latter referred to as ventilator-induced lung injury. Multiple investigations using in vivo and in vitro models have demonstrated anti-inflammatory, anti-apoptotic, and anti-proliferative properties of carbon monoxide in the lung when applied at low dose prior to or during stressful stimuli. The molecular mechanisms that are modulated by carbon monoxide exposure are still not fully understood. Carbon monoxide mediated lung protection involves several signaling pathways including mitogen activated protein kinases, nuclear factor-?B, activator protein-1, Akt, peroxisome proliferating- activated receptor-?, early growth response-1, caveolin-1, hypoxia-inducible factor-1?, caspases, Bcl-2-family members, heat shock proteins, or molecules of the fibrinolytic axis. At present, clinical trials on the efficacy and safety of CO investigate whether the promising laboratory findings might be translatable to humans. PMID:22201607

Faller, Simone; Hoetzel, Alexander



Interstitial Lung Disease (ILD): Treatment  


... MS Dept. of Medicine View full profile Interstitial Lung Disease (ILD): Treatment Treatment for ILD is based ... what oxygen system will best fit your lifestyle. Pulmonary Rehabilitation A pulmonary rehabilitation program is recommended to ...


Understanding Byssinosis (Brown Lung Disease)  


... lung disease caused by exposure to dusts from cotton processing, hemp and flax. The small airways become ... almost completely limited to workers who handle unprocessed cotton. How Serious is Byssinosis? If you have byssinosis, ...


Lung Imaging in Pulmonary Disease.  

National Technical Information Service (NTIS)

Although it has been recognized for several years that chronic obstructive pulmonary disease (COPD) can cause lung perfusion defects which may simulate pulmonary embolism, relatively little use has been made of either the radioxenon or the radioaerosol in...

G. V. Taplin S. K. Chopra



Military service and lung disease.  


Military personnel can be exposed to toxicants and conditions that can contribute to lung diseases. This article describes what is known about these exposures and diseases, focusing on the Iraq and Afghanistan wars. Adverse lung health outcomes have been reported in US military personnel deployed to Iraq and/or Afghanistan. Most studies to date have been hindered by limited deployment-specific exposure assessment, lack of baseline lung health information, and variable medical evaluations and case definitions. Further research is warranted. Medical surveillance has been recommended for returning troops, but the challenges are substantial. PMID:23153610

Rose, Cecile S



Drug Induced Interstitial Lung Disease  

PubMed Central

With an increasing number of therapeutic drugs, the list of drugs that is responsible for severe pulmonary disease also grows. Many drugs have been associated with pulmonary complications of various types, including interstitial inflammation and fibrosis, bronchospasm, pulmonary edema, and pleural effusions. Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. There are no distinct physiologic, radiographic or pathologic patterns of DILD, and the diagnosis is usually made when a patient with interstitial lung disease (ILD) is exposed to a medication known to result in lung disease. Other causes of ILD must be excluded. Treatment is avoidance of further exposure and systemic corticosteroids in patients with progressive or disabling disease.

Schwaiblmair, Martin; Behr, Werner; Haeckel, Thomas; Markl, Bruno; Foerg, Wolfgang; Berghaus, Thomas



Scintigraphic perfusion patterns in patients with diffuse lung disease  

SciTech Connect

Perfusion scintigrams of 55 patients with radiographic evidence of diffuse lung disease were reviewed. Thirty-nine had acute and/or chronic changes caused by congestive heart failure, and 16 had diffuse reticulonodular disease. A normal or near-normal perfusion pattern was seen in 40/55 (73%), and this finding was equally common in the two groups. The authors conclude that perfusion scintigraphy is useful in excluding pulmonary embolism in patients with radiographic evidence of diffuse, symmetrical lung disease.

Newman, G.E. (Duke Univ. Medical Center, Durham, NC); Sullivan, D.C.; Gottschalk, A.; Putman, C.E.



Stem cells in sepsis and acute lung injury  

PubMed Central

Objective Sepsis and acute lung injury continue to be major causes of morbidity and mortality worldwide despite advances in our understanding of pathophysiology and the discovery of new management strategies. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the potential use of endogenous adult tissue-derived stem cells in sepsis and acute lung injury as prognostic markers and also as exogenous cell-based therapy. Data Sources A directed systematic search of the medical literature using PubMed and OVID, with particular emphasis on the time period after 2002, was done to evaluate topics related to 1) the epidemiology and pathophysiology of sepsis and acute lung injury; and 2) the definition, characterization, and potential use of stem cells in these diseases. Data Synthesis and Findings When available, preferential consideration was given to prospective nonrandomized clinical and preclinical studies. Conclusions Stem cells have shown significant promise in the field of critical care both for 1) prognostic value and 2) treatment strategies. Although several recent studies have identified the potential benefit of stem cells in sepsis and acute lung injury, further investigations are needed to more completely understand stem cells and their potential prognostic and therapeutic value.

Cribbs, Sushma K.; Matthay, Michael A.; Martin, Greg S.



How Is Childhood Interstitial Lung Disease Treated?  


... page from the NHLBI on Twitter. How Is Childhood Interstitial Lung Disease Treated? Childhood interstitial lung disease (chILD) is rare, and little ... Health Topics Lung Transplant article. Rate This Content: Childhood Interstitial Lung Disease Clinical Trials Clinical trials are ...


Acute Lung Injury: Making Injured Lungs Perform Better and Rebuilding Healthy Lungs.  

National Technical Information Service (NTIS)

Acute lung injury (ALI) is a complex condition associated with diffuse injury to the alveolar epithelial gas exchange surface, resulting in marked impairment in the ability to oxygenate blood. The goal of our application is to develop ventilatory and cell...

A. Fine



[Ventilator associated acute lung injury].  


Mechanical ventilation plays a central role in the critical care setting; but its use is closely related with some life threatening complications as nosocomial pneumonia and low cardiac performance. One of the most severe complications is called ventilator-associated lung injury (VALI) and it includes: Barotrauma, volutrauma, atelectrauma, biotrauma and oxygen-mediated toxic effects and it is related with an inflammatory response secondary to the stretching and recruitment process of alveoli within mechanical ventilation. The use of some protective ventilatory strategies has lowered the mortality rate 10% approximately. PMID:16187708

Namendys-Silva, Silvio Antonio; Posadas-Calleja, Juan Gabriel


Health-related Quality of Life after Acute Lung Injury  

Microsoft Academic Search

Our study objective was to assess health-related quality of life in survivors of acute lung injury (ALI) and to supplement generic and disease-specific questionnaires with findings from a focus group of ALI survivors. Six patients participated in the focus group, which revealed patient concerns with am- nesia, depressed mood, avoidance behaviors, and a prolonged recovery period. Using a cross-sec- tional




[Mechanical ventilation of acute lung injury].  


Acute lung injury (ALI) is of paramount importance for modern intensive care since it is one of the most frequent conditions necessitating admission to an ICU. ALI is characterised by severe life threatening hypoxemia which is based on ventilation perfusion mismatching within the lung. This is mostly resulting from atelectasis formation due to primary or secondary inflammation of lung tissue. Many studies showed that this inflammatory process is not restricted to the respiratory system but might result in non pulmonary organ failure and hemodynamic compromise as well. Mechanical ventilation is considered the hallmark treatment for ALI patients aimed to recruit lung tissue and thereby reverse hypoxemia without causing additional lung injury potentially resulting from overdistention or cycling collapse during expiration. Scientific evidence shows us that prevention of ventilator induced lung injury by protective ventilation with reduced tidal volumes is resulting in better clinical outcomes. Moreover, different technologies and adjunctive therapies have been suggested based on their pathophysiology. All these treatment options will be summarized in this article. Given the clear evidence for protective ventilation and bearing in mind that clinical application of this easy concept is still not widespread we will focus on this aspect. PMID:17455139

Kuhlen, R; Dembinski, R



Acute Lung Injury: Epidemiology, Pathogenesis, and Treatment  

PubMed Central

Abstract Acute lung injury (ALI) remains a significant source of morbidity and mortality in the critically ill patient population. Defined by a constellation of clinical criteria (acute onset of bilateral pulmonary infiltrates with hypoxemia without evidence of hydrostatic pulmonary edema), ALI has a high incidence (200,000 per year in the US) and overall mortality remains high. Pathogenesis of ALI is explained by injury to both the vascular endothelium and alveolar epithelium. Recent advances in the understanding of pathophysiology have identified several biologic markers that are associated with worse clinical outcomes. Phase III clinical trials by the NHLBI ARDS Network have resulted in improvement in survival and a reduction in the duration of mechanical ventilation with a lung-protective ventilation strategy and fluid conservative protocol. Potential areas of future treatments include nutritional strategies, statin therapy, and mesenchymal stem cells.

Johnson, Elizabeth R.



Potential application of mesenchymal stem cells in acute lung injury  

PubMed Central

Despite extensive research into the pathogenesis of acute lung injury and the acute respiratory distress syndrome (ALI/ARDS), mortality remains high at approximately 40%. Current treatment is primarily supportive, with lung-protective ventilation and a fluid conservative strategy. Pharmacologic therapies that reduce the severity of lung injury in experimental studies have not yet been translated into effective clinical treatment options. Therefore, innovative therapies are needed. Recent studies have suggested that bone-marrow-derived multipotent mesenchymal stem cells (MSC) may have therapeutic applications in multiple clinical disorders including myocardial infarction, diabetes, sepsis, hepatic and acute renal failure. Recently, MSC have been studied in several in vivo models of lung disease. This review focuses on first describing the existing experimental literature that has tested the use of MSC in models of ALI/ARDS, and then the potential mechanisms underlying their therapeutic use with an emphasis on secreted paracrine soluble factors. The review concludes with a discussion of future research directions required for potential clinical trials.

Lee, Jae Woo; Gupta, Naveen; Serikov, Vladimir; Matthay, Michael A



Acute lung injury and acute respiratory distress syndrome  

PubMed Central

Every year, more information accumulates about the possibility of treating patients with acute lung injury or acute respiratory distress syndrome with specially designed mechanical ventilation strategies. Ventilator modes, positive end-expiratory pressure settings, and recruitment maneuvers play a major role in these strategies. However, what can we take from these experimental and clinical data to the clinical practice? In this article, we discuss substantial options of mechanical ventilation together with some adjunctive therapeutic measures, such as prone positioning and inhalation of nitric oxide.

Ragaller, Maximillian; Richter, Torsten



CXCR2 in Acute Lung Injury  

PubMed Central

In pulmonary inflammation, recruitment of circulating polymorphonuclear leukocytes is essential for host defense and initiates the following specific immune response. One pathological hallmark of acute lung injury and acute respiratory distress syndrome is the uncontrolled transmigration of neutrophils into the lung interstitium and alveolar space. Thereby, the extravasation of leukocytes from the vascular system into the tissue is induced by chemokines that are released from the site of inflammation. The most relevant chemokine receptors of neutrophils are CXC chemokine receptor (CXCR) 1 and CXCR2. CXCR2 is of particular interest since several studies implicate a pivotal role of this receptor in development and promotion of numerous inflammatory disorders. CXCR2 gets activated by ELR+ chemokines, including MIP-2, KC (rodents) and IL-8 (human). Since multiple ELR+ CXC chemokines act on both receptors—CXCR1 and CXCR2—a pharmacologic agent blocking both receptors seems to be advantageous. So far, several CXCR1/2 antagonists have been developed and have been tested successfully in experimental studies. A newly designed CXCR1 and CXCR2 antagonist can be orally administered and was for the first time found efficient in humans. This review highlights the role of CXCR2 in acute lung injury and discusses its potential as a therapeutic target.

Konrad, F. M.; Reutershan, J.



Interstitial lung disease associated with drug therapy  

PubMed Central

Drug-associated interstitial lung disease (ILD) is not uncommon, with diverse patterns ranging from benign infiltrates to the potentially fatal acute respiratory distress syndrome. As acute respiratory failure due to drug-associated ILD has an unpredictable onset and rapid time course, establishing a diagnosis is often difficult. An accurate diagnosis is based on clinical, radiological (including high-resolution computed tomography) and histological manifestations, although is often only possible by exclusion. Cancer chemotherapy is commonly associated with acute disease that, on pathology, is often diffuse alveolar damage. Furthermore, a combination of drugs with or without radiotherapy can increase the risk of ILD. This article reviews treatments for non-small-cell lung cancer (NSCLC) that are associated with the development of ILD and how systematic evaluation of the possible role of these drugs in ILD is warranted. A difference between Japan and the rest of the world in reporting rates of ILD when gefitinib (‘Iressa’) has been used in advanced NSCLC is also discussed. However, the difference remains unexplained, leaving important epidemiological and mechanistic questions.

Camus, P; Kudoh, S; Ebina, M



[Hard metal interstitial lung disease].  


Hard metal lung disease is an unusual disease which can occur in individuals exposed to hard metals. Clinically, the condition resembles hypersensitivity pneumonitis depending mainly on individual susceptibility, which eventually progresses to pulmonary fibrosis. We present two patients with pulmonary fibrosis, who were actually diagnosed after an exhaustive anamnesis and examination of the tissue by scanning microscope to discard hard metals. The evaluation of wedge biopsies by scanning electronic microscope can be very helpful in those cases without a specific diagnosis. PMID:19962814

Montero, M Angeles; de Gracia, Javier; Morell, Ferràn



Diagnostic Invasive Procedures in Diffuse Infiltrative Lung Diseases  

Microsoft Academic Search

The diagnosis of infiltrative diffuse lung disease may require invasive procedures after all noninvasive tools have failed. The clinical context in which these diseases develop and the radiological patterns are crucial for defining the timing and the methods to be used. Immunocompromised hosts are usually acutely ill with fever, cough, shortness of breath, and often with progressive hypoxemia. In this

Venerino Poletti; Marco Chilosi; Dario Olivieri



[Eosinophilic diseases of the lungs].  


Pulmonary eosinophilias belong to a heterogenous group of the diseases characterized by pulmonary shadows related to pulmonary tissue and/or peripheral blood eosinophilia. Although the inflammatory infiltrate consists of macrophages, lymphocytes, neutrophils and eosinophils, a significant marker for the diagnosis and treatment is eosinophilia. By etiology eosinophilic diseases of the lungs fall into primary or idiopathic (common pulmonary eosinophilia, chronic eosinophilic pneumonia, hypereosinophilic syndrome), secondary or of known origin (allergic bronchopulmonary aspergillesis, bronchocentric granulematosis, parasitic invasions, drug-induced reactions, fungal and mycobacterial infection, pulmonary diseases caused by radiation or toxins). Pulmonary eosinophilia can be also associated with systemic diseases (Churg-Strauss syndrome) and tumors. Clinicoroentgenological picture of different eosinophilic diseases of the lungs is almost the same. Verification of the diagnosis is based on the presence of bronchial asthma and extrapulmonary manifestations, the level of eosinophilia in the blood, bronchoalveolar lavage and total IgE, histological and chest CT findings. This article presents modern classification, clinicoroentgenological and histological characteristics of different, primarily idiopathic, eosinophilic diseases of the lungs. PMID:22708427



Lung Recruitment in Patients with the Acute Respiratory Distress Syndrome  

Microsoft Academic Search

Background In the acute respiratory distress syndrome (ARDS), positive end-expiratory pressure (PEEP) may decrease ventilator-induced lung injury by keeping lung regions open that otherwise would be collapsed. Since the effects of PEEP probably depend on the recruitability of lung tissue, we conducted a study to examine the relationship between the percentage of potentially recruitable lung, as indicated by computed tomography

Luciano Gattinoni; Pietro Caironi; Massimo Cressoni; Davide Chiumello; V. Marco Ranieri; Michael Quintel; Sebastiano Russo; Nicolò Patroniti; Rodrigo Cornejo; Guillermo Bugedo



Lung disease related to collagen vascular disease.  


Collagen vascular disease is one of the most common causes of chronic infiltrative lung disease. Patterns of lung injury from collagen vascular disease include nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia, organizing pneumonia, bronchiectasis, obliterative bronchiolitis, and pulmonary arterial hypertension. The prevalence of each entity varies according to the specific disease entity. NSIP and pulmonary hypertension are common in scleroderma, whereas usual interstitial pneumonia, bronchiectasis, and obliterative bronchiolitis are commonly found in rheumatoid arthritis. In systemic lupus erythematosus, pleural effusions and pulmonary hemorrhage are the salient features. In polymyositis, a combination of organizing pneumonia and NSIP is characteristic. Sjögren syndrome is characterized by bronchiectasis and lymphoid interstitial pneumonia, often associated with thin-walled cysts. Ankylosing spondylitis is associated with upper lobe fibrosis, and may be complicated by mycetoma. PMID:19935226

Lynch, David A



Disturbances of rhythm in chronic lung disease.  


Patients with chronic obstructive lung disease have a high incidence and wide variety of cardiac arrhythmias. These arrhythmias are often clinically significant and may be life threatening. Although they occur particularly in the context of acute respiratory failure, arrhythmias are not infrequent in clinically stable patients. The relatively high incidence of sudden arrhythmias seen in acute respiratory failure are associated with a very poor prognosis, in particular, ventricular premature beats and multifocal atrial tachycardia. Long-term electrocardiographic monitoring is valuable in increasing the detection of these arrhythmias and in assessing their clinical significance and response to therapy. The mechanisms producing these arrhythmias are poorly understood and probably multiple. However, disturbances of blood gases, blood pH, and electrolytes or the presence of cor pulmonale or associated coronary artery disease is probably important. The therapy of these arrhythmias must include efforts to improve the patient's ventilatory status as well as careful use of standard antiarrhythmic drugs. Further investigation is needed to define the mechanisms, determine the prognosis, and improve the therapy of the arrhythmias found in chronic obstructive lung disease. PMID:584715

Biggs, F D; Lefrak, S S; Kleiger, R E; Senior, R M; Oliver, G C


Rare lung diseases I - Lymphangioleiomyomatosis  

PubMed Central

The present article is the first in a series that will review selected rare lung diseases. The objective of this series is to promote a greater understanding and awareness of these unusual conditions among respirologists. Each article will begin with a case that serves as a focal point for a discussion of the pathophysiology and management of the particular condition. The first article is on lymphangioleiomyomatosis (LAM); subsequent articles will focus on pulmonary alveolar proteinosis, alpha-1-antitrypsin deficiency and primary ciliary dyskinesia. LAM is a rare, progressive and (without intervention) often fatal interstitial lung disease that predominantly affects women of childbearing age. LAM is characterized by progressive interstitial infiltration of the lung by smooth muscle cells, resulting in diffuse cystic changes of the lung parenchyma. The molecular basis of this disorder has been delineated over the past five years and LAM is now known to be a consequence of mutations in the tuberous sclerosis genes. This knowledge, combined with advances in our understanding of the signalling pathways regulated by these genes, has given rise to potential molecular therapies that hold great promise for treating this devastating disease.

Juvet, Stephen C; Hwang, David; Downey, Gregory P



Alcohol abuse and acute lung injury: can we target therapy?  


Recent studies have revealed an important but previously unrecognized association between alcohol abuse and the risk of acute respiratory distress syndrome (ARDS). This devastating form of lung injury strikes individuals of any age following insults, such as major trauma or sepsis, and even with state-of-the-art medical care it has a mortality as high as 50%. Although the precise incidence is unknown, it is estimated that 200,000 individuals develop ARDS each year in the USA alone. Alcohol abuse independently increases the risk approximately two- to fourfold and, therefore, causes tens of thousands of excess deaths annually. When one couples these grim estimates with the well-recognized association between alcohol abuse and severe lung infections, such as bacterial pneumonia and tuberculosis, it is apparent that alcohol-related lung diseases are a major public health problem. Exciting new studies reveal that the alcoholic lung is characterized by discrete changes in cellular function within the lower airways, mediated via oxidant stress and altered signaling pathways and, in experimental models, is highly amenable to targeted therapies. Furthermore, these therapies are already used clinically for other conditions and could readily be tested in clinical studies of alcoholics at high risk for ARDS and/or with severe lung infections. This article focuses on the epidemiology and pathophysiology of alcohol-induced lung dysfunction and discusses potential new treatments that are suggested by recent experimental findings. PMID:20477184

Prout, Matthew; Martin, Greg S; Drexler, Karen; Brown, Lou Ann S; Guidot, David M



Early Detection of Type III Procollagen Peptide in Acute Lung Injury Pathogenetic and Prognostic Significance  

Microsoft Academic Search

The fibroproliferative reaction to acute lung injury may limit restoration of normal lung function and increase mortality in patients with acute lung injury. A biologic marker of collagen synthesis in the lung may be useful for studying the pathogenesis of acute lung injury and for identifying patients with acute lung injury who are at high risk for death and might



Psychiatric aspects of heart and lung disease in critical care.  


Psychiatric issues are important in the management of patients with heart and lung disease in acute, intensive, and critical care. Adjustment disorders, anxiety disorders, depression, and delirium, sometimes in association with substance abuse and withdrawal problems, are the most common issues, and may affect risk and prognosis of the associated general medical conditions and management in the acute care setting. In children with lung and heart diseases requiring critical care, appreciation of cognitive and social-psychologic developmental milestones is necessary to provide adequate care. PMID:18929947

Shapiro, Peter A; Fedoronko, David A; Epstein, Lucy A; Mirasol, Elsa G E; Desai, Chirag V



Psychiatric aspects of heart and lung disease in critical care.  


Psychiatric issues are important in the management of patients with heart and lung disease in acute, intensive, and critical care. Adjustment disorders, anxiety disorders, depression, and delirium, sometimes in association with substance abuse and withdrawal problems, are the most common issues, and may affect risk and prognosis of the associated general medical conditions and management in the acute care setting. In children with lung and heart diseases requiring critical care, appreciation of cognitive and social-psychologic developmental milestones is necessary to provide adequate care. PMID:21109214

Shapiro, Peter A; Fedoronko, David A; Epstein, Lucy A; Mirasol, Elsa G E; Desai, Chirag V



Development of a Multicomponent Prediction Model for Acute Esophagitis in Lung Cancer Patients Receiving Chemoradiotherapy  

Microsoft Academic Search

Purpose: To construct a model for the prediction of acute esophagitis in lung cancer patients receiving chemoradiotherapy by combining clinical data, treatment parameters, and genotyping profile. Patients and Methods: Data were available for 273 lung cancer patients treated with curative chemoradiotherapy. Clinical data included gender, age, World Health Organization performance score, nicotine use, diabetes, chronic disease, tumor type, tumor stage,

Kim De Ruyck; Nick Sabbe; Cary Oberije; Katrien Vandecasteele; Olivier Thas; Dirk De Ruysscher; Phillipe Lambin; Jan Van Meerbeeck; Wilfried De Neve; Hubert Thierens



Exploring lung physiology in health and disease with lung slices  

PubMed Central

The development of therapeutic approaches to treat lung disease requires an understanding of both the normal and disease physiology of the lung. Although traditional experimental approaches only address either organ or cellular physiology, the use of lung slice preparations provides a unique approach to investigate integrated physiology that links the cellular and organ responses. Living lung slices are robust and can be prepared from a variety of species, including humans, and they retain many aspects of the cellular and structural organization of the lung. Functional portions of intrapulmonary airways, arterioles and veins are present within the alveoli parenchyma. The dynamics of macroscopic changes of contraction and relaxation associated with the airways and vessels are readily observed with conventional low-magnification microscopy. The microscopic changes associated with cellular events, that determine the macroscopic responses, can be observed with confocal or two-photon microscopy. To investigate disease processes, lung slices can either be prepared from animal models of disease or animals exposed to disease invoking conditions. Alternatively, the lung slices themselves can be experimentally manipulated. Because of the ability to observe changes in cell physiology and how these responses manifest themselves at the level of the organ, lung slices have become a standard tool for the investigation of lung disease.

Sanderson, Michael J.



Extracorporeal lung support in patients with chronic obstructive pulmonary disease.  


When patients with chronic obstructive lung disease (COPD) and acute on chronic respiratory insufficiency fail non-invasive ventilation (NIV) they are commonly intubated and treated with invasive mechanical ventilation (IMV) to ensure adequate gas exchange. However, IMV itself is associated with considerable complications which can aggravate any pre-existing lung disease and contribute to morbidity and mortality. When lung protective ventilation fails or cannot be maintained, full or partial extracorporeal lung assist (ECLA) is increasingly used to provide oxygenation and/or carbon dioxide removal. This can rescue patients' lives, help resting their lungs until recovery or transplantation or even avoiding intubation and IMV in the first place. Recent technological improvements of extracorporeal devices have made ECLA more efficient and safe. This article discusses different types of ECLA, their potential indications in patients with COPD as well as the preliminary clinical evidence for their effectiveness and safety. PMID:23698548

Braune, S A; Kluge, S



Pathology Case Study: Lung and Liver Disease  

NSDL National Science Digital Library

The University of Pittsburgh School of Medicine's Department of Pathology has compiled a series of case studies to help both students and instructors in the health sciences field. The patient in this case is a 24 year-old man âÂÂadmitted for acute worsening of his respiratory status and liver failure.â The patientâÂÂs history includes end-stage restrictive lung disease and end-stage liver disease. The âÂÂGross Descriptionâ and âÂÂMicroscopic Descriptionâ sections provide key information and images that contributed to the patientâÂÂs diagnosis. Clicking on the âÂÂFinal Diagnosisâ provides a thorough explanation of the diagnosis and illness from the contributing doctors.

Johnson, Douglas R.



Acute- or subacute-onset lung complications in treating patients with rheumatoid arthritis.  


Rheumatoid arthritis (RA) is a common systemic disease that manifests as inflammatory arthritis of multiple joints and produces a wide variety of intrathoracic lesions, including pleural diseases, diffuse interstitial pneumonia, rheumatoid nodules, and airway disease. Patients treated for RA can have associated lung disease that commonly manifests as diffuse interstitial pneumonia, drug-induced lung injury, and infection. The purpose of this pictorial review is to illustrate the radiographic and clinical features of lung complications of acute or subacute onset in patients treated for RA and to show the computed tomography features of these complications. PMID:22704786

Nakajima, Reiko; Sakai, Fumikazu; Mimura, Toshihide; Tokuda, Hitoshi; Takahashi, Masahiro; Kimura, Fumiko



Pulmonary hypertension in parenchymal lung disease.  


Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases. PMID:23094153

Tsangaris, Iraklis; Tsaknis, Georgios; Anthi, Anastasia; Orfanos, Stylianos E



Pulmonary Hypertension in Parenchymal Lung Disease  

PubMed Central

Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases.

Tsangaris, Iraklis; Tsaknis, Georgios; Anthi, Anastasia; Orfanos, Stylianos E.



Acute respiratory distress syndrome and acute lung injury.  


Acute respiratory distress syndrome (ARDS) is a life threatening respiratory failure due to lung injury from a variety of precipitants. Pathologically ARDS is characterised by diffuse alveolar damage, alveolar capillary leakage, and protein rich pulmonary oedema leading to the clinical manifestation of poor lung compliance, severe hypoxaemia, and bilateral infiltrates on chest radiograph. Several aetiological factors associated with the development of ARDS are identified with sepsis, pneumonia, and trauma with multiple transfusions accounting for most cases. Despite the absence of a robust diagnostic definition, extensive epidemiological investigations suggest ARDS remains a significant health burden with substantial morbidity and mortality. Improvements in outcome following ARDS over the past decade are in part due to improved strategies of mechanical ventilation and advanced support of other failing organs. Optimal treatment involves judicious fluid management, protective lung ventilation with low tidal volumes and moderate positive end expiratory pressure, multi-organ support, and treatment where possible of the underlying cause. Moreover, advances in general supportive measures such as appropriate antimicrobial therapy, early enteral nutrition, prophylaxis against venous thromboembolism and gastrointestinal ulceration are likely contributory reasons for the improved outcomes. Although therapies such as corticosteroids, nitric oxide, prostacyclins, exogenous surfactants, ketoconazole and antioxidants have shown promising clinical effects in animal models, these have failed to translate positively in human studies. Most recently, clinical trials with ?2 agonists aiding alveolar fluid clearance and immunonutrition with omega-3 fatty acids have also provided disappointing results. Despite these negative studies, mortality seems to be in decline due to advances in overall patient care. Future directions of research are likely to concentrate on identifying potential biomarkers or genetic markers to facilitate diagnosis, with phenotyping of patients to predict outcome and treatment response. Pharmacotherapies remain experimental and recent advances in the modulation of inflammation and novel cellular based therapies, such as mesenchymal stem cells, may reduce lung injury and facilitate repair. PMID:21642654

Dushianthan, A; Grocott, M P W; Postle, A D; Cusack, R



Interstitial lung diseases in children  

PubMed Central

Interstitial lung disease (ILD) in infants and children comprises a large spectrum of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. These disorders are characterized by inflammatory and fibrotic changes that affect alveolar walls. Typical features of ILD include dyspnea, diffuse infiltrates on chest radiographs, and abnormal pulmonary function tests with restrictive ventilatory defect and/or impaired gas exchange. Many pathological situations can impair gas exchange and, therefore, may contribute to progressive lung damage and ILD. Consequently, diagnosis approach needs to be structured with a clinical evaluation requiring a careful history paying attention to exposures and systemic diseases. Several classifications for ILD have been proposed but none is entirely satisfactory especially in children. The present article reviews current concepts of pathophysiological mechanisms, etiology and diagnostic approaches, as well as therapeutic strategies. The following diagnostic grouping is used to discuss the various causes of pediatric ILD: 1) exposure-related ILD; 2) systemic disease-associated ILD; 3) alveolar structure disorder-associated ILD; and 4) ILD specific to infancy. Therapeutic options include mainly anti-inflammatory, immunosuppressive, and/or anti-fibrotic drugs. The outcome is highly variable with a mortality rate around 15%. An overall favorable response to corticosteroid therapy is observed in around 50% of cases, often associated with sequelae such as limited exercise tolerance or the need for long-term oxygen therapy.



Apoptosis in Lung Injury and Disease  

Microsoft Academic Search

Pulmonary cell death may contribute significantly to acute and chronic lung injuries caused by various adverse environmental\\u000a agents. Pulmonary cells may die by necrosis, apoptosis, and other forms of regulated cell death. Apoptosis exerts a homeostatic\\u000a function in lung defense and development, through the removal of dysfunctional cells and by regulating cellular proliferation.\\u000a Lung cell apoptosis can occur as a

Stefan W. Ryter; Hong Pyo Kim; Augustine M. K. Choi


Amnion Epithelial Cells as a Candidate Therapy for Acute and Chronic Lung Injury  

PubMed Central

Acute and chronic lung injury represents a major and growing global burden of disease. For many of these lung diseases, the damage is irreparable, exhausting the host's ability to regenerate new lung, and current therapies are simply supportive rather than restorative. Cell-based therapies offer the promise of tissue regeneration for many organs. In this paper, we examine the potential application of amnion epithelial cells, derived from the term placenta, to lung regeneration. We discuss their unique properties of plasticity and immunomodulation, reviewing the experimental evidence that amnion epithelial cells can prevent and repair lung injury, offering the potential to be applied to both neonatal, childhood, and adult lung disease. It is amazing to suggest that the placenta may offer renewed life after birth as well as securing new life before.

Hodges, Ryan J.; Lim, Rebecca; Jenkin, Graham; Wallace, Euan M.



Lung oxidative response after acute coal dust exposure.  


Coal dust exposure can induce an acute alveolar and interstitial inflammation that can lead to chronic pulmonary diseases. The objective of this study was to describe the acute and later effects of acute coal dust exposure in lung parenchyma and the involvement of reactive oxygen species in coal dust effects. Forty-eight male Wistar rats (200-250 mg) were separated into four groups: 48 h, 7 days, 30 days, and 60 days after coal dust instillation. Gross mineral coal dust (3 mg/0.5 mL saline) was administered directly in the lungs of the treatment group by intratracheal instillation. Control animals received only saline solution (0.5 mL). Lipid peroxidation was determined by the quantity of thiobarbituric acid-reactive species (TBARS), oxidative damage to protein was obtained by the determination of carbonyl groups, the total radical-trapping antioxidant parameter (TRAP) was estimated by luminol chemoluminescence emission, catalase activity was measured by the rate of decrease in hydrogen peroxide, and superoxide dismutase activity was assayed by the inhibition of adrenaline autooxidation. Histological evaluation of coal dust-treated rats demonstrated an inflammatory infiltration after 48 h of the exposure. Initially, this was a cellular infiltration suggestive of lymphocyte infiltration with lymphoid hyperplasia that remained until 7 days after induction. This initial response was followed by a chronic inflammatory infiltration characterized by aggregates of macrophages 30 days after induction. This inflammatory response tended to resolve 60 days after induction, being similar to that of control animals. During both the acute and chronic phases of lung inflammation we observed a decrease in the TRAP in the lung of coal dust-exposed animals compared to that in control animals. We also observed an activation of superoxide dismutase 60 days after coal dust exposition. TBARS were increased 60 days after coal dust exposure and protein carbonyl groups increased at all times after coal dust exposure (48 h, 7 days, 30 days, and 60 days). These data suggested a biphasic inflammatory response and the involvement of oxidative damage in coal dust-induced lung damage. PMID:15364596

Pinho, Ricardo A; Bonatto, Fernanda; Andrades, Michael; Frota, Mário Luis C; Ritter, Cristiane; Klamt, Fábio; Dal-Pizzol, Felipe; Uldrich-Kulczynski, Jane M; Moreira, José Cláudio F



Targeting maladaptive glutathione responses in lung disease.  


The lung is unique being exposed directly to the atmospheric environment containing xenobiotics, pathogens, and other agents which are continuously inhaled on a daily basis. Additionally, the lung is exposed to higher ambient oxygen levels which can promote the formation of a complex number of reactive oxygen and nitrogen species. Due to this constant barrage of potential damaging agents, the lung has developed a high degree of plasticity in dealing with ever changing conditions. In the present commentary, we will focus on glutathione (GSH) as a key antioxidant in the lung airways and discuss mechanisms by which the lung uses GSH to adapt to its rapidly changing environment. We will then examine the evidence on how defective and inadequate adaptive responses can lead to lung injury, inflammation and disease. Lastly, we will examine some of the recent attempts to alter lung GSH levels with therapies in a number of human lung diseases and discuss some of the limitations of such approaches. PMID:20951119

Gould, Neal S; Day, Brian J



Pulmonary nuclear medicine: Techniques in diagnosis of lung disease  

SciTech Connect

This book presents papers on the application of nuclear medicine to the diagnosis of lung diseases. Topics considered include lung physiology and anatomy, radiopharmaceuticals in pulmonary medicine, pulmonary embolism, obstructive pulmonary disease, diffuse infiltrative lung disease, pneumoconioses, tumor localization scans in primary lung tumors, the interactions of heart diseases and lung diseases on radionuclide tests of lung anatomy and function, radionuclide imaging in pediatric lung diseases, and future possibilities in pulmonary nuclear medicine.

Atkins, H.L.



Wnt signalling in lung development and diseases  

PubMed Central

There are several signalling pathways involved in lung organogenesis including Notch, TGF? /BMP, Sonic hedgehog (Shh), FGF, EGF, and Wnt. Despite the widely acknowledged significance of Wnt signalling in embryonic lung development, the role of different Wnt pathways in lung pathologies has been slow to emerge. In this review, we will present a synopsis of current Wnt research with particular attention paid to the role of Wnt signals in lung development and in pulmonary diseases.

Pongracz, Judit E; Stockley, Robert A



Matrix Metalloproteinase Activity in Pediatric Acute Lung Injury  

PubMed Central

Pediatric Acute Lung Injury (ALI) is associated with a high mortality and morbidity, and dysregulation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis and evolution of ALI. Here we examined MMP expression and activity in pediatric ALI compared with controls. MMP-8, -9, and to a lesser extent, MMP-2, -3, -11 and -12 were identified at higher levels in lung secretions of pediatric ALI patients compared with controls. Tissue Inhibitor of Matrix metalloproteinase-1 (TIMP-1), a natural inhibitor of MMPs was detected in most ALI samples, but MMP-9:TIMP-1 ratios were high relative to controls. In subjects who remained intubated for ?10 days, MMP-9 activity decreased, with > 80% found in the latent form. In contrast, almost all MMP-8 detected at later disease course was constitutively active. Discriminating MMP-9:TIMP-1 ratios were found in those who had a prolonged ALI course. These results identify a specific repertoire of MMP isoforms in the lung secretions of pediatric ALI patients, and demonstrate inverse changes in MMPs -8 and -9 with protracted disease.

Kong, Michele YF; Gaggar, Amit; Li, Yao; Winkler, Margaret; Blalock, J Edwin; Clancy, JP



Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype?  

PubMed Central

A growing understanding of the complexity of the pathophysiology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), coupled with advances in stem cell biology, has led to a renewed interest in the therapeutic potential of stem cells for this devastating disease. Mesenchymal stem cells appear closest to clinical translation, given the evidence that they may favourably modulate the immune response to reduce lung injury, while maintaining host immune-competence and also facilitating lung regeneration and repair. The demonstration that human mesenchymal stem cells exert benefit in the endotoxin-injured human lung is particularly persuasive. Endothelial progenitor cells also demonstrate promise in reducing endothelial damage, which is a key pathophysiological feature of ALI. Embryonic and induced pluripotent stem cells are at an earlier stage in the translational process, but offer the hope of directly replacing injured lung tissue. The lung itself also contains endogenous stem cells, which may ultimately offer the greatest hope for lung diseases, given their physiologic role in replacing and regenerating native lung tissues. However, significant deficits remain in our knowledge regarding the mechanisms of action of stem cells, their efficacy in relevant pre-clinical models, and their safety, particularly in critically ill patients. These gaps need to be addressed before the enormous therapeutic potential of stem cells for ALI/ARDS can be realised.



Interstitial Lung Diseases: Respiratory Review of 2013  

PubMed Central

Interstitial lung diseases are heterogeneous entities with diverse clinical presentations. Among them, idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease are specific categories that pulmonologists are most likely to encounter in the clinical field. Despite the accumulated data from extensive clinical trial and observations, we continue to have many issues which need to be resolved in this field. In this update, we present the review of several articles regarding the clinical presentation, prognosis and treatment of patients with idiopathic pulmonary fibrosis or connective tissue disease-associated interstitial lung disease.

Kim, Yong Hyun



Corticosteroids in infant chronic lung disease  

Microsoft Academic Search

Corticosteroids in infant chronic lung disease. C. May, A. Greenough. Chronic lung disease (CLD), defined as chronic oxygen dependency at 36 weeks postmenstrual age, is increasing and associated with chronic respiratory morbidity and high health care utilisation at follow up. Many strategies, tested in randomised trials, have failed to reduce CLD. In contrast, corticosteroids if given systemically within the first

A. Greenough; Lung Biology; Anne Greenough


Surgical Lung Diseases in Childhood.  

National Technical Information Service (NTIS)

Contents: Roentgenologic examination of the respiratory system; Congenital malformations; Bronchiectasis; Tuberculosis; Staphylococcal pneumonia and pleurisy; Abscess of the lung; Parasites; Neoplasms of the lung and pleura; Injuries of the chest.

W. Poradowska S. Reszke S. Kubicz



No early respiratory benefit with CVVHDF in patients with acute renal failure and acute lung injury  

Microsoft Academic Search

Background. There is debate as to whether, in patients with acute lung injury, continuous renal replacement therapy has beneficial effects on pulmonary gas exchange by mechanisms other than fluid removal. Because continuous renal replacement therapy is associated with potential morbidity and mortality, it seems unethical to perform a randomized trial in patients with acute lung injury without renal failure. Therefore,

Eric A. J. Hoste; Raymond C. Vanholder; Norbert H. Lameire; Carl D. V. K. Roosens; Johan M. A. Decruyenaere; Stijn I. Blot; Francis A. Colardyn



[Positive end-expiratory pressure : adjustment in acute lung injury].  


Treatment of patients suffering from acute lung injury is a challenge for the treating physician. In recent years ventilation of patients with acute hypoxic lung injury has changed fundamentally. Besides the use of low tidal volumes, the most beneficial setting of positive end-expiratory pressure (PEEP) has been in the focus of researchers. The findings allow adaption of treatment to milder forms of acute lung injury and severe forms. Additionally computed tomography techniques to assess the pulmonary situation and recruitment potential as well as bed-side techniques to adjust PEEP on the ward have been modified and improved. This review gives an outline of recent developments in PEEP adjustment for patients suffering from acute hypoxic and hypercapnic lung injury and explains the fundamental pathophysiology necessary as a basis for correct treatment. PMID:22526744

Bruells, C S; Dembinski, R



Stem Cells in Sepsis and Acute Lung Injury  

PubMed Central

Introduction Critical illnesses continue to be major causes of morbidity and mortality worldwide. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the use of stem cells in sepsis and acute lung injury as prognostic biomarkers and also as a potential for exogenous cell-based therapy. Methods A directed search of the medical literature was done using PubMed and OVID to evaluate topics related to pathophysiology of sepsis and acute lung injury, in addition to the characterization and utilization of stem cells in these diseases. Conclusions Stem cells have shown significant promise in the field of critical care medicine both for prognostication and treatment strategies. Although recent studies have been done to describe the mechanistic pathways of stem cells in critical illness, further investigation is necessary to fully delineate the mechanisms behind a stem cell’s immunomodulatory characteristics and its ability to mobilize and engraft in tissues.

Cribbs, Sushma K.; Martin, Greg S.



Drug-Associated Acute Lung Injury  

PubMed Central

Background: A number of drugs have been reported as risk factors for acute lung injury (ALI) and ARDS. However, evidence is largely limited to case reports, and there is a paucity of data on the incidence and outcome of drug-associated ALI (DALI). Methods: Using a population-based retrospective cohort study design, critically ill patients with a diagnosis of ALI were studied. These patients were classified as having DALI or non-DALI, based on whether they were exposed to prespecified drugs prior to development of ALI. Outcomes were compared between the two groups and frequencies and incidences reported. Results: Among 514 patients with ALI, 49 (9.5%) had DALI with an estimated population-based incidence of 6.6 (95% CI, 4.8-8.5) per 100,000 person-years. Of the 49 patients with DALI, 36 received chemotherapeutic/antiinflammatory agents, and 14 received amiodarone. Twelve patients had no additional risk factors for ALI (probable DALI), whereas 37 had alternative risk factors (possible DALI). Patients with and without DALI had similar baseline characteristics. However, the APACHE (Acute Physiology and Chronic Health Evaluation) III scores (median, 83 vs 70, P = .03), ICU mortality (35% vs 20%, P = .03), and hospital mortality (63% vs 32%, P < .001) were significantly higher in the DALI group compared with those of the non-DALI group. Hospital mortality remained significantly higher after adjusting for APACHE III score on admission and the presence of malignancy in logistic regression analysis (OR, 2.8; 95% CI, 1.3-6.4; P = .009). Conclusions: Drugs are important risk factors for ALI, and recognizing them as such may have important implications for early identification of patients at risk, discontinuation of the offending agent, and prognosis.

Li, Guangxi; Schmickl, Christopher N.; Kashyap, Rahul; Assudani, Jyoti; Limper, Andrew H.; Gajic, Ognjen



Human Epidermal Growth Factor Receptor Signaling in Acute Lung Injury  

PubMed Central

Acute lung injury (ALI) is a syndrome marked by increased permeability across the pulmonary epithelium resulting in pulmonary edema. Recent evidence suggests that members of the human epidermal growth factor receptor (HER) family are activated in alveolar epithelial cells during ALI and regulate alveolar epithelial barrier function. These tyrosine kinase receptors, which also participate in the pathophysiology of pulmonary epithelial malignancies, regulate cell growth, differentiation, and migration as well as cell–cell adhesion, all processes that influence epithelial injury and repair. In this review we outline mechanisms of epithelial injury and repair in ALI, activation patterns of this receptor family in pulmonary epithelial cells as a consequence injury, how receptor activation alters alveolar permeability, and the possible intracellular signaling pathways involved. Finally, we propose a theoretical model for how HER-mediated modulation of alveolar permeability might affect lung injury and repair. Understanding how these receptors signal has direct therapeutic implications in lung injury and other diseases characterized by altered epithelial barrier function.

