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Sample records for pneumonitis

  1. Pneumonitis

    MedlinePlus

    ... of lung inflammation. Common causes of pneumonitis include airborne irritants at your job or from your hobbies. ... alveoli into the bloodstream. Many irritants, ranging from airborne molds to chemotherapy drugs, have been linked to ...

  2. Hypersensitivity pneumonitis

    MedlinePlus

    Hypersensitivity pneumonitis usually occurs in people who work in places where there are high levels of organic dusts, fungus, or molds. Long-term exposure can lead to lung inflammation and acute lung disease . ...

  3. [Minocycline pneumonitis and eosinophilia].

    PubMed

    Fink, N; Mouallem, M

    2000-06-15

    Pneumonitis with eosinophilia is one of the less common and severe adverse effects of minocycline. The disease evolves in days or weeks from the beginning of treatment, and is usually characterized by dyspnea, fever and bilateral infiltrates in the chest X-ray. With cessation of the antibiotic, and sometimes adding cortico-steroids, clinical and roentgenological resolution follow. We present a case given minocycline for folliculitis and 3 weeks later fever, cough and shortness of breath developed. The clinical and roentgenological course was consistent with minocycline pneumonitis accompanied by eosinophilia.

  4. Chronic hypersensitivity pneumonitis

    PubMed Central

    Pereira, Carlos AC; Gimenez, Andréa; Kuranishi, Lilian; Storrer, Karin

    2016-01-01

    Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. PMID:27703382

  5. Acute mercurial pneumonitis

    PubMed Central

    Milne, James; Christophers, Allen; Silva, Pamela De

    1970-01-01

    Milne, J., Christophers, A., and de Silva, Pamela (1970).Brit. J. industr. Med.,27, 334-338. Acute mercurial pneumonitis. Mercury vapour has been shown to cause acute effects on the lung when inhaled in high concentrations. Four men, exposed to mercury inside a tank, developed, hours later, signs and symptoms of an acute febrile illness with severe pulmonary irritation, characterized by fever, rigors, cough, dyspnoea, and tightness in the chest. A review of the literature revealed that this syndrome had been described and investigated previously in fewer than 20 cases during the past 40 years, and is apparently little known. Fatalities have been described, particularly in children, and necropsy evidence has consistently revealed the pattern of an acute diffuse interstitial pneumonitis, accompanied by profuse fibrinous exudation and erosion of the bronchial and bronchiolar lining. The two common features in all reports are the heating of mercury or the entering into a confined space, or both. Adequate respiratory protection by an efficient air-supplied respirator is mandatory in industrial circumstances of the kind described in this report. PMID:5488692

  6. Pneumonic Plague Cluster, Uganda, 2004

    PubMed Central

    Asiki, Gershim; Anywaine, Zaccheus; Yockey, Brook; Schriefer, Martin E.; Aleti, Philliam; Ogen-Odoi, Asaph; Staples, J. Erin; Sexton, Christopher; Bearden, Scott W.; Kool, Jacob L.

    2006-01-01

    The public and clinicians have long-held beliefs that pneumonic plague is highly contagious; inappropriate alarm and panic have occurred during outbreaks. We investigated communicability in a naturally occurring pneumonic plague cluster. We defined a probable pneumonic plague case as an acute-onset respiratory illness with bloody sputum during December 2004 in Kango Subcounty, Uganda. A definite case was a probable case with laboratory evidence of Yersinia pestis infection. The cluster (1 definite and 3 probable cases) consisted of 2 concurrent index patient–caregiver pairs. Direct fluorescent antibody microscopy and polymerase chain reaction testing on the only surviving patient's sputum verified plague infection. Both index patients transmitted pneumonic plague to only 1 caregiver each, despite 23 additional untreated close contacts (attack rate 8%). Person-to-person transmission was compatible with transmission by respiratory droplets, rather than aerosols, and only a few close contacts, all within droplet range, became ill. PMID:16704785

  7. Pneumonitis and pneumonia after aspiration

    PubMed Central

    Son, Young Gon; Shin, Jungho

    2017-01-01

    Aspiration pneumonitis and aspiration pneumonia are clinical syndromes caused by aspiration. These conditions are clinically significant due to their high morbidity and mortality. However, aspiration as a preceding event are often unwitnessed, particularly in cases of asymptomatic or silent aspiration. Furthermore, despite the difference in treatment approaches for managing aspiration pneumonitis and aspiration pneumonia, these two disease entities are often difficult to discriminate from one another, resulting in inappropriate treatment. The use of unclear terminologies hinders the comparability among different studies, making it difficult to produce evidence-based conclusions and practical guidelines. We reviewed the most recent studies to define aspiration, aspiration pneumonitis, and aspiration pneumonia, and to further assess these conditions in terms of incidence and epidemiology, pathophysiology, risk factors, diagnosis, management and treatment, and prevention. PMID:28879323

  8. Aripiprazole-induced hypersensitivity pneumonitis.

    PubMed

    Gunasekaran, Kulothungan; Murthi, Swetha; Jennings, Jeffrey; Lone, Nazir

    2017-05-09

    Aripiprazole is an atypical antipsychotic agent commonly used in the management of schizophrenia. Aripiprazole has not been reported to have an association with interstitial lung disease. We describe a case of a 36-year-old woman who began to experience respiratory issues shortly after starting aripiprazole and presented to us 4 years later with progressive exertional shortness of breath. High-resolution CT of the chest showed a bilateral ground glass pattern. Video-assisted thoracoscopy with biopsy revealed alveolar septal thickening and an inflammatory infiltrate composed mainly of lymphocytes, suggestive of chronic hypersensitivity pneumonitis. After discontinuing aripiprazole and initiating prednisolone therapy, the patient's pulmonary symptoms improved. This case highlights that aripiprazole can cause hypersensitivity pneumonitis in susceptible individuals. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Hypersensitivity pneumonitis: an immunopathology review.

    PubMed

    Woda, Bruce A

    2008-02-01

    Hypersensitivity pneumonitis (HSP) is an immunologically mediated alveolar and interstitial lung disease caused by repeated inhalation of organic dusts and some occupational agents. The pathogenesis of HSP is uncertain. A number of unexplained features of HSP remain, namely (1) why do so few exposed individuals develop clinical HSP, (2) what triggers an acute episode after prolonged periods of previous sensitization, and (3) what leads to disease progression. This article considers these issues and aims to discuss and clarify current concepts in pathogenesis. Pertinent literature review in conjunction with the author's personal interpretive opinion. Current data suggest that individuals with a T(H)1 dominant response are likely to develop clinical disease. There is also some evidence that genetic factors such as polymorphisms in the major histocompatibility complex, tumor necrosis factor alpha, and tissue inhibitor of metalloproteinase 3 are associated with the development of or resistance to the disease.

  10. Cockatiel-induced hypersensitivity pneumonitis.

    PubMed

    McCluskey, James D; Haight, Robert R; Brooks, Stuart M

    2002-07-01

    Diagnosing an environmental or occupationally related pulmonary disorder often involves a process of elimination. Unlike commonly diagnosed conditions in other specialties, a cause-and-effect relationship may be implied, yet other factors such as temporality and biologic plausibility are lacking. Our patient was referred with a suspected work-related pulmonary disorder. For several years, she had suffered with dyspnea on exertion and repeated flulike illnesses. She worked at an automobile repair garage that performed a large number of emission tests, and there was concern that her workplace exposures were the cause of her symptoms. After a careful review of her history, physical examination, and laboratory testing, we came to the conclusion that she had hypersensitivity pneumonitis related to pet cockatiels in her home. Clinical points of emphasis include the importance of a complete environmental history and careful auscultation of the chest when performing the physical examination. In addition, we encountered an interesting physical diagnostic clue, a respiratory sound that assisted with the eventual diagnosis.

  11. Cockatiel-induced hypersensitivity pneumonitis.

    PubMed Central

    McCluskey, James D; Haight, Robert R; Brooks, Stuart M

    2002-01-01

    Diagnosing an environmental or occupationally related pulmonary disorder often involves a process of elimination. Unlike commonly diagnosed conditions in other specialties, a cause-and-effect relationship may be implied, yet other factors such as temporality and biologic plausibility are lacking. Our patient was referred with a suspected work-related pulmonary disorder. For several years, she had suffered with dyspnea on exertion and repeated flulike illnesses. She worked at an automobile repair garage that performed a large number of emission tests, and there was concern that her workplace exposures were the cause of her symptoms. After a careful review of her history, physical examination, and laboratory testing, we came to the conclusion that she had hypersensitivity pneumonitis related to pet cockatiels in her home. Clinical points of emphasis include the importance of a complete environmental history and careful auscultation of the chest when performing the physical examination. In addition, we encountered an interesting physical diagnostic clue, a respiratory sound that assisted with the eventual diagnosis. PMID:12117652

  12. A diagnostic model for chronic hypersensitivity pneumonitis.

    PubMed

    Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

    2016-10-01

    The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist's diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. A diagnostic model for chronic hypersensitivity pneumonitis

    PubMed Central

    Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

    2017-01-01

    The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist’s diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. PMID:27245779

  14. Lung Transplantation for Hypersensitivity Pneumonitis

    PubMed Central

    Singer, Jonathan P.; Koth, Laura; Mooney, Joshua; Golden, Jeff; Hays, Steven; Greenland, John; Wolters, Paul; Ghio, Emily; Jones, Kirk D.; Leard, Lorriana; Kukreja, Jasleen; Blanc, Paul D.

    2015-01-01

    BACKGROUND: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). METHODS: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. RESULTS: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. CONCLUSIONS: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. PMID:25412059

  15. [A case of flomoxef-induced pneumonitis].

    PubMed

    Wako, Y; Hamauzu, T; Tamura, M; Yokote, M; Yokote, M; Shoji, S; Takikawa, H; Miyake, K; Yamanaka, M; Goto, H

    1992-04-01

    We report a case of flomoxef-induced pneumonitis. A 22-year-old man was treated with flomoxef following liver biopsy. A few days later he developed a high fever and severe dyspnea, and his chest X-ray film revealed diffuse reticulo-nodular shadows in both lung fields. We suspected interstitial pneumonitis due to flomoxef, and pulse therapy with methylprednisolone was started. He showed rapid recovery of symptoms and marked regression of pulmonary infiltration in his chest X-ray. Lymphocyte stimulation test was positive to flomoxef, which was compatible with the diagnosis of drug-induced pneumonitis. To our knowledge, there has been no previous case of pulmonary hypersensitivity to flomoxef reported in Japan.

  16. Vaccination against bubonic and pneumonic plague.

    PubMed

    Titball, R W; Williamson, E D

    2001-07-20

    Yersinia pestis is the etiological agent of bubonic and pneumonic plague, diseases which have caused over 200 milllion human deaths in the past. Plague still occurs throughout the world today, though for reasons that are not fully understood pandemics of disease do not develop from these outbreaks. Antibiotic treatment of bubonic plague is usually effective, but pneumonic plague is difficult to treat and even with antibiotic therapy death often results. A killed whole cell plague vaccine has been used in the past, but recent studies in animals have shown that this vaccine offers poor protection against pneumonic disease. A live attenuated vaccine is also available. Whilst this vaccine is effective, it retains some virulence and in most countries it is not considered to be suitable for use in humans. We review here work to develop improved sub-unit and live attenuated vaccines against plague. A sub-unit vaccine based on the F1- and V-antigens is highly effective against both bubonic and pneumonic plague, when tested in animal models of disease. This vaccine has been used to explore the utility of different intranasal and oral delivery systems, based on the microencapsulation or Salmonella delivery of sub-units.

  17. Occupational hypersensitivity pneumonitis in a koji brewer.

    PubMed

    Ishiguro, Takashi; Kawai, Shoko; Kojima, Ayako; Shimizu, Yoshihiko; Kamei, Katsuhiko; Takayanagi, Noboru

    2018-03-01

    Koji is a fermenting agent used in many traditional Japanese foods , and Aspergillus oryzae is the most frequently used microorganism in koji production. Few cases of hypersensitivity pneumonitis due to A. oryzae have been reported. However, physicians should recognize the disease because of the increasing globalization of food production.

  18. Bubonic and pneumonic plague - Uganda, 2006.

    PubMed

    2009-07-24

    Plague is a life-threatening fleaborne disease caused by the bacterium Yersinia pestis. The most common clinical form is bubonic plague, which is characterized by high fever and regional lymphadenitis. Without treatment, infection can spread from lymph nodes to the lungs, resulting in pneumonic plague and the potential for person-to-person transmission through respiratory droplets. In November 2006, the Uganda Ministry of Health received reports of an increase in bubonic plague cases and a possible outbreak of pneumonic plague among residents in the Arua and Nebbi districts. In response, the Uganda Ministry of Health and CDC conducted a joint investigation in the two districts during November 28-December 30, 2006. Overall, 127 clinical plague cases were identified, along with evidence of a focal pneumonic outbreak in Nebbi District. Median age of the patients was 14 years (range: 2 weeks-65 years); 65 (51%) were female. Twenty-eight (22%) of the 127 patients died. Among the 102 patients with documented symptoms, 90 (88%) had bubonic plague, and 12 (12%) had pneumonic plague. The results of this investigation underscore the need to 1) continue efforts to educate residents of rural Uganda regarding the source, signs, and symptoms of plague and the life-saving importance of seeking treatment; 2) strengthen plague surveillance and diagnostic capabilities; and 3) improve emergency response and vector-control capacity, especially in remote regions of the country.

  19. Pneumonic Plague Transmission, Moramanga, Madagascar, 2015.

    PubMed

    Ramasindrazana, Beza; Andrianaivoarimanana, Voahangy; Rakotondramanga, Jean Marius; Birdsell, Dawn N; Ratsitorahina, Maherisoa; Rajerison, Minoarisoa

    2017-03-01

    During a pneumonic plague outbreak in Moramanga, Madagascar, we identified 4 confirmed, 1 presumptive, and 9 suspected plague case-patients. Human-to-human transmission among close contacts was high (reproductive number 1.44) and the case fatality rate was 71%. Phylogenetic analysis showed that the Yersinia pestis isolates belonged to group q3, different from the previous outbreak.

  20. Pneumonic Plague in Johannesburg, South Africa, 1904

    PubMed Central

    Egan, Joseph R.; Hall, Ian

    2018-01-01

    Plague is a potentially dangerous reemerging disease. Because modern outbreaks are relatively infrequent, data for epidemiologic study are best found in historical accounts. In 1905, the Rand Plague Committee published a report describing an explosive outbreak of 113 cases of pneumonic plague that occurred in Johannesburg, South Africa, in 1904. Using these data, we investigated social, spatial, and temporal dynamics and quantified transmissibility as measured by the time-varying reproduction number. Risk for transmission was highest when friends, family members, and caregivers approached the sick. Reproduction numbers were 2–4. Transmission rates rapidly diminished after implementation of control measures, including isolation and safer burial practices. A contemporaneous smaller bubonic plague outbreak associated with a low-key epizootic of rats also occurred. Clusters of cases of pneumonic plague were mostly limited to the Indian community; cases of bubonic plague were mostly associated with white communities and their black African servants.

  1. Pneumonic Plague Transmission, Moramanga, Madagascar, 2015

    PubMed Central

    Ramasindrazana, Beza; Andrianaivoarimanana, Voahangy; Rakotondramanga, Jean Marius; Birdsell, Dawn N.; Ratsitorahina, Maherisoa

    2017-01-01

    During a pneumonic plague outbreak in Moramanga, Madagascar, we identified 4 confirmed, 1 presumptive, and 9 suspected plague case-patients. Human-to-human transmission among close contacts was high (reproductive number 1.44) and the case fatality rate was 71%. Phylogenetic analysis showed that the Yersinia pestis isolates belonged to group q3, different from the previous outbreak. PMID:28221119

  2. [A case of loxoprofen-induced pneumonitis pathologically resembling hypersensitivity pneumonitis].

    PubMed

    Tohyama, Masaki; Tamaki, Yuichiro; Toyama, Masato; Ishimine, Tomohiko; Miyazato, Akiko; Nakamoto, Atsushi; Miyara, Takayuki; Higa, Futoshi; Tateyama, Masao; Kawakami, Kazuyoshi; Nakamura, Hiroaki; Saito, Atsushi

    2002-02-01

    A 66-year-old woman was admitted to our hospital because of high fever, general fatigue, hypoxemia and liver dysfunction. Chest radiographs showed diffuse interstitial shadows in both lungs. We suspected drug-induced pneumonitis because of her history of drug administration for upper respiratory infection. Her symptoms and findings were markedly decreased by discontinuation of the drugs. Transbronchial lung biopsy specimens showed infiltration of eosinophils and lymphocytes to the alveolar septa, granuloma with Langhans' giant cells, and Masson bodies in a manner suggestive of hypersensitivity pneumonitis. Drug lymphocyte stimulation tests were negative except for loxoprofen. There was no recurrence of systemic or respiratory symptoms during overnight stays at home. On the basis of these findings, we arrived at a diagnosis of drug-induced pneumonitis caused by loxoprofen.

  3. Current challenges in the development of vaccines for pneumonic plague

    PubMed Central

    Smiley, Stephen T

    2008-01-01

    Inhalation of Yersinia pestis bacilli causes pneumonic plague, a rapidly progressing and exceptionally virulent disease. Extensively antibiotic-resistant Y. pestis strains exist and we currently lack a safe and effective pneumonic plague vaccine. These facts raise concern that Y. pestis may be exploited as a bioweapon. Here, I review the history and status of plague vaccine research and advocate that pneumonic plague vaccines should strive to prime both humoral and cellular immunity. PMID:18324890

  4. [Nonspecific interstitial pneumonitis: a clinicopathologic entity, histologic pattern or unclassified group of heterogeneous interstitial pneumonitis?].

    PubMed

    Morais, António; Moura, M Conceição Souto; Cruz, M Rosa; Gomes, Isabel

    2004-01-01

    Nonspecific interstitial pneumonitis (NSIP) initially described by Katzenstein and Fiorelli in 1994, seems to be a distinct clinicopathologic entity among idiopathic interstitial pneumonitis (IIP). Besides different histologic features from other IIP, NSIP is characterized by a better long-term outcome, associated with a better steroids responsiveness than idiopathic pulmonar fibrosis (IPF), where usually were included. Thus, differentiating NSIP from other IIP, namely IPF is very significant, since it has important therapeutic and prognostic implications. NSIP encloses different pathologies, namely those with inflammatory predominance (cellular subtype) or fibrous predominance (fibrosing subtype). NSIP is reviewed and discussed by the authors, after two clinical cases description.

  5. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hypersensitivity pneumonitis immunological test...

  6. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

  7. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

  8. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

  9. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

  10. Pneumonic Plague: The Darker Side of Yersinia pestis.

    PubMed

    Pechous, Roger D; Sivaraman, Vijay; Stasulli, Nikolas M; Goldman, William E

    2016-03-01

    Inhalation of the bacterium Yersinia pestis results in primary pneumonic plague. Pneumonic plague is the most severe manifestation of plague, with mortality rates approaching 100% in the absence of treatment. Its rapid disease progression, lethality, and ability to be transmitted via aerosol have compounded fears of the intentional release of Y. pestis as a biological weapon. Importantly, recent epidemics of plague have highlighted a significant role for pneumonic plague during outbreaks of Y. pestis infections. In this review we describe the characteristics of pneumonic plague, focusing on its disease progression and pathogenesis. The rapid time-course, severity, and difficulty of treating pneumonic plague highlight how differences in the route of disease transmission can enhance the lethality of an already deadly pathogen. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Occupational hypersensitivity pneumonitis: an EAACI position paper.

    PubMed

    Quirce, S; Vandenplas, O; Campo, P; Cruz, M J; de Blay, F; Koschel, D; Moscato, G; Pala, G; Raulf, M; Sastre, J; Siracusa, A; Tarlo, S M; Walusiak-Skorupa, J; Cormier, Y

    2016-06-01

    The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. CT findings in hydrocarbon pneumonitis after diesel fuel siphonage.

    PubMed

    Yi, Mi Seon; Kim, Kun-Il; Jeong, Yeon Joo; Park, Hye Kyung; Lee, Min Ki

    2009-10-01

    The purpose of this study was to assess CT findings in a series of patients with hydrocarbon pneumonitis after diesel fuel siphonage. The characteristic CT findings of hydrocarbon pneumonitis after diesel fuel siphonage are the presence of air-space consolidations with predominant right middle lobe involvement and areas of low attenuation within consolidation. Occasionally, bronchoalveolar lavage is needed to confirm the diagnosis of hydrocarbon pneumonitis by the presence of lipid-laden macrophages on the basis of a history of diesel fuel aspiration.

  13. Pneumonic Plague Outbreak, Northern Madagascar, 2011

    PubMed Central

    Richard, Vincent; Herindrainy, Perlinot; Soanandrasana, Rahelinirina; Ratsitoharina, Maherisoa; Rakotomanana, Fanjasoa; Andrianalimanana, Samuel; Scholz, Holger C.; Rajerison, Minoarisoa

    2015-01-01

    Yersinia pestis, the causative agent of plague, is endemic to Madagascar, particularly to the central highlands. Although plague has not been previously reported in northern Madagascar, an outbreak of pneumonic plague occurred in this remote area in 2011. Over a 27-day period, 17 suspected, 2 presumptive, and 3 confirmed human cases were identified, and all 15 untreated 20 patients died. Molecular typing of Y. pestis isolated from 2 survivors and 5 Rattus rattus rat samples identified the Madagascar-specific 1.ORI3-k single-nucleotide polymorphism genotype and 4 clustered regularly interspaced short palindromic repeat patterns. This outbreak had a case-fatality rate of 100% for nontreated patients. The Y. pestis 1.ORI3-k single-nucleotide polymorphism genotype might cause larger epidemics. Multidrug-resistant strains and persistence of the pathogen in natural foci near human settlements pose severe risks to populations in plague-endemic regions and require outbreak response strategies. PMID:25530466

  14. Pneumonitis in Adult Onset Still's Disease: Uncommon or Under Diagnosed?

    PubMed

    Fernandes, Silvia; Almeida, Margarida; Pereira da Silva, José Alberto; Romeu, José Carlos

    2017-08-31

    The adult onset Still's Disease is an uncommon entity characterized by multiple clinical manifestations. Pneumonitis, less often considered, deserves particular emphasis given the need for differential diagnosis and because it can progress to severe respiratory failure. With the aim to highlight the pulmonary parenchyma involvement in patients with adult onset Still's Disease, we present a case report which progresses with pneumonitis.

  15. Turpentine-induced chemical pneumonitis with broncho-pleural fistula.

    PubMed

    Rodricks, A; Satyanarayana, M; D'Souza, G A; Ramachandran, P

    2003-07-01

    Turpentine is a volatile hydrocarbon used in polishes, solvents, paints and textile industry. When hydrocarbons are aspirated into the lung, they cause chemical pneumonitis, acute respiratory distress syndrome (ARDS), and rarely pneumatoceles and pneumothorax. We report a 20-year old boy with turpentine-induced chemical pneumonitis that evolved into a bronchopleural fistula. He was treated with oxygen, steroids and intercostal tube drainage. This is the first reported case of turpentine-associated bronchopleural fistula.

  16. Lung Size and the Risk of Radiation Pneumonitis

    SciTech Connect

    Briere, Tina Marie, E-mail: tmbriere@mdanderson.org; Krafft, Shane; Liao, Zhongxing

    2016-02-01

    Purpose: The purpose of this study was to identify patient populations treated for non-small cell lung cancer (NSCLC) who may be more at risk of radiation pneumonitis. Methods and Materials: A total of 579 patients receiving fractionated 3D conformal or intensity modulated radiation therapy (IMRT) for NSCLC were included in the study. Statistical analysis was performed to search for cohorts of patients with higher incidences of radiation pneumonitis. In addition to conventional risk factors, total and spared lung volumes were analyzed. The Lyman-Kutcher-Burman (LKB) and cure models were then used to fit the incidence of radiation pneumonitis as a functionmore » of lung dose and other factors. Results: Total lung volumes with a sparing of less than 1854 cc at 40 Gy were associated with a significantly higher incidence of radiation pneumonitis at 6 months (38% vs 12% for patients with larger volumes, P<.001). This patient cohort was overwhelmingly female and represented 22% of the total female population of patients and nearly 30% of the cases of radiation pneumonitis. An LKB fit to normal tissue complication probability (NTCP) including volume as a dose modifying factor resulted in a dose that results in a 50% probability of complication for the smaller spared volume cohort that was 9 Gy lower than the fit to all mean lung dose data and improved the ability to predict radiation pneumonitis (P<.001). Using an effective dose parameter of n=0.42 instead of mean lung dose further improved the LKB fit. Fits to the data using the cure model produced similar results. Conclusions: Spared lung volume should be considered when treating NSCLC patients. Separate dose constraints based on smaller spared lung volume should be considered. Smaller spared lung volume patients should be followed closely for signs of radiation pneumonitis.« less

  17. Pneumonic plague pathogenesis and immunity in Brown Norway rats.

    PubMed

    Anderson, Deborah M; Ciletti, Nancy A; Lee-Lewis, Hanni; Elli, Derek; Segal, Joshua; DeBord, Kristin L; Overheim, Katie A; Tretiakova, Maria; Brubaker, Robert R; Schneewind, Olaf

    2009-03-01

    The Brown Norway rat was recently described as a bubonic plague model that closely mimics human disease. We therefore evaluated the Brown Norway rat as an alternative small animal model for pneumonic plague and characterized both the efficacy and potency of vaccine candidates. When infected by intranasal instillation, these rats rapidly developed fatal pneumonic plague within 2 to 4 days of infection. Plague disease was characterized by severe alveolar edema and vascular hemorrhage in the lung in addition to fulminant necrotizing pneumonia caused by massive bacterial replication and inflammation. Twenty-four hours before death, animals developed systemic disease with an apparent delayed inflammatory response. We evaluated the ability of the protective antigen, LcrV, and a mutant derivative, V10, to protect these rats from pneumonic plague. Both were highly effective vaccines because complete protection was observed at challenge doses of 7500 LD(50). Antibody analyses suggested stronger potency of V10 immune sera compared with LcrV in the passive transfer of immunity to bubonic plague, with multiple neutralizing epitopes in LcrV. Taken together, these data demonstrate the effectiveness of inhibiting type III secretion in the prevention of pneumonic plague in rats and reveal critical contributions from both the cellular and humoral immune systems. Thus, the Brown Norway rat is an appealing alternative small animal model for the study of pneumonic plague pathogenesis and immunity.

  18. Hypersensitivity pneumonitis: a complex lung disease.

    PubMed

    Riario Sforza, Gian Galeazzo; Marinou, Androula

    2017-01-01

    Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma and specifically the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction. Such reaction is secondary to a repeated and prolonged inhalation of different types of organic dusts or other substances to which the patient is sensitized and hyper responsive, primarily consisting of organic dusts of animal or vegetable origin, more rarely from chemicals. The prevalence of HP is difficult to evaluate because of uncertainties in detection and misdiagnosis and lacking of widely accepted diagnostic criteria, and varies considerably depending on disease definition, diagnostic methods, exposure modalities, geographical conditions, agricultural and industrial practices, and host risk factors. HP can be caused by multiple agents that are present in work places and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals. The number of environment, settings and causative agents is increasing over time. From the clinical point of view HP can be divided in acute/subacute and chronic, depending on the intensity and frequency of exposure to causative antigens. The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties to identify the agent or because its avoidance may lead to major changes in life style or occupational settings. HP is a complex syndrome that needs urgently for more stringent and selective diagnostic criteria and validation, including wider panels of IgG, and a closer collaboration with occupational physicians, as part of a multidisciplinary expertise.

  19. Hypersensitivity pneumonitis due to flavocoxid: are corticosteroids necessary?

    PubMed

    Panduranga, Veena; Atienza, Jonessa; Kumar, Anupam; Metersky, Mark L

    2013-02-01

    Hypersensitivity pneumonitis (HP) is a rare adverse event with flavocoxid (Limbrel) use. Patients present with nonspecific symptoms after exposure to an inciting agent. A 42-year-old female presented with worsening dyspnea on exertion and pleuritic midsternal chest pain. Her symptoms failed to abate with outpatient azithromycin for a diagnosis of community-acquired pneumonia. She was seen again at the emergency department (ED) due to symptom progression and exertional hypoxia. Chest reoentgenogram (x-ray) and computed tomography (CT) chest revealed bilateral infiltrates. Her history was significant for initiation of flavocoxid (Limbrel) two weeks prior, and a diagnosis of hypersensitivity pneumonitis was made. Once flavocoxid was discontinued, symptoms and radiologic studies improved without requiring biopsy or steroids. Hypersensitivity pneumonitis is associated with many pharmacological agents and is challenging to diagnose, given nonspecific symptoms and radiologic findings. In the absence of specific indications to use corticosteroids, symptoms of HP might resolve with cessation of the offending agent, as proven by this case.

  20. Successful osimertinib rechallenge after osimertinib-induced pneumonitis in a patient with lung adenocarcinoma.

    PubMed

    Satoh, Shingo; Shiroyama, Takayuki; Tamiya, Motohiro; Nasu, Shingo; Tanaka, Ayako; Morita, Satomu; Morishita, Naoko; Suzuki, Hidekazu; Okamoto, Norio; Hirashima, Tomonori

    2018-01-01

    Pneumonitis is a serious adverse event of EGFR-TKI treatment. Although several cases of EGFR-TKI rechallenge after EGFR-TKI-induced pneumonitis have been reported, little is known about post-pneumonitis osimertinib rechallenge. We describe a 69-year-old never-smoking Japanese woman with postoperative recurrent lung adenocarcinoma retreated with osimertinib after osimertinib-induced pneumonitis. Although osimertinib rechallenge must be carefully chosen based on risk/benefit analysis, osimertinib rechallenge after osimertinib-induced pneumonitis may be an option, with limited alternative therapeutic options.

  1. Interstitial pneumonitis after acetylene welding: a case report.

    PubMed

    Brvar, Miran

    2014-01-01

    Acetylene is a colorless gas commonly used for welding. It acts mainly as a simple asphyxiant. In this paper, however, we present a patient who developed a severe interstitial pneumonitis after acetylene exposure during aluminum welding. A 44-year old man was welding with acetylene, argon and aluminum electrode sticks in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea appeared and 22 h later he was admitted at the Emergency Department due to severe respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse interstitial infiltration. Pulmonary function and gas diffusion tests revealed a severe restriction (55% of predictive volume) and impaired diffusion capacity (47% of predicted capacity). Toxic interstitial pneumonitis was diagnosed and high-dose systemic corticosteroid methylprednisolone and inhalatory corticosteroid fluticasone therapy was started. Computed Tomography (CT) of the lungs showed a diffuse patchy ground-glass opacity with no signs of small airway disease associated with interstitial pneumonitis. Corticosteroid therapy was continued for the next 8 weeks gradually reducing the doses. The patient's follow-up did not show any deterioration of respiratory function. In conclusion, acetylene welding might result in severe toxic interstitial pneumonitis that improves after an early systemic and inhalatory corticosteroid therapy.

  2. Acute respiratory failure secondary to mesalamine-induced interstitial pneumonitis.

    PubMed

    Abraham, Albin; Karakurum, Ali

    2013-08-20

    Interstitial pneumonitis as an adverse effect of mesalamine therapy is a rare but potentially serious complication. Patients typically have a mild disease course with no documented cases of respiratory failure in published literature. Given its variable latent period and non-specific signs and symptoms, it may be difficult to diagnose. We present the case of a 65-year-old man who presented with symptoms of fever, shortness of breath and a non-productive cough, 2 weeks after initiation of therapy with mesalamine. His hospital course was complicated by acute respiratory failure requiring intubation and mechanical ventilation. Radiographic studies revealed bilateral lower lobe infiltrates and bronchosopy with bronchoalveolar lavage and transbronchial biopsy were consistent with a diagnosis of drug-induced interstitial pneumonitis. The aim of this paper is to highlight the importance of considering a diagnosis of mesalamine-induced lung injury in patients presenting with respiratory symptoms while on mesalamine therapy and to review relevant literature.

  3. Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging.

    PubMed

    Medhora, Meetha; Haworth, Steven; Liu, Yu; Narayanan, Jayashree; Gao, Feng; Zhao, Ming; Audi, Said; Jacobs, Elizabeth R; Fish, Brian L; Clough, Anne V

    2016-08-01

    Our goal is to develop minimally invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently, there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in radiologic terrorism. Our previous studies have shown that a single dose of 15 Gy of x-rays to the thorax causes severe pneumonitis in rats by 6-8 wk. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 wk after radiation. We used 2 functional SPECT probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of (99m)Tc-macroaggregated albumin. Perfused volume was determined by comparing the volume of distribution of (99m)Tc-macroaggregated albumin to the anatomic lung volume obtained by small-animal CT. A second probe, (99m)Tc-labeled Duramycin, which binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. The perfused volume of lung was decreased by about 25% at 1, 2, and 3 wk after receipt of 15 Gy, and (99m)Tc-Duramycin uptake was more than doubled at 2 and 3 wk. There was no change in body weight, breathing rate, or lung histology between irradiated and nonirradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 wk after 15 Gy of irradiation. Our results suggest that SPECT biomarkers have the potential to predict radiation injury to the lungs before substantial functional or histologic damage is observed. Early prediction of radiation pneumonitis in time to initiate mitigation will benefit those exposed to radiation in the context of therapy, accidents, or terrorism. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  4. Biomarkers for radiation pneumonitis using non-invasive molecular imaging

    PubMed Central

    Medhora, Meetha; Haworth, Steven; Liu, Yu; Narayanan, Jayashree; Gao, Feng; Zhao, Ming; Audi, Said; Jacobs, Elizabeth R.; Fish, Brian L.; Clough, Anne V.

    2016-01-01

    Rationale Our goal is to develop minimally-invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in case of radiological terrorism. Our previous studies have shown a single dose of 15 Gy X-rays to the thorax causes severe pneumonitis in rats by 6–8 weeks. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 weeks after radiation. Methods We used two functional single photon emission computed tomography (SPECT) probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of technetium labeled macroaggregated albumin (99mTc-MAA). Perfused volume was determined by comparing the volume of distribution of 99mTc-MAA to the anatomical lung volume obtained by micro-CT. A second probe, technetium labeled duramycin that binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. Results Perfused volume of lung was decreased by ~25% at 1, 2 and 3 weeks after 15 Gy and 99mTc-duramycin uptake was more than doubled at 2 and 3 weeks. There was no change in body weight, breathing rate or lung histology between irradiated and non-irradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 weeks after 15 Gy. Principal conclusions Our results suggest the potential for SPECT biomarkers for predicting radiation injury to the lungs before substantial functional or histological damage is observed. Early prediction of radiation pneumonitis will benefit those receiving radiation in the context of therapy, accidents or terrorism in time to initiate mitigation. PMID:27033892

  5. Biodefense-driven murine model of pneumonic melioidosis.

    PubMed

    Jeddeloh, J A; Fritz, D L; Waag, D M; Hartings, J M; Andrews, G P

    2003-01-01

    A whole-body mouse model of pneumonic melioidosis was established for future evaluation of biodefense vaccine candidates. The aerosol 50% lethal doses of Burkholderia pseudomallei strain 1026b for BALB/c and C57BL/6 mice and the times to death, dissemination in organs, and tissue loads after exposure of the mice to low- and high-dose aerosols are reported. In addition, rpsL mutant backgrounds were attenuated in this acute model of disease.

  6. Antibiotic Treatment of Experimental Pneumonic Plague in Mice

    PubMed Central

    Byrne, William R.; Welkos, Susan L.; Pitt, M. Louise; Davis, Kelly J.; Brueckner, Ralf P.; Ezzell, John W.; Nelson, Gene O.; Vaccaro, Joseph R.; Battersby, Luann C.; Friedlander, Arthur M.

    1998-01-01

    A mouse model was developed to evaluate the efficacy of antibiotic treatment of pneumonic plague; streptomycin was compared to antibiotics with which there is little or no clinical experience. Infection was induced by inhalation of aerosolized Yersinia pestis organisms. Antibiotics were administered by intraperitoneal injection every 6 hours for 5 days, at doses that produced levels of drug in serum comparable to those observed in humans treated for other serious infections. These studies compared in vitro to in vivo activity and evaluated the efficacy of antibiotics started at different times after exposure. Early treatment (started 24 h after challenge, when 0 of 10 mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, ceftriaxone, ceftazidime, aztreonam, ampicillin, and rifampin (but not cefazolin, cefotetan, or ceftizoxime) demonstrated efficacy comparable to streptomycin. Late treatment (started 42 h after exposure, when five of five mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, and a high dose (20 mg/kg of body weight every 6 h) of gentamicin produced survival rates comparable to that with streptomycin, while all of the beta-lactam antibiotics (cefazolin, cefotetan, ceftriaxone, ceftazidime, aztreonam, and ampicillin) and rifampin were significantly inferior to streptomycin. In fact, all groups of mice treated late with beta-lactam antibiotics experienced accelerated mortality rates compared to normal-saline-treated control mice. These studies indicate that netilmicin, gentamicin, ciprofloxacin, and ofloxacin may be alternatives for the treatment of pneumonic plague in humans. However, the beta-lactam antibiotics are not recommended, based upon poor efficacy in this mouse model of pneumonic plague, particularly when pneumonic plague may be associated with bacteremia. PMID:9517950

  7. Occupational hypersensitivity pneumonitis in a smelter exposed to zinc fumes

    SciTech Connect

    Ameille, J.; Brechot, J.M.; Brochard, P.

    1992-03-01

    A smelter exposed to zinc fumes reported severe recurrent episodes of cough, dyspnea and fever. Bronchoalveolar lavage showed a marked increase in lymphocytes count with predominance of CD8 T-lymphocytes. Presence of zinc in alveolar macrophages was assessed by analytic transmission electron microscopy. This is the first case of recurrent bronchoalveolitis related to zinc exposure in which the clinical picture and BAL results indicate a probable hypersensitivity pneumonitis.

  8. Levofloxacin Cures Experimental Pneumonic Plague in African Green Monkeys

    PubMed Central

    McDonald, Jacob D.; Brasel, Trevor L.; Barr, Edward B.; Gigliotti, Andrew P.; Koster, Frederick

    2011-01-01

    Background Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease. Methods and Results Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops) were challenged via head-only aerosol inhalation with 3–145 (mean = 65) 50% lethal (LD50) doses of Y. pestis strain CO92. Telemetered body temperature >39°C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a “humanized” dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53–165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions. Conclusion Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen. PMID:21347450

  9. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Chlamydia Psittaci Vaccine (Feline... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall be...

  10. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Chlamydia Psittaci Vaccine (Feline... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall be...

  11. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Chlamydia Psittaci Vaccine (Feline... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall be...

  12. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Chlamydia Psittaci Vaccine (Feline... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall be...

  13. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Chlamydia Psittaci Vaccine (Feline... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall be...

  14. Hypersensitivity pneumonitis and related conditions in the work environment.

    PubMed

    Zacharisen, Michael C; Fink, Jordan N

    2011-11-01

    Hypersensitivity pneumonitis can occur from a wide variety of occupational exposures. Although uncommon and difficult to recognize, through a detailed work exposure history, physical examination, radiography, pulmonary function studies, and selected laboratory studies using sera and bronchoalveolar lavage fluid, workers can be identified early to effect avoidance of the antigen and institute pharmacologic therapy, if necessary. A lung biopsy may be necessary to rule out other interstitial lung diseases. Despite the varied organic antigen triggers, the presentation is similar with acute, subacute, or chronic forms. Systemic corticosteroids are the only reliable pharmacologic treatment but do not alter the long-term outcome. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Metalworking fluid-associated hypersensitivity pneumonitis: a workshop summary.

    PubMed

    Kreiss, K; Cox-Ganser, J

    1997-10-01

    A workshop discussing eight clusters of hypersensitivity pneumonitis in the automotive industry among metalworking fluid-exposed workers concluded that a risk exists for this granulomatous lung disease where water-based fluids are used and unusual microbial contaminants predominate. Strong candidates for microbial etiology are nontuberculous mycobacteria and fungi. Cases of hypersensitivity pneumonitis occur among cases with other work-related respiratory symptoms and chest diseases. Reversibility of disease has occurred in many cases with exposure cessation, allowing return to work to jobs without metalworking fluid exposures or, in some situations, to jobs without the same metalworking fluid exposures. Cases have been recognized with metalworking fluid exposures generally less than 0.5 mg/m3. The workshop participants identified knowledge gaps regarding risk factors, exposure-response relationships, intervention efficacy, and natural history, as well as surveillance needs to define the extent of the problem in this industry. In the absence of answers to these questions, guidance for prevention is necessarily limited.

  16. Acute respiratory failure secondary to mesalamine-induced interstitial pneumonitis

    PubMed Central

    Abraham, Albin; Karakurum, Ali

    2013-01-01

    Interstitial pneumonitis as an adverse effect of mesalamine therapy is a rare but potentially serious complication. Patients typically have a mild disease course with no documented cases of respiratory failure in published literature. Given its variable latent period and non-specific signs and symptoms, it may be difficult to diagnose. We present the case of a 65-year-old man who presented with symptoms of fever, shortness of breath and a non-productive cough, 2 weeks after initiation of therapy with mesalamine. His hospital course was complicated by acute respiratory failure requiring intubation and mechanical ventilation. Radiographic studies revealed bilateral lower lobe infiltrates and bronchosopy with bronchoalveolar lavage and transbronchial biopsy were consistent with a diagnosis of drug-induced interstitial pneumonitis. The aim of this paper is to highlight the importance of considering a diagnosis of mesalamine-induced lung injury in patients presenting with respiratory symptoms while on mesalamine therapy and to review relevant literature. PMID:23964037

  17. Associated factors of radiation pneumonitis induced by precise radiotherapy in 186 elderly patients with esophageal cancer.

    PubMed

    Cui, Zhen; Tian, Ye; He, Bin; Li, Hongwei; Li, Duojie; Liu, Jingjing; Cai, Hanfei; Lou, Jianjun; Jiang, Hao; Shen, Xueming; Peng, Kaigui

    2015-01-01

    Radiation pneumonitis is one of the most severe complications of esophageal cancer. To explore the factors correlated to radiation pneumonitis induced by precise radiotherapy for elderly patients with esophageal cancer. The retrospective analysis was used to collect clinical data from 186 elderly patients with esophageal cancer. The incidence of radiation pneumonitis was observed, followed by statistical analysis through ANVON or multiple regression analysis. 27 in 186 cases of esophageal cancer suffered from radiation pneumonitis, with incidence of 14.52%. The single factor analysis showed that, Karnofsky performance status (KPS) score, chronic obstructive pulmonary disease, concurrent chemoradiotherapy, gross tumor volume (GTV) dose, lung V20, mean lung dose (MLD) and planning target volume (PTV) were associated with radiation pneumonitis. The logistic regression analysis indicated that, concurrent chemoradiotherapy, GTV dose, lung V20 and PTV were the independent factors of radiation pneumonitis. The concurrent chemoradiotherapy, GTV dose, lung V20, MLD and PTV are the major risk factors of radiation pneumonitis for elderly patients with esophageal cancer.

  18. Childhood hypersensitivity pneumonitis associated with fungal contamination of indoor hydroponics.

    PubMed

    Engelhart, Steffen; Rietschel, Ernst; Exner, Martin; Lange, Lars

    2009-01-01

    Childhood hypersensitivity pneumonitis (HP) is often associated with exposure to antigens in the home environment. We describe a case of HP associated with indoor hydroponics in a 14-year-old girl. Water samples from hydroponics revealed Aureobasidium pullulans as the dominant fungal micro-organism (10(4)CFU/ml). The diagnosis is supported by the existence of serum precipitating antibodies against A. pullulans, lymphocytic alveolitis on bronchoalveolar lavage (BAL) fluid, a corresponding reaction on a lung biopsy, and the sustained absence of clinical symptoms following the removal of hydroponics from the home. We conclude that hydroponics should be considered as potential sources of fungal contaminants when checking for indoor health complaints.

  19. Working with argan cake: a new etiology for hypersensitivity pneumonitis.

    PubMed

    Paris, Christophe; Herin, Fabrice; Reboux, Gabriel; Penven, Emmanuelle; Barrera, Coralie; Guidat, Cécile; Thaon, Isabelle

    2015-03-06

    Argan is now used worldwide in numerous cosmetic products. Nine workers from a cosmetic factory were examined in our occupational medicine department, following the diagnosis of a case of hypersensitivity pneumonitis (HP) related to handling of argan cakes. Operators were exposed to three forms of argan (crude granulates, powder or liquid) depending on the step of the process. All workers systematically completed standardized questionnaires on occupational and medical history, followed by medical investigations, comprising, in particular, physical examination and chest X-rays, total IgE and a systematic screening for specific serum antibodies directed against the usual microbial agents of domestic and farmer's HP and antigens derived from microbiological culture and extracts of various argan products. Subjects with episodes of flu-like syndrome several hours after handling argan cakes, were submitted to a one-hour challenge to argan cakes followed by physical examination, determination of Carbon Monoxide Diffusing Capacity (DLCO) and chest CT-scan on day 2, and, when necessary, bronchoalveolar lavage on day 4. Six of the nine workers experienced flu-like symptoms within 8 hours after argan handling. After challenge, two subjects presented a significant decrease of DLCO and alveolitis with mild lymphocytosis, and one presented ground glass opacities. These two patients and another patient presented significant arcs to both granulates and non-sterile powder. No reactivity was observed to sterile argan finished product, antigens derived from argan cultures (various species of Bacillus) and Streptomyces marokkonensis (reported in the literature to contaminate argan roots). We report the first evidence of hypersensitivity pneumonitis related to argan powder in two patients. This implies preventive measures to reduce their exposure and clinical survey to diagnose early symptoms. As exposure routes are different and antibodies were observed against argan powder and not

  20. Epidemiology of Hypersensitivity Pneumonitis among an Insured Population in the United States: A Claims-based Cohort Analysis.

    PubMed

    Fernández Pérez, Evans R; Kong, Amanda M; Raimundo, Karina; Koelsch, Tilman L; Kulkarni, Rucha; Cole, Ashley L

    2018-04-01

    Hypersensitivity pneumonitis is a complex lung disease resulting from repeated inhalation of a variety of antigens. Limited data exist regarding its epidemiology. To describe the trends in the annual incidence and prevalence of hypersensitivity pneumonitis in the United States. We developed novel claims-based coding algorithms to identify hypersensitivity pneumonitis, chronic hypersensitivity pneumonitis, and fibrotic hypersensitivity pneumonitis cases using the 2004 to 2013 MarketScan Commercial and Medicare Supplemental healthcare claims databases. Algorithm validity and reliability were assessed with clinical data from National Jewish Health. We calculated yearly cumulative incidence and prevalence overall and by age. For the subgroup with vital status, Kaplan-Meier methods were used to analyze survival stratified by evidence of fibrosis. We identified 7,498 cases that met our hypersensitivity pneumonitis definition over the 10-year study period, including 3,902 with chronic hypersensitivity pneumonitis and 1,852 with fibrotic hypersensitivity pneumonitis. On the basis of the clinical-radiological adjudication of the validation sample, 38 cases (95%) were confirmed as hypersensitivity pneumonitis. The mean age was 52 years, and 58% were women. The 1-year prevalence rates for hypersensitivity pneumonitis ranged from 1.67 to 2.71 per 100,000 persons, and 1-year cumulative incidence rates ranged from 1.28 to 1.94 per 100,000 persons. The prevalence increased with age, ranging from 0.95 per 100,000 among 0- to 9-year-olds to 11.2 per 100,000 among those aged 65 years and older. Between 56 and 68% of hypersensitivity pneumonitis cases in each year were classified as chronic hypersensitivity pneumonitis (prevalence, 0.91-1.70 per 100,000 persons; cumulative incidence, 0.63-1.08 per 100,000 persons). Fewer had fibrotic hypersensitivity pneumonitis (prevalence, 0.41-0.80 per 100,000 persons; cumulative incidence: 0.29-0.43 per 100,000 persons). Most cases (74%) were

  1. [Human herpesvirus-6 pneumonitis following autologous peripheral blood stem cell transplantation].

    PubMed

    Saitoh, Yuu; Gotoh, Moritaka; Yoshizawa, Seiichiro; Akahane, Daigo; Fujimoto, Hiroaki; Ito, Yoshikazu; Ohyashiki, Kazuma

    2018-01-01

    A-46-year-old man was diagnosed with peripheral T cell lymphoma, not otherwise specified. He achieved a complete remission after pirarubicin, cyclophosphamide, vincristine, and prednisolone (THP-COP) therapy and successful autologous peripheral blood stem-cell transplantation (AutoSCT). However, 6 months post AutoSCT, he complained of fever. Chest computed tomography of the patient displayed bilateral interstitial pneumonitis. Human herpesvirus-6 (HHV-6) DNA was detected in his bronchoalveolar lavage fluid. Therefore, the patient was confirmed for HHV-6 pneumonitis. The treatment with foscarnet was effective, and no relapse was noticed in the patient. Besides, we have experienced pneumonitis of unknown origin in some patients after autologous or allogeneic stem-cell transplantations. Moreover, most of the above patients were clinically diagnosed using serum or plasma markers. Therefore, examining respiratory symptoms after AutoSCT would enable a more accurate diagnosis as well as treatment of patients with HHV-6 pneumonitis.

  2. Lupus pneumonitis as the initial presentation of systemic lupus erythematosus: case series from a single institution.

    PubMed

    Wan, S A; Teh, C L; Jobli, A T

    2016-11-01

    Objective The aim of this study was to examine the clinical features, treatment and outcome of systemic lupus erythematosus (SLE) patients in our centre who presented with lupus pneumonitis as the initial manifestation. Methods We performed a retrospective review of all patients who presented with lupus pneumonitis during the initial SLE manifestation from March 2006 to March 2015. Results There were a total of five patients in our study who presented with fever and cough as the main clinical features. All patients had pulmonary infiltrates on chest radiographs. High-resolution computed tomography, which was performed in two patients, showed ground glass opacities with patchy consolidations bilaterally. All patients received high-dose steroids, 80% received intravenous cyclophosphamide and 60% received intravenous immunoglobulin. Two patients died from severe lupus pneumonitis within 2 weeks of admission despite treatment with ventilation, steroids, cyclophosphamide and intravenous immunoglobulin. Conclusions Acute lupus pneumonitis is an uncommon presentation of SLE. Mortality in this case series is 40%.

  3. Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells.

    PubMed

    Bewig, B; Haacke, T C; Tiroke, A; Bastian, A; Böttcher, H; Hirt, S W; Rautenberg, P; Haverich, A

    2000-01-01

    Cytomegalovirus (CMV) is known as a common pathogen causing infections after lung transplantation. Rapid diagnosis of CMV infection is important for the initiation of a specific treatment. Evaluation of methods for the rapid diagnosis of CMV pneumonitis. The detection rates of CMV DNA in bronchoalveolar lavage (BAL) and bronchial brushes by polymerase chain reaction (PCR), of viral antigens (p52 and IE1) in BAL and of pp65 antigen in peripheral blood leukocytes were compared to the clinical status after lung transplantation. In 28 patients, 105 BAL, 96 blood samples and 14 brushes were analyzed. In 6 patients, a total of eight episodes of CMV pneumonitis occurred. Five of the 6 with positive CMV antigens in BAL (p52 or IE1) showed signs of CMV pneumonitis. All episodes of CMV pneumonitis were detected by the PCR of BAL cells. Fourteen samples positive for CMV pp65 antigen in blood were negative in BAL PCR. In these cases, no clinical signs of pulmonary CMV infection occurred. Overall sensitivity, specificity, and positive and negative predictive values for the detection of CMV pneumonitis by PCR of BAL cells were 100, 98.9, 88.9 and 100%, respectively. In brush samples, PCR did not provide additional information to the results of the PCR of BAL cells. PCR of DNA from BAL cells is suitable for reliable and rapid detection of CMV pneumonitis. Copyright 2000 S. Karger AG, Basel.

  4. Chronic hypersensitivity pneumonitis: important considerations in the work-up of this fibrotic lung disease.

    PubMed

    Glazer, Craig S

    2015-03-01

    Chronic hypersensitivity pneumonitis is increasingly recognized as an important mimic of other fibrotic lung diseases. This review will summarize recent data regarding the importance and difficulty of determining causative exposures both for accurate diagnosis and prognosis, and describe the expanded pathologic spectrum of the disease, the effects of fibrosis on prognosis and challenges in the diagnostic evaluation. Several recent publications show the potential pathologic patterns induced by chronic hypersensitivity pneumonitis are broader than the classic triad of bronchiolitis, interstitial infiltrates and granulomas. Other pathologic patterns include nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, bronchiolitis and airway centric fibrosis. Detecting a causative antigen in fibrotic hypersensitivity pneumonitis is challenging but critically important both for accurate diagnosis and improved prognosis. The prognosis in hypersensitivity pneumonitis worsens in the presence of fibrosis, but it remains significantly better than idiopathic pulmonary fibrosis. Hypersensitivity pneumonitis is increasingly recognized as an important cause of fibrotic interstitial lung disease. Hypersensitivity pneumonitis demonstrates a remarkable tendency to mimic other idiopathic interstitial pneumonias. A detailed exposure history remains a cornerstone of diagnosis and management.

  5. Prognostic effects of preoperative obstructive pneumonitis or atelectasis and comparison with tumor size in non-small cell lung cancer

    PubMed Central

    Pang, Zhaofei; Ding, Nan; Dong, Wei; Ni, Yang; Zhang, Tiehong; Qu, Xiao

    2017-01-01

    Background In the eighth TNM staging system proposal, lung cancer with part or complete obstructive pneumonitis/atelectasis was classified to T2 category, and dividing lines of T category were changed. We conducted this study to search prognostic effect of preoperative obstructive pneumonitis/atelectasis and its comparison with tumor size. Methods We collected clinical characteristics, preoperative hematological indicators, follow-up information of 1,313 lung cancer patients. Chi-square test was used to search relationship between obstruction pneumonitis/atelectasis and other factors. Kaplan-Meier (K-M) curves and cox regression methods were used for survival analysis. Results Preoperative obstructive pneumonitis/atelectasis indicated shorter OS (HR: 1.308; 95% CI: 1.058–1.619) and RFS (HR: 1.276; 95% CI: 1.032–1.579) as an independent factor. In comparison with tumor size, we found patients with obstructive pneumonitis/atelectasis and T1 size tumor had similar prognosis to those with T2 size but without obstructive pneumonitis/atelectasis, and OS, RFS of patients with obstructive pneumonitis/atelectasis and T2 size were significantly shorter than those with T2 tumor size but without obstructive pneumonitis/atelectasis, while similar to patients with T3 tumor size but without obstructive pneumonitis/atelectasis according to division by the eighth edition. We also found obstructive pneumonitis/atelectasis was significantly related to higher neutrophil (P<0.001), platelet (P<0.001), monocyte (P<0.001), NLR (P<0.001), PLR (P=0.002), ESR (P<0.001) and lower LMR (P<0.001). Conclusions Preoperative obstructive pneumonitis/atelectasis predicted poor survival independently in non-small cell lung cancer (NSCLC). And we suggested which T staging group the patients with obstructive pneumonitis/atelectasis would be divided to should depend on tumor size in the eighth TNM staging system. PMID:28449485

  6. Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis.

    PubMed

    McSharry, Charles; Dye, George M; Ismail, Tengku; Anderson, Kenneth; Spiers, Elizabeth M; Boyd, Gavin

    2006-06-26

    Detecting serum antibody against inhaled antigens is an important diagnostic adjunct for hypersensitivity pneumonitis (HP). We sought to validate a quantitative fluorimetric assay testing serum from bird fanciers. Antibody activity was assessed in bird fanciers and control subjects using various avian antigens and serological methods, and the titer was compared with symptoms of HP. IgG antibody against pigeon serum antigens, quantified by fluorimetry, provided a good discriminator of disease. Levels below 10 mg/L were insignificant, and increasing titers were associated with disease. The assay was unaffected by total IgG, autoantibodies and antibody to dietary hen's egg antigens. Antigens from pigeon serum seem sufficient to recognize immune sensitivity to most common pet avian species. Decreasing antibody titers confirmed antigen avoidance. Increasing antibody titer reflected the likelihood of HP, and decreasing titers confirmed antigen avoidance. Quantifying antibody was rapid and the increased sensitivity will improve the rate of false-negative reporting and obviate the need for invasive diagnostic procedures. Automated fluorimetry provides a method for the international standardization of HP serology thereby improving quality control and improving its suitability as a diagnostic adjunct.