Downey, Gregory P.; Kern, Jeffrey A.



Imaging of occupational and environmental lung diseases  

SciTech Connect

The chest radiograph is the basic tool for identifying occupational and environmental lung diseases; however, its sensitivity and specificity for the diagnosis of occupational and environmental lung diseases are low. High-resolution CT is the optimal method of recognizing parenchymal abnormalities in occupational and environmental disease. With the exception of pleural plaques, the CT findings of occupational and environmental lung diseases are nonspecific. Therefore, correlation of imaging features with history of exposure, other clinical features, and sometimes pathology is needed for the diagnosis of pneumoconiosis.

Akira, M. [Kinki Cuo Chest Medical Center, Osaka (Japan)



Common lung conditions: chronic obstructive pulmonary disease.  


The etiology of chronic obstructive pulmonary disease (COPD) is chronic lung inflammation. In the United States, this inflammation most commonly is caused by smoking. COPD is diagnosed when an at-risk patient presents with respiratory symptoms and has irreversible airway obstruction indicated by a forced expiratory volume in 1 second/forced vital capacity ratio of less than 0.7. Management goals for COPD include smoking cessation, symptom reduction, exacerbation reduction, hospitalization avoidance, and improvement of quality of life. Stable patients with COPD who remain symptomatic despite using short-acting bronchodilators should start inhaled maintenance drugs to reduce symptoms and exacerbations, avoid hospitalizations, and improve quality of life. A long-acting anticholinergic or a long-acting beta2-agonist (LABA) can be used for initial therapy; these drugs have fewer adverse effects than inhaled corticosteroids (ICS). If patients remain symptomatic despite monotherapy, dual therapy with a long-acting anticholinergic and a LABA, or a LABA and an ICS, may be beneficial. Triple therapy (ie, a long-acting anticholinergic, a LABA, and an ICS) also is used, but it is unclear if triple therapy is superior to dual therapy. Roflumilast, an oral selective inhibitor of phosphodiesterase 4, is used to manage moderate to severe COPD. Continuous oxygen therapy is indicated for patients with COPD who have severe hypoxemia (ie, PaO2 less than 55 mm Hg or an oxygen saturation less than 88% on room air). Nonpharmacologic strategies also are useful to improve patient outcomes. Pulmonary rehabilitation improves dyspnea and quality of life. Pulmonary rehabilitation after an acute exacerbation reduces hospitalizations and mortality, and improves quality of life and exercise capacity. Smoking cessation is the most effective management strategy for reducing morbidity and mortality in patients with COPD. Lung volume reduction surgery, bullectomy, and lung transplantation are surgical interventions that are appropriate for some patients with COPD. PMID:23767419

Delzell, John E



Body Temperature Control in Sepsis-induced Acute Lung Injury  

Microsoft Academic Search

Body temperature is precisely regulated to maintain homeostasis in homeothermic animals. Although it remains unproved whether change of body temperature constitutes a beneficial or a detrimental component of the septic response, temperature control should be an important entity in septic experiments. We investigated the effect of body temperature control on the lipopolysaccharide (LPS)-induced lung injury. Acute lung injury in rats

Giueng-Chueng Wang; Wei-Ming Chi; Wan-Cherng Perng; Kun-Lun Huang



Mesenchymal stem cell therapy in lung disorders: Pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell.  


ABSTRACT Lung disorders such as asthma, acute respiratory distress syndrome (ARDS), chronic obstructive lung disease (COPD), and interstitial lung disease (ILD) show a few common threads of pathogenic mechanisms: inflammation, aberrant immune activity, infection, and fibrosis. Currently no modes of effective treatment are available for ILD or emphysema. Being anti-inflammatory, immunomodulatory, and regenerative in nature, the administration of mesenchymal stem cells (MSCs) has shown the capacity to control immune dysfunction and inflammation in the lung. The intravenous infusion of MSCs, the common mode of delivery, is followed by their entrapment in lung vasculature before MSCs reach to other organ systems thus indicating the feasible and promising approach of MSCs therapy for lung diseases. In this review, we discuss the mechanistic basis for MSCs therapy for asthma, ARDS, COPD, and ILD. PMID:23992090

Inamdar, Ajinkya C; Inamdar, Arati A



Asbestos-induced lung disease.  

PubMed Central

This review attempts to deal with two major questions concerning asbestos-induced lung disease: How does inhaled asbestos cause cell proliferation and fibrosis? and Will there continue to be risk from exposure to asbestos in schools and public buildings? The first is a scientific question that has spawned many interesting new experiments over the past 10 years, and there appear to be two hypothetical schemes which could explain, at least in part, the fibroproliferative effects of asbestos fibers. One supports the view that toxic oxygen radicals generated on fiber surfaces and/or intracellularly are the central mediators of disease. The second hypothesis is not mutually exclusive of the first, but, in my opinion, may be integral to it, i.e., the cellular injury induced by oxygen radicals stimulates the elaboration of multiple varieties of growth factors and cytokines that mediate the pathogenesis of asbestosis. There is increasing evidence that molecules such as platelet-derived growth factor and transforming growth factor beta, both synthesized and secreted by activated lung macrophages, are responsible, respectively, for the increased interstitial cell populations and extracellular matrix proteins that are the hallmarks of asbestos-induced fibrosis. The challenge today is to establish which combinations of the many factors released actually are playing a role in disease pathogenesis. The issue of continued risk currently is more a question of policy and perception than science because a sufficient database has not yet been established to allow full knowledge of the circumstances under which asbestos in buildings constitutes an ongoing health hazard. The litigious nature of this question does not help its resolution. In as much as public policy statements and risk assessment are not within my purview, I have focused on the state-of-the-art of asbestos as a complete carcinogen. It appears to be generally nongenotoxic, but all asbestos fiber types can induce chromosomal mutations and aneuploidy, perhaps through their ability to disrupt normal chromosome segregation. Images FIGURE 1. 1a FIGURE 1. 1b FIGURE 2. FIGURE 3. FIGURE 4. 4a FIGURE 4. 4b FIGURE 5. 5a FIGURE 5. 5b FIGURE 6.

Brody, A R



Imaging of Childhood Interstitial Lung Disease  

PubMed Central

The aphorism that children are not little adults certainly applies for the imaging of interstitial lung disease. Acquiring motion-free images of fine pulmonary structures at desired lung volumes is much more difficult in children than in adults. Several forms of interstitial lung disease are unique to children, and some forms of interstitial lung disease encountered in adults rarely, if ever, occur in children. Meticulous attention to imaging technique and specialized knowledge are required to properly perform and interpret chest imaging studies obtained for the evaluation of childhood interstitial lung disease (chILD). This review will address technique recommendations for imaging chILD, the salient imaging findings in various forms of chILD, and the efficacy of imaging in the diagnosis and management of chILD.



Caprine lung diseases and causal bacteria  

Microsoft Academic Search

Pathological conditions in lungs of slaughtered goats were studied. Sixty lungs were examined and tissue samples and swabs obtained for histopathology and bacterial isolation, respectively. The prevalence of lung diseases was 58.3% (n=35). Gross lesions were categorized into: (a) haemorrhage and congestion 25% (b) emphysema 21.7% (c) hepatization 3.3% and (d) granulomatous nodules about 1 mm diameter 8.3%. On histopathological

T. Ferdausi; M. G. Haider; K. J. Alam; M. A. Baki; M. M. Hossain



Type XVIII collagen degradation products in acute lung injury  

PubMed Central

Introduction In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge. Methods Endostatin was measured by ELISA and western blotting. Results Endostatin is elevated within the plasma and bronchoalveolar lavage fluid of patients with acute lung injury. Lavage endostatin reflected the degree of alveolar neutrophilia and the extent of the loss of protein selectivity of the alveolar-capillary barrier. Plasma levels of endostatin correlated with the severity of physiological derangement. Western blotting confirmed elevated type XVIII collagen precursor levels in the plasma and lavage and multiple endostatin-like fragments in the lavage of patients. One lung ventilation and LPS challenge rapidly induce increases in lung endostatin levels. Conclusions Endostatin may adversely affect both alveolar barrier endothelial and epithelial cells, so its presence within both the circulation and the lung may have a pathophysiological role in acute lung injury that warrants further evaluation.

Perkins, Gavin D; Nathani, Nazim; Richter, Alex G; Park, Daniel; Shyamsundar, Murali; Heljasvaara, Ritva; Pihlajaniemi, Taina; Manji, Mav; Tunnicliffe, W; McAuley, Danny; Gao, Fang; Thickett, David R



Effect of Acute Lung Injury on Structure and Function of Pulmonary Surfactant Films  

Microsoft Academic Search

The structural and functional alterations in pulmonary surfactant that occur during acute lung injury were studied using rat lung surfactant large aggregates (LA) isolated from normal nonventi- lated lungs (N), and from standard ventilated (V) and injuriously ventilated (IV) excised lungs. N lungs inflated significantly better than IV lungs, with V lungs intermediate. Although IV LA phosphati- dylcholine levels were

Amiya K. Panda; Kaushik Nag; Robert R. Harbottle; Karina Rodriguez-Capote; Ruud A. W. Veldhuizen; Nils O. Petersen; Fred Possmayer



Pathogenesis of Lung Disease in Cystic Fibrosis  

Microsoft Academic Search

Lung disease in cystic fibrosis is primarily due to a defect in the cystic fibrosis transmembrane regulating protein (CFTR). This results in abnormal chloride transfer across epithelial membranes causing an excessively viscid mucus lining of the airways. Bacterial invasion particularly with Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa stimulates a vigorous and excessive primarily neutrophil-driven inflammatory response throughout the lungs.

R. Dinwiddie



Krypton-81m ventilation scanning: acute respiratory disease  

SciTech Connect

From experience with 700 patients undergoing ventilation and perfusion lung scanning with krypton-81m/technetium-99m technique, 34 patients suffering from nonembolic acute respiratory disease were selected for review. In 16 patients with pneumonia, all had defects of ventilation corresponding to, or larger than, the radiologic consolidation. In 13 patients there was some preservation of perfusion in the consolidated region. In two of the three patients with matched defects, the pneumonia was of long standing. In seven patients with collapse or atelectasis and in 11 patients with acute reversible bronchial obstruction and normal volume lungs, a similar pattern or ventillation and perfusion was observed.

Lavender, J.P. (Royal Postgraduate Medical School, London, England); Irving, H.; Armstrong, J.D. II



Bench-to-bedside review: Acute respiratory distress syndrome – how neutrophils migrate into the lung  

Microsoft Academic Search

Acute lung injury and its more severe form, acute respiratory distress syndrome, are major challenges in critically ill patients. Activation of circulating neutrophils and transmigration into the alveolar airspace are associated with development of acute lung injury, and inhibitors of neutrophil recruitment attenuate lung damage in many experimental models. The molecular mechanisms of neutrophil recruitment in the lung differ fundamentally

Jörg Reutershan; Klaus Ley



What Are Asbestos-Related Lung Diseases?  


... States. For example, it was used to insulate pipes, boilers, and ships; make brakes; strengthen cement; and ... have asbestos-related lung diseases now because the mineral is no longer widely used. The use of ...


Use of perfluorochemical liquid allows earlier detection of gene expression and use of less vector in normal lung and enhances gene expression in acutely injured lung.  


One of the obstacles to successful lung gene transfer is effective delivery of vector to lung, particularly injured or diseased lung. We have previously demonstrated that intratracheal instillation of perfluorochemical (PFC) liquids along with instillation of recombinant adenovirus and adeno-associated virus vectors, or with cationic liposome vectors, increased total lung gene expression and enhanced distribution of gene expression throughout the lung. To further explore the potential benefits of PFC liquid use, we evaluated the effect of PFC liquid instillation on several other aspects of adenovirus-mediated gene expression in lung. Use of PFC liquid resulted in earlier detection of gene expression and allowed the use of less vector to achieve expression comparable to that observed with the use of higher amounts of vector alone. Using PFC liquid also enhanced gene expression in a rodent model of acute lung injury. PFC liquid did cause a transient inflammation when instilled into normal lungs but did not cause any additional inflammation when instilled alone or with adenovirus vector into acutely injured lungs. Thus, PFC liquid may be a useful adjunct for clinical lung gene transfer, particularly for injured or diseased lungs. PMID:11356078

Weiss, D J; Bonneau, L; Liggitt, D



Lung ultrasound-guided management of acute breathlessness during pregnancy.  


Lung ultrasonography is a standard tool in the intensive care unit and in emergency medicine, but has not been described in the particular setting of the labour ward. During pregnancy, acute respiratory failure and pulmonary oedema are not uncommon life-threatening events. We present two case reports outlining the potential of lung ultrasonography in parturients. In case 1, lung ultrasonography allowed early diagnosis and treatment of acute dyspnoea in a parturient admitted for suspected asthma exacerbation. Lung ultrasonography revealed a 'B-pattern' of vertical lines radiating into the lung tissue, indicating severe pulmonary oedema complicating previously undiagnosed pre-eclampsia. In case 2, a pre-eclamptic patient was managed with combined transthoracic echocardiography and lung ultrasonography. The accuracy of lung ultrasonography in detecting interstitial oedema at a pre-clinical stage allowed adequate fluid resuscitation in this patient who had a high risk of alveolar pulmonary oedema. We believe that these cases strongly support the prospective validation of lung ultrasound for management of lung disorders in pregnant women. PMID:23088788

Zieleskiewicz, L; Lagier, D; Contargyris, C; Bourgoin, A; Gavage, L; Martin, C; Leone, M



NET balancing: a problem in inflammatory lung diseases.  


Neutrophil extracellular traps (NETs) are beneficial antimicrobial defense structures that can help fight against invading pathogens in the host. However, recent studies reveal that NETs exert adverse effects in a number of diseases including those of the lung. Many inflammatory lung diseases are characterized with a massive influx of neutrophils into the airways. Neutrophils contribute to the pathology of these diseases. To date, NETs have been identified in the lungs of cystic fibrosis (CF), acute lung injury (ALI), allergic asthma, and lungs infected with bacteria, virus, or fungi. These microbes and several host factors can stimulate NET formation, or NETosis. Different forms of NETosis have been identified and are dependent on varying types of stimuli. All of these pathways however appear to result in the formation of NETs that contain DNA, modified extracellular histones, proteases, and cytotoxic enzymes. Some of the NET components are immunogenic and damaging to host tissue. Innate immune collectins, such as pulmonary surfactant protein D (SP-D), bind NETs, and enhance the clearance of dying cells and DNA by alveolar macrophages. In many inflammatory lung diseases, bronchoalveolar SP-D levels are altered and its deficiency results in the accumulation of DNA in the lungs. Some of the other therapeutic molecules under consideration for treating NET-related diseases include DNases, antiproteases, myeloperoxidase (MPO) inhibitors, peptidylarginine deiminase-4 inhibitors, and anti-histone antibodies. NETs could provide important biological advantage for the host to fight against certain microbial infections. However, too much of a good thing can be a bad thing. Maintaining the right balance of NET formation and reducing the amount of NETs that accumulate in tissues are essential for harnessing the power of NETs with minimal damage to the hosts. PMID:23355837

Cheng, Olivia Z; Palaniyar, Nades



NET balancing: a problem in inflammatory lung diseases  

PubMed Central

Neutrophil extracellular traps (NETs) are beneficial antimicrobial defense structures that can help fight against invading pathogens in the host. However, recent studies reveal that NETs exert adverse effects in a number of diseases including those of the lung. Many inflammatory lung diseases are characterized with a massive influx of neutrophils into the airways. Neutrophils contribute to the pathology of these diseases. To date, NETs have been identified in the lungs of cystic fibrosis (CF), acute lung injury (ALI), allergic asthma, and lungs infected with bacteria, virus, or fungi. These microbes and several host factors can stimulate NET formation, or NETosis. Different forms of NETosis have been identified and are dependent on varying types of stimuli. All of these pathways however appear to result in the formation of NETs that contain DNA, modified extracellular histones, proteases, and cytotoxic enzymes. Some of the NET components are immunogenic and damaging to host tissue. Innate immune collectins, such as pulmonary surfactant protein D (SP-D), bind NETs, and enhance the clearance of dying cells and DNA by alveolar macrophages. In many inflammatory lung diseases, bronchoalveolar SP-D levels are altered and its deficiency results in the accumulation of DNA in the lungs. Some of the other therapeutic molecules under consideration for treating NET-related diseases include DNases, antiproteases, myeloperoxidase (MPO) inhibitors, peptidylarginine deiminase-4 inhibitors, and anti-histone antibodies. NETs could provide important biological advantage for the host to fight against certain microbial infections. However, too much of a good thing can be a bad thing. Maintaining the right balance of NET formation and reducing the amount of NETs that accumulate in tissues are essential for harnessing the power of NETs with minimal damage to the hosts.

Cheng, Olivia Z.; Palaniyar, Nades



Copy number variation in the CCL4L gene is associated with susceptibility to acute rejection in lung transplantation  

Microsoft Academic Search

Lung transplantation (LT) has become an accepted therapy for selected patients with advanced lung disease. One of the main limitations to successful LT is rejection of the transplanted organ where chemokines are pivotal mediators. Here, we test the relationship between copy number variation (CNV) in the CCL4L chemokine gene and rejection risk in LT patients (n=161). Patients with no acute

R Colobran; N Casamitjana; A Roman; R Faner; E Pedrosa; J I Arostegui; R Pujol-Borrell; M Juan; E Palou



Interstitial lung disease - adults - discharge  


... Stay away from strong odors and fumes. Do breathing exercises. Take all the medicines that your doctor prescribed ... doctor A respiratory therapist who can teach you breathing exercises and how to use your oxygen Your lung ...


Understanding Pneumoconiosis (Black Lung Disease)  


... or loading coal for storage, working in a graphite mine or mill, and manufacturing carbon electrodes and ... of pneumoconiosis . A A A Share Print Lung Cancer Education Resource Online Caregiving Coordination Service Bring the ...


Acute and congenital Chagas disease.  


The acute phase of Chagas disease lasts 4-8 weeks and is characterized by microscopically detectable parasitaemia. Symptoms are usually mild with severe acute disease occurring in less than 1% of patients. Orally transmitted Trypanosoma cruzi outbreaks can have more severe acute morbidity and higher mortality than vector-borne infection. Congenital T. cruzi infection occurs in 1-10% of infants of infected mothers. Most congenital infections are asymptomatic or cause non-specific signs, requiring laboratory screening for detection. A small proportion of congenital infections cause severe morbidity with hepatosplenomegaly, anaemia, meningoencephalitis and/or respiratory insufficiency, with an associated high mortality. Infected infants are presumed to carry the same 20-30% lifetime risk of cardiac or gastrointestinal disease as other infected individuals. Most control programs in Latin America employ prenatal serological screening followed by microscopic examination of cord blood from infants of seropositive mothers. Recent data confirm that polymerase chain reaction (PCR) is more sensitive and detects congenital infections earlier than conventional techniques. For infants not diagnosed at birth, conventional serology is recommended at at 6 to 9 months of age. In programs that have been evaluated, less than 20% of at risk infants completed all steps of the screening algorithm. A sensitive, specific and practical screening test for newborns is needed to enable Chagas disease to be added to newborn screening programs. PMID:21820550

Bern, Caryn; Martin, Diana L; Gilman, Robert H



Acute graft versus host disease  

PubMed Central

Acute graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. About 35%–50% of hematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD. The exact risk is dependent on the stem cell source, age of the patient, conditioning, and GVHD prophylaxis used. Given the number of transplants performed, we can expect about 5500 patients/year to develop acute GVHD. Patients can have involvement of three organs: skin (rash/dermatitis), liver (hepatitis/jaundice), and gastrointestinal tract (abdominal pain/diarrhea). One or more organs may be involved. GVHD is a clinical diagnosis that may be supported with appropriate biopsies. The reason to pursue a tissue biopsy is to help differentiate from other diagnoses which may mimic GVHD, such as viral infection (hepatitis, colitis) or drug reaction (causing skin rash). Acute GVHD is staged and graded (grade 0-IV) by the number and extent of organ involvement. Patients with grade III/IV acute GVHD tend to have a poor outcome. Generally the patient is treated by optimizing their immunosuppression and adding methylprednisolone. About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line) immunosuppressive therapy for which there is currently no standard-of-care. Well-organized clinical trials are imperative to better define second-line therapies for this disease. Additional management issues are attention to wound infections in skin GVHD and fluid/nutrition management in gastrointestinal GVHD. About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD.

Jacobsohn, David A; Vogelsang, Georgia B



Postoperative Acute Exacerbation of IPF after Lung Resection for Primary Lung Cancer  

PubMed Central

Idiopathic pulmonary fibrosis (IPF) is characterized by slowly progressive respiratory dysfunction. Nevertheless, some IPF patients experience acute exacerbations generally characterized by suddenly worsening and fatal respiratory failure with new lung opacities and pathological lesions of diffuse alveolar damage. Acute exacerbation of idiopathic pulmonary fibrosis (AEIPF) is a fatal disorder defined by rapid deterioration of IPF. The condition sometimes occurs in patients who underwent lung resection for primary lung cancer in the acute and subacute postoperative phases. The exact etiology and pathogenesis remain unknown, but the condition is characterized by diffuse alveolar damage superimposed on a background of IPF that probably occurs as a result of a massive lung injury due to some unknown factors. This systematic review shows that the outcome, however, is poor, with postoperative mortality ranging from 33.3% to 100%. In this paper, the etiology, risk factors, pathogenesis, therapy, prognosis, and predictors of postoperative AEIPF are described.

Watanabe, Atsushi; Kawaharada, Nobuyoshi; Higami, Tetsuya



Pulmonary function in sickle cell disease with or without acute chest syndrome  

Microsoft Academic Search

Recurrent acute chest syndrome (ACS) has been suggested as a risk fac- tor for chronic lung dysfunction in sickle cell disease. To investigate this hypothesis, lung function tests were performed in 49 sickle cell disease outpatients whose condition was stable, including 23 patients with a history of two to four episodes of ACS (ACS+) and 26 with no history of

F. Santoli; F. Zerah; N. Vasile; D. Bachir; F. Galacteros; G. Atlan



Elastic pressure-volume curves in acute lung injury and acute respiratory distress syndrome  

Microsoft Academic Search

\\u000a \\u000a Background  The principal features of elastic pressure-volume curves of lungs or the respiratory system (Pel\\/V curves) recorded during reexpansion of collapsed lungs and subsequent deflation have been known since the 1950s. In acute\\u000a respiratory failure and acute respiratory distress syndrome such curves have recently attracted increasing interest because\\u000a new knowledge can be acquired from them, and because such curves may be

Björn Jonson


Elastic pressure-volume curves in acute lung injury and acute respiratory distress syndrome  

Microsoft Academic Search

BackgroundThe principal features of elastic pressure-volume curves of lungs or the respiratory system (P el\\/V curves) recorded during reexpansion of collapsed lungs and subsequent deflation have been known since the 1950s. In acute respiratory failure and acute respiratory distress syndrome such curves have recently attracted increasing interest because new knowledge can be acquired from them, and because such curves may

Björn Jonson



High incidence of acute lung injury in children with Down syndrome  

Microsoft Academic Search

Objective  Acute respiratory tract infection is a common reason for hospitalization in children with Down syndrome (CDS) and is characterized\\u000a by a high morbidity. The severe course of disease in CDS may be related to a higher incidence of acute lung injury (ALI).\\u000a This study evaluated the incidence of ALI and acute respiratory distress syndrome (ARDS) in mechanically ventilated CDS.\\u000a \\u000a \\u000a \\u000a Design and setting  Retrospective cohort

M. Bruijn; L. B. van der Aa; R. R. van Rijn; A. P. Bos; J. B. M. van Woensel



Cell Death and Acute Lung Injury  

Microsoft Academic Search

The concept that apoptosis pathways are involved in the onset and long-term consequences of lung injury is important, but\\u000a significant questions remain. More information is needed about the factors that control the balance between tissue injury\\u000a and tissue repair in the lungs. For example, we need to know more about what determines when the Fas pathway leads to tissue\\u000a injury

T. R. Martin; N. Hagimoto; G. Matute-Bello


Common lung conditions: environmental pollutants and lung disease.  


Exposure to environmental pollutants can have short- and long-term effects on lung health. Sources of air pollution include gases (eg, carbon monoxide, ozone) and particulate matter (eg, soot, dust). In the United States, the Environmental Protection Agency regulates air pollution. Elevated ozone concentrations are associated with increases in lung-related hospitalizations and mortality. Elevated particulate matter pollution increases the risk of cardiopulmonary and lung cancer mortality. Occupations with high exposures to pollutants (eg, heavy construction work, truck driving, auto mechanics) pose higher risk of chronic obstructive lung disease. Some industrial settings (eg, agriculture, sawmills, meat packing plants) also are associated with higher risks from pollutants. The Environmental Protection Agency issues an air quality index for cities and regions in the United States. The upper levels on the index are associated with increases in asthma-related emergency department visits and hospitalizations. Damp and moldy housing might make asthma symptoms worse; individuals from lower socioeconomic groups who live in lower quality housing are particularly at risk. Other household exposures that can have negative effects on lung health include radon, nanoparticles, and biomass fuels. PMID:23767420

Delzell, John E



Occupational lung disease induced by reactive chemicals  

Microsoft Academic Search

In industry, a wide variety of reactive chemicals are employed that can cause respiratory disease in exposed workers) As an example, two general classes of chemicals that cause occupational lung disease in the plastic industry include the anhydrides and the isocyanates. Phthalic anhydride has been a known cause of asthma since the late 1930s. ~ The isocyanates have been known

C. R. Zeiss



Kidney-lung cross-talk and acute kidney injury.  


There is a growing appreciation for the role that acute kidney injury (AKI) plays in the propagation of critical illness. In children, AKI is not only an independent predictor of morbidity and mortality, but is also associated with especially negative outcomes when concurrent with acute lung injury (ALI). Experimental data provide evidence that kidney-lung crosstalk occurs and can be bidirectionally deleterious, although details of the precise molecular mechanisms involved in the AKI-ALI interaction remain incomplete. Clinically, ALI, and the subsequent clinical interventions used to stabilize gas exchange, carry consequences for the homeostasis of kidney function. Meanwhile, AKI negatively affects lung physiology significantly by altering the homeostasis of fluid balance, acid-base balance, and vascular tone. Experimental AKI research supports an "endocrine" role for the kidney, triggering a cascade of extra-renal inflammatory responses affecting lung homeostasis. In this review, we will discuss the pathophysiology of kidney-lung crosstalk, the multiple pathways by which AKI affects kidney-lung homeostasis, and discuss how these phenomena may be unique in critically ill children. Understanding how AKI may affect a "balance of communication" that exists between the kidneys and the lungs is requisite when managing critically ill children, in whom imbalance is the norm. PMID:23334385

Basu, Rajit K; Wheeler, Derek S



Integrating microRNAs into a system biology approach to acute lung injury  

PubMed Central

Acute lung injury (ALI), including the ventilator-induced lung injury (VILI) and the more severe acute respiratory distress syndrome (ARDS), are common and complex inflammatory lung diseases potentially affected by various genetic and non-genetic factors. Using the candidate gene approach, genetic variants associated with immune response and inflammatory pathways have been identified and implicated in ALI. Since gene expression is an intermediate phenotype that resides between DNA sequence variation and higher level cellular or whole-body phenotypes, the illustration of gene expression regulatory networks could potentially enhance understanding of disease susceptibility and the development of inflammatory lung syndromes. MicroRNAs (miRNAs) have emerged as a novel class of gene regulators which play critical roles in complex diseases including ALI. Comparisons of global miRNA profiles in animal models of ALI and VILI identified several miRNAs (e.g., miR-146a, miR-155) previously implicated in immune response and inflammatory pathways. Therefore, via regulation of target genes in these biological processes and pathways, miRNAs potentially contribute to the development of ALI. While this line of inquiry exists at a nascent stage, miRNAs have the potential to be critical components of a comprehensive model for inflammatory lung disease built by a systems biology approach that integrates genetic, genomic, proteomic, epigenetic as well environmental stimuli information. Given their particularly recognized role in regulation of immune and inflammatory responses, miRNAs also serve as novel therapeutic targets and biomarkers for ALI/ARDS or VILI, thus facilitating the realization of personalized medicine for individuals with acute inflammatory lung disease.

Zhou, Tong; Garcia, Joe G.N.; Zhang, Wei



Gujjar Lung: A Disease Mimicking Miliary Tuberculosis  

PubMed Central

Gujjar lung is a chronic lung disease caused due to the long-term exposure to pinewood smoke inhalation in Gujjar community and the people residing at the hilly regions of the Indian sub-continent. This is characterized clinically by progressive cough and dyspnea, distinct radiological patterns and pathological features of anthracotic nodules and fibrosis. A typical case with miliary mottling on chest radiograph is presented and the relevant literature reviewed.

Hassan, G.; Qureshi, Waseem; Kadri, S.M.; Khan, G.Q.; Sona-ul-lah; Rather, Rashid A.; Omer, Mir Suhail



Previous Lung Diseases and Lung Cancer Risk: A Pooled Analysis From the International Lung Cancer Consortium  

PubMed Central

To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (1984–2011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk.

Brenner, Darren R.; Boffetta, Paolo; Duell, Eric J.; Bickeboller, Heike; Rosenberger, Albert; McCormack, Valerie; Muscat, Joshua E.; Yang, Ping; Wichmann, H.-Erich; Brueske-Hohlfeld, Irene; Schwartz, Ann G.; Cote, Michele L.; Tj?nneland, Anne; Friis, S?ren; Le Marchand, Loic; Zhang, Zuo-Feng; Morgenstern, Hal; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Zaridze, David; Rudnai, Peter; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Schejbalova, Miriam; Brennan, Paul; Mates, Ioan N.; Lazarus, Philip; Field, John K.; Raji, Olaide; McLaughlin, John R.; Liu, Geoffrey; Wiencke, John; Neri, Monica; Ugolini, Donatella; Andrew, Angeline S.; Lan, Qing; Hu, Wei; Orlow, Irene; Park, Bernard J.; Hung, Rayjean J.



[Radioisotopic diagnosis of regional lung functions in occupational lung diseases].  


The results are reported from the radioisotope investigations of the regional blood supply, ventilation and difussion of 133 Xenon from four zones of both lungs in 78 patients with all stages of silicosis and 43 patients with chronic bronchitis--emphysema. Unsystemic and scattered focal disturbances of the separate respiration processes are established. They should be given consideration separately and together with the classical non-isotope investigations, with a view to the making of a precise functional diagnosis and occupational expertise, because they reflect the changes due to the basic disease as well as the other accompanying lung diseases as pneumosclerosis, chronic bronchitis, emphysema, tumors, etc. The complete safety, lack of unpleasant procedures for the patient and sufficient accuracy urge their wider application in practice, including as screening tests. PMID:654222

Vaskov, L



The role of chemokine receptors in acute lung allograft rejection.  


Recruitment of inflammatory cells to vascularised allografts is a hallmark of rejection, and paves the way for chronic allograft injury. Chemokines play pivotal roles in the directed movement of leukocytes. Herein, we define the distribution of chemokine receptors for the most common cell types during human lung allograft rejection as a prerequisite for therapeutic interventions. Immunohistochemistry was performed on lung allograft biopsies from 54 patients for the chemokine receptors CCR5, CXCR3 and CXCR1 and the Duffy antigen/receptor for chemokines (DARC). Perivascular infiltrates in acute lung rejection are composed of subsets of mononuclear cells expressing the chemokine receptors CXCR1, CXCR3 and CCR5. DARC-positive small vessels and capillary vessels were associated with sites of inflammation and their number was increased during episodes of acute lung rejection. DARC expression correlated with an increase in interstitial CCR5-positive T-cells and CXCR1-positive leukocytes. Leucokytic infiltrates in bronchial/bronchiolar rejection express CXCR1 and CXCR3. This is the first study that demonstrates an induction of the chemokine binding protein DARC at sites of acute human lung allograft rejection. Co-localisation with the chemokine receptors CXCR1 and CCR5 may indicate a role for DARC expression during leukocyte adhesion and interstitial infiltration. PMID:19608592

Geleff, S; Draganovici, D; Jaksch, P; Segerer, S



Aetiology of chronic suppurative lung disease.  

PubMed Central

Forty one (1%) of 4000 children referred for respiratory disease had chronic suppurative lung disease not due to cystic fibrosis. Further investigations showed congenital malformations in six (15%), primary ciliary dyskinesia syndrome in seven (17%), 11 had immunological abnormalities (27%), and two bronchiectasis due to aspiration (5%). Therefore the underlying cause for the disease was found in 63%. Identification of predisposing causes may facilitate prevention of further bronchial damage.

Nikolaizik, W H; Warner, J O



A Clinical Approach to Rare Lung Diseases  

Microsoft Academic Search

\\u000a The National Institutes of Health Office of Rare Diseases (ORD) defines a rare or orphan disease as a disorder with a prevalence\\u000a of fewer than 200,000 affected individuals within the United States whereas in Europe, rare diseases are defined as those\\u000a disorders that affect 1 or fewer individuals per 2,000 persons. Several consortia exist for the compilation of rare lung

Ralph J. Panos


Matrix Metalloproteinase Activity in Pediatric Acute Lung Injury  

Microsoft Academic Search

Pediatric Acute Lung Injury (ALI) is associated with a high mortality and morbidity, and dysregulation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis and evolution of ALI. Here we examined MMP expression and activity in pedi- atric ALI compared with controls. MMP-8, -9, and to a lesser extent, MMP-2, -3, -11 and -12 were identified at

Michele YF Kong; Amit Gaggar; Yao Li; Margaret Winkler; J Edwin Blalock



Lung Compliance and Chronic Obstructive Pulmonary Disease  

PubMed Central

Chronic obstructive pulmonary disease, namely, pulmonary emphysema and chronic bronchitis, is a chronic inflammatory response of the airways to noxious particles or gases, with resulting pathological and pathophysiological changes in the lung. The main pathophysiological aspects of the disease are airflow obstruction and hyperinflation. The mechanical properties of the respiratory system and its component parts are studied by determining the corresponding volume-pressure (P-V) relationships. The consequences of the inflammatory response on the lung structure and function are depicted on the volume-pressure relationships.

Papandrinopoulou, D.; Tzouda, V.; Tsoukalas, G.



Interstitial lung disease as initial manifestation of systemic lupus erythematosus.  


Interstitial lung disease (ILD) is a group of disease characterized by fibrosis and scarring of the lung while Systemic Lupus Erythematosus is a multisystem disorder and both of these diseases are of unknown etiologies. Interstitial lung disease, as a presenting feature of SLE without any significant systemic involvement is a unique presentation and this case reports such example. Keywords: interstitial lung disease; systemic lupus erythematosus. PMID:23787534

Kumar, A; Khan, U; Shrestha, B; Thapa, S; Rizvi, N



Racial and Ethnic Disparities in Mortality from Acute Lung Injury  

PubMed Central

Objective: Little is known about the influence of race and ethnicity on mortality from acute lung injury. We sought to determine whether black race or Hispanic ethnicity are independently associated with mortality among patients with acute lung injury. Design: Retrospective cohort study of patients enrolled in the Acute Respiratory Distress Syndrome (ARDS) Network randomized controlled trials. Setting: Adult intensive care units participating in the ARDS Network trials. Patients: 2362 mechanically ventilated patients (1,715 white, 449 black and 198 Hispanic) with acute lung injury. Measurements and Main Results: The primary outcome was 60-day mortality. A secondary outcome was number of ventilator-free days. Crude mortality was 33% for both blacks and Hispanics compared with 27% for whites (p=0.02). After adjusting for demographic and clinical covariates, the association between race/ethnicity and mortality persisted (OR = 1.42; 95% CI 1.10-1.84 for blacks; OR=1.94; 95% CI, 1.36-2.77 for Hispanics; OR=1 for whites, reference). After adjustment for severity of illness (Acute Physiology Score), black race was no longer significantly associated with mortality (OR =1.25; 95% CI, 0.95-1.66), whereas the association with Hispanic ethnicity persisted (OR=2.00; 95% CI, 1.37-2.90). Hispanics had significantly fewer ventilator-free days compared with whites after adjustment for demographic and clinical covariates (mean difference in days = -2.3; 95% CI -3.9 to -0.7). Conclusions: Black and Hispanic patients with acute lung injury have a significantly higher risk of death compared to white patients. This increased risk appeared to be mediated by increased severity of illness at presentation for blacks, but was unexplained among Hispanics.

Erickson, Sara E.; Shlipak, Michael G.; Martin, Greg S.; Wheeler, Arthur P.; Ancukiewicz, Marek; Matthay, Michael A.; Eisner, Mark D.



New perspectives on basic mechanisms in lung disease. 6. Proteinase imbalance: its role in lung disease  

Microsoft Academic Search

The hypothesis, some 30 years ago, that NE was the sole proteolytic agent responsible for the development of emphysema seems naive in retrospect. The availability of technology to measure NE facilitated the early research into the relationship between NE and lung disease. Despite an abundance of information on the activity of NE in the lung, it will probably require prospective

T D Tetley



Acute Chagas disease in a returning traveler.  


Acute Chagas disease is rarely recognized, and the risk for acquiring the disease is undefined in travelers to Central America. We describe a case of acute Chagas disease in a traveler to Costa Rica and highlight the need for increased awareness of this infection in travelers to Chagas-endemic areas. PMID:23091192

Carter, Yvonne L; Juliano, Jonathan J; Montgomery, Susan P; Qvarnstrom, Yvonne



Idiopathic interstitial lung disease: anatomoradiologic pathogenesis.  


Interstitial lung disease encompasses a large number of clinical disorders that affect the epithelium, the endothelium or both cell surfaces of alveolar wall and satellite structures including terminal and respiratory bronchioles. Causative factors are over 200 from bacteria, fungi, viruses, protozoans, to collagen disease, hypersensitivity and inorganic pneumoconiosis. Clinical and histological findings of open lung and transbronchial biopsies from 50 patients are reported, 18 patients were affected by diffuse alveolar damage (DAD), 15 patients by usual interstitial pneumonia (UIP), 8 patients by non specific interstitial pneumonia-fibrosis (NSIP-F), 9 patients by bronchiolitis obliterans organizing pneumonia (BOOP) correlated with conventional chest radiography in 30 patients and with HRCT in 31 patients. Interstitial lung disease other than histiocytosis X share anatomoradiologic features indicative for activity, chronic progression, chronic quiescence, chronic advanced and irreversible disease. In general, the histologic features correlate with radiographic patterns and even if radiologic findings do not always supply definitive diagnosis, some HRCT patterns are highly suggestive and usually classified into 4 categories: normal; with ground glass attenuation; linear, nodular or reticulo-nodular; honeycombing, suggestive for end-stage fibrosis. Correlation of HRCT with histologic findings in 31 patients with idiopathic interstitial fibrosis (IIF) allowed assessment of disease activity, follow-up and therapeutic result. HRCT definitely better than conventional radiology detects the presence, type and extent of parenchymal alterations, differentiating potential reversible lesions (inflammatory) from potentially irreversible (fibrotic) lesions. In IIF, for diagnostic accuracy the specimen of open lung (the gold standard), transbronchial or video-thoracoscopic biopsy must be preoperative, HRCT-assisted and centered on ground glass opacties (or nodules in suspected histiocytosis X) since a diagnostically reliable biopsy correlates with HRCT morphology of histologic specimen. Interstitial lung disease includes benign as well as malignant forms, thus only a multidisciplinary approach can prevent long term hazardous effects as severe cor pulmonale or a fatal outcome. The histologic HRCT-assisted assessment of "active" lesions is crucial for correct careful treatment of these patients. PMID:9145019

Chiodera, P


Incidence and risk factors of recurrent Acute Lung Injury  

PubMed Central

OBJECTIVE To determine risk factors for development of recurrent acute lung injury (ALI). DESIGN A population-based case-control study. SETTING The study was conducted in Olmsted County, Minnesota from 1999 to 2008. PATIENTS Using a validated electronic screening protocol, investigators identified intensive care patients with acute hypoxemia and bilateral pulmonary infiltrates. MEASUREMENTS The presence of ALI was independently confirmed according to American-European Consensus Conference (AECC) criteria. Recurrent ALI cases were subsequently matched (1:1:1) with two controls (single ALI and no ALI) on age, gender, duration of follow-up, and predisposing conditions. Risk factors evaluated included gastroesophageal reflux disease (GERD), alcohol consumption, smoking, chronic opioid use, and transfusions. MAIN RESULTS We identified 917 patients with ALI, of which 19 developed a second episode, yielding an incidence of 2.02 (95%CI 1.10–2.93) per 100,000 person years. The median time to development of the second episode was 264 days (IQR 80 – 460) days, with a mortality of 47% during the episode. The history of GERD was highly prevalent in patients who developed recurrent ALI: 15/19 patients (79%), compared to 5/19 (26%) matches with single episode of ALI (p=0.006) and 8/19 (42%) matches without ALI (p=0.016). Other exposures were similar between the cases and the two matched controls. CONCLUSIONS Recurrent ALI is not a rare phenomenon in the ICU, and may continue to increase with improvements in survival following ALI. GERD was identified as an important risk factor for recurrent ALI and may suggest an important role of gastric aspiration in the development of this syndrome.

Bice, Thomas; Li, Guangxi; Malinchoc, Michael; Lee, Augustine S.; Gajic, Ognjen



Distinct roles for the A2B adenosine receptor in acute and chronic stages of bleomycin-induced lung injury.  


Adenosine is an extracellular signaling molecule that is generated in response to cell injury where it orchestrates tissue protection and repair. Whereas adenosine is best known for promoting anti-inflammatory activities during acute injury responses, prolonged elevations can enhance destructive tissue remodeling processes associated with chronic disease states. The generation of adenosine and the subsequent activation of the adenosine 2B receptor (A(2B)R) is an important processes in the regulation of both acute and chronic lung disease. The goal of this study was to examine the contribution of the A(2B)R in models of bleomycin-induced lung injury that exhibit varying degrees of acute and chronic injury. Intratracheal bleomycin exposure results in substantial acute lung injury followed by progressive fibrosis. In this model, genetic removal of the A(2B)R resulted in enhanced loss of barrier function and increased pulmonary inflammation, with few differences in indexes of pulmonary fibrosis. These results support an anti-inflammatory role for this receptor in this model of acute lung injury. In contrast, systemic exposure of mice to bleomycin resulted in modest acute lung injury together with progressive pulmonary fibrosis. In this model, the effects of A(2B)R removal on acute lung injury were negligible; however, there were substantial reductions in pulmonary fibrosis, supporting a profibrotic role for this receptor. A(2B)R-dependent regulation of IL-6 production was identified as a potential mechanism involved in the diminished pulmonary fibrosis seen in A(2B)R knockout mice exposed to i.p. bleomycin. These studies highlight the distinct roles of A(2B)R signaling during acute and chronic stages of lung injury. PMID:21149612

Zhou, Yang; Schneider, Daniel J; Morschl, Eva; Song, Ling; Pedroza, Mesias; Karmouty-Quintana, Harry; Le, Thuy; Sun, Chun-Xiao; Blackburn, Michael R



[Interstitial lung disease due to domestic moulds].  