  7. Protection from radiation-induced pneumonitis using cerium oxide nanoparticles.

    PubMed

    Colon, Jimmie; Herrera, Luis; Smith, Joshua; Patil, Swanand; Komanski, Chris; Kupelian, Patrick; Seal, Sudipta; Jenkins, D Wayne; Baker, Cheryl H

    2009-06-01

    In an effort to combat the harmful effects of radiation exposure, we propose that rare-earth cerium oxide (CeO(2)) nanoparticles (free-radical scavengers) protect normal tissue from radiation-induced damage. Preliminary studies suggest that these nanoparticles may be a therapeutic regenerative nanomedicine that will scavenge reactive oxygen species, which are responsible for radiation-induced cell damage. The effectiveness of CeO(2) nanoparticles in radiation protection in murine models during high-dose radiation exposure is investigated, with the ultimate goal of offering a new approach to radiation protection, using nanotechnology. We show that CeO(2) nanoparticles are well tolerated by live animals, and they prevent the onset of radiation-induced pneumonitis when delivered to live animals exposed to high doses of radiation. In the end, these studies provide a tremendous potential for radioprotection and can lead to significant benefits for the preservation of human health and the quality of life for humans receiving radiation therapy.

  8. Predicting Radiation Pneumonitis After Chemoradiation Therapy for Lung Cancer: An International Individual Patient Data Meta-analysis

    SciTech Connect

    Palma, David A., E-mail: david.palma@uwo.ca; Senan, Suresh; Tsujino, Kayoko

    2013-02-01

    Background: Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. Methods and Materials: After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade {>=}2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) wasmore » used to define risk groups. Results: The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving {>=}20 Gy (V{sub 20}) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V{sub 20}, and lower-lobe tumor location. Conclusions: Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.« less

  9. Pneumonic tularaemia: experience of 58 cases from 2000 to 2012 in Northern Finland.

    PubMed

    Väyrynen, Sara A; Saarela, Elina; Henry, Janne; Lahti, Sini; Harju, Terttu; Kauma, Heikki

    2017-10-01

    Pneumonic tularaemia is less common clinical form of tularaemia compared with the ulceroglandular form, with only a limited number of case reports and case series in Europe. In Finland, Northern Ostrobothnia is an endemic area of tularaemia with occasional seasonal outbreaks. In our study, a consecutive series of 58 pneumonic tularaemia cases diagnosed and treated in Oulu University Hospital in 2000-2012 were retrospectively analysed in terms of epidemiology, clinical course, and prognosis. The incidence of pneumonic tularaemia showed peaks in cycles of a few years and most cases were diagnosed in late summer or early autumn. Respiratory symptoms were absent in 47% of patients, and 7% had normal chest X-ray. The chest computed tomography (CT) was performed in 81% of patients, demonstrating variable findings associated with pneumonic tularaemia. Bronchoscopy was performed for 22 (38%) patients and four (18%) of these also proceeded into mediastinoscopy. Moreover, thoracoscopy was performed for one (2%) patient. Two (3%) patients were treated shortly in the intensive care unit (ICU) during their stay in hospital. No mortality was observed. Most cases of pneumonic tularaemia are diagnosed during the seasonal outbreaks. The lack of specific symptoms often complicates the diagnosis and leads to unnecessarily invasive examinations.

  10. Ovine Mannheimia haemolytica isolates from lungs with and without pneumonic lesions belong to similar genotypes.

    PubMed

    García-Alvarez, Andrés; Fernández-Garayzábal, José Francisco; Chaves, Fernando; Pinto, Chris; Cid, Dolores

    2018-06-01

    This study investigated the genetic characteristics of 121 ovine Mannheimia haemolytica isolates from lungs with (n = 75) and without pneumonic lesions (n = 46) using multilocus sequence typing (MLST), virulence-associated gene typing and pulsed-field gel electrophoresis (PFGE). Twelve STs were identified with most isolates (81%) belonged to ST16, ST28 and ST8. Analysis of the M. haemolytica MLST Database indicate a wide distribution of these genotypes in small ruminants, never reported in bovine isolates. This could suggest the adaptation of certain genetic lineages of M. haemolytica to small ruminants. e-BURST analysis grouped most STs into three clonal complexes (CC2, CC8 and CC28), consistent with a clonal population structure of M. haemolytica. Virulence-associated gene typing identified five virulence profiles in 64% and 65.1% of the M. haemolytica isolates from lungs with and without pneumonic lesions, respectively. These data suggest that M. haemolytica isolates from the lungs with and without pneumonic lesions are genetically homogeneous. By PGFE analysis a high level of genetic diversity was observed not only within isolates from lungs without pneumonic lesions but also among isolates from pneumonic lesions (GD 0.69 and GD 0.66, respectively; P > 0.05). These results indicate that multiple strains of M. haemolytica may be associated with individual cases of pneumonia in sheep. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. [Familial summer-type hypersensitivity pneumonitis in a husband and wife].

    PubMed

    Amemiya, Yuka; Shirai, Ryo; Ando, Syunji; Fujii, Hiroyuki; Iwata, Atsuko; Kai, Naoko; Otani, Satoshi; Umeki, Kenji; Ishii, Hiroshi; Kadota, Jun-Ichi

    2008-11-01

    We encountered a family in which two of four members, the husband and his wife, had summer-type hypersensitivity pneumonitis at the same time, about two months after they moved to the residence. A 45-year-old man had cough, fever and exertional dyspnea. Chest computed tomography showed diffuse centriloblar ground-glass attenuation in both lung fields. His 43-year-old wife had chest small nodular shadows and similar symptoms to his husband. Serum anti-Tricosporon cutaneum (T. asahi: serotype II and T. mucoides: serotype I) antibodies of both patients were at the positive level. They were given diagnosis as summer-type hypersensitivity pneumonitis by radiological, serological and histological examinations. The symptoms in both cases were improved immediately after administration of systemic corticosteroid. Summer-type hypersensitivity pneumonitis was assumed to be caused for about two months duration of expousure to antigen.

  12. BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6

    PubMed Central

    2014-01-01

    Background Pneumonitis is a rare complication of bacillus Calmette-Guerin (BCG) immunotherapy seen in patients with urothelial cancer following the repeated administration of BCG. However, no case of BCG-induced pleurisy has been reported. Case presentation We here report the first case of pneumonitis with lymphocytic pleurisy following bacillus Calmette-Guerin (BCG) immunotherapy. Although marked T helper cell alveolitis was found by bronchoalveolar lavage and transbronchial biopsies, no acid-fast bacillus could be identified in recovered BALF or pleural effusion. The lymphocyte stimulation test of BCG was strongly positive. However, levels of serum and bronchoalveolar lavage fluid KL-6, a useful marker for hypersensitivity pneumonitis (HP), were within normal ranges. Conclusion We speculate that the pathogenesis of our case may be a hypersensitive reaction to the proteic component of BCG entering the lung and pleural space, which is different from the etiology of the common type of HP. PMID:24593234

  13. Yacht-maker's lung: A case of hypersensitivity pneumonitis in yacht manufacturing.

    PubMed

    Volkman, Kristen K; Merrick, James G; Zacharisen, Michael C

    2006-10-01

    We present a case of hypersensitivity pneumonitis in a 46-year-old female working at a yacht manufacturing company. She reported a 2-month history of progressive dyspnea, chest tightness, and daytime, nocturnal, and exertional cough in temporal relationship to work where she was exposed to chemicals involved in the manufacture of yachts. Treatment with systemic antibiotic therapy, inhaled bronchodilators, and inhaled corticosteroids provided minimal relief of symptoms. Spirometry revealed a restrictive defect and a chest x-ray demonstrated a diffuse interstitial pattern. She improved on oral corticosteroids and with avoidance of her work environment had resolution of her symptoms and normalization of her spirometry. Among the various chemicals the patient was exposed to, the most likely causative agents for her symptoms were dimethyl phthalate and styrene. Although the specific chemical or antigen could not be determined, the history and objective findings are consistent with occupational hypersensitivity pneumonitis. This represents a case of hypersensitivity pneumonitis related to the manufacture of yachts.

  14. Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy

    SciTech Connect

    Lingos, T.I.; Recht, A.; Vicini, F.

    1991-07-01

    The likelihood of radiation pneumonitis and factors associated with its development in breast cancer patients treated with conservative surgery and radiation therapy have not been well established. To assess these, the authors retrospectively reviewed 1624 patients treated between 1968 and 1985. Median follow-up for patients without local or distant failure was 77 months. Patients were treated with either tangential fields alone (n = 508) or tangents with a third field to the supraclavicular (SC) or SC-axillary (AX) region (n = 1116). Lung volume treated in the tangential fields was generally limited by keeping the perpendicular distance (demagnified) at the isocentermore » from the deep field edges to the posterior chest wall (CLD) to 3 cm or less. Seventeen patients with radiation pneumonitis were identified (1.0%). Radiation pneumonitis was diagnosed when patients presented with cough (15/17, 88%), fever (9/17, 53%), and/or dyspnea (6/17, 35%) and radiographic changes (17/17) following completion of RT. Radiographic infiltrates corresponded to treatment portals in all patients, and in 12 of the 17 patients, returned to baseline within 1-12 months. Five patients had permanent scarring on chest X ray. No patient had late or persistent pulmonary symptoms. The incidence of radiation pneumonitis was correlated with the combined use of chemotherapy (CT) and a third field. Three percent (11/328) of patients treated with a 3-field technique who received chemotherapy developed radiation pneumonitis compared to 0.5% (6 of 1296) for all other patients (p = 0.0001). When patients treated with a 3-field technique received chemotherapy concurrently with radiation therapy, the incidence of radiation pneumonitis was 8.8% (8/92) compared with 1.3% (3/236) for those who received sequential chemotherapy and radiation therapy (p = 0.002).« less

  15. The hypersensitivity pneumonitis diagnostic index: use of non-invasive testing to diagnose hypersensitivity pneumonitis in metalworkers.

    PubMed

    Dangman, Kenneth H; Cole, Solon R; Hodgson, Michael J; Kuhn, Charles; Metersky, Mark L; Schenck, Paula; Storey, Eileen

    2002-08-01

    Since 1993, several outbreaks of hypersensitivity pneumonitis (HP) have been reported in metalworkers. We report the largest outbreak of HP in metalworkers yet known. It occurred in a Connecticut factory that produces precision parts for the aerospace industry. The workers typically presented with systemic and respiratory problems ("sick fatigue," myalgias, cough, dyspnea, wheezing, and chest tightness). They had variable findings on clinical tests, which complicated diagnosis. An HP diagnostic index was developed to help reduce the uncertainties in case identification. Data from 16 biopsy-confirmed cases and 14 non-HP patients were compared, and the HP diagnostic index was derived using variables that best discriminated between the two groups. The index is based on (a) work-related symptoms, (b) dry crackles on auscultation, (c) restrictive spirometry, (d) decreased diffusion capacity and/or increased A-a oxygen gradient, (e) elevated erythrocyte sedimentation rate, (f) abnormal radiographic images, and (g) abnormal gallium scans. We then applied the HP diagnostic index and, for comparison, the "Kenosha epidemiological case criteria" (developed during a recent HP outbreak in an automobile factory) to our data set. The HP diagnostic index and the Kenosha criteria confirmed HP in overlapping sets of 36 and 34 patients, respectively, that were both in good agreement with the clinical diagnoses. The HP diagnostic index relies less heavily on symptoms, subjective evaluations, and invasive tests than the Kenosha criteria, but both identified similar subsets of the 61 patients as having HP. The HP diagnostic index could provide a useful tool in future HP outbreaks, which are increasingly being recognized in metalworking facilities. Copyright 2002 Wiley-Liss, Inc.

  16. Predicting pneumonitis risk: a dosimetric alternative to mean lung dose.

    PubMed

    Tucker, Susan L; Mohan, Radhe; Liengsawangwong, Raweewan; Martel, Mary K; Liao, Zhongxing

    2013-02-01

    To determine whether the association between mean lung dose (MLD) and risk of severe (grade ≥3) radiation pneumonitis (RP) depends on the dose distribution pattern to normal lung among patients receiving 3-dimensional conformal radiation therapy for non-small-cell lung cancer. Three cohorts treated with different beam arrangements were identified. One cohort (2-field boost [2FB]) received 2 parallel-opposed (anteroposterior-posteroanterior) fields per fraction initially, followed by a sequential boost delivered using 2 oblique beams. The other 2 cohorts received 3 or 4 straight fields (3FS and 4FS, respectively), ie, all fields were irradiated every day. The incidence of severe RP was plotted against MLD in each cohort, and data were analyzed using the Lyman-Kutcher-Burman (LKB) model. The incidence of grade ≥3 RP rose more steeply as a function of MLD in the 2FB cohort (N=120) than in the 4FS cohort (N=138), with an intermediate slope for the 3FS group (N=99). The estimated volume parameter from the LKB model was n=0.41 (95% confidence interval, 0.15-1.0) and led to a significant improvement in fit (P=.05) compared to a fit with volume parameter fixed at n=1 (the MLD model). Unlike the MLD model, the LKB model with n=0.41 provided a consistent description of the risk of severe RP in all three cohorts (2FB, 3FS, 4FS) simultaneously. When predicting risk of grade ≥3 RP, the mean lung dose does not adequately take into account the effects of high doses. Instead, the effective dose, computed from the LKB model using volume parameter n=0.41, may provide a better dosimetric parameter for predicting RP risk. If confirmed, these findings support the conclusion that for the same MLD, high doses to small lung volumes ("a lot to a little") are worse than low doses to large volumes ("a little to a lot"). Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Risk of hypersensitivity pneumonitis and interstitial lung diseases among pigeon breeders.

    PubMed

    Cramer, Christine; Schlünssen, Vivi; Bendstrup, Elisabeth; Stokholm, Zara Ann; Vestergaard, Jesper Medom; Frydenberg, Morten; Kolstad, Henrik Albert

    2016-09-01

    We studied the risk of hypersensitivity pneumonitis and other interstitial lung diseases (ILDs) among pigeon breeders.This is a retrospective follow-up study from 1980 to 2013 of 6920 pigeon breeders identified in the records of the Danish Racing Pigeon Association. They were compared with 276 800 individually matched referents randomly drawn from the Danish population. Hospital based diagnoses of hypersensitivity pneumonitis and other ILDs were identified in the National Patient Registry 1977-2013. Stratified Cox regression analyses estimated the hazard ratios (HR) of hypersensitivity pneumonitis and other ILDs adjusted for occupation, residence and redeemed prescription of medication with ILDs as a possible side-effect. Subjects were censored at death, emigration or a diagnosis of connective tissue disease.The overall incidence rate of ILD was 77.4 per 100 000 person-years among the pigeon breeders and 50.0 among the referents. This difference corresponded to an adjusted HR of 1.56 (95% CI 1.26-1.94). The adjusted HRs of hypersensitivity pneumonitis and other ILDs for pigeon breeders were 14.36 (95% CI 8.10-25.44) and 1.33 (95% CI 1.05-1.69), respectively.This study shows an increased risk of ILD among pigeon breeders compared with the referent population. Protective measures are recommended even though ILD leading to hospital contact remains rare among pigeon breeders. Copyright ©ERS 2016.

  18. Effects of proton pump inhibitors on lung cancer precise radiotherapy-induced radiation pneumonitis.

    PubMed

    Su, QiaoLi; Wang, Duoning; Yuan, Bo; Liu, Feng; Lei, Yi; Li, Shuangqing

    2014-11-01

    The objective of this study was to explore the effects of proton pump inhibitors (PPIs) on the development and prognosis of lung cancer precise radiotherapy-induced radiation pneumonitis. Clinical materials of 84 lung cancer patients who had radiation pneumonitis after precise radiotherapy were retrospectively analyzed, and the patients were divided into PPI group and control group, according to whether or not PPIs were applied. The development and prognosis of patients and the effects of different doses of PPI on patient condition from two groups were compared. There were 57 PPI cases in PPI group and 27 cases in control group. Basic characteristics of patients were not statistically different between the two groups; however, white blood cell count, oxygenation indexes, blood gas pH, and lung imaging index were significantly different (p < 0.05), indicating that radiation pneumonitis tended to be more severe in PPI group. As regards effects of PPI on prognosis of two groups, remission rate of radiation pneumonia in PPI group was significantly less than that of the control group. Among 57 cases in PPI group, there were 31 patients applied with PPI ≤ 1DDD and 31 patients applied with PPI > 1DDD. In comparison of the various parameters of patients, 7 days after being applied with different doses of PPI, there were no significant differences between the parameters of radiation pneumonitis. PPIs should be cautiously utilized to avoid the effects of lung cancer radiotherapy-induced radiation pneumonia.

  19. Dynamics of the pneumonic plague epidemic in Madagascar, August to October 2017.

    PubMed

    Tsuzuki, Shinya; Lee, Hyojung; Miura, Fuminari; Chan, Yat Hin; Jung, Sung-Mok; Akhmetzhanov, Andrei R; Nishiura, Hiroshi

    2017-11-01

    Transmission potential and severity of pneumonic plague in Madagascar were assessed. Accounting for reporting delay, the reproduction number was estimated at 1.73. The case fatality risk was estimated as 5.5%. Expected numbers of exported cases from Madagascar were estimated across the world and all estimates were below 1 person from August to October, 2017.

  20. Symptomatic Radiation Pneumonitis After Accelerated Partial Breast Irradiation Using Three-dimensional Conformal Radiotherapy.

    PubMed

    Shikama, Naoto; Kumazaki, Y U; Miyazawa, Kazunari; Miyaura, Kazunori; Kato, Shingo; Nakamura, Naoki; Kawamori, Jiro; Shimizuguchi, Takuya; Saito, Naoko; Saeki, Toshiaki

    2016-05-01

    To examine the relationship between symptomatic radiation pneumonitis and lung dose-volume parameters for patients receiving accelerated partial breast irradiation (APBI) using three dimensional-conformal radiotherapy (3D-CRT). The prescribed radiation dose was 30 Gy in 5 fractions over 10 days. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (version 4.0). Fifty-five patients were enrolled from August 2010 to October 2013 and the median follow-up time was 30 months (range=18-46 months). Three patients (5%) developed grade 2 symptomatic radiation pneumonitis after 3D-CRT APBI. Among 16 patients with ILV10Gy (% ipsilateral lung receiving ≥10 Gy) of 10% or higher, three patients (19%) developed symptomatic radiation pneumonitis. This trend was not observed in any of the patients with ILV10Gy less than 10% (p=0.005). High ILV10Gy might be associated with symptomatic radiation pneumonitis after 3D-CRT APBI. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. A case of hypersensitivity pneumonitis with giant cells in a female dental technician.

    PubMed

    Kim, Yong-Hyun; Chung, Yun Kyung; Kim, Changhwan; Nam, Eun Suk; Kim, Hyun-Jun; Joo, Youngsu

    2013-10-04

    Dental technicians are exposed to methyl methacrylate(MMA) and hard metal dusts while working, and several cases of hypersensitivity pneumonitis caused by the exposure have been reported. The authors experienced a case of hypersensitivity pneumonitis in a female dental technician who had 10 years' work experience and report the case with clinical evidence. The patient's work, personal, social, and past and present medical histories were investigated based on patient questioning and medical records. Furthermore, the workplace conditions and tools and materials the patient worked with were also evaluated. Next, the pathophysiology and risk factors of pneumonitis were studied, and studies on the relationship between hypersensitivity pneumonitis and a dental technician's exposure to dust were reviewed. Any changes in the clinical course of her disease were noted for evaluation of the work-relatedness of the disease. The patient complained of cough and sputum for 1 year. In addition, while walking up the stairs, the patient was not able to ascend without resting due to dyspnea. She visited our emergency department due to epistaxis, and secondary hypertension was incidentally suspected. Laboratory tests including serologic, electrolyte, and endocrinologic tests and a simple chest radiograph showed no specific findings, but chest computed tomography revealed a centrilobular ground-glass pattern in both lung fields. A transbronchial biopsy was performed, and bronchoalveolar washing fluid was obtained. Among the findings of the laboratory tests, microcalcification, noncaseating granuloma containing foreign body-type giant cells, and metal particles within macrophages were identified histologically. Based on these results, hypersensitivity pneumonitis was diagnosed. The patient stopped working due to admission, and she completely quit her job within 2 months of restarting work due to reappearance of the symptoms. In this study, the patient did not have typical radiologic

  2. Risk Analysis of Pneumonitis in Taxane Therapy After Chemoradiotherapy for Patients With Metastatic or Recurrent Esophageal Cancer.

    PubMed

    Kishida, Yoshihiro; Tsushima, Takahiro; Endo, Masahiro; Hamauchi, Satoshi; Todaka, Akiko; Yokota, Tomoya; Machida, Nozomu; Yamazaki, Kentaro; Fukutomi, Akira; Onozawa, Yusuke; Yasui, Hirofumi

    2018-01-01

    Taxane chemotherapy for esophageal cancer causes pneumonitis, not only by itself but also by radiation recall. This study aimed to clarify the risk of pneumonitis in patients with esophageal cancer who receive taxane therapy after chemoradiotherapy. The data of 129 patients with metastatic or recurrent esophageal cancer who initiated taxane therapy between September 2002 and June 2013 were retrospectively analyzed. Patient selection criteria were as follows: performance status ≤2, preserved organ functions, previous chemoradiotherapy with a radiation dose of ≥50 Gy, grade 0 or 1 pneumonitis at taxane initiation, and no concomitant malignancy. Logistic regression analysis was performed to identify risk factors for pneumonitis. Patient characteristics were as follows: males/females, 116/13; median age, 63 years (range, 44 to 80 y); performance status of 0/1/2, 61/60/8; smoking history, 112 (88%); location of the primary tumor Ce/Ut/Mt/Lt/Ae 12/30/66/20/1; median radiation dose, 60 Gy; history of radiation pneumonitis, 39 (30%); history of other pulmonary disease, 4 (3%); and median duration between the last radiation therapy (RT) exposure and taxane initiation, 6.1 months (range, 1.0 to 71 mo). During the median observation period of 7.8 months from taxane initiation, the incidence of grade 2 and 3 pneumonitis was observed in 7 (5.4%) and 3 (2.3%) patients, respectively. No patient died of pneumonitis. The only independent risk factor for pneumonitis was a ≤4-month period between the last RT exposure and taxane initiation (P=0.03). A short period between the last RT exposure and taxane initiation is an independent risk factor for pneumonitis development.

  3. Imaging radiation pneumonitis in a rat model of a radiological terrorism incident

    NASA Astrophysics Data System (ADS)

    Molthen, Robert; Wu, QingPing; Krenz, Gary; Medhora, Meetha; Jacobs, Elizabeth; Moulder, John E.

    2009-02-01

    We have developed a rat model of single, sub-lethal thoracic irradiation. Our irradiation protocol is considered representative of exposures near the detonation site of a dirty bomb or small nuclear device. The model is being used to investigate techniques for identifying, triaging and treating possible victims. In addition to physiological markers of right ventricular hypertrophy, pulmonary vascular resistance, and arterial distensibility, we present two methods for quantifying microvascular density. We used methods including microfocal X-ray imaging to investigate changes in lung structure/function resulting from radiation exposure. Radiation pneumonitis is a complication in subjects receiving thoracic irradiation. A radiographic hallmark of acute radiation pneumonitis is a diffuse infiltrate corresponding to the radiation treatment field. We describe two methods for quantifying small artery dropout that occurs in the model at the same time-period. Rats were examined 3-days, 2-weeks, 1-month (m), 2-m, 5-m, and 12-m post-irradiation and compared with aged-matched controls. Right ventricular hypertrophy and increases in pulmonary vascular resistance were present during the pneumonitis phase. Vascular injury was dependent on dose and post-irradiation duration. Rats irradiated with 5 Gy had few detectable changes, whereas 10 Gy resulted in a significant decrease in both microvascular density and arterial distensibility around 2- m, the decrease in each lessening, but extending through 12-m. In conclusion, rats irradiated with a 10 Gy dose had changes in vascular structure concurrent with the onset of radiation pneumonitis that were detectable with our imaging techniques and these structural changes persist after resolution of the pneumonitis.

  4. Characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain.

    PubMed

    Mellado-Sanchez, Gabriela; Ramirez, Karina; Drachenberg, Cinthia B; Diaz-McNair, Jovita; Rodriguez, Ana L; Galen, James E; Nataro, James P; Pasetti, Marcela F

    2013-03-01

    Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered as a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study.

    PubMed

    Morell, Ferran; Villar, Ana; Montero, María-Ángeles; Muñoz, Xavier; Colby, Thomas V; Pipvath, Sudhakar; Cruz, María-Jesús; Raghu, Ganesh

    2013-11-01

    The clinical features of idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis can be indistinguishable; the need to eliminate occult environmental factors known to cause pulmonary fibrosis in patients suspected to have IPF during diagnostic evaluation is evident. We aimed to investigate occult, putative causes in the environments of patients diagnosed with IPF using tests beyond those conventionally used. In this case-cohort study, 60 consecutive patients diagnosed with IPF on the basis of the 2000 American Thoracic Society (ATS) and the European Respiratory Society (ERS) criteria were prospectively followed up every 4 months for 6 years between Jan 1, 2004, and Dec 31, 2009. At each visit a uniformly applied questionnaire was administered to these 60 patients to identify occult antigen exposure known to cause hypersensitivity pneumonitis. Patients underwent specific IgG determination, bronchoalveolar lavage, bronchial challenge testing with suspected antigens, and re-review of histopathological features in existing and subsequently obtained surgical lung biopsy samples and from lung explants. Specimens obtained from suspected sources from the patient's environment were subjected to cultures in microbiology laboratory. These clinical data and discussions among pulmonologists and radiologists familiar with IPF were used to confirm the diagnosis in accordance with 2011 ATS, ERS, Japanese Respiratory Society, and Latin American Thoracic Association guidelines; 46 of the 60 patients had IPF according to the 2011 guidelines, and our analyses in this study were focused on these 46 patients. 20 of the 46 (43%, 95% CI 29-58) patients with IPF according to 2011 guidelines had a subsequent diagnosis of chronic hypersensitivity pneumonitis: nine patients had positive bronchial challenge testing (eight of whom were also IgG positive and six of these patients also had surgical lung biopsy showing a pattern consistent with chronic hypersensitivity

  6. Life threatening acute pneumonitis during low dose methotrexate treatment for rheumatoid arthritis: a case report and review of the literature.

    PubMed Central

    Ridley, M G; Wolfe, C S; Mathews, J A

    1988-01-01

    A patient is described with definite rheumatoid arthritis (RA) who developed life threatening acute pneumonitis after receiving a total dose of only 12.5 mg methotrexate (MTX). This complication has been previously described, but this is probably the lowest reported dose before development of pneumonitis in a patient with RA. The possible significance of this case is discussed in the light of recent reports suggesting an increased susceptibility of patients with RA to the pulmonary toxicity of MTX. Images PMID:3052323

  7. An Extremely Rapid Case of Pneumonitis with the Use of Nivolumab for Pancreatic Adenocarcinoma

    PubMed Central

    Benson, Al; Yaghmai, Vahid; Costa, Ricardo L. B.; Zhou, Haijun; Behdad, Amir; Kaplan, Jason B.; Sadim, Maureen; Talamantes, Sarah; Kalyan, Aparna

    2018-01-01

    Pancreatic cancer is the fourth most common cancer death in the United States despite comprising a small percentage of the total number of cancer cases. The estimated 5-year overall survival (OS) for patients with distant metastatic disease is approximately 3%. New treatment options are an unmet need and remain an area of active investigation. A 53-year-old male with metastatic pancreatic cancer presented to the hospital with acute-on-chronic respiratory failure approximately 24 hours after receiving a novel therapeutic combination. Chest imaging showed marked changes as concerning for pneumonitis. Infectious workup was negative. The patient had initial clinical improvement after receiving initial intravenous steroids and oxygen support but eventually deteriorated later opting for supportive measures only. With infection ruled out, drug-induced pneumonitis was felt to be the likely cause of the radiologic and clinical changes. The rapidity of onset of symptoms is the aspect being highlighted in this case. PMID:29808141

  8. Septic pneumonic tularaemia caused by Francisella tularensis subsp. holarctica biovar II.

    PubMed

    Fritzsch, Joerg; Splettstoesser, Wolf D

    2010-09-01

    This case of pneumonic tularaemia elucidates two aspects: it is believed to be the first documented case of bacteraemia caused by Francisella tularensis subsp. holarctica biovar II; furthermore, it illustrates the remission of septic pneumonic tularaemia without appropriate anti-infective therapy. A blood culture from a patient with community-acquired pneumonia was found to be positive for F. tularensis subsp. holarctica biovar II after 10 days of cultivation. Meanwhile, the patient had been treated with ceftriaxone, followed by sultamicillin and clindamycin. The patient continued suffering from fever of up to 40.7 degrees C and rising C-reactive protein (CRP) for 4 days before the fever and CRP declined. The isolated strain was later tested and found to be resistant to the antibiotics used. The present case underlines that F. tularensis subsp. holarctica infections may cause severe symptoms but mostly have a favourable outcome.

  9. Prevention of bubonic and pneumonic plague using plant-derived vaccines.

    PubMed

    Alvarez, M Lucrecia; Cardineau, Guy A

    2010-01-01

    Yersinia pestis, the causative agent of bubonic and pneumonic plague, is an extremely virulent bacterium but there are currently no approved vaccines for protection against this organism. Plants represent an economical and safer alternative to fermentation-based expression systems for the production of therapeutic proteins. The recombinant plague vaccine candidates produced in plants are based on the two most immunogenic antigens of Y. pestis: the fraction-1 capsular antigen (F1) and the low calcium response virulent antigen (V) either in combination or as a fusion protein (F1-V). These antigens have been expressed in plants using all three known possible strategies: nuclear transformation, chloroplast transformation and plant-virus-based expression vectors. These plant-derived plague vaccine candidates were successfully tested in animal models using parenteral, oral, or prime/boost immunization regimens. This review focuses on the recent research accomplishments towards the development of safe and effective pneumonic and bubonic plague vaccines using plants as bioreactors.

  10. Cat-transmitted fatal pneumonic plague in a person who traveled from Colorado to Arizona.

    PubMed

    Doll, J M; Zeitz, P S; Ettestad, P; Bucholtz, A L; Davis, T; Gage, K

    1994-07-01

    Plague, primarily a disease of rodents and their infected fleas, is fatal in 50% of infected humans if untreated. In the United States, human cases have been concentrated in the southwest. The most common modes of plague transmission are through flea bites or through contact with infected blood or tissues; however, primary pneumonic plague acquired from cats has become increasingly recognized. We report on the case investigation of a patient, presumably exposed to a plague-infected cat in Colorado, who presented with gastrointestinal symptoms, and subsequently died of primary pneumonic plague. Public health officials should be vigilant for plague activity in rodent populations, veterinarians should suspect feline plague in ill or deceased cats, and physicians should have a high index of suspicion for plague in any person who has traveled to plague enzootic areas.

  11. An Encapsulated Yersinia pseudotuberculosis Is a Highly Efficient Vaccine against Pneumonic Plague

    PubMed Central

    Derbise, Anne; Cerdà Marín, Alba; Ave, Patrick; Blisnick, Thierry; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E.

    2012-01-01

    Background Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. Methodology and Principal Findings The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD50 of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD50). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. Conclusions and Significance The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality. PMID:22348169

  12. An encapsulated Yersinia pseudotuberculosis is a highly efficient vaccine against pneumonic plague.

    PubMed

    Derbise, Anne; Cerdà Marín, Alba; Ave, Patrick; Blisnick, Thierry; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E

    2012-01-01

    Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD(50) of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD(50)). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality.

  13. Asthma, hypersensitivity pneumonitis and other respiratory diseases caused by metalworking fluids.

    PubMed

    Rosenman, Kenneth D

    2009-04-01

    To highlight advances in understanding the respiratory disease associated with metal machining, a common work process involving approximately 1.2 million workers in the USA. Recent studies emphasize that work-related asthma and hypersensitivity pneumonitis continue to be caused by exposure to metalworking fluid. Identification of an individual patient indicates the need for follow-up investigations at the work site to prevent additional disease and/or identify additional effected individuals. Identification of the causal agent for hypersensitivity pneumonitis has centered on microbial contamination of metalworking fluids with a number of studies focusing on Mycobacterium immunogenum. Both asthma and hypersensitivity pneumonitis occur among workers exposed to metalworking fluid. The incidence of these diseases among such workers is unknown. Outbreaks of these conditions continue to be identified among metal machinists. Whether these are true outbreaks associated with some breakdown in workplace controls or, rather the recognition of ongoing endemic disease that is typically misdiagnosed as pneumonia or common adult onset asthma, needs further evaluation. Further work to elucidate the specific causal agent(s) is necessary to affect effective workplace controls. Treating an identified individual case as an index case with a follow-up workplace investigation will only be possible if practicing physicians interact with public health authorities to report newly diagnosed cases.

  14. The Yersiniabactin Transport System Is Critical for the Pathogenesis of Bubonic and Pneumonic Plague▿

    PubMed Central

    Fetherston, Jacqueline D.; Kirillina, Olga; Bobrov, Alexander G.; Paulley, James T.; Perry, Robert D.

    2010-01-01

    Iron acquisition from the host is an important step in the pathogenic process. While Yersinia pestis has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague. Y. pestis mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an ∼24-fold-higher 50% lethal dose (LD50) than transport mutants. In contrast, under iron-restricted conditions in vitro, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Δpgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague. PMID:20160020

  15. The yersiniabactin transport system is critical for the pathogenesis of bubonic and pneumonic plague.

    PubMed

    Fetherston, Jacqueline D; Kirillina, Olga; Bobrov, Alexander G; Paulley, James T; Perry, Robert D

    2010-05-01

    Iron acquisition from the host is an important step in the pathogenic process. While Yersinia pestis has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague. Y. pestis mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an approximately 24-fold-higher 50% lethal dose (LD(50)) than transport mutants. In contrast, under iron-restricted conditions in vitro, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Delta pgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague.

  16. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination

    PubMed Central

    Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E.

    2015-01-01

    Background No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. Methodology/Principal Findings The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1—Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. Significance VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection

  17. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination.

    PubMed

    Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E

    2015-01-01

    No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral

  18. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

    SciTech Connect

    Allen, Aaron M.; Czerminska, Maria; Jaenne, Pasi A.

    2006-07-01

    Purpose: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. Methods and Materials: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m{sup 2}). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patientsmore » received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. Results: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%), 15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy) (p = 0.07), and 90

  19. Oral administration of herbal medicines for radiation pneumonitis in lung cancer patients: A systematic review and meta-analysis

    PubMed Central

    Baek, Hyunjung; Kim, Jae-Hyo; Lee, Beom-Joon

    2018-01-01

    Background Radiation pneumonitis is a common and serious complication of radiotherapy. Many published randomized controlled studies (RCTs) reveal a growing trend of using herbal medicines as adjuvant therapy to prevent radiation pneumonitis; however, their efficacy and safety remain unexplored. Objective The aim of this systematic review is to evaluate the efficacy and safety of herbal medicines as adjunctive therapy for the prevention of radiation pneumonitis in patients with lung cancer who undergo radiotherapy. Methods We searched the following 11 databases: three English medical databases [MEDLINE (PubMed), EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL)], five Korean medical databases (Korean Studies Information, Research information Service System, KoreaMed, DBPIA, National Digital Science Library), and three Chinese medical databases [the China National Knowledge Database (CNKI), Journal Integration Platform (VIP), and WanFang Database]. The primary outcome was the incidence of radiation pneumonitis. The risk of bias was assessed using the Cochrane risk-of-bias tool. Results Twenty-two RCTs involving 1819 participants were included. The methodological quality was poor for most of the studies. Meta-analysis showed that herbal medicines combined with radiotherapy significantly reduced the incidence of radiation pneumonitis (n = 1819; RR 0.53, 95% CI 0.45–0.63, I2 = 8%) and the incidence of severe radiation pneumonitis (n = 903; RR 0.22, 95% CI 0.11–0.41, I2 = 0%). Combined therapy also improved the Karnofsky performance score (n = 420; WMD 4.62, 95% CI 1.05–8.18, I2 = 82%). Conclusion There is some encouraging evidence that oral administration of herbal medicines combined with radiotherapy may benefit patients with lung cancer by preventing or minimizing radiation pneumonitis. However, due to the poor methodological quality of the identified studies, definitive conclusion could not be drawn. To confirm the merits of this approach

  20. [Immune-related pneumonitis caused by programmed death-1 inhibitor Pembrolizumab: a case report and literature review].

    PubMed

    Chen, Y L; Zhao, J; Jia, R; Wang, H Y; Zheng, J; Bai, C Q; Wang, M Z; Xu, J M

    2017-10-12

    Objective: To investigate the risk factors, clinical manifestations, radiological features, diagnosis, treatment and prognosis of immune-related pneumonitis caused by programmed death-1(PD-1)/PD-L1 inhibitors. Methods: The clinical data of immune-related pneumonitis caused by PD-1 inhibitor Pembrolizumab in a patient with advanced esophageal carcinoma admitted to the 307(th) Hospital of Chinese People's Liberation Army was retrospectively analyzed and the related literatures were reviewed. We searched Medline database using the keywords"PD-1 inhibitor","PD-L1 inhibitor","Pembrolizumab","Nivolumab","Atezolizumab"combined with"Pneumonitis"by Mar 31, 2017. Results: The patient was a 60-year-old male presented with progression disease after surgery, local radiation and couples of chemotherapy for his esophageal carcinoma. Then pembrolizumab, a kind of PD-l inhibitors, was given intravenously every 3 weeks with the average dosage 3 mg per kg. After six cycles of pembrolizumab, the patient began to have fever, cough and dyspnea, which aggravated gradually. Chest CT showed diffuse ground glass opacity, exudation and consolidation in both lungs and little pleural effusion in the right side. Cellular interstitial pneumonitis was confirmed by pathological examination. The patient's symptoms were alleviated after enough steroids and chest CT showed pulmonary infiltration was also absorbed. But the pneumonitis reoccurred twice after stopping or tapering steroids quickly and could also be controlled by using steroids again. Now the patient was still given steroids treatment and the primary esophageal cancer remained stable. 14 articles were retrieved and 88 cases of immune-related pneumonitis caused by PD-1/PD-L1 inhibitors were reported. Among these 89 cases with immune-related pneumonitis, both male and female could attack and the median age was 67 years old. Most cases were grade 1 or 2. The common clinical manifestations were dyspnea, cough, fever and other immune

  1. The importance of interleukin-8 as a neutrophil chemoattractant in the lungs of cattle with pneumonic pasteurellosis.

    PubMed Central

    Caswell, J L; Middleton, D M; Gordon, J R

    2001-01-01

    Interleukin-8 (IL-8), an in vitro and in vivo neutrophil chemoattractant, is expressed at high levels in the lesions observed in bovine pneumonic pasteurellosis. Because of the role of neutrophils in the pathogenesis of pneumonic pasteurellosis, we investigated the relative importance of IL-8 as a neutrophil chemoattractant in this disease. Bronchoalveolar lavage (BAL) fluid was harvested from calves experimentally infected with bovine herpesvirus-1 and challenged with Mannheimia haemolytica. Neutrophil chemotactic activity was measured in pneumonic BAL fluid samples treated with a neutralizing monoclonal antibody to ovine IL-8, and compared to the activity in samples treated with an isotype-matched control antibody. Bronchoalveolar lavage fluid was analyzed at a dilution which induced a half-maximal response, and the concentrations of antibody were optimized in a preliminary experiment. Following incubation of replicate samples of diluted pneumonic bovine BAL fluid with 70 microg/mL of IL-8-neutralizing antibody or control antibody, the neutrophil chemotactic activities of the samples were determined using an in vitro microchemotaxis assay. Overall, pretreatment of BAL fluid samples with neutralizing anti-IL-8 antibody reduced neutrophil chemotactic activity by 15% to 60%, compared to pretreatment with control antibody. This effect was highly significant (P < 0.001), and was present in 5 of 5 samples. These data indicate that IL-8 is an important neutrophil chemoattractant in calves with pneumonic pasteurellosis, but that mediators with actions redundant to those of IL-8 must also be present in the lesions. PMID:11768129

  2. An Improved Model for Predicting Radiation Pneumonitis Incorporating Clinical and Dosimetric Variables;Lung cancer; Radiation pneumonitis; Dose-volume histogram; Angiotensin converting enzyme inhibitor

    SciTech Connect

    Jenkins, Peter, E-mail: peter.jenkins@glos.nhs.uk; Watts, Joanne

    2011-07-15

    Purpose: Single dose-volume metrics are of limited value for the prediction of radiation pneumonitis (RP) in day-to-day clinical practice. We investigated whether multiparametric models that incorporate clinical and physiologic factors might have improved accuracy. Methods and Materials: The records of 160 patients who received radiation therapy for non-small-cell lung cancer were reviewed. All patients were treated to the same dose and with an identical technique. Dosimetric, pulmonary function, and clinical parameters were analyzed to determine their ability to predict for the subsequent development of RP. Results: Twenty-seven patients (17%) developed RP. On univariate analysis, the following factors were significantly correlatedmore » with the risk of pneumonitis: fractional volume of lung receiving >5-20 Gy, absolute volume of lung spared from receiving >5-15 Gy, mean lung dose, craniocaudal position of the isocenter, transfer coefficient for carbon monoxide (KCOc), total lung capacity, coadministration of angiotensin converting enzyme inhibitors, and coadministration of angiotensin receptor antagonists. By combining the absolute volume of lung spared from receiving >5 Gy with the KCOc, we defined a new parameter termed Transfer Factor Spared from receiving >5 Gy (TFS{sub 5}). The area under the receiver operator characteristic curve for TFS{sub 5} was 0.778, increasing to 0.846 if patients receiving modulators of the renin-angiotensin system were excluded from the analysis. Patients with a TFS{sub 5} <2.17 mmol/min/kPa had a risk of RP of 30% compared with 5% for the group with a TFS{sub 5} {>=}2.17. Conclusions: TFS{sub 5} represents a simple parameter that can be used in routine clinical practice to more accurately segregate patients into high- and low-risk groups for developing RP.« less

  3. Spatially distinct neutrophil responses within the inflammatory lesions of pneumonic plague.

    PubMed

    Stasulli, Nikolas M; Eichelberger, Kara R; Price, Paul A; Pechous, Roger D; Montgomery, Stephanie A; Parker, Joel S; Goldman, William E

    2015-10-13

    During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (RNA-seq) analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are downregulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both in vitro and in vivo that Y. pestis increases neutrophil survival in a manner that is dependent on the type III secretion system effector YopM. This research explores the complexity of spatially distinct host-microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand Y. pestis virulence. Yersinia pestis is a high-priority pathogen and continues to cause outbreaks worldwide. The ability of Y. pestis to be transmitted via respiratory droplets and its history of weaponization has led to its classification as a select agent most likely to be used as a biological weapon. Unrestricted bacterial growth during the initial preinflammatory phase primes patients to be infectious once disease symptoms begin in the proinflammatory phase, and the rapid disease progression can lead to death before Y. pestis infection can be diagnosed and treated. Using in vivo analyses and focusing on relevant cell types during pneumonic plague infection, we can identify host pathways that may be manipulated to extend the treatment window for pneumonic plague patients. Copyright © 2015 Stasulli et al.

  4. How to Diagnose Early 5-Azacytidine-Induced Pneumonitis: A Case Report.

    PubMed

    Misra, Srimanta Chandra; Gabriel, Laurence; Nacoulma, Eric; Dine, Gérard; Guarino, Valentina

    2017-12-01

    Interstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-azacytidine, a deoxyribonucleic acid methyltransferase inhibitor and cytotoxic drug, has rarely been reported. We report a 67-year-old female myelodysplastic syndrome patient treated with 5-azacytidine at the conventional dosage of 75 mg/m 2 for 7 days. One week after starting she developed moderate fever along with dry cough and subsequently her temperature rose to 39.5 °C. She was placed under broad-spectrum antibiotics based on the protocol for febrile neutropenia, including ciprofloxacin 750 mg twice daily, ceftazidime 1 g three times daily (tid), and sulfamethoxazole/trimethoprim 400 mg/80 mg tid. High-resolution computed tomography of the chest disclosed diffuse bilateral opacities with ground-glass shadowing and pleural effusion bilaterally. Mediastinal and hilar lymph nodes were moderately enlarged. polymerase chain reaction for Mycobacterium tuberculosis, Pneumocystis jiroveci, and cytomegalovirus were negative. Cultures including viral and fungal were all negative. A diagnosis of drug-induced pneumonitis was considered and, given the negative bronchoalveolar lavage in terms of an infection, corticosteroid therapy was given at a dose of 1 mg/kg body weight. Within 4 weeks, the patient became afebrile and was discharged from hospital. Development of symptoms with respect to drug administration, unexplained fever, negative workup for an infection, and marked response to corticosteroid therapy were found in our case. An explanation could be a delayed type of hypersensitivity (type IV) with activation of CD8 T cell which could possibly explain most of the symptoms. We have developed a decision algorithm in order to anticipate timely diagnosis of 5-azacitidine-induced pneumonitis, and with the aim to limit antibiotics abuse and to set up emergency treatment.

  5. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis.

    PubMed

    Tan, Susanna K; Burgener, Elizabeth B; Waggoner, Jesse J; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F; Pinsky, Benjamin A

    2016-01-01

    Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P < .0001) and less likely to have an underlying condition not typically associated with lung disease (3% vs 20%, P < .0001). Histopathology was performed in only 17.3% of CMV-positive bronchoscopy episodes. When CMV diagnostic methods were evaluated against the comprehensive definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

  6. Using patient data similarities to predict radiation pneumonitis via a self-organizing map

    NASA Astrophysics Data System (ADS)

    Chen, Shifeng; Zhou, Sumin; Yin, Fang-Fang; Marks, Lawrence B.; Das, Shiva K.

    2008-01-01

    This work investigates the use of the self-organizing map (SOM) technique for predicting lung radiation pneumonitis (RP) risk. SOM is an effective method for projecting and visualizing high-dimensional data in a low-dimensional space (map). By projecting patients with similar data (dose and non-dose factors) onto the same region of the map, commonalities in their outcomes can be visualized and categorized. Once built, the SOM may be used to predict pneumonitis risk by identifying the region of the map that is most similar to a patient's characteristics. Two SOM models were developed from a database of 219 lung cancer patients treated with radiation therapy (34 clinically diagnosed with Grade 2+ pneumonitis). The models were: SOMall built from all dose and non-dose factors and, for comparison, SOMdose built from dose factors alone. Both models were tested using ten-fold cross validation and Receiver Operating Characteristics (ROC) analysis. Models SOMall and SOMdose yielded ten-fold cross-validated ROC areas of 0.73 (sensitivity/specificity = 71%/68%) and 0.67 (sensitivity/specificity = 63%/66%), respectively. The significant difference between the cross-validated ROC areas of these two models (p < 0.05) implies that non-dose features add important information toward predicting RP risk. Among the input features selected by model SOMall, the two with highest impact for increasing RP risk were: (a) higher mean lung dose and (b) chemotherapy prior to radiation therapy. The SOM model developed here may not be extrapolated to treatment techniques outside that used in our database, such as several-field lung intensity modulated radiation therapy or gated radiation therapy.

  7. Plague in China 2014-All sporadic case report of pneumonic plague.

    PubMed

    Li, Yun-Fang; Li, De-Biao; Shao, Hong-Sheng; Li, Hong-Jun; Han, Yue-Dong

    2016-02-19

    Yersinia pestis is the pathogen of the plague and caused three pandemics worldwide. Pneumonic plague is rarer than bubonic and septicemic plague. We report detailed clinical and pathogenic data for all the three sporadic cases of pneumonic plagues in China in 2014. All the three patients are herders in Gansu province of China. They were all infected by Yersinia pestis and displayed in the form of pneumonic plague respectively without related. We tested patient specimens from the upper (nasopharyngeal swabs) or the lower (sputum) respiratory tract and whole blood, plasma, and serum specimens for Yersinia pestis. All patients had fever, cough and dyspnea, and for patient 2 and 3, unconscious. Respiratory symptoms were predominant with acute respiratory failure. The chest X-ray showed signs consistent with necrotizing inflammation with multiple lobar involvements. Despite emergency treatment, all patients died of refractory multiple organ failure within 24 h after admission to hospital. All the contacts were quarantined immediately and there were no secondary cases. Nowadays, the plague is epidemic in animals and can infect people who contact with the infected animals which may cause an epidemic in human. We think dogs maybe an intermediate vector for plague and as a source of risk for humans who are exposed to pet animals or who work professionally with canines. If a patient has been exposed to a risk factor and has fever and dyspnea, plague should be considered. People who had contact with a confirmed case should be isolated and investigated for F1 antigen analysis and receive post-exposure preventive treatment. A vaccination strategy might be useful for individuals who are occupationally exposed in areas where endemically infected reservoirs of plague-infected small mammals co-exist.

  8. [Prolonged disease in a farmer with simultaneous Q fever pneumonia and subacute hypersensitivity pneumonitis].

    PubMed

    Nielsen, Monica Etler; Hilberg, Ole; Bendstrup, Elisabeth

    2015-06-22

    This case report describes the first incident of a patient with simultaneous occurrence of Q fever pneumonia and subacute hypersensitivity pneumonitis (HP). The 52-year-old patient was from his occupation as a farmer exposed to agents causing both diseases. Except for a weight loss in subacute/chronic incidents of HP the symptoms of Q fever and HP are similar. However, differences in CT findings and histopathology make it possible to differentiate between the two diseases. This report highlights the importance of a thorough occupational history.

  9. Methotrexate-induced Hypersensitivity Pneumonitis appearing after 30 years of use: a case report.

    PubMed

    Salehi, Mashal; Miller, Robertha; Khaing, Myint

    2017-06-28

    Methotrexate has been implicated in a variety of lung complications, one of which is hypersensitivity pneumonitis. Hypersensitivity pneumonitis most often occurs within the first year of starting low-dose orally administered methotrexate. We present a case of methotrexate-induced hypersensitivity pneumonitis after 30 years of methotrexate use, which is the first case to be reported so far. A 77-year-old African American woman with a history of rheumatoid arthritis presented with progressively worsening shortness of breath and nonproductive cough. She was on a daily dose of 2.5 mg of methotrexate that had been orally administered for the last 30 years. A physical examination was significant for fever of 38.2 °C (100.8 °F), tachycardia, bilateral basal crackles, and oxygen saturation of 88% on room air. A laboratory work up was significant for normal white blood cell count, increased eosinophil count of 18.3%, and erythrocyte sedimentation rate of 111 mm/hour. Sputum cultures were negative for any bacterial pathogens including acid-fast bacilli. Influenza and respiratory syncytial viral infection were ruled out. A (1-3)-B-D-glucan assay (Fungitell®) was within normal limits. Pulmonary embolism was ruled out and echocardiography was normal. A chest X-ray showed hazy opacity with prominent reticulation within the upper lung fields bilaterally, right greater than the left with no pleural effusion. Lung computed tomography revealed nonspecific bilateral upper lung opacification. A pulmonary function test was significant for no obstruction, normal maximum voluntary ventilation, and no restriction, with mildly decreased diffusion. Methotrexate was stopped, and our patient was started on prednisone 60 mg orally administered daily with dramatic clinical and radiologic improvement. Methotrexate-induced hypersensitivity pneumonitis usually occurs in the initial few weeks to months of starting treatment with methotrexate; however, it can occur late during therapy too

  10. Can lung function measurements be used to predict which patients will be at risk of developing interstitial pneumonitis after bone marrow transplantation?

    PubMed

    Milburn, H J; Prentice, H G; du Bois, R M

    1992-06-01

    Lung function often deteriorates after bone marrow transplantation for haematological malignancies. Whether pulmonary function measurements are useful for monitoring patients' progress after transplantation and for alerting clinicians to the development of pneumonitis is uncertain. Serial pulmonary function measurements were made in 39 patients with a haematological malignancy, and the values from 18 recipients of T cell depleted allogeneic (n = 17) or autologous (n = 1) bone marrow transplants who developed interstitial pneumonitis were compared retrospectively with values from 21 recipients of allogeneic (n = 17) or autologous (n = 4) transplants who did not develop pneumonitis. Lung function was measured at the onset of a further 18 episodes of pneumonitis. Measurements made before transplantation showed no difference in forced expiratory volume in one second (FEV1), transfer factor for carbon monoxide (TLCO), or total lung capacity between the two groups, but the forced vital capacity (FVC) was slightly higher in those who developed pneumonitis (mean (SD)% predicted 104 (12)) than in those who did not (93 (17%)). Six weeks and three months after transplantation all pulmonary function measurements had fallen slightly in both groups but TLCO had fallen considerably more in those who later developed pneumonitis, being 71% (SD 11%) and 77% (7%) of pretransplant values in patients who later developed pneumonitis compared with 109% (38%) and 96% (26%) in those who did not. All lung function measurements were significantly lower at the onset of pneumonitis than three months after transplantation, even in patients with no abnormal signs and a normal chest radiograph. Serial measurements of gas transfer before and after bone marrow transplantation may be useful for predicting which patients will be at risk of developing pneumonitis and may help to diagnose pneumonitis in breathless patients with no abnormal signs.

  11. Pneumonitis: a serious adverse effect of PD-L1 inhibitors including pembrolizumab.

    PubMed

    Rickard, Frances; Hyams, Catherine; Low, Andrew T

    2018-05-07

    A 70-year-old man presented with breathlessness, cough and fever while receiving pembrolizumab for melanoma. A CT pulmonary angiogram demonstrated small bilateral upper lobe segmental pulmonary emboli with patchy ground-glass opacities and basal perilobular consolidation, in keeping with organising pneumonia. He was treated for community-acquired pneumonia and pulmonary emboli but rapidly deteriorated, with increasing hypoxia and dyspnoea. He was admitted to the intensive care unit for support with continuous positive airway pressure and high flow nasal oxygen. His clinical condition improved once he received high-dose intravenous methylprednisolone to treat pneumonitis. His treatment was continued with a weaning course of high-dose oral steroids, and he was discharged with a persistent oxygen requirement. The patient maintained a requirement for high doses of oral steroids and continued to deteriorate. He was referred to palliative care for symptom management and died a month following hospital discharge, as a result of pneumonitis due to pembrolizumab. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. [Environmental causes of the distal airways disease. Hypersensitivity pneumonitis and rare causes].

    PubMed

    Dalphin, J-C; Didier, A

    2013-10-01

    Hypersensitivity pneumonitis is one of the most frequent causes of distal airways disease. It is associated with inflammation of the bronchioles, predominantly by lymphocytic infiltrates, and with granuloma formation causing bronchial obstruction. This inflammation explains the clinical manifestations and the airways obstruction seen on pulmonary function tests, most often in the distal airways but proximal in almost 20%. CT scan abnormalities reflect the lymphocytic infiltrates and air trapping and, in some cases, the presence of emphysema. Bronchiolitis induced by chronic inhalation of mineral particles or acute inhalation of toxic gases (such as NO2) are other examples of small airways damage due to environmental exposure. The pathophysiological mechanisms are different and bronchiolar damage is either exclusive or predominant. Bronchiolitis induced by tobacco smoke exposure, usually classified as interstitial pneumonitis, is easily diagnosed thanks to broncho-alveolar lavage. Its prognosis is linked to the other consequences of tobacco smoke exposure including respiratory insufficiency. Finally, the complex lung exposure observed in some rare cases (such as the World Trade Center fire or during wars) may lead to a less characteristic pattern of small airways disease. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  13. Impact of the Pla protease substrate α2-antiplasmin on the progression of primary pneumonic plague.

    PubMed

    Eddy, Justin L; Schroeder, Jay A; Zimbler, Daniel L; Bellows, Lauren E; Lathem, Wyndham W

    2015-12-01

    Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. [Human plague and pneumonic plague : pathogenicity, epidemiology, clinical presentations and therapy].

    PubMed

    Riehm, Julia M; Löscher, Thomas

    2015-07-01

    Yersinia pestis is a highly pathogenic gram-negative bacterium and the causative agent of human plague. In the last 1500 years and during three dreaded pandemics, millions of people became victims of Justinian's plague, the Black Death, or modern plague. Today, Y. pestis is endemic in natural foci of Asian, African and American countries. Due to its broad dissemination in mammal species and fleas, eradication of the pathogen will not be possible in the near future. In fact, plague is currently classified as a "re-emerging disease". Infection may occur after the bite of an infected flea, but also after oral ingestion or inhalation of the pathogen. The clinical presentations comprise the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Most human cases can successfully be treated with antibiotics. However, the high transmission rate and lethality of pneumonic plague require international and mandatory case notification and quarantine of patients. Rapid diagnosis, therapy and barrier nursing are not only crucial for the individual patient but also for the prevention of further spread of the pathogen or of epidemics. Therefore, WHO emergency schedules demand the isolation of cases, identification and surveillance of contacts as well as control of zoonotic reservoir animals and vectors. These sanctions and effective antibiotic treatment usually allow a rapid containment of outbreaks. However, multiple antibiotic resistant strains of Y. pestis have been isolated from patients in the past. So far, no outbreaks with such strains have been reported.

  15. Toxic pneumonitis caused by inhalation of hydrocarbon waterproofing spray in two dogs.

    PubMed

    Young, Brian C; Strom, Adam M; Prittie, Jennifer E; Barton, Linda J

    2007-07-01

    2 dogs were evaluated because of vomiting and lethargy (a Toy Poodle; dog 1) and acute respiratory distress, vomiting, and anorexia (a Chihuahua; dog 2). Dog 1 had been exposed to a commercial hydrocarbon waterproofing spray 24 hours before the development of clinical signs, and dog 2 was examined 18 hours after exposure to a waterproofing spray containing heptane, a highly flammable liquid hydrocarbon. In both dogs, major gastrointestinal tract abnormalities were ruled out but respiratory status worsened. Thoracic radiography revealed a diffuse interstitial pulmonary pattern, and hypoxemia was detected. Hospitalization for monitoring and care was required for both dogs. The dogs recovered with supportive care, which included administration of oxygen, fluids, and bronchodilators. Additionally, dog 1 received glucocorticoids via inhalation and supplemental enteral nutrition, whereas dog 2 was treated with an antimicrobial. The dogs of this report developed hydrocarbon pneumonitis following exposure to waterproofing sprays. Such sprays contain potentially toxic hydrocarbons. The severity of the adverse effects associated with exposure may have been amplified because the dogs were physically small and were exposed to a relatively large amount of aerosolized spray within small areas. Development of chemical pneumonitis in pet animals is best prevented by application of waterproofing sprays in well-ventilated or outdoor areas from which pets have been excluded. With prolonged hospitalization and considerable monitoring and care, affected dogs can recover from these exposures.

  16. Impact of the Pla Protease Substrate α2-Antiplasmin on the Progression of Primary Pneumonic Plague

    PubMed Central

    Eddy, Justin L.; Schroeder, Jay A.; Zimbler, Daniel L.; Bellows, Lauren E.

    2015-01-01

    Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection. PMID:26438794

  17. Pneumonic Tularemia in Rabbits Resembles the Human Disease as Illustrated by Radiographic and Hematological Changes after Infection

    PubMed Central

    Reed, Douglas S.; Smith, Le'Kneitah; Dunsmore, Tammy; Trichel, Anita; Ortiz, Luis A.; Cole, Kelly Stefano; Barry, Eileen

    2011-01-01

    Background Pneumonic tularemia is caused by inhalation of the gram negative bacterium, Francisella tularensis. Because of concerns that tularemia could be used as a bioterrorism agent, vaccines and therapeutics are urgently needed. Animal models of pneumonic tularemia with a pathophysiology similar to the human disease are needed to evaluate the efficacy of these potential medical countermeasures. Principal Findings Rabbits exposed to aerosols containing Francisella tularensis strain SCHU S4 developed a rapidly progressive fatal pneumonic disease. Clinical signs became evident on the third day after exposure with development of a fever (>40.5°C) and a sharp decline in both food and water intake. Blood samples collected on day 4 found lymphopenia and a decrease in platelet counts coupled with elevations in erythrocyte sedimentation rate, alanine aminotransferase, cholesterol, granulocytes and monocytes. Radiographs demonstrated the development of pneumonia and abnormalities of intestinal gas consistent with ileus. On average, rabbits were moribund 5.1 days after exposure; no rabbits survived exposure at any dose (190–54,000 cfu). Gross evaluation of tissues taken at necropsy showed evidence of pathology in the lungs, spleen, liver, kidney and intestines. Bacterial counts confirmed bacterial dissemination from the lungs to the liver and spleen. Conclusions/Significance The pathophysiology of pneumonic tularemia in rabbits resembles what has been reported for humans. Rabbits therefore are a relevant model of the human disease caused by type A strains of F. tularensis. PMID:21931798

  18. Refractory acute respiratory failure due to Pneumocystis jiroveci (PCP) and Cytomegalovirus (CMV) pneumonitis: A case report and review of literature.

    PubMed

    Shah, Kairav; Cherabuddi, Kartikeya; Beal, Stacy G; Kalyatanda, Gautam

    2017-01-01

    Opportunistic infections with Pneumocystis jiroveci pneumonia (PCP) are common in patients with HIV (human immunodeficiency virus) and are encountered once the CD4 count decreases below 200 cells/mm3. Cytomegalovirus (CMV) tends to cause disease once the CD4 count drops below 50 cells/mm3. CMV pneumonitis is not common in this population. However, detecting its presence in broncho-alveolar lavage (BAL) fluid has been associated with increased morbidity and mortality. The role of antiviral therapy against CMV remains unclear. We report a newly diagnosed HIV patient with a CD4 count of 44 cells/mm3 presenting with acute respiratory failure secondary to PCP that failed to respond to 3 weeks of standard therapy with trimethoprim-sulfamethoxazole and corticosteroids. He was later diagnosed to have a CMV co-infection causing pneumonitis with BAL cytology findings showing CMV cytopathic effects and PCP. Plasma CMV DNA PCR was 17,424 copies/mL. He responded well after introduction of intravenous ganciclovir. The presence of histopathologic changes demonstrating viral cytopathic effects on BAL cytology along with a high plasma CMV DNA PCR should raise the specificity for diagnosing CMV pneumonitis. True PCP and CMV pneumonitis can occur, and the addition of antiviral therapy with ganciclovir may benefit such patients in the right clinical scenario.

  19. Hypersensitivity Pneumonitis

    MedlinePlus

    ... breed animals or birds, cheese washers, woodworkers, and wine makers—have a greater chance of exposure to ... this test, talk to your doctor about the benefits and possible risks of this procedure. Lung biopsies ...

  20. Chemical pneumonitis

    MedlinePlus

    ... problems. DO NOT siphon gas, kerosene, or other toxic liquid chemicals. Alternative Names Aspiration pneumonia - chemical Images Lungs Respiratory system References Blanc PD. Acute responses to toxic exposures. In: Broaddus VC, Mason RJ, Ernst JD, ...

  1. Pneumonic Plague

    MedlinePlus

    ... Cyanogen chloride (CK) Digitalis Case Definition: Digitalis Poisoning Ethylene glycol Fentanyls and other opioids Case Definition: Opioids ( ... Thallium Toxic alcohols Case Definition: Toxic Alcohol Poisoning Ethylene glycol Trichothecene Case Definition: Trichothecene Mycotoxin Poisoning Unidentified ...

  2. Evaluation of dose response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Tsougos, Ioannis; Mavroidis, Panayiotis; Rajala, Juha; Theodorou, Kyriaki; Järvenpää, Ritva; Pitkänen, Maunu A.; Holli, Kaija; Ojala, Antti T.; Lind, Bengt K.; Hyödynmaa, Simo; Kappas, Constantin

    2005-08-01

    The purpose of this work is to evaluate the predictive strength of the relative seriality, parallel and LKB normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis, in a large group of patients following breast cancer radiotherapy, and furthermore, to illustrate statistical methods for examining whether certain published radiobiological parameters are compatible with a clinical treatment methodology and patient group characteristics. The study is based on 150 consecutive patients who received radiation therapy for breast cancer. For each patient, the 3D dose distribution delivered to lung and the clinical treatment outcome were available. Clinical symptoms and radiological findings, along with a patient questionnaire, were used to assess the manifestation of radiation-induced complications. Using this material, different methods of estimating the likelihood of radiation effects were evaluated. This was attempted by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Additionally, the need for an update of the criteria that are being used in the current clinical practice was also examined. The patient material was selected without any conscious bias regarding the radiotherapy treatment technique used. The treatment data of each patient were applied to the relative seriality, LKB and parallel NTCP models, using published parameter sets. Of the 150 patients, 15 experienced radiation-induced pneumonitis (grade 2) according to the radiation pneumonitis scoring criteria used. Of the NTCP models examined, the relative seriality model was able to predict the incidence of radiation pneumonitis with acceptable accuracy, although radiation pneumonitis was developed by only a few patients. In the case of modern breast radiotherapy, radiobiological modelling appears to be very sensitive to model and parameter selection giving clinically

  3. Risk Factors Associated With Symptomatic Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer.

    PubMed

    Shi, Shiming; Zeng, Zhaochong; Ye, Luxi; Huang, Yan; He, Jian

    2017-06-01

    Radiation pneumonitis is the most frequent acute pulmonary toxicity following stereotactic body radiation therapy for lung cancer. Here, we investigate clinical and dosimetric factors associated with symptomatic radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy. A total of 67 patients with stage I non-small cell lung cancer who received stereotactic body radiation therapy at our institution were enrolled, and their clinicopathological parameters and dosimetric parameters were recorded and analyzed. The median follow-up period was 26.4 months (range: 7-48 months). In univariate analysis, tumor size ( P = .041), mean lung dose ( P = .028), V2.5 ( P = .024), V5 ( P = .014), V10 ( P = .004), V20 ( P = .024), V30 ( P = .020), V40 ( P = .040), and V50 ( P = 0.040) were associated with symptomatic radiation pneumonitis. In multivariable logistic regression analysis, V10 ( P = .049) was significantly associated with symptomatic radiation pneumonitis. In conclusion, this study found that tumor size, mean lung dose, and V2.5 to V50 were risk factors markedly associated with symptomatic radiation pneumonitis. Our data suggested that lung V10 was the most significant factor, and optimizing lung V10 may reduce the risk of symptomatic radiation pneumonitis. For both central and peripheral stage I lung cancer, rate of radiation pneumonitis ≥grade 2 was low after stereotactic body radiation therapy with appropriate fraction dose.

  4. The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

    PubMed Central

    Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

    2018-01-01

    Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule. PMID

  5. An Adult Case of Chronic Active Epstein-Barr Virus Infection with Interstitial Pneumonitis

    PubMed Central

    Joo, Eun-Jeong; Ha, Young Eun; Jung, Dong Sik; Cheong, Hae Suk; Wi, Yu Mi; Song, Jae-Hoon

    2011-01-01

    Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment. PMID:22205850

  6. An adult case of chronic active Epstein-Barr virus infection with interstitial pneumonitis.

    PubMed

    Joo, Eun-Jeong; Ha, Young Eun; Jung, Dong Sik; Cheong, Hae Suk; Wi, Yu Mi; Song, Jae-Hoon; Peck, Kyong Ran

    2011-12-01

    Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment.

  7. Methotrexate-induced pneumonitis in Crohn's disease. Case report and review of the literature

    PubMed Central

    2010-01-01

    Methotrexate (MTX) is a folate-antagonist used in several neoplastic and inflammatory diseases. Reports of pulmonary complications in patients given low-dose MTX therapy are increasing. Pulmonary toxicity from MTX has a variable frequency and can present with different forms. Most often MTX-induced pneumonia in patients affected by rheumatoid arthritis (RA) is reported. In this paper we describe a case of MTX-related pneumonitis in a relatively young woman affected by Crohn's disease who presented non-productive cough, fever and dyspnea on exercise. Chest X-ray demonstrated bilateral interstitial infiltrates and at computed tomography (CT) ground-glass opacities appeared in both lungs. At spirometry an obstructive defect was demonstrated. A rapid improvement of symptoms and the regression of radiographic and spirometric alterations was achieved through MTX withdrawal and the introduction of corticosteroid therapy. PMID:22958737

  8. Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague

    PubMed Central

    Stasulli, Nikolas M.; Eichelberger, Kara R.; Price, Paul A.; Pechous, Roger D.; Montgomery, Stephanie A.; Parker, Joel S.

    2015-01-01

    ABSTRACT During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (RNA-seq) analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are downregulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both in vitro and in vivo that Y. pestis increases neutrophil survival in a manner that is dependent on the type III secretion system effector YopM. This research explores the complexity of spatially distinct host-microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand Y. pestis virulence. PMID:26463167

  9. Diagnosis of hypersensitivity pneumonitis by measurement of antibodies against environmental antigens

    SciTech Connect

    Dewair, M.

    1989-01-01

    Hypersensitivity pneumonitis (HP), an immunologically mediated chronic pulmonary disease, is the result of an inflammatory response of the lung initiated by the inhalation of environmental organic dusts. These organic dusts usually contain substances (antigens) capable of eliciting immune responses in humans. The symptoms of HP generally present as recurrent flu-like episodes which makes it difficult to establish the proper diagnosis. However, detection in patients' sera of high-titer antibodies against the environmental antigens could be of great help in identifying those materials causing the disease and which must be avoided. A highly specific and sensitive serodiagnostic test, a radioimmuno assay (RIA),more » was developed for measurement of antibodies against antigens relevant to Farmer's Lung Disease (FLD), a type of HP affecting farmers.« less

  10. [Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy].

    PubMed

    Gómez Tejada, Ricardo A; Legarreta, Cora G; Enghelmayer, Juan Ignacio; Dianti, Milagros; Acuña, Silvana; Olmedo, Gloria

    2017-01-01

    In a series of nine patients with histopathological diagnosis of hypersensitivity pneumonitis, we retrospectively evaluated clinical data, exposure related factors, pulmonary function tests and chest computed tomography scans. A restrictive abnormality with reduction of diffusion capacity for carbon monoxide was mainly found. Chest scans showed fibrotic patterns in most cases; ground glass attenuation areas with mosaic pattern and consolidation in the rest. Exposure to avian antigens, cereal grains and air conditioners contaminated with fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the cases. Since there are no unique features that allow differentiation from other interstitial lung diseases, a high clinical suspicion is required and a careful search of environmental exposure to possible antigens is needed that, together with clinical, radiological and pathological data, may lead to diagnosis.

  11. Antibiotic Therapy in Comatose Mechanically Ventilated Patients Following Aspiration: Differentiating Pneumonia From Pneumonitis.

    PubMed

    Lascarrou, Jean Baptiste; Lissonde, Floriane; Le Thuaut, Aurélie; Bachoumas, Konstantinos; Colin, Gwenhael; Henry Lagarrigue, Matthieu; Vinatier, Isabelle; Fiancette, Maud; Lacherade, Jean Claude; Yehia, Aihem; Joret, Aurélie; Lebert, Christine; Bourdon, Sandra; Martin Lefèvre, Laurent; Reignier, Jean

    2017-08-01

    To determine the proportion of patients with documented bacterial aspiration pneumonia among comatose ICU patients with symptoms suggesting either bacterial aspiration pneumonia or non-bacterial aspiration pneumonitis. Prospective observational study. University-affiliated 30-bed ICU. Prospective cohort of 250 patients admitted to the ICU with coma (Glasgow Coma Scale score ≤ 8) and treated with invasive mechanical ventilation. None. The primary outcome was the proportion of patients with microbiologically documented bacterial aspiration pneumonia. Patients meeting predefined criteria for aspiration syndrome routinely underwent telescopic plugged catheter sampling during bronchoscopy before starting probabilistic antibiotic treatment. When cultures were negative, the antibiotic treatment was stopped. Of 250 included patients, 98 (39.2%) had aspiration syndrome, including 92 before mechanical ventilation discontinuation. Telescopic plugged catheter in these 92 patients showed bacterial aspiration pneumonia in 43 patients (46.7%). Among the remaining 49 patients, 16 continued to receive antibiotics, usually for infections other than pneumonia; of the 33 patients whose antibiotics were discontinued, only two subsequently showed signs of lung infection. In the six patients with aspiration syndrome after mechanical ventilation, and therefore without telescopic plugged catheter, antibiotic treatment was continued for 7 days. Mechanical ventilation duration, ICU length of stay, and mortality did not differ between the 43 patients with bacterial aspiration pneumonia and the 49 patients with non-bacterial aspiration pneumonitis. The 152 patients without aspiration syndrome did not receive antibiotics. Among comatose patients receiving mechanical ventilation, those without clinical, laboratory, or radiologic evidence of bacterial aspiration pneumonia did not require antibiotics. In those with suspected bacterial aspiration pneumonia, stopping empirical antibiotic therapy

  12. [A case of radiation pneumonitis with eosinophilia in bronchoalveolar lavage fluid].

    PubMed

    Kawai, Seiko; Baba, Kenji; Tanaka, Hiroyuki; Takahashi, Daisuke; Yagi, Takeo; Hattori, Tsutomu; Etsuro, Yamaguchi

    2008-01-01

    A 78-year-old man was admitted to our hospital for irradiation therapy of non-resectable primary lung squamous cell carcinoma of the right middle lobe (T3N2M0). The Linac irradiation through opposing 2 gates (2Gy per day and 60Gy in total) was performed to the affected area including the metastatic right hilar and mediastinal lymphadenopathy. One week after completing the irradiation therapy, fever developed with infiltrates in the area from the right middle lobe to the right lower lobe, which did not necessarily coincide with the irradiated area. Antibiotic therapies were not effective. Both the serum LDH level and eosinophil count in the peripheral blood increased. Bronchoalveolar lavage was performed at the right B8, and differential cell counts of the lavage fluid were: macrophages, 17%; lymphocytes, 60%; neutrophils, 5%; and eosinophils, 18%. No significant organisms were obtained by culture of the lavage fluid. The %VC and DLCO/VA became lower than before the irradiation therapy. Thus, the patient was given a diagnosis of radiation pneumonitis. Treatment with 40mg/day oral prednisolone was commenced with a stepwise dose-reduction (5mg every two weeks) until reaching the maintenance dose of 15mg/day. The serum LDH level and blood eosinophil count recovered promptly to the normal range. The pulmonary infiltrates and the lung functions substantially improved. There have been few reports of radiation pneumonitis in which eosinophil counts increased in peripheral blood and bronchoalveolar lavage fluid after irradiation therapy. In the present case report, the possible mechanisms for the irradiation-induced eosinophilia were also reviewed.

  13. [Cutaneous lesions during hot-tub hypersensitivity pneumonitis: Pseudomonas folliculitis ?

    PubMed

    Sokolowsky, N; Rolland, L; Vandenhende, M-A; Colin, J-Y; Laurent, F; Morlat, P; Bonnet, F; Beylot-Barry, M

    2017-04-01

    Interstitial lung disease, cutaneous rash and elevated serum angiotensin converting enzyme (ACE) may suggest diagnoses other than sarcoidosis. A 58-year-old man had presented dyspnoea for 2 years with increased angiotensin-converting enzyme, as well as an interstitial syndrome and micronodules. The possibility of sarcoidosis was raised. Systemic corticosteroids resulted in improvement of the dyspnoea although it recurred on dose reduction. We noted fluctuating eczematous macules of the limbs with a histology of aspecific folliculitis. The identification of Mycobacterium avium complex (MAC) in the bronchoalveolar wash prompted us to initiate antimycobacterial therapy, but this was to no avail. Review of the CT-scan and questioning of the patient (daily use of a Jacuzzi for 7 years) resulted in diagnosis of hypersensitivity pneumonitis due to MAC. The cutaneous lesions were taken to indicate "hot tub folliculitis". Discontinuation of hot-tub use and a short course of oral corticosteroids resulted in healing within 4 months, with no recurrence at 2 years. HTL is a form of hypersensitivity pneumonitis due to the presence of MAC in the water of Jacuzzis. This condition regresses spontaneously without treatment on discontinuation of Jacuzzi use. Hot-tub folliculitis due to Pseudomonas aeruginosa (PA) presents as macules and papules on covered skin areas (swimsuit) within 48hours of bathing and often declines within 2 weeks. Our case is original as regards the concomitant lung and cutaneous involvement associated with Jacuzzi use, with an immunoallergic mechanism for the MAC and probably an infectious mechanism for the PA. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Decreased Risk of Radiation Pneumonitis With Incidental Concurrent Use of Angiotensin-Converting Enzyme Inhibitors and Thoracic Radiation Therapy

    SciTech Connect

    Kharofa, Jordan; Cohen, Eric P.; Tomic, Rade

    2012-09-01

    Purpose: Angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models. The aim of this study was to evaluate whether ACE inhibitors decrease the risk of radiation pneumonitis in lung cancer patients receiving thoracic irradiation. Methods and Materials: Patients with Stage I through III small-cell and non-small-cell lung cancer treated definitively with radiation from 2004-2009 at the Clement J. Zablocki Veterans Affairs Medical Center were retrospectively reviewed. Acute pulmonary toxicity was quantified within 6 months of completion of treatment according to the Common Terminology Criteria for Adverse Events version 4. The use of ACE inhibitors,more » nonsteroidal anti-inflammatory drugs, inhaled glucocorticosteroids, statins, and angiotensin receptor blockers; dose-volume histogram parameters; and patient factors were assessed for association with Grade 2 or higher pneumonitis. Results: A total of 162 patients met the criteria for inclusion. The majority of patients had Stage III disease (64%) and received concurrent chemotherapy (61%). Sixty-two patients were identified as ACE inhibitor users (38%). All patients had acceptable radiation plans based on dose-volume histogram constraints (V20 [volume of lung receiving at least 20 Gy] {<=}37% and mean lung dose {<=}20 Gy) with the exception of 2 patients who did not meet both criteria. Grade 2 or higher pulmonary toxicity occurred in 12 patients (7.4%). The rate of Grade 2 or higher pneumonitis was lower in ACE inhibitor users vs. nonusers (2% vs. 11%, p = 0.032). Rates of Grade 2 or higher pneumonitis were significantly increased in patients aged greater than 70 years (16% vs. 2%, p = 0.005) or in whom V5 (volume of lung receiving at least 5 Gy) was 50% or greater (13% vs. 4%, p = 0.04). V10 (volume of lung receiving at least 10 Gy), V20, V30 (volume of lung receiving at least 30 Gy), and mean lung dose were not independently associated with Grade

  15. Protection of mice from fatal bubonic and pneumonic plague by passive immunization with monoclonal antibodies against the F1 protein of Yersinia pestis.

    PubMed

    Anderson, G W; Worsham, P L; Bolt, C R; Andrews, G P; Welkos, S L; Friedlander, A M; Burans, J P

    1997-04-01

    Monoclonal antibodies (MAbs) to the fraction 1 (F1) protein of Yersinia pestis protected mice against fatal pneumonic as well as bubonic plague from wild-type F1+ organisms. The rare isolation of a virulent F1- isolate from surviving animals supports earlier studies suggesting that improved vaccines should consist of immunogens to protect against F1- variants. The high degree of protection with IgG MAb suggests that secretory IgA is not required for protection from pneumonic plague.

  16. Protection against experimental bubonic and pneumonic plague by a recombinant capsular F1-V antigen fusion protein vaccine.

    PubMed

    Heath, D G; Anderson, G W; Mauro, J M; Welkos, S L; Andrews, G P; Adamovicz, J; Friedlander, A M

    1998-07-01

    The current human whole-cell vaccine is ineffective against pneumonic plague caused by typical F1 capsule positive (F1+) strains of Yersinia pestis. The authors found this vaccine to also be ineffective against F1-negative (F1-) Y. pestis strains, which have been isolated from a human case and from rodents. For these reasons, the authors developed a recombinant vaccine composed of a fusion protein of F1 with a second protective immunogen, V antigen. This vaccine protected experimental mice against pneumonic as well as bubonic plague produced by either an F1+ or F1- strain of Y. pestis, gave better protection than F1 or V alone against the F1+ strain, and may provide the basis for an improved human plague vaccine.

  17. Hypersensitivity pneumonitis associated with mushroom worker's lung: an update on the clinical significance of the importation of exotic mushroom varieties.

    PubMed

    Moore, John E; Convery, Rory P; Millar, B Cherie; Rao, Juluri R; Elborn, J Stuart

    2005-01-01

    Hypersensitivity pneumonitis remains an important industrial disease in mushroom workers. It has a significant morbidity, and early diagnosis and removal from exposure to the antigen are critically important in its management. Recently, several new allergens have been described, particularly those from mushroom species originating in the Far East, which are of clinical significance to workers occupationally exposed to such allergens in cultivation, picking, and packing of commercial mushroom crops. Importing of exotic mushrooms including Shiitake is common in EU countries, and some of the exotic species of mushrooms are cultivated for local markets. This practice may contribute to an increase in clinical cases of mushroom hypersensitivity pneumonitis. This update reviews the recent literature and examines changing trends of mushroom worker's lung, with increased movement of commercial product and labour markets worldwide.

  18. Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague.

    PubMed

    Arnaboldi, Paul M; Sambir, Mariya; D'Arco, Christina; Peters, Lauren A; Seegers, Jos F M L; Mayer, Lloyd; McCormick, Alison A; Dattwyler, Raymond J

    2016-11-11

    Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y. pestis virulence factors, F1 and LcrV, demonstrated variable levels of protection in primate pneumonic plague models. As the most likely mode of exposure in biological attack with Y. pestis is by aerosol, this raises a question of whether this parenteral vaccine will adequately protect humans against pneumonic plague. In the present study we evaluated two distinct mucosal delivery platforms for the intranasal (IN) administration of LcrV and F1 vaccine proteins, a live bacterial vector, Lactobacillus plantarum, and a Tobacco Mosaic Virus (TMV) based delivery platform. IN administration of L. plantarum expressing LcrV, or TMV-conjugated to LcrV and F1 (TMV-LcrV+TMV-F1) resulted in the similar induction of high titers of IgG antibodies and evidence of proinflammatory cytokine secretion. However, only the TMV-conjugate delivery platform protected against subsequent lethal challenge with Y. pestis. TMV-LcrV+TMV-F1 co-vaccinated mice had no discernable morbidity and no mortality, while mice vaccinated with L. plantarum expressing LcrV or rLcrV+rF1 without TMV succumbed to infection or were only partially protected. Thus, TMV is a suitable mucosal delivery platform for an F1-LcrV subunit vaccine that induces complete protection against pneumonic infection with a lethal dose of Y. pestis in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Risk factors for pneumonic and ulceroglandular tularaemia in Finland: a population-based case-control study.

    PubMed

    Rossow, H; Ollgren, J; Klemets, P; Pietarinen, I; Saikku, J; Pekkanen, E; Nikkari, S; Syrjälä, H; Kuusi, M; Nuorti, J P

    2014-10-01

    Few population-based data are available on factors associated with pneumonic and ulceroglandular type B tularaemia. We conducted a case-control study during a large epidemic in 2000. Laboratory-confirmed case patients were identified through active surveillance and matched control subjects (age, sex, residency) from the national population information system. Data were collected using a self-administered questionnaire. A conditional logistic regression model addressing missing data with Bayesian full-likelihood modelling included 227 case patients and 415 control subjects; reported mosquito bites [adjusted odds ratio (aOR) 9·2, 95% confidence interval (CI) 4·4-22, population-attributable risk (PAR) 82%] and farming activities (aOR 4·3, 95% CI 2·5-7·2, PAR 32%) were independently associated with ulceroglandular tularaemia, whereas exposure to hay dust (aOR 6·6, 95% CI 1·9-25·4, PAR 48%) was associated with pneumonic tularaemia. Although the bulk of tularaemia type B disease burden is attributable to mosquito bites, risk factors for ulceroglandular and pneumonic forms of tularaemia are different, enabling targeting of prevention efforts accordingly.

  20. Predictive factors for acute radiation pneumonitis in postoperative intensity modulated radiation therapy and volumetric modulated arc therapy of esophageal cancer.

    PubMed

    Zhao, Yaqin; Chen, Lu; Zhang, Shu; Wu, Qiang; Jiang, Xiaoqin; Zhu, Hong; Wang, Jin; Li, Zhiping; Xu, Yong; Zhang, Ying Jie; Bai, Sen; Xu, Feng

    2015-01-01

    Radiation pneumonitis (RP) is a common side reaction in radiotherapy for esophageal cancer. There are few reports about RP in esophageal cancer patients receiving postoperative intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). This study aims to analyze clinical or dosimetric factors associated with RP, and provides data for radiotherapy planning. We reviewed 68 postoperative esophageal cancer patients who were treated with radiotherapy at the West China Hospital from October 2010 to November 2012 to identify any correlation between the clinical or dosimetric parameters and acute radiation pneumonitis (ARP) or severe acute radiation pneumonitis (SARP) by t-test, chi-square test, and logistic regression analysis. Of the 68 patients, 33 patients (48.5%) developed ARP, 13 of which (19.1%) developed SARP. Of these 33 patients, 8 (11.8%), 12 (17.6%), 11 (16.2%), and 2 (2.9%) patients were grade 1, 2, 3, and 4 ARP, respectively. Univariate analysis showed that lung infection during radiotherapy, use of VMAT, mean lung dose (MLD), and dosimetric parameters (e.g. V20, V30) are significantly correlated with RP. Multivariate analysis found that lung infection during radiotherapy, MLD ≥ 12 Gy, and V30 ≥ 13% are significantly correlated with an increased risk of RP. Lung infection during radiotherapy and low radiation dose volume distribution were predictive factors associated with RP and should be accounted for during radiation planning.

  1. Hypersensitivity pneumonitis due to metal working fluids: Sporadic or under reported?

    PubMed

    Gupta, Amit; Rosenman, Kenneth D

    2006-06-01

    Occupational exposure to metal working fluids (MWF) is common with over 1.2 million workers in the United States involved in machine finishing, machine tooling, and other metalworking operations. MWF is a known cause of hypersensitivity pneumonitis (HP). Recent reports of outbreaks of hypersensitivity HP secondary to exposure to MWF are reported. Cases were identified through the Occupational Disease surveillance system in the State of Michigan and from referrals for evaluation to the Division of Occupational and Environmental Medicine at Michigan State University (MSU). Each patient underwent a clinical examination including an occupational history, lung function studies, radiographic imaging, and in some cases lung biopsies. Following the diagnosis of definite HP, an industrial hygiene investigation was carried out, which included a plant walk-through, and review of the "Injury and Illness" log. Air monitoring and microbial sampling results were reviewed. As part of Michigan's mandatory surveillance system for occupational illnesses, seven cases of suspected HP were identified in 2003-2004 from three facilities manufacturing automobile parts in Michigan. Each plant used semi-synthetic MWFs, and conducted a MWF management program including biocide additions. Two facilities had recently changed the MWF before the cases arose. Growth of mycobacteria was found in these two MWFs. Breathing zone samples for particulates of two employees in plant A (two cases) ranged from 0.48 to 0.56 mg/m3. In plant B (four cases), two employees' sampling results ranged from 0.10 to 0.14 mg/m3. No air sampling data were available from plant C. Hypersensitivity pneumonitis due to exposure to MWFs is under-recognized by health care providers, and current surveillance systems are inadequate to provide a true estimate of its occurrence. HP arose from environments with exposures well below the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for MWF, and

  2. Immunization with recombinant V10 protects cynomolgus macaques from lethal pneumonic plague.

    PubMed

    Cornelius, Claire A; Quenee, Lauriane E; Overheim, Katie A; Koster, Frederick; Brasel, Trevor L; Elli, Derek; Ciletti, Nancy A; Schneewind, Olaf

    2008-12-01

    Vaccine and therapeutic strategies that prevent infections with Yersinia pestis have been sought for over a century. Immunization with live attenuated (nonpigmented) strains and immunization with subunit vaccines containing recombinant low-calcium-response V antigen (rLcrV) and recombinant F1 (rF1) antigens are considered effective in animal models. Current antiplague subunit vaccines in development for utilization in humans contain both antigens, either as equal concentrations of the two components (rF1 plus rLcrV) or as a fusion protein (rF1-rLcrV). Here, we show that immunization with either purified rLcrV (a protein at the tip of type III needles) or a variant of this protein, recombinant V10 (rV10) (lacking amino acid residues 271 to 300), alone or in combination with rF1, prevented pneumonic lesions and disease pathogenesis. In addition, passive immunization studies showed that specific antibodies of macaques immunized with rLcrV, rV10, or rF1, either alone or in combination, conferred protection against bubonic plague challenge in mice. Finally, we found that when we compared the reactivities of anti-rLcrV and anti-rV10 immune sera from cynomolgus macaques, BALB/c mice, and brown Norway rats with LcrV-derived peptides, rV10, but not rLcrV immune sera, lacked antibodies recognizing linear LcrV oligopeptides.

  3. Eosinophilic pneumonitis induced by aerosol-administered diesel oil and pyrethrum to mice.

    PubMed

    Garcia, Maria Lúcia B; Santos, Ubiratan P; Perini, Adenir; Acencio, Milena M P; Lopes, Fernanda D T Q S; Bueno, Heloisa M S; Saldiva, Paulo H N; Martins, Milton A

    2009-06-01

    To confirm the episode of eosinophilic pneumonitis that occurred in March 2001 in Manaus, Amazon, northern Brazil, as secondary to home aerosolization with 2% cypermethrin diluted in diesel compared with the more conventional 1% cypermethrin and soybean solution used in prophylaxis of dengue. Four groups of Swiss mice were kept in polycarbonate cages aerosolized with one of the following solutions: diesel, diesel and cypermethrin, soy oil and cypermethrin, and saline. Three and 6 days after exposure, resistance and compliance of the respiratory system and white cell kinetics in peripheral blood and lung tissue were analyzed. The group exposed to diesel and cypermethrin showed higher respiratory system resistance (p < 0.001), lower compliance (p = 0.03), and increased eosinophils in blood (p = 0.03) and lung tissue (p = 0.005) compared with the other groups. There was an increase of neutrophils in the blood of all experimental groups on the third day after exposure (p < 0.001). We concluded that diesel associated with cypermethrin induced lung hyperresponsiveness in this experimental model and was associated with increased polymorphonuclear cells (eosinophils and neutrophils) in blood and lungs. This effect is strongest on the third day after exposure. These results are similar to the episode that occurred in Manaus in 2001 and suggest that diesel plus cypermethrin home aerosolization for arbovirosis prophylaxis should be revised.

  4. Interleukin (IL)-1A and IL-6: Applications to the predictive diagnostic testing of radiation pneumonitis

    SciTech Connect

    Chen Yuhchyau; Hyrien, Ollivier; Williams, Jacqueline

    2005-05-01

    Purpose: To explore the application of interleukin (IL)-1{alpha} and IL-6 measurements in the predictive diagnostic testing for symptomatic radiation pneumonitis (RP). Methods and materials: In a prospective protocol investigating RP and cytokines, IL-1{alpha} and IL-6 values were analyzed by enzyme-linked immunosorbent assay from serial weekly blood samples of patients receiving chest radiation. We analyzed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) over selected threshold values for both cytokines in the application to diagnostic testing. Results: The average coefficient of variation was 51% of the weekly mean IL-1{alpha} level and 39% of the weekly mean IL-6 value.more » Interleukin 1{alpha} and IL-6 became positively correlated with time. Specificity for both cytokines was better than sensitivity. IL-6 globally outperformed IL-1{alpha} in predicting RP, with higher PPV and NPV. Conclusions: Our data demonstrate the feasibility of applying IL-1{alpha} and IL-6 measurements of blood specimens to predict RP. Interleukin-6 measurements offer stronger positive predictive value than IL-1{alpha}. This application might be further explored in a larger sample of patients.« less

  5. [Five cases of severe radiation pneumonitis after chemoradiotherapy for esophageal cancer].

    PubMed

    Sakurai, Katsunobu; Kubo, Naoshi; Shibutani, Masatsune; Yamazoe, Sadaaki; Kimura, Kenjiro; Nagahara, Hisashi; Toyokawa, Takahiro; Amano, Ryosuke; Tanaka, Hiroaki; Muguruma, Kazuya; Ohtani, Hiroshi; Yashiro, Masakazu; Maeda, Kiyoshi; Ohira, Masaichi; Hirakawa, Kosei

    2013-11-01

    Chemoradiotherapy( CRT) for esophageal cancer is a useful modality for both locally advanced and resectable cases. Among adverse events related to CRT, radiation pneumonitis( RP) requires special attention because it has been shown to be occasionally associated with a worse acute prognosis. We report 5 cases of severe RP after CRT. All patients were male, and their mean age was 72 years (range: 66-76 years). The clinical stage of esophageal cancer was I in 1 case, II in 2 cases, and IVa in 2 cases. The mean total radiation dose was 51.8 Gy (range: 43.4-61.4). Initial symptoms and first abnormal findings were a high fever in 4 cases and elevated serum C-reactive protein( CRP) levels in 1 case. No patients presented with respiratory symptoms, including dyspnea and coughing, as initial symptoms. All cases were diagnosed as RP by chest computed tomography examination, an average of 6.8 days after the completion of RT. Four patients required intensive care and were put on ventilator support. All patients received steroid pulse therapy. Two patients recovered from RP; however, 3 died( 1 attributable to multi-organ failure and 2 to respiratory failure). It is important to consider RP caused by CRT when patients present with high fever or elevated CRP levels after the completion of RT for esophageal cancer.

  6. Interstitial pneumonitis and the risk of chronic allograft rejection in lung transplant recipients.

    PubMed

    Mihalek, Andrew D; Rosas, Ivan O; Padera, Robert F; Fuhlbrigge, Anne L; Hunninghake, Gary M; DeMeo, Dawn L; Camp, Phillip C; Goldberg, Hilary J

    2013-05-01

    The presence of interstitial pneumonitis (IP) on surveillance lung biopsy specimens in lung transplant recipients is poorly described, and its impact on posttransplant outcomes is not established. The following study assessed the association of posttransplant IP with the development of bronchiolitis obliterans syndrome (BOS). We examined all recipients of primary cadaveric lung transplants at our institution between January 1, 2000, and December 31, 2007 (N = 145). Patients had bronchoscopies with BAL, and transbronchial biopsies performed for surveillance during posttransplant months 1, 3, 6, and 12 as well as when clinically indicated. Patients were given a diagnosis of IP if, in the absence of active infection and organizing pneumonia, they showed evidence of interstitial inflammation and fibrosis on two or more biopsy specimens. IP was a significant predictor of BOS (OR, 7.84; 95% CI, 2.84-21.67; P < .0001) and was significantly associated with time to development of BOS (hazard ratio, 3.8; 95% CI, 1.93-7.39; P = .0001) within the first 6 years posttransplant. The presence of IP did not correlate with a significantly higher risk of mortality or time to death. There was no association between the presence of IP and the development of or time to acute rejection. The presence of IP on lung transplant biopsy specimens suggests an increased risk for BOS, which is independent of the presence of acute cellular rejection.

  7. Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation.

    PubMed

    Barrett, A; Depledge, M H; Powles, R L

    1983-07-01

    Idiopathic and infective interstitial pneumonitis (IPn) is a common complication after bone marrow transplantation (BMT) in many centers and carries a high mortality. We report here a series of 107 patients with acute leukemia grafted at the Royal Marsden Hospital in which only 11 (10.3%) developed IPn and only 5 died (5%). Only one case of idiopathic IPn was seen. Factors which may account for this low incidence are discussed. Sixty of 107 patients were transplanted in first remission of acute myeloid leukemia (AML) and were therefore in good general condition. Lung radiation doses were carefully monitored and doses of 10.5 Gy were not exceeded except in a group of 16 patients in whom a study of escalating doses of TBI (up to 13 Gy) was undertaken. The dose rate used for total body irradiation (TBI) was lower than that used in other centers and as demonstrated elsewhere by ourselves and others, reduction of dose rate to less than 0.05 Gy/min may be expected to lead to substantial reduction in lung damage. Threshold doses of approximately 8 Gy for IPn have been reported, but within the dose range of 8 to 10.5 Gy we suggest that dose rate may significantly affect the incidence. Data so far available suggest a true improvement in therapeutic ratio for low dose rate single fraction TBI compared with high dose rate.

  8. Helminth infections predispose mice to pneumococcal pneumonia but not to other pneumonic pathogens.

    PubMed

    Apiwattanakul, Nopporn; Thomas, Paul G; Kuhn, Raymond E; Herbert, De'Broski R; McCullers, Jonathan A

    2014-10-01

    Pneumonia is the leading killer of children worldwide. Here, we report that helminth-infected mice develop fatal pneumonia when challenged with Streptococcus pneumoniae. Mice were chronically infected with either the flatworm Taenia crassiceps or the roundworm Heligmosomoides polygyrus. Upon challenge with a pneumonic type 3 strain of S. pneumoniae (A66.1), the worm-infected mice developed pneumonia at a rate and to a degree higher than age-matched control mice as measured by bioluminescent imaging and lung titers. This predisposition to pneumonia appears to be specific to S. pneumoniae, as worm-infected mice did not show evidence of increased morbidity when challenged with a lethal dose of influenza virus or sublethal doses of Staphylococcus aureus or Listeria monocytogenes. The defect was also present when worm-infected mice were challenged with a type 2 sepsis-causing strain (D39); an increased rate of pneumonia, decreased survival, and increased lung and blood titers were found. Pneumococcal colonization and immunity against acute otitis media were unaffected. Anti-helminthic treatment in the H. polygyrus model reversed this susceptibility. We conclude that helminth coinfection predisposes mice to fatal pneumococcal pneumonia by promoting increased outgrowth of bacteria in the lungs and blood. These data have broad implications for the prevention and treatment for pneumonia in the developing world, where helminth infections are endemic and pneumococcal pneumonia is common.

  9. Computed tomography in hypersensitivity pneumonitis: main findings, differential diagnosis and pitfalls.

    PubMed

    Dias, Olívia Meira; Baldi, Bruno Guedes; Pennati, Francesca; Aliverti, Andrea; Chate, Rodrigo Caruso; Sawamura, Márcio Valente Yamada; Carvalho, Carlos Roberto Ribeiro de; Albuquerque, André Luis Pereira de

    2018-01-01

    Hypersensitivity pneumonitis (HP) is a disease with variable clinical presentation in which inflammation in the lung parenchyma is caused by the inhalation of specific organic antigens or low molecular weight substances in genetically susceptible individuals. Alterations of the acute, subacute and chronic forms may eventually overlap, and the diagnosis based on temporality and presence of fibrosis (acute/inflammatory HP vs. chronic HP) seems to be more feasible and useful in clinical practice. Differential diagnosis of chronic HP with other interstitial fibrotic diseases is challenging due to the overlap of the clinical history, and the functional and imaging findings of these pathologies in the terminal stages. Areas covered: This article reviews the essential features of HP with emphasis on imaging features. Moreover, the main methodological limitations of high-resolution computed tomography (HRCT) interpretation are discussed, as well as new perspectives with volumetric quantitative CT analysis as a useful tool for retrieving detailed and accurate information from the lung parenchyma. Expert commentary: Mosaic attenuation is a prominent feature of this disease, but air trapping in chronic HP seems overestimated. Quantitative analysis has the potential to estimate the involvement of the pulmonary parenchyma more accurately and could correlate better with pulmonary function results.

  10. Hypersensitivity pneumonitis in a hardwood processing plant related to heavy mold exposure.

    PubMed

    Veillette, Marc; Cormier, Yvon; Israël-Assayaq, Evelyne; Meriaux, Anne; Duchaine, Caroline

    2006-06-01

    Two workers employed in a hardwood floor plant presented symptoms suggestive of hypersensitivity pneumonitis (HP). At that plant, kiln-dried wood often shows moldy growth and is subsequently brought inside for processing. This study evaluated the environment in attempt to identify the causative antigen and verify whether other workers of this and similar plants had or were at risk of developing HP. Dust from dust-removing systems and molds on the surface of wood planks were collected and air samples taken from a sister plant. Blood samples, spirometry, and symptoms' questionnaires were obtained from 11 co-workers. Dense Paecilomyces growth was observed on the surface of the dried processed wood in the index plant. This fungal genus was not detected in the sister plant. An additional worker had symptoms suggestive of HP, and his bronchoalveolar lavage revealed a lymphocytic alveolitis. The 3 confirmed cases of HP and the other 10 workers had positive specific IgG antibodies to Paecilomyces. We report 3 cases of HP out of 13 workers and a 100% sensitization to molds in workers of a hardwood processing plant. This rate is much higher than what is commonly seen in other environments associated with HP. The drying process is suspected of being responsible for the massive Paecilomyces contamination likely responsible for the HP.

  11. Does Bleomycin Lung Toxicity Increase the Risk of Radiation Pneumonitis in Hodgkin Lymphoma?

    SciTech Connect

    Abou Yehia, Zeinab; Mikhaeel, George N.; Smith, Grace

    Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients. Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariatemore » and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP. Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively. Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT.« less

  12. Polarized type 1 cytokine profile in bronchoalveolar lavage T cells of patients with hypersensitivity pneumonitis.

    PubMed

    Yamasaki, H; Ando, M; Brazer, W; Center, D M; Cruikshank, W W

    1999-09-15

    Hypersensitivity pneumonitis (HP) is characterized by an inflammatory lymphocytic alveolitis comprised of both CD8+ and CD4+ T cells. Animal models suggest that HP is facilitated by overproduction of IFN-gamma, and that IL-10 ameliorates severity of the disease, indicating a Th1-type response. To determine whether a Th1 phenotype in HP also exists clinically, bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells were obtained from HP individuals and analyzed for Th1 vs Th2 cytokine profiles. It was determined that soluble OKT3-stimulated BAL T cells cocultured with alveolar macrophages produced more IFN-gamma and less IL-10 than PB T cells cocultured with monocytes, but no difference was observed in IL-4 production. The monocytic cells did not account for this difference, as CD80 and CD86 expressions were similar, and coculturing PB T cells with alveolar macrophages resulted in no difference in IFN-gamma production. Similarly, there was no difference in IL-12 production between stimulated BAL or PB T cells; however, addition of rIL-12 significantly increased production of IFN-gamma by BAL T cells, but not by PB T cells. This effect was due to a difference in IL-12R expression. High affinity IL-12R were only present in association with BAL T cells. These studies indicate that clinical HP is characterized by a predominance of IFN-gamma-producing T cells, perhaps resulting from a reduction in IL-10 production and an increase in high affinity IL-12R compared with blood T cells.

  13. TU-CD-BRB-01: Normal Lung CT Texture Features Improve Predictive Models for Radiation Pneumonitis

    SciTech Connect

    Krafft, S; The University of Texas Graduate School of Biomedical Sciences, Houston, TX; Briere, T

    2015-06-15

    Purpose: Existing normal tissue complication probability (NTCP) models for radiation pneumonitis (RP) traditionally rely on dosimetric and clinical data but are limited in terms of performance and generalizability. Extraction of pre-treatment image features provides a potential new category of data that can improve NTCP models for RP. We consider quantitative measures of total lung CT intensity and texture in a framework for prediction of RP. Methods: Available clinical and dosimetric data was collected for 198 NSCLC patients treated with definitive radiotherapy. Intensity- and texture-based image features were extracted from the T50 phase of the 4D-CT acquired for treatment planning. Amore » total of 3888 features (15 clinical, 175 dosimetric, and 3698 image features) were gathered and considered candidate predictors for modeling of RP grade≥3. A baseline logistic regression model with mean lung dose (MLD) was first considered. Additionally, a least absolute shrinkage and selection operator (LASSO) logistic regression was applied to the set of clinical and dosimetric features, and subsequently to the full set of clinical, dosimetric, and image features. Model performance was assessed by comparing area under the curve (AUC). Results: A simple logistic fit of MLD was an inadequate model of the data (AUC∼0.5). Including clinical and dosimetric parameters within the framework of the LASSO resulted in improved performance (AUC=0.648). Analysis of the full cohort of clinical, dosimetric, and image features provided further and significant improvement in model performance (AUC=0.727). Conclusions: To achieve significant gains in predictive modeling of RP, new categories of data should be considered in addition to clinical and dosimetric features. We have successfully incorporated CT image features into a framework for modeling RP and have demonstrated improved predictive performance. Validation and further investigation of CT image features in the context of RP

  14. Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.

    PubMed

    Fellows, Patricia; Price, Jessica; Martin, Shannon; Metcalfe, Karen; Krile, Robert; Barnewall, Roy; Hart, Mary Kate; Lockman, Hank

    2015-09-01

    The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P < 0.0001). Vaccination also decreased signs of pneumonic plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥ 12 μg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Development and testing of a rapid diagnostic test for bubonic and pneumonic plague.

    PubMed

    Chanteau, Suzanne; Rahalison, Lila; Ralafiarisoa, Lalao; Foulon, Jeanine; Ratsitorahina, Mahery; Ratsifasoamanana, Lala; Carniel, Elisabeth; Nato, Farida

    2003-01-18

    Plague is often fatal without prompt and appropriate treatment. It affects mainly poor and remote populations. Late diagnosis is one of the major causes of human death and spread of the disease, since it limits the effectiveness of control measures. We aimed to develop and assess a rapid diagnostic test (RDT) for plague. We developed a test that used monoclonal antibodies to the F1 antigen of Yersinia pestis. Sensitivity and specificity were assessed with a range of bacterial cultures and clinical samples, and compared with findings from available ELISA and bacteriological tests for plague. Samples from patients thought to have plague were tested with the RDT in the laboratory and by health workers in 26 pilot sites in Madagascar. The RDT detected concentrations of F1 antigen as low as 0.5 ng/mL in up to 15 min, and had a shelf life of 21 days at 60 degrees C. Its sensitivity and specificity were both 100%. RDT detected 41.6% and 31% more positive clinical specimens than did bacteriological methods and ELISA, respectively. The agreement rate between tests done at remote centres and in the laboratory was 89.8%. With the combination of bacteriological methods and F1 ELISA as reference standard, the positive and negative predictive values of the RDT were 90.6% and 86.7%, respectively. Our RDT is a specific, sensitive, and reliable test that can easily be done by health workers at the patient's bedside, for the rapid diagnosis of pneumonic and bubonic plague. This test will be of key importance for the control of plague in endemic countries.

  16. Incorporating Single-nucleotide Polymorphisms Into the Lyman Model to Improve Prediction of Radiation Pneumonitis

    SciTech Connect

    Tucker, Susan L., E-mail: sltucker@mdanderson.org; Li Minghuan; Xu Ting

    2013-01-01

    Purpose: To determine whether single-nucleotide polymorphisms (SNPs) in genes associated with DNA repair, cell cycle, transforming growth factor-{beta}, tumor necrosis factor and receptor, folic acid metabolism, and angiogenesis can significantly improve the fit of the Lyman-Kutcher-Burman (LKB) normal-tissue complication probability (NTCP) model of radiation pneumonitis (RP) risk among patients with non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen SNPs from 10 different genes (XRCC1, XRCC3, APEX1, MDM2, TGF{beta}, TNF{alpha}, TNFR, MTHFR, MTRR, and VEGF) were genotyped in 141 NSCLC patients treated with definitive radiation therapy, with or without chemotherapy. The LKB model was used to estimate the risk ofmore » severe (grade {>=}3) RP as a function of mean lung dose (MLD), with SNPs and patient smoking status incorporated into the model as dose-modifying factors. Multivariate analyses were performed by adding significant factors to the MLD model in a forward stepwise procedure, with significance assessed using the likelihood-ratio test. Bootstrap analyses were used to assess the reproducibility of results under variations in the data. Results: Five SNPs were selected for inclusion in the multivariate NTCP model based on MLD alone. SNPs associated with an increased risk of severe RP were in genes for TGF{beta}, VEGF, TNF{alpha}, XRCC1 and APEX1. With smoking status included in the multivariate model, the SNPs significantly associated with increased risk of RP were in genes for TGF{beta}, VEGF, and XRCC3. Bootstrap analyses selected a median of 4 SNPs per model fit, with the 6 genes listed above selected most often. Conclusions: This study provides evidence that SNPs can significantly improve the predictive ability of the Lyman MLD model. With a small number of SNPs, it was possible to distinguish cohorts with >50% risk vs <10% risk of RP when they were exposed to high MLDs.« less

  17. Systemic lupus erythematosus (SLE) pneumonitis mimicking swine influenza pneumonia during the swine influenza (H1N1) pandemic.

    PubMed

    Cunha, Burke A; Syed, Uzma; Mickail, Nardeen

    2011-01-01

    We present a young woman with a negative medical history who presented with acute systemic lupus erythematosus (SLE) pneumonitis mimicking swine influenza (H1N1) pneumonia. Because this case occurred during the H1N1 pandemic, the initial diagnostic impression was of H1N1 pneumonia. Although her clinical and laboratory findings were consistent with the diagnosis of H1N1 pneumonia, e.g., fever, sore throat, dry cough, arthralgias, myalgias, thrombocytopenia, relative lymphopenia, and elevated serum transaminases, some findings suggested an alternate diagnosis, e.g., leukopenia, a highly elevated erythrocyte sedimentation rate, highly elevated serum ferritin levels, elevated antinuclear antibody (ANA) levels, and double-stranded (DS) DNA titers. Her chest x-ray showed an accentuation of basilar lung markings, with a small pleural effusion similar to the chest x-ray findings of early H1N1 pneumonia. Initially, her headaches were thought to be related to central nervous system manifestations of H1N1. After laboratory test results demonstrated elevated ANA and anti-DS DNA titers, she was diagnosed with acute SLE pneumonitis. The take-home lesson for clinicians is that other infectious diseases, e.g., human parainfluenza virus or Legionnaires' disease, can mimic H1N1 pneumonia during an influenza pandemic. Excluding asthma, congestive heart failure, exacerbations of acute bronchitis, chronic obstructive pulmonary disorder, and pulmonary interstitial disease, noninfectious mimics of H1N1 are extremely rare. To the best of our knowledge, this is the first reported case of de novo SLE pneumonitis mimicking H1N1 pneumonia during the swine influenza pandemic. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Regional Radiation Pneumonitis After SIRT of a Subcapsular Liver Metastasis: What is the Effect of Direct Beta Irradiation?

    SciTech Connect

    Dobrocky, Tomas, E-mail: tomas.dobrocky@insel.ch; Fuerstner, Markus, E-mail: markus.fuerstner@insel.ch; Klaeser, Bernd, E-mail: bernd.klaeser@insel.ch

    2015-08-15

    We herein present a patient undergoing selective internal radiation therapy with an almost normal lung shunt fraction of 11.5 %, developing histologically proven radiation pneumonitis. Due to a predominance of pulmonary consolidations in the right lower lung and its proximity to a large liver metastases located in the dome of the right liver lobe a Monte Carlo simulation was performed to estimate the effect of direct irradiation of the lung parenchyma. According to our calculations direct irradiation seems negligible and RP is almost exclusively due to ectopic draining of radioactive spheres.

  19. [A patient with acute hypersensitivity pneumonitis with a diagnosis of air-conditioner lung, who responded to therapy].