Identifying the role of fungi present in the domestic environment in the development of interstitial pneumonia can be a difficult clinical problem. We report a case of interstitial lung disease case occurring in a 53-year-old patient. He presented with profound hypoxemia (PaO(2) 54mmHg). Chest CT showed diffuse ground glass opacities. Initial blood tests for allergy and autoimmune disease were negative. Faced with a worsening of his clinical status after returning home he was hospitalized several times. At fibreoptic bronchoscopy, multiple white deposits were observed. Bronchoalveolar lavage with differential cell count was performed, revealing a 23% lymphocytosis. Serology for specific household molds showed moderate reaction to various molds found in homes, especially Stachybotrys chartarum. Pulmonary function tests revealed a moderate restrictive pattern with impaired diffusion of carbon monoxide and a bronchiolocentric interstitial pneumonia was found at lung biopsy. After a permanent move to a new residence, clinical parameters, radiological, biological and functional normalized. The final diagnosis was interstitial lung disease related to mycotoxins of S. Chartarum. The diagnosis of hypersensitivity pneumonitis to domestic mold or interstitial lung disease secondary to mycotoxins should be considered in patients presenting with interstitial pneumonia and requires specific investigations to ensure that an environmental cause with an allergic or toxic role is not missed. PMID:21943538

Blanc, A-L; Delhaes, L; Copin, M-C; Stach, B; Faivre, J-B; Wallaert, B



Update in Diffuse Parenchymal Lung Diseases 2005  

Microsoft Academic Search

CLINICAL ADVANCES A number of publications have shed light on important clinical concepts surrounding the clinical evaluation and management of diffuse parenchymal lung diseases (DPLDs). These include approaches to idiopathic interstitial pneumonias (IIPs), includ- ing nonspecific interstitial pneumonia (NSIP) and idiopathic pul- monary fibrosis (IPF; idiopathic usual interstitial pneumonia (UIP)), connective tissue-associated DPLD, hypersensitivity pneumonitis (HP), and lymphangioleiomyomatosis (LAM). IIPs

Fernando J. Martinez; Michael P. Keane


Praeruptorin D and E attenuate lipopolysaccharide/hydrochloric acid induced acute lung injury in mice.  


Acute lung injury is a life-threatening syndrome characterized by overwhelming lung inflammation and increased microvascular permeability, which causes a high mortality rate worldwide. The dry root of Peucedanum praeruptorum Dunn has been long used to treat respiratory diseases in China. In the present study, Praeruptorin A, C, D and E (PA, PC, PD and PE), four pyranocoumarins extracted from this herb, have been investigated for the pharmacological effects in experimental lung injury mouse models. In lipopolysaccharide (LPS) challenged mice, PA and PC did not show protective effect against lung injury at the dose of 80 mg/kg. However, PD and PE significantly inhibited the infiltration of activated polymorphonuclear leukocytes (PMNs) and decreased the levels of TNF-? and IL-6 in bronchoalveolar lavage fluid at the same dose. There was no statistically significant difference between PD and PE group. Further study demonstrated that PD and PE suppressed protein extravasations in bronchoalveolar lavage fluid, attenuated myeloperoxidase (MPO) activity and the pathological changes in the lung. Both PD and PE suppressed LPS induced Nuclear Factor-kappa B (NF-?B) pathway activation in the lung by decreasing the cytoplasmic loss of Inhibitor ?B-? (I?B-?) protein and inhibiting the translocation of p65 from cytoplasm to nucleus. We also extended our study to acid-induced acute lung injury and found that these two compounds protected mice from hydrochloric acid (HCl)-induced lung injury by inhibiting PMNs influx, IL-6 release and protein exudation. Taken together, these results suggested that PD and PE might be useful in the therapy of lung injury. PMID:23588118

Yu, Peng-Jiu; Li, Jing-Rong; Zhu, Zheng-Guang; Kong, Huan-Yu; Jin, Hong; Zhang, Jun-Yan; Tian, Yuan-Xin; Li, Zhong-Huang; Wu, Xiao-Yun; Zhang, Jia-Jie; Wu, Shu-Guang



Acute lung injury after inhalation of nitric acid.  


We report two cases of acute lung injury after the inhalation of nitric acid fumes in an industrial accident. The first patient, who was not using a respirator and standing in close proximity to the site of spillage of concentrated nitric acid, presented within 12 h with worsening dyspnea and required noninvasive ventilation for type 1 respiratory failure. The second case presented 1 day later with similar symptoms, but only required supportive treatment with high-flow oxygen. Both patients' chest radiographs showed widespread bilateral airspace shadows consistent with acute lung injury. Both received treatment with systemic steroids. They were discharged from hospital 5 days postexposure. Initial lung function test showed a restrictive pattern that normalized by 3 weeks postexposure. This case series describes the natural history after acute inhalation of nitric acid fumes, and demonstrates that the severity of lung injury is directly dependent on the exposure level. It also highlights the use of noninvasive ventilatory support in the management of such patients. PMID:19078840

Kao, Shih Ling; Yap, Eng Soo; Khoo, See Meng; Lim, Tow Keang; Mukhopadhyay, Amartya; Teo, Sylvia Tzu Li



Reversing disability of irreversible lung disease.  

PubMed Central

Pulmonary rehabilitation is a comprehensive multifaceted team approach for integrating medical management, coping skills, self-management techniques, and exercise reconditioning. It provides patients with chronic lung disease the ability to adapt and live full and nearly normal lives. These changes are possible because the overall disability includes significant reversible components: Patients have bronchospasm, infection, and cor pulmonale; they respond to progressively impaired lungs by progressive inactivity, leading to physical deconditioning. Both factors contribute to dyspnea. Because patients naturally fear dyspnea, they panic easily. During panic, their work of breathing may increase and respiratory failure may result. Pulmonary rehabilitation provides good medical management; provides exercises to increase strength, endurance, and tolerance to dyspnea; and trains patients in panic control. These programs have not been shown to lengthen life span or improve static lung function. They increase exercise performance and render patients functional, independent, and subject to fewer hospital admissions. Pulmonary rehabilitation is the only approach to chronic lung disease short of lung transplantation that improves the long-term outlook for these patients. Images

Tiep, B. L.



Extracellular matrix mechanics in lung parenchymal diseases  

PubMed Central

In this review, we examine how the extracellular matrix (ECM) of the lung contributes to the overall mechanical properties of the parenchyma, and how these properties change in disease. The connective tissues of the lung are composed of cells and ECM, which includes a variety of biological macromolecules and water. The macromolecules that are most important in determining the mechanical properties of the ECM are collagen, elastin, and proteoglycans. We first discuss the various components of the ECM and how their architectural organization gives rise to the mechanical properties of the parenchyma. Next, we examine how mechanical forces can affect the physiological functioning of the lung parenchyma. Collagen plays an especially important role in determining the homeostasis and cellular responses to injury because it is the most important load-bearing component of the parenchyma. We then demonstrate how the concept of percolation can be used to link microscopic pathologic alterations in the parenchyma to clinically measurable lung function during the progression of emphysema and fibrosis. Finally, we speculate about the possibility of using targeted tissue engineering to optimize treatment of these two major lung diseases.

Suki, Bela; Bates, Jason H.T.



Antioxidant vitamins and prevention of lung disease  

SciTech Connect

Although the evidence for oxidative stress for air pollution in the human lung is fragmentary, the hypothesis that oxidative stress is an important, if not the sole, mechanism of toxicity of oxidizing air pollutants and tobacco smoke is compelling and growing. First, biochemical mechanisms have been worked out for oxidation of lung lipids by the gas phase of cigarette smoke, NO[sub 2] and O[sub 3]. The oxidation of lung lipids can be prevented by both vitamins C and E. Vitamin C is more effective in preventing oxidation by NO[sub 2], and vitamin E is more effective against O[sub 3]. Second, multiple species of experimental animals develop lung disease similar to human bronchitis and emphysema from exposure to NO[sub 2] and O[sub 3], respectively. The development of these diseases occurs over a near lifetime exposure when the levels of NO[sub 2] or O[sub 3] are at near ambient air pollution values. Third, isolated human cells are protected against oxidative damage from NO[sub 2] and O[sub 3] by both vitamins C and E. Fourth, the vitamin C level in the lung either declines on exposure to NO[sub 2] for short-term exposures or increases on chronic cigarette smoke exposure. The effects of cigarette smoking on serum vitamin C is apparently complex and may be related to the daily intake of vitamin C as well as smoking. Serum vitamin C levels may be poor indicators of lung demands when daily vitamin C intakes are above 100 mg/day. Fifth, vitamin C supplementation protects against the effects of ambient levels of air pollution in adults as measured by histamine challenge. An augmented response to histamine challenge may represent increased lung permeability brought about by air pollution. In experimental animal and human experiments, the amount of vitamin C or E that afforded protection was in excess of the current recommended dietary allowance.

Menzel, D.B. (Univ. of California, Irvine (United States))



Long-Term Control Medications for Lung Diseases  


... Term Control Medications Long-Term Control Medications for Lung Diseases Long-term control medications are taken daily ... RN, MSN, CNS, AE-C (December, 2012). Related Lung Disease Information About Asthma About COPD Respiratory Treatment ...


Diabetes, insulin, and development of acute lung injury  

PubMed Central

Objectives Recently, many studies have investigated the immunomodulatory effects of insulin and glucose control in critical illness. This review examines evidence regarding the relationship between diabetes and the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), reviews studies of lung injury related to glycemic and nonglycemic metabolic features of diabetes, and examines the effect of diabetic therapies. Data Sources and Study Selection A MEDLINE/PubMed search from inception to August 1, 2008, was conducted using the search terms acute lung injury, acute respiratory distress syndrome, hyperglycemia, diabetes mellitus, insulin, hydroxymethylglutaryl-CoA reductase inhibitors (statins), angiotensin-converting enzyme inhibitor, and peroxisome proliferator-activated receptors, including combinations of these terms. Bibliographies of retrieved articles were manually reviewed. Data Extraction and Synthesis Available studies were critically reviewed, and data were extracted with special attention to the human and animal studies that explored a) diabetes and ALI; b) hyperglycemia and ALI; c) metabolic nonhyperglycemic features of diabetes and ALI; and d) diabetic therapies and ALI. Conclusions Clinical and experimental data indicate that diabetes is protective against the development of ALI/ARDS. The pathways involved are complex and likely include effects of hyperglycemia on the inflammatory response, metabolic abnormalities in diabetes, and the interactions of therapeutic agents given to diabetic patients. Multidisciplinary, multifaceted studies, involving both animal models and clinical and molecular epidemiology techniques, are essential.

Honiden, Shyoko; Gong, Michelle N.



Severe Transfusion-Related Acute Lung Injury  

Microsoft Academic Search

A 46-yr-old man developed severe hypoxemia, pulmo- nary infiltrates, and an acute decrease in his leukocyte count shortly after transfusion of fresh-frozen plasma (FFP) during recovery from cardiac surgery. Cardiogenic pulmonary edema was excluded. Granulocyte-reactive and agglutinating alloantibodies were detected in the se- rum of the fresh-frozen plasma donor. The cross-match with the patient's granulocytes revealed antibodies specific for HLA

Lukas Brander; Angelika Reil; Juergen Bux; Behrouz Mansouri Taleghani; Bruno Regli; Jukka Takala



Undifferentiated Connective Tissue Disease-Associated Interstitial Lung Disease: Changes in Lung Function  

Microsoft Academic Search

Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung\\u000a disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely\\u000a to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We\\u000a identified subjects enrolled in the UCSF ILD

Brent W. Kinder; Cyrus Shariat; Harold R. Collard; Laura L. Koth; Paul J. Wolters; Jeffrey A. Golden; Ralph J. Panos; Talmadge E. King



Acute chest syndrome in sickle cell disease.  


Acute chest syndrome is a common cause of death among patients with sickle cell disease, and an unfamiliar condition to most Australian medical practitioners. We present a case of acute chest syndrome successfully treated with inhaled nitric oxide and exchange transfusion. In the discussion we review current and future management options of acute chest syndrome. PMID:20575992

Laurie, G A



New concepts of the pathogenesis of cystic fibrosis lung disease  

Microsoft Academic Search

New concepts of the pathogenesis of cystic fibrosis lung disease. R.C. Boucher. #ERS Journals Ltd 2004. ABSTRACT: Although there has been impressive progress in the elucidation of the genetic and molecular basis of cystic fibrosis (CF), the pathogenesis of CF lung disease remains obscure. The elucidation of the pathogenesis of CF lung disease requires both a full description of normal

R. C. Boucher



Acute dacryoadenitis in Crohn's disease  

PubMed Central

A 48-year-old Filipino female presented with unilateral acute onset painful red eye, blurred vision and yellow discharge. On examination she had a corrected visual acuity of 6/5 in the right eye and 6/18 in the left eye. There was a left-sided periorbital swelling, with chemosis involving the bulbar conjunctiva on the temporal aspect. Ocular motility showed limitation of left-sided abduction with mild limitation of laevoelevation and laevodepression. She was afebrile and systemic examination was unremarkable. Medical history included diagnosis of Crohn's disease since the age of 20. She was on oral mesalamine 1 g for mildly active colitis. Full blood count was normal but erythrocyte sedimentation rate and C reactive protein were raised. Blood culture and conjunctival swab were negative. Contrast-enhanced CT scan demonstrated enlargement of the lacrimal gland. She was managed conservatively with acetaminophen and codeine for pain and swelling. She recovered completely in 2 weeks with no sequelae.

Wagh, Vijay; Raman, S V; Parrish, R



Acute Kidney Injury Increases Mortality After Lung Transplantation  

PubMed Central

Background Acute kidney injury requiring renal replacement therapy (RRT) is associated with increased mortality after cardiac surgery. Studies examining the impact of RRT after lung transplantation (LTx) are limited. We evaluated risk factors and outcomes associated with RRT after LTx. Methods We retrospectively reviewed all LTx recipients in the United Network for Organ Sharing database. Preoperative renal function was stratified by glomerular filtration rate (GFR) as determined by the Modification of Diet in Renal Disease formula (strata: ?90, 60 to 90, and <60 mL · min?1 · 1.73m?2). Primary outcomes were 30-day, 1-year, and 5-year survival and need for post-LTx RRT. Risk adjusted multivariable Cox proportional hazards regression examined mortality. A multivariable logistic regression model evaluated risk factors for RRT. Results From 2001 to 2011, 12,108 patients underwent LTx. After LTx, 655 patients (5.51%) required RRT. Patients requiring post-LTx RRT had decreased survival at 30 days (96.7% versus 76.0%, p < 0.001), 1 year (85.5% versus 35.8%, p < 0.001), and 5 years (56.4% versus 20.0%, p < 0.001). These differences persisted on multivariable analysis at 30 days (hazard ratio [HR] 7.98 [6.16 to 10.33], p < 0.001), 1 year (HR 7.93 [6.84 to 9.19], p < 0.001), and 5 years (HR 5.39 [4.75 to 6.11], p < 0.001). Preoperative kidney function was an important predictor of post-LTx RRT for a GFR of 60 to 90 (odds ratio 1.42 [1.16 to 1.75], p = 0.001) and a GFR less than 60 (odds ratio 2.68 [2.07 to 3.46], p < 0.001]. High center volume was protective. Conclusions In the largest study to evaluate acute kidney injury after LTx, the incidence of RRT is 5.51%. The need for post-LTx RRT dramatically increases both short- and long-term mortality. Several variables, including preoperative renal function, are predictors of post-LTx RRT and could be used to identify transplant candidates at risk for acute kidney injury.

George, Timothy J.; Arnaoutakis, George J.; Beaty, Claude A.; Pipeling, Matthew R.; Merlo, Christian A.; Conte, John V.; Shah, Ashish S.



Pulmonary oxygen consumption: a hypothesis to explain the increase in oxygen consumption of low birth weight infants with lung disease  

Microsoft Academic Search

Objective: We determined pulmonary oxygen consumption (VO2lung) in low-birthweight infants with acute lung disease to help explain the greater whole-body oxygen consumption (VO2wb) in these infants with than in those without lung disease. Methods and materials: Eleven infants (birth weight 1,076넴 g; gestational age 28Dž weeks) undergoing mechanical ventilation for respiratory distress syndrome were studied in their first week of

Andreas Schulze; Kabir Abubakar; Gerald Gill; John C. Sinclair



Presumptive acute lung injury following multiple surgeries in a cat  

PubMed Central

A 12-year-old, 3.5-kg spayed female domestic shorthair cat had a tracheal mass identified as malignant B-cell lymphoma. The cat had tracheal resection and subsequently developed laryngeal paralysis. Due to multiple episodes of respiratory distress the cat subsequently had tracheal surgeries. Finally, the cat had a sudden onset of severe respiratory distress and collapsed. Computed tomography imaging and arterial blood gas analysis supported a diagnosis of acute lung injury.

Katayama, Masaaki; Okamura, Yasuhiko; Katayama, Rieko; Sasaki, Jun; Shimamura, Shunsuke; Uzuka, Yuji; Kamishina, Hiroaki; Nezu, Yoshinori



[Sodium dichloroisocyanurate-induced acute lung injury in a child].  


Intoxication, by cyanurate and its chlorated derivatives in children, is increasingly reported in the literature due to accidental ingestion compared to accidental inhalation. We report a case in a 5-year-old child who presented with acute lung injury due to accidental inhalation of gas formed after a reaction of sodium dichloroisocyanurate tablets with water. Prevention remains the best way to reduce the risk of children being intoxicated by inhalation of the gas formed after contact of tablets with water. PMID:23433843

Wiel, E; Sicot, J; Leteurtre, S; Binoche, A; Nisse, P; Assez, N



Recruitment Maneuvers for Acute Lung Injury A Systematic Review  

Microsoft Academic Search

Rationale: There are conflicting data regarding the safety and efficacy of recruitmentmaneuvers(RMs) in patients with acute lung injury (ALI). Objectives: To summarize the physiologic effects and adverse events in adult patients with ALI receiving RMs. Methods:Systematicreviewofcaseseries,observationalstudies,and randomized clinical trials with pooling of study-level data. Measurements and Main Results: Forty studies (1,185 patients) met inclusion criteria. Oxygenation (31 studies; 636 patients)

Eddy Fan; M. Elizabeth Wilcox; Roy G. Brower; Thomas E. Stewart; Sangeeta Mehta; Stephen E. Lapinsky; Maureen O. Meade; Niall D. Ferguson


Beyond mortality: future clinical research in acute lung injury.  


Mortality in National Heart, Lung and Blood Institute-sponsored clinical trials of treatments for acute lung injury (ALI) has decreased dramatically during the past two decades. As a consequence, design of such trials based on a mortality outcome requires ever-increasing numbers of patients. Recognizing that advances in clinical trial design might be applicable to these trials and might allow trials with fewer patients, the National Heart, Lung and Blood Institute convened a workshop of extramural experts from several disciplines. The workshop assessed the current state of clinical research addressing ALI, identified research needs, and recommended: (1) continued performance of trials evaluating treatments of patients with ALI; (2) development of strategies to perform ALI prevention trials; (3) observational studies of patients without ALI undergoing prolonged mechanical ventilation; and (4) development of a standardized format for reporting methods, endpoints, and results of ALI trials. PMID:20224063

Spragg, Roger G; Bernard, Gordon R; Checkley, William; Curtis, J Randall; Gajic, Ognjen; Guyatt, Gordon; Hall, Jesse; Israel, Elliott; Jain, Manu; Needham, Dale M; Randolph, Adrienne G; Rubenfeld, Gordon D; Schoenfeld, David; Thompson, B Taylor; Ware, Lorraine B; Young, Duncan; Harabin, Andrea L




PubMed Central

The increasing number of population-based and epidemiological associations between oxidant pollutant exposures and cardiopulmonary disease exacerbation, decrements in pulmonary function, and mortality underscores the important detrimental effects of oxidants on public health. Because inhaled oxidants initiate a number of pathologic processes, including inflammation of the airways which may contribute to the pathogenesis and/or exacerbation of airways disease, it is critical to understand the mechanisms through which exogenous and endogenous oxidants interact with molecules in the cells, tissues, and epithelial lining fluid (ELF) of the lung. Furthermore, it is clear that inter-individual variation in response to a given exposure also exists across an individual lifetime. Because of the potential impact that oxidant exposures may have on reproductive outcomes and infant, child, and adult health, identification of the intrinsic and extrinsic factors that may influence susceptibility to oxidants remains an important issue. In this review, we discuss mechanisms of oxidant stress in the lung, the role of oxidants in lung disease pathogenesis and exacerbation (e.g. asthma, COPD, and ARDS), and the potential risk factors (e.g. age, genetics) for enhanced susceptibility to oxidant-induced disease.

Ciencewicki, Jonathan; Trivedi, Shweta; Kleeberger, Steven R.



Recent Trends in Acute Lung Injury Mortality: 1996-2005  

PubMed Central

Background: Studies from single centers have suggested that mortality from acute lung injury (ALI) has declined over time. However, recent trends in ALI mortality from centers across the U.S. are unknown. Whether recent advances in the treatment of ALI or related critical illnesses have resulted in decreased mortality from ALI is not clear. Methods: In a study of 2451 mechanically ventilated patients with ALI enrolled in the Acute Respiratory Distress Syndrome (ARDS) Network randomized controlled trials between 1996-2005, we evaluated whether there was a temporal improvement in 60-day mortality. We also investigated whether there were temporal improvements in mortality specific to individual causes of lung injury (pneumonia, sepsis, trauma, aspiration, transfusion). Results: Crude mortality was 35% in 1996-1997 and declined during each subsequent time period to a low of 26% in 2004-2005 (test for trend p<0.0005). After adjusting for demographic and clinical covariates, including receipt of lower tidal volume ventilation and severity of illness, the temporal trend persisted (test for trend p=0.002). When analyzed by individual causes of lung injury, there were not any statistically significant temporal trends in 60-day mortality for the most common causes of lung injury (pneumonia, sepsis, aspiration, trauma). Conclusions: Over the past decade, there appears to be a clear temporal improvement in survival among patients with ALI treated at ARDS Network centers. Our findings strongly suggest that other advancements in critical care, aside from lower tidal volume ventilation, accounted for this improvement in mortality.

Erickson, Sara E.; Martin, Greg S.; Davis, J. Lucian; Matthay, Michael A.; Eisner, Mark D.



Physiologic response and lung distribution of lavage versus bolus Exosurf in piglets with acute lung injury.  


Despite evidence of surfactant dysfunction in the acute respiratory distress syndrome (ARDS), treatment with exogenous surfactant remains experimental. Uneven pulmonary distribution is one factor that may limit response. We investigated whether exogenous surfactant administered by lavage, consisting of a 35 ml/kg volume instilled by gravity and followed immediately by passive drainage (LAVAGE), would result in better lung distribution and physiologic response than with surfactant administered as a 5 ml/kg bolus (BOLUS). Exosurf, an artificial surfactant, was administered after acute lung injury induced by saline lung lavage in neonatal piglets. In the LAVAGE group (n= 9), 10.1 +/- 0.4 ml/kg of surfactant was retained, corresponding to a phospholipid dose of 136 +/- 5 mg/kg. In the BOLUS group (n = 9), the dose administered was 203 mg/kg phospholipid. Piglets in the LAVAGE group demonstrated greater improvement in pulmonary function, including PaO2, PaCO2, ventilation efficiency index, functional residual capacity (FRC), and pressure-volume curves than piglets in the BOLUS group. Some differences were found in lung distribution of surfactant. We conclude that Exosurf is more effective when administered by lavage in this lung injury model. We speculate that the lavage method of administration holds promise as an alternative method of surfactant administration in patients with ARDS. PMID:8665043

Balaraman, V; Sood, S L; Finn, K C; Hashiro, G; Uyehara, C F; Easa, D



Severe airflow obstruction and eosinophilic lung disease after Stevens-Johnson syndrome  

Microsoft Academic Search

Respiratory involvement is a frequent complication of Stevens-Johnson syndrome (SJS). However, there are very few convincing reports of persistent pulmonary sequelae, as demonstrated by spirometry, radiology and pathology. The current study presents a case of a 13-yr-old female with T-cell acute lymphocytic leukaemia who developed persistent, severe, obstructive lung disease following an episode of SJS. A lung biopsy demonstrated bronchiolar

A. P. Shah; H. Xu; P. J. Sime; D. R. Trawick



The Epithelial Cell and Lung Cancer: The Link between Chronic Obstructive Pulmonary Disease and Lung Cancer  

Microsoft Academic Search

Chronic obstructive pulmonary disease (COPD) and lung cancer currently form the basis for an enormous disease burden in the developed world. As a result of changing smoking trends and tobacco use, regrettably, a similar picture is arising rapidly within the developing world. COPD is a recognised risk factor for lung cancer, and a significant proportion of patients diagnosed with lung

Claire Rooney; Tariq Sethi



Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders*  

PubMed Central

Objective Patients with trauma-associated acute lung injury have better outcomes than patients with other clinical risks for lung injury, but the mechanisms behind these improved outcomes are unclear. We sought to compare the clinical and biological features of patients with trauma-associated lung injury with those of patients with other risks for lung injury and to determine whether the improved outcomes of trauma patients reflect their baseline health status or less severe lung injury, or both. Design, Setting, and Patients Analysis of clinical and biological data from 1,451 patients enrolled in two large randomized, controlled trials of ventilator management in acute lung injury. Measurements and Main Results Compared with patients with other clinical risks for lung injury, trauma patients were younger and generally less acutely and chronically ill. Even after adjusting for these baseline differences, trauma patients had significantly lower plasma levels of intercellular adhesion molecule-1, von Willebrand factor antigen, surfactant protein-D, and soluble tumor necrosis factor receptor-1, which are biomarkers of lung epithelial and endothelial injury previously found to be prognostic in acute lung injury. In contrast, markers of acute inflammation, except for interleukin-6, and disordered coagulation were similar in trauma and nontrauma patients. Trauma-associated lung injury patients had a significantly lower odds of death at 90 days, even after adjusting for baseline clinical factors including age, gender, ethnicity, comorbidities, and severity of illness (odds ratio, 0.44; 95% confidence interval, 0.24 – 0.82; p = .01). Conclusions Patients with trauma-associated lung injury are less acutely and chronically ill than other lung injury patients; however, these baseline clinical differences do not adequately explain their improved outcomes. Instead, the better outcomes of the trauma population may be explained, in part, by less severe lung epithelial and endothelial injury.

Calfee, Carolyn S.; Eisner, Mark D.; Ware, Lorraine B.; Thompson, B. Taylor; Parsons, Polly E.; Wheeler, Arthur P.; Korpak, Anna; Matthay, Michael A.



Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs  

PubMed Central

Background Phorbol myristate acetate (PMA) is a strong neutrophil activator and has been used to induce acute lung injury (ALI). Niacinamide (NAC) is a compound of B complex. It exerts protective effects on the ALI caused by various challenges. The purpose was to evaluate the protective effects of niacinamide (NAC) on the PMA-induced ALI and associated changes. Methods The rat's lungs were isolated in situ and perfused with constant flow. A total of 60 isolated lungs were randomized into 6 groups to received Vehicle (DMSO 100 ?g/g), PMA 4 ?g/g (lung weight), cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight). There were 10 isolated lungs in each group. We measured the lung weight and parameters related to ALI. The pulmonary arterial pressure and capillary filtration coefficient (Kfc) were determined in isolated lungs. ATP (adenotriphosphate) and PARP [poly(adenosine diphophate-ribose) polymerase] contents in lung tissues were detected. Real-time PCR was employed to display the expression of inducible and endothelial NO synthases (iNOS and eNOS). The neutrophil-derived mediators in lung perfusate were determined. Results PMA caused increases in lung weight parameters. This agent produced pulmonary hypertension and increased microvascular permeability. It resulted in decrease in ATP and increase in PARP. The expression of iNOS and eNOS was upregulated following PMA. PMA increased the neutrophil-derived mediators. Pathological examination revealed lung edema and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive cells in macrophages and endothelial cells. These pathophysiological and biochemical changes were diminished by NAC treatment. The NAC effects were dose-dependent. Conclusions Our results suggest that neutrophil activation and release of neutrophil-derived mediators by PMA cause ALI and associated changes. NO production through the iNOS-producing cells plays a detrimental role in the PMA-induced lung injury. ATP is beneficial, while PARP plays a deteriorative effect on the PMA-induced ALI. NAC exerts protective effects on the inflammatory cascade leading to pulmonary injury. This B complex compound may be applied for clinical usage and therapeutic regimen.



Nilotinib-induced interstitial lung disease.  


Nilotinib is a second-generation tyrosine kinase inhibitor active in patients with chronic myeloid leukemia (CML) resistant to imatinib, and has been recently approved for newly diagnosed patients. We present a case of nilotinib-induced interstitial lung disease (ILD). A 67-year-old female patient was initially treated with imatinib for chronic-phase Philadelphia chromosome-positive (Ph(+)) CML. Imatinib was replaced by nilotinib because of hematological toxicity. The patient had received nilotinib for about 3 years without significant adverse effects. She visited the clinic due to chronic cough; chest X-ray revealed consolidations in both lung fields. Nilotinib-induced ILD was diagnosed based on intensive workup, including lung biopsy. She responded dramatically to corticosteroid therapy. To our knowledge, this is the first reported case of nilotinib-induced ILD in a patient with Ph(+) CML. We emphasize that if unexplained lung abnormalities progress in patients receiving nilotinib, physicians should consider this potentially fatal complication in their differential diagnoses. PMID:23877149

Go, Se-Il; Lee, Won Sup; Lee, Gyeong-Won; Kang, Jung Hun; Kang, Myung Hee; Lee, Jeong-Hee; Kim, Hoon-Gu



Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge  

PubMed Central

Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days. Interestingly, lung inflammation was more prevalent following viral clearance, as leukocyte numbers peaked at 14 days postinfection (dpi) and remained elevated at 28 dpi compared to those of mock-infected controls. Lung macrophages but not dendritic cells were rapidly activated, and both cell types had high activation marker expression at late infection time points. Lung proinflammatory cytokines were induced at 1 to 14 dpi, but most returned to baseline by 28 dpi except interleukin 12 (IL-12) and gamma interferon. In SARS-CoV homologous rechallenge studies, 11 of the 12 animals were free of replicating virus at day 5 after rechallenge. However, incidence and severity of lung inflammation was not reduced despite the limited viral replication upon rechallenge. Evaluating the role of antibodies in immune protection or potentiation revealed a progressive increase in anti-SARS-CoV antibodies in lung and serum that did not correlate temporally or spatially with enhanced viral replication. This study represents one of the first comprehensive analyses of lung immunity, including changes in leukocyte populations, lung-specific cytokines, and antibody responses following SARS-CoV rechallenge in AGMs.

Clay, Candice; Donart, Nathan; Fomukong, Ndingsa; Knight, Jennifer B.; Lei, Wanli; Price, Lance; Hahn, Fletcher; Van Westrienen, Jesse



Primary severe acute respiratory syndrome coronavirus infection limits replication but not lung inflammation upon homologous rechallenge.  


Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days. Interestingly, lung inflammation was more prevalent following viral clearance, as leukocyte numbers peaked at 14 days postinfection (dpi) and remained elevated at 28 dpi compared to those of mock-infected controls. Lung macrophages but not dendritic cells were rapidly activated, and both cell types had high activation marker expression at late infection time points. Lung proinflammatory cytokines were induced at 1 to 14 dpi, but most returned to baseline by 28 dpi except interleukin 12 (IL-12) and gamma interferon. In SARS-CoV homologous rechallenge studies, 11 of the 12 animals were free of replicating virus at day 5 after rechallenge. However, incidence and severity of lung inflammation was not reduced despite the limited viral replication upon rechallenge. Evaluating the role of antibodies in immune protection or potentiation revealed a progressive increase in anti-SARS-CoV antibodies in lung and serum that did not correlate temporally or spatially with enhanced viral replication. This study represents one of the first comprehensive analyses of lung immunity, including changes in leukocyte populations, lung-specific cytokines, and antibody responses following SARS-CoV rechallenge in AGMs. PMID:22345460

Clay, Candice; Donart, Nathan; Fomukong, Ndingsa; Knight, Jennifer B; Lei, Wanli; Price, Lance; Hahn, Fletcher; Van Westrienen, Jesse; Harrod, Kevin S



Ventilator-induced lung injury and the evolution of lung-protective strategies in acute respiratory distress syndrome.  


Traditional ventilator management of acute respiratory distress syndrome (ARDS), emphasizing normalization of blood gases, promoted high rates of conventional barotrauma. Research revealed a broader range of ventilator-induced lung injury, physiologically and histopathologically indistinguishable from ARDS itself. It is now known that overdistention and cyclic inflation of injured lung can exacerbate lung injury and probably promote systemic inflammation, effects minimized by low tidal volumes/plateau pressures and by application of positive end-expiratory pressure. No compelling data suggest a safe interval for nonprotective ventilation in humans; historically defined "low" tidal volumes may remain excessive for certain patients. Protective ventilation, however, entails carbon dioxide accumulation ("permissive hypercapnia"). Despite extensive study, debate remains, even over whether consequent respiratory acidosis is harmful, tolerable with physiologic adaptation, or intrinsically adaptive. Its gross systemic effects seem generally tolerated by critically ill patients; however, subsets, including those with ischemic heart disease, left or right heart failure, pulmonary hypertension, or cranial injury, may be at higher risk. In controlled trials demonstrating mortality benefit from lung-protective ventilation, acidosis was more tightly controlled than in negative studies. Decreased acidosis-associated dyspnea probably explains reduced use of sedatives and paralytics noted in those trials. There may thus be disparate goals in ARDS management: rapid institution of a restrictive ventilatory strategy, and avoidance of significant acidosis. We review data pertaining to ARDS physiology, ventilator-induced lung injury, lung-protective ventilatory strategies, and the physiology of respiratory acidosis. Tracheal gas insufflation is considered as a means to reconcile the clinical goals of ventilatory reduction and control of acidosis. PMID:11175242

Gillette, M A; Hess, D R



Therapeutic Effect of the Tuber of Alisma orientale on Lipopolysaccharide-Induced Acute Lung Injury  

PubMed Central

Although Alisma orientale, an ethnic herb, has been prescribed for treating various diseases in Asian traditional medicine, experimental evidence to support its therapeutic effects is lacking. Here, we sought to determine whether A. orientale has a therapeutic effect on acute lung injury (ALI). Ethanol extract of the tuber of A. orientale (EEAO) was prepared and fingerprinted by HPLC for its constituents. Mice received an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) for the induction of ALI. At 2?h after LPS treatment, mice received an intratracheal (i.t.) spraying of various amounts of EEAO to the lung. Bioluminescence imaging of transgenic NF-?B/luciferase reporter mice shows that i.t. EEAO posttreatment suppressed lung inflammation. In similar experiments with C57BL/6 mice, EEAO posttreatment significantly improved lung inflammation, as assessed by H&E staining of lung sections, counting of neutrophils in bronchoalveolar lavage fluid, and semiquantitative RT-PCR analyses of proinflammatory cytokines and Nrf2-dependent genes in the inflamed lungs. Furthermore, EEAO posttreatment enhanced the survival of mice that received a lethal dose of LPS. Together, our results provide evidence that A. orientale has a therapeutic effect on ALI induced by sepsis.

Kwun, Min Jung; Choi, Jun-Yong; Ahn, Kyung-Seop; Oh, Sei-Ryang; Lee, Yong Gyu; Christman, John W.; Sadikot, Ruxana T.



Genetic Predisposition to Respiratory Diseases: Infiltrative Lung Diseases  

Microsoft Academic Search

The availability of high-throughput genotyping and large collaborative clinical networks creating well-characterized patient populations with DNA repositories has facilitated genome-wide scans and candidate gene studies to identify susceptibility alleles for the development of interstitial lung disease. The association of pulmonary fibrosis with rare inherited disorders, and the variable susceptibility of inbred mouse strains to this disease indicate that pulmonary fibrosis

Mark P. Steele; Kevin K. Brown



Diarrheal Diseases - Acute and Chronic  


... doctor if you have a family history of celiac disease, inflammatory bowel disease (IBD), have unintentional weight loss, ... common small bowel disease in the U.S. is celiac disease, also called celiac sprue. Crohn’s disease can also ...


Bench-to-bedside review: Adjuncts to mechanical ventilation in patients with acute lung injury  

Microsoft Academic Search

Mechanical ventilation is indispensable for the survival of patients with acute lung injury and acute respiratory distress syndrome. However, excessive tidal volumes and inadequate lung recruitment may contribute to mortality by causing ventilator-induced lung injury. This bench-to-bedside review presents the scientific rationale for using adjuncts to mechanical ventilation aimed at optimizing lung recruitment and preventing the deleterious consequences of reduced

Jean-Jacques Rouby; Qin Lu



Lung Transplantation and Lung Volume Reduction Surgery versus Transplantation in Chronic Obstructive Pulmonary Disease  

PubMed Central

Lung transplantation and lung volume reduction surgery are surgical options for patients with advanced chronic obstructive pulmonary disease that is refractory to medical treatment. In this review, we discuss the differential indications for each procedure, as well as compare their risks and benefits. We also present an algorithm for selecting the most appropriate procedure for individual patients. Finally, we discuss the feasibility and role of lung transplantation after lung volume reduction surgery in the management of selected patients with chronic obstructive pulmonary disease.

Patel, Namrata; DeCamp, Malcolm; Criner, Gerard J.



Honokiol attenuates the severity of acute pancreatitis and associated lung injury via acceleration of acinar cell apoptosis.  


Severe acute pancreatitis remains a life-threatening disease with a high mortality rate among a defined proportion of those affected. Apoptosis has been hypothesized to be a beneficial form of cell death in acute pancreatitis. Honokiol, a low-molecular-weight natural product, possesses the ability of anti-inflammation and apoptosis induction. Here, we investigate whether honokiol can ameliorate severe acute pancreatitis and the associated acute lung injury in a mouse model. Mice received six injections of cerulein at 1-h intervals, then given one intraperitoneal injection of bacterial lipopolysaccharide for the induction of severe acute pancreatitis. Moreover, mice were intraperitoneally given vehicle or honokiol 10 min after the first cerulein injection. Honokiol protected against the severity of acute pancreatitis in terms of increased serum amylase and lipase levels, pancreas pathological injury, and associated acute lung injury. Honokiol significantly reduced the increases in serum tumor necrosis factor-?, interleukin 1, and nitric oxide levels 3 h and serum high-mobility group box 1 24 h after acute pancreatitis induction. Honokiol also significantly decreased myeloperoxidase activities in the pancreas and the lungs. Endoplasmic reticulum stress-related molecules eIF2? (phosphorylated) and CHOP protein expressions, apoptosis, and caspase-3 activity were increased in the pancreas of mice with severe acute pancreatitis, which was unexpectedly enhanced by honokiol treatment. These results suggest that honokiol protects against acute pancreatitis and limits the spread of inflammatory damage to the lung in a severe acute pancreatitis mouse model. The acceleration of pancreatic cell apoptosis by honokiol may play a pivotal role. PMID:22258232

Weng, Te I; Wu, Hsiao Yi; Chen, Bo Lin; Liu, Shing Hwa



Nilotinib ameliorates lipopolysaccharide-induced acute lung injury in rats  

SciTech Connect

The present study aimed to investigate the effect of the new tyrosine kinase inhibitor, nilotinib on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and explore its possible mechanisms. Male Sprague-Dawley rats were given nilotinib (10 mg/kg) by oral gavage twice daily for 1 week prior to exposure to aerosolized LPS. At 24 h after LPS exposure, bronchoalveolar lavage fluid (BALF) samples and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathological changes in lungs. Malondialdehyde (MDA) content, superoxidase dismutase (SOD) and reduced glutathione (GSH) activities as well as nitrite/nitrate (NO{sub 2}{sup -}/NO{sub 3}{sup -}) levels were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-{alpha} (TNF-{alpha}), transforming growth factor-{beta}{sub 1} (TGF-{beta}{sub 1}) and inducible nitric oxide synthase (iNOS) were determined in lung tissues. Treatment with nilotinib prior to LPS exposure significantly attenuated the LPS-induced pulmonary edema, as it significantly decreased lung W/D ratio, protein concentration and the accumulation of the inflammatory cells in the BALF. This was supported by the histopathological examination which revealed marked attenuation of LPS-induced ALI in nilotinib treated rats. In addition, nilotinib significantly increased SOD and GSH activities with significant decrease in MDA content in the lung. Nilotinib also reduced LPS mediated overproduction of pulmonary NO{sub 2}{sup -}/NO{sub 3}{sup -} levels. Importantly, nilotinib caused down-regulation of the inflammatory cytokines TNF-{alpha}, TGF-{beta}{sub 1} and iNOS levels in the lung. Taken together, these results demonstrate the protective effects of nilotinib against the LPS-induced ALI. This effect can be attributed to nilotinib ability to counteract the inflammatory cells infiltration and hence ROS generation and regulate cytokine effects. - Research highlights: > The protective effects of nilotinib against LPS-induced ALI in rats were studied. > Nilotinib showed potent anti-inflammatory activity as it attenuated PMN infiltration and hence ROS generation. > In addition, nilotinib caused down-regulation of proinflammatory cytokine production.

El-Agamy, Dina S., E-mail:



Epithelial Cell Apoptosis Causes Acute Lung Injury Masquerading as Emphysema  

PubMed Central

Theories of emphysema traditionally revolved around proteolytic destruction of extracellular matrix. Models have recently been developed that show airspace enlargement with the induction of pulmonary cell apoptosis. The purpose of this study was to determine the mechanism by which a model of epithelial cell apoptosis caused airspace enlargement. Mice were treated with either intratracheal microcystin (MC) to induce apoptosis, intratracheal porcine pancreatic elastase (PPE), or their respective vehicles. Mice from all groups were inflated and morphometry was measured at various time points. Physiology measurements were performed for airway resistance, tissue elastance, and lung volumes. The groups were further analyzed by air–saline quasistatic measurements, surfactant staining, and surfactant functional studies. Mice treated with MC showed evidence of reversible airspace enlargement. In contrast, PPE-treated mice showed irreversible airspace enlargement. The airspace enlargement in MC-treated mice was associated with an increase in elastic recoil due to an increase in alveolar surface tension. PPE-treated mice showed a loss of lung elastic recoil and normal alveolar surface tension, a pattern more consistent with human emphysema. Airspace enlargement that occurs with the MC model of pulmonary epithelial cell apoptosis displays physiology distinct from human emphysema. Reversibility, restrictive physiology due to changes in surface tension, and alveolar enlargement associated with heterogeneous alveolar collapse are most consistent with a mild acute lung injury. Inflation near total lung capacity gives the appearance of enlarged alveoli as neighboring collapsed alveoli exert tethering forces.

Mouded, Majd; Egea, Eduardo E.; Brown, Matthew J.; Hanlon, Shane M.; Houghton, A. McGarry; Tsai, Larry W.; Ingenito, Edward P.; Shapiro, Steven D.




PubMed Central

Since its introduction in the 1950s, the forced oscillation technique (FOT) and the measurement of respiratory impedance have evolved into powerful tools for the assessment of various mechanical phenomena in the mammalian lung during health and disease. In this review, we highlight the most recent developments in instrumentation, signal processing, and modeling relevant to FOT measurements. We demonstrate how FOT provides unparalleled information on the mechanical status of the respiratory system compared to more widely-used pulmonary function tests. The concept of mechanical impedance is reviewed, as well as the various measurement techniques used to acquire such data. Emphasis is placed on the analysis of lower, physiologic frequency ranges (typically less than 10 Hz) that are most sensitive to normal physical processes as well as pathologic structural alterations. Various inverse modeling approaches used to interpret alterations in impedance are also discussed, specifically in the context of three common respiratory diseases: asthma, chronic obstructive pulmonary disease, and acute lung injury. Finally, we speculate on the potential role for FOT in the clinical arena.

Kaczka, David W.; Dellaca, Raffaele L.



Experimental Models and Emerging Hypotheses for Acute Lung Injury  

PubMed Central

Acute Lung Injury (ALI) is a complex illness involving the activation of multiple pathways leading to lung injury, resolution and repair. Since the first description of ALI, a great deal of effort has been devoted to exploring the roles of individual pathways in humans and animal models. These have led to a much greater understanding of the complexity of ALI and the links between ALI and systemic multiorgan failure. Despite progress in many areas, we still do not have an integrated understanding of the initiating factors, the key steps in the progression of ALI, and the central processes involved in repair. Although animal models have suggested a range of new hypotheses for study, the major need is for a better understanding of how pathways interact to explain the complexity of the human ALI syndrome and how complementary treatments can be used simultaneously or sequentially to modify the onset, severity and outcome of ALI in humans.

Martin, Thomas R.; Matute-Bello, Gustavo



Acute myelogenous leukemia associated with Ollier disease.  


Ollier disease is a rare disorder characterized by the presence of multiple enchondromas and a propensity to develop malignancies. We report the case of a 7-year-old Caucasian male with Ollier disease who developed acute myelogenous leukemia (AML). This report describes a patient with Ollier disease and AML and may offer a clue into the genetic pathogenesis of these disorders. PMID:16991136

White, Matthew S; Martin, Paul L; McLean, Thomas W



Differential modulation of surfactant protein D under acute and persistent hypoxia in acute lung injury.  


Hypoxia contributes to the development of fibrosis with epithelial-mesenchymal transition (EMT) via stimulation of hypoxia-inducible factor 1? (HIF-1?) and de novo twist expression. Although hypoxemia is associated with increasing levels of surfactant protein D (SP-D) in acute lung injury (ALI), the longitudinal effects of hypoxia on SP-D expression in lung tissue injury/fibrosis have not been fully evaluated. Here, the involvement of hypoxia and SP-D modulation was evaluated in a model of bleomycin-induced lung injury. We also investigated the molecular mechanisms by which hypoxia might modulate SP-D expression in alveolar cells, by using a doxycycline (Dox)-dependent HIF-1? expression system. Tissue hypoxia and altered SP-D levels were present in bleomycin-induced fibrotic lesions. Acute hypoxia induced SP-D expression, supported by the finding that Dox-induced expression of HIF-1? increased SP-D expression. In contrast, persistent hypoxia repressed SP-D expression coupled with an EMT phenotype and twist expression. Long-term expression of HIF-1? caused SP-D repression with twist expression. Ectopic twist expression repressed SP-D expression. The longitudinal observation of hypoxia and SP-D levels in ALI in vivo was supported by the finding that HIF-1? expression stabilized by acute hypoxia induced increasing SP-D expression in alveolar cells, whereas persistent hypoxia induced de novo twist expression in these cells, causing repression of SP-D and acquisition of an EMT phenotype. Thus this is the first study to demonstrate the molecular mechanisms, in which SP-D expression under acute and persistent hypoxia in acute lung injury might be differentially modulated by stabilized HIF-1? expression and de novo twist expression. PMID:22561461

Sakamoto, Koji; Hashimoto, Naozumi; Kondoh, Yasuhiro; Imaizumi, Kazuyoshi; Aoyama, Daisuke; Kohnoh, Takashi; Kusunose, Masaaki; Kimura, Motohiro; Kawabe, Tsutomu; Taniguchi, Hiroyuki; Hasegawa, Yoshinori



Acute Liver Disease after Cutaneous Thermal Injury.  

National Technical Information Service (NTIS)

The incidence, clinical characteristics, and natural history of acute liver disease complicating thermal injury have not been fully described. Postmortem surveys and laboratory investigations have recognized congestion, fatty degeneration, and focal necro...

A. J. Czaja T. A. Rizzo W. R. Smith B. A. Pruitt



Neuraminidase reprograms lung tissue and potentiates lipopolysaccharide-induced acute lung injury in mice.  


We previously reported that removal of sialyl residues primed PBMCs to respond to bacterial LPS stimulation in vitro. Therefore, we speculated that prior desialylation can sensitize the host to generate an enhanced inflammatory response upon exposure to a TLR ligand, such as LPS, in a murine model of acute lung injury. Intratracheal instillation of neuraminidase (NA) 30 min prior to intratracheal administration of LPS increased polymorphonuclear leukocytes (PMNs) in the bronchoalveolar lavage fluid and the wet-to-dry lung weight ratio, a measure of pulmonary edema, compared with mice that received LPS alone. Administration of NA alone resulted in desialylation of bronchiolar and alveolar surfaces and induction of TNF-?, IL-1?, and chemokines in lung homogenates and bronchoalveolar lavage fluid; however, PMN recruitment in mice treated with NA alone did not differ from that of PBS-administered controls. NA pretreatment alone induced apoptosis and markedly enhanced LPS-induced endothelial apoptosis. Administration of recombinant Bcl-2, an antiapoptotic molecule, abolished the effect of NA treatment on LPS-induced PMN recruitment and pulmonary edema formation. We conclude that NA pretreatment potentiates LPS-induced lung injury through enhanced PMN recruitment, pulmonary edema formation, and endothelial and myeloid cell apoptosis. A similar "reprogramming" of immune responses with desialylation may occur during respiratory infection with NA-expressing microbes and contribute to severe lung injury. PMID:24068662

Feng, Chiguang; Zhang, Lei; Nguyen, Chinh; Vogel, Stefanie N; Goldblum, Simeon E; Blackwelder, William C; Cross, Alan S



Mannose prevents lipopolysaccharide-induced acute lung injury in rats  

Microsoft Academic Search

.\\u000a Objective:  To investigate the effect of mannose on lipopolysaccharide (LPS) induced acute lung injury (ALI) in rats.\\u000a \\u000a \\u000a \\u000a Methods:  Ten groups of Sprague–Dawley rats were used: 1) the control group received an intratracheal instillation of saline, 2) the LPS group received an intratracheal instillation of LPS (3 mg\\/kg), 3–6) the mannose groups were injected i.v. with 15, 45, 135, and 405 mg\\/kg mannose, 7–9)

X. L. Xu; Q. M. Xie; Y. H. Shen; J. J. Jiang; Y. Y. Chen; H. Y. Yao; J. Y. Zhou



Advances in monitoring and management of pediatric acute lung injury.  


This article focuses on the respiratory management and monitoring of pediatric acute lung injury (ALI) as a specific cause for respiratory failure. Definitive, randomized, controlled trials in pediatrics to guide optimal ventilatory management are few. The only adjunct therapy that has been proved to improve clinical outcome is low tidal volume ventilation, but only in adult patients. Careful monitoring of the patient's respiratory status with airway graphic analysis and capnography can be helpful. Definitive data are needed in the pediatric population to assist in the care of infants, children, and adolescents with ALI to improve survival and functional outcome. PMID:23639659

Cheifetz, Ira M



Oxidized Phospholipids Reduce Vascular Leak and Inflammation in Rat Model of Acute Lung Injury  

Microsoft Academic Search

Rationale: Acute inflammation and vascular leak are cardinal fea- tures of acute lung injury and the acute respiratory distress syn- drome. Nonspecific tissue inflammation and injury in response to infectious and noninfectious insults lead to oxidative stress and the generation of lipid oxidation products, which may inhibit the acute inflammatory response to bacterial components. Objective: To test the hypothesis that

Stephanie Nonas; Ian Miller; Kamon Kawkitinarong; Santipongse Chatchavalvanich; Irina Gorshkova; Valery N. Bochkov; Norbert Leitinger; Viswanathan Natarajan; Joe G. N. Garcia; Konstantin G. Birukov



Surfactant Protein D Protects against Acute Hyperoxic Lung Injury  

PubMed Central

Rationale: Surfactant protein D (SP-D) is a member of the collectin family of soluble, innate, host defense molecules with demonstrated immunomodulatory properties in vitro. Constitutive absence of SP-D in mice is associated with lung inflammation, alteration in surfactant lipid homeostasis, and increased oxidative-nitrative stress. Objectives: To test the hypothesis that SP-D would protect against acute lung injury from hyperoxia in vivo. Methods: Transgenic mice overexpressing rat SP-D constitutively (SP-D OE) or conditionally via regulation with doxycycline (SP-D Dox-on) were subjected to continuous hyperoxic challenge for up to 14 days. Measurements and Main Results: Compared with littermate control mice (wild-type [WT]), SP-D OE mice exposed to 80% O2 demonstrated substantially increased survival accompanied by significant reductions in wet to dry lung ratios and bronchoalveolar lavage (BAL) protein. Although SP-D OE and WT mice exhibited a twofold increase in total BAL cells and neutrophilia in response to hyperoxia, the SP-D OE group had lower levels of BAL proinflammatory cytokines and chemokines, including IL-6, tumor necrosis factor-?, and monocyte chemotactic protein-1; increased mRNA levels of the transcription factor NF-E2 related factor-2 (NRF-2) and phase 2 antioxidants hemoxygenase-1 (HO-1), glutathione peroxidase-2 (GPx-2) and NAD(P)H quinone oxidoreductase-1 (Nqo-1); and decreases in lung tissue thiobarbituric acid–reactive substances. As proof of principle, the protective role of SP-D on hyperoxic injury was confirmed as SP-D Dox-on mice exposed to 85% O2 demonstrated increased mortality upon withdrawal of doxycycline. Conclusions: Local expression of SP-D protects against hyperoxic lung injury through modulation of proinflammatory cytokines and antioxidant enzymatic scavenger systems.

Jain, Deepika; Atochina-Vasserman, Elena N.; Tomer, Yaniv; Kadire, Helchem; Beers, Michael F.



Liver cold preservation induce lung surfactant changes and acute lung injury in rat liver transplantation  

PubMed Central

AIM: To investigate the relationship between donor liver cold preservation, lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation. METHODS: Liver transplantation models were established using male Wistar rats. Donor livers were preserved in University of Wisconsin solution at 4??°C for different lengths of time. The effect of ammonium pyrrolidinedithiocarbamate (PDTC) on ALI was also detected. All samples were harvested after 3 h reperfusion. The severity of ALI was evaluated by lung weight/body weight ratio, lung histopathological score, serum nitric oxide (NO) and endothelin (ET)-1 levels, lung tumor necrosis factor (TNF)-? and interleukin (IL)-1? levels. Lung surfactants (LSs) were determined by micellar electrokinetic capillary chromatography. RESULTS: With extended donor liver cold preservation time (CPT), lung histopathological scores, serum ET-1 levels, lung weight/body weight ratio and the level of TNF-? and IL-1? in lung were increased significantly in the 180-min group compared with the sham group (3.16 ± 0.28 vs 1.12 ± 0.21, P < 0.001; 343.59 ± 53.97 vs 141.53 ± 48.48, P < 0.001; 0.00687 ± 0.00037 vs 0.00557 ± 0.00056, P < 0.001; 17.5 ± 3.0 vs 1.3 ± 0.3, P < 0.001; 10.8 ± 2.3 vs 1.8 ± 0.4, P < 0.001), but serum NO levels decreased remarkably (74.67 ± 10.01 vs 24.97 ± 3.18, P < 0.001). The expression of lung phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS) increased when CPT was < 120 min, and decreased when CPT was > 180 min (PC: 1318.89 ± 54.79 vs 1011.18 ± 59.99, P < 0.001; PE: 1504.45 ± 119.96 vs 1340.80 ± 76.39, P = 0.0019; PI: 201.23 ± 34.82 vs 185.88 ± 17.04, P = 0.2265; PS: 300.43 ± 32.95 vs 286.55 ± 55.55, P = 0.5054). All these ALI-associated indexes could be partially reversed by PDTC treatment. CONCLUSION: Prolonged CPT could induce or inhibit the expression of LSs at the compensation or decompensation stage, and some antioxidants (e.g., PDTC) may reverse the pathological process partially.

Jiang, An; Liu, Chang; Liu, Feng; Song, Yu-Long; Li, Quan-Yuan; Yu, Liang; Lv, Yi



Characterization of lung's emphysema distribution: Numerical assessment of disease development  

Microsoft Academic Search

Chronic Obstructive Pulmonary Disease (COPD) refers to a group of lung diseases that block airflow and make it increasingly difficult for you to breathe. Emphysema and chronic bronchitis are the two main conditions that make up COPD, but COPD can also refer to damage caused by chronic asthmatic bronchitis. Pulmonary emphysema is defined as a lung disease characterized by “abnormal

M. Emam; J.-F. R. de la Faverie; N. Gharbi; M. I. El-Gohary



Efficacy and safety of videothoracoscopic lung biopsy in the diagnosis of interstitial lung disease  

Microsoft Academic Search

Objective: The aim of this study was to determine the efficacy and safety of videothoracoscopic lung biopsy (VTLB) in the diagnosis of infiltrative lung disease (ILD) and compare the results of VTLB with the results previously obtained in patients with open lung biopsy at the same institution. Methods: Forty-one patients undergoing VTLB between May 1991 and December 1994 were retrospectively

Jérôme Mouroux; Claude Clary-Meinesz; Bernard Padovani; Christophe Perrin; Christine Rotomondo; Jean-Michel Chavaillon; Bruno Blaive; Henri Richelme



Acute lung injury in preterm fetuses and neonates: mechanisms and molecular pathways.  


Abstract Acute lung injury (ALI) results in high morbidity and mortality among preterm neonates and efforts have therefore been devoted to both antenatal and postnatal prevention of the disease. ALI is the result of an inflammatory response which is triggered by a variety of different mechanisms. It mostly affects the fetal lung and, in particular, causes damage to the integrity of the lung's alveolar-capillary unit while weakening its cellular linings. Chemotactic activity and inflammatory products, such as proinflammatory cytokines TNF-?, IL-1, IL-6, IL-11, VEGF,TGF-? and TGF-?, provoke serious damage to the capillary endothelium and the alveolar epithelium, resulting in hyaline membrane formation and leakage of protein-rich edema fluid into the alveoli. Chorioamnionitis plays a major part in triggering fetal lung inflammation, while mechanical ventilation, the application of which is frequently necessary in preterm neonates, also causes ALI by inducing proinflammatory cytokines. Many different ventilation-strategies have been developed in order to reduce potential lung injury. Furthermore, tissue injury may occur as a result of injurious oxygen by-products (Reactive Oxygen Species, ROS), secondary to hyperoxia. Knowledge of the inflammatory pathways that connect intra-amniotic inflammation and ALI can lead to the formulation of novel interventional procedures. Future research should concentrate on the pathophysiology of ALI in preterm neonates and ?n possible pharmaceutical interventions targeting prevention and/or resolution of ALI. PMID:23611524

Iliodromiti, Zoe; Zygouris, Dimitrios; Sifakis, Stavros; Pappa, Kalliopi I; Tsikouras, Panagiotis; Salakos, Nikolaos; Daniilidis, Angelos; Siristatidis, Charalambos; Vrachnis, Nikolaos



Early detection of type III procollagen peptide in acute lung injury. Pathogenetic and prognostic significance.  


The fibroproliferative reaction to acute lung injury may limit restoration of normal lung function and increase mortality in patients with acute lung injury. A biologic marker of collagen synthesis in the lung may be useful for studying the pathogenesis of acute lung injury and for identifying patients with acute lung injury who are at high risk for death and might benefit from new therapeutic modalities. Using an immunoassay, type III procollagen NH2 terminal peptide was measured in the pulmonary edema fluid of 44 patients with either acute lung injury or hydrostatic pulmonary edema (control group) within the first 24 h after endotracheal intubation for acute respiratory failure. Patients with acute lung injury (n = 33) or hydrostatic edema (n = 11) had the same degree of lung dysfunction as measured by the severity of oxygenation defect, the level of positive end-expiratory pressure, the decrease in static lung compliance, and the extent of infiltrates on the chest radiograph. However, the median procollagen III level was 5-fold higher in the pulmonary edema fluid of patients with acute lung injury than in the patients with hydrostatic pulmonary edema (p = 0.0001). Of the 33 patients with acute lung injury, 21 patients died and 12 lived. Nonsurvivors had significantly higher procollagen III levels than did survivors (p = 0.05). The positive and negative predictive values for nonsurvival for a procollagen III level > or = 1.75 U/ml were 74 and 83%, respectively. The relative risk of dying in the presence of a procollagen III value > or = 1.75 U/ml was 4.5 (95% CI, 0.7 to 27). Collagen synthesis in the lung, as reflected by elevated levels of procollagen III in pulmonary edema fluid, begins within the first 24 h of acute lung injury concurrent with the acute phase of increased endothelial and epithelial permeability to protein. This evidence suggests that fibrosing alveolitis begins much earlier in the course of clinical acute lung injury than has previously been appreciated. In addition, the presence of an elevated level of procollagen III is an early predictor of poor outcome. Thus, elevation of procollagen III in pulmonary edema fluid may have both pathogenetic and prognostic significance in patients with acute lung injury. PMID:9310002

Chesnutt, A N; Matthay, M A; Tibayan, F A; Clark, J G



Nonventilatory Treatments for Acute Lung Injury and ARDS  

PubMed Central

Over the past decade, advances in the ventilatory management of acute lung injury (ALI) and ARDS have improved outcomes; however, until recently the search for other therapies has been less fruitful. Recently, the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial reported that a conservative fluid management strategy, compared with a fluid liberal strategy, increased the mean (± SE) number of ventilator-free days in patients with ALI (14.6 ± 0.5 vs 12.1 ± 0.5 days, respectively; p < 0.001). In addition to this beneficial effect on outcomes, the study found that the conservative fluid strategy did not increase the incidence of renal failure or the development of shock. Other studies have demonstrated that albumin and furosemide therapy may be beneficial in hypoproteinemic patients with lung injury, though data on outcomes is still lacking. Although several pharmacologic therapies, such as corticosteroids, surfactant, and nitric oxide, have been demonstrated to be ineffective in improving outcomes, several promising new treatments are being investigated in ongoing or upcoming clinical trials. This article reviews these developments and other recent research on the optimal nonventilatory management of patients with ALI.

Calfee, Carolyn S.; Matthay, Michael A.



Peroxisome Proliferator-Activated Receptors and Acute Lung Injury  

PubMed Central

Peroxisome proliferator-activated receptors are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. PPARs regulate several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of target genes, including lipid biosynthesis and glucose metabolism. Recently, PPARs and their respective ligands have been implicated as regulators of cellular inflammatory and immune responses. These molecules are thought to exert anti-inflammatory effects by negatively regulating the expression of proinflammatory genes. Several studies have demonstrated that PPAR ligands possess anti-inflammatory properties and that these properties may prove helpful in the treatment of inflammatory diseases of the lung. This review will outline the anti-inflammatory effects of PPARs and PPAR ligands and discuss their potential therapeutic effects in animal models of inflammatory lung disease.

Paola, Rosanna Di; Cuzzocrea, Salvatore



Role of endothelin-1 in acute lung injury  

PubMed Central

The alveolar–capillary membrane serves as a barrier that prevents the accumulation of fluid in the alveolar space and restricts the diffusion of large solutes while facilitating an efficient gas exchange. When this barrier becomes dysfunctional, patients develop acute lung injury (ALI), which is characterized by pulmonary edema and increased lung inflammation that leads to a life-threatening impairment of gas exchange. In addition to the increase of inflammatory cytokines, plasma levels of endothelin-1 (ET-1), which is a primarily endothelium-derived vasoconstrictor, are increased in patients with ALI. As patients recover, ET-1 levels decrease, which suggests that ET-1 may not only be a marker of endothelial dysfunction but may have a role in the pathogenesis of ALI. While pulmonary edema accumulates, alveolar fluid clearance (AFC) is of critical importance, as failure to return to normal clearance is associated with poor prognosis in patients with pulmonary edema. AFC involves active transport mechanisms where sodium (Na+) is actively transported from the alveolar airspaces, across the alveolar epithelium, and into the pulmonary circulation, which creates an osmotic gradient that is responsible for the clearance of lung edema. In this article, we review the relevance of ET-1 in the development of ALI, not only as a vasoconstrictor molecule but also by inhibiting AFC via the activation of endothelial ET-B receptors and generation. Furthermore, this review highlights the therapeutic role of drugs such as beta-adrenergic agonists and, in particular, of endothelin receptor antagonists in patients with ALI.




Randomized Clinical Trial of Activated Protein C for the Treatment of Acute Lung Injury  

Microsoft Academic Search

Rationale: Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days. Objectives: To test the efficacy of activated protein C (APC) as a therapy for patients with ALI. Methods: Eligible subjects were

Kathleen D. Liu; J oseph Levitt; Hanjing Zhuo; R ichard H. Kallet; S andra Brady; J. Steingrub; M. Tidswell; M. D. Siegel; G. Soto; M. W. Peterson; M. S. Chesnutt; C. Phillips; A. Weinacker; B. T. Thompson; M. D. Eisner; M. A. Matthay



Increased plasma concentrations of brain natriuretic peptide in patients with acute lung injury  

Microsoft Academic Search

Purpose: This study was performed to elucidate the pathophysiological role of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in acute lung injury.Materials and Methods: We sequentially measured plasma concentrations of immunoreactive BNP and ANP in 10 patients (mean age, 63 years) with acute lung injury and compared those with hemodynamic parameters and pulmonary functions.Results: Plasma concentrations of immunoreactive

Chieko Mitaka; Yukio Hirata; Takashi Nagura; Yukio Tsunoda; Masao Itoh; Keisuke Amaha



A quality assessment of genetic association studies supporting susceptibility and outcome in acute lung injury  

Microsoft Academic Search

INTRODUCTION: Clinical observations and animal models provide evidence that the development of acute lung injury (ALI), a phenomenon of acute diffuse lung inflammation in critically ill patients, is influenced by genetic factors. Association studies are the main tool for exploring common genetic variations underlying ALI susceptibility and\\/or outcome. We aimed to assess the quality of positive genetic association studies with

Carlos Flores; Maria del Mar Pino-Yanes; Jesús Villar



Differential Gene Expression in the Initiation and Progression of Nickel-Induced Acute Lung Injury  

Microsoft Academic Search

Acute lung injury, an often fatal condition, can result from a wide range of insults leading to a complex series of biologic re- sponses. Despite extensive research, questions remain about the interplay of the factors involved and their role in acute lung injury. We proposed that assessing the temporal and functional relationships of differentially expressed genes after pulmonary insult would

Susan A. McDowell; Kelly Gammon; Cindy J. Bachurski; Jonathan S. Wiest; John E. Leikauf; Daniel R. Prows; George D. Leikauf



Clinical review: The implications of experimental and clinical studies of recruitment maneuvers in acute lung injury  

Microsoft Academic Search

Mechanical ventilation can cause and perpetuate lung injury if alveolar overdistension, cyclic collapse, and reopening of alveolar units occur. The use of low tidal volume and limited airway pressure has improved survival in patients with acute lung injury or acute respiratory distress syndrome. The use of recruitment maneuvers has been proposed as an adjunct to mechanical ventilation to re-expand collapsed

Enrique Piacentini; Ana Villagrá; Josefina López-Aguilar; Lluis Blanch



Acute cholestatic liver disease protects against glycerol-induced acute renal failure in the rat  

Microsoft Academic Search

Acute cholestatic liver disease protects against glycerol-induced acute renal failure in the rat.BackgroundIt is widely held that liver disease predisposes toward acute tubular necrosis. The present study examines the effect of acute cholestatic liver disease on the susceptibility to glycerol-induced acute tubular necrosis in the rat.MethodsAcute cholestatic liver disease was induced by ligation of the common bile duct, while the

Nelson Leung; Anthony J. Croatt; Jill J. Haggard; Joseph P. Grande; Karl A. Nath



Evolution of Endotoxin-Induced Lung Injury in the Rat beyond the Acute Phase  

Microsoft Academic Search

Objectives: Intratracheal endotoxin in rats causes acute lung injury. Here we have addressed the cellular physiopathology of lung recovery from that injury. Methods: The lungs of 5 untreated rats and rats treated with intratracheal endotoxin from 2, 3, 5, 8 (5 rats each) and 15 days (2 rats) were studied by light and electron microscopy and immunohistochemistry. Results: In the

L. Domenici; L. Pieri; M. B. Gallè; P. Romagnoli; C. Adembri



Enhancement Effects of Hypercapnia on the Acute Lung Injury Caused by Acid Aspiration  

Microsoft Academic Search

Acid aspiration or intrapulmonary instillation of gastric particles causes lung inflammation leading to acute lung injury (ALI). Hypercapnia exerts different effects on ALI caused by various in- sults. The effects of hypercapnia on lung inflammation and injury due to acid aspiration are yet to be determined. The present study was designed to investigate the involvement of inducible nitric oxide synthase

Demeral David Liu; Hen I Lin; Nan-Kuang Hsieh; Hsing I Chen



Analysis of reports on orphan lung diseases in Korean children  

PubMed Central

Purpose Orphan lung diseases are defined as lung diseases with a prevalence of 1 or less in 2,000 individuals. Despite an increase in the numbers of patients with such diseases, few studies on Korean children have appeared. To obtain epidemiologic and demographic data on these diseases, we systematically reviewed reports on pediatric orphan lung diseases in Korea over the last 50 years. Methods We reviewed 223 articles that have appeared since 1958 on orphan lung diseases in Korean children. These articles described a total of 519 patients aged between 0 and 18 years. We classified patients by year of publication, diagnosis, geographic region, and journal. Results Of 519 patients, 401 had congenital cystic lung diseases and 66 had bronchiolitis obliterans. About 80% of patients were described in reports published in three journals, Pediatric Allergy and Respiratory Disease (Korea), the Korean Journal of Pediatrics, and the Korean Journal of Thoracic and Cardiovascular Surgery, in which papers on 157 (30.2%), 138 (26.6%), and 111 (21.4%) patients appeared, respectively. The frequency of publication of case reports has increased since 1990. Of the 519 patients, 401 (77.3%) were from Seoul/Gyeonggi-do and 72 (13.9%) from Busan/Gyeongsangnam-do. Conclusion The prevalence of pediatric orphan lung disease has increased since 1990, and some provinces of Korea have a higher incidence of these diseases than do others. Studies exploring the incidence of pediatric orphan lung diseases in Korea are needed for effective disease management.

Jang, Sun Jung; Seo, Hyun Kyung; Yi, Sung Jae; Kim, Kyong Min; Jee, Hye Mi



Risk Factors for Underuse of Lung Protective Ventilation in Acute Lung Injury  

PubMed Central

Purpose We assessed factors associated with underutilization of lung protective ventilation (LPV) in patients with acute lung injury (ALI). Methods Secondary analysis of ARDSNet trial data, 1999-2005. Tidal volumes recorded prior to trial randomization were analyzed to determine receipt of LPV [tidal volume ? 6.5 cc/kg of predicted body weight (PBW)]. Results 430/1385 (31.2%) participants received LPV. Average tidal volume was 7.65±1.82 cc/kg PBW; measured tidal volumes were greater than “lung protective” tidal volumes predicted by 6.5cc/kg PBW (mean difference 67±108cc, p<0.0001). Multivariate predictors of LPV underutilization were older age [odds ratio (OR) per standard deviation (std) year 1.18 (95% confidence interval: 1.02-1.38)], white race [OR, 1.40 (1.05-1.88)], shorter stature [OR per std centimeter 0.55 (0.48-0.63)], lower Simplified Acute Physiology Score (SAPS)II [OR per std, 0.78 (0.67-0.92)], lower lung injury score [OR per std 0.83 (0.70-0.95)], decreased serum bicarbonate [OR per std mmol/l 0.83 (0.71-0.97)], shorter pre-enrollment ICU stay [OR per std day 0.84 (0.73-0.98)], and use of non-volume-controlled ventilation [OR 3.07 (1.78, 5.27)]. Setting tidal volumes to 450ml (men) or 350ml (women) would provide LPV to 80% of patients with ALI. Conclusions Simple interventions could substantially improve adherence with LPV among patients with ALI and warrant prospective study.

Walkey, Allan J.



The Nitrated Fatty Acid 10-Nitro-oleate Diminishes Severity of LPS-Induced Acute Lung Injury in Mice  

PubMed Central

Acute lung injury (ALI) is an inflammatory condition culminating in respiratory failure. There is currently no effective pharmacological treatment. Nitrated fatty acids (NFAs) have been shown to exert anti-inflammatory effects. We therefore hypothesized that delivery of NFAs directly to the site of inflammation would reduce the severity of ALI. Pulmonary delivery of 10-nitro-oleate following endotoxin-induced ALI in mice reduced markers of lung inflammation and injury, including capillary leakage, lung edema, infiltration of neutrophils into the lung, and oxidant stress, as well as plasma levels of proinflammatory cytokines. Nitro-oleate delivery likewise downregulated expression of proinflammatory genes by alveolar macrophages, key cells in regulation of lung inflammation. These effects may be accounted for by the observed increases in the activity of PPAR-? and the PPAR-?-induced antioxidant transcription factor Nrf2, together with the decreased activity of NF-?B. Our results demonstrate that pulmonary delivery of NFAs reduces severity of acute lung injury and suggest potential utility of these molecules in other inflammatory lung diseases.

Reddy, Aravind T.; Lakshmi, Sowmya P.; Reddy, Raju C.



A novel mechanical lung model of pulmonary diseases to assist with teaching and training  

PubMed Central

Background A design concept of low-cost, simple, fully mechanical model of a mechanically ventilated, passively breathing lung is developed. An example model is built to simulate a patient under mechanical ventilation with accurate volumes and compliances, while connected directly to a ventilator. Methods The lung is modelled with multiple units, represented by rubber bellows, with adjustable weights placed on bellows to simulate compartments of different superimposed pressure and compliance, as well as different levels of lung disease, such as Acute Respiratory Distress Syndrome (ARDS). The model was directly connected to a ventilator and the resulting pressure volume curves recorded. Results The model effectively captures the fundamental lung dynamics for a variety of conditions, and showed the effects of different ventilator settings. It was particularly effective at showing the impact of Positive End Expiratory Pressure (PEEP) therapy on lung recruitment to improve oxygenation, a particulary difficult dynamic to capture. Conclusion Application of PEEP therapy is difficult to teach and demonstrate clearly. Therefore, the model provide opportunity to train, teach, and aid further understanding of lung mechanics and the treatment of lung diseases in critical care, such as ARDS and asthma. Finally, the model's pure mechanical nature and accurate lung volumes mean that all results are both clearly visible and thus intuitively simple to grasp.

Chase, J Geoffrey; Yuta, Toshinori; Mulligan, Kerry J; Shaw, Geoffrey M; Horn, Beverley



Effects of Liver x receptor agonist treatment on signal transduction pathways in acute lung inflammation  

PubMed Central

Background Liver × receptor ? (LXR?) and ? (LXR?) are members of the nuclear receptor super family of ligand-activated transcription factors, a super family which includes the perhaps better known glucocorticoid receptor, estrogen receptor, thyroid receptor, and peroxisome proliferator-activated receptors. There is limited evidence that LXL activation may reduces acute lung inflammation. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse model of carrageenan-induced pleurisy. Methods Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), tumor necrosis factor-?, (TNF-?) and interleukin-1? (IL-1?). Furthermore, carrageenan induced the expression of iNOS, nitrotyrosine and PARP, as well as induced apoptosis (TUNEL staining and Bax and Bcl-2 expression) in the lung tissues. Results Administration of T0901317, 30 min after the challenge with carrageenan, caused a significant reduction in a dose dependent manner of all the parameters of inflammation measured. Conclusions Thus, based on these findings we propose that LXR ligand such as T0901317, may be useful in the treatment of various inflammatory diseases.



[Air pollution and lung diseases in adults].  


Short-time exposure to air pollutants and in particular to sulfur dioxide, nitrogen oxides and photochemical oxidants may cause respiratory symptoms similar to acute bronchial asthma. In healthy adults however the concentrations required to evoke significant bronchial obstruction lie still above the level of atmospheric air pollution usually observed in our country. In contrast patients with preexisting pulmonary diseases or with impaired bronchopulmonary defense mechanisms may show harmful reactions even at concentrations which actually occur in urban and rural atmospheres. In addition there is evidence of on increased prevalence of chronic obstructive pulmonary diseases in countries with high chemical pollution indicating that long-term exposure of ambient air pollution may cause chronic illness as well. Since air pollution is accepted to produce adverse health effects, emergent efforts are required to improve air quality in order to avoid further injuries in man. PMID:3962495

Keller, R



[Lung resection for patients with lung cancer and chronic obstructive pulmonary disease].  


The number of lung resection for patients with lung cancer has been increasing lineally for last two decades in Japan. It reached more than 30,000 in 2009. Subsequently those combined with chronic obstructive pulmonary disease (COPD) also have increased. As pulmonary vascular bed has already been lost to some extent due to chronic alveolar destruction, a careful preoperative physiologic assessment according to a guideline by American College of Chest Physicians (ACCP) or European Respiratory Society( ERS)/European Society of Thoracic Surgeons( ESTS) is important to select patients to be underwent lung resection within acceptable risk. The process to evaluate the risk of lung resection for a lung cancer patient has three steps structured by forced expiratory volume in 1 sec( FEV1), diffusion capacitiy for carbon monoxide (DLco), and exercise capacity. We suggested that it would be more practical to add global initiative for obstructive lung disease( GOLD) staging of each patient and distribution of emphysematous lung obtained by functional imaging modarities to the pathway of flow chart of the guideline. Some patients with very low FEV1 demonstrate increase in FEV1 after lung resection by so called lung volume reduction effect. To utilize lots of findings and experiences obtained from lung volume reduction surgery( LVRS) contributes to select patients with lung cancer and COPD and to perform lung resection and perioperative care properly. PMID:22868433

Nishikawa, S; Chihara, K



Inhaled nitric oxide exacerbated phorbol-induced acute lung injury in rats.  


In this study, we determined the effect of inhaled nitric oxide (NO) on the acute lung injury induced by phorbol myristate acetate (PMA) in isolated rat lung. Typical acute lung injury was induced successfully by PMA during 60 min of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability, (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/body weight ratio, pulmonary arterial pressure (PAP) and protein concentration of the bronchoalveolar lavage fluid. Pretreatment with inhaled NO (30 ppm) significantly exacerbated acute lung injury. All of the parameters reflective of lung injury increased significantly except PAP (P<0.05). Coadministration of Nomega-nitro-L-arginine methyl ester (L-NAME) (5 mM) attenuated the detrimental effect of inhaled NO in PMA-induced lung injury, except for PAP. In addition, L-NAME (5 mM) significantly attenuated PMA-induced acute lung injury except for PAP. These experimental data suggest that inhaled NO significantly exacerbated acute lung injury induced by PMA in rats. L-NAME attenuated the detrimental effect of inhaled NO. PMID:14643171

Lin, Hen I; Chu, Shi Jye; Hsu, Kang; Wang, David



Structural and functional lung disease in primary ciliary dyskinesia  

Microsoft Academic Search

Background: High-resolution CT (HRCT) scan data on primary ciliary dyskinesia (PCD) related lung disease are scarce. Study objectives: We evaluated the lung disease in children and adults with PCD by a modified Brody composite HRCT scan score to assess the prevalence of the structural abnormalities; to evaluate the correlation among HRCT scan scores, spirometry findings, and clinical data; and to

F. Santamaria; S. Montella; H. A. W. M. Tiddens; G. Guidi; V. Casotti; M. Maglione; Jong de P. A



Hard metal lung disease in an oil industry worker.  


Hard metal lung disease, which manifests as giant cell interstitial pneumonia, is caused by exposure to hard metal dust. We report the case of an oil industry worker diagnosed with hard metal lung disease. The diagnosis was based on the clinical, radiological and anatomopathological analysis, as well as on pulmonary function testing. PMID:20126930

Bezerra, Patrícia Nunes; Vasconcelos, Ana Giselle Alves; Cavalcante, Lílian Loureiro Albuquerque; Marques, Vanessa Beatriz de Vasconcelos; Nogueira, Teresa Neuma Albuquerque Gomes; Holanda, Marcelo Alcantara



Complications of albendazole treatment in hydatid disease of lung  

Microsoft Academic Search

We present rupture of lung hydatid cyst in a patient with multiple organ involvement during albendazole treatment. The patient was first provided mechanical ventilation than residue cavity and the other intact cyst was treated surgically. We concluded that albendazole should be used in postoperative period in patients with hydatid disease of the lung to prevent recurrent disease.

Ibrahim Can Kurkcuoglu; Atilla Eroglu; Nurettin Karaoglanoglu; Pinar Polat



Hydatid disease of the lung presenting with hemoptysis and simulating a lung abscess.  


Hydatidosis is one of the most important zoonotic diseases in the world. In this report, we describe a 25-year-old patient from Guntur district of Andhra Pradesh who presented with cough, chest pain, dyspnoea, and hemoptysis due to hydatid disease of the lung. Although it is one of the less common causes of hemoptysis, hydatid disease of the lung requires greater attention in countries such as India, where hydatid cyst disease is common. PMID:23508291

Toleti, Sunita; Subbarao, Mv; Dwarabu, Pragathi



Hydatid disease of the lung presenting with hemoptysis and simulating a lung abscess  

PubMed Central

Hydatidosis is one of the most important zoonotic diseases in the world. In this report, we describe a 25-year-old patient from Guntur district of Andhra Pradesh who presented with cough, chest pain, dyspnoea, and hemoptysis due to hydatid disease of the lung. Although it is one of the less common causes of hemoptysis, hydatid disease of the lung requires greater attention in countries such as India, where hydatid cyst disease is common.

Toleti, Sunita; Subbarao, MV; Dwarabu, Pragathi



Higher urine desmosine levels are associated with mortality in patients with acute lung injury  

PubMed Central

Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher mortality in 579 of 861 patients included in the recent Acute Respiratory Distress Syndrome Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indexes of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from days 0, 1, and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline (day 0) urine desmosine-to-creatinine concentration was associated with a higher risk of death on adjusted analysis (odds ratio 1.36, 95% confidence interval 1.02-1.82, P = 0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3, but the average rise was higher in the 12-ml/kg predicted body weight group compared with the 6-ml/kg predicted body weight group (P = 0.053, repeated-measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biological markers that may have prognostic and pathogenetic significance in acute lung injury.

McClintock, Dana E.; Starcher, Barry; Eisner, Mark D.; Thompson, B. Taylor; Hayden, Doug L.; Church, Gwynne D.; Matthay, Michael A.



Interstitial Lung Disease in a Patient with Chronic Granulomatous Disease  

PubMed Central

Background Chronic granulomatous disease (CGD) is an inherited phagocytes defect, characterized by defects of NADPH-oxidase and inability of bacterial killing, which leads to recurrent life-threatening infections. Respiratory problems, which are the major cause of morbidity in CGD, usually result from recurrent severe infections; however, vigorous inflammatory response could also cause respiratory diseases. Case Presentation Herein, an 11 year-old patient with CGD is presented who suffered from chronic cough and dyspnea for 7 years. Considering the results of chest X-ray, high-resolution computed tomography, and pulmonary function test, the diagnosis of interstitial lung disease was made. Conclusion Early recognition of manifestations associated with CGD and appropriate treatment could prevent further complications and reduce morbidity and mortality in this group of patients.

Moghtaderi, Mozhgan; Kashef, Sara; Rezaei, Nima



Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome*  

PubMed Central

Objective The coagulation and inflammatory cascades may be linked in the pathogenesis of acute lung injury and acute respiratory distress syndrome. However, direct evidence for the contribution of abnormalities in coagulation and fibrinolysis proteins to outcomes in patients with acute lung injury/acute respiratory distress syndrome is lacking. Design Retrospective measurement of plasma levels of protein C and plasminogen activator inhibitor-1 in plasma samples that were collected prospectively as part of a large multicenter clinical trial. The primary outcome was hospital mortality. To evaluate the potential additive value of abnormalities of these biomarkers, the excess relative risk of death was calculated for each combination of quartiles of protein-C and plasminogen activator inhibitor-1 levels. Setting Ten university medical centers. Patients The study included 779 patients from a multicenter clinical trial of a protective ventilatory strategy in acute lung injury/acute respiratory distress syndrome and 99 patients with acute cardiogenic pulmonary edema, as well as ten normal controls. Measurements and Main Results Compared with plasma from controls and patients with acute cardiogenic pulmonary edema, baseline protein-C levels were low and baseline plasminogen activator inhibitor-1 levels were elevated in acute lung injury/acute respiratory distress syndrome. By multivariate analysis, lower protein C and higher plasminogen activator inhibitor-1 were strong independent predictors of mortality, and ventilator-free and organ-failure-free days. Plasminogen activator inhibitor-1 and protein C had a synergistic interaction for the risk of death. Conclusions Early acute lung injury/acute respiratory distress syndrome is characterized by decreased plasma levels of protein C and increased plasma levels of plasminogen activator inhibitor-1 that are independent risk factors for mortality and adverse clinical outcomes. Measurement of plasminogen activator inhibitor-1 and protein-C levels may be useful to identify those at highest risk of adverse clinical outcomes for the development of new therapies.

Ware, Lorraine B.; Matthay, Michael A.; Parsons, Polly E.; Thompson, B. Taylor; Januzzi, James L.; Eisner, Mark D.



Inhaled nitric oxide aggravates phosgene model of acute lung injury.  


The principal acute mode of action of inhaled phosgene gas is related to an increase alveolar fluid exudation under pathologic conditions. This paper considers some aspects in modeling phosgene-induced acute lung injury (ALI) in an acute rat bioassay and whether edema formation can be modulated by inhaled nitric oxide (iNO). Protein analysis in bronchoalveolar lavage (BAL) fluid is amongst the most sensitive method to quantify the phosgene-induced non-cardiogenic, pulmonary high-permeability edema following acute inhalation exposure. Maximum concentrations in BAL-protein occur within one day postexposure, typically within a latency period up to about 15 h as a consequence of an increasingly exhausted lymphatic drainage. An almost similar sensitivity was given by the functional endpoint 'enhanced pause (Penh)' when measured by non-invasive whole-body barometric plethysmography over a time period of 20 h. The magnitude of edema formation follows a concentration x time (C¹xt) relationship, although animal model-specific deviations may occur at very short exposure durations (1-20 min) due to a rodent-specific, reflexively induced transient decreased ventilation. This has to be accounted for when simulating accidental exposure scenarios to study the mechanisms involved in pharmacological modulation of fluid transport in this type of ALI. Therefore, a special focus has to be given to the dosimetry of inhaled phosgene, otherwise any change in effect magnitude, as a result of under-dosing of phosgene, may be misconceived as promising therapy. This study demonstrates that accidental exposures can be modeled best in rats by exposure durations of at least 20-30?min. Lung function measurements (Penh) show that pathophysiological effects appear to occur concomitant with the exposure to phosgene; however, its full clinical manifestation requires a gross imbalance of pulmonary fluid clearance. When applying this concept, post-phosgene exposure iNO at 1.5?ppm?×?6?h or 15 pm?×?20 h led to an aggravation of edema formation while L-NAME, a non-selective inhibitor of nitric oxide synthase, led to attenuation. Ethyl pyruvate, given either prophylactically or therapeutically, was ineffective. PMID:22035124

Li, Wen-Li; Hai, Chun-Xu; Pauluhn, Jürgen



Transfusion-related acute lung injury: a clinical review.  