    PubMed

    Ishikawa, Rie; Kamiya, Hiroyuki; Ikushima, Souichiro; Oristu, Masaru; Takemura, Tamiko

    2010-02-01

    The patient was a 48-year-old woman and current smoker. In May 2007, she moved to a new residence. In the middle of the following month, she developed acute respiratory distress and a fever (38 degrees C) after running her air conditioner continuously throughout the night. The chest X-ray film showed diffuse infiltrative shadows in the middle and lower lung fields. After hospital admission, her oxygenation improved without treatment and the infiltrates improved over the clinical course. As a consequence, we suspected hypersensitivity pneumonitis. The bronchoalveolar lavage showed predominant lymphocytes of 72.6%, with a low CD 4/8 ratio of 0.2. Transbronchial lung biopsy findings corresponded to acute hypersensitivity pneumonitis. The results of the environmental challenge test were positive only when her air conditioner was on, resulting, in a diagnosis of air-conditioner lung. Several microorganisms were detected in an environmental sample, but 20 kinds of serum precipitating antibodies were negative on a thorough screening, so no responsible antigen could be identified. The patient's symptoms did not recur after her air conditioner was replaced.

  20. Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model

    PubMed Central

    Stinson, Elizabeth; Smith, Le'Kneitah P.; Cole, Kelly Stefano; Barry, Eileen M.; Reed, Douglas S.

    2016-01-01

    Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis. We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. PMID:27511964

  1. Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model.

    PubMed

    Stinson, Elizabeth; Smith, Le'Kneitah P; Cole, Kelly Stefano; Barry, Eileen M; Reed, Douglas S

    2016-10-01

    Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Bayesian network ensemble as a multivariate strategy to predict radiation pneumonitis risk

    SciTech Connect

    Lee, Sangkyu, E-mail: sangkyu.lee@mail.mcgill.ca; Ybarra, Norma; Jeyaseelan, Krishinima

    2015-05-15

    Purpose: Prediction of radiation pneumonitis (RP) has been shown to be challenging due to the involvement of a variety of factors including dose–volume metrics and radiosensitivity biomarkers. Some of these factors are highly correlated and might affect prediction results when combined. Bayesian network (BN) provides a probabilistic framework to represent variable dependencies in a directed acyclic graph. The aim of this study is to integrate the BN framework and a systems’ biology approach to detect possible interactions among RP risk factors and exploit these relationships to enhance both the understanding and prediction of RP. Methods: The authors studied 54 nonsmall-cellmore » lung cancer patients who received curative 3D-conformal radiotherapy. Nineteen RP events were observed (common toxicity criteria for adverse events grade 2 or higher). Serum concentration of the following four candidate biomarkers were measured at baseline and midtreatment: alpha-2-macroglobulin, angiotensin converting enzyme (ACE), transforming growth factor, interleukin-6. Dose-volumetric and clinical parameters were also included as covariates. Feature selection was performed using a Markov blanket approach based on the Koller–Sahami filter. The Markov chain Monte Carlo technique estimated the posterior distribution of BN graphs built from the observed data of the selected variables and causality constraints. RP probability was estimated using a limited number of high posterior graphs (ensemble) and was averaged for the final RP estimate using Bayes’ rule. A resampling method based on bootstrapping was applied to model training and validation in order to control under- and overfit pitfalls. Results: RP prediction power of the BN ensemble approach reached its optimum at a size of 200. The optimized performance of the BN model recorded an area under the receiver operating characteristic curve (AUC) of 0.83, which was significantly higher than multivariate logistic regression (0

  3. Identifying an Inciting Antigen Is Associated With Improved Survival in Patients With Chronic Hypersensitivity Pneumonitis

    PubMed Central

    Swigris, Jeffrey J.; Forssén, Anna V.; Tourin, Olga; Solomon, Joshua J.; Huie, Tristan J.; Olson, Amy L.; Brown, Kevin K.

    2013-01-01

    Background: The cornerstone of hypersensitivity pneumonitis (HP) management is having patients avoid the inciting antigen (IA). Often, despite an exhaustive search, an IA cannot be found. The objective of this study was to examine whether identifying the IA impacts survival in patients with chronic HP. Methods: We used the Kaplan-Meier method to display, and the log-rank test to compare, survival curves of patients with well-characterized chronic HP stratified on identification of an IA exposure. A Cox proportional hazards (PH) model was used to identify independent predictors in time-to-death analysis. Results: Of 142 patients, 67 (47%) had an identified IA, and 75 (53%) had an unidentified IA. Compared with survivors, patients who died (n = 80, 56%) were older, more likely to have smoked, had lower total lung capacity % predicted and FVC % predicted, had higher severity of dyspnea, were more likely to have pulmonary fibrosis, and were less likely to have an identifiable IA. In a Cox PH model, the inability to identify an IA (hazard ratio [HR], 1.76; 95% CI, 1.01-3.07), older age (HR, 1.04; 95% CI, 1.01-1.07), the presences of pulmonary fibrosis (HR, 2.43; 95% CI, 1.36-4.35), a lower FVC% (HR, 1.36; 95% CI, 1.10-1.68), and a history of smoking (HR, 2.01; 95% C1, 1.15-3.50) were independent predictors of shorter survival. After adjusting for mean age, presence of fibrosis, mean FVC%, mean diffusing capacity of the lung for carbon monoxide (%), and history of smoking, survival was longer for patients with an identified IA exposure than those with an unidentified IA exposure (median, 8.75 years vs 4.88 years; P = .047). Conclusions: Among patients with chronic HP, when adjusting for a number of potentially influential predictors, including the presence of fibrosis, the inability to identify an IA was independently associated with shortened survival. PMID:23828161

  4. [Correlation study of physical and biologic parameters to acute radiation pneumonitis].

    PubMed

    Zhao, Yan-hai; Li, Zhi-ping; Chen, Xiao-mei; Liu, Xiao-jing; Wu, Wen-chao; Xu, Yong; Li, Ping; Zhang, Jin-tao; Zeng, Hui

    2008-09-01

    To study the relationship between the level of plasma transform growth factor-betal (TGF-betal), interleukin-6 (IL-6), thrombomodulin (TM) dose-volume factors and acute radiation pneumonitis (ARP). Three dimensional conformal radiation therapy and chemotherapy were applied to 27 lung cancer patients, 15 esophageal carcinoma, and 1 thymoma patients. 19 patients received adjuvant radiochemotherapy, and 25 patients received concurrent radio-chemotherapy. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the serum IL-6, TGF-betal and TM levels of patients before radiotherapy (B-RT) and at 30 Gy(M-RT). ARP was graded according to NCI common toxicity criteria (CTCAE v 3.0), Grade 2 or more ARP was taken as the main end point. The relationship between the levels of serum TGF-betal, IL-6, TM, parameters of lung function and dose-volume factors, and the incidence rate of ARP were analyzed. Mean lung dose (MLD) and the Vx were considered as the dose-volume factors. Among 44 patients, 15 of them had ARP. 9 got grade 2 ARP and 6 had grade 3. After received a dose of 30 Gy, TGF-betal value in M-RT was (396 +/- 338) and (866 +/- 270) pg/mL in non-ARP and ARP group (P = 0.000). The ARP incidence rate in <60 and > or =60 age group were 46.15% (12/26) and 16.67% (3/18) (P = 0.042), and 45.45% (15/33), 0% (0/11) (P = 0.017) in had smoking history and nonsmoking history group, respectively. 1 out of 13 patients (7.69%) who had increased M-RT TM value suffered of ARP, while 14 out of 31 patients (45.16%) whose M-RT TM value lower than pr-RT suffered of ARP (P = 0.044). The results of multivariate analysis implied that the MLD and the value of TGF-betal in M-RT were associated with severe ARP. TGF-beta1 and MLD are significant indicators of ARP. FEV1 actual value/predicted value% might have predicting effect for the severity of ARP.

  5. The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4.

    PubMed

    Hutt, Julie A; Lovchik, Julie A; Dekonenko, Alexander; Hahn, Andrew C; Wu, Terry H

    2017-02-01

    The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4. Our results are consistent with initial uptake of aerosolized SCHU S4 from the nasal cavity, lungs, and possibly the gastrointestinal tract. Bacteremia with hematogenous dissemination was first detected 2 days after exposure. Shortly thereafter, the infected rats exhibited fever, tachypnea, and hypertension that persisted for 24 to 36 hours and then rapidly decreased as animals succumbed to infection between days 5 and 8 after exposure. Tachycardia was observed briefly, but only after the core body temperature and blood pressure began to decrease as the animals were near death. Initial neutrophilic and histiocytic inflammation in affected tissues became progressively more fibrinous and necrotizing over time. At death, as many as 10 10 colony-forming units were found in the lungs, spleen, and liver. Death was attributed to sepsis and disseminated intravascular coagulation. Overall, the pathogenesis of pneumonic tularemia in the female F344 rat model appears to replicate the disease in humans. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Analysis of dose-volume parameters predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-conformal radiation therapy or IMRT.

    PubMed

    Kumar, Gaurav; Rawat, Sheh; Puri, Abhishek; Sharma, Manoj Kumar; Chadha, Pranav; Babu, Anand Giri; Yadav, Girigesh

    2012-01-01

    Multimodality therapy for esophageal cancer can cause various kinds of treatment-related sequelae, especially pulmonary toxicities. This prospective study aims to investigate the clinical and dosimetric parameters predicting lung injury in patients undergoing radiation therapy for esophageal cancer. Forty-five esophageal cancer patients were prospectively analyzed. The pulmonary toxicities (or sequelae) were evaluated by comparing chest X-ray films, pulmonary function tests and symptoms caused by pulmonary damage before and after treatment. All patients were treated with either three-dimensional radiotherapy (3DCRT) or with intensity-modulated radiotherapy (IMRT). The planning dose volume histogram was used to compute the lung volumes receiving more than 5, 10, 20 and 30 Gy (V5, V10, V20, V30) and mean lung dose. V20 was larger in the IMRT group than in the 3DCRT group (p = 0.002). V20 (>15%) and V30 (>20%) resulted in a statistically significant increase in the occurrence of chronic pneumonitis (p = 0.03) and acute pneumonitis (p = 0.007), respectively. The study signifies that a larger volume of lung receives lower doses because of multiple beam arrangement and a smaller volume of lung receives higher doses because of better dose conformity in IMRT plans. Acute pneumonitis correlates more with V30 values, whereas chronic pneumonitis was predominantly seen in patients with higher V20 values.

  7. Analysis of the Protective Biochemical and Pathologic Effects of Aminoguanidine on an Experimental Aspiration Pneumonitis Model Induced by Bile Acids

    PubMed Central

    Karli, Rifat; Alacam, Hasan; Duran, Latif; Alici, Omer; Kati, Celal; Karli, Arzu; Guzel, Ahmet

    2012-01-01

    Background Gastroesophageal reflux (GER) is a common clinical pathology detected in childhood. Bile acids (BAs) are present in reflux and cause various pathologies in the esophagus, the larynx, and the lungs. Objective We aimed to show if aminoguanidine (AG) contributes to the biochemical and histopathologic treatment of experimental aspiration pneumonitis induced by BAs. Methods Twenty-eight female Sprague Dawley rats were used. There were 4 groups in the study: (1) group aspirated with 0.9% saline (n = 7), (2) group aspirated with 0.9% saline and treated with AG (n = 7), (3) group aspirated with a solution of 10 mg/kg taurocholic acid and 5 mg/kg taurochenodeoxycholate (n = 7), and (4) group aspirated with BA and treated with AG (n = 7). The saline and BA solutions were administered as 1 mL/kg intratracheally. The AG was administered intraperitoneally twice a day at a 150 mg/kg dose for 7 days. The different histopathologic and biochemical parameters were analyzed. Results Clara cell protein 16 and malondialdehyde levels were found to be significantly higher in the BA group than in the group where saline was administered; however, they were significantly lower in the BA + AG group than in the BA group. The total superoxide dismutase activity decreased significantly in the BA group compared with the group where saline was administered. A significant increase in superoxide dismutase activity was observed in the BA + AG group when compared with the group where only BA was administered. When the group where BA was administered solely was compared with the group where saline was administered, peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar histiocytes, interstitial fibrosis, and granuloma were significantly higher in the BA group than in the saline group. When the BA + AG group was compared with the BA group, peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar histiocytes, interstitial fibrosis, and

  8. Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

    NASA Astrophysics Data System (ADS)

    Valdes, Gilmer; Solberg, Timothy D.; Heskel, Marina; Ungar, Lyle; Simone, Charles B., II

    2016-08-01

    To develop a patient-specific ‘big data’ clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm.

  9. PCR assay detects Mannheimia haemolytica in culture-negative pneumonic lung tissues of bighorn sheep (Ovis canadensis) from outbreaks in the western USA, 2009-2010.

    PubMed

    Shanthalingam, Sudarvili; Goldy, Andrea; Bavananthasivam, Jegarubee; Subramaniam, Renuka; Batra, Sai Arun; Kugadas, Abirami; Raghavan, Bindu; Dassanayake, Rohana P; Jennings-Gaines, Jessica E; Killion, Halcyon J; Edwards, William H; Ramsey, Jennifer M; Anderson, Neil J; Wolff, Peregrine L; Mansfield, Kristin; Bruning, Darren; Srikumaran, Subramaniam

    2014-01-01

    Mannheimia haemolytica consistently causes severe bronchopneumonia and rapid death of bighorn sheep (Ovis canadensis) under experimental conditions. However, Bibersteinia trehalosi and Pasteurella multocida have been isolated from pneumonic bighorn lung tissues more frequently than M. haemolytica by culture-based methods. We hypothesized that assays more sensitive than culture would detect M. haemolytica in pneumonic lung tissues more accurately. Therefore, our first objective was to develop a PCR assay specific for M. haemolytica and use it to determine if this organism was present in the pneumonic lungs of bighorns during the 2009-2010 outbreaks in Montana, Nevada, and Washington, USA. Mannheimia haemolytica was detected by the species-specific PCR assay in 77% of archived pneumonic lung tissues that were negative by culture. Leukotoxin-negative M. haemolytica does not cause fatal pneumonia in bighorns. Therefore, our second objective was to determine if the leukotoxin gene was also present in the lung tissues as a means of determining the leukotoxicity of M. haemolytica that were present in the lungs. The leukotoxin-specific PCR assay detected leukotoxin gene in 91% of lung tissues that were negative for M. haemolytica by culture. Mycoplasma ovipneumoniae, an organism associated with bighorn pneumonia, was detected in 65% of pneumonic bighorn lung tissues by PCR or culture. A PCR assessment of distribution of these pathogens in the nasopharynx of healthy bighorns from populations that did not experience an all-age die-off in the past 20 yr revealed that M. ovipneumoniae was present in 31% of the animals whereas leukotoxin-positive M. haemolytica was present in only 4%. Taken together, these results indicate that culture-based methods are not reliable for detection of M. haemolytica and that leukotoxin-positive M. haemolytica was a predominant etiologic agent of the pneumonia outbreaks of 2009-2010.

  10. A plague on five of your houses--statistical re-assessment of three pneumonic plague outbreaks that occurred in Suffolk, England, between 1906 and 1918.

    PubMed

    Egan, Joseph R

    2010-10-25

    Plague is a re-emerging disease and its pneumonic form is a high priority bio-terrorist threat. Epidemiologists have previously analysed historical outbreaks of pneumonic plague to better understand the dynamics of infection, transmission and control. This study examines 3 relatively unknown outbreaks of pneumonic plague that occurred in Suffolk, England, during the first 2 decades of the twentieth century. The Kolmogorov-Smirnov statistical test is used to compare the symptomatic period and the length of time between successive cases (i.e. the serial interval) with previously reported values. Consideration is also given to the case fatality ratio, the average number of secondary cases resulting from each primary case in the observed minor outbreaks (termed R(minor)), and the proportion of individuals living within an affected household that succumb to pneumonic plague via the index case (i.e. the household secondary attack rate (SAR)). 2 of the 14 cases survived giving a case fatality ratio of 86% (95% confidence interval (CI) = {57%, 98%}). For the 12 fatal cases, the average symptomatic period was 3.3 days (standard deviation (SD) = 1.2 days) and, for the 11 non index cases, the average serial interval was 5.8 days (SD = 2.0 days). R(minor) was calculated to be 0.9 (SD = 1.0) and, in 2 households, the SAR was approximately 14% (95% CI = {0%, 58%}) and 20% (95% CI = {1%, 72%}), respectively. The symptomatic period was approximately 1 day longer on average than in an earlier study but the serial interval was in close agreement with 2 previously reported values. 2 of the 3 outbreaks ended without explicit public health interventions; however, non-professional caregivers were particularly vulnerable - an important public health consideration for any future outbreak of pneumonic plague.

  11. Deletion of Braun lipoprotein and plasminogen-activating protease-encoding genes attenuates Yersinia pestis in mouse models of bubonic and pneumonic plague.

    PubMed

    van Lier, Christina J; Sha, Jian; Kirtley, Michelle L; Cao, Anthony; Tiner, Bethany L; Erova, Tatiana E; Cong, Yingzi; Kozlova, Elena V; Popov, Vsevolod L; Baze, Wallace B; Chopra, Ashok K

    2014-06-01

    Currently, there is no FDA-approved vaccine against Yersinia pestis, the causative agent of bubonic and pneumonic plague. Since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y. pestis CO92. The Δlpp Δpla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous route were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of proinflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and livers of mice infected with the Δlpp Δpla double mutant compared to the level of damage in wild-type (WT) CO92-challenged animals was observed. The Δlpp Δpla mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from mutant-immunized animals exhibited significantly higher proliferative responses, when stimulated ex vivo with heat-killed WT CO92 antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more gamma interferon (IFN-γ) and interleukin-4. These animals had an increasing number of tumor necrosis factor alpha (TNF-α)-producing CD4(+) and CD8(+) T cells than WT CO92-infected mice. These data emphasize the role of TNF-α and IFN-γ in protecting mice against pneumonic plague. Overall, our studies provide evidence that deletion of the lpp and pla genes acts synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection.

  12. Deletion of Braun Lipoprotein and Plasminogen-Activating Protease-Encoding Genes Attenuates Yersinia pestis in Mouse Models of Bubonic and Pneumonic Plague

    PubMed Central

    van Lier, Christina J.; Sha, Jian; Kirtley, Michelle L.; Cao, Anthony; Tiner, Bethany L.; Erova, Tatiana E.; Cong, Yingzi; Kozlova, Elena V.; Popov, Vsevolod L.; Baze, Wallace B.

    2014-01-01

    Currently, there is no FDA-approved vaccine against Yersinia pestis, the causative agent of bubonic and pneumonic plague. Since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y. pestis CO92. The Δlpp Δpla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous route were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of proinflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and livers of mice infected with the Δlpp Δpla double mutant compared to the level of damage in wild-type (WT) CO92-challenged animals was observed. The Δlpp Δpla mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from mutant-immunized animals exhibited significantly higher proliferative responses, when stimulated ex vivo with heat-killed WT CO92 antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more gamma interferon (IFN-γ) and interleukin-4. These animals had an increasing number of tumor necrosis factor alpha (TNF-α)-producing CD4+ and CD8+ T cells than WT CO92-infected mice. These data emphasize the role of TNF-α and IFN-γ in protecting mice against pneumonic plague. Overall, our studies provide evidence that deletion of the lpp and pla genes acts synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection. PMID:24686064

  13. A plague on five of your houses - statistical re-assessment of three pneumonic plague outbreaks that occurred in Suffolk, England, between 1906 and 1918

    PubMed Central

    2010-01-01

    Background Plague is a re-emerging disease and its pneumonic form is a high priority bio-terrorist threat. Epidemiologists have previously analysed historical outbreaks of pneumonic plague to better understand the dynamics of infection, transmission and control. This study examines 3 relatively unknown outbreaks of pneumonic plague that occurred in Suffolk, England, during the first 2 decades of the twentieth century. Methods The Kolmogorov-Smirnov statistical test is used to compare the symptomatic period and the length of time between successive cases (i.e. the serial interval) with previously reported values. Consideration is also given to the case fatality ratio, the average number of secondary cases resulting from each primary case in the observed minor outbreaks (termed Rminor), and the proportion of individuals living within an affected household that succumb to pneumonic plague via the index case (i.e. the household secondary attack rate (SAR)). Results 2 of the 14 cases survived giving a case fatality ratio of 86% (95% confidence interval (CI) = {57%, 98%}). For the 12 fatal cases, the average symptomatic period was 3.3 days (standard deviation (SD) = 1.2 days) and, for the 11 non index cases, the average serial interval was 5.8 days (SD = 2.0 days). Rminor was calculated to be 0.9 (SD = 1.0) and, in 2 households, the SAR was approximately 14% (95% CI = {0%, 58%}) and 20% (95% CI = {1%, 72%}), respectively. Conclusions The symptomatic period was approximately 1 day longer on average than in an earlier study but the serial interval was in close agreement with 2 previously reported values. 2 of the 3 outbreaks ended without explicit public health interventions; however, non-professional caregivers were particularly vulnerable - an important public health consideration for any future outbreak of pneumonic plague. PMID:20973955

  14. Treatment of experimentally induced pneumonic pasteurellosis of young calves with tilmicosin.

    PubMed Central

    Morck, D W; Merrill, J K; Gard, M S; Olson, M E; Nation, P N

    1997-01-01

    concentrations of the antibiotic were comparatively high, even at 72 h post-infection (6.50 +/- 0.75 ppm). Lung tissue concentrations at 72 h were significantly higher in experimentally infected calves than in non-infected tilmicosin-treated animals (P < 0.05). These data demonstrate that tilmicosin was effective in treating experimentally-induced pneumonic pasteurellosis as determined by alleviation of clinical signs, pathological findings at post mortem, and presence of viable bacteria from the lung. Concentrations substantially above MIC for P. haemolytica were present in lung tissue even at 72 h following a single subcutaneous injection of 10 mg tilmicosin per kg body weight. Images Figure 2A. Figure 2B. PMID:9242998

  15. Pneumonitis in Syrian golden hamsters (Mesocricetus auratus) infected with Rio Mamoré virus (family Bunyaviridae, genus Hantavirus).

    PubMed

    Milazzo, Mary Louise; Eyzaguirre, Eduardo J; Fulhorst, Charles F

    2014-10-13

    Rio Mamoré virus is an etiological agent of hantavirus pulmonary syndrome in South America. The purpose of this study was to determine whether Rio Mamoré virus strain HTN-007 in Syrian golden hamsters is pathogenic. None of 37 adult hamsters infected by intramuscular injection of HTN-007, including 10 animals killed on Day 42 or 43 post-inoculation, exhibited any symptom of disease. Histological abnormalities included severe or moderately severe pneumonitis in 6 (46.2%) of the 13 animals killed on Day 7 or 10 post-inoculation. The primary target of infection in lung was the endothelium of the microvasculature. Collectively, these results indicate that Rio Mamoré virus strain HTN-007 in adult Syrian golden hamsters can cause a nonlethal disease that is pathologically similar to hantavirus pulmonary syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Pneumonitis in Syrian golden hamsters (Mesocricetus auratus) infected with Río Mamoré virus (family Bunyaviridae, genus Hantavirus)

    PubMed Central

    Milazzo, Mary Louise; Eyzaguirre, Eduardo J.; Fulhorst, Charles F.

    2014-01-01

    Rio Mamoré virus is an etiological agent of hantavirus pulmonary syndrome in South America. The purpose of this study was to determine whether Rio Mamoré virus strain HTN-007 in Syrian golden hamsters is pathogenic. None of 37 adult hamsters infected by intramuscular injection of HTN-007, including 10 animals killed on Day 42 or 43 post-inoculation, exhibited any symptom of disease. Histological abnormalities included severe or moderately severe pneumonitis in 6 (46.2%) of the 13 animals killed on Day 7 or 10 post-inoculation. The primary target of infection in lung was the endothelium of the microvasculature. Collectively, these results indicate that Rio Mamoré virus strain HTN-007 in adult Syrian golden hamsters can cause a nonlethal disease that is pathologically similar to hantavirus pulmonary syndrome. PMID:25064267

  17. Surveillance for pneumonic plague in the United States during an international emergency: a model for control of imported emerging diseases.

    PubMed Central

    Fritz, C. L.; Dennis, D. T.; Tipple, M. A.; Campbell, G. L.; McCance, C. R.; Gubler, D. J.

    1996-01-01

    In September 1994, in response to a reported epidemic of plague in India, the Centers for Disease Control and Prevention (CDC) enhanced surveillance in the United States for imported pneumonic plague. Plague information materials were rapidly developed and distributed to U.S. public health officials by electronic mail, facsimile, and expedited publication. Information was also provided to medical practitioners and the public by recorded telephone messages and facsimile transmission. Existing quarantine protocols were modified to effect active surveillance for imported plague cases at U.S. airports. Private physicians and state and local health departments were relied on in a passive surveillance system to identify travelers with suspected plague not detected at airports. From September 27 to October 27, the surveillance system identified 13 persons with suspected plague; no case was confirmed. This coordinated response to an international health emergency may serve as a model for detecting other emerging diseases and preventing their importation. PMID:8964057

  18. Surveillance for pneumonic plague in the United States during an international emergency: a model for control of imported emerging diseases.

    PubMed

    Fritz, C L; Dennis, D T; Tipple, M A; Campbell, G L; McCance, C R; Gubler, D J

    1996-01-01

    In September 1994, in response to a reported epidemic of plague in India, the Centers for Disease Control and Prevention (CDC) enhanced surveillance in the United States for imported pneumonic plague. Plague information materials were rapidly developed and distributed to U.S. public health officials by electronic mail, facsimile, and expedited publication. Information was also provided to medical practitioners and the public by recorded telephone messages and facsimile transmission. Existing quarantine protocols were modified to effect active surveillance for imported plague cases at U.S. airports. Private physicians and state and local health departments were relied on in a passive surveillance system to identify travelers with suspected plague not detected at airports. From September 27 to October 27, the surveillance system identified 13 persons with suspected plague; no case was confirmed. This coordinated response to an international health emergency may serve as a model for detecting other emerging diseases and preventing their importation.

  19. Yersinia pestis endowed with increased cytotoxicity is avirulent in a bubonic plague model and induces rapid protection against pneumonic plague.

    PubMed

    Zauberman, Ayelet; Tidhar, Avital; Levy, Yinon; Bar-Haim, Erez; Halperin, Gideon; Flashner, Yehuda; Cohen, Sara; Shafferman, Avigdor; Mamroud, Emanuelle

    2009-06-16

    An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica Oratio8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence. To test the relationship between cytotoxic potential and virulence, we replaced Y. pestis YopJ with YopP. The YopP-expressing Y. pestis strain exhibited high cytotoxic activity against macrophages in vitro. Following subcutaneous infection, this strain had reduced ability to colonize internal organs, was unable to induce septicemia and exhibited at least a 10(7)-fold reduction in virulence. Yet, upon intravenous or intranasal infection, it was still as virulent as the wild-type strain. The subcutaneous administration of the cytotoxic Y. pestis strain appears to activate a rapid and potent systemic, CTL-independent, immunoprotective response, allowing the organism to overcome simultaneous coinfection with 10,000 LD(50) of virulent Y. pestis. Moreover, three days after subcutaneous administration of this strain, animals were also protected against septicemic or primary pneumonic plague. Our findings indicate that an inverse relationship exists between the cytotoxic potential of Y. pestis and its virulence following subcutaneous infection. This appears to be associated with the ability of the engineered cytotoxic Y. pestis strain to induce very rapid, effective and long-lasting protection against bubonic and pneumonic plague. These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed new light on the

  20. Braun lipoprotein (Lpp) contributes to virulence of yersiniae: potential role of Lpp in inducing bubonic and pneumonic plague.

    PubMed

    Sha, Jian; Agar, Stacy L; Baze, Wallace B; Olano, Juan P; Fadl, Amin A; Erova, Tatiana E; Wang, Shaofei; Foltz, Sheri M; Suarez, Giovanni; Motin, Vladimir L; Chauhan, Sadhana; Klimpel, Gary R; Peterson, Johnny W; Chopra, Ashok K

    2008-04-01

    Yersinia pestis evolved from Y. pseudotuberculosis to become the causative agent of bubonic and pneumonic plague. We identified a homolog of the Salmonella enterica serovar Typhimurium lipoprotein (lpp) gene in Yersinia species and prepared lpp gene deletion mutants of Y. pseudotuberculosis YPIII, Y. pestis KIM/D27 (pigmentation locus minus), and Y. pestis CO92 with reduced virulence. Mice injected via the intraperitoneal route with 5 x 10(7) CFU of the Deltalpp KIM/D27 mutant survived a month, even though this would have constituted a lethal dose for the parental KIM/D27 strain. Subsequently, these Deltalpp KIM/D27-injected mice were solidly protected against an intranasally administered, highly virulent Y. pestis CO92 strain when it was given as five 50% lethal doses (LD(50)). In a parallel study with the pneumonic plague mouse model, after 72 h postinfection, the lungs of animals infected with wild-type (WT) Y. pestis CO92 and given a subinhibitory dose of levofloxacin had acute inflammation, edema, and masses of bacteria, while the lung tissue appeared essentially normal in mice inoculated with the Deltalpp mutant of CO92 and given the same dose of levofloxacin. Importantly, while WT Y. pestis CO92 could be detected in the bloodstreams and spleens of infected mice at 72 h postinfection, the Deltalpp mutant of CO92 could not be detected in those organs. Furthermore, the levels of cytokines/chemokines detected in the sera were significantly lower in animals infected with the Deltalpp mutant than in those infected with WT CO92. Additionally, the Deltalpp mutant was more rapidly killed by macrophages than was the WT CO92 strain. These data provided evidence that the Deltalpp mutants of yersiniae were significantly attenuated and could be useful tools in the development of new vaccines.

  1. The Case of a Zebra That Was Misdiagnosed as a Horse: Pulmonary Tumor Thrombotic Microangiopathy, a New Paraneoplastic Syndrome, Mimicking PD-1-Induced Pneumonitis

    PubMed Central

    Carter, Corey A.; Browning, Robert; Oronsky, Bryan T.; Scicinski, Jan J.; Brzezniak, Christina

    2016-01-01

    A case report of a 47-year-old woman with triple-negative breast cancer on a clinical trial called PRIMETIME (NCT02518958) who received the anti-PD-1 inhibitor nivolumab and the experimental anticancer agent RRx-001 is presented. Although initially diagnosed and treated for anti-PD-1-induced pneumonitis, clinical and radiological abnormalities triggered further investigation, leading to the diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM). This example highlights the importance of exercising due diligence in determining immune-related adverse events and suggests that PD-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default. A case history and review of the literature are presented for PTTM, which we propose to define as a paraneoplastic syndrome. PMID:26933422

  2. The Case of a Zebra That Was Misdiagnosed as a Horse: Pulmonary Tumor Thrombotic Microangiopathy, a New Paraneoplastic Syndrome, Mimicking PD-1-Induced Pneumonitis.

    PubMed

    Carter, Corey A; Browning, Robert; Oronsky, Bryan T; Scicinski, Jan J; Brzezniak, Christina

    2016-01-01

    A case report of a 47-year-old woman with triple-negative breast cancer on a clinical trial called PRIMETIME (NCT02518958) who received the anti-PD-1 inhibitor nivolumab and the experimental anticancer agent RRx-001 is presented. Although initially diagnosed and treated for anti-PD-1-induced pneumonitis, clinical and radiological abnormalities triggered further investigation, leading to the diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM). This example highlights the importance of exercising due diligence in determining immune-related adverse events and suggests that PD-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default. A case history and review of the literature are presented for PTTM, which we propose to define as a paraneoplastic syndrome.

  3. The search for early markers of plague: evidence for accumulation of soluble Yersinia pestis LcrV in bubonic and pneumonic mouse models of disease.

    PubMed

    Flashner, Yehuda; Fisher, Morly; Tidhar, Avital; Mechaly, Adva; Gur, David; Halperin, Gideon; Zahavy, Eran; Mamroud, Emanuelle; Cohen, Sara

    2010-07-01

    Markers of the early stages of plague, a rapidly progressing deadly disease, are crucial for enabling the onset of an effective treatment. Here, we show that V-antigen protein (LcrV) is accumulated in the serum of Yersinia pestis-infected mice before bacterial colonization of the spleen and dissemination to blood, in a model of bubonic plague. LcrV accumulation is detected earlier than that of F1 capsular antigen, an established marker of disease. In a mouse model of pneumonic plague, LcrV can be determined in the bronchoalveolar lavage fluid somewhat later than F1, but before dissemination of Y. pestis to the blood. Thus, determination of soluble LcrV is suggested as a potential useful tool for monitoring disease progression in both bubonic and pneumonic plague. Moreover, it may be of particular advantage in cases of infections with F1 nonproducing strains.

  4. Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose-escalating study.

    PubMed

    Thomas, A L; Cox, G; Sharma, R A; Steward, W P; Shields, F; Jeyapalan, K; Muller, S; O'Byrne, K J

    2000-12-01

    The aim of this phase I/II dose escalating study was to establish the maximum tolerated dose (MTD) of gemcitabine and paclitaxel given in combination in non-small cell lung cancer (NSCLC). 12 patients with stage IIIB and IV NSCLC received paclitaxel administered intravenously over 1 h followed by gemcitabine given over 30 min on days 1, 8 and 15 every 28 days. Pneumonitis was the principal side-effect observed with 4 patients affected. Of these, 1 experienced grade 3 toxicity after one cycle of treatment and the others had grade 2 toxicity. All 4 cases responded to prednisolone. No other significant toxicities were observed. Of the 8 evaluable patients, 3 had a partial response and 2 had minor responses. The study was discontinued due to this dose-limiting toxicity. The combination of paclitaxel and gemcitabine shows promising antitumour activity in NSCLC, however, this treatment schedule may predispose to pneumonitis.

  5. Intensity-Modulated Radiotherapy Might Increase Pneumonitis Risk Relative to Three-Dimensional Conformal Radiotherapy in Patients Receiving Combined Chemotherapy and Radiotherapy: A Modeling Study of Dose Dumping

    SciTech Connect

    Vogelius, Ivan S.; Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI; Department of Radiation Oncology, Rigshospitalet

    2011-07-01

    Purpose: To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis. Methods and Materials: A total of 18 non-small-cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for the present modeling study. Three treatment plans were considered: the delivered tomotherapy plans; a three-dimensional conformal radiotherapy (3D-CRT) plan; and a fixed-field intensity-modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for the present study. The plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeledmore » as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose added to all voxels of the organ at risk. The risk of radiation pneumonitis was estimated for all plans using the Lyman and the critical volume models. Results: For radiotherapy alone, the critical volume model predicts that the two IMRT plans are associated with a lower risk of radiation pneumonitis than the 3D-CRT plan. However, when the chemotherapy equivalent radiation dose exceeds a certain threshold, the radiation pneumonitis risk after IMRT is greater than after 3D-CRT. This threshold dose is in the range estimated from clinical chemoradiotherapy data sets. Conclusions: Cytotoxic chemotherapy might affect the relative merit of competing radiotherapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and the radiation dose distribution in clinical settings.« less

  6. Immunogenicity and protective immunity against bubonic plague and pneumonic plague by immunization of mice with the recombinant V10 antigen, a variant of LcrV.

    PubMed

    DeBord, Kristin L; Anderson, Deborah M; Marketon, Melanie M; Overheim, Katie A; DePaolo, R William; Ciletti, Nancy A; Jabri, Bana; Schneewind, Olaf

    2006-08-01

    In contrast to Yersinia pestis LcrV, the recombinant V10 (rV10) variant (lacking residues 271 to 300) does not suppress the release of proinflammatory cytokines by immune cells. Immunization with rV10 generates robust antibody responses that protect mice against bubonic plague and pneumonic plague, suggesting that rV10 may serve as an improved plague vaccine.

  7. Host transcriptomic responses to pneumonic plague reveal that Yersinia pestis inhibits both the initial adaptive and innate immune responses in mice.

    PubMed

    Yang, Huiying; Wang, Tong; Tian, Guang; Zhang, Qingwen; Wu, Xiaohong; Xin, Youqian; Yan, Yanfeng; Tan, Yafang; Cao, Shiyang; Liu, Wanbing; Cui, Yujun; Yang, Ruifu; Du, Zongmin

    2017-01-01

    Pneumonic plague is the most deadly form of infection caused by Yersinia pestis and can progress extremely fast. However, our understanding on the host transcriptomic response to pneumonic plague is insufficient. Here, we used RNA-sequencing technology to analyze transcriptomic responses in mice infected with fully virulent strain 201 or EV76, a live attenuated vaccine strain lacking the pigmentation locus. Approximately 600 differentially expressed genes (DEGs) were detected in lungs from both 201- and EV76-infected mice at 12h post-infection (hpi). DEGs in lungs of 201-infected mice exceeded 2000 at 48hpi, accompanied by sustained large numbers of DEGs in the liver and spleen; however, limited numbers of DEGs were detected in those organs of EV-infected mice. Remarkably, DEGs in lungs were significantly enriched in critical immune responses pathways in EV76-infected but not 201-infected mice, including antigen processing and presentation, T cell receptor signaling among others. Pathological and bacterial load analyses confirmed the rapid systemic dissemination of 201-infection and the confined EV76-infection in lungs. Our results suggest that fully virulent Y. pestis inhibits both the innate and adaptive immune responses that are substantially stimulated in a self-limited infection, which update our holistic views on the transcriptomic response to pneumonic plague. Copyright © 2016 Elsevier GmbH. All rights reserved.

  8. Combined Ventilation and Perfusion Imaging Correlates With the Dosimetric Parameters of Radiation Pneumonitis in Radiation Therapy Planning for Lung Cancer

    SciTech Connect

    Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp; Doi, Yoshiko; Nakashima, Takeo

    2015-11-15

    Purpose: The purpose of this study was to prospectively investigate clinical correlations between dosimetric parameters associated with radiation pneumonitis (RP) and functional lung imaging. Methods and Materials: Functional lung imaging was performed using four-dimensional computed tomography (4D-CT) for ventilation imaging, single-photon emission computed tomography (SPECT) for perfusion imaging, or both (V/Q-matched region). Using 4D-CT, ventilation imaging was derived from a low attenuation area according to CT numbers below different thresholds (vent-860 and -910). Perfusion imaging at the 10th, 30th, 50th, and 70th percentile perfusion levels (F10-F70) were defined as the top 10%, 30%, 50%, and 70% hyperperfused normal lung, respectively.more » All imaging data were incorporated into a 3D planning system to evaluate correlations between RP dosimetric parameters (where fV20 is the percentage of functional lung volume irradiated with >20 Gy, or fMLD, the mean dose administered to functional lung) and the percentage of functional lung volume. Radiation pneumonitis was evaluated using Common Terminology Criteria for Adverse Events version 4.0. Statistical significance was defined as a P value of <.05. Results: Sixty patients who underwent curative radiation therapy were enrolled (48 patients for non-small cell lung cancer, and 12 patients for small cell lung cancer). Grades 1, 2, and ≥3 RP were observed in 16, 44, and 6 patients, respectively. Significant correlations were observed between the percentage of functional lung volume and fV20 (r=0.4475 in vent-860 and 0.3508 in F30) or fMLD (r=0.4701 in vent-860 and 0.3128 in F30) in patients with grade ≥2 RP. F30∩vent-860 results exhibited stronger correlations with fV20 and fMLD in patients with grade ≥2 (r=0.5509 in fV20 and 0.5320 in fMLD) and grade ≥3 RP (r=0.8770 in fV20 and 0.8518 in fMLD). Conclusions: RP dosimetric parameters correlated significantly with functional lung imaging.« less

  9. Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials.

    PubMed

    Khunger, Monica; Rakshit, Sagar; Pasupuleti, Vinay; Hernandez, Adrian V; Mazzone, Peter; Stevenson, James; Pennell, Nathan A; Velcheti, Vamsidhar

    2017-08-01

    Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use. MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian-Laird random effects models. We compared incidences between PD-1 and PD-L1 inhibitors and between treatment naive and previously treated patients. Nineteen trials (12 with PD-1 inhibitors [n = 3,232] and 7 with PD-L1 inhibitors [n = 1,806]) were identified. PD-1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD-L1 inhibitors (3.6%; 95% CI, 2.4%-4.9% vs 1.3%; 95% CI, 0.8%-1.9%, respectively; P = .001). PD-1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%-1.7% vs 0.4%; 95% CI, 0%-0.8%; P = .02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%-6.3% vs 2.8%; 95% CI, 1.7%- 4%; P = .03). There was a higher incidence of pneumonitis with use of PD-1 inhibitors compared with PD-L1 inhibitors. Higher rate of pneumonitis was more common in treatment naive patients. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  10. On the use of published radiobiological parameters and the evaluation of NTCP models regarding lung pneumonitis in clinical breast radiotherapy.

    PubMed

    Svolos, Patricia; Tsougos, Ioannis; Kyrgias, Georgios; Kappas, Constantine; Theodorou, Kiki

    2011-04-01

    In this study we sought to evaluate and accent the importance of radiobiological parameter selection and implementation to the normal tissue complication probability (NTCP) models. The relative seriality (RS) and the Lyman-Kutcher-Burman (LKB) models were studied. For each model, a minimum and maximum set of radiobiological parameter sets was selected from the overall published sets applied in literature and a theoretical mean parameter set was computed. In order to investigate the potential model weaknesses in NTCP estimation and to point out the correct use of model parameters, these sets were used as input to the RS and the LKB model, estimating radiation induced complications for a group of 36 breast cancer patients treated with radiotherapy. The clinical endpoint examined was Radiation Pneumonitis. Each model was represented by a certain dose-response range when the selected parameter sets were applied. Comparing the models with their ranges, a large area of coincidence was revealed. If the parameter uncertainties (standard deviation) are included in the models, their area of coincidence might be enlarged, constraining even greater their predictive ability. The selection of the proper radiobiological parameter set for a given clinical endpoint is crucial. Published parameter values are not definite but should be accompanied by uncertainties, and one should be very careful when applying them to the NTCP models. Correct selection and proper implementation of published parameters provides a quite accurate fit of the NTCP models to the considered endpoint.

  11. Epidemiology of occupational hypersensitivity pneumonitis; reports from the SWORD scheme in the UK from 1996 to 2015

    PubMed Central

    Barber, C M; Wiggans, R E; Carder, M; Agius, R

    2017-01-01

    Objective To estimate the reported incidence of occupational hypersensitivity pneumonitis (OHP) in the UK and to consider whether the pattern of attributed causation has changed over time. Methods All cases of OHP reported to the SWORD scheme between January 1996 and December 2015 were classified into 1 of 10 categories of the suspected agent. Cases were grouped into four 5-year time periods to examine any changing pattern in incidence or suspected causation. For each time period, the annual incidence was calculated using the estimated number of reported cases and the working population of the UK. Results Between 1996 and 2015, there were 202 actual cases of OHP reported to SWORD, equating to an estimated 818 cases, when adjusting for the sampling ratio. Over this period, the annual UK incidence was 1.4 per million workers. The mean (SD) age of reported cases was 52 (13) years, and cases were four-times more likely to be men than women. Over the study period, there was a fall in the proportion of cases reported to be due to agricultural exposures (44–12%), and an increase in cases due to metalworking fluids (MWFs, 2–45%). Conclusions Over the last 20 years, the incidence of OHP in the UK has been ∼1–2 cases per million workers per year. Working with water-based MWFs is now the most commonly suspected causative exposure for OHP cases reported to the SWORD scheme in the UK. PMID:27919062

  12. [A case of Grave's disease with MPO-ANCA-associated glomerulonephritis during propylthiouracil (PTU) therapy following interstitial pneumonitis].

    PubMed

    Saeki, T; Miyamura, S; Nakano, M; Arakawa, M

    1997-03-01

    A 68-year-old man who developed MPO-ANCA-associated glomerulonephritis during propylthiouracil (PTU) treatment is reported. In 1986, he was diagnosed as having interstitial pneumonitis. Although he tested positive for antinuclear antibody and rheumatoid factor, he had no symptoms and was followed up without therapy. Five years later, the diagnosis of Graves's disease was made after complaints of body weight loss, diplopia and exophthalmos. Tests showed positivity for anti-thyroid stimulating hormone (TSH) receptor antibody, antithyroidperoxidase antibody and antithyroglobulin antibody. He was treated with PTU and prednisolone for four years. In November 1995, hematuria and proteinuria developed, and renal function deteriorated rapidly. A renal biopsy revealed crescentic glomerulonephritis and the serum titer of MPO-ANCA was markedly elevated. He was treated with a high dose of prednisolone and cyclophosphamide. Although the serum creatinine level gradually decreased, irreversible renal dysfunction persisted. In this patient, the presence of various autoantibodies had been recognized for several years before MPO-ANCA-associated glomerulonephritis developed. Polyclonal B-cell activation and PTU treatment may have played a role in the pathogenesis of MPO-ANCA-associated glomerulonephritis.

  13. Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation.

    PubMed

    Chiang, Yun; Tsai, Cheng-Hong; Kuo, Sung-Hsin; Liu, Chieh-Yu; Yao, Ming; Li, Chi-Cheng; Huang, Shang-Yi; Ko, Bor-Sheng; Lin, Chien-Ting; Hou, Hsin-An; Chou, Wen-Chien; Liu, Jia-Hau; Lin, Chien-Chin; Wu, Shang-Ju; Hsu, Szu-Chun; Chen, Yao-Chang; Lin, Kai-Hsin; Lin, Dong-Tsamn; Chou, Hsien-Tang; Lu, Meng-Yu; Yang, Yung-Li; Chang, Hsiu-Hao; Liu, Ming-Chih; Liao, Xiu-Wen; Wu, Jian-Kuen; Chou, Sheng-Chieh; Cheng, Chieh-Lung; Chen, Chien-Yuan; Tsay, Woei; Tien, Hwei-Fang; Tang, Jih-Luh; Chen, Yu-Hsuan

    2016-11-10

    Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy.

  14. Chronic Hypersensitivity Pneumonitis With a Usual Interstitial Pneumonia-Like Pattern: Correlation Between Histopathologic and Clinical Findings.

    PubMed

    Chiba, Sahoko; Tsuchiya, Kimitake; Akashi, Takumi; Ishizuka, Masahiro; Okamoto, Tsukasa; Furusawa, Haruhiko; Tateishi, Tomoya; Kishino, Mitsuhiro; Miyazaki, Yasunari; Tateishi, Ukihide; Takemura, Tamiko; Inase, Naohiko

    2016-06-01

    Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of environmental antigens. The relationship between clinical, radiologic, and histopathologic findings of chronic HP remains unclear. Sixteen patients with proven chronic bird-related HP with a usual interstitial pneumonia-like pattern were analyzed retrospectively. Histopathologic findings were semiquantitatively assessed and compared with clinical and radiologic findings. We also evaluated the histopathologic findings affecting prognosis. The extent of centrilobular fibrosis was negatively correlated with Pao2 (r = -0.55, P = .03). The extent of bridging fibrosis was positively correlated with the ratio of maximal expiratory flow at 50% of forced vital capacity to that at 25% (r = 0.60, P = .02). Patients with a greater extent of fibroblastic foci (FF) had more radiologic reticulation (P = .01), honeycombing (P = .01), and traction bronchiectasis (P = .02), and had significantly shorter survival time (P = .01) than patients with a lesser extent of FF. Multivariate analysis showed that the extent of FF was a significant prognostic factor (hazard ratio, 2.36; 95% confidence interval, 1.02-5.48; P = .04). Our findings demonstrated that the extent of FF was significantly associated with reticulation, honeycombing, and traction bronchiectasis on high-resolution CT scanning. Moreover, the extent of FF could be a useful predictor of mortality in chronic HP with a usual interstitial pneumonia-like pattern. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  15. New-onset systemic lupus erythematosus in a long-term hemodialysis patient with acute pleuritis and pneumonitis.

    PubMed

    Hiyamuta, Hiroto; Yamada, Shunsuke; Yotsueda, Ryusuke; Hasegawa, Shoko; Nakano, Toshiaki; Taniguchi, Masatomo; Tsukamoto, Hiroshi; Kitazono, Takanari; Tsuruya, Kazuhiko

    2015-11-01

    A 61-year-old woman, with a 25-year history of maintenance hemodialysis due to end-stage renal disease of unknown causes, was admitted because of systemic joint pain and inflammatory response of unknown etiology that persisted for 1 month. Laboratory data on admission revealed leukocytopenia, lymphocytopenia, high serum C-reactive protein, and positivity for antinuclear antibody (ANA) and anti-double strand DNA. After admission, she progressively developed cough and dyspnea. A chest radiograph revealed bilateral ground glass opacity and pleural effusion. A thoracentesis revealed lupus erythematosus cells, suggesting lupus pleuritis. A chest computed tomography showed a pattern of diffuse alveolar damage compatible with acute lupus pneumonitis. She fulfilled the American Rheumatism Association diagnostic criteria for systemic lupus erythematosus (SLE). Methylprednisolone pulse therapy followed by oral prednisone treatment improved the clinical symptoms and laboratory abnormalities. ANA was negative 25 years earlier when she first started hemodialysis and she had neither clinical nor serological abnormalities related to SLE during the last 25 years. Further, she had neither received drugs that can cause drug-induced SLE, nor had a history of ultraviolet ray exposure, pregnancy, blood transfusion, trauma and smoking. This report suggests that new-onset SLE can develop in patients undergoing long-term dialysis. Hence, when we encounter dialysis patients with arthralgia and/or respiratory disorders, we should consider the possibility of new-onset SLE.

  16. Hypersensitivity pneumonitis in a cluster of sawmill workers: a 10-year follow-up of exposure, symptoms, and lung function

    PubMed Central

    Færden, Karl; Lund, May Brit; Aaløkken, Trond Mogens; Eduard, Wijnand; Søstrand, Per; Langård, Sverre; Kongerud, Johny

    2014-01-01

    Background: The long-term prognosis of repeated acute episodes of hypersensitivity pneumonitis (HP) is not well described. We report on a 10-year follow-up of a 10-person cluster from a Norwegian sawmill who had all experienced relapsing episodes of HP. Objectives: To evaluate the health symptoms, work-related sick-leave, and lung function of 10 workers exposed to mold in a Norwegian sawmill. Methods: Participants were evaluated at baseline and 10 years later at follow-up. A structured interview, measurement of serum IgG antibodies to Rhizopus microsporus (R. microsporus) antigens, lung function tests, high resolution computed tomography (HRCT) of the chest, and personal measurements of exposure to mold spores and dust were completed for each participant. Results: At baseline, nearly all workers reported acute episodes of HP more than twice a month. At follow-up, both the frequency and intensity of symptoms had declined. Sick-leave was reduced and gas diffusing capacity improved – paralleling the gradually reduced air levels of mold spores. Conclusions: In spite of an initially high occurrence of symptoms, long-term clinical and physiological outcome was good. With reduced exposure to mold spores, symptoms declined and lung function was restored. PMID:24999852

  17. Chemical pneumonitis and subsequent reactive airways dysfunction syndrome after a single exposure to a household product: a case report.

    PubMed

    Khalid, Imran; Godfrey, Amanda M; Ouellette, Daniel R

    2009-11-09

    Household products are usually safe to use. Adverse events arising from their use are mostly reported in patients with pre-existing atopy or pulmonary problems and usually only after a prolonged exposure to such products. We report the case of a patient with no prior problems who developed significant side effects from a single exposure to a domestic product. A 43-year-old Caucasian American man, previously in good health, used a domestic aerosol product called 'Stand N' Seal "Spray-On" Grout Sealer' in an enclosed room in his house. The product contained n-butyl acetate (<5%), propane (10%), isobutane (<5%), C8-C9 petroleum hydrocarbon solvent (80%), a fluoropolymer resin and a solvent. Within a few hours of exposure to the sealant, he developed rapidly progressive shortness of breath and a severe non-productive cough. By the time he reached the emergency room he was severely hypoxic. A diagnosis of chemical pneumonitis was made based on the clinical scenario and the diffuse infiltrates on the computer tomography scan. With supportive therapy, his condition improved and he was discharged from the hospital. However, he continued to have symptoms of intermittent cough and shortness of breath in response to strong odours, fumes, cold air and exertion even after his chest radiograph had normalized. Three months later, bronchial hyper-responsiveness was documented by a methacholine inhalation test and a diagnosis of reactive airways dysfunction syndrome was made. The patient was started on high-dose inhaled steroids and his symptoms improved. The mechanism of toxicity and determination of the exact agent responsible is still under investigation. A household product may still prove unsafe to use even after it has gone through vigorous testing and approval processes. Even healthy individuals are susceptible to adverse outcomes after a brief exposure. Extra precautions should be taken when using any chemical product at home.

  18. Feasibility and potential utility of multicomponent exhaled breath analysis for predicting development of radiation pneumonitis after stereotactic ablative radiotherapy.

    PubMed

    Moré, Jayaji M; Eclov, Neville C W; Chung, Melody P; Wynne, Jacob F; Shorter, Joanne H; Nelson, David D; Hanlon, Alexandra L; Burmeister, Robert; Banos, Peter; Maxim, Peter G; Loo, Billy W; Diehn, Maximilian

    2014-07-01

    In this prospective pilot study, we evaluated the feasibility and potential utility of measuring multiple exhaled gases as biomarkers of radiation pneumonitis (RP) in patients receiving stereotactic ablative radiotherapy (SABR) for lung tumors. Breath analysis was performed for 26 patients receiving SABR for lung tumors. Concentrations of exhaled nitric oxide (eNO), carbon monoxide (eCO), nitrous oxide (eN2O), and carbon dioxide (eCO2) were measured before and immediately after each fraction using real-time, infrared laser spectroscopy. RP development (CTCAE grade ≥2) was correlated with baseline gas concentrations, acute changes in gas concentrations after each SABR fraction, and dosimetric parameters. Exhaled breath analysis was successfully completed in 77% of patients. Five of 20 evaluable patients developed RP at a mean of 5.4 months after SABR. Acute changes in eNO and eCO concentrations, defined as percent changes between each pre-fraction and post-fraction measurement, were significantly smaller in RP versus non-RP cases (p = 0.022 and 0.015, respectively). In an exploratory analysis, a combined predictor of baseline eNO greater than 24 parts per billion and acute decrease in eCO less than 5.5% strongly correlated with RP incidence (p =0.0099). Neither eN2O nor eCO2 concentrations were significantly associated with RP development. Although generally higher in patients destined to develop RP, dosimetric parameters were not significantly associated with RP development. The majority of SABR patients in this pilot study were able to complete exhaled breath analysis. Baseline concentrations and acute changes in concentrations of exhaled breath components were associated with RP development after SABR. If our findings are validated, exhaled breath analysis may become a useful approach for noninvasive identification of patients at highest risk for developing RP after SABR.

  19. Epidemiology of occupational hypersensitivity pneumonitis; reports from the SWORD scheme in the UK from 1996 to 2015.

    PubMed

    Barber, C M; Wiggans, R E; Carder, M; Agius, R

    2017-07-01

    To estimate the reported incidence of occupational hypersensitivity pneumonitis (OHP) in the UK and to consider whether the pattern of attributed causation has changed over time. All cases of OHP reported to the SWORD scheme between January 1996 and December 2015 were classified into 1 of 10 categories of the suspected agent. Cases were grouped into four 5-year time periods to examine any changing pattern in incidence or suspected causation. For each time period, the annual incidence was calculated using the estimated number of reported cases and the working population of the UK. Between 1996 and 2015, there were 202 actual cases of OHP reported to SWORD, equating to an estimated 818 cases, when adjusting for the sampling ratio. Over this period, the annual UK incidence was 1.4 per million workers. The mean (SD) age of reported cases was 52 (13) years, and cases were four-times more likely to be men than women. Over the study period, there was a fall in the proportion of cases reported to be due to agricultural exposures (44-12%), and an increase in cases due to metalworking fluids (MWFs, 2-45%). Over the last 20 years, the incidence of OHP in the UK has been ∼1-2 cases per million workers per year. Working with water-based MWFs is now the most commonly suspected causative exposure for OHP cases reported to the SWORD scheme in the UK. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. Effect of induction chemotherapy on estimated risk of radiation pneumonitis in bulky non–small cell lung cancer

    SciTech Connect

    Amin, Neha P., E-mail: npamin@gmail.com; Miften, Moyed; Thornton, Dale

    2013-10-01

    Patients with bulky non–small cell lung cancer (NSCLC) may be at a high risk for radiation pneumonitis (RP) if treated with up-front concurrent chemoradiation. There is limited information about the effect of induction chemotherapy on the volume of normal lung subsequently irradiated. This study aims to estimate the reduction in risk of RP in patients with NSCLC after receiving induction chemotherapy. Between 2004 and 2009, 25 patients with Stage IV NSCLC were treated with chemotherapy alone (no surgery or radiation therapy [RT]) and had computed tomography (CT) scans before and after 2 cycles of chemotherapy. Simulated RT plans were createdmore » for the prechemotherapy and postchemotherapy scans so as to deliver 60 Gy to the thoracic disease in patients who had either a >20% volumetric increase or decrease in gross tumor volume (GTV) from chemotherapy. The prechemotherapy and postchemotherapy scans were analyzed to compare the percentage of lung volume receiving≥20 Gy (V20), mean lung dose (MLD), and normal tissue complication probability (NTCP). Eight patients (32%) had a GTV reduction >20%, 2 (8%) had GTV increase >20%, and 15 (60%) had stable GTV. In the 8 responders, there was an absolute median GTV decrease of 88.1 cc (7.3 to 351.6 cc) or a 48% (20% to 62%) relative reduction in tumor burden. One had >20% tumor progression during chemotherapy, yet had an improvement in dosimetric parameters postchemotherapy. Among these 9 patients, the median decrease in V20, MLD, and NTCP was 2.6% (p<0.01), 2.1 Gy (p<0.01), and 5.6% (p<0.01), respectively. Less than one-third of patients with NSCLC obtain >20% volumetric tumor reduction from chemotherapy alone. Even with that amount of volumetric reduction, the 5% reduced risk of RP was only modest and did not convert previously ineligible patients to safely receive definitive thoracic RT.« less

  1. Human monocyte-derived dendritic cells exposed to microorganisms involved in hypersensitivity pneumonitis induce a Th1-polarized immune response.

    PubMed

    Bellanger, Anne-Pauline; Pallandre, Jean-René; Borg, Christophe; Loeffert, Sophie; Gbaguidi-Haore, Houssein; Millon, Laurence

    2013-08-01

    Hypersensitivity pneumonitis (HP) is an immunoallergic disease characterized by a prominent interstitial infiltrate composed predominantly of lymphocytes secreting inflammatory cytokines. Dendritic cells (DCs) are known to play a pivotal role in the lymphocytic response. However, their cross talk with microorganisms that cause HP has yet to be elucidated. This study aimed to investigate the initial interactions between human monocyte-derived DCs (MoDCs) and four microorganisms that are different in nature (Saccharopolyspora rectivirgula [actinomycetes], Mycobacterium immunogenum [mycobacteria], and Wallemia sebi and Eurotium amstelodami [filamentous fungi]) and are involved in HP. Our objectives were to determine the cross talk between MoDCs and HP-causative agents and to determine whether the resulting immune response varied according to the microbial extract tested. The phenotypic activation of MoDCs was measured by the increased expression of costimulatory molecules and levels of cytokines in supernatants. The functional activation of MoDCs was measured by the ability of MoDCs to induce lymphocytic proliferation and differentiation in a mixed lymphocytic reaction (MLR). E. amstelodami-exposed (EA) MoDCs expressed higher percentages of costimulatory molecules than did W. sebi-exposed (WS), S. rectivirgula-exposed (SR), or M. immunogenum-exposed (MI) MoDCs (P < 0.05, Wilcoxon signed-rank test). EA-MoDCs, WS-MoDCs, SR-MoDCs, and MI-MoDCs induced CD4(+) T cell proliferation and a Th1-polarized immune response. The present study provides evidence that, although differences were initially observed between MoDCs exposed to filamentous fungi and MoDCs exposed to bacteria, a Th1 response was ultimately promoted by DCs regardless of the microbial extract tested.

  2. A comparison of health-related quality of life in idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

    PubMed

    Lubin, Molly; Chen, Hubert; Elicker, Brett; Jones, Kirk D; Collard, Harold R; Lee, Joyce S

    2014-06-01

    Patients with interstitial lung disease (ILD) have poor health-related quality of life (HRQL). However, whether HRQL differs among different subtypes of ILD is unclear. The aim of this study was to determine whether HRQL was different among patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP). We identified patients from an ongoing longitudinal cohort of patients with ILD. HRQL was assessed using the Short Form (SF)-36 medical outcomes form (version 2.0). Regression analysis was used to determine the association between clinical covariates and HRQL, primarily the physical component summary (PCS) and mental component summary (MCS) score. A multivariate regression model was created to identify potential covariates that could help explain the association between the ILD subtype and HRQL. Patients with IPF (n = 102) were older, more likely to be men, and more likely to have smoked. Pulmonary function was similar between the groups. The patients with CHP (n = 69) had worse HRQL across all eight domains of the SF-36, as well as the PCS and MCS, compared with patients with IPF (P < .01-.09). This pattern remained after controlling for age and pulmonary function (P < .01-.02). Covariates explaining part of the relationship between disease subtype and PCS score included severity of dyspnea (P < .01) and fatigue (P < .01). Covariates explaining part of the relationship between disease subtype and MCS score included severity of dyspnea (P < .01), female sex (P = .02), and fatigue (P = .02). HRQL is worse in CHP compared with IPF. HRQL differences between ILD subtypes are explained in part by differences in sex, dyspnea, and fatigue.

  3. ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    SciTech Connect

    Xiong, Huihua; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Liao, Zhongxing, E-mail: zliao@mdanderson.org

    2013-03-15

    Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. Results: Of 362more » patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.« less

  4. Design and testing for a nontagged F1-V fusion protein as vaccine antigen against bubonic and pneumonic plague.

    PubMed

    Powell, Bradford S; Andrews, Gerard P; Enama, Jeffrey T; Jendrek, Scott; Bolt, Chris; Worsham, Patricia; Pullen, Jeffrey K; Ribot, Wilson; Hines, Harry; Smith, Leonard; Heath, David G; Adamovicz, Jeffrey J

    2005-01-01

    A two-component recombinant fusion protein antigen was re-engineered and tested as a medical counter measure against the possible biological threat of aerosolized Yersinia pestis. The active component of the proposed subunit vaccine combines the F1 capsular protein and V virulence antigen of Y. pestis and improves upon the design of an earlier histidine-tagged fusion protein. In the current study, different production strains were screened for suitable expression and a purification process was optimized to isolate an F1-V fusion protein absent extraneous coding sequences. Soluble F1-V protein was isolated to 99% purity by sequential liquid chromatography including capture and refolding of urea-denatured protein via anion exchange, followed by hydrophobic interaction, concentration, and then transfer into buffered saline for direct use after frozen storage. Protein identity and primary structure were verified by mass spectrometry and Edman sequencing, confirming a purified product of 477 amino acids and removal of the N-terminal methionine. Purity, quality, and higher-order structure were compared between lots using RP-HPLC, intrinsic fluorescence, CD spectroscopy, and multi-angle light scattering spectroscopy, all of which indicated a consistent and properly folded product. As formulated with aluminum hydroxide adjuvant and administered in a single subcutaneous dose, this new F1-V protein also protected mice from wild-type and non-encapsulated Y. pestis challenge strains, modeling prophylaxis against pneumonic and bubonic plague. These findings confirm that the fusion protein architecture provides superior protection over the former licensed product, establish a foundation from which to create a robust production process, and set forth assays for the development of F1-V as the active pharmaceutical ingredient of the next plague vaccine.

  5. Oral vaccination with salmonella simultaneously expressing Yersinia pestis F1 and V antigens protects against bubonic and pneumonic plague.

    PubMed

    Yang, Xinghong; Hinnebusch, B Joseph; Trunkle, Theresa; Bosio, Catharine M; Suo, Zhiyong; Tighe, Mike; Harmsen, Ann; Becker, Todd; Crist, Kathryn; Walters, Nancy; Avci, Recep; Pascual, David W

    2007-01-15

    The gut provides a large area for immunization enabling the development of mucosal and systemic Ab responses. To test whether the protective Ags to Yersinia pestis can be orally delivered, the Y. pestis caf1 operon, encoding the F1-Ag and virulence Ag (V-Ag) were cloned into attenuated Salmonella vaccine vectors. F1-Ag expression was controlled under a promoter from the caf1 operon; two different promoters (P), PtetA in pV3, PphoP in pV4, as well as a chimera of the two in pV55 were tested. F1-Ag was amply expressed; the chimera in the pV55 showed the best V-Ag expression. Oral immunization with Salmonella-F1 elicited elevated secretory (S)-IgA and serum IgG titers, and Salmonella-V-Ag(pV55) elicited much greater S-IgA and serum IgG Ab titers than Salmonella-V-Ag(pV3) or Salmonella-V-Ag(pV4). Hence, a new Salmonella vaccine, Salmonella-(F1+V)Ags, made with a single plasmid containing the caf1 operon and the chimeric promoter for V-Ag allowed the simultaneous expression of F1 capsule and V-Ag. Salmonella-(F1+V)Ags elicited elevated Ab titers similar to their monotypic derivatives. For bubonic plague, mice dosed with Salmonella-(F1+V)Ags and Salmonella-F1-Ag showed similar efficacy (>83% survival) against approximately 1000 LD(50) Y. pestis. For pneumonic plague, immunized mice required immunity to both F1- and V-Ags because the mice vaccinated with Salmonella-(F1+V)Ags protected against 100 LD(50) Y. pestis. These results show that a single Salmonella vaccine can deliver both F1- and V-Ags to effect both systemic and mucosal immune protection against Y. pestis.

  6. Risk of radiation pneumonitis in patients receiving taxane-based trimodality therapy for locally advanced esophageal cancer.

    PubMed

    Shaikh, Talha; Churilla, Thomas M; Monpara, Pooja; Scott, Walter J; Cohen, Steven J; Meyer, Joshua E

    There are limited data regarding clinical and treatment factors associated with radiation pneumonitis (RP) in patients receiving taxane-based trimodality therapy for esophageal cancer. The purpose of this study was to identify predictors of RP in patients undergoing trimodality therapy. We retrospectively reviewed patients undergoing chemoradiation followed by esophagectomy between 2006 and 2011. The association between clinical and dosimetric factors with RP was assessed using χ 2 test and Mann-Whitney U test. Multivariable regression was used to assess the relationship between grade 2+ RP and clinical/dosimetric factors. Receiver operator curves were generated to identify threshold doses for RP. A total of 139 patients were included; 19 (13.7%) patients experienced grade 2+ RP. Patients with upper/middle thoracic tumors (P = .038) and receiving higher radiation doses (P = .038) were more likely to develop grade 2+ RP. There was no association between taxane-based therapy and grade 2+ RP (P = .728). The percent volume of lung receiving 5 Gy (V5; P < .001), 10 Gy (P < .001), 20 Gy (V20; P < .001), and 30 Gy (P < .001) was associated with an increased risk of grade 2+ RP. On multivariable regression, the lung V5 (odds ratio, 1.101; 95% confidence interval, 1.1014-1.195) and V20 (odds ratio, 1.149; 95% confidence interval, 1.1015-1.301) remained associated with grade 2+ RP. A V5 ≤65% and V20 ≤25% were identified as optimal thresholds for increased grade 2+ RP. Dosimetric parameters are strong predictors of symptomatic RP in patients undergoing trimodality therapy for esophageal cancer. Mitigating the risk of RP in these patients should be an important consideration during treatment planning. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  7. Pre–Radiation Therapy Fluorine 18 Fluorodeoxyglucose PET Helps Identify Patients with Esophageal Cancer at High Risk for Radiation Pneumonitis

    PubMed Central

    Castillo, Richard; Pham, Ngoc; Castillo, Edward; Aso-Gonzalez, Samantha; Ansari, Sobiya; Hobbs, Brian; Palacio, Diana; Skinner, Heath

    2015-01-01

    Purpose To examine the association between pre–radiation therapy (RT) fluorine 18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis (RP). Materials and Methods In accordance with the retrospective study protocol approved by the institutional review board, 228 esophageal cancer patients who underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were evaluated by using the Common Terminology Criteria for Adverse Events, version 4.0, from the consensus of five clinicians. By using the cumulative distribution of standardized uptake values (SUVs) within the lungs, those values greater than 80%–95% of the total lung voxels were determined for each patient. The effect of pre-chemotherapy and RT FDG uptake, dose, and patient or treatment characteristics on RP toxicity was studied by using logistic regression. Results The study subjects were treated with three-dimensional conformal RT (n = 36), intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related to expression of RP symptoms. Study subjects with elevated 95% percentile of the SUV (SUV95) were more likely to develop symptomatic RP (P < .000012); each 0.1 unit increase in SUV95 was associated with a 1.36-fold increase in the odds of symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77), sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT imaging and dosimetric parameters were found to be poor predictors of RP symptoms. Conclusion The SUV95, a biomarker of pretreatment pulmonary metabolic activity, was shown to be prognostic of symptomatic RP. Elevation in this pretreatment biomarker identifies patients at high risk for posttreatment symptomatic RP. © RSNA, 2015 PMID:25584706

  8. Pre-Radiation Therapy Fluorine 18 Fluorodeoxyglucose PET Helps Identify Patients with Esophageal Cancer at High Risk for Radiation Pneumonitis.

    PubMed

    Castillo, Richard; Pham, Ngoc; Castillo, Edward; Aso-Gonzalez, Samantha; Ansari, Sobiya; Hobbs, Brian; Palacio, Diana; Skinner, Heath; Guerrero, Thomas M

    2015-06-01

    To examine the association between pre-radiation therapy (RT) fluorine 18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis (RP). In accordance with the retrospective study protocol approved by the institutional review board, 228 esophageal cancer patients who underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were evaluated by using the Common Terminology Criteria for Adverse Events, version 4.0, from the consensus of five clinicians. By using the cumulative distribution of standardized uptake values (SUVs) within the lungs, those values greater than 80%-95% of the total lung voxels were determined for each patient. The effect of pre-chemotherapy and RT FDG uptake, dose, and patient or treatment characteristics on RP toxicity was studied by using logistic regression. The study subjects were treated with three-dimensional conformal RT (n = 36), intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related to expression of RP symptoms. Study subjects with elevated 95% percentile of the SUV (SUV95) were more likely to develop symptomatic RP (P < .000012); each 0.1 unit increase in SUV95 was associated with a 1.36-fold increase in the odds of symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77), sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT imaging and dosimetric parameters were found to be poor predictors of RP symptoms. The SUV95, a biomarker of pretreatment pulmonary metabolic activity, was shown to be prognostic of symptomatic RP. Elevation in this pretreatment biomarker identifies patients at high risk for posttreatment symptomatic RP. RSNA, 2015

  9. Chronic hypersensitivity pneumonitis caused by Saccharopolyspora rectivirgula is not associated with a switch to a Th2 response

    PubMed Central

    Andrews, Kelly; Ghosh, Manik C.; Schwingshackl, Andreas; Rapalo, Gabriel; Luellen, Charlean; Waters, Christopher M.

    2015-01-01

    Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease results in alveolitis and granuloma formation and may progress to a chronic form associated with fibrosis; a greater understanding of the immunopathogenic mechanisms leading to chronic HP is needed. We used the Saccharopolyspora rectivirgula (SR) mouse model of HP to determine the extent to which a switch to a Th2-type immune response is associated with chronic HP. Exposure of wild-type (WT) and tlr2/9−/− mice to SR for 14 wk resulted in neutrophilic and lymphocytic alveolitis that was not dependent on Toll-like receptors (TLRs) 2 and 9. Long-term exposure of WT mice to SR resulted in a significant increase in collagen deposition, protein leakage, and IL-1α accompanied by a decrease in quasistatic compliance and total lung capacity compared with unexposed mice. This was associated with an increase in IL-17 but not IL-4 production or recruitment of Th2 cells. tlr2/9−/− mice exhibited an increase in protein leakage but less IL-1α and collagen deposition in the lungs compared with WT mice, yet they still displayed a decrease in quasistatic compliance, although total lung capacity was not affected. These mice exhibited an increase in both IL-13 and IL-17, which suggests that IL-13 may ameliorate some of the lung damage caused by long-term SR exposure. Our results suggest that lung pathology following long-term SR exposure in WT mice is associated with the IL-17 response and that TLRs 2 and 9 may inhibit the development of the IL-13/Th2 response. PMID:26719148

  10. The efficacy of prophylactic antibiotics in the management of children with kerosene-associated pneumonitis: a double-blind randomised controlled trial.

    PubMed

    Balme, Kate H; Zar, Heather; Swift, Donne K; Mann, Michael D

    2015-01-01

    Hydrocarbons, especially kerosene (paraffin), are the most common agents causing childhood poisoning in low and middle income countries (LMICs). Aspiration of kerosene causes an inflammatory sterile chemical pneumonitis, which may increase susceptibility to secondary lower respiratory tract bacterial infection. This study aimed to assess the efficacy of prophylactic antibiotics in the management of kerosene-associated pneumonitis in children and to identify risk factors associated with severity or outcome. A double-blind placebo-controlled trial of prophylactic antibiotics in the management of kerosene-associated pneumonitis of children presenting to a referral hospital was performed from July 2010 to September 2011. Sequential children with a history of kerosene ingestion and mild respiratory illness were randomised to receive placebo or amoxicillin. Each child was followed-up at Day 3 and Day 5 post-ingestion. The primary outcome measure was the number of treatment failures in each group, defined as any child who deteriorated within this time, necessitating a change in treatment regimen. Secondary outcome measures were length of hospital stay and symptoms and signs at follow-up. Seventy-four patients were enrolled. Thirty-five (47%) received placebo and 39 (53%) active treatment. There was no significant difference in treatment failures between placebo (3/35, 9%; 95% CI, 3-22) and active (2/39, 5%; 95% CI, 1-17) groups (relative risk, 0.60; 95% CI, 0.11-3.37). The median length of hospital stay was identical (placebo 0.5 days; IQR, 0-1.0 and active 0.5 days; IQR, 0.5-1.0). Symptoms and signs at Days 3 and 5 post-ingestion were similar. The only significant risk factor for treatment failure was residence in formal housing. Clinical severity at presentation was similar for treatment successes and failures. Prophylactic antibiotics do not improve the outcome in children with mild respiratory illness after kerosene ingestion.

  11. LETTER TO THE EDITOR: Clinical validation of the LKB model and parameter sets for predicting radiation-induced pneumonitis from breast cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Tsougos, Ioannis; Mavroidis, Panayiotis; Theodorou, Kyriaki; Rajala, J.; Pitkänen, M. A.; Holli, K.; Ojala, A. T.; Hyödynmaa, S.; Järvenpää, Ritva; Lind, Bengt K.; Kappas, Constantin

    2006-02-01

    The choice of the appropriate model and parameter set in determining the relation between the incidence of radiation pneumonitis and dose distribution in the lung is of great importance, especially in the case of breast radiotherapy where the observed incidence is fairly low. From our previous study based on 150 breast cancer patients, where the fits of dose-volume models to clinical data were estimated (Tsougos et al 2005 Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy Phys. Med. Biol. 50 3535-54), one could get the impression that the relative seriality is significantly better than the LKB NTCP model. However, the estimation of the different NTCP models was based on their goodness-of-fit on clinical data, using various sets of published parameters from other groups, and this fact may provisionally justify the results. Hence, we sought to investigate further the LKB model, by applying different published parameter sets for the very same group of patients, in order to be able to compare the results. It was shown that, depending on the parameter set applied, the LKB model is able to predict the incidence of radiation pneumonitis with acceptable accuracy, especially when implemented on a sub-group of patients (120) receiving \\bar{\\bar{D}}|EUD higher than 8 Gy. In conclusion, the goodness-of-fit of a certain radiobiological model on a given clinical case is closely related to the selection of the proper scoring criteria and parameter set as well as to the compatibility of the clinical case from which the data were derived.

  12. A non-invasive in vivo imaging system to study dissemination of bioluminescent Yersinia pestis CO92 in a mouse model of pneumonic plague.

    PubMed

    Sha, Jian; Rosenzweig, Jason A; Kirtley, Michelle L; van Lier, Christina J; Fitts, Eric C; Kozlova, Elena V; Erova, Tatiana E; Tiner, Bethany L; Chopra, Ashok K

    2013-02-01

    The gold standard in microbiology for monitoring bacterial dissemination in infected animals has always been viable plate counts. This method, despite being quantitative, requires sacrificing the infected animals. Recently, however, an alternative method of in vivo imaging of bioluminescent bacteria (IVIBB) for monitoring microbial dissemination within the host has been employed. Yersinia pestis is a Gram-negative bacterium capable of causing bubonic, septicemic, and pneumonic plague. In this study, we compared the conventional counting of bacterial colony forming units (cfu) in the various infected tissues to IVIBB in monitoring Y. pestis dissemination in a mouse model of pneumonic plague. By using a transposon mutagenesis system harboring the luciferase (luc) gene, we screened approximately 4000 clones and obtained a fully virulent, luc-positive Y. pestis CO92 (Y. pestis-luc2) reporter strain in which transposition occurred within the largest pMT1 plasmid which possesses murine toxin and capsular antigen encoding genes. The aforementioned reporter strain and the wild-type CO92 exhibited similar growth curves, formed capsule based on immunofluorescence microscopy and flow cytometry, and had a similar LD(50). Intranasal infection of mice with 15 LD(50) of CO92-luc2 resulted in animal mortality by 72 h, and an increasing number of bioluminescent bacteria were observed in various mouse organs over a 24-72 h period when whole animals were imaged. However, following levofloxacin treatment (10 mg/kg/day) for 6 days 24 h post infection, no luminescence was observed after 72 h of infection, indicating that the tested antimicrobial killed bacteria preventing their detection in host peripheral tissues. Overall, we demonstrated that IVIBB is an effective and non-invasive way of monitoring bacterial dissemination in animals following pneumonic plague having strong correlation with cfu, and our reporter CO92-luc2 strain can be employed as a useful tool to monitor the efficacy

  13. A non-invasive in vivo imaging system to study dissemination of bioluminescent Yersinia pestis CO92 in a mouse model of pneumonic plague

    PubMed Central

    Sha, Jian; Rosenzweig, Jason A.; Kirtley, Michelle L.; van Lier, Christina J.; Fitts, Eric C.; Kozlova, Elena V.; Erova, Tatiana E.; Tiner, Bethany L.; Chopra, Ashok K.

    2012-01-01

    The gold standard in microbiology for monitoring bacterial dissemination in infected animals has always been viable plate counts. This method, despite being quantitative, requires sacrificing the infected animals. Recently, however, an alternative method of in vivo imaging of bioluminescent bacteria (IVIBB) for monitoring microbial dissemination within the host has been employed. Yersina pestis is a Gram-negative bacterium capable of causing bubonic, septicemic, and pneumonic plague. In this study, we compared the conventional counting of bacterial colony forming units (cfu) in the various infected tissues to IVIBB in monitoring Y. pestis dissemination in a mouse model of pneumonic plague. By using a transposon mutagenesis system harboring the luciferase (luc) gene, we screened approximately 4000 clones and obtained a fully virulent, luc-positive Y. pestis CO92 (Y. pestis-luc2) reporter strain in which transposition occurred within the largest pMT1 plasmid which possesses murine toxin and capsular antigen encoding genes. The aforementioned reporter strain and the wild-type CO92 exhibited similar growth curves, formed capsule based on immunofluorescence microscopy and flow cytometry, and had a similar LD50. Intranasal infection of mice with 15 LD50 of CO92-luc2 resulted in animal mortality by 72 h, and an increasing number of bioluminescent bacteria were observed in various mouse organs over a 24–72 h period when whole animals were imaged. However, following levofloxacin treatment (10 mg/kg/day) for 6 days 24 h post infection, no luminescence was observed after 72 h of infection, indicating that the tested antimicrobial killed bacteria preventing their detection in host peripheral tissues. Overall, we demonstrated that IVIBB is an effective and non-invasive way of monitoring bacterial dissemination in animals following pneumonic plague having strong correlation with cfu, and our reporter CO92-luc2 strain can be employed as a useful tool to monitor the efficacy of

  14. Recombinant V antigen protects mice against pneumonic and bubonic plague caused by F1-capsule-positive and -negative strains of Yersinia pestis.

    PubMed

    Anderson, G W; Leary, S E; Williamson, E D; Titball, R W; Welkos, S L; Worsham, P L; Friedlander, A M

    1996-11-01

    The purified recombinant V antigen from Yersinia pestis, expressed in Escherichia coli and adsorbed to aluminum hydroxide, an adjuvant approved for human use, was used to immunize outbred Hsd:ND4 mice subcutaneously. Immunization protected mice from lethal bubonic and pneumonic plague caused by CO92, a wild-type F1+ strain, or by the isogenic F1- strain C12. This work demonstrates that a subunit plague vaccine formulated for human use provides significant protection against bubonic plague caused by an F1- strain (C12) or against substantial aerosol challenges from either F1+ (CO92) or F1-(C12) Y. pestis.

  15. Remote monitoring of the progression of primary pneumonic plague in Brown Norway rats in high-capacity, high-containment housing

    PubMed Central

    Coate, Eric A.; Kocsis, Andrew G.; Peters, Kristen N.; Anderson, Paul E.; Ellersieck, Mark R.; Fine, Deborah M.; Anderson, Deborah M.

    2014-01-01

    Development of new vaccines, diagnostics and therapeutics for biodefense or other relatively rare infectious diseases is hindered by the lack of naturally occurring human disease on which to conduct clinical trials of efficacy. To overcome this experimental gap, the U.S. Food and Drug Administration established the Animal Rule, in which efficacy testing in two well-characterized animal models that closely resemble human disease may be accepted in lieu of large scale clinical trials for diseases with limited natural human incidence. In this report, we evaluated the Brown Norway rat as a model for pneumonic plague and describe the natural history of clinical disease following inhalation exposure to Yersinia pestis. In high-capacity, high-containment housing, we monitored temperature, activity, heart rate and rhythm by capturing electronic impulses transmitted from abdominal telemeter implants. Using this system, we show that reduced activity and development of fever are sensitive indications of disease progression. Furthermore, we identified heart arrhythmias as contributing factors to the rapid progression to lethality following the fever response. Together these data validate the Brown Norway rat as an experimental model for human pneumonic plague and provide new insight that may ultimately lead to novel approaches in post-exposure treatment of this devastating infection. PMID:24719212

  16. Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

    SciTech Connect

    Pinnix, Chelsea C., E-mail: ccpinnix@mdanderson.org; Smith, Grace L.; Milgrom, Sarah

    Purpose: Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a singlemore » institution. Methods and Materials: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ{sup 2} test and logistic multivariate regression. Results: Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V{sub 20} of >30%, V{sub 15} of >35%, V{sub 10} of >40%, and V{sub 5} of >55%. The likelihood ratio χ{sup 2} value was highest for V{sub 5} >55% (χ{sup 2} = 19.37). Conclusions: In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with

  17. Association Between White Blood Cell Count Following Radiation Therapy With Radiation Pneumonitis in Non-Small Cell Lung Cancer

    SciTech Connect

    Tang, Chad; Gomez, Daniel R.; Wang, Hongmei

    Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We assessed the association between RP and white blood cell (WBC) count, an established metric of systemic inflammation, after RT for non-small cell lung cancer. Methods and Materials: We retrospectively analyzed 366 patients with non-small cell lung cancer who received ≥60 Gy as definitive therapy. The primary endpoint was whether WBC count after RT (defined as 2 weeks through 3 months after RT completion) was associated with grade ≥3 or grade ≥2 RP. Median lung volume receiving ≥20 Gy (V{sub 20}) was 31%, and post-RT WBC counts rangedmore » from 1.7 to 21.2 × 10{sup 3} WBCs/μL. Odds ratios (ORs) associating clinical variables and post-RT WBC counts with RP were calculated via logistic regression. A recursive-partitioning algorithm was used to define optimal post-RT WBC count cut points. Results: Post-RT WBC counts were significantly higher in patients with grade ≥3 RP than without (P<.05). Optimal cut points for post-RT WBC count were found to be 7.4 and 8.0 × 10{sup 3}/μL for grade ≥3 and ≥2 RP, respectively. Univariate analysis revealed significant associations between post-RT WBC count and grade ≥3 (n=46, OR=2.6, 95% confidence interval [CI] 1.4‒4.9, P=.003) and grade ≥2 RP (n=164, OR=2.0, 95% CI 1.2‒3.4, P=.01). This association held in a stepwise multivariate regression. Of note, V{sub 20} was found to be significantly associated with grade ≥2 RP (OR=2.2, 95% CI 1.2‒3.4, P=.01) and trended toward significance for grade ≥3 RP (OR=1.9, 95% CI 1.0-3.5, P=.06). Conclusions: Post-RT WBC counts were significantly and independently associated with RP and have potential utility as a diagnostic or predictive marker for this toxicity.« less

  18. Nintedanib Compared With Placebo in Treating Against Radiation-Induced Pneumonitis in Patients With Non-small Cell Lung Cancer That Cannot Be Removed by Surgery and Are Undergoing Chemoradiation Therapy

    ClinicalTrials.gov

    2017-07-08

    Radiation-Induced Pneumonitis; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  19. Combinational Deletion of Three Membrane Protein-Encoding Genes Highly Attenuates Yersinia pestis while Retaining Immunogenicity in a Mouse Model of Pneumonic Plague

    PubMed Central

    Tiner, Bethany L.; Kirtley, Michelle L.; Erova, Tatiana E.; Popov, Vsevolod L.; Baze, Wallace B.; van Lier, Christina J.; Ponnusamy, Duraisamy; Andersson, Jourdan A.; Motin, Vladimir L.; Chauhan, Sadhana

    2015-01-01

    Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its lpp single and Δlpp ΔmsbB double mutants. While the Δail single mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the Δlpp Δail double mutant and the Δlpp ΔmsbB Δail triple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD50) equivalent to 6,800 LD50s of WT CO92. The mutant-infected animals developed balanced TH1- and TH2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD50s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time by in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of the ail gene from the Δlpp ΔmsbB double mutant severely attenuated Y. pestis CO92 to evoke pneumonic plague in a

  20. Combinational deletion of three membrane protein-encoding genes highly attenuates yersinia pestis while retaining immunogenicity in a mouse model of pneumonic plague.

    PubMed

    Tiner, Bethany L; Sha, Jian; Kirtley, Michelle L; Erova, Tatiana E; Popov, Vsevolod L; Baze, Wallace B; van Lier, Christina J; Ponnusamy, Duraisamy; Andersson, Jourdan A; Motin, Vladimir L; Chauhan, Sadhana; Chopra, Ashok K

    2015-04-01

    Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its lpp single and Δlpp ΔmsbB double mutants. While the Δail single mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the Δlpp Δail double mutant and the Δlpp ΔmsbB Δail triple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD50) equivalent to 6,800 LD50s of WT CO92. The mutant-infected animals developed balanced TH1- and TH2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD50s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time by in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of the ail gene from the Δlpp ΔmsbB double mutant severely attenuated Y. pestis CO92 to evoke pneumonic plague in a

  1. [Low dose volume histogram analysis of the lungs in prediction of acute radiation pneumonitis in patients with esophageal cancer treated with three-dimensional conformal radiotherapy].

    PubMed

    Shen, Wen-bin; Zhu, Shu-chai; Gao, Hong-mei; Li, You-mei; Liu, Zhi-kun; Li, Juan; Su, Jing-wei; Wan, Jun

    2013-01-01

    To investigate the predictive value of low dose volume of the lung on acute radiation pneumonitis (RP) in patients with esophageal cancer treated with three-dimensional conformal radiotherapy (3D-CRT) only, and to analyze the relation of comprehensive parameters of the dose-volume V5, V20 and mean lung dose (MLD) with acute RP. Two hundred and twenty-two patients with esophageal cancer treated by 3D-CRT have been followed up. The V5-V30 and MLD were calculated from the dose-volume histogram system. The clinical factors and treatment parameters were collected and analyzed. The acute RP was evaluated according to the RTOG toxicity criteria. The acute RP of grade 1, 2, 3 and 4 were observed in 68 (30.6%), 40 (18.0%), 8 (3.6%) and 1 (0.5%) cases, respectively. The univariate analysis of measurement data:The primary tumor length, radiation fields, MLD and lung V5-V30 had a significant relationship with the acute RP. The magnitude of the number of radiation fields, the volume of GTV, MLD and Lung V5-V30 had a significant difference in whether the ≥ grade 1 and ≥ grade 2 acute RP developed or not. Binary logistic regression analysis showed that MLD, Lung V5, V20 and V25 were independent risk factors of ≥ grade 1 acute RP, and the radiation fields, MLD and Lung V5 were independent risk factors of ≥ grade 2 acute RP. The ≥ grade 1 and ≥ grade 2 acute RP were significantly decreased when MLD less than 14 Gy, V5 and V20 were less than 60% and 28%,respectively. When the V20 ≤ 28%, the acute RP was significantly decreased in V5 ≤ 60% group. When the MLD was ≤ 14 Gy, the ≥ 1 grade acute RP was significantly decreased in the V5 ≤ 60% group. When the MLD was >14 Gy, the ≥ grade 2 acute RP was significantly decreased in the V5 ≤ 60% group. The low dose volume of the lung is effective in predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-CRT only. The comprehensive parameters combined with V5, V20 and MLD may increase the

  2. Clinical and Dosimetric Predictors of Radiation Pneumonitis in a Large Series of Patients Treated With Stereotactic Body Radiation Therapy to the Lung

    SciTech Connect

    Baker, Ryan; Han Gang; Sarangkasiri, Siriporn

    2013-01-01

    Purpose: To report clinical and dosimetric factors predictive of radiation pneumonitis (RP) in patients receiving lung stereotactic body radiation therapy (SBRT) from a series of 240 patients. Methods and Materials: Of the 297 isocenters treating 263 patients, 240 patients (n=263 isocenters) had evaluable information regarding RP. Age, gender, current smoking status and pack-years, O{sub 2} use, Charlson Comorbidity Index, prior lung radiation therapy (yes/no), dose/fractionation, V{sub 5}, V{sub 13}, V{sub 20}, V{sub prescription}, mean lung dose, planning target volume (PTV), total lung volume, and PTV/lung volume ratio were recorded. Results: Twenty-nine patients (11.0%) developed symptomatic pneumonitis (26 grade 2, 3more » grade 3). The mean V{sub 20} was 6.5% (range, 0.4%-20.2%), and the average mean lung dose was 5.03 Gy (0.547-12.2 Gy). In univariable analysis female gender (P=.0257) and Charlson Comorbidity index (P=.0366) were significantly predictive of RP. Among dosimetric parameters, V{sub 5} (P=.0186), V{sub 13} (P=.0438), and V{sub prescription} (where dose = 60 Gy) (P=.0128) were significant. There was only a trend toward significance for V{sub 20} (P=.0610). Planning target volume/normal lung volume ratio was highly significant (P=.0024). In multivariable analysis the clinical factors of female gender, pack-years smoking, and larger gross internal tumor volume and PTV were predictive (P=.0094, .0312, .0364, and .052, respectively), but no dosimetric factors were significant. Conclusions: Rate of symptomatic RP was 11%. Our mean lung dose was <600 cGy in most cases and V20 <10%. In univariable analysis, dosimetric factors were predictive, while tumor size (or tumor/lung volume ratio) played a role in multivariable and univariable and analysis, respectively.« less

  3. Bone marrow transplantation alters lung antigen presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection

    PubMed Central

    Zhou, Xiaofeng; Loomis-King, Hillary; Gurczynski, Stephen J.; Wilke, Carol A.; Konopka, Kristine E.; Ptaschinski, Catherine; Coomes, Stephanie M; Iwakura, Yoichiro; van Dyk, Linda F.; Lukacs, Nicholas W.; Moore, Bethany B.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplant (BMT) followed by infection with murine gamma herpesvirus (γHV-68) that results in pneumonitis and fibrosis and mimics human “non-infectious” HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection (dpi). CD4 T cells in BMT mice are skewed towards IL-17A rather than IFN-γ production. Transplantation of bone marrow from Il-17a−/− donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more TGF-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest “non-infectious” HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  4. BIO 300, a nanosuspension of genistein, mitigates pneumonitis/fibrosis following high-dose radiation exposure in the C57L/J murine model.

    PubMed

    Jackson, Isabel L; Zodda, Andrew; Gurung, Ganga; Pavlovic, Radmila; Kaytor, Michael D; Kuskowski, Michael A; Vujaskovic, Zeljko

    2017-12-01

    BIO 300 nanosuspension (Humanetics Corporation) is being developed as a medical countermeasure (MCM) for the mitigation of the delayed effects of acute radiation exposure, specifically pneumonitis and fibrosis of the lung. The objective of this study was to determine the best dose and treatment duration of BIO 300 to mitigate lung injury and improve the likelihood for survival in C57L/J mice exposed to whole thorax lung irradiation (WTLI). Age- and sex-matched C57L/J mice received a single dose of 11.0 or 12.5 Gy WTLI. BIO 300 (200 or 400 mg·kg -1 , oral gavage) was administered daily starting 24 h post-exposure for a duration of 2, 4, 6 or, in some cases, 10 weeks. Non-treated controls were included for comparison in both sexes. Animals were observed daily for signs of major morbidity. Respiratory function was assessed biweekly. Lungs were collected, weighed and paraffin embedded for histological evaluation post mortem. BIO 300 administered at an oral dose of 400 mg·kg -1 for 4 to 6 weeks starting 24 h post-WTLI reduced morbidity associated with WTLI. The improvement in survival correlated with reduced respiratory frequency and enhanced pause. The irradiated lungs of mice treated with BIO 300 (400 mg·kg -1 ) for 4 to 6 weeks displayed less morphological damage and airway loss due to oedema, congestion and fibrotic scarring than the untreated, irradiated controls. BIO 300 is a promising MCM candidate to mitigate pneumonitis/fibrosis when administered daily for 4-6 weeks starting 24 h post-exposure. © 2017 The British Pharmacological Society.

  5. Recovery of pulmonary functions, exercise capacity, and quality of life after pulmonary rehabilitation in survivors of ARDS due to severe influenza A (H1N1) pneumonitis.

    PubMed

    Hsieh, Meng-Jer; Lee, Wei-Chun; Cho, Hsiu-Ying; Wu, Meng-Fang; Hu, Han-Chung; Kao, Kuo-Chin; Chen, Ning-Hung; Tsai, Ying-Huang; Huang, Chung-Chi

    2018-04-20

    Acute respiratory distress syndrome (ARDS) due to severe influenza A H1N1 pneumonitis would result in impaired pulmonary functions and health-related quality of life (HRQoL) after hospital discharge. The recovery of pulmonary functions, exercise capacity, and HRQoL in the survivors of ARDS due to 2009 pandemic influenza A H1N1 pneumonitis (H1N1-ARDS) was evaluated in a tertiary teaching hospital in northern Taiwan between May 2010 and June 2011. Data of spirometry, total lung capacity (TLC), diffusing capacity of carbon monoxide (DL CO ), and 6-minute walk distance (6MWD) in the patients survived from H1N1-ARDS were collected 1, 3, and 6 months post-hospital discharge. HRQoL was evaluated with St. George respiratory questionnaire (SGRQ). Nine survivors of H1N1-ARDS in the study period were included. All these patients received 2 months' pulmonary rehabilitation program. Pulmonary functions and exercise capacity included TLC, forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1 ), DL CO , and 6MWD improved from 1 to 3 months post-hospital discharge. Only TLC had further significant improvement from 3 to 6 months. HRQoL represented as the total score of SGRQ had no significant improvement in the first 3 months but improved significantly from 3 to 6 months post-discharge. The impaired pulmonary functions and exercise capacity in the survivors of H1N1-ARDS improved soon at 3 months after hospital discharge. Their quality of life had keeping improved at 6 months even though there was no further improvement of their pulmonary functions and exercise capacity. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  6. Distribution of the ompA-types among ruminant and swine pneumonic strains of Pasteurella multocida exhibiting various cap-locus and toxA patterns.

    PubMed

    Vougidou, C; Sandalakis, V; Psaroulaki, A; Siarkou, V; Petridou, E; Ekateriniadou, L

    2015-05-01

    Pasteurella multocida is an important pathogen in food-producing animals and numerous virulence genes have been identified in an attempt to elucidate the pathogenesis of pasteurellosis. Currently, some of these genes including the capsule biosynthesis genes, the toxA and the OMPs-encoding genes have been suggested as epidemiological markers. However, the number of studies concerning ruminant isolates is limited, while, no attempt has ever been made to investigate the existence of ompA sequence diversity among P. multocida isolates. The aim of the present study was the comparative analysis of 144 P. multocida pneumonic isolates obtained from sheep, goats, cattle and pigs by determining the distribution of the ompA-types in conjunction with the cap-locus and toxA patterns. The ompA genotypes of the isolates were determined using both a PCR-RFLP method and DNA sequence analysis. The most prevalent capsule biosynthesis gene among the isolates was capA (86.1%); a noticeable, however, rate of capD-positive isolates (38.6%) was found among the ovine isolates that had been associated primarily with the capsule type A in the past. Moreover, an unexpectedly high percentage of toxA-positive pneumonic isolates was noticed among small ruminants (93.2% and 85.7% in sheep and goats, respectively), indicating an important epidemiological role of toxigenic P. multocida for these species. Despite their great heterogeneity, certain ompA-genotypes were associated with specific host species, showing evidence of a host preference. The OmpA-based PCR-RFLP method developed proved to be a valuable tool in typing P. multocida strains. Copyright © 2015 Elsevier GmbH. All rights reserved.

  7. Zinc transporters YbtX and ZnuABC are required for the virulence of Yersinia pestis in bubonic and pneumonic plague in mice.

    PubMed

    Bobrov, Alexander G; Kirillina, Olga; Fosso, Marina Y; Fetherston, Jacqueline D; Miller, M Clarke; VanCleave, Tiva T; Burlison, Joseph A; Arnold, William K; Lawrenz, Matthew B; Garneau-Tsodikova, Sylvie; Perry, Robert D

    2017-06-21

    A number of bacterial pathogens require the ZnuABC Zinc (Zn 2+ ) transporter and/or a second Zn 2+ transport system to overcome Zn 2+ sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn 2+ transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn 2+ transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic plague while a ybtX mutant retains high virulence in both plague models. While sequestration of host Zn is a key nutritional immunity factor, excess Zn appears to have a significant antimicrobial role in controlling intracellular bacterial survival. Here, we demonstrate that ZntA, a Zn 2+ exporter, plays a role in resistance to Zn toxicity in vitro, but that a zntA zur double mutant retains high virulence in both pneumonic and bubonic plague models and survival in macrophages. We also confirm that Ybt does not directly bind Zn 2+ in vitro under the conditions tested. However, we detect a significant increase in Zn 2+ -binding ability of filtered supernatants from a Ybt + strain compared to those from a strain unable to produce the siderophore, supporting our previously published data that Ybt biosynthetic genes are involved in the production of a secreted Zn-binding molecule (zincophore). Our data suggest that Ybt or a modified Ybt participate in or promote Zn-binding activity in culture supernatants and is involved in Zn acquisition in Y. pestis.

  8. A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

    PubMed

    Bozue, Joel; Cote, Christopher K; Chance, Taylor; Kugelman, Jeffrey; Kern, Steven J; Kijek, Todd K; Jenkins, Amy; Mou, Sherry; Moody, Krishna; Fritz, David; Robinson, Camenzind G; Bell, Todd; Worsham, Patricia

    2014-01-01

    Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

  9. A Yersinia pestis tat Mutant Is Attenuated in Bubonic and Small-Aerosol Pneumonic Challenge Models of Infection but Not As Attenuated by Intranasal Challenge

    PubMed Central

    Bozue, Joel; Cote, Christopher K.; Chance, Taylor; Kugelman, Jeffrey; Kern, Steven J.; Kijek, Todd K.; Jenkins, Amy; Mou, Sherry; Moody, Krishna; Fritz, David; Robinson, Camenzind G.; Bell, Todd; Worsham, Patricia

    2014-01-01

    Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge. PMID:25101850

  10. Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

    PubMed Central

    Reynolds, H Y; Fulmer, J D; Kazmierowski, J A; Roberts, W C; Frank, M M; Crystal, R G

    1977-01-01

    To evaluate cellular and protein components in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP), limited broncho-alveolar lavage was done in 58 patients (19 IPF, 7 CHP, and 32 controls). Analysis of the cells and protein in the lavage fluids from patients with IPF revealed an inflammatory and eosinophilic response and a significant elevation of IgG in the lungs. With corticosteroid therapy, inflammation diminished but eosinophils remained. Lavage fluid from patients with CHP also had eosinophils and elevated levels of IgG. However, in contrast to IPF, lavage fluid from CHP patients contained IgM, fewer inflammatory cells, and a strikingly increased number (38-74%) of lymphocytes. Identification of lavage lymphocytes in CHP showed that T lymphocytes were significantly elevated and B lymphocytes were decreased compared to peripheral blood. These studies suggest nthat the lung in IPF and CHP may function as a relatively independent immune organ, and that analysis of cells and proteins in broncho-alveolar lavage fluid may be of diagnostic, therapeutic, and investigative value in evaluating patients with fibrotic lung disease. PMID:830661

  11. Effects of cigarette smoking on diagnostic tests for work-related hypersensitivity pneumonitis: data from an outbreak of lung disease in metalworkers.

    PubMed

    Dangman, Kenneth H; Storey, Eileen; Schenck, Paula; Hodgson, Michael J

    2004-05-01

    It is widely believed that development of hypersensitivity pneumonitis (HP) is forestalled in cigarette smokers. We encountered the largest outbreak of HP in metalworkers yet reported [Hodgson et al. (2001): Am J Ind Med 39:616-628] and subsequently did a chart review of the 61 patients seen in connection with the outbreak [Dangman et al. (2002a): Am J Resp Crit Care Med 165(8):A528; Dangman et al. (2002b): Am J Ind Med 42:150-162], developing a diagnostic index for this disease. A re-examination of data from the chart review was carried out to explore possible effects of cigarette smoking on the clinical tests used to diagnose HP [Hodgson et al. (2001): Am J Ind Med 39:616-628]. Cigarette smokers with HP were less likely than non-smokers with HP to develop crackles in the lungs, elevated erythrocyte sedimentation rates (ESRs), and restrictive spirometry. Smoking habits had little effect on diffusion capacity and alveolar-arterial oxygen gradients in the patients with HP. Smokers were more likely to have abnormal gallium scans than non-smokers. It appears that cigarette smoking can affect the physical examination findings, spirometry, and ESR changes associated with HP, making these tests less sensitive and specific, and potentially obscuring the diagnosis. Such changes may contribute to the apparent "protective" effect of smoking on the development of HP.

  12. Discovery of a Leptospirosis Cluster Amidst a Pneumonic Plague Outbreak in a Miners’ Camp in the Democratic Republic of the Congo

    PubMed Central

    Bertherat, Eric; Mueller, Melissa J.; Shako, Jean-Christophe; Picardeau, Mathieu

    2014-01-01

    Conditions in the Democratic Republic of the Congo provide an ideal environment for leptospirosis and plague, both of which can cause severe pulmonary manifestations. In December 2004, an outbreak of lethal pneumonia occurred in a local mining camp, affecting 130 persons and killing 57 of them. Clinical signs, fast disease spread, and initial laboratory investigations suggested pneumonic plague. While leptospirosis had not recently been described in the region, it was considered as a differential diagnosis. Anti-Leptospira antibodies were detected by microscopic agglutination test (MAT). A confirmed case of leptospirosis was defined as having consistent clinical signs and any one of the following: seroconversion or four-fold increase in MAT titre for paired serum samples, or a MAT titre ≥ 1:400 for acute-phase serum samples. Twenty-nine of the 54 patients or convalescents tested for leptospirosis were seropositive. Two cases showed a confirmed infection for both plague and leptospirosis. While evidence supports the plague nature of this outbreak, the results suggest that some of the suspected plague cases might be due to leptospirosis. In any case, this diagnosis will have to be evoked in the future if a similar outbreak occurs in this region of Africa. PMID:24514425

  13. Discovery of a leptospirosis cluster amidst a pneumonic plague outbreak in a miners' camp in the Democratic Republic of the Congo.

    PubMed

    Bertherat, Eric; Mueller, Melissa J; Shako, Jean-Christophe; Picardeau, Mathieu

    2014-02-07

    Conditions in the Democratic Republic of the Congo provide an ideal environment for leptospirosis and plague, both of which can cause severe pulmonary manifestations. In December 2004, an outbreak of lethal pneumonia occurred in a local mining camp, affecting 130 persons and killing 57 of them. Clinical signs, fast disease spread, and initial laboratory investigations suggested pneumonic plague. While leptospirosis had not recently been described in the region, it was considered as a differential diagnosis. Anti-Leptospira antibodies were detected by microscopic agglutination test (MAT). A confirmed case of leptospirosis was defined as having consistent clinical signs and any one of the following: seroconversion or four-fold increase in MAT titre for paired serum samples, or a MAT titre ≥ 1:400 for acute-phase serum samples. Twenty-nine of the 54 patients or convalescents tested for leptospirosis were seropositive. Two cases showed a confirmed infection for both plague and leptospirosis. While evidence supports the plague nature of this outbreak, the results suggest that some of the suspected plague cases might be due to leptospirosis. In any case, this diagnosis will have to be evoked in the future if a similar outbreak occurs in this region of Africa.

  14. A live attenuated strain of Yersinia pestis ΔyscB provides protection against bubonic and pneumonic plagues in mouse model.

    PubMed

    Zhang, Xuecan; Qi, Zhizhen; Du, Zongmin; Bi, Yujing; Zhang, Qingwen; Tan, Yafang; Yang, Huiying; Xin, Youquan; Yang, Ruifu; Wang, Xiaoyi

    2013-05-24

    To develop a safe and effective live plague vaccine, the ΔyscB mutant was constructed based on Yersinia pestis biovar Microtus strain 201 that is avirulent to humans, but virulent to mice. The virulence, immunogenicity and protective efficacy of the ΔyscB mutant were evaluated in this study. The results showed that the ΔyscB mutant was severely attenuated, elicited a higher F1-specific antibody titer and provided protective efficacy against bubonic and pneumonic plague in mouse model. The ΔyscB mutant could induce the secretion of both Th1-associated cytokines (IFN-γ, IL-2 and TNF-α) and Th2-associated cytokines (IL-4 and IL-10). Taken together, the ΔyscB mutant represented a potential vaccine candidate based on its ability to generate strong humoral and cell-mediated immune responses and to provide good protection against both subcutaneous and intranasal Y. pestis challenge. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. CpG oligodeoxynucleotides augment the murine immune response to the Yersinia pestis F1-V vaccine in bubonic and pneumonic models of plague.

    PubMed

    Amemiya, Kei; Meyers, Jennifer L; Rogers, Taralyn E; Fast, Randy L; Bassett, Anthony D; Worsham, Patricia L; Powell, Bradford S; Norris, Sarah L; Krieg, Arthur M; Adamovicz, Jeffrey J

    2009-04-06

    The current U.S. Department of Defense candidate plague vaccine is a fusion between two Yersinia pestis proteins: the F1 capsular protein, and the low calcium response (Lcr) V-protein. We hypothesized that an immunomodulator, such as CpG oligodeoxynucleotide (ODN)s, could augment the immune response to the plague F1-V vaccine in a mouse model for plague. CpG ODNs significantly augmented the antibody response and efficacy of a single dose of the plague vaccine in murine bubonic and pneumonic models of plague. In the latter study, we also found an overall significant augmentation the immune response to the individual subunits of the plague vaccine by CpG ODN 2006. In a long-term, prime-boost study, CpG ODN induced a significant early augmentation of the IgG response to the vaccine. The presence of CpG ODN induced a significant increase in the IgG2a subclass response to the vaccine up to 5 months after the boost. Our studies showed that CpG ODNs significantly augmented the IgG antibody response to the plague vaccine, which increased the probability of survival in murine models of plague (P<0.0001).

  16. Yersinia pestis YopE contains a dominant CD8 T cell epitope that confers protection in a mouse model of pneumonic plague.

    PubMed

    Lin, Jr-Shiuan; Szaba, Frank M; Kummer, Lawrence W; Chromy, Brett A; Smiley, Stephen T

    2011-07-15

    Septic bacterial pneumonias are a major cause of death worldwide. Several of the highest priority bioterror concerns, including anthrax, tularemia, and plague, are caused by bacteria that acutely infect the lung. Bacterial resistance to multiple antibiotics is increasingly common. Although vaccines may be our best defense against antibiotic-resistant bacteria, there has been little progress in the development of safe and effective vaccines for pulmonary bacterial pathogens. The Gram-negative bacterium Yersinia pestis causes pneumonic plague, an acutely lethal septic pneumonia. Historic pandemics of plague caused millions of deaths, and the plague bacilli's potential for weaponization sustains an ongoing quest for effective countermeasures. Subunit vaccines have failed, to date, to fully protect nonhuman primates. In mice, they induce the production of Abs that act in concert with type 1 cytokines to deliver high-level protection; however, the Y. pestis Ags recognized by cytokine-producing T cells have yet to be defined. In this study, we report that Y. pestis YopE is a dominant Ag recognized by CD8 T cells in C57BL/6 mice. After vaccinating with live attenuated Y. pestis and challenging intranasally with virulent plague, nearly 20% of pulmonary CD8 T cells recognize this single, highly conserved Ag. Moreover, immunizing mice with a single peptide, YopE(69-77), suffices to confer significant protection from lethal pulmonary challenge. These findings suggest YopE could be a valuable addition to subunit plague vaccines and provide a new animal model in which sensitive, pathogen-specific assays can be used to study CD8 T cell-mediated defense against acutely lethal bacterial infections of the lung.

  17. Risk factors for radiation pneumonitis after stereotactic radiation therapy for lung tumours: clinical usefulness of the planning target volume to total lung volume ratio.

    PubMed

    Ueyama, Tomoko; Arimura, Takeshi; Takumi, Koji; Nakamura, Fumihiko; Higashi, Ryutaro; Ito, Soichiro; Fukukura, Yoshihiko; Umanodan, Tomokazu; Nakajo, Masanori; Koriyama, Chihaya; Yoshiura, Takashi

    2018-06-01

    To identify risk factors for symptomatic radiation pneumonitis (RP) after stereotactic radiation therapy (SRT) for lung tumours. We retrospectively evaluated 68 lung tumours in 63 patients treated with SRT between 2011 and 2015. RP was graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. SRT was delivered at 7.0-12.0 Gy per each fraction, once daily, to a total of 48-64 Gy (median, 50 Gy). Univariate analysis was performed to assess patient- and treatment-related factors, including age, sex, smoking index (SI), pulmonary function, tumour location, serum Krebs von den Lungen-6 value (KL-6), dose-volume metrics (V5, V10, V20, V30, V40 and VS5), homogeneity index of the planning target volume (PTV), PTV dose, mean lung dose (MLD), contralateral MLD and V2, PTV volume, lung volume and the PTV/lung volume ratio (PTV/Lung). Performance of PTV/Lung in predicting symptomatic RP was also analysed using receiver operating characteristic (ROC) analysis. The median follow-up period was 21 months. 10 of 63 patients (15.9%) developed symptomatic RP after SRT. On univariate analysis, V10, V20, PTV volume and PTV/Lung were significantly associated with occurrence of RP  ≥Grade 2. ROC curves indicated that symptomatic RP could be predicted using PTV/Lung [area under curve (AUC): 0.88, confidence interval (CI: 0.78-0.95), cut-off value: 1.09, sensitivity: 90.0% and specificity: 72.4%]. PTV/Lung is a good predictor of symptomatic RP after SRT. Advances in knowledge: The cases with high PTV/Lung should be carefully monitored with caution for the occurrence of RP after SRT.

  18. Evaluation of Psn, HmuR and a modified LcrV protein delivered to mice by live attenuated Salmonella as a vaccine against bubonic and pneumonic Yersinia pestis challenge.