Three decades ago, transfusion-related acute lung injury (TRALI) was considered a rare complication of transfusion medicine. Nowadays, the US Food and Drug Administration acknowledge the syndrome as the leading cause of transfusion-related mortality. Understanding of the pathogenesis of TRALI has resulted in the design of preventive strategies from a blood-bank perspective. A major breakthrough in efforts to reduce the incidence of TRALI has been to exclude female donors of products with high plasma volume, resulting in a decrease of roughly two-thirds in incidence. However, this strategy has not completely eradicated the complication. In the past few years, research has identified patient-related risk factors for the onset of TRALI, which have empowered physicians to take an individualised approach to patients who need transfusion. PMID:23642914

Vlaar, Alexander P J; Juffermans, Nicole P



Biomarkers in Acute Lung Injury - Marking Forward Progress  

PubMed Central

In this article we review the ‘state of the art’ with regards to biomarkers for prediction, diagnosis and prognosis in acute lung injury (ALI). We begin by defining biomarkers and the goals of biomarker research in ALI including their ability to define more homogenous populations for recruitment into trials of novel therapies as well as to identify important biological pathways in the pathogenesis of ALI. Progress along four general routes is then examined. First the results of wide-ranging existing protein biomarkers are reported. Secondly, we describe newer biomarkers awaiting or with strong potential for validation. Thirdly, we report progress in the fields of genomics and proteomics. Finally given the complexity and number of potential biomarkers, we examine the results of combining clinical predictors with protein and other biomarkers to produce better prognostic and diagnostic indices.

Barnett, Nicolas; Ware, Lorraine B.



Biomarkers of acute lung injury: worth their salt?  

PubMed Central

The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI) and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.



Connective Tissue Disease-associated Interstitial Lung Disease: A review  

PubMed Central

Interstitial lung disease (ILD) is commonly encountered in patients with connective tissue diseases (CTD). Besides the lung parenchyma, the airways, pulmonary vasculature and structures of the chest wall may all be involved, depending on the type of CTD. As a result of this so-called multi-compartment involvement, airflow limitation, pulmonary hypertension, vasculitis and extrapulmonary restriction can occur alongside fibro-inflammatory parenchymal abnormalities in CTD. Rheumatoid arthritis (RA), systemic sclerosis (SSc), poly-/dermatomyositis (PM/DM), Sjögren’s syndrome (SjS), systemic lupus erythematosus (SLE), and undifferentiated (UCTD) as well as mixed connective tissue disease (MCTD) can all be associated with the development of ILD. Non-specific interstitial pneumonia (NSIP) is the most commonly observed histopathological pattern in CTD-ILD, but other patterns including usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP) may occur. Although the majority of patients with CTD-ILD experience stable or slowly advancing ILD, a small yet significant group exhibits a more severe and progressive course. Randomized placebo-controlled trials evaluating the efficacy of immunomodulatory treatments have been conducted only in SSc-associated ILD. However, clinical experience suggests that a handful of immunosuppressive medications are potentially effective in a sizeable portion of patients with ILD caused by other CTDs. In this manuscript, we review the clinical characteristics and management of the most common CTD-ILDs.

Gutsche, Markus; Rosen, Glenn D.; Swigris, Jeffrey J.



Acute hepatic sequestration in sickle cell disease.  

PubMed Central

Sickle cell anemia is a disease that affects one out of every 600 African Americans. It is often debilitating and can cause many physical restrictions to individuals with the disease. The disease has many complications which can be vexing for patients and their physicians. The hepatic complications attributed to vascular occlusion encompass a variety of clinical syndromes of which the relationship among clinical presentation, biochemical findings, and histologic features remains unclear. The conditions range from the self-limiting hepatic right upper quadrant syndrome (hepatic crisis) to the potentially lethal intrahepatic cholestasis and acute hepatic sequestration syndromes. Few cases have been documented, and there have not been many sizable studies on acute hepatic sequestration in sickle cell disease. This case is useful for clinicians who are not familiar with the intrahepatic vaso-occlusive syndromes in sickle cell disease. It provides insight into the presentation, diagnosis, and management of these syndromes.

Norris, William E.



Ultrahigh resolution optical coherence tomography imaging of diseased rat lung using Gaussian shaped super continuum sources  

NASA Astrophysics Data System (ADS)

We have been investigating ultrahigh resolution optical coherence tomography (UHR-OCT) imaging of lung tissues using fiber super continuum sources. The high power, low-noise, Gaussian shaped supercontinuum generated with ultrashort pulses and optical fibers at several wavelengths were used as the broadband light sources for UHR-OCT. For the 800 nm wavelength region, the axial resolution was 3.0 um in air and 2.0 um in tissue. Since the lung consists of tiny alveoli which are separated by thin wall, the UHR-OCT is supposed to be effective for lung imaging. The clear images of alveoli of rat were observed with and without index matching effects by saline. In this work, we investigated the UHR-OCT imaging of lung disease model. The lipopolysaccharide (LPS) induced acute lung injury / acute respiratory distress syndrome (ALI/ARDS) model of rat was prepared as the sample with disease and the UHR-OCT imaging of the disease part was demonstrated. The increment of signal intensity by pleural thickening was observed. The accumulation of exudative fluid in alveoli was also observed for two samples. By the comparison with normal lung images, we can obviously show the difference in the ALI/ARDS models. Since the lung consists of alveolar surrounded by capillary vessels, the effect of red-blood cells (RBC) is considered to be important. In this work, ex-vivo UHR-OCT imaging of RBC was demonstrated. Each RBC was able to be observed individually using UHR-OCT. The effect of RBC was estimated with the rat lung perfused with PBS.

Nishizawa, N.; Ishida, S.; Kitatsuji, M.; Ohshima, H.; Hasegawa, Y.; Matsushima, M.; Kawabe, T.



Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury  

PubMed Central

Background Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury. Method A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n = 7) or 15 min (group 2; n = 7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview®; Institut National des Télécommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated. Results Injection of contrast material significantly increased the apparent volume of lung tissue by 83 ± 57 ml in group 1 and 102 ± 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 ± 52 ml and 31 ± 18 ml. Conclusion Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury, it seems prudent to avoid this procedure in critically ill patients undergoing a thoracic CT scan and to reserve its use for specific indications.

Bouhemad, Belaid; Richecoeur, Jack; Lu, Qin; Malbouisson, Luiz M; Cluzel, Philippe; Rouby, Jean-Jacques



Lung disease with chronic obstruction in opium smokers in Singapore  

PubMed Central

Fifty-four opium smokers with chronic obstructive lung disease were studied for two-and-a-half years. Forty-eight patients had a cough for at least two years before the onset of inappropriate exertional dyspnoea. Fine, bubbling adventitious sounds suggesting small airway disease were heard on auscultation over the middle and lower lobes in 38 patients. The prevalence of inflammatory lung disease and chronic respiratory failure in this series is suggested as the main cause for the frequent finding of right ventricular hypertrophy and congestive heart failure. Physiological studies revealed moderate to severe airways obstruction with gross over-inflation and, in 32 patients, an additional restrictive defect probably due to peribronchiolar fibrosis. Radiological evidence of chronic bronchitis and bronchiolitis was observed in 45 patients, `pure' chronic bronchiolitis in six patients, and `widespread' emphysema in 25 patients respectively. Necropsy examinations in nine patients, however, showed destructive emphysema of variable severity in all. Chronic bronchiolitis often associated with striking bronchiolectasis was present in six cases. More severe bronchiolar rather than bronchial inflammation was noted. The heavy opium smokers had characteristic nodular shadows on chest radiography, sometimes associated with a striking reticular pattern not seen in `pure' cigarette smokers. This was due to gross pigmented dust (presumably carbon) deposition in relation to blood vessels, lymphatics, and bronchioles, and also within the alveoli. It is speculated that the initial lesion is an acquired bronchiolitis. Opium smoking induces an irritative bronchopathy favouring repeated attacks of acute bronchiolitis and eventually resulting in obliterative bronchiolitis, peribronchiolar fibrosis, chronic bronchitis, and destructive emphysema. Images

Da Costa, J. L.; Tock, E. P. C.; Boey, H. K.



IL-17 response mediates acute lung injury induced by the 2009 pandemic influenza A (H1N1) virus.  


The 2009 flu pandemic involved the emergence of a new strain of a swine-origin H1N1 influenza virus (S-OIV H1N1) that infected almost every country in the world. Most infections resulted in respiratory illness and some severe cases resulted in acute lung injury. In this report, we are the first to describe a mouse model of S-OIV virus infection with acute lung injury and immune responses that reflect human clinical disease. The clinical efficacy of the antiviral oseltamivir (Tamiflu) administered in the early stages of S-OIV H1N1 infection was confirmed in the mouse model. Moreover, elevated levels of IL-17, Th-17 mediators and IL-17-responsive cytokines were found in serum samples of S-OIV-infected patients in Beijing. IL-17 deficiency or treatment with monoclonal antibodies against IL-17-ameliorated acute lung injury induced by the S-OIV H1N1 virus in mice. These results suggest that IL-17 plays an important role in S-OIV-induced acute lung injury and that monoclonal antibodies against IL-17 could be useful as a potential therapeutic remedy for future S-OIV H1N1 pandemics. PMID:22025253

Li, Chenggang; Yang, Penghui; Sun, Yang; Li, Taisheng; Wang, Chen; Wang, Zhong; Zou, Zhen; Yan, Yiwu; Wang, Wei; Wang, Chen; Chen, Zhongwei; Xing, Li; Tang, Chong; Ju, Xiangwu; Guo, Feng; Deng, Jiejie; Zhao, Yan; Yang, Peng; Tang, Jun; Wang, Huanling; Zhao, Zhongpeng; Yin, Zhinan; Cao, Bin; Wang, Xiliang; Jiang, Chengyu



Coronary Artery Disease Is Under-diagnosed and Under-treated in Advanced Lung Disease  

PubMed Central

BACKGROUND Coronary artery disease is a potentially treatable comorbidity observed frequently in both chronic obstructive pulmonary disease and interstitial lung disease. The prevalence of angiographically proven coronary artery disease in advanced lung disease is not well described. We sought to characterize the treatment patterns of coronary artery disease complicating advanced lung disease and to describe the frequency of occult coronary artery disease in this population. METHODS We performed a 2-center, retrospective cross-sectional study of patients with either chronic obstructive pulmonary disease or interstitial lung disease evaluated for lung transplantation. Medications and diagnoses before the transplant evaluation were recorded in conjunction with left heart catheterization results. RESULTS Of 473 subjects, 351 had chronic obstructive pulmonary disease, and 122 had interstitial lung disease. In subjects diagnosed clinically with coronary artery disease, medical regimens included a statin in 78%, antiplatelet therapy in 62%, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in 42%, and a beta-blocker in 37%. Ten percent were on no medication from these 4 classes. Fifty-seven percent of these subjects were on an antiplatelet agent as well as a statin, and 13% were on neither. Beta-blockers were less frequently prescribed in chronic obstructive pulmonary disease than interstitial lung disease (23% vs 58%, P = .007). Coronary angiography was available in 322 subjects. It demonstrated coronary artery disease in 60% of subjects, and severe coronary artery disease in 16%. Occult coronary artery disease and severe occult coronary artery disease were found in 53% and 9%, respectively. There were no significant differences in angiographic results between chronic obstructive pulmonary disease and interstitial lung disease, despite imbalanced risk factors. CONCLUSIONS Coronary artery disease is common in patients with advanced lung disease attributable to chronic obstructive pulmonary disease or interstitial lung disease and is under-diagnosed. Guideline-recommended cardioprotective medications are suboptimally utilized in this population.

Reed, Robert M.; Eberlein, Michael; Girgis, Reda E.; Hashmi, Salman; Iacono, Aldo; Jones, Steven; Netzer, Giora; Scharf, Steven



Granulocyte Inflammatory Markers and Airway Infection during Acute Exacerbation of Chronic Obstructive Pulmonary Disease  

Microsoft Academic Search

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation in the air- ways and lung parenchyma; however, little is known about the in- flammatory response during acute COPD exacerbation. The objec- tives of this study were ( 1 ) to determine if inflammatory markers associated with neutrophilic inflammation and activation increase at times of




Acute exacerbations and respiratory failure in chronic obstructive pulmonary disease.  


Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) describe the phenomenon of sudden worsening in airway function and respiratory symptoms in patients with COPD. These exacerbations can range from self-limited diseases to episodes of florid respiratory failure requiring mechanical ventilation. The average patient with COPD experiences two such episodes annually, and they account for significant consumption of health care resources. Although bacterial infections are the most common causes of AECOPD, viral infections and environmental stresses are also implicated. AECOPD episodes can be triggered or complicated by other comorbidities, such as heart disease, other lung diseases (e.g., pulmonary emboli, aspiration, pneumothorax), or systemic processes. Pharmacologic management includes bronchodilators, corticosteroids, and antibiotics in most patients. Oxygen, physical therapy, mucolytics, and airway clearance devices may be useful in selected patients. In hypercapneic respiratory failure, noninvasive positive pressure ventilation may allow time for other therapies to work and thus avoid endotracheal intubation. If the patient requires invasive mechanical ventilation, the focus should be on avoiding ventilator-induced lung injury and minimizing intrinsic positive end-expiratory pressure. These may require limiting ventilation and "permissive hypercapnia." Although mild episodes of AECOPD are generally reversible, more severe forms of respiratory failure are associated with a substantial mortality and a prolonged period of disability in survivors. PMID:18453367

MacIntyre, Neil; Huang, Yuh Chin



The role of female hormones on lung function in chronic lung diseases  

Microsoft Academic Search

Background  The prevalence, morbidity, and mortality of inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease\\u000a (COPD) and cystic fibrosis (CF) are increasing in women. There is a dearth of data on the biological mechanisms to explain\\u000a such observations. However, some large epidemiologic studies suggest that lung function fluctuates during the menstrual cycle\\u000a in female patients with airways disease but

Anthony Tam; Don Morrish; Samuel Wadsworth; Delbert Dorscheid; SF Paul Man; Don D Sin



Selectins revisited: the emerging role of platelets in inflammatory lung disease  

PubMed Central

Neutrophil infiltration into the lung is considered a crucial step in the pathogenesis of acute lung injury, yet data on the underlying mechanisms have been ambiguous: although selectin-mediated leukocyte rolling is absent in lung capillaries, therapeutic strategies targeted at selectin-mediated cell-cell interactions yield partial protection. The study by Zarbock and coworkers in this issue of the JCI solves this apparent contradiction by identifying selectin-mediated platelet-neutrophil interaction as a critical step in the mutual activation of leukocytes and endothelial cells (see the related article beginning on page 3211). The emerging role of platelets may be of broad clinical relevance in lung inflammatory disorders, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis.

Kuebler, Wolfgang M.



Genetic Risk Factors in Acute Coronary Disease  

Microsoft Academic Search

Objective: We investigate whether each of the following: HPA-1, Factor V Leiden, prothrombin gene variant and the methylene tetrahydrofolate reductase gene (MTHFR) mutation, are risk factors for acute coronary disease in Portuguese patients. Material and Methods: 100 blood donors and 52 patients with an established diagnosis of myocardial infarction or unstable angina were evaluated for genetic risk factors, by determining

F. Araújo; A. Santos; V. Araújo; I. Henriques; F. Monteiro; E. Meireles; I. Moreira; D. David; M. J. Maciel; L. M. Cunha-Ribeiro



Contagious caprine pleuropneumonia and Mannheimia haemolytica-associated acute respiratory disease of goats and sheep in Afar Region, Ethiopia  

Microsoft Academic Search

Summary In April 2002, an investigation into an outbreak of acute respiratory disease in goats and sheep in Milae (Afar), Ethiopia was conducted. The investigation involved 4 flocks (722 sheep and 750 goats in total) and comprised the disease history, clinical and post-mortem examination, and microbiological analysis of nasal swabs, lung lesions, and pleural fluid samples. Clinically diseased animals exhibited

G. Shiferaw; S. Tariku; G. Ayelet; Z. Abebe


Factors associated with chronic lung disease in preterm infants.  

PubMed Central

Among 659 infants of 30 weeks' gestation or less born in a regional perinatal centre between 1983 and 1989, 195 were ventilated for four days or more and survived to 28 days, and 87 of these developed chronic lung disease. There was a sevenfold increase in the annual incidence of chronic lung disease over time. During the same period there were significant increases in the number of infants who survived, the incidence of septicaemia, and the use of parenteral lipid emulsions. Chronic lung disease was significantly associated with low birth weight, shorter gestation, duration of ventilation, vaginal delivery, sepsis, and the use of lipid. Respiratory and physiological measurements at 96 hours were significantly worse in infants who subsequently developed chronic lung disease. Initial logistic regression showed that gestation, arterial carbon dioxide tension (PaCO2), and ventilation rate at 96 hours; and birth in 1988 or 1989, were independently associated with chronic lung disease, but when septicaemia and use of lipid during the first 21 days were included, only gestational age (odds ratio 0.64, 95% confidence interval (CI), 0.49 to 0.81 for each week) and use of lipid (odds ratio 8.1, 95% CI, 2.32 to 28.0) remained significantly associated with chronic lung disease. The observed increase in incidence of chronic lung disease in this population was associated with earlier use of parenteral lipids in infants of very low gestation rather than with changes in population, survival, or ventilator treatment of respiratory distress syndrome.

Cooke, R W



Significance of the microbiome in obstructive lung disease  

PubMed Central

The composition of the lung microbiome contributes to both health and disease, including obstructive lung disease. Because it has been estimated that over 70% of the bacterial species on body surfaces cannot be cultured by currently available techniques, traditional culture techniques are no longer the gold standard for microbial investigation. Advanced techniques that identify bacterial sequences, including the 16S ribosomal RNA gene, have provided new insights into the depth and breadth of microbiota present both in the diseased and normal lung. In asthma, the composition of the microbiome of the lung and gut during early childhood development may play a key role in the development of asthma, while specific airway microbiota are associated with chronic asthma in adults. Early bacterial stimulation appears to reduce asthma susceptibility by helping the immune system develop lifelong tolerance to innocuous antigens. By contrast, perturbations in the microbiome from antibiotic use may increase the risk for asthma development. In chronic obstructive pulmonary disease, bacterial colonisation has been associated with a chronic bronchitic phenotype, increased risk of exacerbations, and accelerated loss of lung function. In cystic fibrosis, studies utilising culture-independent methods have identified associations between decreased bacterial community diversity and reduced lung function; colonisation with Pseudomonas aeruginosa has been associated with the presence of certain CFTR mutations. Genomic analysis of the lung microbiome is a young field, but has the potential to define the relationship between lung microbiome composition and disease course. Whether we can manipulate bacterial communities to improve clinical outcomes remains to be seen.

Han, MeiLan K; Huang, Yvonne J; LiPuma, John J; Boushey, Homer A; Boucher, Richard C; Cookson, William O; Curtis, Jeffrey L; Erb-Downward, John; Lynch, Susan V; Sethi, Sanjay; Toews, Galen B; Young, Vincent B; Wolfgang, Matthew C; Huffnagle, Gary B; Martinez, Fernando J



Congenital cystic lung disease: contemporary antenatal and postnatal management  

Microsoft Academic Search

Congenital cystic lung disease comprises a broad spectrum of rare but clinically significant developmental abnormalities,\\u000a including congenital pulmonary adenomatoid malformations, bronchopulmonary sequestrations, bronchogenic cysts, and congenital\\u000a lobar emphysema that result from perturbations in lung and airway embryogenesis. As congenital lung lesions are now more commonly\\u000a recognized antenatally, mothers require accurate prenatal counseling and appropriate perinatal management. In light of long-term

Richard G. Azizkhan; Timothy M. Crombleholme



Sex Differences and Sex Steroids in Lung Health and Disease  

PubMed Central

Sex differences in the biology of different organ systems and the influence of sex hormones in modulating health and disease are increasingly relevant in clinical and research areas. Although work has focused on sex differences and sex hormones in cardiovascular, musculoskeletal, and neuronal systems, there is now increasing clinical evidence for sex differences in incidence, morbidity, and mortality of lung diseases including allergic diseases (such as asthma), chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, as well as pulmonary hypertension. Whether such differences are inherent and/or whether sex steroids play a role in modulating these differences is currently under investigation. The purpose of this review is to define sex differences in lung structure/function under normal and specific disease states, with exploration of whether and how sex hormone signaling mechanisms may explain these clinical observations. Focusing on adult age groups, the review addresses the following: 1) inherent sex differences in lung anatomy and physiology; 2) the importance of certain time points in life such as puberty, pregnancy, menopause, and aging; 3) expression and signaling of sex steroid receptors under normal vs. disease states; 4) potential interplay between different sex steroids; 5) the question of whether sex steroids are beneficial or detrimental to the lung; and 6) the potential use of sex steroid signaling as biomarkers and therapeutic avenues in lung diseases. The importance of focusing on sex differences and sex steroids in the lung lies in the increasing incidence of lung diseases in women and the need to address lung diseases across the life span.

Townsend, Elizabeth A.; Miller, Virginia M.



Loss of Extracellular Superoxide Dismutase Leads to Acute Lung Damage in the Presence of Ambient Air  

PubMed Central

The extracellular superoxide dismutase 3 (SOD3) is highly expressed in both blood vessels and lungs. In different models of pulmonary injury, SOD3 is reduced; however, it is unclear whether this contributes to lung injury. To study the role of acute SOD3 reduction in lung injury, the SOD3 gene was deleted in adult mice by using the Cre-Lox technology. Acute reduction of SOD3 led to a fivefold increase in lung superoxide, marked inflammatory cell infiltration, a threefold increase in the arterial-alveolar gradient, respiratory acidosis, histological changes similar to those observed in adult respiratory distress syndrome, and 85% mortality. Treatment with the SOD mimetic MnTBAP and intranasal administration of SOD-containing polyketal microparticles reduced mortality, prevented the histological alterations, and reduced lung superoxide levels. To understand how mice with the SOD3 embryonic deletion survived without lung injury, gene array analysis was performed. These data demonstrated the up-regulation of 37 genes and down-regulation of nine genes, including those involved in cell signaling, inflammation, and gene transcription in SOD3?/? mice compared with either mice with acute SOD3 reduction or wild-type controls. These studies show that SOD3 is essential for survival in the presence of ambient oxygen and that acute loss of this enzyme can lead to severe lung damage. Strategies either to prevent SOD3 inactivation or to augment its levels might prove useful in the treatment of acute lung injury.

Gongora, Maria Carolina; Lob, Heinrich E.; Landmesser, Ulf; Guzik, Tomasz J.; Martin, W. David; Ozumi, Kiyoski; Wall, Susan M.; Wilson, David Scott; Murthy, Niren; Gravanis, Michael; Fukai, Tohru; Harrison, David G.



Biomarkers in acute coronary artery disease.  


Death from coronary artery disease is by far the leading cause of death worldwide. There is no doubt that a better understanding of atherothrombosis has guided development of improved diagnostic facilities as well as revascularization technologies in combination with current antithrombotic strategies that have altogether impressively reduced acute thromboembolic complications and death from cardiovascular causes within the last decades. However, the rate of ischemic complications even after optimal revascularization and medical therapy remains high. Similarly, morbidity and death associated with chronic ischemic heart disease and ischemic cardiomyopathy respectively are constantly rising. Therefore, there is still a strong need for effective primary prevention strategies, fast and accurate diagnostic procedures as well as for new and smart antithrombotic drugs. The review focuses on cardiac troponins, as relevant markers of myocardial necrosis, currently used in the diagnostic process of acute coronary syndrome. Furthermore, we will discuss the potential role of copeptin, a new marker of acute endogenous stress in acute coronary syndrome patients, as faster diagnosis might lead to faster treatment as well as improved short- and long-term outcome following acute coronary syndrome. Finally, platelets are an old, yet rediscovered biomarker for ischemic cardiovascular outcomes that might be used to estimate the individual bleeding or thrombotic risk and to tailor antiplatelet therapy. PMID:23143510

Freynhofer, Matthias K; Tajsi?, Miloš; Wojta, Johann; Huber, Kurt



Interstitial Lung Disease in a Patient with Dyskeratosis Congenita  

PubMed Central

Dyskeratosis congenita is a rare congenital disorder characterized by a triad of reticular pigmentation of the skin, dystrophic nails, and leukoplakia of the mucous membrane. Sometimes it is associated with bone marrow failure, secondary malignancy and interstitial lung disease. Though it is rare, Dyskeratosis congenita is diagnosed relatively easily when clinicians suspect it. It can be diagnosed just by gross inspection with care. Dyskeratosis congenita should be considered as one cause associated with interstitial lung disease. In Korea, interstitial lung disease with dyskeratosis congenita has not been reported. We report a case and review the literature.

Kim, Hyun Jung; Kim, Kyu Jin; Lee, Kwan Ho; Shin, Kyeong-Cheol; Hyun, Myung Soo; Kim, Ki-Hong



Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury  

PubMed Central

Background Proline-rich tyrosine kinase 2 (Pyk2) is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI) remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo. Methods C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically. Results Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1) myeloperoxidase content in lung tissues, 2) vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3) the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment. Conclusions These results suggest that Pyk2 plays an important role in the development of acute lung injury in mice and that pharmacological inhibition of Pyk2 might provide a potential therapeutic strategy in the pretreatment for patients at imminent risk of developing acute lung injury.



VATS Lung Biopsy in Suspected, Diffuse Interstitial Lung Disease Provides Diagnosis, and Alters Management Strategies  

Microsoft Academic Search

Objectives.In patients with suspected diffuse interstitial lung disease, open lung biopsy is associated with high mortality (16%). This risk is only acceptable if diagnosis is made and management enhanced. We reviewed the role of VATS techniques in this group to determine the morbidity, mortality and outcomes in terms of diagnosis and enhanced management.

Adrian Ooi; Sri Iyenger; Jonathan Ferguson; Andrew J. Ritchie



Interstitial lung disease associated with vindesine and radiation therapy for carcinoma of the lung  

SciTech Connect

Diffuse interstitial lung disease and pulmonary fibrosis occurred after the use of vindesine and radiation therapy in a patient with squamous cell carcinoma of the lung. Clinical improvement occurred after the drug was discontinued and corticosteroid therapy was initiated. Review of the literature reveals no previously reported cases of pulmonary toxicity due to vindesine when used alone or in combination with other therapeutic modalities.

Bott, S.J.; Stewart, F.M.; Prince-Fiocco, M.A.



Lung volume reduction surgery and lung transplantation in chronic obstructive pulmonary disease  

PubMed Central

Medical treatment of emphysema does not alter the natural progression of the disease. Surgical techniques are an attractive conceptual approach to treat hyperinflation in these patients. Lung volume reduction surgery and lung transplantation are appropriate therapeutic options for a selected population with emphysema. We will review the available evidence to support these approaches.

Mora, Jorge I; Hadjiliadis, Denis



Fatal interstitial lung disease associated with oral erlotinib therapy for lung cancer  

Microsoft Academic Search

BACKGROUND: Erlotinib is a Human Epidermal Growth Factor Receptor Type 1\\/tyrosine kinase (EGFR) inhibitor which is used for non-small-cell lung cancer treatment. Despite that erlotinib is considered to have a favorable safety profile, adverse events such as interstitial lung disease (ILD) were reported in pivotal studies. The authors report the first histologically confirmed case of fatal ILD associated with erlotinib

Demosthenes Makris; Arnaud Scherpereel; Marie Christine Copin; Guillaume Colin; Luc Brun; Jean Jacques Lafitte; Charles Hugo Marquette



Development of a Multicomponent Prediction Model for Acute Esophagitis in Lung Cancer Patients Receiving Chemoradiotherapy  

SciTech Connect

Purpose: To construct a model for the prediction of acute esophagitis in lung cancer patients receiving chemoradiotherapy by combining clinical data, treatment parameters, and genotyping profile. Patients and Methods: Data were available for 273 lung cancer patients treated with curative chemoradiotherapy. Clinical data included gender, age, World Health Organization performance score, nicotine use, diabetes, chronic disease, tumor type, tumor stage, lymph node stage, tumor location, and medical center. Treatment parameters included chemotherapy, surgery, radiotherapy technique, tumor dose, mean fractionation size, mean and maximal esophageal dose, and overall treatment time. A total of 332 genetic polymorphisms were considered in 112 candidate genes. The predicting model was achieved by lasso logistic regression for predictor selection, followed by classic logistic regression for unbiased estimation of the coefficients. Performance of the model was expressed as the area under the curve of the receiver operating characteristic and as the false-negative rate in the optimal point on the receiver operating characteristic curve. Results: A total of 110 patients (40%) developed acute esophagitis Grade {>=}2 (Common Terminology Criteria for Adverse Events v3.0). The final model contained chemotherapy treatment, lymph node stage, mean esophageal dose, gender, overall treatment time, radiotherapy technique, rs2302535 (EGFR), rs16930129 (ENG), rs1131877 (TRAF3), and rs2230528 (ITGB2). The area under the curve was 0.87, and the false-negative rate was 16%. Conclusion: Prediction of acute esophagitis can be improved by combining clinical, treatment, and genetic factors. A multicomponent prediction model for acute esophagitis with a sensitivity of 84% was constructed with two clinical parameters, four treatment parameters, and four genetic polymorphisms.

De Ruyck, Kim, E-mail: [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium); Sabbe, Nick [Department of Applied Mathematics, Biometrics and Process Control, Ghent University, Ghent (Belgium); Oberije, Cary [Department of Radiation Oncology (MAASTRO Clinic), Research Institute of Growth and Development, Maastricht University Medical Center, Maastricht (Netherlands); Vandecasteele, Katrien [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Thas, Olivier [Department of Applied Mathematics, Biometrics and Process Control, Ghent University, Ghent (Belgium); De Ruysscher, Dirk; Lambin, Phillipe [Department of Radiation Oncology (MAASTRO Clinic), Research Institute of Growth and Development, Maastricht University Medical Center, Maastricht (Netherlands); Van Meerbeeck, Jan [Department of Respiratory Medicine, Ghent University Hospital, Ghent (Belgium); De Neve, Wilfried [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Thierens, Hubert [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium)



Haplotype Association Mapping of Acute Lung Injury in Mice Implicates Activin A Receptor, Type 1  

PubMed Central

Rationale: Because acute lung injury is a sporadic disease produced by heterogeneous precipitating factors, previous genetic analyses are mainly limited to candidate gene case-control studies. Objectives: To develop a genome-wide strategy in which single nucleotide polymorphism associations are assessed for functional consequences to survival during acute lung injury in mice. Methods: To identify genes associated with acute lung injury, 40 inbred strains were exposed to acrolein and haplotype association mapping, microarray, and DNA-protein binding were assessed. Measurements and Main Results: The mean survival time varied among mouse strains with polar strains differing approximately 2.5-fold. Associations were identified on chromosomes 1, 2, 4, 11, and 12. Seven genes (Acvr1, Cacnb4, Ccdc148, Galnt13, Rfwd2, Rpap2, and Tgfbr3) had single nucleotide polymorphism (SNP) associations within the gene. Because SNP associations may encompass “blocks” of associated variants, functional assessment was performed in 91 genes within ± 1 Mbp of each SNP association. Using 10% or greater allelic frequency and 10% or greater phenotype explained as threshold criteria, 16 genes were assessed by microarray and reverse real-time polymerase chain reaction. Microarray revealed several enriched pathways including transforming growth factor-? signaling. Transcripts for Acvr1, Arhgap15, Cacybp, Rfwd2, and Tgfbr3 differed between the strains with exposure and contained SNPs that could eliminate putative transcriptional factor recognition sites. Ccdc148, Fancl, and Tnn had sequence differences that could produce an amino acid substitution. Mycn and Mgat4a had a promoter SNP or 3?untranslated region SNPs, respectively. Several genes were related and encoded receptors (ACVR1, TGFBR3), transcription factors (MYCN, possibly CCDC148), and ubiquitin-proteasome (RFWD2, FANCL, CACYBP) proteins that can modulate cell signaling. An Acvr1 SNP eliminated a putative ELK1 binding site and diminished DNA–protein binding. Conclusions: Assessment of genetic associations can be strengthened using a genetic/genomic approach. This approach identified several candidate genes, including Acvr1, associated with increased susceptibility to acute lung injury in mice.

Leikauf, George D.; Concel, Vincent J.; Liu, Pengyuan; Bein, Kiflai; Berndt, Annerose; Ganguly, Koustav; Jang, An Soo; Brant, Kelly A.; Dietsch, Maggie; Pope-Varsalona, Hannah; Dopico, Richard A.; Di, Y. P. Peter; Li, Qian; Vuga, Louis J.; Medvedovic, Mario; Kaminski, Naftali; You, Ming; Prows, Daniel R.



Immunopathophysiologic mechanisms of cystic fibrosis lung disease.  


Cystic fibrosis is a life-threatening autosomal recessive disorder with a highly variable clinical presentation. The pathophysiology is related to the mutant transmembrane conductance regulator (CFTR), a chloride channel that is encoded by the CF single gene located on chromosome 7. The variability of the clinical presentations, even among patients carrying the same mutation, is extensive enough to justify the hypothesis that other pathophysiologic mechanisms participate in the evolution of the disease phenotype. Presented here are recent lines of research on the contributing factors to respiratory tract morbidity, as well as the innate defense mechanisms in the CF lungs, the cytokines and chemokines that influence the inflammatory processes, the antioxidative system, and the composition of the airways surface fluid. These studies concluded that the clinical presentation is determined by pathology of the CFTR as well as by other mechanisms, some of which are related to the CFTR functions and others to the products of modifier genes as well as the influence of the environment. PMID:16450752

Soferman, Ruth



How Are Asbestos-Related Lung Diseases Treated?  


... Pleural Disorders Chest X Ray Chest CT Scan Lung Function Tests Bronchoscopy Related Media Videos Widgets Quizzes Send a link to NHLBI to someone by E-MAIL | PRINT PAGE | PRINT ENTIRE ... How Are Asbestos-Related Lung Diseases Treated? No treatments can reverse the effects ...


Chronic Obstructive Pulmonary Disease and Lung Cancer: New Molecular Insights  

Microsoft Academic Search

Both chronic obstructive pulmonary disease (COPD) and lung cancer are major causes of death worldwide. In most cases this reflects cigarette smoke exposure which is able to induce an inflammatory response in the airways of smokers. Indeed, COPD is characterized by lower airway inflammation, and importantly, the presence of COPD is by far the greatest risk factor for lung cancer

Ian M. Adcock; Gaetano Caramori; Peter J. Barnes



Out-Patient Management of Patients with Chronic Obstructive Lung Disease  

PubMed Central

The treatment of chronic obstructive lung disease is multifaceted. If the patient smokes, he or she must quit. Treatment includes bronchodilator therapy, glucocorticosteroids, antibiotics for acute exacerbations, oxygen therapy for patients with chronic hypoxemia (it can also help patients with nocturnal and exercise-induced hypoxemia), and respiratory rehabilitation for motivated patients. Inhaled ?-agonists and anticholinergic agents have additive effects in recommended doses, as do theophylline and ?-agonists.

Tullis, Elizabeth; Grossman, Ronald F.



Early Identification of Patients at Risk of Acute Lung Injury  

PubMed Central

Rationale: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies. Objectives: To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS). Methods: In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions. Measurements and Main Results: Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1–4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78–0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9–5.7). Conclusions: ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with (NCT00889772).

Gajic, Ognjen; Dabbagh, Ousama; Park, Pauline K.; Adesanya, Adebola; Chang, Steven Y.; Hou, Peter; Anderson, Harry; Hoth, J. Jason; Mikkelsen, Mark E.; Gentile, Nina T.; Gong, Michelle N.; Talmor, Daniel; Bajwa, Ednan; Watkins, Timothy R.; Festic, Emir; Yilmaz, Murat; Iscimen, Remzi; Kaufman, David A.; Esper, Annette M.; Sadikot, Ruxana; Douglas, Ivor; Sevransky, Jonathan



Non-invasive pressure support ventilation in patients with acute respiratory failure after bilateral lung transplantation  

Microsoft Academic Search

Objective: To evaluate non-invasive ventilation (NIV) prospectively in a group of patients developing acute respiratory failure (ARF) after bilateral lung transplantation (BLT). Setting: General intensive care unit (ICU) of Rome \\

M. Rocco; G. Conti; M. Antonelli; M. Bufi; M. Costa; D. Alampi; F. Ruberto; G. Stazi; P. Pietropaoli



Pathogenesis of Septic Acute Lung Injury and Strategies for Immuno-Pharmacological Therapy.  

National Technical Information Service (NTIS)

During the report period, we studied sepsis-associated acute lung injury using a porcine model. In multiple protocols we found that deletion of certain proinflammatory mediators or disruption of neutrophil - endothelial cellular adhesion molecules effecti...

H. J. Sugerman A. A. Fowler



Acute cerebrovascular disease in women.  


In 2,000 consecutive stroke patients collected in a prospective hospital-based stroke registry over a 10-year period, we assessed whether stroke in men and women was different in respect to vascular risk factors, clinical features and natural history. The frequency of the different variable in men and women was analyzed by means of univariate analysis and logistic regression models. Women accounted for 48% of the study population (n = 967) and were older than men (mean age 75 vs. 69 years, p < 0.001). In the age group of 85 years or older, stroke was more frequent in women than in men (69.8 vs. 30.2%, p < 0.001). Women showed a higher frequency of cardioembolic infarction and a lower occurrence of lacunar infarction and stroke of undetermined cause than men. In-hospital mortality (17.4 vs. 13.3%) and length of hospital stay (19.6 vs. 16.7 days) was significantly higher (p < 0.001) in women than in men. In the model based on demographic variables and cardiovascular risk factors, obesity, heart failure, atrial fibrillation and age were significant predictors of stroke in women, while intermittent claudication, ischemic heart disease, chronic obstructive pulmonary disease, cigarette smoking and alcohol abuse were predictors in male sex. Hypertension and limb weakness were predictors for stroke in women, and absence of neurological deficit at hospital discharge, lacunar syndrome and ataxia were predictors in men in the models based on all variables. Women differ from men in the distribution of risk factors and stroke subtype, stroke severity and outcome. Differences in stroke pathology and/or differences in functional anatomy or plasticity of the brain between sexes may account for these findings. PMID:11385256

Arboix, A; Oliveres, M; García-Eroles, L; Maragall, C; Massons, J; Targa, C



Endothelium-derived microparticles induce endothelial dysfunction and acute lung injury.  


Acute lung injury (ALI) carries a high mortality in critically ill patients. Recent reports correlate elevated concentrations of endothelium-derived microparticles (EMPs) with diseases of endothelial dysfunction. Many of these diseases have ALI sequelae. We hypothesize that EMPs contribute to endothelial cell (EC) dysfunction and development of ALI. To test this hypothesis, we treated isolated vessels with EMPs and examined changes in vasodilation. Endothelial cell cultures were incubated with EMPs and examined for changes in stimulated nitric oxide (*NO) production and nitric oxide synthase (eNOS) activation. Finally, EMPs were injected into rats and mice and lungs examined for ALI. In both mouse and human ex vivo vessel preparations, we found a marked attenuation of endothelium-mediated vasodilation after EMP treatment (4 x 10(6)/mL). This dysfunction was not corrected by pretreatment of EMPs with free radical scavengers. Coincubation of EMPs with EC cultures yielded a three-fold reduction in A23187-stimulated *NO release. Western analysis of these cells showed a corresponding decrease in eNOS phosphorylation at Ser1179 and a decrease in hsp90 association. Measurements of lung permeability, myeloperoxidase activity, and histology of EMPs-treated Brown Norway rats demonstrated pulmonary edema, neutrophil recruitment, and compromise of the endothelial-alveolar barrier as a second hit phenomenon. In C57BL/6 mice, exogenous EMPs caused a significant rise in pulmonary capillary permeability both as a primary and secondary injury. These findings demonstrate EMPs are capable of inducing significant lung injury at pathophysiologically relevant concentrations. Endothelium-derived microparticles inhibit endothelium-mediated vasodilation and *NO generation from eNOS. Once elucidated, EMP mechanisms of inducing ALI and endothelial dysfunction may present new therapeutic targets. PMID:17047516

Densmore, John C; Signorino, Paul R; Ou, Jingsong; Hatoum, Ossama A; Rowe, J Jordi; Shi, Yang; Kaul, Sushma; Jones, Deron W; Sabina, Robert E; Pritchard, Kirkwood A; Guice, Karen S; Oldham, Keith T



Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury  

Microsoft Academic Search

Background  Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from\\u000a pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was\\u000a to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury.\\u000a \\u000a \\u000a \\u000a \\u000a Method  A spiral thoracic CT scan, consisting

Bélaid Bouhemad; Jack Richecoeur; Qin Lu; Luiz M Malbouisson; Philippe Cluzel; Jean-Jacques Rouby



Lung volume reduction surgery after lung transplantation for emphysema-chronic obstructive pulmonary disease.  


Lung Volume Reduction Surgery (LVRS) has become a palliative treatment for patients with advanced emphysema and disabling dyspnea. After single lung transplantation in chronic obstructive pulmonary disease, LVRS may be indicated to improve graft dysfunction caused by native lung hyperinflation compressing the grafted lung. This common complication is the subject of our study, which showed LVRS to be helpful to manage this situation. We performed an observational retrospective and descriptive study using the data of 293 patients transplanted in our center between January 1996 and October 2011. Some of the patients who underwent a single lung transplantation developed native lung hyperinflation years after the transplantation, interfering with respiratory function due to graft compression. PMID:22974928

Arango, E; Espinosa, D; Illana, J; Carrasco, G; Moreno, P; Algar, F J; Alvarez, A; Cerezo, F; Baamonde, C; Requejo, A; Redel, J; Vaquero, J; Santos, F; Salvatierra, A



Erythropoetin as a novel agent with pleiotropic effects against acute lung injury  

Microsoft Academic Search

Current pharmacotherapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is not optimal, and the\\u000a biological and physiological complexity of these severe lung injury syndromes requires consideration of combined-agent treatments\\u000a or agents with pleiotropic action. In this regard, exogenous erythropoietin (EPO) represents a possible candidate since a\\u000a number of preclinical studies have revealed beneficial effects of EPO

Sotirios Kakavas; Theano Demestiha; Panagiotis Vasileiou; Theodoros Xanthos



Humanized monoclonal antibody against the chemokine CXCL-8 (IL8) effectively prevents acute lung injury  

Microsoft Academic Search

As one of the most important endogenous chemotactic factors for neutrophils, the chemokine CXCL8 (IL-8) is involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), characterized by massive neutrophil infiltration in the lung. Since neutralization of CXCL8 with polyclonal antibody has been shown to reduce the severity of ALI\\/ARDS in animal models, we explored

ZhiYao Bao; QingWei Ye; WangHua Gong; Yi Xiang; HuanYing Wan



Bench-to-bedside review: Adenosine receptors – promising targets in acute lung injury?  

Microsoft Academic Search

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening disorders that have substantial\\u000a adverse effects on outcomes in critically ill patients. ALI\\/ARDS develops in response to pulmonary or extrapulmonary injury\\u000a and is characterized by increased leakage from the pulmonary microvasculature and excessive infiltration of polymorphonuclear\\u000a cells into the lung. Currently, no therapeutic strategies are available to control

Carsten P Schepp; Jörg Reutershan



Antithymocyte globulin-induced acute lung injury during transplantation for aplastic anemia.  


A 10-year-old boy with acquired, very severe aplastic anemia developed acute lung injury after the administration of equine antithymocyte globulin, during conditioning for allogenic bone marrow transplantation. Limited cases of antithymocyte globulin-induced acute lung injury have been described in adults. The respiratory worsening was sudden and required mechanical ventilation. The clinical course was complicated by sepsis with Escherichia coli, vancomycin-resistant enterococci, and Stenotrophomonas maltophilia. Implications for treatment are discussed and earlier literature is reviewed. PMID:21285902

Oberoi, Sapna; Bansal, Deepak; Sharma, Ratti Ram; Gautam, Vikas; Marwaha, Neelam; Marwaha, Ram Kumar



Ventilation-perfusion scan in the acutely ill patient with unilateral hyperlucent lung  

SciTech Connect

A patient with a unilateral hyperlucent lung with acute respiratory complaints is presented. A ventilation-perfusion scan was performed to rule out pulmonary embolism. The perfusion scan ( (/sup 99m/TC)MAA) showed peripheral perfusion defects in the hyperlucent lung. The ventilation study (/sup 133/Xe) demonstrated peripheral ventilatory defects on the single breath image in the hyperlucent lung, the filling in of these on the equilibrium view, and diffusely delayed washout in the affected lung. These findings were suggestive of the Swyer-James syndrome and critical in excluding the numerous other causes of unilateral hyperlucent lung, which are discussed. The importance of the ventilation-perfusion study (and particularly the ventilation scan) in the patient with unilateral hyperlucent lung and acute respiratory symptoms is stressed. In addition, a discussion of the Swyer-James syndrome is included.

Miller, M.B.; Caride, V.J.



Cotton Dust and Lung Disease: Presumptive Criteria for Disability Compensation.  

National Technical Information Service (NTIS)

The objective of this report is to present a set of presumptive criteria for the assessment of lung damage in cotton textile workers. The criteria are different for total, irreversible disabling disease, for partial disability which may eventually lead to...

A. Bouhuys



Spirometry: Simulations of Obstructive and Restrictive Lung Diseases  

NSDL National Science Digital Library

Description of spirometry exercises that enhance studentsÃÂ understanding of pulmonary physiology and pathophysiology, as well as allowing them to experience the difficulty, discomfort, and apprehension associated with lung disease

Mr. David W. Rodenbaugh (Wayne State University Department of Physiology); PhD Heidi L. Collins (Wayne State Univ. School of Medicine Dept. of Physiology); PhD Stephen M. DiCarlo (Wayne State Univ Sch Med Dept of Physiology)



Work-Related Lung Disease: All Pneumoconioses and Related Exposures  


... Home Work-Related Lung Disease Surveillance System (eWoRLD) All Pneumoconioses and Related Exposures Thumbnail Table/Figure Title Date Posted All pneumoconioses: Number of deaths, crude and age-adjusted ...


Effects of partial liquid ventilation with FC-77 on acute lung injury in newborn piglets.  


Partial liquid ventilation (PLV) with various types of perfluorochemicals (PFC) has been shown to be beneficial in treating acute lung injury. FC-77 is a type of PFC with relatively high vapor pressure and evaporative losses during PLV. This study tested the hypothesis that using FC-77 for PLV with hourly replacement is effective in treating acute lung injury. Fifteen neonatal piglets were randomly and evenly divided into 3 study groups: 1) lavage-induced lung injury followed by conventional mechanical ventilation (Lavage-CMV); 2) lavage-induced lung injury followed by PLV using FC-77 with hourly replacement (11.2 +/- 1.5 mL/kg/hr) (Lavage-PLV); and 3) sham lavage injury followed by conventional mechanical ventilation (Control). Immediately after induction, repeated saline lavages induced acute lung injury characterized by decreases in dynamic lung compliance, arterial oxygen tension, and arterial pH, and increases in arterial CO(2) tension and oxygenation index, whereas the sham lavage procedure failed to do so. During the 3-hr period of CMV, these pulmonary and cardiovascular parameters remained stable in the Control group, but deteriorated in the Lavage-CMV group. In contrast, after acute lung injury, low lung compliance, abnormal gas exchange, acidosis, and inadequate oxygenation significantly improved in the Lavage-PLV group. Histological analysis of these 3 study groups revealed that the Lavage-CMV group had the highest lung injury score and the Control group had the lowest. These results suggest that, in comparison to CMV, PLV with FC-77 and hourly replacement of FC-77 promotes more favorable pulmonary mechanics, gas exchange, oxygenation, and lung histology in a piglet model of acute lung injury. PMID:11747255

Jeng, Mei-Jy; Kou, Yu Ru; Sheu, Ching-Chung; Hwang, Betau



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. PMID:23375643

Xu, Lauren; Drachenberg, Cinthia; Tavora, Fabio; Burke, Allen



Lung cancer in Hodgkin's disease: association with previous radiotherapy  

SciTech Connect

Seven cases of lung cancer were observed in patients with Hodgkin's disease (HD) since 1970. The risk ratio for the development of lung cancer among HD patients was 5.6 times that expected in the general population. The pertinent clinical data from these patients are described and compared to 28 additional patients reported from other institutions. Small-cell lung cancer represented the predominant histologic type of lung cancer encountered in both smoking and nonsmoking patients with HD, accounting for 42% of cases overall and greater than 55% of cases reported in reviews of second malignancies. Tobacco use was noted in only 53% of patients. Twenty-eight (94%) of 30 patients developing metachronous lung cancer received supradiaphragmatic irradiation as primary therapy for HD. Nineteen (68%) of these patients received subsequent chemotherapy salvage. The median age at diagnosis of HD and lung cancer was 39 and 45 years, respectively. The interval between diagnosis of HD and metachronous lung cancer averaged seven years but appeared to vary inversely with age. HD patients treated with supradiaphragmatic irradiation or combined modality therapy may be at increased risk for developing lung cancer. The high frequency of in-field malignancies that the authors observed and the prevalence of small-cell lung cancer in both smoking and nonsmoking patients suggests that chest irradiation may influence the development of metachronous lung cancer in these patients. The finding of a mean latent interval in excess of seven years emphasizes the need for close long-term observation.

List, A.F.; Doll, D.C.; Greco, F.A.



Lung Cancer Following Chemotherapy and Radiotherapy for Hodgkin's Disease  

Microsoft Academic Search

Background: Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well de- scribed.We quantified the risk of treatment-associated lung cancer, taking into account tobacco use. Methods: Within a population-based cohort of 19 046 Hodgkin's disease patients (diagnosed from 1965 through 1994), a case-control study of

Lois B. Travis; Mary Gospodarowicz; Rochelle E. Curtis; E. Aileen Clarke; Michael Andersson; Bengt Glimelius; Timo Joensuu; Charles F. Lynch; Eric Holowaty; Hans Storm; Ingrid Glimelius; Eero Pukkala; Marilyn Stovall; Joseph F. Fraumeni; John D. Boice; Ethel Gilbert



The Treatment of Acidosis in Acute Lung Injury with Tris-Hydroxymethyl Aminomethane (THAM)  

Microsoft Academic Search

Mechanical hyperventilation of acidemic patients with acute lung injury (ALI) requires the use of high volumes and pressures that may worsen lung injury. However, permissive hypercapnia in the presence of shock, metabolic acidosis, and multi-organ system dysfunction may compromise normal cellular function. Tris-hy- droxymethyl aminomethane (THAM) may be an effective method to control acidosis in this circumstance. Protonated THAM is




Acute and Short-term Effects of Secondhand Smoke on Lung Function and Cytokine Production  

Microsoft Academic Search

Rationale: The acute effect of secondhand smoke (SHS) on lung function and the duration of system disruption remain unknown. Objectives: To assess the SHS effects and their duration on lung function and inflammatory markers. Methods: In a randomized single-blind crossover experiment data were obtained from 16 (8 women) nonsmoking adults at baseline and at 0, 1, and 3 hours after

Andreas D. Flouris; Giorgos S. Metsios; Andres E. Carrillo; Athanasios Z. Jamurtas; Konstantinos Gourgoulianis; Theodoros Kiropoulos; Manolis N. Tzatzarakis; Aristidis M. Tsatsakis; Yiannis Koutedakis



Diagnosis and management of drug-associated interstitial lung disease  

PubMed Central

Symptoms of drug-associated interstitial lung disease (ILD) are nonspecific and can be difficult to distinguish from a number of illnesses that commonly occur in patients with non-small-cell lung cancer (NSCLC) on therapy. Identification of drug involvement and differentiation from other illnesses is problematic, although radiological manifestations and clinical tests enable many of the alternative causes of symptoms in advanced NSCLC to be excluded. In lung cancer patients, high-resolution computed tomography (HRCT) is more sensitive than a chest radiograph in evaluating the severity and progression of parenchymal lung disease. Indeed, the use of HRCT imaging has led to the recognition of many distinct patterns of lung involvement and, along with clinical signs and symptoms, helps to predict both outcome and response to treatment. This manuscript outlines the radiology of drug-associated ILD and its differential diagnosis in NSCLC. An algorithm that uses clinical tests to exclude alternative diagnoses is also described.

Muller, N L; White, D A; Jiang, H; Gemma, A



Prevention of Endotracheal Suctioning-induced Alveolar Derecruitment in Acute Lung Injury  

Microsoft Academic Search

We studied endotracheal suctioning-induced alveolar derecruit- concentrated on reversing or preventing hypoxemia resulting ment and its prevention in nine patients with acute lung injury. from such a procedure. Few data exist about the effect of Changes in end-expiratory lung volume measured by inductive endotracheal suctioning on lung volumes (3-5), and no study plethysmography, positive end-expiratory pressure-induced alveo- has assessed the

Salvatore M. Maggiore; Francois Lellouche; Jerome Pigeot; Solenne Taille; Nicolas Deye; Xavier Durrmeyer; Jean-Christophe Richard; Jordi Mancebo; Laurent Brochard


Chronic or high dose acute caffeine treatment protects mice against oleic acid-induced acute lung injury via an adenosine A2A receptor-independent mechanism.  


The antagonism or genetic deletion of adenosine A(2A) receptors has been shown to exacerbate tissue damage in acute lung injury. Caffeine, a widely consumed behavioral drug, acts as a non-selective antagonist of A(2A) receptor and also has additional pharmacological effects. Thus, the protective vs. deleterious effects of caffeine in acute lung injury should be evaluated. In a murine oleic acid-induced model of acute lung injury, we found that chronic caffeine treatment by drinking water (0.1g/l or 0.25g/l for 2 weeks before acute lung injury) or acute caffeine treatment at high dose (i.p. 50mg/kg, injection, 30min before acute lung injury) significantly attenuated the lung edema, hemorrhage, neutrophil recruitment as well as the inflammatory cytokine tumor necrosis factor-? (TNF-?) and interleukin-1 (IL-1) expressions in both of the wild type (WT) and A(2A) receptor knockout (KO) mice. This profile was accompanied by increased cAMP levels and up-regulation of A2B receptor mRNAs in the lungs. In contrast, acute caffeine treatment at low dose (i.p. 5mg/kg or 15mg/kg, injection, 30min before acute lung injury) enhanced the inflammation and lung damage in WT mice with decreasing cAMP but not in A(2A) receptor KO mice. These results indicate that caffeine either enhances lung damage by antagonizing A(2A) receptor or exerts protection against lung damage via A(2A) receptor-independent mechanisms, depending on the timing of exposure (chronic vs. acute) and dose of administration (low vs. high). These findings provide new insight of caffeine in acute lung injury and highlight the potential benefit and strategy of caffeine intake or administration for preventing acute lung injury. PMID:21238452

Li, Jun; Li, Gongbo; Hu, Jian-Lin; Fu, Xiao-Hong; Zeng, Yi-Jun; Zhou, Yuan-Guo; Xiong, Gang; Yang, Nan; Dai, Shuang-Shuang; He, Feng-Tian



Acute onset of adult Alexander disease.  


Adult-onset Alexander disease (AOAD) is a rare leukoencephalopathy affecting predominantly the brainstem and cervical cord with insidious onset of clinical features. Acute onset is very rare and has yet been described only twice, to our knowledge. We report a 32-year-old hitherto healthy male who, after excessive consumption of alcohol, presented with stroke-like onset of symptoms including rigidospasticity, loss of consciousness, and bulbar dysfunction. MRI features comprised bilateral T2-hyperintensities of frontal white matter and basal ganglia as well as atrophy of medulla oblongata with a peculiar "tadpole" appearance, a pattern characteristic of AOAD. Mutation analysis of the GFAP gene revealed a heterozygous de novo 9-bp microduplication in exon 1. Adult Alexander disease may present with stroke-like features. MRI patterns of chronic neurodegenerative conditions may be recognizable even in acute neurological emergencies. PMID:23706596

Schmidt, Holger; Kretzschmar, Benedikt; Lingor, Paul; Pauli, Silke; Schramm, Peter; Otto, Markus; Ohlenbusch, Andreas; Brockmann, Knut



Coal mine dust lung disease. New lessons from old exposure.  


Coal mining remains a sizable industry, with millions of working and retired coal miners worldwide. This article provides an update on recent advances in the understanding of respiratory health issues in coal miners and focuses on the spectrum of disease caused by inhalation of coal mine dust, termed coal mine dust lung disease. In addition to the historical interstitial lung diseases (coal worker's pneumoconiosis, silicosis, and mixed dust pneumoconiosis), coal miners are at risk for dust-related diffuse fibrosis and chronic airway diseases, including emphysema and chronic bronchitis. Recent recognition of rapidly progressive pneumoconiosis in younger miners, mainly in the eastern United States, has increased the sense of urgency and the need for vigilance in medical research, clinical diagnosis, and exposure prevention. Given the risk for disease progression even after exposure removal, along with few medical treatment options, there is an important role for chest physicians in the recognition and management of lung disease associated with work in coal mining. PMID:23590267

Petsonk, Edward L; Rose, Cecile; Cohen, Robert



Effect of acute lung injury on pulmonary alveolar macrophage superoxide production  

SciTech Connect

Pulmonary alveolar macrophages (PAM) are present during acute lung inflammation, yet the role of these cells in both initiation and resolution of lung injury is not well defined. PAMs, depending on their state of activation will produce varying quantities of superoxide anion (O/sub 2//sup -/) and other reactive oxygen metabolites (ROM). Since ROMs are bactericidal and capable of causing lung injury, the authors examined the ability of PAMs to generate (O/sub 2//sup -/) at various times after initiation of acute lung injury via the reverse passive arthus reaction in pathogen free Sprague Dawley rats. PAMs isolated from lungs 24 hours after induction of injury generated 3.5 times as much (O/sub 2//sup -/) in response to phorbol myristate acetate (PMA) as did PAMs from uninjured lungs. Similarly, exposure to zymosan stimulated a 50% increase in (O/sub 2//sup -/) production. Six days after induction of the injury, when the lungs appeared histologically normal, the isolated PAMs produced twice as much (O/sub 2//sup -/) in response to stimulation by PMA when compared to controls. The mechanism of enhanced NADPH oxidase activity in PAMs from injured lung is presently being investigated. Alteration of NADPH oxidase activity may modify PAM bactericidal activity as well as the extent of lung injury in acute pulmonary inflammation.

Brieland, J.; Fantone, J.



Genetic variant associations of human SP-A and SP-D with acute and chronic lung injury  

PubMed Central

Pulmonary surfactant, a lipoprotein complex, maintains alveolar integrity and plays an important role in lung host defense, and control of inflammation. Altered inflammatory processes and surfactant dysfunction are well described events that occur in patients with acute or chronic lung disease that can develop secondary to a variety of insults. Genetic variants of surfactant proteins, including single nucleotide polymorphisms, haplotypes, and other genetic variations have been associated with acute and chronic lung disease throughout life in several populations and study groups. The hydrophilic surfactant proteins SP-A and SP-D, also known as collectins, in addition to their surfactant-related functions, are important innate immunity molecules as these, among others, exhibit the ability to bind and enhance clearance of a wide range of pathogens and allergens. This review focuses on published association studies of human surfactant proteins A and D genetic polymorphisms with respiratory, and non-respiratory diseases in adults, children, and newborns. The potential role of genetic variations in pulmonary disease or pathogenesis is discussed following an evaluation, and comparison of the available literature.

Silveyra, Patricia; Floros, Joanna



Lung Transplantation for Pulmonary Vascular Disease  

Microsoft Academic Search

Background. Pulmonary hypertension (PHT) is a lethal condition resulting in markedly diminished life expect- ancy. Continuous prostaglandin I2 infusion has made an important contribution to symptom management, but it is not a panacea. Lung or heart-lung transplantation remains an important treatment option for end-stage PHT patients unresponsive to prostaglandin I2. This study reviews the outcomes after transplantation for PHT in

Eric N. Mendeloff; Bryan F. Meyers; Thoralf M. Sundt; Tracey J. Guthrie; Stuart C. Sweet; Maite de la Morena; Steve Shapiro; David T. Balzer; Elbert P. Trulock; John P. Lynch; Michael K. Pasque; Joel D. Cooper; Charles B. Huddleston; G. Alexander Patterson


Lung transplantation for pulmonary vascular disease  

Microsoft Academic Search

Background. Pulmonary hypertension (PHT) is a lethal condition resulting in markedly diminished life expectancy. Continuous prostaglandin I2 infusion has made an important contribution to symptom management, but it is not a panacea. Lung or heart-lung transplantation remains an important treatment option for end-stage PHT patients unresponsive to prostaglandin I2. This study reviews the outcomes after transplantation for PHT in our

Eric N Mendeloff; Bryan F Meyers; Thoralf M Sundt; Tracey J Guthrie; Stuart C Sweet; Maite de la Morena; Steve Shapiro; David T Balzer; Elbert P Trulock; John P Lynch; Michael K Pasque; Joel D Cooper; Charles B Huddleston; G. Alexander Patterson



Terfenadine and risk of acute liver disease  

PubMed Central

Aims To estimate the risk of idiopathic acute liver disease among users of terfenadine. Methods We conducted a population-based cohort study based on the General Practice Research Database (GPRD) in the U.K. All persons who received at least one prescription for terfenadine during the period 1991 through 1995 were eligible for the study. Among these patients we identified all those with a diagnosis of a liver disorder requiring hospitalization or referral to a consultant within 60 days of a prior prescription for terfenadine. We obtained clinical records, including hospital discharge summaries, consultant reports and relevant laboratory results in order to identify a potentially drug-inducible liver illness. Results From a cohort of 210 683 recipients of terfenadine, we found only three cases of acute liver disease where a causal connection to terfenadine could not be ruled out, yielding a risk estimate of 1.4/100 000 users (95% CI 0.5, 4.2) and 0.5/100 000 prescriptions (95% CI 0.2, 1.4). All cases were receiving a concomitant hepatotoxic drug and all had a full recovery. Conclusion The use of terfenadine is rarely associated with idiopathic acute liver disease.

Wald Myers, Marian; Jick, Hershel



Overexpression of CREM? in T cells aggravates lipopolysaccharide-induced acute lung injury.  


Transcription factor cAMP response element modulator (CREM)? contributes to various cellular and molecular abnormalities in T cells, including increased IL-17 and decreased IL-2 expression. For development of acute lung injury (ALI), the invasion and regulation of immune cells are highly important, but the role of T cells remains unclear. In this study, we show that CREM? is upregulated in LPS-induced ALI. During the early phase of ALI (day 1), T cell-specific CREM? overexpression enhances the numbers of T cells and expression of TNF-? in bronchoalveolar lavage fluid and deteriorates lung functions. On day 3 of ALI, CREM? transgenic mice present a stronger inflammatory response with higher levels of TNF-?, IL-6, and IL-17 correlating with increased numbers of T cells and neutrophils in bronchoalveolar lavage fluid, whereas expression of Foxp3 and IL-2 and numbers of regulatory T cells are decreased. These changes result in restricted lung function in CREM? transgenic mice. Finally, an adoptive transfer of CREM(-/-) CD4(+) T cells, but not of wild-type T cells into RAG-1(-/-) mice results in ameliorated disease levels. Thus, levels of CREM in T cells determine the outcome of ALI, and CREM? transgenic animals represent a model in which proinflammatory T cells aggravate ALI in different phases of the disease. Given the fact that patients with autoimmune diseases like systemic lupus erythematosus show higher levels of CREM? and an increased susceptibility toward infectious complications, our finding is of potential clinical significance and may enable new therapeutic strategies. PMID:23785120

Verjans, Eva; Ohl, Kim; Yu, Yin; Lippe, Ralph; Schippers, Angela; Wiener, Anastasia; Roth, Johannes; Wagner, Norbert; Uhlig, Stefan; Tenbrock, Klaus; Martin, Christian



Effects of experimental acute pancreatitis in dogs on metabolism of lung surfactant phosphatidylcholine.  


Acute haemorrhagic pancreatitis was produced in the dogs by transduodenal injection of autologous bile into the main pancreatic duct. There was no significant change in the activity of three regulatory enzymes of phosphatidylcholine biosynthesis (glycerophosphate acyltransferase, cytidyltransferase and cholinephosphotransferase) in lung; however, there was a 42% decrease in the amount of dipalmitoyl phosphatidylcholine (surfactant) in lung lavage due to acute pancreatitis. The decrease in lavage phospholipid content was associated with 5-fold increase in phospholipase A2 activity of lung lavage, and massive accumulation of osmiophilic spheroid structures in the alveolar space. PMID:3036136

Das, S K; Scott, M T; McCuiston, S



Effects of a Clinical Trial on Mechanical Ventilation Practices in Patients with Acute Lung Injury  

Microsoft Academic Search

Rationale: In a clinical trial by the Acute Respiratory Distress Syn- drome Network (ARDSNet), mechanical ventilation with tidal volumes of 6 ml\\/kg decreased mortality from acute lung injury. However, interpretations of these results generated controversy and it was unclear if this trial would change usual-care practices. Objectives: First, to determine if clinical practices at ARDSNet hospi- tals changed after the

William Checkley; Roy Brower; Anna Korpak; B. Taylor Thompson


Identification of Immunoglobulins that Recognize 3-Nitrotyrosine in Patients with Acute Lung Injury after Major Trauma  

Microsoft Academic Search

Tyrosinenitrationisanitricoxide-derivedpost-translationalmodifi- cation of proteins. Elevated levels of specific plasma proteins modi- fied by tyrosine nitration have been detected during acute and chronic inflammatory conditions, including acute lung injury (ALI). Inthepresentstudyweexaminedwhethercirculatingimmunoglob- ulins against nitrated proteins are present in the plasma of subjects with clinically documented ALI. Affinity chromatography using co- valently linked 3-nitrotyrosine was employed to identify plasma proteins that bind

Leonor Thomson; Jason Christie; Caryn Vadseth; Paul N. Lanken; Xiaoming Fu; Stanley L. Hazen; Harry Ischiropoulos


[Diffuse lung disease--advances in patient management].  


Diffuse lung diseases (DLD), known as interstitial lung diseases or diffuse parenchymal lung diseases, are a large group of disorders of diverse etiology and causes, however, sharing similar clinical, radiological and pathophysiological characteristics. In the last fifteen years, DLD have attracted considerable interest of medical society. During that period, a consensus of the British Thoracic Society on the Diffuse Parenchymal Lung Disease and Statement of the American Thoracic Society (ATS) and European Respiratory Society (ERS) on idiopathic pulmonary fibrosis, idiopathic interstitial pneumonias and sarcoidosis have helped precisely define certain phenotypes. The newly developed technique of high resolution computed tomography, which can show finest details of lung parenchyma, has also helped precisely define diverse entities, which have aroused interest among molecular biologists and genetic researchers with a goal to define the etiology, pathogenesis and progression of these diseases. The renaissance of interest in this scientific field has also stimulated pharmaceutical industry to enhance its activity, which has resulted in intensified research of potentially new drugs, especially for fibrotic lung processes such as idiopathic pulmonary fibrosis. The disease outcome is very difficult to estimate in these, most often chronic diseases; however, it is very important to achieve the best possible if not the same quality of life as before the disease onset. Different questionnaires have been used and the results were not always as expected; for instance, worsened lung function tests were not most important in defining the quality of life. These vivacious activities have stimulated us to present to the patient and diligent reader recent advances in the management of DLD patient; the article is mostly dedicated to recent advances made in diagnostic procedures, hoping for a comparable success to be achieved in therapeutic approach. PMID:19205419

Peros-Golubici?, Tatjana



Increased T cell glucose uptake reflects acute rejection in lung grafts.  


Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [(18) F]fluorodeoxyglucose ([(18) F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the grafts of syngeneic and allogeneic recipients with or without immunosuppression treatment. Pulmonary microPET scans demonstrated significantly higher [(18) F]FDG uptake in rejecting allografts when compared to transplanted lungs of either immunosuppressed or syngeneic recipients. [(18) F]FDG uptake was also markedly attenuated following T cell depletion therapy in lung recipients with ongoing acute rejection. Flow cytometric analysis using the fluorescent deoxyglucose analog 2-NBDG revealed that T cells, and in particular CD8(+) T cells, were the largest glucose utilizers in acutely rejecting lung grafts followed by neutrophils and antigen-presenting cells. These data indicate that imaging modalities tailored toward assessing T cell metabolism may be useful in identifying acute rejection in lung recipients. PMID:23927673

Chen, D L; Wang, X; Yamamoto, S; Carpenter, D; Engle, J T; Li, W; Lin, X; Kreisel, D; Krupnick, A S; Huang, H J; Gelman, A E



The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy  

PubMed Central

No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.

Kamaruzaman, Nurfatin Asyikhin; Kamaldin, Nurulain 'Atikah; Latahir, Ahmad Zaeri; Yahaya, Badrul Hisham



Role of the pulmonary epithelium and inflammatory signals in acute lung injury  

PubMed Central

Acute lung injury (ALI) is a clinical disease marked by respiratory failure due to disruption of the epithelial and endothelial barrier, flooding of the alveolar compartment with protein-rich fluid and recruitment of neutrophils into the alveolar space. ALI affects approximately 200,000 patients annually in the USA and results in approximately 75,000 deaths. It is associated with prolonged mechanical ventilation, intensive medical care, high morbidity and mortality, and rising healthcare costs. Owing to its impact on public health, great strides have been made towards understanding the pathobiology of ALI to affect outcome. This review will focus on the role of the epithelial cell in the pathogenesis and resolution of ALI and the role of various inflammatory mediators in ALI.

Manicone, Anne M



Copy number variation in the CCL4L gene is associated with susceptibility to acute rejection in lung transplantation.  


Lung transplantation (LT) has become an accepted therapy for selected patients with advanced lung disease. One of the main limitations to successful LT is rejection of the transplanted organ where chemokines are pivotal mediators. Here, we test the relationship between copy number variation (CNV) in the CCL4L chemokine gene and rejection risk in LT patients (n=161). Patients with no acute rejection showed a significantly lower mean number of CCL4L copies than patients that showed acute rejection (1.66 vs 1.96, P=0.014), with an even greater number of gene copies seen in patients with more than one episode of acute rejection (1.66 vs 2.30, P=0.001). Additionally, patients with > or =2 CCL4L copies had a significantly higher risk of acute rejection compared with patients that had 0-1 CCL4L copies (odds ratio 2.65; 95% confidence interval, 1.33-5.28; P=0.0046). A combined analysis of CCL4L CNV and the rs4796195 CCL4L single nucleotide polymorphism demonstrated that the effect of CCL4L copy number in acute rejection is mainly because of the number of copies of the CCL4L1 allelic variant. This finding constitutes the first report of CNV as a correlate factor in allograft rejection. PMID:19148142

Colobran, R; Casamitjana, N; Roman, A; Faner, R; Pedrosa, E; Arostegui, J I; Pujol-Borrell, R; Juan, M; Palou, E



Genetic predisposition to respiratory diseases: infiltrative lung diseases.  


The availability of high-throughput genotyping and large collaborative clinical networks creating well-characterized patient populations with DNA repositories has facilitated genome-wide scans and candidate gene studies to identify susceptibility alleles for the development of interstitial lung disease. The association of pulmonary fibrosis with rare inherited disorders, and the variable susceptibility of inbred mouse strains to this disease indicate that pulmonary fibrosis is determined by genetic factors. Sarcoidosis represents a complex disease with racial and ethnic differences in disease prevalence, and evidence of familial clustering. Familial aggregation of sarcoidosis from 'A Case-Control Etiologic Study of Sarcoidosis' (ACCESS) reveals a familial odds ratio (OR) of sarcoidosis of 5.8 (95% CI 2.1-15.9) for sibs and 3.8 (95% CI 1.2-11.3) for parents. Several HLA class II alleles have been associated with either increased or decreased risk of sarcoidosis, and results vary depending on study populations of different ethnicity. Genome-wide screening has conclusively identified linkage to chromosome 5q11and the development of sarcoidosis, and HLA genes and BTNL2 are susceptibility genes located in this region. Familial aggregation of idiopathic interstitial pneumonia (IIP) has been established by several groups, and a large US-based study suggests autosomal dominant inheritance with reduced penetrance; furthermore, cigarette smoking was associated with affection status among siblings (OR = 3.6, 95% CI 1.3-9.8, p = 0.01). Families demonstrate more than one type of IIP, suggesting various subtypes of IIP may share a common pathogenesis. Genome-wide linkage scans in familial interstitial pneumonia demonstrate linkage to chromosomes 4, 5 and 11. Candidate gene studies indicate that surfactant protein C and telomerase are susceptibility genes for the development of pulmonary fibrosis. Future challenges include determining how multiple susceptibility alleles interact with each other and environmental factors resulting in disease risk and multiple phenotypes, and determining the mechanism of action and cellular pathways involving susceptibility alleles. Further insight into these areas may lead to new therapeutic interventions. PMID:18037811

Steele, Mark P; Brown, Kevin K



Acute lung injury and the coagulation pathway: potential role of gene polymorphisms in the protein C and fibrinolytic pathways  

Microsoft Academic Search

There is evidence that dysregulation of coagulation and fibrinolysis may \\u000aparticipate in the pathogenesis of acute lung injury (ALI) and the acute \\u000arespiratory distress syndrome (ARDS). Altered concentrations of several \\u000aproteins of the coagulation and fibrinolytic pathways in plasma and \\u000apulmonary edema fluid from patients with acute lung injury have been related \\u000ato the severity of lung injury and clinical

Anil Sapru; Joseph L. Wiemels; John S. Witte; Lorraine B. Ware; Michael A. Matthay



Acute Myocardial Infarction Mortality in Comparison with Lung and Bladder Cancer Mortality in Arsenic-exposed Region II of Chile from 1950 to 2000  

Microsoft Academic Search

Arsenic in drinking water is known to be a cause of lung, bladder, and skin cancer, and some studies report cardiovascular disease effects. The authors investigated mortality from 1950 to 2000 in the arsenic-exposed region II of Chile (population: 477,000 in 2000) in comparison with the unexposed region V. Increased risks were found for acute myocardial infarction (AMI), with mortality

Yan Yuan; Guillermo Marshall; Catterina Ferreccio; Craig Steinmaus; Steve Selvin; Jane Liaw; Michael N. Bates; Allan H. Smith



Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome.  


Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening form of respiratory failure that affects a heterogeneous population of critically ill patients. Although overall mortality appears to be decreasing in recent years due to improvements in supportive care, there are presently no proven, effective pharmacological therapies to treat ARDS and prevent its associated complications. The most common cause of death in ARDS is not hypoxemia or pulmonary failure, but rather multiple organ dysfunction syndrome (MODS), suggesting that improving survival in patients with ARDS may be linked to decreasing the incidence or severity of MODS. The key to developing novel treatments depends, in part, on identifying and understanding the mechanisms by which ARDS leads to MODS, although the heterogeneity and complexity of this disorder certainly poses a challenge to investigators. Novel therapies in development for treatment of ALI/ARDS include exogenous surfactant, therapies aimed at modulating neutrophil activity, such as prostaglandin and complement inhibitors, and treatments targeting earlier resolution of ARDS, such as beta-agonists and granulocyte macrophage colony-stimulating factor. From a clinical perspective, identifying subpopulations of patients most likely to benefit from a particular therapy and recognising the appropriate stage of illness in which to initiate treatment could potentially lead to better outcomes in the short term. PMID:17874973

Bosma, Karen J; Lewis, James F



Use of risk reclassification with multiple biomarkers improves mortality prediction in acute lung injury  

PubMed Central

Objective Multiple single biomarkers have been associated with poor outcomes in acute lung injury; however, no single biomarker has sufficient discriminating power to clearly indicate prognosis. Using both derivation and replication cohorts, we tested novel risk reclassification methods to determine whether measurement of multiple plasma biomarkers at the time of acute lung injury diagnosis would improve mortality prediction in acute lung injury. Design Analysis of plasma biomarker levels and prospectively collected clinical data from patients enrolled in two randomized controlled trials of ventilator therapy for acute lung injury. Setting Intensive care units of university hospitals participating in the National Institutes of Health Acute Respiratory Distress Syndrome Network. Patients Subjects enrolled in a trial of lower tidal volume ventilation (derivation cohort) and subjects enrolled in a trial of higher vs. lower positive end-expiratory pressure (replication cohort). Interventions None. Measurements and Main Results The plasma biomarkers were intercellular adhesion molecule-1, von Willebrand factor, interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D. In the derivation cohort (n = 547), adding data on these biomarkers to clinical predictors (Acute Physiology and Chronic Health Evaluation III score) at the time of study enrollment improved the accuracy of risk prediction, as reflected by a net reclassification improvement of 22% (95% confidence interval 13% to 32%; p < .001). In the replication cohort (n = 500), the net reclassification improvement was 17% (95% confidence interval 7% to 26%; p < .001). A reduced set of three biomarkers (interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D) had nearly equivalent prognostic value in both cohorts. Conclusions When combined with clinical data, plasma biomarkers measured at the onset of acute lung injury can improve the accuracy of risk prediction. Combining three or more biomarkers may be useful for selecting a high-risk acute lung injury population for enrollment in clinical trials of novel therapies.

Calfee, Carolyn S.; Ware, Lorraine B.; Glidden, David V.; Eisner, Mark D.; Parsons, Polly E.; Thompson, B. Taylor; Matthay, Michael A.



Annual lung function changes in young patients with chronic lung disease  

Microsoft Academic Search

Reference equations for ventilatory function that use different\\u000a statistical models may introduce artifacts that affect the estimated\\u000a change of lung function during growth in young subjects. The effect of\\u000a differently modelled reference equations on the estimated annual change of\\u000a forced expiratory volume in one second (FEV1) and forced vital capacity\\u000a (FVC) in young patients with chronic lung disease was assessed.

P. J. F. M. Merkus; H. A. W. M. Tiddens; Jongste de J. C



Systems biology approaches to identify developmental bases for lung diseases  

PubMed Central

A greater understanding of the regulatory processes contributing to lung development could be helpful to identify strategies to ameliorate morbidity and mortality in premature infants and to identify individuals at risk for congenital and/or chronic lung diseases. Over the past decade, genomics technologies have enabled the production of rich gene expression databases providing information for all genes across developmental time or in diseased tissue. These data sets facilitate systems biology approaches for identifying underlying biological modules and programs contributing to the complex processes of normal development, and those that may be associated with disease states. The next decade will undoubtedly see rapid and significant advances in redefining both lung development and disease at the systems level.

Bhattacharya, Soumyaroop; Mariani, Thomas J.



Scintigraphic studies of inflammation in diffuse lung disease  

SciTech Connect

67Ga lung scintigraphy is an established means to assess alveolar inflammation in a wide variety of diffuse lung diseases. It can be used to monitor the extent and activity of the alveolitis during the course of the disease and as a follow-up evaluation to therapy. Although the mechanism of 67Ga localization is not established firmly, the isotope appears to act as a tracer for disturbed protein and cellular fluxes within the interstitium and alveolar spaces. The radiolabeled aerosol study may also be applied to the study of these fluxes as a reflection of inflammation and injury. Although Tc-DTPA clearance studies are highly sensitive to lung injury, they may be too nonspecific to separate lung injury from other physiologic processes effectively. 117 references.

Line, B.R. (Albany Medical College, New York (USA))



Lung Cancer Diseases Diagnostic Asistance Using Gray Color Analysis  

Microsoft Academic Search

Errors in diagnosing the disease is a critical risk that must be faced by any person giving treatment to the hospital. Medical treatment can not always be done with perfect accuracy. Lung cancer is one of the most deadly disease that prone to misdiagnose. In general, some practitioners tend to “read” cancer in x-ray rontgen image as tumor this could

P. Paulus; F. L. Gaol




EPA Science Inventory

This Work-Related Lung Disease (WoRLD) Surveillance Report is the fifth in a series of occupational respiratory disease surveillance reports (see page iv) produced by the National Institute for Occupational Safety and Health (NIOSH). It presents summary tables and figures of occu...


Smoking and Occupational Lung Disease Epidemiology  

Microsoft Academic Search

Epidemiology studies of lung cancer which may be the result of workplace exposure contrast the risk ratios or SMRs of the exposed population with a control group. If a dose-response relationship can be detected then this suggests a causal relationship between the exposure and its effect. Smoking is clearly a substantial confound ing factor but unfortunately adjustment for this is

J. Bernard L. Gee



Smoking and Occupational Lung Disease Epidemiology  

Microsoft Academic Search

Epidemiology studies of lung cancer which may be the result of workplace exposure contrast the risk ratios or SMRs of the exposed population with a control group. If a dose-response relationship can be detected then this suggests a causal relationship between the exposure and its effect. Smoking is clearly a substantial confounding factor but unfortunately adjustment for this is often

J. Bernard L. Gee



Treatment with exogenous hydrogen sulfide attenuates hyperoxia-induced acute lung injury in mice.  


The aim of this work was to test the effect of treatment with hydrogen sulfide (H2S) on hyperoxia-induced acute lung injury in mice. Mice were exposed to room air or 95 % O2, and treated with NaHS (intraperitoneal injection of 0.1 ml/kg/day of 0.56 mol/l NaHS). Treatment with H2S partly restored the reduced H2S levels in plasma and lungs of mice exposed to hyperoxia. Treatment with H2S attenuated hyperoxia-induced acute lung injury marked by reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, and cell numbers and protein content in bronchoalveolar lavage (BAL) and decreased apoptosis. Treatment with H2S markedly prolonged the survival of mice under oxygen exposure. Treatment with H2S abated hyperoxia-induced oxidative stress marked by reduced malondialdehyde and peroxynitrite formation, reduced NADPH oxidase activity, enhanced translocation of nuclear factor E2-related factor (Nrf2) into nucleus and increased activity of HO-1. Treatment with H2S decreased IL-1?, MCP-1, and MIP-2, and increased IL-10 expression in lungs of mice exposed to hyperoxia. Treatment with H2S decreased NF?B activity and iNOS expression in lungs, and reduced NOx content in BAL of mice exposed to hyperoxia. Treatment with H2S reduced lung permeability and suppressed VEGF release and VEGFR2 expression in lungs of mice under oxygen exposure. Treatment with exogenous H2S attenuated hyperoxia-induced acute lung injury through abating oxidative stress, suppressing inflammation, and reducing lung permeability in mice. PMID:23307012

Li, Huai-Dong; Zhang, Zhao-Rui; Zhang, Qing-Xiang; Qin, Zhi-Chu; He, Deng-Ming; Chen, Jin-Song



Divers' lung function: small airways disease?  

PubMed Central

Pulmonary function was measured in 152 professional saturation divers and in a matched control group of 106 subjects. Static lung volumes, dynamic lung volumes and flows, transfer factor for carbon monoxide (T1CO), transfer volume per unit alveolar volume (KCO), delta-N2, and closing volume (CV) were measured and compared with reference values from recent Scandinavian studies, British submariners, and the European Community for Coal and Steel (ECCS) recommended reference values. Diving exposure was assessed as years of diving experience, total number of days in saturation and depth, and as the product of days in saturation and mean depth. Divers had significantly lower values for forced expired volume in one second (FEV1), FEV1/forced vital capacity (FVC) ratio, FEF25-75%, FEF75-85%, FEF50%, FEF75%, T1CO, and KCO compared with the controls and a significantly higher CV. There was a positive correlation between diving exposure and CV, whereas the other variables had negative correlations with diving exposure. Values for the control group were not different from the predictive values of Scandinavian reference studies or British submariners, although the ECCS standard predicted significantly lower values for the lung function variables both in divers and the control group. The pattern of the differences in lung function variables between the divers and controls is consistent with small airways dysfunction and with the transient changes in lung function found immediately after a single saturation dive. The association between reduced pulmonary function and previous diving exposure further indicates the presence of cumulative long term effects of diving on pulmonary function.

Thorsen, E; Segadal, K; Kambestad, B; Gulsvik, A



Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management  

Microsoft Academic Search

Interstitial lung disease (ILD) is a challenging clinical entity associated with multiple connective tissue diseases, and is a significant cause of morbidity and mortality. Effective therapies for connective tissue disease-associated interstitial lung disease (CTD-ILD) are still lacking. Multidisciplinary clinics dedicated to the early diagnosis and improved management of patients with CTD-ILD are now being established. There is rapid progress in

Flavia V Castelino; John Varga




PubMed Central

The cellular and biochemical mechanisms leading to acute lung injury and subsequent multiple organ failure are only partially understood. In order to study the potential role of eicosanoids, particularly leukotrienes, as possible mediators of acute lung injury, we used a murine experimental model of acute lung injury induced by hemorrhagic shock after blood removal via cardiac puncture. Neutrophil sequestration as shown by immunofluorescence, and protein leakage into the alveolar space, were measured as markers of injury. We used liquid chromatography coupled to tandem mass spectrometry to unequivocally identify several eicosanoids in the bronchoalveolar lavage fluid of experimental animals. MK886, a specific inhibitor of the 5-lipoxygenase pathway, as well as transgenic mice deficient in 5-lipoxygenase, were used to determine the role of this enzymatic pathway in this model. Leukotriene B4 and leukotriene C4 were consistently elevated in shock-treated mice compared to sham-treated mice. MK886 attenuated neutrophil infiltration and protein extravasation induced by hemorrhagic shock. 5-lipoxygenase-deficient mice showed reduced neutrophil infiltration and protein extravasation after shock treatment, indicating greatly reduced lung injury. These results support the hypothesis that 5-lipoxygenase, most likely through the generation of leukotrienes, plays an important role in the pathogenesis of acute lung injury induced by hemorrhagic shock in mice. This pathway could represent a new target for pharmacological intervention to reduce lung damage following severe primary injury.

Eun, John C.; Moore, Ernest E.; Mauchley, David C.; Johnson, Chris A.; Meng, Xianzhong; Banerjee, Anirban; Wohlauer, Max V.; Zarini, Simona; Gijon, Miguel A.; Murphy, Robert C.



Clinical review: The implications of experimental and clinical studies of recruitment maneuvers in acute lung injury  

PubMed Central

Mechanical ventilation can cause and perpetuate lung injury if alveolar overdistension, cyclic collapse, and reopening of alveolar units occur. The use of low tidal volume and limited airway pressure has improved survival in patients with acute lung injury or acute respiratory distress syndrome. The use of recruitment maneuvers has been proposed as an adjunct to mechanical ventilation to re-expand collapsed lung tissue. Many investigators have studied the benefits of recruitment maneuvers in healthy anesthetized patients and in patients ventilated with low positive end-expiratory pressure. However, it is unclear whether recruitment maneuvers are useful when patients with acute lung injury or acute respiratory distress syndrome are ventilated with high positive end-expiratory pressure, and in the presence of lung fibrosis or a stiff chest wall. Moreover, it is unclear whether the use of high airway pressures during recruitment maneuvers can cause bacterial translocation. This article reviews the intrinsic mechanisms of mechanical stress, the controversy regarding clinical use of recruitment maneuvers, and the interactions between lung infection and application of high intrathoracic pressures.