    PubMed

    Branger, Christine G; Sun, Wei; Torres-Escobar, Ascención; Perry, Robert; Roland, Kenneth L; Fetherston, Jacqueline; Curtiss, Roy

    2010-12-16

    We evaluated the ability of Yersinia pestis antigens HmuR, Psn and modified forms of LcrV delivered by live attenuated Salmonella strains to stimulate a protective immune response against subcutaneous or intranasal challenge with Y. pestis CO92. LcrV196 is a previously described truncated protein that includes aa 131-326 of LcrV and LcrV5214 has been modified to replace five key amino acids required for interaction with the TLR2 receptor. Psn is the outer membrane receptor for the siderophore, yersiniabactin, and the bacteriocin, pesticin. Mice immunized with Salmonella synthesizing Psn, LcrV196 or LcrV5214 developed serum IgG responses to the respective Yersinia antigen and were protected against pneumonic challenge with Y. pestis. Immunization with Salmonella synthesizing Psn or LcrV196 was sufficient to afford nearly full protection against bubonic challenge, while immunization with the strain synthesizing LcrV5214 was not protective. Immunization with Salmonella synthesizing HmuR, an outer membrane protein involved in heme acquisition in Y. pestis, was poorly immunogenic and did not elicit a protective response against either challenge route. These findings indicate that both Psn and LcrV196 delivered by Salmonella provide protection against both bubonic and pneumonic plague. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Characterization of an F1 Deletion Mutant of Yersinia pestis CO92, Pathogenic Role of F1 Antigen in Bubonic and Pneumonic Plague, and Evaluation of Sensitivity and Specificity of F1 Antigen Capture-Based Dipsticks▿

    PubMed Central

    Sha, Jian; Endsley, Janice J.; Kirtley, Michelle L.; Foltz, Sheri M.; Huante, Matthew B.; Erova, Tatiana E.; Kozlova, Elena V.; Popov, Vsevolod L.; Yeager, Linsey A.; Zudina, Irina V.; Motin, Vladimir L.; Peterson, Johnny W.; DeBord, Kristin L.; Chopra, Ashok K.

    2011-01-01

    We evaluated two commercial F1 antigen capture-based immunochromatographic dipsticks, Yersinia Pestis (F1) Smart II and Plague BioThreat Alert test strips, in detecting plague bacilli by using whole-blood samples from mice experimentally infected with Yersinia pestis CO92. To assess the specificities of these dipsticks, an in-frame F1-deficient mutant of CO92 (Δcaf) was generated by homologous recombination and used as a negative control. Based on genetic, antigenic/immunologic, and electron microscopic analyses, the Δcaf mutant was devoid of a capsule. The growth rate of the Δcaf mutant generally was similar to that of the wild-type (WT) bacterium at both 26 and 37°C, although the mutant's growth dropped slightly during the late phase at 37°C. The Δcaf mutant was as virulent as WT CO92 in the pneumonic plague mouse model; however, it was attenuated in developing bubonic plague. Both dipsticks had similar sensitivities, requiring a minimum of 0.5 μg/ml of purified F1 antigen or 1 × 105 to 5 × 105 CFU/ml of WT CO92 for positive results, while the blood samples were negative for up to 1 × 108 CFU/ml of the Δcaf mutant. Our studies demonstrated the diagnostic potential of two plague dipsticks in detecting capsular-positive strains of Y. pestis in bubonic and pneumonic plague. PMID:21367990

  20. Lung Texture in Serial Thoracic Computed Tomography Scans: Correlation of Radiomics-based Features With Radiation Therapy Dose and Radiation Pneumonitis Development

    SciTech Connect

    Cunliffe, Alexandra; Armato, Samuel G.; Castillo, Richard

    2015-04-01

    Purpose: To assess the relationship between radiation dose and change in a set of mathematical intensity- and texture-based features and to determine the ability of texture analysis to identify patients who develop radiation pneumonitis (RP). Methods and Materials: A total of 106 patients who received radiation therapy (RT) for esophageal cancer were retrospectively identified under institutional review board approval. For each patient, diagnostic computed tomography (CT) scans were acquired before (0-168 days) and after (5-120 days) RT, and a treatment planning CT scan with an associated dose map was obtained. 32- × 32-pixel regions of interest (ROIs) were randomly identifiedmore » in the lungs of each pre-RT scan. ROIs were subsequently mapped to the post-RT scan and the planning scan dose map by using deformable image registration. The changes in 20 feature values (ΔFV) between pre- and post-RT scan ROIs were calculated. Regression modeling and analysis of variance were used to test the relationships between ΔFV, mean ROI dose, and development of grade ≥2 RP. Area under the receiver operating characteristic curve (AUC) was calculated to determine each feature's ability to distinguish between patients with and those without RP. A classifier was constructed to determine whether 2- or 3-feature combinations could improve RP distinction. Results: For all 20 features, a significant ΔFV was observed with increasing radiation dose. Twelve features changed significantly for patients with RP. Individual texture features could discriminate between patients with and those without RP with moderate performance (AUCs from 0.49 to 0.78). Using multiple features in a classifier, AUC increased significantly (0.59-0.84). Conclusions: A relationship between dose and change in a set of image-based features was observed. For 12 features, ΔFV was significantly related to RP development. This study demonstrated the ability of radiomics to provide a quantitative

  1. SU-E-J-251: Incorporation of Pre-Therapy 18F-FDG Uptake with CT Texture Features in a Predictive Model for Radiation Pneumonitis Development

    SciTech Connect

    Anthony, G; Cunliffe, A; Armato, S

    2015-06-15

    Purpose: To determine whether the addition of standardized uptake value (SUV) statistical variables to CT lung texture features can improve a predictive model of radiation pneumonitis (RP) development in patients undergoing radiation therapy. Methods: Anonymized data from 96 esophageal cancer patients (18 RP-positive cases of Grade ≥ 2) were retrospectively collected including pre-therapy PET/CT scans, pre-/posttherapy diagnostic CT scans and RP status. Twenty texture features (firstorder, fractal, Laws’ filter and gray-level co-occurrence matrix) were calculated from diagnostic CT scans and compared in anatomically matched regions of the lung. The mean, maximum, standard deviation, and 50th–95th percentiles of the SUV valuesmore » for all lung voxels in the corresponding PET scans were acquired. For each texture feature, a logistic regression-based classifier consisting of (1) the average change in that texture feature value between the pre- and post-therapy CT scans and (2) the pre-therapy SUV standard deviation (SUV{sub SD}) was created. The RP-classification performance of each logistic regression model was compared to the performance of its texture feature alone by computing areas under the receiver operating characteristic curves (AUCs). T-tests were performed to determine whether the mean AUC across texture features changed significantly when SUV{sub SD} was added to the classifier. Results: The AUC for single-texturefeature classifiers ranged from 0.58–0.81 in high-dose (≥ 30 Gy) regions of the lungs and from 0.53–0.71 in low-dose (< 10 Gy) regions. Adding SUVSD in a logistic regression model using a 50/50 data partition for training and testing significantly increased the mean AUC by 0.08, 0.06 and 0.04 in the low-, medium- and high-dose regions, respectively. Conclusion: Addition of SUVSD from a pre-therapy PET scan to a single CT-based texture feature improves RP-classification performance on average. These findings demonstrate the

  2. Using Generalized Equivalent Uniform Dose Atlases to Combine and Analyze Prospective Dosimetric and Radiation Pneumonitis Data From 2 Non-Small Cell Lung Cancer Dose Escalation Protocols

    SciTech Connect

    Liu Fan; Yorke, Ellen D.; Belderbos, Jose S.A.

    2013-01-01

    Purpose: To demonstrate the use of generalized equivalent uniform dose (gEUD) atlas for data pooling in radiation pneumonitis (RP) modeling, to determine the dependence of RP on gEUD, to study the consistency between data sets, and to verify the increased statistical power of the combination. Methods and Materials: Patients enrolled in prospective phase I/II dose escalation studies of radiation therapy of non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) (78 pts) and the Netherlands Cancer Institute (NKI) (86 pts) were included; 10 (13%) and 14 (17%) experienced RP requiring steroids (RPS) within 6 months after treatment. gEUD wasmore » calculated from dose-volume histograms. Atlases for each data set were created using 1-Gy steps from exact gEUDs and RPS data. The Lyman-Kutcher-Burman model was fit to the atlas and exact gEUD data. Heterogeneity and inconsistency statistics for the fitted parameters were computed. gEUD maps of the probability of RPS rate {>=}20% were plotted. Results: The 2 data sets were homogeneous and consistent. The best fit values of the volume effect parameter a were small, with upper 95% confidence limit around 1.0 in the joint data. The likelihood profiles around the best fit a values were flat in all cases, making determination of the best fit a weak. All confidence intervals (CIs) were narrower in the joint than in the individual data sets. The minimum P value for correlations of gEUD with RPS in the joint data was .002, compared with P=.01 and .05 for MSKCC and NKI data sets, respectively. gEUD maps showed that at small a, RPS risk increases with gEUD. Conclusions: The atlas can be used to combine gEUD and RPS information from different institutions and model gEUD dependence of RPS. RPS has a large volume effect with the mean dose model barely included in the 95% CI. Data pooling increased statistical power.« less

  3. Evaluation of visual and computer-based CT analysis for the identification of functional patterns of obstruction and restriction in hypersensitivity pneumonitis.

    PubMed

    Jacob, Joseph; Bartholmai, Brian J; Brun, Anne Laure; Egashira, Ryoko; Rajagopalan, Srinivasan; Karwoski, Ronald; Kouranos, Vasileios; Kokosi, Maria; Hansell, David M; Wells, Athol U

    2017-11-01

    To determine whether computer-based quantification (CALIPER software) is superior to visual computed tomography (CT) scoring in the identification of CT patterns indicative of restrictive and obstructive functional indices in hypersensitivity pneumonitis (HP). A total of 135 consecutive HP patients had CT parenchymal patterns evaluated quantitatively by both visual scoring and CALIPER. Results were evaluated against: forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DL CO ) and a composite physiological index (CPI) to identify which CT scoring method better correlated with functional indices. CALIPER-derived scores of total interstitial lung disease extent correlated more strongly than visual scores: FVC (CALIPER R = 0.73, visual R = 0.51); DL CO (CALIPER R = 0.61, visual R = 0.48); and CPI (CALIPER R = 0·70, visual R = 0·55). The CT variable that correlated most strongly with restrictive functional indices was CALIPER pulmonary vessel volume (PVV): FVC R = 0.75, DL CO R = 0.68 and CPI R = 0.76. Ground-glass opacity quantified by CALIPER alone demonstrated strong associations with restrictive functional indices: CALIPER FVC R = 0.65; DL CO R = 0.59; CPI R = 0.64; and visual = not significant. Decreased attenuation lung quantified by CALIPER was a better morphological measure of obstructive lung disease than equivalent visual scores as judged by relationships with TLC (CALIPER R = 0.63 and visual R = 0.12). All results were maintained on multivariate analysis. CALIPER improved on visual scoring in HP as judged by restrictive and obstructive functional correlations. Decreased attenuation regions of the lung quantified by CALIPER demonstrated better linkages to obstructive lung physiology than visually quantified CT scores. A novel CALIPER variable, the PVV, demonstrated the strongest linkages with restrictive functional indices and could represent a new

  4. Hypersensitivity pneumonitis in a beautician.

    PubMed

    Soumagne, Thibaud; Reboux, Gabriel; Degano, Bruno; Dalphin, Jean Charles

    2016-11-01

    A 52-year-old non-smoking beautician using a skincare device spraying steam and ozone (a "vapozone" facial steamer) was referred for progressive dyspnea and dry cough during working periods. Although spirometry was normal, she had decreased diffusing capacity of the lung for carbon monoxide, bronchiolitis with air trapping on high-resolution CT scan and 60% lymphocytosis by bronchoalveolar lavage. Twenty-six antigens were tested and serum-specific precipitins were found mainly against Pseudomonas sp. and Mycobacterium mucogenicum. Cultures from her skincare device isolated Pseudomonas sp. Outcome was favorable with cessation of occupational exposure to the device, without any medication. This is the first report of a case of HP in a beautician due to steam contaminated by Pseudomonas sp. from a vapozone. HP, and not only asthma and contact dermatitis, should be suspected in beauticians with respiratory symptoms. Am. J. Ind. Med. 59:1041-1045, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague.

    PubMed

    Tiner, Bethany L; Sha, Jian; Ponnusamy, Duraisamy; Baze, Wallace B; Fitts, Eric C; Popov, Vsevolod L; van Lier, Christina J; Erova, Tatiana E; Chopra, Ashok K

    2015-12-01

    Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 10(6) CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD(50)) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but

  6. SU-C-207A-07: Cumulative 18F-FDG Uptake Histogram Relative to Radiation Dose Volume Histogram of Lung After IMRT Or PSPT and Their Association with Radiation Pneumonitis

    SciTech Connect

    Shusharina, N; Choi, N; Bortfeld, T

    2016-06-15

    Purpose: To determine whether the difference in cumulative 18F-FDG uptake histogram of lung treated with either IMRT or PSPT is associated with radiation pneumonitis (RP) in patients with inoperable stage II and III NSCLC. Methods: We analyzed 24 patients from a prospective randomized trial to compare IMRT (n=12) with vs. PSPT (n=12) for inoperable NSCLC. All patients underwent PET-CT imaging between 35 and 88 days post-therapy. Post-treatment PET-CT was aligned with planning 4D CT to establish a voxel-to-voxel correspondence between post-treatment PET and planning dose images. 18F-FDG uptake as a function of radiation dose to normal lung was obtained formore » each patient. Distribution of the standard uptake value (SUV) was analyzed using a volume histogram method. The image quantitative characteristics and DVH measures were correlated with clinical symptoms of pneumonitis. Results: Patients with RP were present in both groups: 5 in the IMRT and 6 in the PSPT. The analysis of cumulative SUV histograms showed significantly higher relative volumes of the normal lung having higher SUV uptake in the PSPT patients for both symptomatic and asymptomatic cases (VSUV=2: 10% for IMRT vs 16% for proton RT and VSUV=1: 10% for IMRT vs 23% for proton RT). In addition, the SUV histograms for symptomatic cases in PSPT patients exhibited a significantly longer tail at the highest SUV. The absolute volume of the lung receiving the dose >70 Gy was larger in the PSPT patients. Conclusion: 18F-FDG uptake – radiation dose response correlates with RP in both groups of patients by means of the linear regression slope. SUV is higher for the PSPT patients for both symptomatic and asymptomatic cases. Higher uptake after PSPT patients is explained by larger volumes of the lung receiving high radiation dose.« less

  7. Characterization of an F1 deletion mutant of Yersinia pestis CO92, pathogenic role of F1 antigen in bubonic and pneumonic plague, and evaluation of sensitivity and specificity of F1 antigen capture-based dipsticks.

    PubMed

    Sha, Jian; Endsley, Janice J; Kirtley, Michelle L; Foltz, Sheri M; Huante, Matthew B; Erova, Tatiana E; Kozlova, Elena V; Popov, Vsevolod L; Yeager, Linsey A; Zudina, Irina V; Motin, Vladimir L; Peterson, Johnny W; DeBord, Kristin L; Chopra, Ashok K

    2011-05-01

    We evaluated two commercial F1 antigen capture-based immunochromatographic dipsticks, Yersinia Pestis (F1) Smart II and Plague BioThreat Alert test strips, in detecting plague bacilli by using whole-blood samples from mice experimentally infected with Yersinia pestis CO92. To assess the specificities of these dipsticks, an in-frame F1-deficient mutant of CO92 (Δcaf) was generated by homologous recombination and used as a negative control. Based on genetic, antigenic/immunologic, and electron microscopic analyses, the Δcaf mutant was devoid of a capsule. The growth rate of the Δcaf mutant generally was similar to that of the wild-type (WT) bacterium at both 26 and 37 °C, although the mutant's growth dropped slightly during the late phase at 37 °C. The Δcaf mutant was as virulent as WT CO92 in the pneumonic plague mouse model; however, it was attenuated in developing bubonic plague. Both dipsticks had similar sensitivities, requiring a minimum of 0.5 μg/ml of purified F1 antigen or 1 × 10(5) to 5 × 10(5) CFU/ml of WT CO92 for positive results, while the blood samples were negative for up to 1 × 10(8) CFU/ml of the Δcaf mutant. Our studies demonstrated the diagnostic potential of two plague dipsticks in detecting capsular-positive strains of Y. pestis in bubonic and pneumonic plague.

  8. Prevention of pneumonic plague in mice, rats, guinea pigs and non-human primates with clinical grade rV10, rV10-2 or F1-V vaccines

    PubMed Central

    Quenee, Lauriane E.; Ciletti, Nancy A.; Elli, Derek; Hermanas, Timothy M.; Schneewind, Olaf

    2012-01-01

    Yersinia pestis causes plague, a disease with high mortality in humans that can be transmitted by fleabite or aerosol. A US Food and Drug Administration (FDA)-licensed plague vaccine is currently not available. Vaccine developers have focused on two subunits of Y. pestis: LcrV, a protein at the tip of type III secretion needles, and F1, the fraction 1 pilus antigen. F1-V, a hybrid generated via translational fusion of both antigens, is being developed for licensure as a plague vaccine. The rV10 vaccine is a non-toxigenic variant of LcrV lacking residues 271–300. Here we developed Current Good Manufacturing Practice (cGMP) protocols for rV10. Comparison of clinical grade rV10 with F1-V did not reveal significant differences in plague protection in mice, guinea pigs or cynomolgus macaques. We also developed cGMP protocols for rV10-2, a variant of rV10 with an altered affinity tag. Immunization with rV10-2 adsorbed to aluminum hydroxide elicited antibodies against LcrV and conferred pneumonic plague protection in mice, rats, guinea pigs, cynomolgus macaques and African Green monkeys. The data support further development of rV10-2 for FDA Investigational New Drug (IND) authorization review and clinical testing. PMID:21763383

  9. Functional Polymorphisms of Base Excision Repair Genes XRCC1 and APEX1 Predict Risk of Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    SciTech Connect

    Yin Ming; Liao Zhongxing; Liu Zhensheng

    2011-11-01

    Purpose: To explore whether functional single nucleotide polymorphisms (SNPs) of base-excision repair genes are predictors of radiation treatment-related pneumonitis (RP), we investigated associations between functional SNPs of ADPRT, APEX1, and XRCC1 and RP development. Methods and Materials: We genotyped SNPs of ADPRT (rs1136410 [V762A]), XRCC1 (rs1799782 [R194W], rs25489 [R280H], and rs25487 [Q399R]), and APEX1 (rs1130409 [D148E]) in 165 patients with non-small cell lung cancer (NSCLC) who received definitive chemoradiation therapy. Results were assessed by both Logistic and Cox regression models for RP risk. Kaplan-Meier curves were generated for the cumulative RP probability by the genotypes. Results: We found that SNPsmore » of XRCC1 Q399R and APEX1 D148E each had a significant effect on the development of Grade {>=}2 RP (XRCC1: AA vs. GG, adjusted hazard ratio [HR] = 0.48, 95% confidence interval [CI], 0.24-0.97; APEX1: GG vs. TT, adjusted HR = 3.61, 95% CI, 1.64-7.93) in an allele-dose response manner (Trend tests: p = 0.040 and 0.001, respectively). The number of the combined protective XRCC1 A and APEX1 T alleles (from 0 to 4) also showed a significant trend of predicting RP risk (p = 0.001). Conclusions: SNPs of the base-excision repair genes may be biomarkers for susceptibility to RP. Larger prospective studies are needed to validate our findings.« less

  10. Transforming growth factor-beta-1 is a serum biomarker of radiation-induced pneumonitis in esophageal cancer patients treated with thoracic radiotherapy: preliminary results of a prospective study.

    PubMed

    Li, Jingxia; Mu, Shuangfeng; Mu, Lixiang; Zhang, Xiaohui; Pang, Ranran; Gao, Shegan

    2015-01-01

    To examine the relationship between cytokine levels of transforming growth factor-beta-1 (TGF-β1), interleukin-1 beta (IL-1β), and angiotensin-converting enzyme (ACE) in the plasma of esophageal carcinoma patients and radiation-induced pneumonitis (RP). Sixty-three patients with esophageal carcinoma were treated with three-dimensional conformal radiotherapy (RT) using the Elekta Precise treatment planning system with a prescribed dose of 50-70 Gy. Dose-volume histograms were collected from three-dimensional conformal RT to determine the volume percentage of the lung received V5, V10, V20, and the normal tissue complication probability. RP was diagnosed based on computed tomography imaging, respiratory symptoms, and signs. The severity of radiation-induced lung toxicity was determined using the Lent-Soma scale defined by the Radiation Therapy Oncology Group. Plasma samples obtained before RT, during RT (at 40 Gy), and at 1 day, 1 month, and 3 months after RT were assayed for TGF-β1, IL-1β, and ACE levels by enzyme-linked immunosorbent assay. From the 63 patients, 17 (27%) developed RP, and 13 (21%) had RP of grade I and four (6%) had grade II or higher. We found plasma TGF-β1 levels were elevated in the patients that had RP when compared with the other 46 patients who did not have RP. The plasma IL-1β levels were not changed. The ACE levels were significantly lower in the 17 patients with RP compared to the 46 patients without RP throughout the RT. As expected, RP is associated with a higher dose of irradiation (>60 Gy); no other factors, including dose-volume histogram, age, sex, smoking status, location of tumor, and methods of treatment, are associated with RP. Elevated plasma TGF-β1 levels can be used as a marker for RP.

  11. Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer After Definitive Radiation Therapy? Analysis of a Single-Institution Database

    SciTech Connect

    Wang, Hongmei; Liao, Zhongxing, E-mail: zliao@mdanderson.org; Zhuang, Yan

    2013-12-01

    Purpose: Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for non–small cell lung cancer (NSCLC). Methods and Materials: We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available formore » analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results: Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ≥2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ≥2 among patients who received a low (≤20-Gy) MLD (P<.01) or were male (P=.04). Conclusions: A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.« less

  12. Amiodarone induced pneumonitis and hyperthyroidism: case report.

    PubMed

    Grabczak, Elzbieta Magdalena; Zielonka, Tadeusz M; Wiwała, Joanna; Bareła, Anna Dagmara; Opuchlik, Andrzej; Potulska, Anna; Ambroziak, Urszula; Chazan, Ryszarda

    2008-09-01

    Amiodarone is a highly effective antiarrhythmic agent used in life-threatening ventricular and supraventricular arrhythmias. Its long-term use may however lead to several adverse effects, including corneal deposits, liver and thyroid gland dysfunction, lung lesions, bone marrow injury, skin lesions, or neurological abnormalities. The article presents the case of a 56-year-old man with a history of a stroke, who after a few days of amiodarone therapy for an episode of atrial fibrillation was diagnosed with amiodarone-induced hyperthyroidism and interstitial pulmonary lesions. Clinical and laboratory symptoms of hyperthyroidism and radiographic signs of pulmonary involvement did not occur until several weeks after discontinuation of amiodarone therapy. Differential diagnosis of causes of hyperthyroidism and diseases causing nodular pulmonary lesions did not demonstrate any other pathologies. Empirical antibiotic therapy and administration of thiamazole and high doses of propranolol failed to improve the patient's clinical status. It was not until thiamazole was given in combination with glucocorticosteroids, when a slow relief of hyperthyroidism symptoms and resolution of radiographic pulmonary signs were observed. Based on the presented case, the risk of appearance of 2 serious concomitant adverse effects was demonstrated, even following a short-term amiodarone therapy. This paper also contains an overview of adverse effects which may be encountered during or after therapy with this effective antiarrhythmic agent. It was emphasized how important it is to select patients appropriately, and to monitor potential adverse effects during amiodarone therapy.

  13. Comparison of the clinical efficacy between tigecycline plus extended-infusion imipenem and sulbactam plus imipenem against ventilator-associated pneumonia with pneumonic extensively drug-resistant Acinetobacter baumannii bacteremia, and correlation of clinical efficacy with in vitro synergy tests.

    PubMed

    Jean, Shio-Shin; Hsieh, Tai-Chin; Hsu, Chin-Wan; Lee, Wen-Sen; Bai, Kuan-Jen; Lam, Carlos

    2016-12-01

    To compare the clinical efficacy between salvage antimicrobial regimen consisting of tigecycline plus extended-infusion imipenem/cilastatin (TIC) and regimen of sulbactam plus imipenem/cilastatin (SIC) for patients with ventilator-associated pneumonia and pneumonic bacteremia due to extensively drug-resistant (XDR) Acinetobacter baumannii (Ab) isolates, and determine the correlation of results of in vitro tigecycline-imipenem synergy test with clinical efficacy. The comparative survey was conducted at a medical center in Taiwan in 2013. Patients comprising the TIC group (n = 28) received tigecycline plus extended-infusion imipenem/cilastatin following unresponsiveness to 3-day sulbactam-imipenem/cilastatin therapy, and those in the SIC group (n = 56) received sulbactam-imipenem/cilastatin throughout the course. Univariate and multivariate analyses were applied to explore 30-day case-fatality independent predictors. Additionally, the checkerboard test and time-kill analysis were performed for the bloodstream XDR-Ab isolates from patients in the TIC group, and molecular characterization was done for the bloodstream XDR-Ab strains of all patients. We found that the TIC scheme has a significant benefit on improving patients' survival status (the mortality rate of TIC and SIC group patients was 14.3% and 64.3%, respectively), corresponding well with in vitro synergy or additivity results by the checkerboard test. Twenty TIC group cases had monomicrobial XDR-Ab cultured from tracheal aspirates after 10 days of tigecycline-imipenem/cilastatin therapy, but none developed subsequent pneumonia. However, breakthrough primary Burkholderia cepacia (n = 3) and Pseudomonas aeruginosa (n = 1) bacteremias were attributed to four TIC case fatalities. Shock, SIC regimen usage, and development of breakthrough bacteremia were independent predictors of 30-day in-hospital mortality. Although the TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator

  14. HYPERSENSITIVITY PNEUMONITIS IN A METAL-WORKING ENVIRONMENT. (R825251)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  15. DEVELOPMENT OF RADIATION PNEUMONITIS TIME AND DOSE FACTORS

    SciTech Connect

    Jennings, F.L.; Arden, A.

    1962-10-01

    Histologic evaluation of the lungs was done at autopsy in 215 patients who had received thoracic radiation. The presence or absence of tissue changes noted were: edema, congestion, atelectasis, fibrin exudate in alveoli, epithelial changes, fibrillar thickening of alveolar septa, increased cellularity of alveolar septa, fibrosis of alveolar septa, and proliferative changes in blood vessels. Some or all of the tissue changes listed were found in 165 cases. Two changes were particularly frequent: accumulation of a fibrin-rich exudate within alveoli, often forming a membrane in the lation of fibrillar material, by cellular proliferation, or by increase of fibrous tissue. Suchmore » fibrin accumulations were found at radiation doses below 500 r and in excess of 6000 r, and at postirradiation intervals of less than 30 days and over 5 yr. Fibrin accumulations formed within 90 days after less than 1500-r x-ray exposure were similar to those seen almost 9 yr after 5000 r. Three separate types of proliferative changes in the connective tissue of the alveolar septa appeared to be secondary to radiation; 27% showed a fibrillar deposit in the septa which tended to thicken the septa markedly. The time interval appeared to make little difference in the development of this lesion. Increased septal cellularity, due primarily to accumulation of histiocytes and fibroblasts, was seen in 18% of the cases, most commonly at doses between 2000 r and 5000 r. Fibrosis of alveolar septa was the third type of proliferative change and was seen in 42% of the cases. (P.C.H.)« less

  16. THE HYPERSENSITIVITY PNEUMONITIS DIAGNOSTIC INDEX: USE OF NON-INVASIVE TESTING TO DIAGNOSE HYPERSENSITIVITY PNEUMONITIS IN METALWORKERS. (R825251)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  17. Plant-made subunit vaccine against pneumonic and bubonic plague is orally immunogenic in mice.

    PubMed

    Alvarez, M Lucrecia; Pinyerd, Heidi L; Crisantes, Jason D; Rigano, M Manuela; Pinkhasov, Julia; Walmsley, Amanda M; Mason, Hugh S; Cardineau, Guy A

    2006-03-24

    Yersinia pestis, the causative agent of plague, is an extremely virulent bacterium but there are no approved vaccines for protection against it. Our goal was to produce a vaccine that would address: ease of delivery, mucosal efficacy, safety, rapid scalability, and cost. We developed a novel production and delivery system for a plague vaccine of a Y. pestis F1-V antigen fusion protein expressed in tomato. Immunogenicity of the F1-V transgenic tomatoes was confirmed in mice that were primed subcutaneously with bacterially-produced F1-V and boosted orally with transgenic tomato fruit. Expression of the plague antigens in fruit allowed producing an oral vaccine candidate without protein purification and with minimal processing technology.

  18. A case of pulmonary hemorrhage due to drug-induced pneumonitis secondary to ticagrelor therapy.

    PubMed

    Whitmore, Timothy J; O'Shea, John P; Starac, Diana; Edwards, Mark G; Waterer, Grant W

    2014-03-01

    We report a case of significant pulmonary hemorrhage developing shortly after commencing ticagrelor and aspirin therapy and requiring coronary artery bypass grafting to safely cease the antiplatelet therapy. Lung biopsy findings were consistent with drug-induced lung injury. Clinicians should be aware of this significant adverse event with this drug class.

  19. Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis

    DTIC Science & Technology

    2016-03-22

    urea nitrogen (BUN), Fig 2. Potentially activated and inhibited GoI-Time enriched pathways across the time course. The canonical pathways enriched by up...journal.pone.0151788 March 22, 2016 8 / 21 The quantitative measurements of Y. pestis present in the exposed animals’ blood and urine samples and...leukocytes (S5B Fig), formation of cellular inclusion bodies, synthesis of extracellular matrix, and myocardial and liver failure. Protein ubiquitination

  20. Protection against bubonic and pneumonic plague with a single dose microencapsulated sub-unit vaccine.

    PubMed

    Elvin, Stephen J; Eyles, James E; Howard, Kenneth A; Ravichandran, Easwaran; Somavarappu, Satyanarayan; Alpar, H Oya; Williamson, E Diane

    2006-05-15

    Protection against virulent plague challenge by the parenteral and aerosol routes was afforded by a single administration of microencapsulated Caf1 and LcrV antigens from Yersinia pestis in BALB/c mice. Recombinant Caf1 and LcrV were individually encapsulated in polymeric microspheres, to the surface of which additional antigen was adsorbed. The microspheres containing either Caf1 or LcrV were blended and used to immunise mice on a single occasion, by either the intra-nasal or intra-muscular route. Both routes of immunisation induced systemic and local immune responses, with high levels of serum IgG being developed in response to both vaccine antigens. In Elispot assays, secretion of cytokines by spleen and draining lymph node cells was demonstrated, revealing activation of both Th1 and Th2 associated cytokines; and spleen cells from animals immunised by either route were found to proliferate in vitro in response to both vaccine antigens. Virulent challenge experiments demonstrated that non-invasive immunisation by intra-nasal instillation can provide strong systemic and local immune responses and protect against high level challenge. Microencapsulation of these vaccine antigens has the added advantage that controlled release of the antigens occurs in vivo, so that protective immunity can be induced after only a single immunising dose.

  1. HYPERSENSITIVITY PNEUMONITIS AND METAL WORKING FLUIDS: THE METALWORKER'S MALAISE DIAGNOSTIC INDEX. (R825251)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. Design and Testing for a Nontagged F1-V Fusion Protein as Vaccine Antigen Against Bubonic and Pneumonic Plague

    DTIC Science & Technology

    2005-08-01

    analysis. Bovine serum albumin (BSA) (Pierce) was used to normalize the detectors, applying a refractive index increment (dn/dc) value of 0.185 mL/g for...D.; Eley, S. M.; Stagg, A. J.; Green, M.; Russell, P.; Titball, R. W. A subunit vaccine elicits IgG in serum , spleen cell cultures and bronchial...hydrophobic interaction, concentration, and then transfer into buffered saline for direct use after frozen storage. Protein identity and primary structure

  3. Pulmonary manifestations in systemic lupus erythematosus: pleural involvement, acute pneumonitis, chronic interstitial lung disease and diffuse alveolar hemorrhage.

    PubMed

    Aguilera-Pickens, Georgina; Abud-Mendoza, Carlos

    2018-05-14

    Systemic lupus erythematosus is the diffuse autoimmune connective tissue disease that most frequently involves pulmonary involvement, affecting 20% of 90% of the patients. The percentage varies depending on the defining criteria (symptoms, pulmonary tests or histopathological studies). At least once during the disease course, 50% of those affected have pleural and/or pulmonary manifestations, which are associated with higher morbidity and mortality. Pulmonary involvement has no correlation with lupus activity biomarkers, and it is necessary to rule out infectious processes in the initial approach. Bacterial infection is most frequently the cause of lung involvement in lupus and is one of the most important causes of death. Pulmonary involvement is considered to be primary when it is associated with disease activity, and secondary when other causes participate. Drugs have been reported to be associated with pulmonary damage, including interstitial disease. The incidence of malignant lung diseases is increased in systemic lupus erythematosus. Treatment depends on the type and severity of pulmonary involvement. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Case report of electronic cigarettes possibly associated with eosinophilic pneumonitis in a previously healthy active-duty sailor.

    PubMed

    Thota, Darshan; Latham, Emi

    2014-07-01

    Electronic cigarettes (e-cigarettes) are a technology that has been touted as a safe and effective alternative to traditional cigarettes. There is, however, a paucity of literature showing the adverse outcomes of e-cigarettes and a correlation with acute eosinophilic pneumonia (AEP). To present a possible association between e-cigarettes and AEP. A 20-year-old previously healthy man was found to develop AEP after smoking an e-cigarette. He was treated with antibiotics and steroids and his symptoms improved. Though an alternative to traditional cigarettes, e-cigarettes can have unpredictable and potentially serious adverse effects. More research needs to be conducted to determine their safety. If seeing a patient in the ED with pulmonary symptoms after use of e-cigarettes, AEP should be considered in the differential. Published by Elsevier Inc.

  5. A Cluster of Primary Pneumonic Plague Transmitted in a Truck Cab in a New Enzootic Focus in China

    PubMed Central

    Luo, Huiming; Dong, Xingqi; Li, Furong; Xie, Xu; Song, Zhizhong; Shao, Zhujun; Li, Zhongjie; Tong, Zhaohui; Wang, Guangfa; Zhang, Hongtao; Yang, Tielong; He, Gao; He, Zeyuan; Fontaine, Robert E.; Zeng, Guang

    2013-01-01

    We investigated a cluster of five cases of severe pneumonia from one village in Yunnan Province, China. We searched for severe pneumonia in the village and hospitals. We interviewed patients and family members about exposures. We tested acute and convalescent sera for antigen and antibody of severe acute respiratory syndrome, avian influenza, and plague. The only common exposure of the five patients was riding together in the enclosed cab of a truck for 1.5 hours while taking the first patient to the hospital. Seroconversion to plague F1 antigen confirmed plague in three survivors. Unfamiliarity of clinicians with plague and lack of sputum examination, blood culture, or postmortem examination delayed the diagnosis. No plague cases occurred among family and village contacts and health care workers. High infectivity in this cluster was limited to a crowded, poorly ventilated truck. PMID:23509116

  6. Herpes simplex type 1 pneumonitis and acute respiratory distress syndrome in a patient with chronic lymphatic leukemia: a case report.

    PubMed

    Luginbuehl, Miriam; Imhof, Alexander; Klarer, Alexander

    2017-11-23

    Pulmonary pathogenicity of herpes simplex virus type 1 in patients in intensive care without classic immunosuppression as well as the necessity of antiviral treatment in the case of herpes simplex virus detection in respiratory specimens in these patients is controversial. We present a case of acute respiratory distress syndrome in a patient with stable chronic lymphatic leukemia not requiring treatment, in whom we diagnosed herpes simplex virus type 1 bronchopneumonitis based on herpes simplex virus type 1 detection in bronchoalveolar lavage fluid and clinical response to antiviral treatment. A 72-year-old white man presented with symptoms of lower respiratory tract infection. His medical history was significant for chronic lymphatic leukemia, which had been stable without treatment, arterial hypertension, multiple squamous cell carcinomas of the scalp, and alcohol overuse. Community-acquired pneumonia was suspected and appropriate broad-spectrum antibacterial treatment was initiated. Within a few hours, rapid respiratory deterioration led to cardiac arrest. He was successfully resuscitated, but developed acute respiratory distress syndrome. Furthermore, he remained febrile and inflammation markers remained elevated despite antibacterial treatment. Polymerase chain reaction from bronchoalveolar lavage fluid and viral culture from tracheobronchial secretions tested positive for herpes simplex virus type 1. We initiated antiviral treatment with acyclovir. Concomitantly we further escalated the antibacterial treatment, although no bacterial pathogen had been isolated at any point. Defervescence occurred rapidly and his C-reactive protein and leukocyte levels decreased. He was successfully weaned from mechanical ventilation, transferred to the ward, and eventually discharged to home. Herpes simplex virus should be considered a cause for lower respiratory tract infection in critically ill patients, especially in the setting of an underlying disease.

  7. Kinetics of the immune response to the (F1+V) vaccine in models of bubonic and pneumonic plague.

    PubMed

    Williamson, E D; Stagg, A J; Eley, S M; Taylor, R; Green, M; Jones, S M; Titball, R W

    2007-01-22

    Protection against aerosol challenge with > 300 MLD of Yersinia pestis was observed 7 days after a single immunisation of mice with the F1+V vaccine. At day 60, mice were protected against injected challenge (10(7)MLD) in a vaccine dose-related manner. Recall responses to rV in splenocytes ex vivo at day 98 correlated significantly (p<0.001) with the immunising dose-level of V antigen; no memory response or anti-V serum IgG was detected in killed whole cell vaccine (KWCV) recipients. This may explain the susceptibility of KWCV recipients to aerosol challenge and the enhanced protection conferred by the F1+V sub-unit vaccine, particularly since the anti-F1 responses induced by either vaccine were similarly IgG1-polarised.

  8. AN OUTBREAK OF HYPERSENSITIVITY PNEUMONITIS AT A METALWORKING PLANT: A LONGITUDINAL ASSESSMENT OF INTERVENTION EFFECTIVENESS. (R825251)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  9. Evaluation of imipenem for prophylaxis and therapy of Yersinia pestis delivered by aerosol in a mouse model of pneumonic plague.

    PubMed

    Heine, Henry S; Louie, Arnold; Adamovicz, Jeffrey J; Amemiya, Kei; Fast, Randy L; Miller, Lynda; Opal, Steven M; Palardy, John; Parejo, Nicolas A; Sörgel, Fritz; Kinzig-Schippers, Martina; Drusano, George L

    2014-06-01

    It has been previously shown that mice subjected to an aerosol exposure to Yersinia pestis and treated with β-lactam antibiotics after a delay of 42 h died at an accelerated rate compared to controls. It was hypothesized that endotoxin release in antibiotic-treated mice accounted for the accelerated death rate in the mice exposed to aerosol Y. pestis. Imipenem, a β-lactam antibiotic, binds to penicillin binding protein 2 with the highest affinity and produces rounded cells. The binding of imipenem causes cells to lyse quickly and thereby to release less free endotoxin. Two imipenem regimens producing fractions of time that the concentration of free, unbound drug was above the MIC (fT>MIC) of approximately 25% (6/24 h) and 40% (9.5/24 h) were evaluated. In the postexposure prophylaxis study, the 40% and 25% regimens produced 90% and 40% survivorship, respectively. In the 42-h treatment study, both regimens demonstrated a 40 to 50% survivorship at therapy cessation and some deaths thereafter, resulting in a 30% survivorship. As this was an improvement over the results with other β-lactams, a comparison of both endotoxin and cytokine levels in mice treated with imipenem and ceftazidime (a β-lactam previously demonstrated to accelerate death in mice during treatment) was performed and supported the original hypotheses; however, the levels observed in animals treated with ciprofloxacin (included as an unrelated antibiotic that is also bactericidal but should cause little lysis due to a different mode of action) were elevated and significantly (7-fold) higher than those with ceftazidime. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  10. Evaluation of Imipenem for Prophylaxis and Therapy of Yersinia pestis Delivered by Aerosol in a Mouse Model of Pneumonic Plague

    PubMed Central

    Louie, Arnold; Adamovicz, Jeffrey J.; Amemiya, Kei; Fast, Randy L.; Miller, Lynda; Opal, Steven M.; Palardy, John; Parejo, Nicolas A.; Sörgel, Fritz; Kinzig-Schippers, Martina; Drusano, George L.

    2014-01-01

    It has been previously shown that mice subjected to an aerosol exposure to Yersinia pestis and treated with β-lactam antibiotics after a delay of 42 h died at an accelerated rate compared to controls. It was hypothesized that endotoxin release in antibiotic-treated mice accounted for the accelerated death rate in the mice exposed to aerosol Y. pestis. Imipenem, a β-lactam antibiotic, binds to penicillin binding protein 2 with the highest affinity and produces rounded cells. The binding of imipenem causes cells to lyse quickly and thereby to release less free endotoxin. Two imipenem regimens producing fractions of time that the concentration of free, unbound drug was above the MIC (fT>MIC) of approximately 25% (6/24 h) and 40% (9.5/24 h) were evaluated. In the postexposure prophylaxis study, the 40% and 25% regimens produced 90% and 40% survivorship, respectively. In the 42-h treatment study, both regimens demonstrated a 40 to 50% survivorship at therapy cessation and some deaths thereafter, resulting in a 30% survivorship. As this was an improvement over the results with other β-lactams, a comparison of both endotoxin and cytokine levels in mice treated with imipenem and ceftazidime (a β-lactam previously demonstrated to accelerate death in mice during treatment) was performed and supported the original hypotheses; however, the levels observed in animals treated with ciprofloxacin (included as an unrelated antibiotic that is also bactericidal but should cause little lysis due to a different mode of action) were elevated and significantly (7-fold) higher than those with ceftazidime. PMID:24687492

  11. THE VIABILITY OF THE PNEUMOCOCCUS AFTER DRYING: A STUDY OF ONE OF THE FACTORS IN PNEUMONIC INFECTION

    PubMed Central

    Wood, Francis Carter

    1905-01-01

    I. In moist sputum kept in the dark at room temperatures the average life of the pneumococcus is eleven days, though considerable variations may be noted in different specimens of sputum. In the same sputum kept at o° C. the average life of the organism is thirty-five days. In sputum kept at room temperature and in a strong light the pneumococcus lives less than five days. II. In dried sputum (a) in the dark the pneumococcus lives on an average thirty-five days; (b) in diffuse light, thirty days; (c) in sunlight, less than four hours. III. In powdered sputum even when kept in the dark the death of the pneumococcus takes place in from one to four hours. When exposed to sunlight death occurs within an hour. IV. No important differences were noted in the life of the pneumococcus when dried on glass, tin, or wood. On cloth the life was usually slightly longer than on non-absorbing surfaces. V. Sprayed sputum particles remain in suspension for twenty-four hours, but all masses of a size sufficient to contain bacteria settle at a rate of about 40 cm. per hour. VI. When sputum containing pneumococci is sprayed the organisms rarely survive for more than an hour, and often die in less time. The substance upon which the particles fall makes but little difference in the life of the organism. On cloth a slight prolongation is occasionally noted, due perhaps to the slow drying. VII. The mucus of the sputum exerts a destructive action on the pneumococcus. VIII. Exposure of bacterial spray to sunlight while in suspension results in the destruction of the pneumococcus within half an hour. PMID:19867014

  12. Extrinsic Allergic Alveolitis (Hypersensitivity Pneumonitis) Caused by Sphingobacterium spiritivorum from the Water Reservoir of a Steam Iron

    PubMed Central

    Kämpfer, Peter; Engelhart, S.; Rolke, M.; Sennekamp, J.

    2005-01-01

    A case of extrinsic allergic alveolitis (EAA) caused by Sphingobacterium spiritivorum is described. The symptoms were associated with the use of a steam iron. The water reservoir was heavily contaminated with S. spiritivorum (106 CFU ml−1). This is the first report of S. spiritivorum as a causative agent of EAA. PMID:16145174

  13. Bivalent vaccination against pneumonic pasteurellosis in domestic sheep and goats with modified-live in-frame lktA deletion mutants of Mannheimia haemolytica.

    PubMed

    Briggs, Robert E; Hauglund, Melissa J; Maheswaran, Samuel K; Tatum, Fred M

    2013-11-01

    A temperature-sensitive shuttle vector, pBB80C, was utilized to generate in-frame deletion mutants of the leukotoxin structural gene (lktA) of Mannheimia haemolytica serotypes 1, 2, 5, 6, 7, 8, 9, and 12. Culture supernatants from the mutants contained a truncated protein with an approximate molecular weight of 66 kDa which was reactive to anti-leukotoxin monoclonal antibody. No protein reactive to anti-LktA monoclonal antibody was detected at the molecular weight 100-105 kDa of native LktA. Sheep and goats vaccinated intramuscularly with a mixture of serotypes 5 and 6 mutants were resistant to virulent challenge with a mixture of the wild-type parent strains. These vaccinates responded serologically to both vaccine serotypes and exhibited markedly-reduced lung lesion volume and pulmonary infectious load compared to control animals. Control animals yielded a mixture of serotypes from lung lobes, but the proportion even within an individual animal varied widely from 95% serotype 5-95% serotype 6. Cultures recovered from liver were homogeneous, but two animals yielded serotype 5 and the other two yielded serotype 6 in pure culture. Published by Elsevier Ltd.

  14. Increased prevalence of IgG-induced sensitization and hypersensitivity pneumonitis (humidifier lung) in nonsmokers exposed to aerosols of a contaminated air conditioner.

    PubMed

    Baur, X; Richter, G; Pethran, A; Czuppon, A B; Schwaiblmair, M

    1992-01-01

    Specific IgG antibodies against antigens of a contaminated air conditioner were estimated in serum of 134 workers of a printing company. Altogether 64% of the workers investigated revealed significantly elevated levels (> 3 U/ml) of IgG antibodies specific to these antigens as compared to a nonexposed control group. The occurrence of IgG antibodies for microbial extracts were 25% for Fusarium, 23% for Penicillium notatum, 13% for Alternaria tenuis, 12% for Aureobasidium pullulans, 9% for Sphaeropsidales species, 3% for Micropolyspora faeni, 2% for Aspergillus fumigatus and 2% for Thermoactionomyces vulgaris. Out of the 86 workers with elevated IgG antibodies for air conditioner antigens, 59 were nonsmokers. Considering a cut-off level of 10 U/ml IgG for high values, the proportion of smokers to nonsmokers becomes even more pronounced (6 to 36 respectively, binominal test p < 0.001). This is despite the fact that the distribution of smokers and nonsmokers among the 134 workers is approximately equal (60 to 74). All 3 workers with clinical diagnosis of humidifier lung or humidifier fever belonged to the nonsmoker group. Our findings indicate that crude water extracts of contaminated air conditioners are the best choice as antigen source for the diagnosis of humidifier lung in exposed workers. Nonsmokers are shown to have a high risk for immunological sensitization.

  15. WE-AB-207B-02: A Bayesian Network Approach for Joint Prediction of Tumor Control and Radiation Pneumonitis (RP) in Non-Small-Cell Lung Cancer (NSCLC)

    SciTech Connect

    Luo, Y; McShan, D; Matuszak, M

    Purpose: NSCLC radiotherapy treatment is a trade-off between controlling the tumor while limiting radiation-induced toxicities. Here we identify hierarchical biophysical relationships that could simultaneously influence both local control (LC) and RP by using an integrated Bayesian Networks (BN) approach. Methods: We studied 79 NSCLC patients treated on prospective protocol with 56 cases of LC and 21 events of RP. Beyond dosimetric information, each patient had 193 features including 12 clinical factors, 60 circulating blood cytokines before and during radiotherapy, 62 microRNAs, and 59 single-nucleotide polymorphisms (SNPs). The most relevant biophysical predictors for both LC and RP were identified using amore » Markov blanket local discovery algorithm and the corresponding BN was constructed using a score-learning algorithm. The area under the free-response receiver operating characteristics (AU-FROC) was used for performance evaluation. Cross-validation was employed to guard against overfitting pitfalls. Results: A BN revealing the biophysical interrelationships jointly in terms of LC and RP was developed and evaluated. The integrated BN included two SNPs, one microRNA, one clinical factor, three pre-treatment cytokines, relative changes of two cytokines between pre and during-treatment, and gEUDs of the GTV (a=-20) and lung (a=1). On cross-validation, the AUC prediction of independent LC was 0.85 (95% CI: 0.75–0.95) and RP was 0.83 (0.73–0.92). The AU-FROC of the integrated BN to predict both LC/RP was 0.81 (0.71–0.90) based on 2000 stratified bootstrap, indicating minimal loss in joint prediction power. Conclusions: We developed a new approach for multiple outcome utility application in radiotherapy based on integrated BN techniques. The BN developed from large-scale retrospective data is able to simultaneously predict LC and RP in NSCLC treatments based on individual patient characteristics. The joint prediction is only slightly compromised compared to independent predictions. Our approach shows promise for use in clinical decision support system for personalized radiotherapy subject to multiple endpoints. These studies were supported by a grant from the NCI/NIH P01-CA59827.« less

  16. Outbreak of Human Pneumonic Plague with Dog-to-Human and Possible Human-to-Human Transmission--Colorado, June-July 2014.

    PubMed

    Runfola, Janine K; House, Jennifer; Miller, Lisa; Colton, Leah; Hite, Donna; Hawley, Alex; Mead, Paul; Schriefer, Martin; Petersen, Jeannine; Casaceli, Colleen; Erlandson, Kristine M; Foster, Clayton; Pabilonia, Kristy L; Mason, Gary; Douglas, John M

    2015-05-01

    On July 8, 2014, the Colorado Department of Public Health and Environment (CDPHE) laboratory identified Yersinia pestis, the bacterium that causes plague, in a blood specimen collected from a man (patient A) hospitalized with pneumonia. The organism had been previously misidentified as Pseudomonas luteola by an automated system in the hospital laboratory. An investigation led by Tri-County Health Department (TCHD) revealed that patient A's dog had died recently with hemoptysis. Three other persons who had contact with the dog, one of whom also had contact with patient A, were ill with fever and respiratory symptoms, including two with radiographic evidence of pneumonia. Specimens from the dog and all three human contacts yielded evidence of acute Y. pestis infection. One of the pneumonia cases might have resulted through human-to-human transmission from patient A, which would be the first such event reported in the United States since 1924. This outbreak highlights 1) the need to consider plague in the differential diagnosis of ill domestic animals, including dogs, in areas where plague is endemic; 2) the limitations of automated diagnostic systems for identifying rare bacteria such as Y. pestis; and 3) the potential for milder plague illness in patients taking antimicrobial agents. Hospital laboratorians should be aware of the limitations of automated identification systems, and clinicians should suspect plague in patients with clinically compatible symptoms from whom P. luteola is isolated.

  17. Neoadjuvant Therapy for Esophageal Cancer and Cardiopulmonary Physiology

    ClinicalTrials.gov

    2018-03-05

    Esophageal Cancer; Radiation Pneumonitis; Pulmonary Fibrosis; Respiratory Failure; Pneumonia; Surgery; Chemotherapy Effect; Radiation Fibrosis; Radiation Toxicity; Adenocarcinoma; Squamous Cell Carcinoma

  18. WE-H-BRA-02: Radiobiological Modeling of Tumor Control Probability (TCP) and Radiation-Induced Pneumonitis (RP) for Lung Cancer Patients Treated with Monte Carlo-Based Lung SBRT

    SciTech Connect

    Pokhrel, D; Sood, S; Shen, X

    2016-06-15

    Purpose: To present radiobiological modeling of TCP using tumor size-adjusted BED(s-BED)and PTV(D99) to lung SBRT patients treated with X-ray Voxel Monte Carlo(XVMC) algorithm, apply parameterized Lyman-NTCP model to predict grade-2 RP and subsequently, compare with clinical outcomes/observations. Methods: Dosimetric parameters and clinical follow-up for XVMC-based lung-SBRT patients were retrospectively evaluated. Patients were treated at Novalis-TX with hybrid(2 non-coplanar partial-arcs plus 3–6 static-beams)plan using HD-MLC/6MV-SRS-beam.For TCP,s-BED modelling was utilized: TCP=EXP[sBED-TCD50]/k/(1.0+EXP[sBED-TCD50]/k), where k=31Gy corresponding to TCD50=0Gy and s-BED was defined as BED10 minus 10 times the tumor diameter(in centimeters)by Ohri et al.(IJROBP,2012). For 2-yr local-control, we used more-realistic MC-computed PTVD99 as amore » predictive parameter, s-BED(D99).Due to relatively shorter median follow-up interval(12-months),Kaplan-Meier curves were generated to estimate 2-yr observed local-control and compared to predicted-rate by TCP modeling. For NTCP, we employed parameterized Lyman-NTCP model utilizing normal-lung DVH and α/β=3Gy fitted to predict grade-2 RP after lung-SBRT. Results: Total 108 patients (137 tumors) treated for 35–70Gy in 3–5 fractions, either primary-lung(n=74)or metastatic-lung(n=53)tumors were included.F or the given prescription dose with MC-computed MUs, 2-yr local-control rates with s-BED(D99) was 87±8%. Kaplan-Meier generated observed local-control rate at 2-yr was 87.5%,suggesting that PTV(D99) could be a potential predictor (p-value=0.38). Observed vs predicted TCP for primary-lung tumors and metastatic tumors were 97% vs 88±7% and 94% vs 86±9%.NTCP model predicted well for symptomatic-RP with predicted vs observed (3±5% vs 2%). Radiographic and clinically significant RP was observed in 13% and 2% of patients. Higher rates of radiographic change were observed in patients who received >50Gy compared to ≤50Gy(24% vs 10%). Conclusion: Utilizing MC-computed PTVD99, our TCP results were well correlated with clinical outcome. The predicted grade-2 RP rate was comparable to clinical observations. Clinical application of these radiobiological models may potentially allow for target dose escalation and/or lung-toxicity reduction. Further validation of these radiobiological models with longer follow up interval for large cohorts of lung-SBRT patients is anticipated.« less

  19. Aspiration pneumonia

    MedlinePlus

    Anaerobic pneumonia; Aspiration of vomitus; Necrotizing pneumonia; Aspiration pneumonitis ... The type of bacteria that caused the pneumonia depends on: Your ... facility, for example) Whether you were recently hospitalized ...

  20. What Is Cough?

    MedlinePlus

    ... Visit Children and Clinical Studies to hear experts, parents, and children talk about their experiences with clinical ... Pneumonitis Idiopathic Pulmonary Fibrosis Pneumonia Pulmonary Function ...

  1. Asbestosis

    MedlinePlus

    Pulmonary fibrosis - from asbestos exposure; Interstitial pneumonitis - from asbestos exposure ... Breathing in asbestos fibers can cause scar tissue (fibrosis) to form inside the lung. Scarred lung tissue does not expand and ...

  2. Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT

    ClinicalTrials.gov

    2018-06-08

    Pulmonary Arterial Hypertension; Pulmonary Hypertension; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Respiratory Bronchiolitis Associated Interstitial Lung Disease; Desquamative Interstitial Pneumonia; Cryptogenic Organizing Pneumonia; Acute Interstitial Pneumonitis; Idiopathic Lymphoid Interstitial Pneumonia; Idiopathic Pleuroparenchymal Fibroelastosis

  3. Early emergence of Yersinia pestis as a severe respiratory pathogen

    PubMed Central

    Zimbler, Daniel L.; Schroeder, Jay A.; Eddy, Justin L.; Lathem, Wyndham W.

    2015-01-01

    Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia. Here we show that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity. While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague. These findings indicate that Y. pestis was capable of causing pneumonic plague before it evolved to optimally cause invasive infections in mammals. PMID:26123398

  4. Early emergence of Yersinia pestis as a severe respiratory pathogen.

    PubMed

    Zimbler, Daniel L; Schroeder, Jay A; Eddy, Justin L; Lathem, Wyndham W

    2015-06-30

    Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia. Here we show that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity. While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague. These findings indicate that Y. pestis was capable of causing pneumonic plague before it evolved to optimally cause invasive infections in mammals.

  5. SciTech Connect

    Sakamoto, Susumu, E-mail: susumu1029@gmail.com; Kikuchi, Naoshi; Ichikawa, Atsuo

    Despite the wide use of everolimus as an antineoplastic coating agent for coronary stents to reduce the rate of restenosis, little is known about the health hazards of everolimus-eluting stents (EES). We describe a case of pneumonitis that developed 2 months after EES implantation for angina. Lung pathology demonstrated an organizing pneumonia pattern that responded to corticosteroid therapy. Although the efficacy of EES for ischemic heart disease is well established, EES carries a risk of pneumonitis.

  6. Evaluation of Quantitative Anti-F1 IgG and Anti-V IgG ELISAs for use as an in Vitro-Based Potency Assay of Plague Vaccine in Mice

    DTIC Science & Technology

    2008-04-01

    Andrews GP, Welkos SL, Friedlander AM, et al. Protection of mice from fatal bubonic and pneu- monic plague by passive immunization with monoclonal...SL, Andrews GP, Adamovicz J, et al. Protection against experimental bubonic and pneumonic plague by a recombinant capsular F1-V antigen fusion...fusion protein as vaccine antigen against bubonic and pneumonic plague . Biotechnol Prog 2005; 21:1490e510.[21] Simpson WJ, Thomas RE, Schwan TG

  7. Plague in Guinea pigs and its prevention by subunit vaccines.

    PubMed

    Quenee, Lauriane E; Ciletti, Nancy; Berube, Bryan; Krausz, Thomas; Elli, Derek; Hermanas, Timothy; Schneewind, Olaf

    2011-04-01

    Human pneumonic plague is a devastating and transmissible disease for which a Food and Drug Administration-approved vaccine is not available. Suitable animal models may be adopted as a surrogate for human plague to fulfill regulatory requirements for vaccine efficacy testing. To develop an alternative to pneumonic plague in nonhuman primates, we explored guinea pigs as a model system. On intranasal instillation of a fully virulent strain, Yersinia pestis CO92, guinea pigs developed lethal lung infections with hemorrhagic necrosis, massive bacterial replication in the respiratory system, and blood-borne dissemination to other organ systems. Expression of the Y. pestis F1 capsule was not required for the development of pulmonary infection; however, the capsule seemed to be important for the establishment of bubonic plague. The mean lethal dose (MLD) for pneumonic plague in guinea pigs was estimated to be 1000 colony-forming units. Immunization of guinea pigs with the recombinant forms of LcrV, a protein that resides at the tip of Yersinia type III secretion needles, or F1 capsule generated robust humoral immune responses. Whereas LcrV immunization resulted in partial protection against pneumonic plague challenge with 250 MLD Y. pestis CO92, immunization with recombinant F1 did not. rV10, a vaccine variant lacking LcrV residues 271-300, elicited protection against pneumonic plague, which seemed to be based on conformational antibodies directed against LcrV. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Plague in Guinea Pigs and Its Prevention by Subunit Vaccines

    PubMed Central

    Quenee, Lauriane E.; Ciletti, Nancy; Berube, Bryan; Krausz, Thomas; Elli, Derek; Hermanas, Timothy; Schneewind, Olaf

    2011-01-01

    Human pneumonic plague is a devastating and transmissible disease for which a Food and Drug Administration–approved vaccine is not available. Suitable animal models may be adopted as a surrogate for human plague to fulfill regulatory requirements for vaccine efficacy testing. To develop an alternative to pneumonic plague in nonhuman primates, we explored guinea pigs as a model system. On intranasal instillation of a fully virulent strain, Yersinia pestis CO92, guinea pigs developed lethal lung infections with hemorrhagic necrosis, massive bacterial replication in the respiratory system, and blood-borne dissemination to other organ systems. Expression of the Y. pestis F1 capsule was not required for the development of pulmonary infection; however, the capsule seemed to be important for the establishment of bubonic plague. The mean lethal dose (MLD) for pneumonic plague in guinea pigs was estimated to be 1000 colony-forming units. Immunization of guinea pigs with the recombinant forms of LcrV, a protein that resides at the tip of Yersinia type III secretion needles, or F1 capsule generated robust humoral immune responses. Whereas LcrV immunization resulted in partial protection against pneumonic plague challenge with 250 MLD Y. pestis CO92, immunization with recombinant F1 did not. rV10, a vaccine variant lacking LcrV residues 271-300, elicited protection against pneumonic plague, which seemed to be based on conformational antibodies directed against LcrV. PMID:21406168

  9. Yersinia pestis: still a plague in the 21st century.

    PubMed

    Josko, Deborah

    2004-01-01

    Yersinia pestis, the causative agent of plague, is an aerobic, non-motile, gram-negative bacillus belonging to the family Enterobacteriacea. It is a zoonotic infection transmitted to humans via the bite of a flea. Three clinical forms of human plague exist: bubonic, pneumonic, and septicemic. Many important virulence factors associated with this organism are responsible for its extreme pathogenicity and high mortality rates. The bubonic form of plague is usually not transmitted human to human but the pneumonic form is--through inhalation of contaminated aerosol droplets. The pneumonic plague would be the form most likely implicated in the event of an intentional attack. Inhalation of aerosols can cause devastating consequences resulting in many casualties. Unless antibiotics are administered within 24 hours of the initial symptoms, death is inevitable. Its potential for use as a biological weapon is of major concern to public health officials.

  10. Plague: from natural disease to bioterrorism.

    PubMed

    Riedel, Stefan

    2005-04-01

    Yersinia pestis is the causative agent of plague, an enzootic vectorborne disease usually infecting rodents (rats) and fleas. Humans can become infected after being bitten by fleas that have fed on infected rodents. In humans, the disease usually occurs in the form of bubonic plague. In rare cases, the infection spreads to the lungs via the bloodstream and causes secondary pneumonic plague. Person-to-person transmission has been described for pneumonic plague but is rare in primary bubonic plague. Bubonic plague can usually be treated successfully with antibiotics; however, pneumonic plague develops rapidly and carries a high fatality rate despite immediate treatment with antibiotics. Plague is also recognized as a potential agent of bioterrorism. It has been used, or considered for use, as a biologic weapon on several occasions. It is important for the medical community to be familiar with the epidemiology, diagnosis, and symptoms of plague so it can deliver an appropriate and calm response should the unthinkable happen.

  11. Plague: from natural disease to bioterrorism

    PubMed Central

    2005-01-01

    Yersinia pestis is the causative agent of plague, an enzootic vectorborne disease usually infecting rodents (rats) and fleas. Humans can become infected after being bitten by fleas that have fed on infected rodents. In humans, the disease usually occurs in the form of bubonic plague. In rare cases, the infection spreads to the lungs via the bloodstream and causes secondary pneumonic plague. Person-to-person transmission has been described for pneumonic plague but is rare in primary bubonic plague. Bubonic plague can usually be treated successfully with antibiotics; however, pneumonic plague develops rapidly and carries a high fatality rate despite immediate treatment with antibiotics. Plague is also recognized as a potential agent of bioterrorism. It has been used, or considered for use, as a biologic weapon on several occasions. It is important for the medical community to be familiar with the epidemiology, diagnosis, and symptoms of plague so it can deliver an appropriate and calm response should the unthinkable happen. PMID:16200159

  12. Pulmonary infection by Yersinia pestis rapidly establishes a permissive environment for microbial proliferation.

    PubMed

    Price, Paul A; Jin, Jianping; Goldman, William E

    2012-02-21

    Disease progression of primary pneumonic plague is biphasic, consisting of a preinflammatory and a proinflammatory phase. During the long preinflammatory phase, bacteria replicate to high levels, seemingly uninhibited by normal pulmonary defenses. In a coinfection model of pneumonic plague, it appears that Yersinia pestis quickly creates a localized, dominant anti-inflammatory state that allows for the survival and rapid growth of both itself and normally avirulent organisms. Yersinia pseudotuberculosis, the relatively recent progenitor of Y. pestis, shows no similar trans-complementation effect, which is unprecedented among other respiratory pathogens. We demonstrate that the effectors secreted by the Ysc type III secretion system are necessary but not sufficient to mediate this apparent immunosuppression. Even an unbiased negative selection screen using a vast pool of Y. pestis mutants revealed no selection against any known virulence genes, demonstrating the transformation of the lung from a highly restrictive to a generally permissive environment during the preinflammatory phase of pneumonic plague.

  13. Plague.

    PubMed

    Williamson, E D

    2009-11-05

    Killed whole cell vaccines for plague were first produced as long ago as the late 1890s and modified versions of these are still used, with evidence that they are efficacious against bubonic plague. Renewed efforts with modern technology have yielded new candidate vaccines which are less reactogenic, can be produced in a conventional pharmaceutical manufacturing plant and are protective against the life-threatening pneumonic form of the disease. This paper reviews the progress towards an improved vaccine for plague and assesses the likely impact of a prophylactic vaccine for bubonic and pneumonic plague.

  14. Fatal Diesel Poisoning: A Case Report and Brief Review of Literature.

    PubMed

    Srinivasa Murthy, Abilash; Das, Siddhartha; Bheemanathi Hanuman, Srinivas

    2018-06-01

    Hydrocarbons are volatile substances that are used in routine life activities for cooking or as automobile fuel. Diesel is one of the commonly used automobile fuels obtained from crude oil. Death due to poisoning by diesel is rarely reported. Most commonly affected is the respiratory system either after aspiration or ingestion. The most common presentation is chemical pneumonitis or aspiration pneumonitis from which patient usually recovers. Gas chromatography techniques help in the detection of volatile substances like diesel. Here, we report a rare case of fatal pediatric accidental diesel poisoning.

  15. Evaluation of rare but severe immune related adverse effects in PD-1 and PD-L1 inhibitors in non-small cell lung cancer: a meta-analysis

    PubMed Central

    Hu, Yang-Bo; Zhang, Qun; Li, Hui-Juan; Michot, Jean Maire; Liu, Hong-Bing

    2017-01-01

    Background Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitor therapy is showing marked efficacy in advanced non-small cell lung cancer (NSCLC). Meanwhile, it is concomitant with distinctive immune-related adverse effects. We aim to describe the incidence of pneumonitis and other rare but severe immune-related adverse effects (IRAEs), as well as treatment related deaths. In addition, we analyze the differences in incidence of pneumonitis between PD-1 and PD-L1 inhibitors and standard-of-care chemotherapy. Methods PubMed was searched up to 24 March 2017 for clinical trials of PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, avelumab and durvalumab) in treatment of NSCLC. Besides, references of relevant articles were screened. Results Finally, 22 trials were included in our study, 14 with data of pneumonitis, 19 with other severe IRAEs or treatment related deaths and 5 with control groups. Incidence of all-grade pneumonitis was 2.9% (95% CI, 2.0–4.8%) and grade 3 or higher pneumonitis 2.0% (95% CI, 1.0–2.0%). Incidence of all-grade pneumonitis in PD-1 and PD-L1 inhibitor therapy (n=1,313) was significantly higher than that in chemotherapy (n=918) (OR=2.35, 95% CI, 1.32–4.20, P=0.004), but had no significance in grade 3–5 pneumonitis. Incidence of cardiorespiratory arrest (n=537) was 1.0% (95% CI, 0–2.0%), cardiac failure (n=214) 2.0% (95% CI, 1.0–5.7%), myocardial infarction (n=402) 1.0% (95% CI, 0–3.8%), stroke (n=135) 2.0% (95% CI, 0–13.0%), disease progression (n=391) 1.0% (95% CI, 0–2.9%), pancreatitis (n=700) 1.0% (95% CI, 0–2.0%) and severe skin reactions (n=836) 2.0% (95% CI, 1.0–3.8%). Incidence of treatment related deaths was 0.7%. Conclusions Immune related adverse effects can on occasion be life-threatening even though usually rare. Incidence of pneumonitis in PD-1 and PD-L1 inhibitors was significantly higher than that in chemotherapy. More studies should be conducted to

  16. Isocyanates and respiratory disease: current status

    SciTech Connect

    Musk, A.W.; Peters, J.M.; Wegman, D.H.

    This paper reviews the known respiratory effects of isocyanates. There is good evidence to indicate that isocyanates: cause chemical bronchitis/pneumonitis; are potent pulmonary sensitizers capable of causing isocyanate asthma; cause nonspecific airways disease, including chronic bronchitis; can induce a general asthmatic state; and can cause hypersensitivity pneumonitis. Similar dose-response relationships are seen for both acute and chronic effects. There are plants operating in which exposures are well controlled and in which no respiratory effects can be detected. Suggestions are provided for preplacement assessment and periodic surveillance for workers exposed to these compounds.114 references.

  17. Pasteurellosis

    USDA-ARS?s Scientific Manuscript database

    This book chapter for the 11th edition of Diseases of Swine describes the current state of knowledge regarding diseases of swine caused by Pasteurella multocida, including progressive atrophic rhinitis and pneumonic and septicemic pasteurellosis. Topics covered include traditional and novel typing ...

  18. Pulmonary toxoplasmosis after allogeneic bone marrow transplantation: case report and review.

    PubMed

    Saad, R; Vincent, J F; Cimon, B; de Gentile, L; Francois, S; Bouachour, G; Ifrah, N

    1996-07-01

    We report an isolated case of toxoplasma pneumonitis in a 27-year-old man. This acute infection occurred after induction chemotherapy for AMLo relapsing 3 years post-allogeneic BMT. The detection of Toxoplasma gondii in the bronchoalvolar lavage (BAL), by culture in fibroblast cell line MRC5 enabled us to make the diagnosis. Pyrimethamine and sulfadiazine were effective.

  19. Synergistic protection of mice against plague with monoclonal antibodies specific for the F1 and V antigens of Yersinia pestis.

    PubMed

    Hill, Jim; Copse, Catherine; Leary, Sophie; Stagg, Anthony J; Williamson, E Diane; Titball, Richard W

    2003-04-01

    Monoclonal antibodies specific for Yersinia pestis V antigen and F1 antigen, administered singly or in combination, protected mice in models of bubonic and pneumonic plague. Antibodies showed synergy when administered prophylactically and as a therapy 48 h postinfection. Monoclonal antibodies therefore have potential as a treatment for plague.

  20. Yersinia pestis CO92 delta yopH is a potent live, attenuated plague vaccine.

    PubMed

    Bubeck, Sarah S; Dube, Peter H

    2007-09-01

    An in-frame deletion of the yopH gene in Yersinia pestis CO92 attenuates virulence in both bubonic and pneumonic plague models. When it is used as a live, attenuated vaccine, CO92 delta yopH provides a high degree of protection from parental and respiratory challenge with Y. pestis CO92.

  1. Phenotypic and genotypic characterization of Klebsiella pneumonia recovered from nonhuman primates

    USDA-ARS?s Scientific Manuscript database

    Klebsiella pneumoniae is a zoonotic, Gram-negative member of the family Enterobacteriaceae and is the causative agent of nosocomial septicemic, pneumonic, and urinary tract infections. Recently, pathogenic strains of K. pneumoniae sharing a hypermucoviscosity (HMV) phenotype have been attributed to ...

  2. Field Evaluation of Solvent-Free Sampling with Di-n-butylamine for the Determination of Airborne Monomeric and Oligomeric 1,6-Hexamethylene Diisocyanate

    DTIC Science & Technology

    2014-03-27

    cause contact dermatitis , asthma, and hypersensitivity pneumonitis; the most common adverse health outcome associated with isocyanate exposure is...linked to allergic contact dermatitis in humans and respiratory sensitization in animals. Chronic dermal exposure has resulted in skin irritation and...derivatization stabilizes the highly reactive isocyanates and enhances recovery of the isocyanates that do not come into contact with the derivatization

  3. [The importance of endotoxin producing bacterias for practical purposes

    PubMed

    Schimmel, Dietrich

    1994-01-01

    Lipopolysaccharides (endotoxin) cause according to resorption out of the intestinal tract or aerogenic inhalation or by a septic infection clinical signs. The clinical reactions are praeshock symptoms, acute forms of shock and death. The experimental intratracheally administration of lipopolysaccharides into calves caused pneumonic lesions without bacterial experimental infection.

  4. Proximity-dependent inhibition of growth of mannheimia haemolytica by pasteurella multocida.

    USDA-ARS?s Scientific Manuscript database

    Mannheimia haemolytica, Pasteurella multocida, and Bibersteinia trehalosi have been identified in the lungs of pneumonic bighorn sheep (BHS; Ovis canadensis). Of these pathogens, M. haemolytica has been shown to consistently cause fatal pneumonia in BHS under experimental conditions. However, M. hae...

  5. Obstetric aspects of the Guillan-Barré syndrome.

    PubMed

    Sudo, N; Weingold, A B

    1975-01-01

    Two additional cases of Guillain-Barre syndrome complicating pregnancy are reported and the 25 previously published cases reviewed. While fetal prognosis is generally favorable, the occurrence of the disease in late pregnancy is a high-rish maternal condition. Respiratory failure and aspiration pneumonitis may result in premature labor and maternal mortality.

  6. Role of bibersteinia trehalosi, respiratory syncytial virus, and parainfluenza-3 virus in bighorn sheep pneumonia

    USDA-ARS?s Scientific Manuscript database

    Pneumonic bighorn sheep (BHS) have been found to be culture- and/or sero-positive for Bibersteinia trehalosi, respiratory syncytial virus (RSV), and parainfluenza-3 virus (PI-3). The objective of this study was to determine whether these pathogens can cause fatal pneumonia in BHS. In the first study...

  7. Mycoplasma ovipneumoniae can predispose bighorn sheep to fatal Mannheimia haemolytica pneumonia

    USDA-ARS?s Scientific Manuscript database

    Mycoplasma ovipneumoniae has been isolated from the lungs of pneumonic bighorn sheep (BHS). However experimental reproduction of fatal pneumonia in BHS with M. ovipneumoniae was not successful. Therefore the specific role, if any, of M. ovipneumoniae in BHS pneumonia is unclear. The objective of th...

  8. Co-expression of ovine LPS receptor CD14 with Mannheimia haemolytica leukotoxin receptor LFA-1 or Mac-1 does not enhance leukotoxin-induced cytotoxicity

    USDA-ARS?s Scientific Manuscript database

    Leukotoxin (Lkt) and LPS are the major virulence determinants of Mannheimia haemolytica that contribute to the pathogenesis of bovine and ovine pneumonic pasteurellosis. We have previously identified bovine and ovine CD18 as the functional receptor for Lkt. LPS complexes with Lkt resulting in incre...

  9. Successful Treatment of Human Plague with Oral Ciprofloxacin.

    PubMed

    Apangu, Titus; Griffith, Kevin; Abaru, Janet; Candini, Gordian; Apio, Harriet; Okoth, Felix; Okello, Robert; Kaggwa, John; Acayo, Sarah; Ezama, Geoffrey; Yockey, Brook; Sexton, Christopher; Schriefer, Martin; Mbidde, Edward Katongole; Mead, Paul

    2017-03-01

    The US Food and Drug Administration recently approved ciprofloxacin for treatment of plague (Yersina pestis infection) based on animal studies. Published evidence of efficacy in humans is sparse. We report 5 cases of culture-confirmed human plague treated successfully with oral ciprofloxacin, including 1 case of pneumonic plague.

  10. Successful Treatment of Human Plague with Oral Ciprofloxacin

    PubMed Central

    Apangu, Titus; Griffith, Kevin; Abaru, Janet; Candini, Gordian; Apio, Harriet; Okoth, Felix; Okello, Robert; Kaggwa, John; Acayo, Sarah; Ezama, Geoffrey; Yockey, Brook; Sexton, Christopher; Schriefer, Martin; Mbidde, Edward Katongole

    2017-01-01

    The US Food and Drug Administration recently approved ciprofloxacin for treatment of plague (Yersina pestis infection) based on animal studies. Published evidence of efficacy in humans is sparse. We report 5 cases of culture-confirmed human plague treated successfully with oral ciprofloxacin, including 1 case of pneumonic plague. PMID:28125398

  11. Association of Mycoplasma ovipneumoniae Infection with Population-Limiting Respiratory Disease in Free-Ranging Rocky Mountain Bighorn Sheep (Ovis canadensis canadensis)▿

    PubMed Central

    Besser, Thomas E.; Cassirer, E. Frances; Potter, Kathleen A.; VanderSchalie, John; Fischer, Allison; Knowles, Donald P.; Herndon, David R.; Rurangirwa, Fred R.; Weiser, Glen C.; Srikumaran, Subramaniam

    2008-01-01

    Bronchopneumonia is a population-limiting disease in bighorn sheep in much of western North America. Previous investigators have isolated diverse bacteria from the lungs of affected sheep, but no single bacterial species is consistently present, even within single epizootics. We obtained high-quality diagnostic specimens from nine pneumonic bighorn sheep in three populations and analyzed the bacterial populations present in bronchoalveolar lavage specimens of seven by using a culture-independent method (16S rRNA gene amplification and clone library analyses). Mycoplasma ovipneumoniae was detected as a predominant member of the pneumonic lung flora in lambs with early lesions of bronchopneumonia. Specific PCR tests then revealed the consistent presence of M. ovipneumoniae in the lungs of pneumonic bighorn sheep in this study, and M. ovipneumoniae was isolated from lung specimens of five of the animals. Retrospective application of M. ovipneumoniae PCR to DNA extracted from archived formalin-fixed, paraffin-embedded lung tissues of historical adult bighorn sheep necropsy specimens supported the association of this agent with bronchopneumonia (16/34 pneumonic versus 0/17 nonpneumonic sheep were PCR positive [P < 0.001]). Similarly, a very strong association was observed between the presence of one or more M. ovipneumoniae antibody-positive animals and the occurrence of current or recent historical bronchopneumonia problems (seropositive animals detected in 9/9 versus 0/9 pneumonic and nonpneumonic populations, respectively [P < 0.001]). M. ovipneumoniae is strongly associated with bronchopneumonia in free-ranging bighorn sheep and is a candidate primary etiologic agent for this disease. PMID:18057131

  12. A case of pneumocystis pneumonia associated with everolimus therapy for renal cell carcinoma.

    PubMed

    Saito, Yoshinobu; Nagayama, Mikie; Miura, Yukiko; Ogushi, Satoko; Suzuki, Yasutomo; Noro, Rintaro; Minegishi, Yuji; Kimura, Go; Kondo, Yukihiro; Gemma, Akihiko

    2013-05-01

    A 76-year-old female with advanced renal cell carcinoma had been treated with everolimus for 3 months. She visited our hospital because of a cough and fever lasting a few days. Chest X-rays showed bilateral infiltrative shadows, and a chest computed tomography scan showed homogeneous ground-glass opacities with mosaic patterns, especially in the apical region. The laboratory results revealed a decreased white blood cell count with lymphocytopenia and high levels of lactate dehydrogenase, C-reactive protein and KL-6. Pneumonitis was suspected and, therefore, everolimus therapy was interrupted. At that time, the pneumonitis was thought to be drug-induced interstitial lung disease. However, it was not possible to rule out pneumocystis pneumonia, because the patient was immunocompromised and the computed tomography findings suggested the possibility of pneumocystis pneumonia. The pneumonitis progressed rapidly and the patient developed respiratory failure, so we performed bronchoalveolar lavage to make a definitive diagnosis, and simultaneously started treatment with prednisolone and trimethoprim-sulfamethoxazole to cover both interstitial lung disease and pneumocystis pneumonia. A polymerase chain reaction assay of the bronchoalveolar lavage fluid was positive for Pneumocystis carinii DNA, and the serum level of β-d-glucan was significantly elevated. Thus, the patient was diagnosed with pneumocystis pneumonia, which was cured by the treatment. Interstitial lung disease is a major adverse drug reaction associated with everolimus, and interstitial lung disease is the first condition suspected when a patient presents with pneumonitis during everolimus therapy. Pneumocystis pneumonia associated with everolimus therapy is rare, but our experience suggests that pneumocystis pneumonia should be considered as a differential diagnosis when pneumonitis is encountered in patients receiving everolimus therapy.

  13. Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: A multicenter retrospective cohort study.

    PubMed

    Fujimoto, Daichi; Yoshioka, Hiroshige; Kataoka, Yuki; Morimoto, Takeshi; Kim, Young Hak; Tomii, Keisuke; Ishida, Tadashi; Hirabayashi, Masataka; Hara, Satoshi; Ishitoko, Manabu; Fukuda, Yasushi; Hwang, Moon Hee; Sakai, Naoki; Fukui, Motonari; Nakaji, Hitoshi; Morita, Mitsunori; Mio, Tadashi; Yasuda, Takehiro; Sugita, Takakazu; Hirai, Toyohiro

    2018-05-01

    Nivolumab has been shown to be effective and safe in previously treated patients with advanced non-small cell lung cancer (NSCLC). However, little is known regarding its performance in real-world (i.e., non-trial) settings. Furthermore, nivolumab efficacy is unknown in patients who are ineligible for clinical trials or who are categorized into small subgroups in such trials. We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016. Of 613 patients included in our study, 141 had poor performance status (PS) and 106 were EGFR mutation - or ALK rearrangement-positive. The response and disease control rates were 20% and 44%, respectively; the estimated 1-year progression-free survival (PFS) was 18%. Multivariate analysis identified never smoking, poor PS, and EGFR mutation/ALK rearrangement as independent negative predictors of PFS. The most frequently reported grade ≥3 adverse event was pneumonitis (5% of patients). Severe pneumonitis (grade ≥3) occurred significantly earlier than mild pneumonitis (1.6 vs. 2.3 months, P = 0.031). Patients with pneumonitis achieved higher response rates and longer PFS than those without (37% vs. 18%, and 5.8 vs. 2.1 months, respectively; P = 0.002). Smoking status, PS, and EGFR mutation/ALK rearrangement were independent predictors of PFS. Our study elucidated nivolumab's efficacy in previously underreported patient populations; i.e., those with poor PS and/or with driver oncogenes. We also found that pneumonitis is not infrequent, and carries key implications for outcomes. These data should be useful for improving the clinical courses of nivolumab-treated patients with NSCLC. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Evaluation of protective potential of Yersinia pestis outer membrane protein antigens as possible candidates for a new-generation recombinant plague vaccine.

    PubMed

    Erova, Tatiana E; Rosenzweig, Jason A; Sha, Jian; Suarez, Giovanni; Sierra, Johanna C; Kirtley, Michelle L; van Lier, Christina J; Telepnev, Maxim V; Motin, Vladimir L; Chopra, Ashok K

    2013-02-01

    Plague caused by Yersinia pestis manifests itself in bubonic, septicemic, and pneumonic forms. Although the U.S. Food and Drug Administration recently approved levofloxacin, there is no approved human vaccine against plague. The capsular antigen F1 and the low-calcium-response V antigen (LcrV) of Y. pestis represent excellent vaccine candidates; however, the inability of the immune responses to F1 and LcrV to provide protection against Y. pestis F1(-) strains or those which harbor variants of LcrV is a significant concern. Here, we show that the passive transfer of hyperimmune sera from rats infected with the plague bacterium and rescued by levofloxacin protected naive animals against pneumonic plague. Furthermore, 10 to 12 protein bands from wild-type (WT) Y. pestis CO92 reacted with the aforementioned hyperimmune sera upon Western blot analysis. Based on mass spectrometric analysis, four of these proteins were identified as attachment invasion locus (Ail/OmpX), plasminogen-activating protease (Pla), outer membrane protein A (OmpA), and F1. The genes encoding these proteins were cloned, and the recombinant proteins purified from Escherichia coli for immunization purposes before challenging mice and rats with either the F1(-) mutant or WT CO92 in bubonic and pneumonic plague models. Although antibodies to Ail and OmpA protected mice against bubonic plague when challenged with the F1(-) CO92 strain, Pla antibodies were protective against pneumonic plague. In the rat model, antibodies to Ail provided protection only against pneumonic plague after WT CO92 challenge. Together, the addition of Y. pestis outer membrane proteins to a new-generation recombinant vaccine could provide protection against a wide variety of Y. pestis strains.

  15. Evaluation of Protective Potential of Yersinia pestis Outer Membrane Protein Antigens as Possible Candidates for a New-Generation Recombinant Plague Vaccine

    PubMed Central

    Erova, Tatiana E.; Rosenzweig, Jason A.; Sha, Jian; Suarez, Giovanni; Sierra, Johanna C.; Kirtley, Michelle L.; van Lier, Christina J.; Telepnev, Maxim V.; Motin, Vladimir L.

    2013-01-01

    Plague caused by Yersinia pestis manifests itself in bubonic, septicemic, and pneumonic forms. Although the U.S. Food and Drug Administration recently approved levofloxacin, there is no approved human vaccine against plague. The capsular antigen F1 and the low-calcium-response V antigen (LcrV) of Y. pestis represent excellent vaccine candidates; however, the inability of the immune responses to F1 and LcrV to provide protection against Y. pestis F1− strains or those which harbor variants of LcrV is a significant concern. Here, we show that the passive transfer of hyperimmune sera from rats infected with the plague bacterium and rescued by levofloxacin protected naive animals against pneumonic plague. Furthermore, 10 to 12 protein bands from wild-type (WT) Y. pestis CO92 reacted with the aforementioned hyperimmune sera upon Western blot analysis. Based on mass spectrometric analysis, four of these proteins were identified as attachment invasion locus (Ail/OmpX), plasminogen-activating protease (Pla), outer membrane protein A (OmpA), and F1. The genes encoding these proteins were cloned, and the recombinant proteins purified from Escherichia coli for immunization purposes before challenging mice and rats with either the F1− mutant or WT CO92 in bubonic and pneumonic plague models. Although antibodies to Ail and OmpA protected mice against bubonic plague when challenged with the F1− CO92 strain, Pla antibodies were protective against pneumonic plague. In the rat model, antibodies to Ail provided protection only against pneumonic plague after WT CO92 challenge. Together, the addition of Y. pestis outer membrane proteins to a new-generation recombinant vaccine could provide protection against a wide variety of Y. pestis strains. PMID:23239803

  16. Phase I Results of Vinorelbine With Concurrent Radiotherapy in Elderly Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer: West Japan Thoracic Oncology Group (WJTOG3005-DI)

    SciTech Connect

    Harada, Hideyuki, E-mail: h.harada@scchr.jp; Seto, Takashi; Igawa, Satoshi

    Purpose: To investigate the safety and efficacy of concurrent vinorelbine and thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients were 71 years of age or older with unresectable Stage III NSCLC. Patients were treated with thoracic radiotherapy (60 Gy) and concurrent vinorelbine (20 mg/m{sup 2} in Level 1 and 25 mg/m{sup 2} in Level 2) on Days 1 and 8 every 3 weeks for two cycles, followed by adjuvant vinorelbine (25 mg/m{sup 2}) on Days 1 and 8 every 3 weeks for two cycles. Results: Four patients were enrolled at Levelmore » 1. One patient experienced Grade 3 febrile neutropenia at Level 1 and the dose was escalated to Level 2. At Level 2, 2 of 6 patients experienced dose-limiting toxicities (Grade 4 neutropenia in 1 patient and Grade 3 infection in another). Three of 6 patients developed late Grade 2 or 3 pneumonitis. Therefore, the dose was de-escalated to Level 1. An additional 6 patients were enrolled at Level 1, 4 of whom experienced dose-limiting toxicities (incomplete radiotherapy because of Grade 2 pneumonitis in 1 patient and Grade 3 infection in 1, Grade 3 febrile neutropenia in 1, and Grade 3 esophagitis in 1). Moreover, late Grade 3 pneumothorax and Grade 5 pneumonitis occurred in 1 and 1 patient, respectively. Overall, Grade 2, 3 and 5 pneumonitis occurred in 3, 3, and 1 among 16 patients, respectively. Conclusions: Concurrent vinorelbine and thoracic radiotherapy resulted in a high incidence of severe pneumonitis when the standard dose of this agent was used for elderly patients. We therefore recommend caution in the use of this regimen and schedule for elderly patients.« less

  17. Targeting oxidant-dependent mechanisms for the treatment of respiratory diseases and their comorbidities.

    PubMed

    Thomson, Neil C

    2018-06-01

    Oxidative stress is implicated in the pathogenesis of respiratory diseases, such as COPD and its comorbidities, asthma, idiopathic pulmonary fibrosis and radiation pneumonitis. Antioxidants drugs, such as small molecule thiols, nuclear erythroid-2 related factor 2 activators and catalytic enzyme mimetics have been developed to target oxidant-dependent mechanisms. The therapeutic effects of antioxidants have been generally disappointing. A small number of antioxidants are approved for clinical use, such as the small molecule thiol N-acetyl-l-cysteine for chronic obstructive pulmonary disease, and in the United States, the superoxide dismutase mimetic AEOL 10150 for severe radiation pneumonitis. The future use of antioxidants for the treatment of chronic respiratory diseases may require a precision medicine approach to identify responsive patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Neutrophils are important in early control of lung infection by Yersinia pestis.

    PubMed

    Laws, Thomas R; Davey, Martin S; Titball, Richard W; Lukaszewski, Roman

    2010-04-01

    In this paper we evaluate the role of neutrophils in pneumonic plague. Splenic neutrophils from naïve BALB/c mice were found to reduce numbers of culturable Yersinia pestis strain GB in suspension. A murine, BALB/c, intranasal model of pneumonic plague was used in conjunction with in vivo neutrophil ablation, using the GR-1 antibody. This treatment reduced neutrophil numbers without affecting other leukocyte numbers. Neutrophil ablated mice exhibited increased bacterial colonisation of the lung 24h post infection. Furthermore, exposure of Y. pestis to human neutrophils resulted in a 5-fold reduction in the number of viable bacterial cells, whereas, PBMCs had no effect. Crown Copyright 2010. Published by Elsevier SAS. All rights reserved.

  19. Aspiration lung disorders in bovines: a case report and review.

    PubMed

    Shakespeare, Anthony S

    2012-11-01

    Lung aspiration disorders in bovines are invariably diagnosed as infectious aspiration pneumonias. There is a distinct differentiation between aspiration pneumonia and aspiration pneumonitis in humans that can be applied to bovines. The nature and quantity of the aspirate can result in differing pathogeneses which can require differing therapeutic approaches. Whilst blood gases were important in detecting and prognosticating lung problems, changes in barometric pressure with altitude have to be considered when interpreting partial pressures of oxygen. Anatomical differences in the lungs of bovines can explain why this species is more prone to certain pneumonic problems. Pulmonary physiotherapy is important in treating lung disorders in humans and should be considered as an adjunct therapy in bovine respiratory conditions. A case work-up was used to highlight some of the points discussed in this article.

  20. Mycobacterial Aerosols and Respiratory Disease

    PubMed Central

    2003-01-01

    Environmental opportunistic mycobacteria, including Mycobacterium avium, M. terrae, and the new species M. immunogenum, have been implicated in outbreaks of hypersensitivity pneumonitis or respiratory problems in a wide variety of settings. One common feature of the outbreaks has been exposure to aerosols. Aerosols have been generated from metalworking fluid during machining and grinding operations as well as from indoor swimming pools, hot tubs, and water-damaged buildings. Environmental opportunistic mycobacteria are present in drinking water, resistant to disinfection, able to provoke inflammatory reactions, and readily aerosolized. In all outbreaks, the water sources of the aerosols were disinfected. Disinfection may select for the predominance and growth of mycobacteria. Therefore, mycobacteria may be responsible, in part, for many outbreaks of hypersensitivity pneumonitis and other respiratory problems in the workplace and home. PMID:12890314

  1. Mycobacterial aerosols and respiratory disease.

    PubMed

    Falkinham, Joseph O

    2003-07-01

    Environmental opportunistic mycobacteria, including Mycobacterium avium, M. terrae, and the new species M. immunogenum, have been implicated in outbreaks of hypersensitivity pneumonitis or respiratory problems in a wide variety of settings. One common feature of the outbreaks has been exposure to aerosols. Aerosols have been generated from metalworking fluid during machining and grinding operations as well as from indoor swimming pools, hot tubs, and water-damaged buildings. Environmental opportunistic mycobacteria are present in drinking water, resistant to disinfection, able to provoke inflammatory reactions, and readily aerosolized. In all outbreaks, the water sources of the aerosols were disinfected. Disinfection may select for the predominance and growth of mycobacteria. Therefore, mycobacteria may be responsible, in part, for many outbreaks of hypersensitivity pneumonitis and other respiratory problems in the workplace and home.

  2. Legionnaires disease presenting as acute kidney injury in the absence of pneumonia.

    PubMed

    Yogarajah, Meera; Sivasambu, Bhradeev

    2015-02-17

    Legionnaires disease is a pneumonic illness with multisystem involvement. In 1987, Haines et al reported the only reported case of isolated renal disease of legionellosis without concurrent respiratory disease. A 62-year-old man presented with generalised weakness and malaise and watery diarrhoea, and was found to have acute kidney injury on admission. He was initially managed as acute gastroenteritis complicated with dehydration and acute kidney injury with intravenous hydration. Despite adequate hydration, his renal function was worsening day by day. Later in the course of his sickness he developed pneumonic illness and was diagnosed with Legionnaires disease after a positive urine antigen test. We are reporting the second case of Legionnaires disease presenting as an isolated acute kidney injury in the absence of respiratory symptoms on presentation. 2015 BMJ Publishing Group Ltd.

  3. [Bronchoalveolar carcinoma].

    PubMed

    Wislez, Marie; Cadranel, Jacques; Milleron, Bernard

    2003-04-01

    Bronchoalveolar carcinoma is one of the four histologic subtypes of adenocarcinoma and its incidence is increasing. It grows in a lepidic fashion along the alveolar septa without invasive growth. The lack of invasive growth is an essential criterion based on data indicating that patients may be curable by surgical resection. The revised definition seems to be suitable for its solitary nodular form but less for multifocal or pneumonic-type form. High-resolution lung CT-scan is necessary to evaluate pulmonary involvement because of the high frequency of multifocal disease at initial presentation and because of the presence of ground glass opacity that could be one of the first manifestation of cancer bronchiolo-alvéolaireon CT. Therapeutic management does not differ from the one of non small cell lung cancer. Solitary nodules are treated by surgical resection with a good prognosis while multifocal and/or pneumonic forms are treated by systemic chemotherapy with a worse prognosis.

  4. Bird fanciers lung in mushroom workers.

    PubMed

    Hayes, J; Barrett, M

    2015-04-01

    Hypersensitivity pneumonitis has been described in mushrooms workers caused by exposure to mushroom or fungal spores in the compost used to grow mushrooms. We describe two mushroom workers who developed hypersensitivity pneumonitis due to exposure to avian proteins found in poultry manure which was used in producing mushroom compost. Both workers were employed in the compost production area. Both presented with typical features of HP. Both workers had negative serological and precipitin studies to Apergillus fumigatus, Saccarhopolyspora rectivirgula and thermophilic actinomycetes but had positive responses to poultry antibodies. Neither was exposed to mushroom spores. Both workers required initial therapy with corticosteroids. Relocation with avoidance of further exposure resulted in complete cure in one worker and change in work practice with the use of personal protections equipment resulted in the second workerclinical stabilisation. These are the first reported cases of bird fanciers lung in mushroom workers.

  5. Current Epidemiologic Trends of the Nontuberculous Mycobacteria (NTM).

    PubMed

    Falkinham, Joseph O

    2016-06-01

    The nontuberculous mycobacteria (NTM) are waterborne opportunistic pathogens of humans. They are normal inhabitants of premise plumbing, found, for example, in household and hospital shower heads, water taps, aerators, and hot tubs. The hydrophobic NTM are readily aerosolized, and pulmonary infections and hypersensitivity pneumonitis have been traced to the presence of NTM in shower heads. Hypersensitivity pneumonitis in automotive workers was traced to the presence of NTM in metal recovery fluid used in grinding operations. Recently, NTM bacteremia in heart transplant patients has been traced to the presence of NTM in water reservoirs of instruments employed in operating rooms to heat and cool patient blood during periods of mechanical circulation. Although NTM are difficult to eradicate from premise plumbing as a consequence of their disinfectant-resistance and formation of biofilms, measures such as reduction of turbidity and reduction in carbon and nitrogen for growth and the installation of microbiological filters can reduce exposure of NTM to susceptible individuals.

  6. Atypical Presentations of Tularemia.

    PubMed

    Odegaard, Karah; Boersma, Beth; Keegan, James

    2017-05-01

    Francisella tularensis is a gram-negative coccobacillus that causes a condition commonly referred to as tularemia. There has been a dramatic increase in tularemia cases reported in South Dakota, many of which were challenging to diagnose due to atypical clinical manifestations. We describe an interesting case of pneumonic tularemia and summarize six similar cases, several of which presented with lung nodules suggestive of malignancy. According to the literature, this is only the third outbreak of pneumonic tularemia reported in the U.S. We believe it is important for clinicians to be aware of the increased incidence of tularemia in the area and to be vigilant in the diagnosis and management of these atypically presenting cases. Copyright© South Dakota State Medical Association.

  7. [Hydroxyurea-induced pneumonia].

    PubMed

    Girard, A; Ricordel, C; Poullot, E; Claeyssen, V; Decaux, O; Desrues, B; Delaval, P; Jouneau, S

    2014-05-01

    Hydroxyurea is an antimetabolite drug used in the treatment of myeloproliferative disorders. Common adverse effects include haematological, gastrointestinal cutaneous manifestations, and fever. Hydroxyurea-induced pneumonitis is unusual. A female patient was treated with hydroxyurea for polycythemia vera. She was admitted 20 days after commencing treatment with a high fever, productive cough, clear sputum and nausea. A chest CT-scan showed diffuse ground-glass opacities. Microbiological investigations were negative. The symptoms disappeared a few days after discontinuation of the drug and rechallenge led to a relapse of symptoms. Our case and 15 earlier cases of hydroxyurea-induced pneumonitis are reviewed. Two patterns of this disease may exist: an acute febrile form occurring within 1 month of introduction of hydroxyurea and a subacute form without fever. Even if uncommon, one should be aware of this complication of hydroxyurea. Copyright © 2013. Published by Elsevier Masson SAS.

  8. [A rich and blessed professional illness - organizing pneumonia due to gold dust].

    PubMed

    Ribeiro, P A; Girão, F; Henriques, P

    2011-01-01

    A 47-year-old man, restorer of religious art, presents a three week history of asthenia, myalgia, dry cough and fever, coinciding with recent, unprotected exposure, to golden dust. He had fever, crackles in lung bases, hypoxemia and elevation of inflammatory markers. Imaging studies showed areas of parenchymal consolidation with air bronchograms in posterior-basal regions of both lungs, suggesting a pneumonic process. Lung function tests: mild restrictive pattern. Bronchoalveolar lavage: lymphocytosis with low CD4/CD8 ratio. Lung biopsy: intraalveolar pneumonia with exsudative process and organization. Treatment with Prednisolone 40mg id was started with excellent response. First month follow-up CT scan showed areas of ground glass suggesting residual pneumonitis, and he resumed normal activities with excellent exercise tolerance, under appropriate protection measures. Copyright © 2010 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  9. Pneumonia in the tropics: Report from the Task Force on tropical diseases by the World Federation of Societies of Intensive and Critical Care Medicine.

    PubMed

    Nor, Mohd Basri Mat; Richards, Guy A; McGloughlin, Steve; Amin, Pravin R

    2017-12-01

    The aetiology of community acquired pneumonia varies according to the region in which it is acquired. This review discusses those causes of CAP that occur in the tropics and might not be readily recognizable when transplanted to other sites. Various forms of pneumonia including the viral causes such as influenza (seasonal and avian varieties), the coronaviruses and the Hantavirus as well as bacterial causes, specifically the pneumonic form of Yersinia pestis and melioidosis are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Inactivation of Viruses by Benzalkonium Chloride

    PubMed Central

    Armstrong, J. A.; Froelich, E. J.

    1964-01-01

    Benzalkonium chloride (as Roccal or Zephiran) was found to inactivate influenza, measles, canine distemper, rabies, fowl laryngotracheitis, vaccinia, Semliki Forest, feline pneumonitis, meningopneumonitis, and herpes simplex viruses after 10 min of exposure at 30 C or at room temperature. Poliovirus and encephalomyocarditis virus were not inactivated under the same conditions. It was concluded that all viruses tested were sensitive except members of the picorna group. The literature was reviewed. PMID:4288740

  11. Decision analytic modeling for the economic analysis of proton radiotherapy for non-small cell lung cancer

    PubMed Central

    Richard, Patrick J.; Zeng, Jing; Apisarnthanarax, Smith; Rengan, Ramesh; Phillips, Mark H.

    2018-01-01

    Background Although proton radiation treatments are more costly than photon/X-ray therapy, they may lower overall treatment costs through reducing rates of severe toxicities and the costly management of those toxicities. To study this issue, we created a decision-model comparing proton vs. X-ray radiotherapy for locally advanced non-small cell lung cancer patients. Methods An influence diagram was created to model for radiation delivery, associated 6-month pneumonitis/esophagitis rates, and overall costs (radiation plus toxicity costs). Pneumonitis (age, chemo type, V20, MLD) and esophagitis (V60) predictors were modeled to impact toxicity rates. We performed toxicity-adjusted, rate-adjusted, risk group-adjusted, and radiosensitivity analyses. Results Upfront proton treatment costs exceeded that of photons [$16,730.37 (3DCRT), $23,893.83 (IMRT), $41,061.80 (protons)]. Based upon expected population pneumonitis and esophagitis rates for each modality, protons would be expected to recover $1,065.62 and $1,139.63 of the cost difference compared to 3DCRT or IMRT. For patients treated with IMRT experiencing grade 4 pneumonitis or grade 4 esophagitis, costs exceeded patients treated with protons without this toxicity. 3DCRT patients with grade 4 esophagitis had higher costs than proton patients without this toxicity. For the risk group analysis, high risk patients (age >65, carboplatin/paclitaxel) benefited more from proton therapy. A biomarker may allow patient selection for proton therapy, although the AUC alone is not sufficient to determine if the biomarker is clinically useful. Conclusions The comparison between proton and photon/X-ray radiation therapy for NSCLC needs to consider both the up-front cost of treatment and the possible long term cost of complications. In our analysis, current costs favor X-ray therapy. However, relatively small reductions in the cost of proton therapy may result in a shift to the preference for proton therapy.

  12. Critical Factors for Parameterisation of Disease Diagnosis Modelling for Anthrax, Plague and Smallpox

    DTIC Science & Technology

    2012-09-01

    infectious mononucleosis , cat-scratch fever, and other cause of acute lymphadenopathy. The primary pneumonic form cannot be easily distinguished from...of an infectious disease. The major objective of this review is to describe the epidemiological and clinical parameters for three biological agents...means of detecting dangerous epidemic outbreaks [1]. There are different approaches to track the propagation of an infectious disease. Information

  13. Endoarterial pulmonary metastasis of malignant trophoblast associated with a term intrauterine pregnancy.

    PubMed

    Carlson, J A; Day, T G; Kuhns, J G; Howell, R S; Masterson, B J

    1984-02-01

    A previously healthy gravida 4, para 3, developed preclampsia and progressive dyspnea at the 37th gestational week and had bilateral pulmonary infiltrates on chest roentgenogram. She delivered a healthy, term, male infant with a normal appearing placenta. Postpartum, her respiratory status gradually worsened. A lung biopsy on the 20th postpartum day revealed intravascular trophoblasts, diffuse arteriolar thrombosis with pulmonary infarction, and subacute interstitial pneumonitis. Combination chemotherapy was instituted, but the patient died from respiratory insufficiency.

  14. Preliminary assessment of the oral toxicity of 1,5-diazido-3-nitrazapentane, 2- and 6-week feeding study, male and female rats. Final report

    SciTech Connect

    Haight, E.A.; Harvey, J.G.; Bell, P.A.

    1993-02-01

    A 2 and 6 week gavage feeding of DANPE caused testicular hypospermatogenesis in male rats and pneumonitis in female rats. A NOAEL was not achieved in male rats but was achieved in female rats at the 56.00 mg/kg/day dose level.... 1,5-Diazido-3-Nitrazapentane (DANPE), Gavage, Testicular hypospermatogenesis, Insterstitual Inflammation No-observed-Adverse-Effect-Level(NOAEL), Feeding study.

  15. Future Deployable Medical Capabilities and Platforms for Navy Medicine

    DTIC Science & Technology

    2002-02-01

    allow isolation of infectious patients from those patients and medical providers who are not infected (e.g., smallpox and pneumonic plague). 20...large need for respiratory support for victims that survive will be great, and they will need this sup- port for months. Surviving patients will not...Transmit Incubation Duration of Vaccine Disease to man Infective dose period illness Lethality Persistence available? Inhala- No 8,000-50,000 1-6

  16. Assessment of Geographical Variation in the Respiratory Toxicity of Desert Dust Particles

    DTIC Science & Technology

    2013-01-01

    following inhalation of fine Saudi dust and pigeon droppings (Korenyi-Both et al., 1992, 1997). Sporadic cases of severe acute eosinophilic pneumonitis with...have not been completed. The overarching goal of this project is to further characterize the relative hazard associated with exposure to soluble...overall objective of this study was to evaluate the pulmonary hazard potential of different sand particles of relevance to US military personnel. Our

  17. [Acquired hypogammaglobulinemia associated with thymoma: Good syndrome].

    PubMed

    Aouadi, Samira; Ghrairi, Najla; Braham, Emna; Kaabi, Manel; Maâlej, Sonia; Elgharbi, Leila Douik

    2017-01-01

    Good syndrome (GS) is defined as the association between thymoma and immune deficiency. It is often complicated by broncho-pulmonary bacterial infections and rhinosinusitis. This disease accounts for only 5% of all parathymic syndromes. These recurrent respiratory infections can cause bronchiectasis associated with Good syndrome. We report the case of a 52-year old woman hospitalized for non resolutive infectious pneumonitis. Chest CT scan showed bronchiectasis associated with thymoma confirmed by biopsy. The discovery of hypogammaglobulinemia allowed the diagnosis of Good syndrome.

  18. Review of Chemical, Biological, Radiological, and Nuclear (CBRN) Terminology in Technical Guide 316 (TG 316) and Allied Medical Publication 8(C) (AMedP-8(C))

    DTIC Science & Technology

    2013-05-01

    tularensis causing pneumonic tularemia (Aberdeen Proving Ground, MD: USAPHC, January 2012); USAPHC, Technical Guide 316 Supplement F1; USAPHC, Technical...Phase I preliminary BMEGs are completed for anthrax, plague, tularemia , ricin, and Staphylococcal Enterotoxin B (SEB). The Phase II process has been...Exposure to Specified Biological Agents: Brucellosis, Glanders, Q Fever, SEB and Tularemia , IDA Document D-4132 (Alexandria, VA: Institute for Defense

  19. Community-acquired Legionella micdadei (Pittsburgh pneumonia agent) infection in Sweden.

    PubMed

    Bäck, E; Schvarcz, R; Kallings, I

    1983-01-01

    The first case of Legionella micdadei (Pittsburgh Pneumonia Agent) infection in Sweden is presented. A previously healthy 68-yr-old man fell ill with diarrhoea, fever, and mental confusion. Subsequently chest roentgenography revealed pneumonic infiltrates and a seroconversion to L. micdadei was shown. No source or transmission of infection was established. The only notable event was that the patient had been drinking rain-water from a barrel 1 day prior to his illness. An alimentary route of infection was considered.

  20. Effects of Climate Change on Volcanic Emissions and Health Security in Hawaii by 2050

    DTIC Science & Technology

    2017-08-01

    pulmonary edema (fluid in the lungs), and acute respiratory distress syndrome (ARDS) (Weinstein et al 2013). Acute symptoms increase as SO2 levels and/or...vulnerable populations (Longo et al 2010). At high concentrations, the acute systemic effects of SO2 include: upper airway irritation, pneumonitis...Hydrogen sulfide (H2S) causes cough, shortness of breath and pulmonary edema. At high frequency inhalation, the acute systemic effects of fluoride

  1. International Conference on Natural Orifice Transluminal Endoscopic Surgery (NOTES)

    DTIC Science & Technology

    2006-06-01

    causing evisceration. At exploration, a pancreatic stump leak also was noted. Drains were placed, and the patient was placed on total parenteral nutrition ...Department of Surgery. St. Joseph Clinic. Liege, Belgium Hospital Dr. Peset Aleixandre. Valencia. Spain 4 Clinica de Merida. Merida. Yucatan ...pneumonitis (n = 3), and parenteral nutrition (n = 1). There was conversion to laparotomy for 28 patients (2.7%), and surgical time ranged from 32 to 132

  2. Immunology and Pathology of Arena Virus Infections.

    DTIC Science & Technology

    1992-04-15

    histopathologic findings; hepatic inflammation, steatosis , lymph node sinus histiocytosis, pneumonitis etc., appeared to be distributed evenly among the two...administration (Tracey, 1988). TNF has been shown to induce hepatic lipogenesis (Feingold, 1987), correlating with the impressive histologic fatty change seen...D. (1990) Lassa Fever. Br. J. Hosp. Med. 43: 186-191. Feingold, K.R., and C. Grunfeld. (1987) Tumor Necrosis Factor Alpha stimulates hepatic

  3. Complications of varicella zoster.

    PubMed

    Gücüyener, Kivilcim; Citak, Elvan Cağlar; Elli, Murat; Serdaroğlu, Ayse; Citak, Funda Erkasar

    2002-02-01

    Primary infection with varicella zoster is characterzed by a generalized vesicular rash usually without significant systemic illness. Encephalitis, pneumonitis, pancreatitis, nephritis, Reye and Guillan-Barre syndrome transvers myelitis, myocarditis have been reported before, but there is not any case having all these system to be involved during the same infection in a sequential manner ending up with multiorgan failure. We wanted to represent 21-month-old boy had a multiorgan failure due to varicella zoster infection.

  4. Drug Reaction with Eosinophilia and Systemic Symptom in a Patient with Pneumonia and Hyperthyroidism.

    PubMed

    Jin, Hualiang; Wang, Limin; Ye, Jian

    2017-01-01

    Drug rash with eosinophilia and systemic symptoms syndrome is an idiosyncratic drug reaction characterized by fever, skin eruption, lymph node enlargement, and internal organ involvement. We report a case of a patient with pneumonia who developed clinical manifestations of fever, rash, lymphadenopathy, hypereosinophilia, and visceral involvement (renal failure and eosinophilic pneumonitis) caused by methimazole. The patient improved remarkably with drug withdrawal. A high index of clinical suspicion is emphasized to facilitate prompt diagnosis of medication-related adverse effect and its discontinuation.

  5. Broad T Cell Immunity to the LcrV Virulence Protein is Induced by Targeted Delivery to DEC-205/CD205-Positive Mouse Dendritic Cells

    DTIC Science & Technology

    2007-08-13

    to its potential use as a biological weapon [1, 2]. Bubonic plague is the most common clinical form of disease and is characterized by swollen lymph...naive mice. Prior plague vaccines, such as killed whole-cell vaccine and attenuated vaccine, induce protection against bubonic plague , but the...R. W. and Williamson, E. D., Vaccination against bubonic and pneumonic plague . Vaccine 2001. 19: 4175–4184. 5 Du, Y., Rosqvist, R. and Forsberg, A

  6. Enzootic Plague Reduces Black-Footed Ferret (Mustela nigripes) Survival in Montana

    DTIC Science & Technology

    2010-01-01

    al. Design and testing for a non-tagged F1-V fusion protein as vaccine antigen against bubonic and pneumonic plague . Biotechnol Prog 2005; 21:1490–1510...Enzootic Plague Reduces Black-Footed Ferret (Mustela nigripes) Survival in Montana Marc R. Matchett,1 Dean E. Biggins,2 Valerie Carlson,3,* Bradford...and prey. Epizootic plague kills both prairie dogs and ferrets and is a major factor limiting recovery of the highly endangered ferret. In addition to

  7. Intraluminal fibrosis in interstitial lung disorders.

    PubMed Central

    Basset, F.; Ferrans, V. J.; Soler, P.; Takemura, T.; Fukuda, Y.; Crystal, R. G.