Piacentini, Enrique; Villagra, Ana; Lopez-Aguilar, Josefina; Blanch, Lluis



Oxidized Phospholipids Reduce Vascular Leak and Inflammation in Rat Model of Acute Lung Injury  

PubMed Central

Rationale: Acute inflammation and vascular leak are cardinal features of acute lung injury and the acute respiratory distress syndrome. Nonspecific tissue inflammation and injury in response to infectious and noninfectious insults lead to oxidative stress and the generation of lipid oxidation products, which may inhibit the acute inflammatory response to bacterial components. Objective: To test the hypothesis that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) may attenuate the acute lung inflammatory response to lipopolysaccharide (LPS) and enhance lung vascular barrier recovery, we used in vivo and in vitro models of LPS-induced lung injury. Methods: Rats received intratracheal aerosolized LPS (5 mg/kg) or sterile water with concurrent intravenous injection of OxPAPC (0.5–6.0 mg/kg) or saline alone. Nonoxidized PAPC was used as a control. At 18 h, bronchoalveolar lavage was performed and the lungs were removed for histologic analysis. Measurements of endothelial transmonolayer electrical resistance and immunofluorescent analysis of monolayer integrity were used in an in vitro model of LPS-induced lung vascular barrier dysfunction. Measurements and Main Results: In vivo, aerosolized intratracheal LPS induced lung injury with profound increases in bronchoalveolar lavage neutrophils, protein content, and the inflammatory cytokines interleukin 6 and interleukin 1?, as well as tissue neutrophils. OxPAPC, but not nonoxidized PAPC, markedly attenuated the LPS-induced tissue inflammation, barrier disruption, and cytokine production over a range of doses. In vitro, oxidized phospholipids attenuated LPS-induced endothelial barrier disruption and reversed LPS-induced cytoskeletal remodeling and disruption of monolayer integrity. Conclusions: These studies demonstrate in vivo and in vitro protective effects of oxidized phospholipids on LPS-induced lung dysfunction.

Nonas, Stephanie; Miller, Ian; Kawkitinarong, Kamon; Chatchavalvanich, Santipongse; Gorshkova, Irina; Bochkov, Valery N.; Leitinger, Norbert; Natarajan, Viswanathan; Garcia, Joe G. N.; Birukov, Konstantin G.



Functional genomics of chlorine-induced acute lung injury in mice.  


Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high ( approximately 74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm x 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury. PMID:20601635

Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J; Liu, Pengyuan; Bein, Kiflai; Brant, Kelly A; Dopico, Richard A; Di, Y Peter; Jang, An-Soo; Dietsch, Maggie; Medvedovic, Mario; Li, Qian; Vuga, Louis J; Kaminski, Naftali; You, Ming; Prows, Daniel R



Lung sonography and recruitment in patients with early acute respiratory distress syndrome: A pilot study  

PubMed Central

Introduction Bedside lung sonography is a useful imaging tool to assess lung aeration in critically ill patients. The purpose of this study was to evaluate the role of lung sonography in estimating the nonaerated area changes in the dependent lung regions during a positive end-expiratory pressure (PEEP) trial of patients with early acute respiratory distress syndrome (ARDS). Methods Ten patients (mean ± standard deviation (SD): age 64 ± 7 years, Acute Physiology and Chronic Health Evaluation II (APACHE II) score 21 ± 4) with early ARDS on mechanical ventilation were included in the study. Transthoracic sonography was performed in all patients to depict the nonaerated area in the dependent lung regions at different PEEP settings of 5, 10 and 15 cm H2O. Lung sonographic assessment of the nonaerated lung area and arterial blood gas analysis were performed simultaneously at the end of each period. A control group of five early ARDS patients matched for APACHE II score was also included in the study. Results The nonaerated areas in the dependent lung regions were significantly reduced during PEEP increases from 5 to 10 to 15 cm H2O (27 ± 31 cm2 to 20 ± 24 cm2 to 11 ± 12 cm2, respectively; P < 0.01). These changes were associated with a significant increase in arterial oxygen partial pressure (74 ± 15 mmHg to 90 ± 19 mmHg to 102 ± 26 mmHg; P < 0.001, respectively). No significant changes were observed in the nonaerated areas in the dependent lung regions in the control group. Conclusions In this study, we show that transthoracic lung sonography can detect the nonaerated lung area changes during a PEEP trial of patients with early ARDS. Thus, transthoracic lung sonography might be considered as a useful clinical tool in the management of ARDS patients.



Priorities in prevention of chronic lung diseases  

Microsoft Academic Search

We recorded the prevalence of respiratory symptoms as well as smoking habits, occupational and other environmental exposures,\\u000a and lung function (maximum expiratory flow-volume [MEFV]) curves in 7,984 community residents (age 7 + years) and in 691 cotton\\u000a textile workers (age 45 + years). Apart from a slight but significant excess among urban nonsmoking adults of usual cough,\\u000a usual phlegm and

A. Bouhuys; G. J. Beck; Janet B. Schoenberg



Crucial role of group IIA phospholipase A(2) in oleic acid-induced acute lung injury in rabbits.  


Group IIA secretory phospholipase A(2) (sPLA(2)) has been implicated in a variety of inflammatory diseases including acute lung injury (ALI); however, the role of sPLA(2) in this disorder remains unclear. The aim of the present investigation was to examine the role of this enzyme in a model of ALI induced by oleic acid (OA) in rabbits by testing human group IIA phospholipase A(2) (PLA(2)) inhibitor, S-5920/LY315920Na. Experimental groups consisted of a saline control group (n = 8), an OA control group (n = 10) infused intravenously with OA (0.1 ml/kg/h for 2 h), and three groups given OA + S-5920/LY315920Na (three different doses, n = 8, respectively). Infusion of OA provoked pulmonary hemorrhage and edema formation, protein leakage, and massive neutrophil infiltration, resulting in severe hypoxemia and impaired lung compliance. PLA(2) activity was detected in the bronchoalveolar lavage fluid (BALF), but not plasma, which correlated well with severity of lung injury in this model. Pretreatment with S-5920/LY315920Na diminished the OA-induced PLA(2) activity in the BALF and dose-dependently attenuated the previously described lung injury induced by OA, accompanied by protection against lung surfactant degradation and production of thromboxane A(2) (TXA(2)) and leukotriene B(4) (LTB(4)). S-5920/LY315920Na also inhibited the OA-induced production of interleukin-8 (IL-8), both in plasma and BALF. Thus, sPLA(2) appears to play a key role in OA-induced lung injury, suggesting that the group IIA PLA(2) inhibitor may be a promising agent for patients with acute respiratory distress syndrome (ARDS). PMID:10508821

Furue, S; Kuwabara, K; Mikawa, K; Nishina, K; Shiga, M; Maekawa, N; Ueno, M; Chikazawa, Y; Ono, T; Hori, Y; Matsukawa, A; Yoshinaga, M; Obara, H



Human Amnion-Derived Cells: Prospects for the Treatment of Lung Diseases.  


Lung diseases represent a significant burden of morbidity and mortality worldwide. Current therapies have not proven adequate in the long term and are often associated with significant side effects. There has been recent interest in the regenerative/reparative potential of cell-based therapies, including cells derived from the placental tissues. Amnion-derived cells are fetal-derived and characterized by expression profile and differentiative capacity of pluripotent cells. Moreover, because placenta is discarded after delivery, they represent an ethical source for the purposes of regenerative medicine. Amnion-derived cells are endowed with immunomodulatory, anti-inflammatory, anti-scarring and antibacterial properties, which may explain many of the beneficial effects observed with administration of the cells in animal models for a large number of inflammatory diseases. Both human amniotic epithelial cells (hAEC) and mesenchymal stromal cells (hAMSC) have been shown to acquire in vitro and in vivo some characteristics of epithelial cells, i.e. CFTR (cystic fibrosis transmembrane conductance regulator) and surfactant proteins. Administration of hAEC or hAMSC in vivo in the bleomycin-induced lung injury model has proven their therapeutic effects in term of reduction of pulmonary fibrosis and inflammation, as well as recovery of lung mechanical function. Many biological and clinical informations have to be gathered before proposing amnion-derived cells in the clinic for the treatment of acute and chronic lung diseases. PMID:23597268

Carbone, Annalucia; Paracchini, Valentina; Castellani, Stefano; Di Gioia, Sante; Seia, Manuela; Colombo, Carla; Conese, Massimo



Scleroderma-related lung disease: are adipokines involved pathogenically?  


Scleroderma is a systemic autoimmune disease of unknown etiology whose characteristic features include endothelial cell dysfunction, fibroblast proliferation, and immune dysregulation. Although almost any organ can be pathologically involved in scleroderma, lung complications including interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading cause of death in patients with this condition. Currently, the molecular mechanisms leading to development of scleroderma-related lung disease are poorly understood; however, the systemic nature of this condition has led many to implicate circulating factors in the pathogenesis of some of its organ impairment. In this article we focus on a new class of circulating factors derived from adipose-tissue called adipokines, which are known to be altered in scleroderma. Recently, the adipokines adiponectin and leptin have been found to regulate biological activity in endothelial, fibroblast, and immune cell types in lung and in many other tissues. The pleiotropic nature of these circulating factors and their functional activity on many cell types implicated in the pathogenesis of ILD and PAH suggest these hormones may be mechanistically involved in the onset and/or progression of scleroderma-related lung diseases. PMID:24173692

Haley, Shannon; Shah, Dilip; Romero, Freddy; Summer, Ross



Lung Transplantation for Respiratory Failure Resulting From Systemic Disease  

Microsoft Academic Search

Background. Lung transplantation for pulmonary failure resulting from systemic disease is controversial. We reviewed our transplant experience in patients with sarcoidosis, scleroderma, lymphangioleiomyomatosis, and graft-versus-host disease.Methods. This retrospective review examined the outcome of 23 patients who underwent pulmonary transplantation for these systemic diseases. Group 1 included 15 patients with pulmonary hypertension who underwent transplantation (9 for sarcoidosis, 6 for scleroderma),

Frank A. Pigula; Bartley P. Griffith; Marco A. Zenati; James H. Dauber; Samuel A. Yousem; Robert J. Keenan




PubMed Central

Objective In the Fluid and Catheter Treatment Trial (FACTT)(NCT00281268), adults with acute lung injury (ALI) randomized to a conservative versus liberal fluid management protocol had increased days alive and free of mechanical ventilator support (ventilator-free days). Recruiting sufficient children with ALI into a pediatric trial is challenging. A Bayesian statistical approach relies on the adult trial for the a priori effect estimate, requiring fewer patients. Preparing for a Bayesian pediatric trial mirroring FACTT, we aimed to: a.)Identify an inverse association between fluid balance and VFDs; and b.)Determine if fluid balance over time is more similar to adults in the FACTT liberal or conservative arms. Design Multi-centered retrospective cohort study. Setting Five pediatric intensive care units. Patients Mechanically ventilated children (age ?1 month to <18 years) with ALI admitted 2007–2010. Interventions None. Measurements and Main Results Fluid intake, output and net fluid balance were collected days 1–7 in 168 children with ALI (median age 3 years, median PaO2/FiO2 138) and weight-adjusted (ml/kg). Using multivariable linear regression to adjust for age, gender, race, admission day illness severity, PaO2/FiO2 and vasopressor use, increasing cumulative fluid balance (ml/kg) at day 3 was associated with fewer VFDs (p=0.02). Adjusted for weight, daily fluid balance on days 1–3 and cumulative fluid balance on days 1–7 were higher in these children compared to adults in the FACTT conservative arm (p<0.001, each day) and was similar to adults in the liberal arm. Conclusions Increasing fluid balance at day three in children with ALI at these centers is independently associated with fewer VFDs. Our findings and the similarity of fluid balance patterns in our cohort to adults in the FACTT liberal arm demonstrate the need to determine whether a conservative fluid management strategy improves clinical outcomes in children with ALI and support a Bayesian trial mirroring the FACTT trial.

Valentine, Stacey L.; Sapru, Anil; Higgerson, Renee A.; Spinella, Phillip C.; Flori, Heidi R.; Graham, Dionne A.; Brett, Molly; Convery, Maureen; Christie, LeeAnn M.; Karamessinis, Laurie; Randolph, Adrienne G.



Randomized Clinical Trial of Activated Protein C for the Treatment of Acute Lung Injury  

PubMed Central

Rationale: Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days. Objectives: To test the efficacy of activated protein C (APC) as a therapy for patients with ALI. Methods: Eligible subjects were critically ill patients who met the American/European consensus criteria for ALI. Patients with severe sepsis and an APACHE II score of 25 or more were excluded. Participants were randomized to receive APC (24 ?g/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days. Measurements and Main Results: APC increased plasma protein C levels (P = 0.002) and decreased pulmonary dead space fraction (P = 0.02). However, there was no statistically significant difference between patients receiving placebo (n = 38) or APC (n = 37) in the number of ventilator-free days (median [25–75% interquartile range]: 19 [0–24] vs. 19 [14–22], respectively; P = 0.78) or in 60-day mortality (5/38 vs. 5/37 patients, respectively; P = 1.0). There were no differences in the number of bleeding events between the two groups. Conclusions: APC did not improve outcomes from ALI. The results of this trial do not support a large clinical trial of APC for ALI in the absence of severe sepsis and high disease severity. Clinical trial registered with (NCT 00112164).

Liu, Kathleen D.; Levitt, Joseph; Zhuo, Hanjing; Kallet, Richard H.; Brady, Sandra; Steingrub, Jay; Tidswell, Mark; Siegel, Mark D.; Soto, Graciela; Peterson, Michael W.; Chesnutt, Mark S.; Phillips, Charles; Weinacker, Ann; Thompson, B. Taylor; Eisner, Mark D.; Matthay, Michael A.



Protective role of metallothionein in acute lung injury induced by bacterial endotoxin  

PubMed Central

Background: Metallothionein (MT) is a protein that can be induced by inflammatory mediators and participate in cytoprotection. However, its role in inflammation remains to be established. A study was undertaken to determine whether intrinsic MT protects against acute inflammatory lung injury induced by bacterial endotoxin in MT-I/II knock out (–/–) and wild type (WT) mice. Methods: MT (–/–) and WT mice were given vehicle or lipopolysaccharide (LPS, 125 µg/kg) intratracheally and the cellular profile of the bronchoalveolar lavage (BAL) fluid, pulmonary oedema, lung histology, expression of proinflammatory molecules, and nuclear localisation of nuclear factor-?B (NF-?B) in the lung were evaluated. Results: MT (–/–) mice were more susceptible than WT mice to lung inflammation, especially to lung oedema induced by intratracheal challenge with LPS. After LPS challenge, MT deficiency enhanced vacuolar degeneration of pulmonary endothelial cells and type I alveolar epithelial cells and caused focal loss of the basement membrane. LPS treatment caused no significant differences in the enhanced expression of proinflammatory cytokines and chemokines nor in the activation of the NF-?B pathway in the lung between the two genotypes. Lipid peroxide levels in the lungs were significantly higher in LPS treated MT (–/–) mice than in LPS treated WT mice. Conclusions: Endogenous MT protects against acute lung injury related to LPS. The effects are possibly mediated by the enhancement of pulmonary endothelial and epithelial integrity, not by the inhibition of the NF-?B pathway.

Takano, H; Inoue, K; Yanagisawa, R; Sato, M; Shimada, A; Morita, T; Sawada, M; Nakamura, K; Sanbongi, C; Yoshikawa, T



NLRP3 deletion protects from hyperoxia-induced acute lung injury.  


Inspiration of a high concentration of oxygen, a therapy for acute lung injury (ALI), could unexpectedly lead to reactive oxygen species (ROS) production and hyperoxia-induced acute lung injury (HALI). Nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) senses the ROS, triggering inflammasome activation and interleukin-1? (IL-1?) production and secretion. However, the role of NLRP3 inflammasome in HALI is unclear. The main aim of this study is to determine the effect of NLRP3 gene deletion on inflammatory response and lung epithelial cell death. Wild-type (WT) and NLRP3(-/-) mice were exposed to 100% O2 for 48-72 h. Bronchoalveolar lavage fluid and lung tissues were examined for proinflammatory cytokine production and lung inflammation. Hyperoxia-induced lung pathological score was suppressed in NLRP3(-/-) mice compared with WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1?, TNF?, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 were attenuated in NLRP3(-/-) mice. NLRP3 deletion decreased lung epithelial cell death and caspase-3 levels and a suppressed NF-?B levels compared with WT controls. Taken together, this research demonstrates for the first time that NLRP3-deficient mice have suppressed inflammatory response and blunted lung epithelial cell apoptosis to HALI. PMID:23636457

Fukumoto, Jutaro; Fukumoto, Itsuko; Parthasarathy, Prasanna Tamarapu; Cox, Ruan; Huynh, Bao; Ramanathan, Gurukumar Kollongod; Venugopal, Rajan Babu; Allen-Gipson, Diane S; Lockey, Richard F; Kolliputi, Narasaiah



["Blind" trans-bronchial biopsy of the lung in the diagnosis of interstitial lung diseases].  


The aim of the study was to assess the diagnostic effectiveness and safety of "blind" transbronchial lung biopsy (B-TBLB) in interstitial lung diseases (ILD). The diagnostic yield of B-TBLB performed in 44 patients was compared with similar yield of classical TBLB carried out in 25 patients. A diagnosis was made by B-TBLB in 29 patients (65.9%) and 14 (56%) by classical TBLB. Most often sarcoidosis, allergic alveolitis, pneumoconioses were found. Side effects were seen in both groups: in the B-TBLB group in 11.4%, in patients that underwent classical TBLB in 32%. It seems that blind transbronchial lung biopsy is a safe, effective and acceptable diagnostical method of interstitial lung disorders. PMID:1843920

Pirozy?ski, M; Szyma?ska, D; Targosz, L; Cie?licki, J; Meleniewska-Maciszewska, A; Za?eska, J



Research on smoking and lung cancer: a landmark in the history of chronic disease epidemiology.  

PubMed Central

This paper describes the history of the epidemiologic research on lung cancer prior to 1970 and its effect on chronic disease epidemiology. In the 1930s, epidemiology was largely concerned with acute infectious diseases. As the evidence grew that the incidence of lung cancer was increasing among men, however, epidemiologists undertook research into the etiology of the disease. In 1950, Doll and Hill, in England, and Wynder and Graham, in the United States, published substantial case-control studies that implicated the use of tobacco as a major risk factor for the disease. A controversy developed over the credibility of this finding and was increased in 1954 when a cohort study by Doll and Hill and another by Hammond and Horn each gave estimates that the risk of lung cancer was greatly increased among smokers relative to the risk among comparable non-smokers. An account is given of the disputes surrounding these and related studies. The controversy had a stimulating effect in fostering the developing discipline of chronic disease and epidemiology.

White, C.



Recent Advances in Tuberculosis and Nontuberculous Mycobacteria Lung Disease  

PubMed Central

Tuberculosis (TB) is one of the largest health problems in the world today. And the incidence of nontuberculous mycobacteria (NTM) lung disease appears to be increasing worldwide. Recently, an automated, nucleic acid amplification assay for the rapid detection of both Mycobacterium tuberculosis and rifampin resistance was developed (Xpert MTB/RIF). And fixed-dose combinations of anti-TB drugs and linezolid have been introduced in the treatment of TB. And new NTM species, named Mycobacterium massiliense, which is very closely related to Mycobacterium abscessus was reported. In this review, these recent advances in the diagnosis and treatment of TB and clinical characteristics of M. massiliense lung disease are discussed.



Recent advances in tuberculosis and nontuberculous mycobacteria lung disease.  


Tuberculosis (TB) is one of the largest health problems in the world today. And the incidence of nontuberculous mycobacteria (NTM) lung disease appears to be increasing worldwide. Recently, an automated, nucleic acid amplification assay for the rapid detection of both Mycobacterium tuberculosis and rifampin resistance was developed (Xpert MTB/RIF). And fixed-dose combinations of anti-TB drugs and linezolid have been introduced in the treatment of TB. And new NTM species, named Mycobacterium massiliense, which is very closely related to Mycobacterium abscessus was reported. In this review, these recent advances in the diagnosis and treatment of TB and clinical characteristics of M. massiliense lung disease are discussed. PMID:23814596

Park, Jae Seuk



Endogenous lung stem cells and contribution to disease  

PubMed Central

Epithelial branching during the process of lung development results in the establishment of distinct functional zones, each of which is characterized by a unique cellular composition and repertoire of local progenitor cells. Significant new insights into cellular and molecular mechanisms of epithelial maintenance that provide insights into the pathophysiology of lung disease have been made in recent years. This review focuses on the complex structure–function relationship in the airway epithelium, how this epithelium is maintained in the normal state and repaired following injury, and how deregulation may contribute to airway disease and cancer.

Snyder, JC; Teisanu, RM; Stripp, BR



Acute lung injury after inhalation of water-proofing spray while smoking a cigarette.  


A 34-year-old Japanese woman developed acute lung injury soon after inhaling a water-proofing spray which she applied onto her ski suit while smoking a cigarette at the same time. She initially demonstrated arterial hypoxemia (PaO2 = 59 mm Hg) and ground-glass opacities in both lung fields on the CT scan, which both returned to normal without any medication. Several water-proofing sprays, which are easily obtainable in Japan, contain 1,1,1-trichloroethane, liquefied petroleum gas and fluoride resin. Although these components have not been reported to be toxic to the lung yet, high concentrations of these components and/or the pyrolytic products of fluoride resin may have caused acute lung injury in this case. PMID:9817966

Jinn, Y; Akizuki, N; Ohkouchi, M; Inase, N; Ichioka, M; Marumo, F



Arterial occlusion in patients with peripheral vascular disease treated with platinum-based regimens for lung cancer  

Microsoft Academic Search

Background:?Patients with cancer may be hypercoagulable, and smoking can cause both lung cancer and peripheral vascular disease. Cisplatin-based\\u000a chemotherapy has been reported to cause a variety of vascular side effects. Case reports:?Five patients with bronchogenic carcinoma and peripheral vascular disease developed acute arterial occlusion soon after receiving\\u000a a combination of cisplatin or carboplatin plus etoposide. All these patients had risk

John Mathews; Rakesh Goel; William K. Evans; Farid Shamji; David J. Stewart



CGS 21680, an agonist of the adenosine (A2A) receptor, decreases acute lung inflammation.  


Adenosine A(2A) receptor agonists may be important regulators of inflammation. The aim of this study was to investigate the effects of CGS 21680 (0.1mg/kgi.p.), an agonist of the adenosine (A(2A)) receptor, in a mouse model of carrageenan-induced pleurisy. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterised by: infiltration of neutrophils in lung tissues and subsequent lipid peroxidation, increased production of nitric oxide (NO), cytokines such as tumour necrosis factor-? (TNF-?) and interleukin-1? (IL-1?) and increased expression of intercellular adhesion molecule (ICAM-1) and platelet-adhesion molecule (P-selectin). Furthermore, carrageenan induced the expression of nuclear factor-?B (NF-?B), inducible nitric oxide synthase (iNOS), nitrotyrosine, the activation of poly-ADP-ribosyl polymerase (PARP), as well as induced apoptosis (FAS-ligand expression, Bax and Bcl-2 expression) in the lung tissues. Administration of CGS 21680, 30 min prior to challenge with carrageenan, caused a significant reduction of all the parameters of inflammation measured. In addition, to confirm the anti-inflammatory effect of CGS 21680, we have also evaluated the effects of CGS 21680 post-treatment (30 min after the challenge with carrageenan) and we have demonstrated that also it caused a reduction of neutrophil infiltration and the degree of lung injury. Thus, based on these findings we propose that adenosine A(2A) receptor agonists such as CGS 21680 may be useful in the treatment of various inflammatory diseases. PMID:21756897

Impellizzeri, Daniela; Di Paola, Rosanna; Esposito, Emanuela; Mazzon, Emanuela; Paterniti, Irene; Melani, Alessia; Bramanti, Placido; Pedata, Felicita; Cuzzocrea, Salvatore



Bone Marrow Stromal Cells Attenuate Lung Injury in a Murine Model of Neonatal Chronic Lung Disease  

PubMed Central

Rationale: Neonatal chronic lung disease, known as bronchopulmonary dysplasia (BPD), remains a serious complication of prematurity despite advances in the treatment of extremely low birth weight infants. Objectives: Given the reported protective actions of bone marrow stromal cells (BMSCs; mesenchymal stem cells) in models of lung and cardiovascular injury, we tested their therapeutic potential in a murine model of BPD. Methods: Neonatal mice exposed to hyperoxia (75% O2) were injected intravenously on Day 4 with either BMSCs or BMSC-conditioned media (CM) and assessed on Day 14 for lung morphometry, vascular changes associated with pulmonary hypertension, and lung cytokine profile. Measurements and Main Results: Injection of BMSCs but not pulmonary artery smooth muscle cells (PASMCs) reduced alveolar loss and lung inflammation, and prevented pulmonary hypertension. Although more donor BMSCs engrafted in hyperoxic lungs compared with normoxic controls, the overall low numbers suggest protective mechanisms other than direct tissue repair. Injection of BMSC-CM had a more pronounced effect than BMSCs, preventing both vessel remodeling and alveolar injury. Treated animals had normal alveolar numbers at Day 14 of hyperoxia and a drastically reduced lung neutrophil and macrophage accumulation compared with PASMC–CM-treated controls. Macrophage stimulating factor 1 and osteopontin, both present at high levels in BMSC-CM, may be involved in this immunomodulation. Conclusions: BMSCs act in a paracrine manner via the release of immunomodulatory factors to ameliorate the parenchymal and vascular injury of BPD in vivo. Our study suggests that BMSCs and factor(s) they secrete offer new therapeutic approaches for lung diseases currently lacking effective treatment.

Aslam, Muhammad; Baveja, Rajiv; Liang, Olin D.; Fernandez-Gonzalez, Angeles; Lee, Changjin; Mitsialis, S. Alex; Kourembanas, Stella



Clinical knowledge-based inference model for early detection of acute lung injury.  


Acute lung injury (ALI) is a devastating complication of acute illness and one of the leading causes of multiple organ failure and mortality in the intensive care unit (ICU). The detection of this syndrome is limited due to the complexity of the disease, insufficient understanding of its development and progression, and the large amount of risk factors and modifiers. In this preliminary study, we present a novel mathematical model for ALI detection. It is constructed based on clinical and research knowledge using three complementary techniques: rule-based fuzzy inference systems, Bayesian networks, and finite state machines. The model is developed in Matlab(®)'s Simulink environment and takes as input pre-ICU and ICU data feeds of critically ill patients. Results of the simulation model were validated against actual patient data from an epidemiologic study. By appropriately combining all three techniques the performance attained is in the range of 71.7-92.6% sensitivity and 60.3-78.4% specificity. PMID:22167531

Chbat, Nicolas W; Chu, Weiwei; Ghosh, Monisha; Li, Guangxi; Li, Man; Chiofolo, Caitlyn M; Vairavan, Srinivasan; Herasevich, Vitaly; Gajic, Ognjen



Longitudinal Monitoring of Lung Injury in Children after Acute Chlorine Exposure in a Swimming Pool  

PubMed Central

Rationale: Acute exposure to chlorine gas results in respiratory impairment, but few data are available on the pathobiology of the underlying lung damage. Objectives: To assess lung function and potential lung damage pathways in the acute phase and longitudinally over a 15-mo follow-up after acute chlorine exposure. Methods: Ten previously healthy children were accidentally exposed to chlorine gas at a swimming pool because of an erroneous servicing procedure. The fraction of nitric oxide in exhaled air (FeNO), exhaled breath condensate compounds, and serum Clara cell–specific protein CC16 were repeatedly measured. Main results: In the acute phase, all patients had respiratory distress (one child required mechanical ventilation) and reduced lung function (median and interquartile range: FVC, 51 [43–60]% predicted; FEV1, 51 [46–60]% predicted). This was accompanied by low FeNO (4.7 [3.9–7.9] ppb), high exhaled breath condensate leukotriene B4 (LTB4) levels (24.4 [22.5–24.9] pg/ml), and increased serum CC16 levels (mean ± SEM, 23.4 ± 2.5 ?g/L). Lung function returned to normal in 15 d (FVC, 97% predicted [82–108], and FEV1, 92% predicted [77–102]). FeNO reached normal values after 2 mo (12.6 [11.4–15] ppb), whereas LTB4 levels were still increased (12 [9.3–17.1] pg/ml). Conclusion: Children acutely exposed to chlorine in a swimming pool presented a substantial lung function impairment associated with biochemical exhaled breath alterations, represented mainly by an increase in LTB4 and a reduction in FeNO. Although lung function and FeNO improved within a few weeks, the increased levels of exhaled LTB4 persisted for several months.

Bonetto, Gea; Corradi, Massimo; Carraro, Silvia; Zanconato, Stefania; Alinovi, Rossella; Folesani, Giuseppina; Da Dalt, Liviana; Mutti, Antonio; Baraldi, Eugenio



Perinatal factors in neonatal and pediatric lung diseases.  


Wheezing and asthma are significant clinical problems for infants and young children, particularly following premature birth. Recurrent wheezing in infants can progress to persistent asthma. As in adults, altered airway structure (remodeling) and function (increased bronchoconstriction) are also important in neonatal and pediatric airway diseases. Accumulating evidence suggests that airway disease in children is influenced by perinatal factors including perturbations in normal fetal lung development, postnatal interventions in the intensive care unit (ICU) and environmental and other insults in the neonatal period. Here, in addition to genetics, maternal health, environmental processes, innate immunity and impaired lung development/function can all influence pathogenesis of airway disease in children. We summarize current understanding of how prenatal and postnatal factors can contribute to development of airway diseases in neonates and children. Understanding these mechanisms will help identify and develop novel therapies for childhood airway diseases. PMID:24090092

Britt, Rodney D; Faksh, Arij; Vogel, Elizabeth; Martin, Richard J; Pabelick, Christina M; Prakash, Ys



Assessment of early acute lung injury in rodents exposed to phosgene  

Microsoft Academic Search

Phosgene is a highly reactive oxidant gas used in the chemical industry. Phosgene can cause life-threatening pulmonary edema\\u000a by reacting with peripheral lung compartment tissue components. Clinical evidence of edema is not usually apparent until well\\u000a after the initial exposure. This study was designed to investigate early signs of acute lung injury in rodents within 45–60?min\\u000a after the start of

Alfred M. Sciuto



Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase  

PubMed Central

Objective Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.



[Erlotinib in non-small cell lung cancer: experience of clinical hospital for lung diseases Jordanovac].  


Treatment with erlotinib, an inhibitor of the epidermal growth factor receptors, has significantly improved the overall survival rate and quality of life in patients with non-small cell lung cancer who had failed the standard first- or second-line chemotherapy. In Clinical hospital for lung diseases "Jordanovac" a total of 36 patients were treated with erlotinib. The response rate was as follows: in four patients (11%) complete response was achieved, in five (4%) partial response, while fourteen patients (39%) had stable disease. Hence, the evident clinical benefit of treatment with erlotinib was registered in 23 patients (64%) altogether. The treatment was well tolerated and it was not associated with significant toxicity. Our results confirm the antitumour efficacy of erlotinib and show a clear treatment benefit for patients with non-small cell lung cancer in our country. PMID:18383740

Plestina, Sanja; Samarzija, Miroslav; Plestina, Stjepko; Chalfe, Nabil; Zuljevi?, Ervin



Proposed National Strategies for the Prevention of Leading Work-Related Diseases and Injuries. Occupational Lung Diseases.  

National Technical Information Service (NTIS)

The document summarizes what actions need to be taken to prevent occupational lung diseases. The United States Public Health Service has established the following national objectives for the prevention of occupational lung diseases: 'By 1990, among worker...



Short people got no reason: gender, height, and disparities in the management of acute lung injury.  


Though the benefits of lung protective ventilation (LPV) in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) have been known for more than a decade, widespread clinical adoption has been slow. Han and colleagues demonstrate that women with ALI/ARDS are less likely than men to receive LPV, though this disparity resolves when the analysis is adjusted for patient height. This analysis identifies patient height as a significant factor in predicting provider adherence with LPV guidelines, and illuminates why some disparities in intensive care exist and how they may be resolved via improved utilization of evidence-driven protocols. PMID:22221554

Dickson, Robert P; Hyzy, Robert C



Short people got no reason: gender, height, and disparities in the management of acute lung injury  

PubMed Central

Though the benefits of lung protective ventilation (LPV) in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) have been known for more than a decade, widespread clinical adoption has been slow. Han and colleagues demonstrate that women with ALI/ARDS are less likely than men to receive LPV, though this disparity resolves when the analysis is adjusted for patient height. This analysis identifies patient height as a significant factor in predicting provider adherence with LPV guidelines, and illuminates why some disparities in intensive care exist and how they may be resolved via improved utilization of evidence-driven protocols.



Modeling the dynamics of recruitment and derecruitment in mice with acute lung injury.  


Lung recruitment and derecruitment contribute significantly to variations in the elastance of the respiratory system during mechanical ventilation. However, the decreases in elastance that occur with deep inflation are transient, especially in acute lung injury. Bates and Irvin (8) proposed a model of the lung that recreates time-varying changes in elastance as a result of progressive recruitment and derecruitment of lung units. The model is characterized by distributions of critical opening and closing pressures throughout the lung and by distributions of speeds with which the processes of opening and closing take place once the critical pressures have been achieved. In the present study, we adapted this model to represent a mechanically ventilated mouse. We fit the model to data collected in a previous study from control mice and mice in various stages of acid-induced acute lung injury (3). Excellent fits to the data were obtained when the normally distributed critical opening pressures were about 5 cmH(2)O above the closing pressures and when the hyperbolically distributed opening velocities were about an order of magnitude greater than the closing velocities. We also found that, compared with controls, the injured mice had markedly increased opening and closing pressures but no change in the velocities, suggesting that the key biophysical change wrought by acid injury is dysfunction of surface tension at the air-liquid interface. Our computational model of lung recruitment and derecruitment dynamics is thus capable of accurately mimicking data from mice with acute lung injury and may provide insight into the altered biophysics of the injured lung. PMID:18948446

Massa, Christopher B; Allen, Gilman B; Bates, Jason H T



Microbiology specimens obtained at the time of surgical lung biopsy for interstitial lung disease: clinical yield and cost analysis  

Microsoft Academic Search

Objectives: In efforts to obtain complete results, current practice in surgical lung biopsy (LB) for interstitial lung disease (ILD) recommends sending lung tissue samples for bacterial, mycobacterial, fungal, and viral cultures. This study assesses the value of this practice by evaluating the microbiology findings obtained from LB for ILD and their associated costs. Methods: A total of 296 consecutive patients

Juan J. Fibla; Alessandro Brunelli; Mark S. Allen; Dennis Wigle; Robert Shen; Francis Nichols; Claude Deschamps; Stephen D. Cassivi


Inhaled activated protein C: a novel therapy for acute lung injury?  

PubMed Central

Acute lung injury (ALI) is characterized by the presence of dysregulated coagulation and inflammation. Therefore, Waerhaug and colleagues hypothesized that administration of activated protein C (APC) via the inhaled route would be a novel and effective treatment for ALI. They demonstrated that inhaled APC improved oxygenation and lung aeration in a sheep model of lipopolysaccharide-induced ALI, but did not alter lung water or hemodynamics. Future studies are needed to determine plasma and airspace APC levels when administered by the inhaled route, and to determine if inhaled APC has a similar effect in other models of ALI.

Liu, Kathleen D; Looney, Mark R; Matthay, Michael A



Angiogenesis in Lung Development, Injury and Repair: Implications for Chronic Lung Disease of Prematurity  

Microsoft Academic Search

Since the initial description of bronchopulmonary dysplasia (BPD) 40 years ago, advances in perinatal care have allowed the survival of infants that are more immature. The disease has not disappeared, but it now affects infants with undeveloped distal airspaces, resulting in an arrest of alveolar development. The histological changes that occur during normal lung development are well described, but little

Bernard Thébaud



in vivo tomographic velocimetry of the lung for the detailed study of lung disease and its treatments  

NASA Astrophysics Data System (ADS)

All lung disease dramatically alters the local motion of the lung during breathing. It stands to reason, therefore, that detailed measurement of lung motion could provide dramatic improvements in assessment of lung function. Using synchrotron-based phase contrast imaging, we have developed and applied tools for lung motion and function measurement. We demonstrate a low-dose alternative to traditional 4D-CT methods, capable of measuring instantaneous 3D tissue motion using only 6 projection images. Additionally, our technique provides estimation of the airflow distribution throughout the bronchial tree during the breathing cycle. The ability to measure lung function at a regional level will provide invaluable information for studies into normal and pathological lung dynamics, and may provide new pathways for diagnosis of regional lung diseases. Although proof-of-concept data were acquired on a synchrotron, the low-dose methodology developed lends itself to clinical scanning and offers translational opportunities.

Dubsky, Stephen; Hooper, Stuart B.; Siu, Karen K. W.; Fouras, Andreas



Prevention of endotracheal suctioning-induced alveolar derecruitment in acute lung injury.  


We studied endotracheal suctioning-induced alveolar derecruitment and its prevention in nine patients with acute lung injury. Changes in end-expiratory lung volume measured by inductive plethysmography, positive end-expiratory pressure-induced alveolar recruitment assessed by pressure-volume curves, oxygen saturation, and respiratory mechanics were recorded. Suctioning was performed after disconnection from the ventilator, through the swivel adapter of the catheter mount, with a closed system, and with the two latter techniques while performing recruitment maneuvers during suctioning (40 cm H2O pressure-supported breaths). End-expiratory lung volume after disconnection fell more than with all other techniques (-1,466 +/- 586, -733 +/- 406, -531 +/- 228, -168 +/- 176, and -284 +/- 317 ml after disconnection, through the swivel adapter, with the closed system, and with the two latter techniques with pressure-supported breaths, respectively, p < 0.001), and was not fully recovered 1 minute after suctioning. Recruitment decreased after disconnection and using the swivel adapter (-104 +/- 31 and -63 +/- 25 ml, respectively), was unchanged with the closed system (-1 +/- 10 ml), and increased when performing recruitment maneuvers during suctioning (71 +/- 37 and 60 +/- 30 ml) (p < 0.001). Changes in alveolar recruitment correlated with changes in lung volume (rho = 0.88, p < 0.001) and compliance (rho = 0.9, p < 0.001). Oxygenation paralleled lung volume changes. Suctioning-induced lung derecruitment in acute lung injury can be prevented by performing recruitment maneuvers during suctioning and minimized by avoiding disconnection. PMID:12615633

Maggiore, Salvatore M; Lellouche, Francois; Pigeot, Jerome; Taille, Solenne; Deye, Nicolas; Durrmeyer, Xavier; Richard, Jean-Christophe; Mancebo, Jordi; Lemaire, Francois; Brochard, Laurent



Bench-to-bedside review: Adjuncts to mechanical ventilation in patients with acute lung injury  

PubMed Central

Mechanical ventilation is indispensable for the survival of patients with acute lung injury and acute respiratory distress syndrome. However, excessive tidal volumes and inadequate lung recruitment may contribute to mortality by causing ventilator-induced lung injury. This bench-to-bedside review presents the scientific rationale for using adjuncts to mechanical ventilation aimed at optimizing lung recruitment and preventing the deleterious consequences of reduced tidal volume. To enhance CO2 elimination when tidal volume is reduced, the following are possible: first, ventilator respiratory frequency can be increased without necessarily generating intrinsic positive end-expiratory pressure; second, instrumental dead space can be reduced by replacing the heat and moisture exchanger with a conventional humidifier; and third, expiratory washout can be used for replacing the CO2-laden gas present at end expiration in the instrumental dead space by a fresh gas (this method is still experimental). For optimizing lung recruitment and preventing lung derecruitment there are the following possibilities: first, recruitment manoeuvres may be performed in the most hypoxaemic patients before implementing the preset positive end-expiratory pressure or after episodes of accidental lung derecruitment; second, the patient can be turned to the prone position; third, closed-circuit endotracheal suctioning is to be preferred to open endotracheal suctioning.

Rouby, Jean-Jacques; Lu, Qin



Therapeutic Potential of Heme Oxygenase-1/Carbon Monoxide in Lung Disease  

PubMed Central

Heme oxygenase (HO), a catabolic enzyme, provides the rate-limiting step in the oxidative breakdown of heme, to generate carbon monoxide (CO), iron, and biliverdin-IX?. Induction of the inducible form, HO-1, in tissues is generally regarded as a protective mechanism. Over the last decade, considerable progress has been made in defining the therapeutic potential of HO-1 in a number of preclinical models of lung tissue injury and disease. Likewise, tissue-protective effects of CO, when applied at low concentration, have been observed in many of these models. Recent studies have expanded this concept to include chemical CO-releasing molecules (CORMs). Collectively, salutary effects of the HO-1/CO system have been demonstrated in lung inflammation/acute lung injury, lung and vascular transplantation, sepsis, and pulmonary hypertension models. The beneficial effects of HO-1/CO are conveyed in part through the inhibition or modulation of inflammatory, apoptotic, and proliferative processes. Recent advances, however, suggest that the regulation of autophagy and the preservation of mitochondrial homeostasis may serve as additional candidate mechanisms. Further preclinical and clinical trials are needed to ascertain the therapeutic potential of HO-1/CO in human clinical disease.

Constantin, Myrna; Choi, Alexander J. S.; Cloonan, Suzanne M.; Ryter, Stefan W.



Overexpression of pulmonary extracellular superoxide dismutase attenuates endotoxin-induced acute lung injury  

Microsoft Academic Search

Purpose  Superoxide is produced by activated neutrophils during the inflammatory response to stimuli such as endotoxin, can directly\\u000a or indirectly injure host cells, and has been implicated in the pathogenesis of acute lung injury (ALI)\\/acute respiratory\\u000a distress syndrome (ARDS). We wished to determine the potential for pulmonary overexpression of the extracellular isoform of\\u000a superoxide dismutase (EC-SOD) to reduce the severity of

Patrick Hassett; Gerard F. Curley; Maya Contreras; Claire Masterson; Brendan D. Higgins; Timothy O’Brien; James Devaney; Daniel O’Toole; John G. Laffey


Effects of prone position on alveolar recruitment and oxygenation in acute lung injury  

Microsoft Academic Search

Objective: To investigate the effects of prone position (PP) on alveolar recruitment and oxygenation in acute respiratory failure.¶Design: Prospective physiologic study.¶Setting: Medical ICU two in a university hospital.¶Patients: Twelve adult patients intubated and mechanically ventilated with medical primary acute lung injury\\/adult respiratory distress\\u000a syndrome (ALI\\/ARDS) in whom PP was indicated.¶Measurements and results: We constructed the static inflation volume-pressure curves (V-P)

C. Guerin; M. Badet; S. Rosselli; L. Heyer; J.-M. Sab; B. Langevin; F. Philit; G. Fournier; D. Robert



Study protocol: The Improving Care of Acute Lung Injury Patients (ICAP) study  

Microsoft Academic Search

INTRODUCTION: The short-term mortality benefit of lower tidal volume ventilation (LTVV) for patients with acute lung injury\\/acute respiratory distress syndrome (ALI\\/ARDS) has been demonstrated in a large, multi-center randomized trial. However, the impact of LTVV and other critical care therapies on the longer-term outcomes of ALI\\/ARDS survivors remains uncertain. The Improving Care of ALI Patients (ICAP) study is a multi-site,

Dale M Needham; Cheryl R Dennison; David W Dowdy; Pedro A Mendez-Tellez; Nancy Ciesla; Sanjay V Desai; Jonathan Sevransky; Carl Shanholtz; Daniel Scharfstein; Margaret S Herridge; Peter J Pronovost



Palliative care services for those with chronic lung disease  

Microsoft Academic Search

Excellent palliative care is available for patients with advanced lung cancer. Whether the same services are available for those with nonmalignant respiratory disease is less clear. A questionnaire was sent to 210 named respiratory physicians, each representing a major hospital in England, Wales, and Northern Ireland. A total of 107 replies were received; the response rate was 51.0%. Respondents cared

Partridge; A Khatri; L Sutton; S Welham; SH Ahmedzai



Factors Influencing Survival in Children with Chronic Interstitial Lung Disease  

Microsoft Academic Search

To investigate factors influencing survival in children with chronic interstitial lung disease (ILD), we extracted specific clinical information from a data base of 99 children with ILD who met entry criteria for our study. The effects of a weight below the fifth percentile for the patient's age, crackles, club- bing, family history of ILD, symptom duration, and severity-of-illness score on




Rare Infiltrative Lung Diseases: A Challenge for Clinicians  

Microsoft Academic Search

Rare diffuse infiltrative lung diseases are a challenge for clinicians, radiologists, and pathologists for at least three reasons: (a) their low incidence and prevalence hamper the acquisition of expertise and frequently the diagnosis is delayed; (b) therapeutic actions are mainly empirical and based on steroid use, and (c) pathogenetic events are difficult to explain and only recently new therapeutic measures

Venerino Poletti; Ulrich Costabel; Gian Luca Casoni; Caterina Bigliazzi; Marjolein Drent; Dario Olivieri



[The differential diagnosis of ecological and professional lung diseases].  


Ecological pulmonology appeared due to the technical revolution and increase of toxic substances entering the body through the upper respiratory tract to the lungs. In distinction from professional, ecological diseases are spread among the population in general and not only among those working in conditions of increased professional noxae. PMID:1292213

Pilipchuk, N S


Postnatal steroids and chronic lung disease in the newborn  

Microsoft Academic Search

Introduction: Chronic lung disease (CLD) represents a condition of persistent inflammation within the airways which may have its origin either in utero or after birth. Corticosteroids, because of their anti- inflammatory actions, have been used to modify the course of CLD. There have been almost 40 randomised controlled trials of postnatal dexamethasone and 12 of inhaled steroids. Methods: Systematic reviews

Henry L. Halliday



Relative importance of cigarette smoking in occupational lung disease  

Microsoft Academic Search

Since 1900 respiratory disease has remained a constant serious cause of chronic ill health and premature death in Britain. The falling importance of tuberculosis and pneumonia has been off-set by the rise in lung cancer. Bronchitis morbidity and mortality have fallen only slightly since 1935. To produce any real improvement in the future existing information as to cause must be

P C Elmes



Utility of CT findings on diagnosis of occupational lung disease  

Microsoft Academic Search

IntroductionWe experienced two occupational lung diseases on a different situation in military training. The purpose of this study was to investigate the use of CT images for inhaled pulmonary edema from the standpoint of early diagnosis and assessment of severity.

Y. Masaki; K. Sugiyama; H. Tanaka; Y. Uwabe; M. Takayama; M. Sakai; T. Hayashi; M. Otsuka; S. Suzuki




EPA Science Inventory

The potential role of ozone in the induction of chronic lung diseases remains unclear. sing an ambient profile adopted from aerometric data from the Southwest Air Basin, rats were exposed to O3 for up to 18 months before assessments of pulmonary structure, function and biochemist...


An overview of the pathogenesis of cystic fibrosis lung disease  

Microsoft Academic Search

The pathogenesis of cystic fibrosis (CF) lung disease is reviewed, focusing on an overview of the physiologic mechanisms that regulate mucus transport. A major emphasis is placed on the active transport systems that regulate the airway surface liquid (ASL) volume and, particularly, regulate the volume of the periciliary liquid (PCL) layer. A sequence is developed for CF whereby there is

R. C Boucher



`Vineyard sprayer's lung': a new occupational disease  

PubMed Central

The mildew of the vineyards is prevented by the use of sprays with a solution of copper sulphate neutralized with hydrated lime. The inhalation of this solution while spraying may give rise to predominantly interstitial pulmonary lesions which may lead to respiratory insufficiency. These lesions, which were experimentally reproduced in guinea-pigs, have a well-defined histological picture characterized by three stages—intra-alveolar desquamation of macrophages, formation of predominantly histiocytic granulomas in the septa, and the healing of these lesions generally under the form of fibro-hyaline nodules very similar to those found in silicosis. These lesions contain variable amounts of copper. The pathogenesis of these lesions and the possibility of their regression when the offending agent is removed are discussed; and the value of lung biopsy and the necessity of protecting these workers are stressed. Images

Pimentel, J. Cortez; Marques, Fernando



Pulmonary functional magnetic resonance imaging for paediatric lung disease.  


A better understanding of the anatomic structure and physiological function of the lung is fundamental to understanding the pathogenesis of pulmonary disease and how to design and deliver better treatments and measure response to intervention. Magnetic resonance imaging (MRI) with the hyperpolarised noble gases helium-3 ((3)He) and xenon-129 ((129)Xe) provides both structural and functional pulmonary measurements, and because it does not require the use of x-rays or other ionising radiation, offers the potential for intensive serial and longitudinal studies in paediatric patients. These facts are particularly important in the evaluation of chronic lung diseases such as asthma and cystic fibrosis- both of which can be considered paediatric respiratory diseases with unmet therapy needs. This review discusses MRI-based imaging methods with a focus on hyperpolarised gas MRI. We also discuss the strengths and limitations as well as the future work required for clinical translation towards paediatric respiratory disease. PMID:23522599

Kirby, Miranda; Coxson, Harvey O; Parraga, Grace



Fibrocytes in chronic lung disease--facts and controversies.  


Fibrocytes are bone marrow-derived mesenchymal cell precursors, defined primarily by their ability to co-express markers of both haematopoietic (e.g. CD45 or CXCR4) and stromal (e.g. collagen) lineages. Fibrocytes in culture also have ultrastructural cell surface features that distinguish them from other leukocytes. Extensive efforts have helped to characterise fibrocytes phenotypically and functionally, but it is still unclear exactly how these cells contribute to tissue repair and/or pathologic fibrosis. Nevertheless, the varied levels of fibrocytes in blood have raised considerable interest as a biomarker of disease activity, such as chronic lung diseases, including pulmonary fibrosis, asthma and pulmonary hypertension. These cells also may become a novel therapeutic target for these difficult to treat disorders. This review will briefly summarize the current knowledge about fibrocytes in human lung disease and in animal disease models and highlight areas of consensus as well as issues that remain controversial to date. PMID:21951688

Maharaj, Shyam S; Baroke, Eva; Gauldie, Jack; Kolb, Martin R J



Acute diarrhoeal disease in less developed countries  

PubMed Central

The programme presented in this article for controlling the diarrhoeas and dysenteries of less developed countries is based on epidemiological principles applicable to acute undifferentiated diarrhoeal disease—its specific as well as its non-specific elements. The dominant importance of weanling diarrhoea requires a main emphasis on maternal and child health procedures, with nutrition singled out for attention, along with public health education and medical care of patients: this in addition to the established worth of means for promoting environmental sanitation. The several features of the suggested programme are within four broad divisions: preventive measures; control of patients, contacts and the immediate environment; measures specifically useful in epidemics; and international measures conducive to broad restriction of the syndrome.

Gordon, John E.; Behar, Moises; Scrimshaw, Nevin S.



Measurement of alveolar derecruitment in patients with acute lung injury: computerized tomography versus pressure–volume curve  

Microsoft Academic Search

Introduction  Positive end-expiratory pressure (PEEP)-induced lung derecruitment can be assessed by a pressure–volume (P–V) curve method\\u000a or by lung computed tomography (CT). However, only the first method can be used at the bedside. The aim of the study was to\\u000a compare both methods for assessing alveolar derecruitment after the removal of PEEP in patients with acute lung injury or\\u000a acute respiratory

Qin Lu; Jean-Michel Constantin; Ania Nieszkowska; Marilia Elman; Silvia Vieira; Jean-Jacques Rouby



Current Status of Gene Therapy for Inherited Lung Diseases  

PubMed Central

Gene therapy as a treatment modality for pulmonary disorders has attracted significant interest over the past decade. Since the initiation of the first clinical trials for cystic fibrosis lung disease using recombinant adenovirus in the early 1990s, the field has encountered numerous obstacles including vector inflammation, inefficient delivery, and vector production. Despite these obstacles, enthusiasm for lung gene therapy remains high. In part, this enthusiasm is fueled through the diligence of numerous researchers whose studies continue to reveal great potential of new gene transfer vectors that demonstrate increased tropism for airway epithelia. Several newly identified serotypes of adeno-associated virus have demonstrated substantial promise in animal models and will likely surface soon in clinical trials. Furthermore, an increased understanding of vector biology has also led to the development of new technologies to enhance the efficiency and selectivity of gene delivery to the lung. Although the promise of gene therapy to the lung has yet to be realized, the recent concentrated efforts in the field that focus on the basic virology of vector development will undoubtedly reap great rewards over the next decade in treating lung diseases.

Driskell, Ryan R.; Engelhardt, John F.



Increased carrageenan-induced acute lung inflammation in old rats  

PubMed Central

Ageing is associated with increased susceptibility to lung infections and delayed resolution of pulmonary infiltrates. The purpose of this study was to investigate the effect of age on the onset of carrageenan-induced lung inflammation. When compared with carrageenan-treated young rats (3 months old), old rats (> 18 months old) exhibited a preponderance of pleural exudation and polymorphonuclear cell infiltration. Lung myeloperoxidase activity, an index of neutrophil infiltration and activation, was significantly increased in old rats in comparison with young rats. Consistent with the biochemical markers of inflammation, increased lung damage, as assessed by nitrosative stress and lipid peroxidation, was observed in carrageenan-treated old rats. In the lung exudate obtained from old rats, a significant reduction in interleukin-10 (IL-10) was observed, while similar expression of monocyte chemotactic protein-1 was induced, suggesting that a decrease in IL-10 rather than increased chemotaxis may account for the preponderance of the inflammatory cellular infiltrate in old rats. Similar to the in vivo situation, freshly isolated alveolar macrophages obtained from old rats produced less IL-10. This defective IL-10 production could be explained by a reduction in the cAMP-dependent signalling pathway, which mediates IL-10 production. Indeed, we found decreased cAMP-responsive element binding protein (CREB) and phosphorous-CREB (P-CREB) expression in old rats, which may account for reduced IL-10 production in old rats.

Corsini, Emanuela; Di Paola, Rosanna; Viviani, Barbara; Genovese, Tiziana; Mazzon, Emanuela; Lucchi, Laura; Marinovich, Marina; Galli, Corrado Lodovico; Cuzzocrea, Salvatore



Lung injury in mice and rats acutely exposed to beryllium  

SciTech Connect

The effect of lung injury, in rats and mice, exposed to an aerosol of beryllium sulfate (BE) for one hour, through nose-only inhalation, was evaluated by the methods of bronchoalveolar lavage (BAL) and lung cell kinetics. The BAL in rats, sacrificed over a 21 day period following exposure, showed lactate dehydrogenase (LDH) and alkaline phosphatase (Alk Pase) activities as the most sensitive indicators of lung damage. LDH activity peaked at day 8 while Alk Pase activity peaked at day 5, both being 30 times greater than comparable control values. Acid phosphatase activity and albumin levels were also increased, but not to the same extent as LDH and Alk Pase. The BAL of mice showed LDH activity as the most sensitive indicator of lung damage, with a maximum response 3 times greater than controls at day 5. In another series of experiments, animals were treated with three agents capable of inducing fibrosis: beryllium sulfate, bleomycin, and butylated hydroxytoluene (BHT). Cy A completely inhibited the fibrogenic effects of BHT in mice, as measured through total lung hydroxyproline content. Bleomycin-induced fibrosis was significantly reduced by Cy A treatment in rats, but showed no effect in mice. Additionally, the effect of iron salt administration to rats decreased the intravenous LD/sub 50/ dose, and significantly reduced the inhalation toxicity, of beryllium sulfate. The protective mechanism of iron salt administration, through the induction of ferritin synthesis, is postulated.

Sendelbach, L.E. Jr.



LPS-Induced Lung Inflammation in Marmoset Monkeys - An Acute Model for Anti-Inflammatory Drug Testing  

PubMed Central

Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS)-induced inflammation model was established in marmoset monkeys (Callithrix jacchus) to reflect crucial features of inflammatory lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of comparison, human precision-cut lung slices (PCLS) were stimulated with LPS in the presence or absence of the phosphodiesterase-4 (PDE4) inhibitor roflumilast. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-?) and macrophage inflammatory protein-1 beta (MIP-1?) were measured. The corticosteroid dexamethasone was used as treatment control. Secondly, in an in vivo approach marmosets were pre-treated with roflumilast or dexamethasone and unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL) was conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for neutrophils, TNF-?, and MIP-1?. TNF-? release in marmoset PCLS correlated significantly with human PCLS. Roflumilast treatment significantly reduced TNF-? secretion ex vivo in both species, with comparable half maximal inhibitory concentration (IC50). LPS instillation into marmoset lungs caused a profound inflammation as shown by neutrophilic influx and increased TNF-? and MIP-1? levels in BAL fluid. This inflammatory response was significantly suppressed by roflumilast and dexamethasone. The close similarity of marmoset and human lungs regarding LPS-induced inflammation and the significant anti-inflammatory effect of approved pharmaceuticals assess the suitability of marmoset monkeys to serve as a promising model for studying anti-inflammatory drugs.

Seehase, Sophie; Lauenstein, Hans-Dieter; Schlumbohm, Christina; Switalla, Simone; Neuhaus, Vanessa; Forster, Christine; Fieguth, Hans-Gerd; Pfennig, Olaf; Fuchs, Eberhard; Kaup, Franz-Josef; Bleyer, Martina; Hohlfeld, Jens M.; Braun, Armin



Genetic segregation of inflammatory lung disease and autoimmune disease severity in SHIP-1-/- mice.  


Alternatively activated M2 macrophages are implicated as both regulators and agents of lung disease, but their control is poorly understood. SHIP-1 is a 5' inositol phosphatase that negatively regulates the PI3K signaling pathway implicated in inflammation. SHIP-1-deficient mice have defects in hematopoiesis and B cell development, and die prematurely due to consolidation of lungs with M2-skewed macrophages. SHIP-1 is thought to restrain M2 macrophage polarization, with deregulated M2 skewing coinciding with severe lung disease in SHIP-1-deficient mice. To determine the influence of genetic background on the lung phenotype in SHIP-1(-/-) mice, we backcrossed the SHIP-1 null mutation onto C57BL/6 (Th2-resistant) and BALB/c (Th2-prone) backgrounds. Remarkably, we found that inflammatory lung disease was severe in C57.SHIP-1(-/-) mice, but absent in BALB.SHIP-1(-/-) mice. C57.SHIP-1(-/-), but not BALB.SHIP-1(-/-) mice had greatly increased myeloid progenitors, myeloid hyperplasia, markedly enhanced numbers of activated alveolar macrophages, and elevated amounts of Th2 and proinflammatory cytokines in bronchoalveolar lavage fluid and serum, suggesting that deregulated cytokine production induced disease. C57.SHIP-1(-/-) mice also developed severe B cell-dependent autoimmune disease, which was markedly attenuated on the BALB/c background. These data demonstrate that, contrary to current concepts, loss of SHIP-1 alone is not sufficient to cause lung inflammation, with disease only manifest on a permissive genetic background. This finding questions the nature of the lung disease in SHIP-1(-/-) mice, suggesting that its M2 classification is not strictly correct. Future identification of disease-promoting loci might reveal determinants of comorbid lung disease and autoimmunity and uncover potentially useful therapeutic targets. PMID:21572033

Maxwell, Mhairi J; Duan, Mubing; Armes, Jane E; Anderson, Gary P; Tarlinton, David M; Hibbs, Margaret L



Signaling through the A2B Adenosine Receptor Dampens Endotoxin-Induced Acute Lung Injury  

PubMed Central

Sepsis and septic acute lung injury are among the leading causes for morbidity and mortality of critical illness. Extracellular adenosine is a signaling molecule implicated in the cellular adaptation to hypoxia, ischemia or inflammation. Therefore, we pursued the role of the A2B adenosine receptor (A2BAR) as potential therapeutic target in endotoxin-induced acute lung injury. We gained initial insight from in vitro studies of cultured endothelia or epithelia exposed to inflammatory mediators showing time-dependent induction of the A2BAR (up to 12.9±3.4-fold, p<0.05). Similarly, murine studies of endotoxin-induced lung injury identified an almost 4.6-fold induction of A2BAR transcript and corresponding protein induction with LPS-exposure. Studies utilizing A2BAR promoter constructs and RNA-protection assays indicated that A2BAR induction involved mRNA stability. Functional studies of LPS-induced lung injury revealed that pharmacological inhibition or genetic deletion of the A2BAR was associated with dramatic increases in lung inflammation and histologic tissue injury. Studies of A2BAR-bone marrow chimeric mice suggested pulmonary A2BAR signaling in lung protection. Finally, studies with a specific A2BAR agonist (BAY 60-6583) demonstrated attenuation of lung inflammation and pulmonary edema in wild-type but not in gene-targeted mice for the A2BAR. These studies suggest the A2BAR as potential therapeutic target in the treatment of endotoxin-induced forms of acute lung injury.

Schingnitz, Ulrich; Hartman, Katherine; MacManus, Christopher F.; Eckle, Tobias; Zug, Stephanie; Colgan, Sean P.; Eltzschig, Holger K.



Signaling through the A2B adenosine receptor dampens endotoxin-induced acute lung injury.  


Sepsis and septic acute lung injury are among the leading causes for morbidity and mortality of critical illness. Extracellular adenosine is a signaling molecule implicated in the cellular adaptation to hypoxia, ischemia, or inflammation. Therefore, we pursued the role of the A2B adenosine receptor (AR) as potential therapeutic target in endotoxin-induced acute lung injury. We gained initial insight from in vitro studies of cultured endothelia or epithelia exposed to inflammatory mediators showing time-dependent induction of the A2BAR (up to 12.9 + or - 3.4-fold, p < 0.05). Similarly, murine studies of endotoxin-induced lung injury identified an almost 4.6-fold induction of A2BAR transcript and corresponding protein induction with LPS exposure. Studies utilizing A2BAR promoter constructs and RNA protection assays indicated that A2BAR induction involved mRNA stability. Functional studies of LPS-induced lung injury revealed that pharmacological inhibition or genetic deletion of the A2BAR was associated with dramatic increases in lung inflammation and histologic tissue injury. Studies of A2BAR bone marrow chimeric mice suggested pulmonary A2BAR signaling in lung protection. Finally, studies with a specific A2BAR agonist (BAY 60-6583) demonstrated attenuation of lung inflammation and pulmonary edema in wild-type but not in gene-targeted mice for the A2BAR. These studies suggest the A2BAR as potential therapeutic target in the treatment of endotoxin-induced forms of acute lung injury. PMID:20348420

Schingnitz, Ulrich; Hartmann, Katherine; Macmanus, Christopher F; Eckle, Tobias; Zug, Stephanie; Colgan, Sean P; Eltzschig, Holger K



Oxygenation Inhibits the Physiological Tissue-Protecting Mechanism and Thereby Exacerbates Acute Inflammatory Lung Injury  

PubMed Central

Acute respiratory distress syndrome (ARDS) usually requires symptomatic supportive therapy by intubation and mechanical ventilation with the supplemental use of high oxygen concentrations. Although oxygen therapy represents a life-saving measure, the recent discovery of a critical tissue-protecting mechanism predicts that administration of oxygen to ARDS patients with uncontrolled pulmonary inflammation also may have dangerous side effects. Oxygenation may weaken the local tissue hypoxia-driven and adenosine A2A receptor (A2AR)-mediated anti-inflammatory mechanism and thereby further exacerbate lung injury. Here we report experiments with wild-type and adenosine A2AR-deficient mice that confirm the predicted effects of oxygen. These results also suggest the possibility of iatrogenic exacerbation of acute lung injury upon oxygen administration due to the oxygenation-associated elimination of A2AR-mediated lung tissue-protecting pathway. We show that this potential complication of clinically widely used oxygenation procedures could be completely prevented by intratracheal injection of a selective A2AR agonist to compensate for the oxygenation-related loss of the lung tissue-protecting endogenous adenosine. The identification of a major iatrogenic complication of oxygen therapy in conditions of acute lung inflammation attracts attention to the need for clinical and epidemiological studies of ARDS patients who require oxygen therapy. It is proposed that oxygen therapy in patients with ARDS and other causes of lung inflammation should be combined with anti-inflammatory measures, e.g., with inhalative application of A2AR agonists. The reported observations may also answer the long-standing question as to why the lungs are the most susceptible to inflammatory injury and why lung failure usually precedes multiple organ failure.



Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models.  


Isoforskolin was isolated from Coleus forskohlii native to Yunnan in China. We hypothesize that isoforskolin pretreatment attenuates acute lung injury induced by lipopolysaccharide (endotoxin). Three acute lung injury models were used: situ perfused rat lung, rat and mouse models of endotoxic shock. Additionally, lipopolysaccharide stimulated proinflammatory cytokine production was evaluated in human mononuclear leukocyte. In situ perfused rat lungs, pre-perfusion with isoforskolin (100, and 200 ?M) and dexamethasone (65 ?M, positive control) inhibited lipopolysaccharide (10 mg/L) induced increases in lung neutrophil adhesion rate, myeloperoxidase activity, lung weight Wet/Dry ratio, permeability-surface area product value, and tumor necrosis factor (TNF)-? levels. In rats, pretreatments with isoforskolin (5, 10, and 20 mg/kg, i.p.) and dexamethasone (5mg/kg, i.p.) markedly reduced lipopolysaccharide (6 mg/kg i.v.) induced increases of karyocyte, neutrophil counts and protein content in bronchoalveolar lavage fluid, and plasma myeloperoxidase activity. Lung histopathology showed that morphologic changes induced by lipopolysaccharide were less pronounced in the isoforskolin and dexamethasone pretreated rats. In mice, 5 mg/kg isoforskolin and dexamethasone caused 100% and 80% survival, respectively, after administration of lipopolysaccharide (62.5mg/kg, i.v., 40% survival if untreated). In human mononuclear leukocyte, isoforskolin (50, 100, and 200 ?M) and dexamethasone (10 ?M) pre-incubation lowered lipopolysaccharide (2 ?g/mL) induced secretion of the cytokine TNF-?, and interleukins (IL)-1?, IL-6, and IL-8. In conclusion, pretreatment with isoforskolin attenuates lipopolysaccharide-induced acute lung injury in several models, and it is involved in down-regulation of inflammatory responses and proinflammatory cytokines TNF-?, IL-1?, IL-6, and IL-8. PMID:21272678

Yang, Weimin; Qiang, Dongjin; Zhang, Min; Ma, Limei; Zhang, Yonghui; Qing, Chen; Xu, Yunlong; Zhen, Chunlan; Liu, Jikai; Chen, Yan-Hua



Successful extracorporeal membranous oxygenation for a patient with life-threatening transfusion-related acute lung injury.  


A case of transfusion-related acute lung injury (TRALI) that was successfully treated with extracorporeal membranous oxygenation (ECMO) is reported. A 58-year-old male patient underwent hepatectomy, and pulmonary edema occurred after the administration of fresh-frozen plasma and packed red cells. In the postoperative period, the impaired oxygenation progressively worsened, resulting in life-threatening hypoxemia, despite vigorous treatments. ECMO was therefore applied to the patient as a method of safe emergency support. Aggressive treatments under ECMO led to the successful improvement of the impaired oxygenation. TRALI is recognized as part of acute respiratory distress syndrome (ARDS). As a treatment for ARDS, ECMO does not cure the underlying disease of the lungs, however, with ECMO, TRALI, usually improves within 96 h with respiratory support. ECMO for TRALI-induced lethal hypoxemia is useful for providing time to allow the injured lung to recover. It is suggested that ECMO might be a useful option for the treatment of TRALI-induced, potentially lethal hypoxemia. PMID:19685127

Kuroda, Hiromitsu; Masuda, Yoshiki; Imaizumi, Hitoshi; Kozuka, Yuji; Asai, Yasufumi; Namiki, Akiyoshi



Cysteinyl leukotriene involvement in chronic lung disease in premature infants.  


The pathophysiology of chronic lung disease (CLD) in premature infants who require mechanical ventilation and prolonged oxygen supplementation has been well-described but the underlying mechanisms are not understood. Our aim was to test the hypothesis that excess cysteinyl leukotriene (LT) production was a contributing factor in CLD. We compared LT production and lung function, at 7 months of age, in nine premature infants with CLD and in eight control infants without CLD. None of the control infants developed any neonatal respiratory problems, but two subsequently required bronchodilator therapy. Respiratory function was assessed by the measurement of thoracic gas volume (TGV), airways resistance (Raw) and functional residual capacity (FRC). Total cysteinyl LT production was quantified by measurement of leukotriene E4 (LTE4) in a spot urine sample. Although all patients were asymptomatic at follow-up, there was evidence of significant lung function abnormalities in infants with CLD. The CLD infants had significantly elevated TGV, Raw and FRC values reflecting airway obstruction when compared to the controls. Urinary LTE4 levels were significantly higher in the CLD infants when compared to the controls (geometric mean: 741 and 337 pmol.mmol-1 creatinine, respectively). There was no direct correlation between urinary LTE4 levels in the CLD group and TGV, Raw or FRC values. Although this study is small and a direct correlation between lung function and urinary leukotriene E4 was not demonstrated, pathological lung function and an enhanced urinary leukotriene E4 production in infants with chronic lung disease would tend to suggest that the cysteinyl leukotrienes were involved in the sequelae of this disease. PMID:8880111

Cook, A J; Yuksel, B; Sampson, A P; Greenough, A; Price, J F



High-frequency oscillatory ventilation attenuates oxidative lung injury in a rabbit model of acute lung injury.  


Mechanical ventilation (MV) can induce lung oxidative stress, which plays an important role in pulmonary injury. This study compared protective conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) for oxygenation, oxidative stress, inflammatory and histopathological lung injury in a rabbit model of acute lung injury (ALI). Rabbits (n = 30) were ventilated at FiO(2) 1.0. Lung injury was induced by tracheal saline infusion (30 mL/kg, 38°C). Animals were randomly assigned to: (a) sham control (CG: tidal volume [V(T)] 6 mL/kg, positive end expiratory pressure [PEEP] 5 cmH(2)O, respiratory rate [RR] 40 ipm); (b) ALI + CMV (CMVG: V(T) 6 mL/kg, PEEP 10 cmH(2)O, RR 40 ipm); or (c) ALI + HFOV (HFG: mean airway pressure [Paw] 14 cmH(2)O, RR 10 Hz) groups. Lung oxidative stress was assessed by total antioxidant performance assay, inflammatory response by the number of polymorphonuclear leukocytes/bronchoalveolar lavage fluid/lung and pulmonary histological damage was quantified by a score. Ventilatory and hemodynamic parameters were recorded every 30 min. Both ALI groups showed worse oxygenation after lung injury induction. After four hours of ventilation, HFG showed better oxygenation (partial pressure of oxygen [PaO(2)] - CG: 465.9 ± 30.5 = HFG: 399.1 ± 98.2 > CMVG: 232.7 ± 104 mmHg, P < 0.05) and inflammatory responses (CMVG: 4.27 ± 1.50 > HFG: 0.33 ± 0.20 = CG: 0.16 ± 0.15; polymorphonuclear cells/bronchoalveolar lavage fluid/lung, P < 0.05), less histopathological injury score (CMVG: 5 [1-16] > HFG: 1 [0-5] > CG: 0 [0-3]; P < 0.05), and lower lung oxidative stress than CMVG (CG: 59.4 ± 4.52 = HFG: 69.0 ± 4.99 > CMVG: 47.6 ± 2.58% protection/g protein, P < 0.05). This study showed that HFOV had an important protective role in ALI. It improved oxygenation, reduced inflammatory process and histopathological damage, and attenuated oxidative lung injury compared with protective CMV under these experimental conditions considering the study limitations. PMID:21930717

Ronchi, Carlos Fernando; dos Anjos Ferreira, Ana Lucia; Campos, Fabio Joly; Kurokawa, Cilmery Suemi; Carpi, Mario Ferreira; de Moraes, Marcos Aurelio; Bonatto, Rossano Cesar; Defaveri, Julio; Yeum, Kyung-Jin; Fioretto, Jose Roberto



Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury  

PubMed Central

Introduction Recruitment maneuvers (RMs) seem to be more effective in extrapulmonary acute lung injury (ALI), caused mainly by sepsis, than in pulmonary ALI. Nevertheless, the maintenance of adequate volemic status is particularly challenging in sepsis. Since the interaction between volemic status and RMs is not well established, we investigated the effects of RMs on lung and distal organs in the presence of hypovolemia, normovolemia, and hypervolemia in a model of extrapulmonary lung injury induced by sepsis. Methods ALI was induced by cecal ligation and puncture surgery in 66 Wistar rats. After 48 h, animals were anesthetized, mechanically ventilated and randomly assigned to 3 volemic status (n = 22/group): 1) hypovolemia induced by blood drainage at mean arterial pressure (MAP)?70 mmHg; 2) normovolemia (MAP?100 mmHg), and 3) hypervolemia with colloid administration to achieve a MAP?130 mmHg. In each group, animals were further randomized to be recruited (CPAP = 40 cm H2O for 40 s) or not (NR) (n = 11/group), followed by 1 h of protective mechanical ventilation. Echocardiography, arterial blood gases, static lung elastance (Est,L), histology (light and electron microscopy), lung wet-to-dry (W/D) ratio, interleukin (IL)-6, IL-1?, caspase-3, type III procollagen (PCIII), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) mRNA expressions in lung tissue, as well as lung and distal organ epithelial cell apoptosis were analyzed. Results We observed that: 1) hypervolemia increased lung W/D ratio with impairment of oxygenation and Est,L, and was associated with alveolar and endothelial cell damage and increased IL-6, VCAM-1, and ICAM-1 mRNA expressions; and 2) RM reduced alveolar collapse independent of volemic status. In hypervolemic animals, RM improved oxygenation above the levels observed with the use of positive-end expiratory pressure (PEEP), but increased lung injury and led to higher inflammatory and fibrogenetic responses. Conclusions Volemic status should be taken into account during RMs, since in this sepsis-induced ALI model hypervolemia promoted and potentiated lung injury compared to hypo- and normovolemia.



Probiotics in the management of lung diseases.  


The physiology and pathology of the respiratory and gastrointestinal tracts are closely related. This similarity between the two organs may underlie why dysfunction in one organ may induce illness in the other. For example, smoking is a major risk factor for COPD and IBD and increases the risk of developing Crohn's disease. Probiotics have been defined as "live microorganisms which, when administered in adequate amounts, confer health benefits on the host." In model systems probiotics regulate innate and inflammatory immune responses. Commonly used probiotics include lactic acid bacteria, particularly Lactobacillus, Bifidobacterium, and Saccharomyces, and these are often used as dietary supplements to provide a health benefit in gastrointestinal diseases including infections, inflammatory bowel disease, and colon cancer. In this respect, probiotics probably act as immunomodulatory agents and activators of host defence pathways which suggest that they could influence disease severity and incidence at sites distal to the gut. There is increasing evidence that orally delivered probiotics are able to regulate immune responses in the respiratory system. This review provides an overview of the possible role of probiotics and their mechanisms of action in the prevention and treatment of respiratory diseases. PMID:23737654

Mortaz, Esmaeil; Adcock, Ian M; Folkerts, Gert; Barnes, Peter J; Paul Vos, Arjan; Garssen, Johan



Nose and lungs: one way, one disease  

PubMed Central

It’s well established that asthma, allergic rhinitis and rhinosinusitis are three closely related disease. In pediatrics, these conditions represent a common issue in daily practice. The scientific community has recently started to simply evaluate them as different manifestations of a common pathogenic phenomenon. This consideration relates to important implications in the clinical management of these diseases, which may affect the daily activity of a pediatrician. The unity of the respiratory tract is confirmed both from a morphological and from a functional point of view. When treating rhinitis, it is often necessary to assess the presence of asthma. Patients with sinusitis should be evaluated for a possible concomitant asthma. Conversely, patients with asthma should always be evaluated for possible nasal disease, especially those suffering from difficult-to-treat asthma, in which an occult sinusitis may be detected. The medications that treat nasal diseases appear to be useful in improving asthma control and in reducing bronchial hyperresponsiveness. It seems therefore important to analyze the link between asthma and sinusitis, both in terms of clinical and pathogenic features, as well the therapeutic approach of those patients presenting with these diseases.



Role of Kinase Suppressor of Ras-1 in Lipopolysaccharide-Induced Acute Lung Injury  

PubMed Central

Kinase suppressor of ras-1 (Ksr1) has been recently shown to be a central signaling molecule in the host response to Pseudomonas aeruginosa infections in the lung. Ksr1 functions to regulate the release of nitric oxide (NO)-radicals upon P. aeruginosa infections. Ksr1 also enhances Raf-1/MEK/ERK signaling and is involved in a variety of cellular responses, including cell differentiation, proliferation, and apoptosis. Here, we investigated whether Ksr1 is involved in the host immune response to lipopolysaccharide (LPS), one of the major components of gram-negative bacteria, in the lung. To this end, we induced an acute lung injury in wild type and Ksr1-deficient mice by intratracheal instillation of LPS. We found that LPS-induces acute lung injury, as characterized by cytokine expression, neutrophil infiltration and protein extrusion in wildtype mice. Ksr1-deficient mice showed a very similar reaction to LPS as the wildtype mice. In freshly isolated alveolar macrophages from wild type and Ksr1-deficient mice, LPS increased ERK activation, nuclear translocation of NF?B and expression of inflammatory cytokines and chemokines in a similar pattern. Inhibition of Src or Raf-1 blocked LPS-induced ERK activation. Taken together, these findings indicate that Ksr1 plays a dispensable role in LPS-induced ERK activation in alveolar macrophages and does not contribute to the development of acute lung injury in the LPS model.

Li, Xiang; Gulbins, Erich; Zhang, Yang



Gap Junction Channel Modulates Pulmonary Vascular Permeability through Calcium in Acute Lung Injury: An Experimental Study  

Microsoft Academic Search

Background: Increased pulmonary vascular permeability is a hallmark of acute lung injury (ALI). Gap junction channels (GJCs) connect adjacent cells and facilitate ion exchange. It remained unclear whether GJCs modulate pulmonary permeability in ALI through intracellular calcium. Objectives: This study aimed to verify if GJCs in pulmonary microvessel endothelial cells (PMVECs) modulate pulmonary vascular permeability in ALI via intracellular calcium.

Jinzhou Zhang; Wen Wang; Jing Sun; Qiang Li; Jincheng Liu; Hailong Zhu; Tao Chen; Hongbing Wang; Shiqiang Yu; Guocheng Sun; Wensheng Chen; Dinghua Yi



Cardiovascular stability during arteriovenous extracorporeal therapy: a randomized controlled study in lambs with acute lung injury  

Microsoft Academic Search

INTRODUCTION: Clinical application of arteriovenous (AV) extracorporeal membrane oxygenation (ECMO) requires assessment of cardiovascular ability to respond adequately to the presence of an AV shunt in the face of acute lung injury (ALI). This ability may be age dependent and vary with the experimental model. We studied cardiovascular stability in a lamb model of severe ALI, comparing conventional mechanical ventilation

Balagangadhar R Totapally; Jeffrey B Sussmane; Dan Torbati; Javier Gelvez; Harun Fakioglu; Yongming Mao; Jose L Olarte; Jack Wolfsdorf



Effect of abdominal trauma on hemorrhagic shock-induced acute lung injury in rats  

Microsoft Academic Search

AIM: To evaluate the effects of abdominal trauma on hemorrhagic shock-induced acute lung injury in rats. METHODS: Five groups were allocated (n = 8) in the study. Group I was taken as the control group, group II as the hemorrhagic shock group, group III as hemorrhagic shock + laparotomy, group IV as hemor- rhagic shock + splenectomy and group V

Bulent Kilicoglu; Erol Eroglu; Sibel Serin Kilicoglu; Kemal Kismet; Fusun Eroglu; Kilicoglu SS



Towards the prevention of acute lung injury: a population based cohort study protocol  

Microsoft Academic Search

BACKGROUND: Acute lung injury (ALI) is an example of a critical care syndrome with limited treatment options once the condition is fully established. Despite improved understanding of pathophysiology of ALI, the clinical impact has been limited to improvements in supportive treatment. On the other hand, little has been done on the prevention of ALI. Olmsted County, MN, geographically isolated from

Sweta J Thakur; Cesar A Trillo-Alvarez; Michael M Malinchoc; Rahul Kashyap; Lokendra Thakur; Adil Ahmed; Martin K Reriani; Rodrigo Cartin-Ceba; Jeff A Sloan; Ognjen Gajic



A phase 1 trial of nebulised heparin in acute lung injury  

Microsoft Academic Search

INTRODUCTION: Animal studies of acute lung injury (ALI) suggest nebulised heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. No human studies have been undertaken to date. We assessed the feasibility, safety and potential anticoagulant effects of administration of nebulised heparin to patients with ALI. METHODS: An open label phase 1 trial of four escalating doses

Barry Dixon; John D Santamaria; Duncan J Campbell




EPA Science Inventory

We have previously demonstrated in CD-1 mice that pre-administration of N-acetyl cysteine (NAC) or the p38 MAP kinase inhibitor (SB203580) reduces acute lung injury and inflammation following pulmonary exposures to diesel exhaust particles (DEP) or lipopolysaccharide (LPS). Here ...


Diagnosing acute lung injury in the critically ill: a national survey among critical care physicians  

Microsoft Academic Search

Background Incidence reports on acute lung injury (ALI) vary widely. An insight into the diagnostic preferences of critical care physicians when diagnosing ALI may improve identification of the ALI patient population. Methods Critical care physicians in the Netherlands were surveyed using vignettes involving hypothetical patients and a questionnaire. The vignettes varied in seven diagnostic determinants based on the North American

A. P. J. Vlaar; W. B. Honselaar; J. M. Binnekade; A. B. Groeneveld; P. E. Spronk; M.J. Schultz; N. P. Juffermans



Gene Expression Profiles Characterize Inflammation Stages in the Acute Lung Injury in Mice  

Microsoft Academic Search

Acute Lung Injury (ALI) carries about 50 percent mortality and is frequently associated with an infection (sepsis). Life-support treatment with mechanical ventilation rescues many patients, although superimposed infection or multiple organ failure can result in death. The outcome of a patient developing sepsis depends on two factors: the infection and the pre-existing inflammation. In this study, we described each stage

Isabelle Lesur; Julien Textoris; Béatrice Loriod; Cécile Courbon; Stéphane Garcia; Marc Leone; Catherine Nguyen; Carol Feghali-Bostwick



Lung disease in FLNA mutation: confirmatory report.  


Recently in this journal, Masurel-Paulet et al. reported the association between pulmonary disease and a mutation in X-linked FLNA in a male patient. We confirm this association in a female patient, showing that this complication is not sex-specific. Our patient has a FLNA missense mutation (c.220G > A) and presented with cerebral periventricular nodular heterotopia, cardiovascular abnormalities, and pulmonary disease consisting of lobar emphysema of the right middle pulmonary lobe with severe malacia of the right sided bronchus intermedius. Surgical resection of the right middle lobe was necessary and she had long-term oxygen dependency. Symptoms improved with age. PMID:21194575

de Wit, M C Y; Tiddens, H A W M; de Coo, I F M; Mancini, G M S



Chronic kidney disease in acute coronary syndromes  

PubMed Central

Chronic kidney disease (CKD) is associated with a high burden of coronary artery disease. In patients with acute coronary syndromes (ACS), CKD is highly prevalent and associated with poor short- and long-term outcomes. Management of patients with CKD presenting with ACS is more complex than in the general population because of the lack of well-designed randomized trials assessing therapeutic strategies in such patients. The almost uniform exclusion of patients with CKD from randomized studies evaluating new targeted therapies for ACS, coupled with concerns about further deterioration of renal function and therapy-related toxic effects, may explain the less frequent use of proven medical therapies in this subgroup of high-risk patients. However, these patients potentially have much to gain from conventional revascularization strategies used in the general population. The objective of this review is to summarize the current evidence regarding the epidemiology and the clinical and prognostic relevance of CKD in ACS patients, in particular with respect to unresolved issues and uncertainties regarding recommended medical therapies and coronary revascularization strategies.

Marenzi, Giancarlo; Cabiati, Angelo; Assanelli, Emilio



Nocturnal hypoxaemia and quality of sleep in patients with chronic obstructive lung disease  

Microsoft Academic Search

Fifty patients with chronic obstructive lung disease were questioned about their sleep quality and their responses were compared with those of 40 similarly aged patients without symptomatic lung disease. Patients with chronic obstructive lung disease reported more difficulty in getting to sleep and staying asleep and more daytime sleepiness than the control group. More than twice as many patients (28%)

W Cormick; L G Olson; M J Hensley; N A Saunders



PPARgamma: a novel molecular target in lung disease.  


Interest in peroxisome proliferator-activated receptors (PPARs) has steadily increased over the past 15 years. The recognition that subclasses of this receptor played critical roles in regulation of metabolism led to the development of synthetic ligands and their widespread application in the treatment of type 2 diabetes. At the same time, emerging evidence demonstrated that the influence of PPARs extends well beyond metabolism and diabetes. A salient example of this can be seen in studies that explore the role of PPARs in lung cell biology. In fact, current literature suggests that PPAR receptors may well represent exciting new targets for treatment in a variety of lung disorders. In an attempt to keep the scientific and medical communities abreast of these developments, a symposium sponsored by the American Federation for Medical Research entitled "PPARgamma: A Novel Molecular Target in Lung Disease" was convened on April 29, 2007, at the Experimental Biology Meeting in Washington, DC. During that symposium, 4 speakers reviewed the latest developments in basic and translational research as they relate to specific lung diseases. Jesse Roman, MD, professor and director of the Emory University Division of Pulmonary, Allergy, and Critical Care Medicine, reviewed the role of PPARgamma in the pathogenesis of lung cancer and its implications for therapy. Raju Reddy, MD, assistant professor of Medicine at the University of Michigan, presented data regarding the immunomodulatory role of PPARgamma in alveolar macrophages. Patricia J. Sime, MD, associate professor of Medicine, Environmental Medicine, and Oncology at the University of Rochester School of Medicine, discussed the antifibrogenic potential of PPARgamma ligands in pulmonary fibrosis. Finally, C. Michael Hart, MD, professor of Medicine at Emory University and chief of the Atlanta Veterans Affairs Medical Center Pulmonary Section, reviewed the role of PPARgamma in pulmonary vascular disease. This brief introduction to the symposium will provide background information about PPARs to facilitate the general reader's appreciation of the more in-depth and disease-specific discussions that follow. PMID:18317433

Hart, C Michael; Roman, Jesse; Reddy, Raju; Sime, Patricia J