    1986-01-01

    The histopathologic and ultrastructural features of intraluminal organizing and fibrotic changes were studied in open lung biopsies and autopsy specimens from 373 patients with interstitial lung disorders, including hypersensitivity pneumonitis (n = 44), idiopathic pulmonary fibrosis (n = 92), collagen-vascular diseases (n = 20), chronic eosinophilic pneumonia (n = 10), pulmonary histiocytosis X (n-90), pulmonary sarcoidosis (n = 62), pneumoconioses (n = 25), Legionnaire's disease (n = 5), drug- and toxin-induced pneumonitis (n = 4), radiation-induced pneumonitis (n = 2), lymphangioleiomyomatosis (n = 11), and chronic organizing pneumonia of unknown cause (n = 8). Three patterns of intraluminal organization and fibrosis were recognized: 1) intraluminal buds, which partially filled the alveoli, alveolar ducts and/or distal bronchioles; 2) obliterative changes, in which loose connective tissue masses obliterated the lumens of alveoli, alveolar ducts or distal bronchioles, and 3) mural incorporation of previously intraluminal connective tissue masses, which fused with alveolar, alveolar ductal, or bronchiolar structures and frequently became reepithelialized. All three patterns had common morphologic features, suggesting that, regardless of their severity, they resulted from a common pathogenetic mechanism, ie, the migration of activated connective tissue cells, through defects in the epithelial lining and its basement membrane, from the interstitial into the intraluminal compartment. Intraluminal buds were observed most frequently in hypersensitivity pneumonitis, chronic eosinophilic pneumonia, and organizing pneumonia of unknown cause. Mural incorporation and, to a lesser extent, obliterative changes were observed in most interstitial disorders and were very prominent in idiopathic pulmonary fibrosis. Mural incorporation and obliterative changes play an important role in pulmonary remodeling, especially when several adjacent alveoli and/or other air spaces are

  8. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    DTIC Science & Technology

    2012-09-01

    diarrhea and interstitial lung disease/pneumonitis. From largest to smallest, our multiple dose (1,250 mg q24 h) model-predicted ratios of lapatinib...1977) A model for the kinetics of distribution of actinomycin-D in the beagle dog . J Pharmacol Exp Ther 200(3):469–478 31. Collins JM, Dedrick RL, King...a single agent for various tumor types (n = 2045), nausea (39%), diarrhea (39%) and vomiting (22%) were observed; other gastrointestinal events

  9. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    DTIC Science & Technology

    2013-03-01

    diarrhea and interstitial lung disease/pneumonitis. From largest to smallest, our multiple dose (1,250 mg q24 h) model-predicted ratios of lapatinib...1977) A model for the kinetics of distribution of actinomycin-D in the beagle dog . J Pharmacol Exp Ther 200(3):469–478 31. Collins JM, Dedrick RL, King...as a single agent for various tumor types (n = 2045), nausea (39%), diarrhea (39%) and vomiting (22%) were observed; other gastrointestinal events

  10. The Role of Transition Metal Transporters for Iron, Zinc, Manganese, and Copper in the Pathogenesis of Yersinia pestis

    PubMed Central

    Perry, Robert D.; Bobrov, Alexander G.; Fetherston, Jacqueline D.

    2015-01-01

    Yersinia pestis, the causative agent of bubonic, septicemic and pneumonic plague, encodes a multitude of Fe transport systems. Some of these are defective due to frameshift or IS element insertions, while others are functional in vitro but have no established role in causing infections. Indeed only 3 Fe transporters (Ybt, Yfe and Feo) have been shown to be important in at least one form of plague. The yersiniabactin (Ybt) system is essential in the early dermal/lymphatic stages of bubonic plague, irrelevant in the septicemic stage, and critical in pneumonic plague. Two Mn transporters have been characterized (Yfe and MntH). These two systems play a role in bubonic plague but the double yfe mntH mutant is fully virulent in a mouse model of pneumonic plague. The same in vivo phenotype occurs with a mutant lacking two (Yfe and Feo) of four ferrous transporters. A role for the Ybt siderophore in Zn acquisition has been revealed. Ybt-dependent Zn acquisition uses a transport system completely independent of the Fe-Ybt uptake system. Together Ybt components and ZnuABC play a critical role in Zn acquisition in vivo. Single mutants in either system retain high virulence in a mouse model of septicemic plague while the double mutant is completely avirulent. PMID:25891079

  11. Adaptive radiotherapy of lung cancer patients with pleural effusion or atelectasis.

    PubMed

    Møller, Ditte Sloth; Khalil, Azza Ahmed; Knap, Marianne Marquard; Hoffmann, Lone

    2014-03-01

    Changes in lung density due to atelectasis, pleural effusion and pneumonia/pneumonitis are observed in lung cancer patients. These changes may be an indication for adaptive radiotherapy in order to maintain target coverage and avoid increased risk of normal tissue complications. CBCT scans of 163 patients were reviewed to score lung changes and find the incidence, the impact of geometric and dosimetric changes and the timing of appearance and disappearance of changes. 23% of the patients had changes in the lung related to pleural effusion, atelectasis or pneumonia/pneumonitis. In 9% of all patients, the appearance or disappearance of a change introduced a shift of the tumor or lymph nodes relative to the spine >5mm. Only major density changes affected the dose distribution, and 9% of all patients needed adaptive treatment planning due to density changes. In total, 12% of all patients did benefit from an adaptive treatment plan and in 85% of these patients, an atelectasis did change. An adaptive strategy was indicated for 12% of the patients due to atelectasis, pleural effusion or pneumonia/pneumonitis. The predominant cause for adaptation was atelectasis. No systematic pattern in the appearance and disappearance of the changes were observed and hence weekly evaluation is preferable. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Pathology and polymerase chain reaction detection of ovine progressive pneumonia (maedi) cases in slaughtered sheep in India

    PubMed Central

    Singh, Rahul; Kumar, Pawan; Singh, Rajendra; Dhama, Kuldeep; Kumari, Swati; Yadav, Jay Prakash; Kashyap, Gayatri; Singh, Karam Pal; Singh, Vidya; Sahoo, Monalisa

    2017-01-01

    Aim: The small ruminant lentiviruses are known to cause maedi-visna (MV) and caprine arthritis - encephalitis in sheep and goats, typically affecting joints, udder, lungs, and the central nervous system. The diagnosis usually involves serology, clinical signs, immunohistochemistry, and polymerase chain reaction (PCR). In the present study, the histopathologically positive pneumonia cases of MV were confirmed by PCR in lung tissue probably for the first time in India. Materials and Methods: A total of 888 lungs of adult sheep, aged between 2 and 5 years, were screened during slaughter, of which 121 were found to have pneumonic lesions. The tissues from each pneumonic lung including associated lymph nodes were collected in 10% neutral buffered formalin for histopathology. The frozen tissues of the same were also collected and stored at −20°C for PCR confirmation. Results: Three of 121 cases of pneumonic lungs of sheep revealed gross and histopathological lesions suggestive of maedi or ovine progressive pneumonia infection. These 3 cases were further confirmed by PCR technique that amplified 291-base pair DNA in the long terminal repeat sequence of MV provirus. Conclusion: This study suggests the low occurrence of MV virus (MVV) infection in India in naturally affected sheep based on pathomorphological lesions and using the molecular tool of PCR detection of the virus in tissues. Further, a combination of pathomorphology or/and PCR testing might be optimal for detecting the animals infected with MVV. PMID:29263606

  13. Icotinib combined with rapamycin in a renal transplant recipient with epidermal growth factor receptor-mutated non-small cell lung cancer: A case report.

    PubMed

    Zhao, Qiong; Wang, Yina; Tang, Yemin; Peng, Ling

    2014-01-01

    As kidney transplant recipients are at increased risk of developing cancer, regular monitoring should be undertaken to monitor the balance between immunosuppression and graft function and to identify malignancy. The present study reports the outcome of the treatment of adenocarcinoma of the lung (T1aN0M1a, stage IV) using the molecular-targeted therapy, icotinib, in a 66-year-old male renal transplant patient receiving rapamycin and prednisolone as ongoing renal immunosuppressive therapy. An initial partial response to icotinib was achieved, and graft function remained good. However, the patient subsequently developed interstitial pneumonitis. The plasma concentrations of rapamycin and icotinib were within the normal ranges, which excluded the possibility of a pharmacokinetic drug interaction and indicated that the interstitial pneumonitis was likely to be associated with the side-effects of icotinib. Drug therapy was discontinued and the patient underwent a segmentectomy. Tacrolimus was administered for ongoing renal graft immunosuppression. To the best of our knowledge, this is the first report of the concomitant administration of icotinib and rapamycin in post-transplant de novo lung cancer. It is also the first report of interstitial pneumonitis associated with icotinib in a post-transplant patient.

  14. Using the numerical method in 1836, James Jackson bridged French therapeutic epistemology and American medical pragmatism.

    PubMed

    Kahn, Linda G; Morabia, Alfredo

    2015-04-01

    To review James Jackson's analysis of bloodletting among pneumonitis patients at the newly founded Massachusetts General Hospital, in which he implemented the numerical method advocated by Pierre-Charles-Alexandre Louis. The study sample included 34 cases of clinically diagnosed pneumonitis admitted to Massachusetts General Hospital between April 19, 1825, and May 10, 1835, and discharged alive. Patient data were extracted from meticulously kept case books. Jackson calculated mean number of venesections, ounces of blood taken, and days of convalescence within groups stratified by day of the disease when first bloodletting occurred. He also calculated average convalescence within groups stratified by age, sex, prior health, vesication, and day of the disease when the patients were admitted to the hospital. To Jackson's surprise, it "seemed to be of less importance, whether our patients were bled or not, than whether they entered the hospital early or late" after the onset of the pneumonitis. Bloodletting was ineffective. Our multivariate reanalysis of his data confirms his conclusion. Outstandingly for his time, Jackson ruled out unwarranted effects of covariates by tabulating their numerical relations to the duration of pneumonia. Using novel gathering of patient clinical data from hospital records and quantitative analytical methods, Jackson contributed results that challenged conventional wisdom and bridged French therapeutic epistemology and American medical pragmatism. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. The role of transition metal transporters for iron, zinc, manganese, and copper in the pathogenesis of Yersinia pestis.

    PubMed

    Perry, Robert D; Bobrov, Alexander G; Fetherston, Jacqueline D

    2015-06-01

    Yersinia pestis, the causative agent of bubonic, septicemic and pneumonic plague, encodes a multitude of Fe transport systems. Some of these are defective due to frameshift or IS element insertions, while others are functional in vitro but have no established role in causing infections. Indeed only 3 Fe transporters (Ybt, Yfe and Feo) have been shown to be important in at least one form of plague. The yersiniabactin (Ybt) system is essential in the early dermal/lymphatic stages of bubonic plague, irrelevant in the septicemic stage, and critical in pneumonic plague. Two Mn transporters have been characterized (Yfe and MntH). These two systems play a role in bubonic plague but the double yfe mntH mutant is fully virulent in a mouse model of pneumonic plague. The same in vivo phenotype occurs with a mutant lacking two (Yfe and Feo) of four ferrous transporters. A role for the Ybt siderophore in Zn acquisition has been revealed. Ybt-dependent Zn acquisition uses a transport system completely independent of the Fe-Ybt uptake system. Together Ybt components and ZnuABC play a critical role in Zn acquisition in vivo. Single mutants in either system retain high virulence in a mouse model of septicemic plague while the double mutant is completely avirulent.

  16. Surgical Management of Complicated Necrotizing Pneumonia in Children.

    PubMed

    Lai, Jin-Yao; Yang, Wendy; Ming, Yung-Ching

    2017-08-01

    There are no well-established indications for the surgical management of acute necrotizing pneumonitis in children. This study presents our experience regarding this challenging topic. Between 2002 and 2009, 56 necrotizing pneumonitis patients with empyema were treated surgically. The outcomes were analyzed retrospectively. Computed tomography findings of massive lung necrosis or large cavities involving more than 50% of the involved lobe were deemed to be complicated necrotizing pneumonitis. Patients without the above indications were considered uncomplicated. Thirty-one cases were uncomplicated and 25 were complicated. Operative procedures included 38 decortications (31 uncomplicated and seven complicated), 14 wedge resections, and four lobectomies (complicated only). Preoperatively, patients with complicated necrotizing pneumonia had a higher incidence of pneumothorax (32% vs. 14.3%; p = 0.001), endotracheal intubation (44% vs. 9.7%; p = 0.008), and hemolytic uremic syndrome (20% vs. 3.2%; p = 0.01). These patients also had higher incidences of intraoperative transfusion (68% vs. 9.7%; p = 0.03), major postoperative complications (16% vs. 0%; p = 0.02), reoperations (16% vs. 0%; p = 0.02), and longer postoperative stay (19.8 ± 24.2 days vs. 11.2 ± 5.8 days; p = 0.03). Four complicated patients, who initially had decortications and limited resections, underwent reoperations. Compared with uncomplicated patients, those who underwent decortications and wedge resection required longer postoperative stays (23.6 ± 9.9 days, p < 0.01 and 21.1 ± 30.7 days, p = 0.04, respectively), whereas patients who had lobectomy had a similar duration of recovery (9.0 ± 2.1 days, p = 0.23). All patients improved significantly at follow-up. Children with complicated necrotizing pneumonitis have more preoperative morbidities, more major postoperative complications, and require longer postoperative stays. Aggressive surgical treatment results in

  17. High-Throughput, Signature-Tagged Mutagenic Approach To Identify Novel Virulence Factors of Yersinia pestis CO92 in a Mouse Model of Infection

    PubMed Central

    Ponnusamy, Duraisamy; Fitts, Eric C.; Erova, Tatiana E.; Kozlova, Elena V.; Kirtley, Michelle L.; Tiner, Bethany L.; Andersson, Jourdan A.

    2015-01-01

    The identification of new virulence factors in Yersinia pestis and understanding their molecular mechanisms during an infection process are necessary in designing a better vaccine or to formulate an appropriate therapeutic intervention. By using a high-throughput, signature-tagged mutagenic approach, we created 5,088 mutants of Y. pestis strain CO92 and screened them in a mouse model of pneumonic plague at a dose equivalent to 5 50% lethal doses (LD50) of wild-type (WT) CO92. From this screen, we obtained 118 clones showing impairment in disseminating to the spleen, based on hybridization of input versus output DNA from mutant pools with 53 unique signature tags. In the subsequent screen, 20/118 mutants exhibited attenuation at 8 LD50 when tested in a mouse model of bubonic plague, with infection by 10/20 of the aforementioned mutants resulting in 40% or higher survival rates at an infectious dose of 40 LD50. Upon sequencing, six of the attenuated mutants were found to carry interruptions in genes encoding hypothetical proteins or proteins with putative functions. Mutants with in-frame deletion mutations of two of the genes identified from the screen, namely, rbsA, which codes for a putative sugar transport system ATP-binding protein, and vasK, a component of the type VI secretion system, were also found to exhibit some attenuation at 11 or 12 LD50 in a mouse model of pneumonic plague. Likewise, among the remaining 18 signature-tagged mutants, 9 were also attenuated (40 to 100%) at 12 LD50 in a pneumonic plague mouse model. Previously, we found that deleting genes encoding Braun lipoprotein (Lpp) and acyltransferase (MsbB), the latter of which modifies lipopolysaccharide function, reduced the virulence of Y. pestis CO92 in mouse models of bubonic and pneumonic plague. Deletion of rbsA and vasK genes from either the Δlpp single or the Δlpp ΔmsbB double mutant augmented the attenuation to provide 90 to 100% survivability to mice in a pneumonic plague model at 20

  18. High-throughput, signature-tagged mutagenic approach to identify novel virulence factors of Yersinia pestis CO92 in a mouse model of infection.

    PubMed

    Ponnusamy, Duraisamy; Fitts, Eric C; Sha, Jian; Erova, Tatiana E; Kozlova, Elena V; Kirtley, Michelle L; Tiner, Bethany L; Andersson, Jourdan A; Chopra, Ashok K

    2015-05-01

    The identification of new virulence factors in Yersinia pestis and understanding their molecular mechanisms during an infection process are necessary in designing a better vaccine or to formulate an appropriate therapeutic intervention. By using a high-throughput, signature-tagged mutagenic approach, we created 5,088 mutants of Y. pestis strain CO92 and screened them in a mouse model of pneumonic plague at a dose equivalent to 5 50% lethal doses (LD50) of wild-type (WT) CO92. From this screen, we obtained 118 clones showing impairment in disseminating to the spleen, based on hybridization of input versus output DNA from mutant pools with 53 unique signature tags. In the subsequent screen, 20/118 mutants exhibited attenuation at 8 LD50 when tested in a mouse model of bubonic plague, with infection by 10/20 of the aforementioned mutants resulting in 40% or higher survival rates at an infectious dose of 40 LD50. Upon sequencing, six of the attenuated mutants were found to carry interruptions in genes encoding hypothetical proteins or proteins with putative functions. Mutants with in-frame deletion mutations of two of the genes identified from the screen, namely, rbsA, which codes for a putative sugar transport system ATP-binding protein, and vasK, a component of the type VI secretion system, were also found to exhibit some attenuation at 11 or 12 LD50 in a mouse model of pneumonic plague. Likewise, among the remaining 18 signature-tagged mutants, 9 were also attenuated (40 to 100%) at 12 LD50 in a pneumonic plague mouse model. Previously, we found that deleting genes encoding Braun lipoprotein (Lpp) and acyltransferase (MsbB), the latter of which modifies lipopolysaccharide function, reduced the virulence of Y. pestis CO92 in mouse models of bubonic and pneumonic plague. Deletion of rbsA and vasK genes from either the Δlpp single or the Δlpp ΔmsbB double mutant augmented the attenuation to provide 90 to 100% survivability to mice in a pneumonic plague model at 20

  19. Proteolysis of plasminogen activator inhibitor-1 by Yersinia pestis remodulates the host environment to promote virulence.

    PubMed

    Eddy, J L; Schroeder, J A; Zimbler, D L; Caulfield, A J; Lathem, W W

    2016-09-01

    Essentials Effect of plasminogen activator inhibitor (PAI)-1 on plague and its Y. pestis cleavage is unknown. An intranasal mouse model of infection was used to determine the role of PAI-1 in pneumonic plague. PAI-1 is cleaved and inactivated by the Pla protease of Y. pestis in the lung airspace. PAI-1 impacts both bacterial outgrowth and the immune response to respiratory Y. pestis infection. Click to hear Dr Bock discuss pathogen activators of plasminogen. Background The hemostatic regulator plasminogen activator inhibitor-1 (PAI-1) inactivates endogenous plasminogen activators and aids in the immune response to bacterial infection. Yersinia pestis, the causative agent of plague, produces the Pla protease, a virulence factor that is required during plague. However, the specific hemostatic proteins cleaved by Pla in vivo that contribute to pathogenesis have not yet been fully elucidated. Objectives To determine whether PAI-1 is cleaved by the Pla protease during pneumonic plague, and to define the impact of PAI-1 on Y. pestis respiratory infection in the presence or absence of Pla. Methods An intranasal mouse model of pneumonic plague was used to assess the levels of total and active PAI-1 in the lung airspace, and the impact of PAI-1 deficiency on bacterial pathogenesis, the host immune response and plasmin generation following infection with wild-type or ∆pla Y. pestis. Results We found that Y. pestis cleaves and inactivates PAI-1 in the lungs in a Pla-dependent manner. The loss of PAI-1 enhances Y. pestis outgrowth in the absence of Pla, and is associated with increased conversion of plasminogen to plasmin. Furthermore, we found that PAI-1 regulates immune cell recruitment, cytokine production and tissue permeability during pneumonic plague. Conclusions Our data demonstrate that PAI-1 is an in vivo target of the Pla protease in the lungs, and that PAI-1 is a key regulator of the pulmonary innate immune response. We conclude that the inactivation of PAI-1 by Y

  20. Predicting radiotherapy outcomes using statistical learning techniques

    NASA Astrophysics Data System (ADS)

    El Naqa, Issam; Bradley, Jeffrey D.; Lindsay, Patricia E.; Hope, Andrew J.; Deasy, Joseph O.

    2009-09-01

    Radiotherapy outcomes are determined by complex interactions between treatment, anatomical and patient-related variables. A common obstacle to building maximally predictive outcome models for clinical practice is the failure to capture potential complexity of heterogeneous variable interactions and applicability beyond institutional data. We describe a statistical learning methodology that can automatically screen for nonlinear relations among prognostic variables and generalize to unseen data before. In this work, several types of linear and nonlinear kernels to generate interaction terms and approximate the treatment-response function are evaluated. Examples of institutional datasets of esophagitis, pneumonitis and xerostomia endpoints were used. Furthermore, an independent RTOG dataset was used for 'generalizabilty' validation. We formulated the discrimination between risk groups as a supervised learning problem. The distribution of patient groups was initially analyzed using principle components analysis (PCA) to uncover potential nonlinear behavior. The performance of the different methods was evaluated using bivariate correlations and actuarial analysis. Over-fitting was controlled via cross-validation resampling. Our results suggest that a modified support vector machine (SVM) kernel method provided superior performance on leave-one-out testing compared to logistic regression and neural networks in cases where the data exhibited nonlinear behavior on PCA. For instance, in prediction of esophagitis and pneumonitis endpoints, which exhibited nonlinear behavior on PCA, the method provided 21% and 60% improvements, respectively. Furthermore, evaluation on the independent pneumonitis RTOG dataset demonstrated good generalizabilty beyond institutional data in contrast with other models. This indicates that the prediction of treatment response can be improved by utilizing nonlinear kernel methods for discovering important nonlinear interactions among model

  1. Infection biomarkers in primary care patients with acute respiratory tract infections-comparison of Procalcitonin and C-reactive protein.

    PubMed

    Meili, Marc; Kutz, Alexander; Briel, Matthias; Christ-Crain, Mirjam; Bucher, Heiner C; Mueller, Beat; Schuetz, Philipp

    2016-03-24

    There is a lack of studies comparing the utility of C-reactive protein (CRP) with Procalcitonin (PCT) for the management of patients with acute respiratory tract infections (ARI) in primary care. Our aim was to study the correlation between these markers and to compare their predictive accuracy in regard to clinical outcome prediction. This is a secondary analysis using clinical and biomarker data of 458 primary care patients with pneumonic and non-pneumonic ARI. We used correlation statistics (spearman's rank test) and multivariable regression models to assess association of markers with adverse outcome, namely days with restricted activities and persistence of discomfort from infection at day 14. At baseline, CRP and PCT did not correlate well in the overall population (r(2) = 0.16) and particularly in the subgroup of patients with non-pneumonic ARI (r(2) = 0.08). Low correlation of biomarkers were also found when comparing cut-off ranges, day seven levels or changes from baseline to day seven. High baseline levels of CRP (>100 mg/dL, regression coefficient 1.6, 95 % CI 0.5 to 2.6, sociodemographic-adjusted model) as well as PCT (>0.5ug/L regression coefficient 2.0, 95 % CI 0.0 to 4.0, sociodemographic-adjusted model) were significantly associated with larger number of days with restricted activities. There were no associations of either biomarker with persistence of discomfort at day 14. CRP and PCT levels do not well correlate, but both have moderate prognostic accuracy in primary care patients with ARI to predict clinical outcomes. The low correlation between the two biomarkers calls for interventional research comparing these markers head to head in regard to their ability to guide antibiotic decisions. Current Controlled Trials, ISRCTN73182671.

  2. Cethromycin-mediated protection against the plague pathogen Yersinia pestis in a rat model of infection and comparison with levofloxacin.

    PubMed

    Rosenzweig, Jason A; Brackman, Sheri M; Kirtley, Michelle L; Sha, Jian; Erova, Tatiana E; Yeager, Linsey A; Peterson, Johnny W; Xu, Ze-Qi; Chopra, Ashok K

    2011-11-01

    The Gram-negative plague bacterium, Yersinia pestis, has historically been regarded as one of the deadliest pathogens known to mankind, having caused three major pandemics. After being transmitted by the bite of an infected flea arthropod vector, Y. pestis can cause three forms of human plague: bubonic, septicemic, and pneumonic, with the latter two having very high mortality rates. With increased threats of bioterrorism, it is likely that a multidrug-resistant Y. pestis strain would be employed, and, as such, conventional antibiotics typically used to treat Y. pestis (e.g., streptomycin, tetracycline, and gentamicin) would be ineffective. In this study, cethromycin (a ketolide antibiotic which inhibits bacterial protein synthesis and is currently in clinical trials for respiratory tract infections) was evaluated for antiplague activity in a rat model of pneumonic infection and compared with levofloxacin, which operates via inhibition of bacterial topoisomerase and DNA gyrase. Following a respiratory challenge of 24 to 30 times the 50% lethal dose of the highly virulent Y. pestis CO92 strain, 70 mg of cethromycin per kg of body weight (orally administered twice daily 24 h postinfection for a period of 7 days) provided complete protection to animals against mortality without any toxic effects. Further, no detectable plague bacilli were cultured from infected animals' blood and spleens following cethromycin treatment. The antibiotic was most effective when administered to rats 24 h postinfection, as the animals succumbed to infection if treatment was further delayed. All cethromycin-treated survivors tolerated 2 subsequent exposures to even higher lethal Y. pestis doses without further antibiotic treatment, which was related, in part, to the development of specific antibodies to the capsular and low-calcium-response V antigens of Y. pestis. These data demonstrate that cethromycin is a potent antiplague drug that can be used to treat pneumonic plague.

  3. Combating Multidrug-Resistant Pathogens with Host-Directed Nonantibiotic Therapeutics.

    PubMed

    Andersson, Jourdan A; Sha, Jian; Kirtley, Michelle L; Reyes, Emily; Fitts, Eric C; Dann, Sara M; Chopra, Ashok K

    2018-01-01

    Earlier, we reported that three Food and Drug Administration-approved drugs, trifluoperazine (TFP; an antipsychotic), amoxapine (AXPN; an antidepressant), and doxapram (DXP; a breathing stimulant), identified from an in vitro murine macrophage cytotoxicity screen, provided mice with 40 to 60% protection against pneumonic plague when administered at the time of infection for 1 to 3 days. In the present study, the therapeutic potential of these drugs against pneumonic plague in mice was further evaluated when they were administered at up to 48 h postinfection. While the efficacy of TFP was somewhat diminished as treatment was delayed to 24 h, the protection of mice with AXPN and DXP increased as treatment was progressively delayed to 24 h. At 48 h postinfection, these drugs provided the animals with significant protection (up to 100%) against challenge with the agent of pneumonic or bubonic plague when they were administered in combination with levofloxacin. Likewise, when they were used in combination with vancomycin, all three drugs provided mice with 80 to 100% protection from fatal oral Clostridium difficile infection when they were administered at 24 h postinfection. Furthermore, AXPN provided 40 to 60% protection against respiratory infection with Klebsiella pneumoniae when it was administered at the time of infection or at 24 h postinfection. Using the same in vitro cytotoxicity assay, we identified an additional 76/780 nonantibiotic drugs effective against K. pneumoniae For Acinetobacter baumannii , 121 nonantibiotic drugs were identified to inhibit bacterium-induced cytotoxicity in murine macrophages. Of these 121 drugs, 13 inhibited the macrophage cytotoxicity induced by two additional multiple-antibiotic-resistant strains. Six of these drugs decreased the intracellular survival of all three A. baumannii strains in macrophages. These results provided further evidence of the broad applicability and utilization of drug repurposing screening to identify new

  4. Sex steroid receptor expression in idiopathic pulmonary fibrosis.

    PubMed

    Mehrad, Mitra; Trejo Bittar, Humberto E; Yousem, Samuel A

    2017-08-01

    Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Pulmonary atelectasis and survival in advanced non-small cell lung carcinoma.

    PubMed

    Bulbul, Yilmaz; Eris, Bulent; Orem, Asim; Gulsoy, Ayhan; Oztuna, Funda; Ozlu, Tevfik; Ozsu, Savas

    2010-08-01

    Atelectasis was reported as a favorable prognostic sign of pulmonary carcinoma; however, the underlying mechanism in those patients is not known. In this study, we aimed to investigate prospectively the potential impact of atelectasis and/or obstructive pneumonitis (AO) on survival and the relation between atelectasis and some laboratory blood parameters. The study was conducted on 87 advanced stage non-small cell lung cancer (NSCLC) patients. Clinical and laboratory parameters of patients at first presentation were recorded, and patients were divided into two groups according to the presence of AO in thorax computed tomography (CT). Survival was calculated using Kaplan-Meier and univariate Cox's regression analyses. Laboratory parameters that might be related with prolonged survival in atelectasis were compared using chi-square, Student's t, and Mann-Whitney U tests. Of the patients, 54% had stage IV disease, and AO was detected in 48.3% of all cases. Overall median survival was 13.2 months for all cases, 10.9 months for patients without AO, and 13.9 months for patients with AO (P=0.067). Survival was significantly longer in stage III patients with AO (14.5 months versus 9.2 months, P=0.032), but not in stage IV patients. Patients with AO in stage III had significantly lower platelet counts (P=0.032) and blood sedimentation rates than did those with no AO (P=0.045). We concluded that atelectasis and/or obstructive pneumonitis was associated with prolonged survival in locally advanced NSCLC. There was also a clear association between atelectasis and/or obstructive pneumonitis and platelets and blood sedimentation rate.

  6. Pulmonary atelectasis and survival in advanced non-small cell lung carcinoma

    PubMed Central

    2010-01-01

    Atelectasis was reported as a favorable prognostic sign of pulmonary carcinoma; however, the underlying mechanism in those patients is not known. In this study, we aimed to investigate prospectively the potential impact of atelectasis and/or obstructive pneumonitis (AO) on survival and the relation between atelectasis and some laboratory blood parameters. The study was conducted on 87 advanced stage non-small cell lung cancer (NSCLC) patients. Clinical and laboratory parameters of patients at first presentation were recorded, and patients were divided into two groups according to the presence of AO in thorax computed tomography (CT). Survival was calculated using Kaplan-Meier and univariate Cox's regression analyses. Laboratory parameters that might be related with prolonged survival in atelectasis were compared using chi-square, Student's t, and Mann-Whitney U tests. Of the patients, 54% had stage IV disease, and AO was detected in 48.3% of all cases. Overall median survival was 13.2 months for all cases, 10.9 months for patients without AO, and 13.9 months for patients with AO (P = 0.067). Survival was significantly longer in stage III patients with AO (14.5 months versus 9.2 months, P = 0.032), but not in stage IV patients. Patients with AO in stage III had significantly lower platelet counts (P = 0.032) and blood sedimentation rates than did those with no AO (P = 0.045). We concluded that atelectasis and/or obstructive pneumonitis was associated with prolonged survival in locally advanced NSCLC. There was also a clear association between atelectasis and/or obstructive pneumonitis and platelets and blood sedimentation rate. PMID:20636252

  7. Lung damage following bone marrow transplantation. II. The contribution of cyclophosphamide

    SciTech Connect

    Varekamp, A.E.; de Vries, A.J.; Zurcher, C.

    1987-10-01

    The effect of high-dose cyclophosphamide (Cy), either alone or in combination with irradiation, upon the development of interstitial pneumonitis (IP) after bone marrow transplantation (BMT) was investigated in a Brown Norway rat model. The parameters that were examined included ventilation rate, mortality, and histopathology. No damage to the lungs was observed in rats given Cy alone in supralethal dosages plus BMT, and mortality resulted from severe aplasia of hemopoietic and lymphoid tissues with multifocal hemorrhages, secondary infections, and sepsis. Two separate periods of mortality were observed within the first 180 days following whole thorax irradiation with a high dose ratemore » (HDR; 0.8 Gy/min) or a low dose rate (LDR; 0.05 Gy/min). The addition of Cy prior to irradiation resulted in an increased mortality in the first period (before day 100) in all experimental groups. The influence of Cy on mortality at 180 days however, was different for the HDR and LDR experiments. The LD50-180 after HDR irradiation, dose range 8 to 18 Gy, was not significantly altered by the addition of Cy (100 mg/kg) 1 day prior to irradiation, whereas Cy (100 mg/kg) 1 day prior to LDR irradiation, dose range: 16 to 24 Gy, caused an enhancement of radiation damage with a decrease of the LD50-180 by 1.33 Gy. The dose modification factor (DMF) was 1.07. This enhancement was no longer significant after splitting up the dose of Cy in two dosages of 50 mg/kg given on 2 consecutive days prior to irradiation with a LDR. The extrapolation of the data in this rat model to available dose-response curves on IP after BMT and radiation pneumonitis in humans, implied that non-infectious IP is a radiation pneumonitis that is only slightly enhanced by Cy.« less

  8. Inactivation of Peroxiredoxin 6 by the Pla Protease of Yersinia pestis

    PubMed Central

    Zimbler, Daniel L.; Eddy, Justin L.; Schroeder, Jay A.

    2015-01-01

    Pneumonic plague represents the most severe form of disease caused by Yersinia pestis due to its ease of transmission, rapid progression, and high mortality rate. The Y. pestis outer membrane Pla protease is essential for the development of pneumonic plague; however, the complete repertoire of substrates cleaved by Pla in the lungs is not known. In this study, we describe a proteomic screen to identify host proteins contained within the bronchoalveolar lavage fluid of mice that are cleaved and/or processed by Y. pestis in a Pla-dependent manner. We identified peroxiredoxin 6 (Prdx6), a host factor that contributes to pulmonary surfactant metabolism and lung defense against oxidative stress, as a previously unknown substrate of Pla. Pla cleaves Prdx6 at three distinct sites, and these cleavages disrupt both the peroxidase and phospholipase A2 activities of Prdx6. In addition, we found that infection with wild-type Y. pestis reduces the abundance of extracellular Prdx6 in the lungs compared to that after infection with Δpla Y. pestis, suggesting that Pla cleaves Prdx6 in the pulmonary compartment. However, following infection with either wild-type or Δpla Y. pestis, Prdx6-deficient mice exhibit no differences in bacterial burden, host immune response, or lung damage from wild-type mice. Thus, while Pla is able to disrupt Prdx6 function in vitro and reduce Prdx6 levels in vivo, the cleavage of Prdx6 has little detectable impact on the progression or outcome of pneumonic plague. PMID:26553463

  9. Inactivation of Peroxiredoxin 6 by the Pla Protease of Yersinia pestis.

    PubMed

    Zimbler, Daniel L; Eddy, Justin L; Schroeder, Jay A; Lathem, Wyndham W

    2016-01-01

    Pneumonic plague represents the most severe form of disease caused by Yersinia pestis due to its ease of transmission, rapid progression, and high mortality rate. The Y. pestis outer membrane Pla protease is essential for the development of pneumonic plague; however, the complete repertoire of substrates cleaved by Pla in the lungs is not known. In this study, we describe a proteomic screen to identify host proteins contained within the bronchoalveolar lavage fluid of mice that are cleaved and/or processed by Y. pestis in a Pla-dependent manner. We identified peroxiredoxin 6 (Prdx6), a host factor that contributes to pulmonary surfactant metabolism and lung defense against oxidative stress, as a previously unknown substrate of Pla. Pla cleaves Prdx6 at three distinct sites, and these cleavages disrupt both the peroxidase and phospholipase A2 activities of Prdx6. In addition, we found that infection with wild-type Y. pestis reduces the abundance of extracellular Prdx6 in the lungs compared to that after infection with Δpla Y. pestis, suggesting that Pla cleaves Prdx6 in the pulmonary compartment. However, following infection with either wild-type or Δpla Y. pestis, Prdx6-deficient mice exhibit no differences in bacterial burden, host immune response, or lung damage from wild-type mice. Thus, while Pla is able to disrupt Prdx6 function in vitro and reduce Prdx6 levels in vivo, the cleavage of Prdx6 has little detectable impact on the progression or outcome of pneumonic plague. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Feasibility of radiotherapy after high-dose dense chemotherapy with epirubicin, preceded by dexrazoxane, and paclitaxel for patients with high-risk Stage II-III breast cancer

    SciTech Connect

    De Giorgi, Ugo; Giannini, Massimo; Department of Radiotherapy, Pierantoni Hospital, Forli

    Purpose: To verify the feasibility of, and quantify the risk of, pneumonitis from locoregional radiotherapy (RT) after high-dose dense chemotherapy with epirubicin and paclitaxel with peripheral blood progenitor cell support in patients with high-risk Stage II-III breast cancer. Methods and Materials: Treatment consisted of a mobilizing course of epirubicin 150 mg/m{sup 2}, preceded by dexrazoxane (Day 1), paclitaxel 175 mg/m{sup 2} (Day 2), and filgrastim; followed by three courses of epirubicin 150 mg/m{sup 2}, preceded by dexrazoxane (Day 1), paclitaxel 400 mg/m{sup 2} (Day 2), and peripheral blood progenitor cell support and filgrastim, every 16-19 days. After chemotherapy, patients weremore » treated with locoregional RT, which included the whole breast or the chest wall, axilla, and supraclavicular area. Results: Overall, 64 of 69 patients were evaluable. The interval between the end of chemotherapy and the initiation of RT was at least 1.5-2 months (mean 2). No treatment-related death was reported. After a median follow-up of 27 months from RT (range 5-77 months), neither clinically relevant radiation pneumonitis nor congestive heart failure had been reported. Minor and transitory lung and cardiac toxicities were observed. Conclusion: Sequential high doses of epirubicin, preceded by dexrazoxane, and paclitaxel did not adversely affect the tolerability of locoregional RT in breast cancer patients. The risk of pneumonitis was not affected by the use of sequential paclitaxel with an interval of at least 1.5-2 months between the end of chemotherapy and the initiation of RT. Long-term follow-up is needed to define the risk of cardiotoxicity in these patients.« less

  11. Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer.

    PubMed

    Colaco, Rovel J; Huh, Soon; Nichols, Romaine C; Morris, Christopher G; D'Agostino, Harry; Flampouri, Stella; Li, Zuofeng; Pham, Dat C; Bajwa, Abubakr A; Hoppe, Bradford S

    2013-04-01

    Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Six patients were treated: five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT.

  12. Associations of Adverse Clinical Course and Ingested Substances among Patients with Deliberate Drug Poisoning: A Cohort Study from an Intensive Care Unit in Japan.

    PubMed

    Ichikura, Kanako; Okumura, Yasuyuki; Takeuchi, Takashi

    2016-01-01

    Some patients with deliberate drug poisoning subsequently have an adverse clinical course. The present study aimed to examine whether the type of drugs ingested and psychiatric diagnoses were related to an adverse clinical course. We conducted a cohort study of patients with deliberate drug poisoning admitted to the intensive care unit of a university hospital located in Tokyo, Japan, between September 2006 and June 2013. Intensive care unit (ICU) stay of ≥4 days was used as a primary outcome measure, while the incidence of aspiration pneumonitis was used as a secondary outcome measure. Ingested substances and psychiatric diagnoses were used as explanatory variables. Of the 676 patients with deliberate drug poisoning, 88% had a history of psychiatric treatment and 82% had ingested psychotropic drugs. Chlorpromazine-promethazine-phenobarbital combination drug (Vegetamin®) ranked fifth among the most frequently ingested substances in cases of deliberate drug poisoning and had the highest incidence of prolonged ICU stay (20%) and aspiration pneumonitis (29%). The top three major classes consisted of benzodiazepines (79%), new-generation antidepressants (25%), and barbiturates/non-barbiturates (23%). Barbiturate overdose was independently associated with increased odds of both prolonged ICU stay (8% vs. 17%; odds ratio [OR], 2.97; 95% confidence interval [CI], 1.60-5.55) and aspiration pneumonitis (8% vs. 24%; OR, 3.83; 95% CI, 2.18-6.79) relative to those associated with overdose of only other sedative-hypnotics (i.e., benzodiazepines). These results suggest that judicious prescribing of barbiturates by psychiatrists could reduce the risk of an adverse clinical course when a patient attempts an overdose.

  13. The 2017 plague outbreak in Madagascar: Data descriptions and epidemic modelling.

    PubMed

    Nguyen, Van Kinh; Parra-Rojas, César; Hernandez-Vargas, Esteban A

    2018-06-01

    From August to November 2017, Madagascar endured an outbreak of plague. A total of 2417 cases of plague were confirmed, causing a death toll of 209. Public health intervention efforts were introduced and successfully stopped the epidemic at the end of November. The plague, however, is endemic in the region and occurs annually, posing the risk of future outbreaks. To understand the plague transmission, we collected real-time data from official reports, described the outbreak's characteristics, and estimated transmission parameters using statistical and mathematical models. The pneumonic plague epidemic curve exhibited multiple peaks, coinciding with sporadic introductions of new bubonic cases. Optimal climate conditions for rat flea to flourish were observed during the epidemic. Estimate of the plague basic reproduction number during the large wave of the epidemic was high, ranging from 5 to 7 depending on model assumptions. The incubation and infection periods for bubonic and pneumonic plague were 4.3 and 3.4 days and 3.8 and 2.9 days, respectively. Parameter estimation suggested that even with a small fraction of the population exposed to infected rat fleas (1/10,000) and a small probability of transition from a bubonic case to a secondary pneumonic case (3%), the high human-to-human transmission rate can still generate a large outbreak. Controlling rodent and fleas can prevent new index cases, but managing human-to-human transmission is key to prevent large-scale outbreaks. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Comparison of Toxicity Between Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy for Locally Advanced Non-small-cell Lung Cancer.

    PubMed

    Ling, Diane C; Hess, Clayton B; Chen, Allen M; Daly, Megan E

    2016-01-01

    The role of intensity-modulated radiotherapy (IMRT) in reducing treatment-related toxicity for locally advanced non-small-cell lung cancer (NSCLC) remains incompletely defined. We compared acute toxicity and oncologic outcomes in a large cohort of patients treated with IMRT or 3-dimensional conformal radiotherapy (3-DCRT), with or without elective nodal irradiation (ENI). A single-institution retrospective review was performed evaluating 145 consecutive patients with histologically confirmed stage III NSCLC treated with definitive chemoradiotherapy. Sixty-five (44.8%) were treated with 3-DCRT using ENI, 43 (30.0%) with 3-DCRT using involved-field radiotherapy (IFRT), and 37 (25.5%) with IMRT using IFRT. All patients received concurrent chemotherapy. Comparison of acute toxicities by treatment technique (IMRT vs. 3-DCRT) and extent of nodal irradiation (3-DCRT-IFRT vs. 3-DCRT-ENI) was performed for grade 2 or higher esophagitis or pneumonitis, number of acute hospitalizations, incidence of opioid requirement, percutaneous endoscopic gastrostomy utilization, and percentage weight loss during treatment. Local control and overall survival were analyzed by the Kaplan-Meier method. We identified no significant differences in any measures of acute toxicity by treatment technique or extent of nodal irradiation. There was a trend toward lower rates of grade 2 or higher pneumonitis among IMRT patients compared to 3-DCRT patients (5.4% vs. 23.0%; P = .065). Local control and overall survival were similar between cohorts. Acute and subacute toxicities were similar for patients treated with IMRT and with 3-DCRT with or without ENI, with a nonsignificant trend toward a reduction in pneumonitis with IMRT. Larger studies are needed to better define which patients will benefit from IMRT. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. SciTech Connect

    Felson, B.; Ralaisomay, G.

    The authors have encountered four cases of oil aspiration pneumonia complicated by carcinoma. Each had a clear-cut history of chronic intake of an oily substance, radiographic changes, and histologically documented oil aspiration pneumonia. Lung cancer later appeared in the involved area. A small number of similar cases also have been reported. The implication is that oil aspiration pneumonitis may induce bronchogenic carcinoma, particularly either the alveolar cell or the squamous cell variety. The radiographic diagnosis of the malignant transformation is difficult, and consequently the prognosis is poor.

  16. SciTech Connect

    Keane, T.J.; Van Dyk, J.; Rider, W.D.

    Interstitial pneumonia is a frequent and often fatal complication of allogenic bone marrow transplantation. Thirty to 40 percent of such cases are of unknown etiology and have been labelled as cases of idiopathic interstitial pneumonia. Idiopathic cases are more commonly associated with the use of total body irradiation; their occurrence appears to be independent of immunosupression or graft versus host disease. Evidence is presented from the literature suggesting that the development of idiopathic interstitial pneumonia is related to the absolute absorbed dose of radiation to lung. The similarity of idiopathic pneumonia to radiation pneumonitis seen in a different clinical settingmore » is described.« less

  17. Two unusual organisms, Aspergillus terreus and Metschnikowia pulcherrima, associated with the lung disease of ankylosing spondylitis

    PubMed Central

    Kennedy, W. P. U.; Milne, L. J. R.; Blyth, W.; Crompton, G. K.

    1972-01-01

    Two male patients with ankylosing spondylitis and upper lobe fibrosis and cavitation are described. A pneumonic disease in one was associated with mycological and serological evidence of infection with Aspergillus terreus but no other aspergillus species. A large pulmonary mycetoma developed in the second patient and among a number of other fungal isolates was found the yeast Metschnikowia pulcherrima. The association of ankylosing spondylitis with bronchopulmonary aspergillosis is considered; A. terreus is described for the first time as a human pulmonary pathogen, and the possible pathogenicity of M. pulcherrima in the debilitated human subject is discussed. Images PMID:4628429

  18. Emergency treatment of petroleum distillate and turpentine ingestion

    PubMed Central

    Ng, Raymond C.; Darwish, H.; Stewart, Donald A.

    1974-01-01

    A comparative study was made of pulmonary complications following the use of ipecac syrup and gastric lavage for hydrocarbon ingestion. The selected 255 patients had chest radiography when first seen and again two to five days later. Of these patients 74 or 29% had been treated with ipecac syrup, 41 or 16% by gastric lavage. On follow-up radiographs 19% of the ipecac-treated group were unchanged or worsened, compared with 39% of the lavage group, suggesting that pneumonitis was significantly less severe in the ipecac-treated patients. Use of ipecac is preferred over gastric lavage for alert patients who have ingested an excessive amount of hydrocarbon. PMID:4153346

  19. Treatment of advanced esophageal cancer

    SciTech Connect

    Kelsen, D.

    1982-12-01

    When radiation therapy is used for palliation of obstruction in patients with advanced esophageal carcinoma, an improvement in dysphagia can be expected in approximately 50% of patients. Major objective responses have rarely been quantitied but, in one study, were seen in 33% patients. Recurrence of dysphagia is usually seen within 2-6 months of treatment. Radiation toxicities and complications, even when used with palliative intent, can be substantial and include esophagitis, tracheoesophageal or esophageal-aortic fistula, mediastinitis, hemorrhage, pneumonitis, and myelosuppression. (JMT)

  20. Yersiniabactin iron uptake: mechanisms and role in Yersinia pestis pathogenesis

    PubMed Central

    Perry, Robert D.; Fetherston, Jacqueline D.

    2011-01-01

    Yersiniabactin (Ybt) is a siderophore-dependent iron uptake system encoded on a pathogenicity island that is widespread among pathogenic bacteria including the Yersiniae. While biosynthesis of the siderophore has been elucidated, the secretion mechanism and a few components of the uptake/utilization pathway are unidentified. ybt genes are transcriptionally repressed by Fur but activated by YbtA, likely in combination with the siderophore itself. The Ybt system is essential for the ability of Y. pestis to cause bubonic plague and important in pneumonic plague as well. However, the ability to cause fatal septicemic plague is independent of Ybt. PMID:21609780

  1. Decortication of the Lung

    PubMed Central

    Lynn, R. B.; Wellington, J. L.

    1963-01-01

    Excision of an empyema sac and thickened pleura from the lung and chest wall has been performed for over 70 years. The most appropriate fields of application of this procedure are in treatment of tuberculous empyema, empyema complicating pneumonic processes (most frequently caused by staphylococcal infection), and clotted hemothorax following chest injury. The authors' experience with 33 such decortications in the past five years is described, observations concerning the techniques, complications, and end results of the procedure are discussed, and illustrative case reports are presented. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9 PMID:14098889

  2. Microbiology and Epidemiology of Legionnaire's Disease.

    PubMed

    Burillo, Almudena; Pedro-Botet, María Luisa; Bouza, Emilio

    2017-03-01

    Legionnaire's disease (LD) is the pneumonic form of legionellosis caused by aerobic gram-negative bacilli of the genus Legionella. Individuals become infected when they inhale aerosolized water droplets contaminated with Legionella species. Forty years after the identification of Legionella pneumophila as the cause of the 1976 pneumonia outbreak in a hotel in Philadelphia, we have non-culture-based diagnostic tests, effective antibiotics, and preventive measures to handle LD. With a mortality rate still around 10%, underreporting, and sporadic outbreaks, there is still much work to be done. In this article, the authors review the microbiology, laboratory diagnosis, and epidemiology of LD. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Gasoline immersion injury

    SciTech Connect

    Simpson, L.A.; Cruse, C.W.

    1981-01-01

    Chemical burns and pulmonary complications are the most common problems encountered in the patient immersed in gasoline. Our patient demonstrated a 46-percent total-body-surface area, partial-thickness chemical burn. Although he did not develop bronchitis or pneumonitis, he did display persistent atelectasis, laryngeal edema, and subsequent upper airway obstruction. This had not previously been reported in gasoline inhalation injuries. Hydrocarbon hepatitis secondary to the vascular endothelial damage is apparently a reversible lesion with no reported long-term sequelae. Gasoline immersion injuries may be a series multisystem injury and require the burn surgeon to take a multisystem approach to its diagnosis and treatment.

  4. Cytomegalovirus peritonitis after kidney transplantation diagnosed through histopathological examination.

    PubMed

    Hotta, Kiyohiko; Fukasawa, Yuichiro; Wada, Yoshiki; Fukuzawa, Nobuyuki; Seki, Toshimori; Harada, Hiroshi

    2017-08-01

    Among organ transplant recipients, cytomegalovirus (CMV) commonly results in various types of infection such as pneumonitis, hepatitis, and enterocolitis. However, CMV peritonitis is very rare and difficult to diagnose owing to lack of visible clinical signs. We present a case of a 35-year-old female kidney recipient who developed abdominal pain and urinary retention caused by CMV peritonitis. To our knowledge, this is the first case report of CMV peritonitis after organ transplantation to be diagnosed through histopathological examination. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Pulmonary cytomegalic inclusion-body disease in a diabetic

    PubMed Central

    Heard, Brian E.; Hassan, A. M.; Wilson, Stephanie M.

    1962-01-01

    Cytomegalic inclusion-body disease was found at necropsy in the lungs of a 57-year-old diabetic man. The characteristic large cells were found in all parts of the lungs. The alveolar walls showed no cellular infiltration, supporting Hamperl's suggestion that the cytomegalic virus alone may be incapable of causing pneumonitis. A small focus of aspergillosis was also found in one lung. The rarity of cytomegalic inclusion-body disease in adults was confirmed by re-examining histologically the lungs of 15 further cases of diabetes as well as 60 of other chronic diseases. No further example of pulmonary cytomegaly was found. Images PMID:13905763

  6. Proposed national strategies for the prevention of leading work-related diseases and injuries. Part 1

    SciTech Connect

    Not Available

    1986-01-01

    Preliminary strategies developed at the National Symposium on the Prevention of Leading Work Related Diseases and Injuries, held in Atlanta, Georgia on May 1 to 3, 1985 were revised, elaborated, and further developed. Strategies were developed for the prevention of occupational lung diseases, musculoskeletal injuries, occupational cancers, severe occupational traumatic injuries, and occupational cardiovascular diseases. Lung diseases considered included silicosis, asbestosis, lung cancer mesothelioma, coal workers' pneumoconiosis, byssinosis, occupational asthma, hypersensitivity pneumonitis, asphyxiation, irritation, pulmonary edema, brucellosis, psitticosis, anthrax, mycobacterioses, histoplasmosis, aspergillosis, and coccidioidomycosis. Occupational cancers were discussed as they occur in the lung, pleura, peritoneum, bladder, kidneys, blood, nasalmore » cavity, skin, nasal sinuses, and liver.« less

  7. Effect of gamma interferon on resolution of murine chlamydial genital infection.

    PubMed Central

    Rank, R G; Ramsey, K H; Pack, E A; Williams, D M

    1992-01-01

    Mice infected in the genital tract with the Chlamydia trachomatis agent of mouse pneumonitis were treated with monoclonal rat anti-gamma interferon (anti-IFN-gamma) antibody to determine whether IFN-gamma participated in the resolution of the infection. In two experiments, anti-IFN-gamma antibody treatment resulted in significantly prolonged infections. In support of these data, passive administration of recombinant IFN-gamma to chronically infected nu/nu mice was able to bring about resolution of the infection in some animals. PMID:1398955

  8. Immunologic and clinical responses to "Monday morning miseries" antigens.

    PubMed

    Cernelc, S; Stropnik, Z

    1987-01-01

    Authors analysed 96 workers exposed to air conditioning system (Group A), and 71 workers (Group B) breathing normal ambient air. 38 workers in group A had a positive clinical history of "Monday morning miseries". Eight cases with the diagnosis hypersensitivity pneumonitis, acute and chronic form was based on environmental history, clinical investigations, physical examination, Chest-X-ray examination, immunological test "in vivo" and "in vitro" with common allergens and antigen "Monday morning miseries", ELISA, spirometry and PEFR (Peak Expiratory Flow-Rate) measurements. Exposure to contaminated air may be responsible for morbidity and reduced performance of workers.

  9. Cunninghamella bertholletiae Infection in a HLA-Haploidentical Hematopoietic Stem Cell Transplant Recipient with Graft Failure: Case Report and Review of the Literature.

    PubMed

    Luo, Chao; Wang, Jiasheng; Hu, Yongxian; Luo, Yi; Tan, Yamin; Jin, Aiyun; Wei, Bin; Hu, Huixian; Huang, He

    2016-10-01

    Cunninghamella bertholletiae as a rare cause of mucormycosis has been described almost exclusively in immunosuppressed patients such as hematopoietic stem cell transplant (HSCT) recipients. The infection is associated with high rates of mortality despite aggressive treatment. We describe a 40-year-old male with HLA-haploidentical HSCT developed fungal pneumonitis caused by C. bertholletiae complicated by graft failure and prolonged neutropenia. The patient died 102 days after HSCT despite early use of posaconazole and amphotericin B, which are believed to be the two most effective antifungal antibiotics against C. bertholletiae. The case highlights extreme unfavorable outcome in C. bertholletiae infection and neutropenia as a major risk factor.

  10. Outbreak of Legionnaires' disease on a cruise ship: lessons for international surveillance and control.

    PubMed

    Regan, C M; McCann, B; Syed, Q; Christie, P; Joseph, C; Colligan, J; McGaffin, A

    2003-06-01

    A sporadic case of Legionnaires' disease was linked to travel on a cruise ship. Investigation identified two further cases of Legionnaires' Disease and one case of non-pneumonic Legionella infection. An Incident Team confirmed the source to be the ship's water system and control measures were instituted that included pasteurisation, super chlorination and chlorine dioxide dosing. The Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC), through the European Surveillance Scheme for Travel Associated Legionnaires' Disease, identified three previous cases associated with the same ship's water system including one fatality. Lessons for the international surveillance and control of Legionnaires' disease on cruise ships are discussed.

  11. Infection prevention for patients with acute leukemia using laminar air flow rooms.

    PubMed

    Masaoka, T

    1986-01-01

    Infection prevention using laminar air flow (LAF) rooms was studied. For the effective and economical usage of LAF rooms, our trials with ozone decontamination were deemed very convenient and effective. In maintaining LAF clean, insects were found to be a critical factor regarding fungus contamination of LAF. As to its efficacy of infection prevention, LAF decreased infection during remission induction from 113/100 to 28/100. The infections reduced by LAF were pneumonia, upper respiratory infection and skin abscess, while sepsis and perianal infection were not affected. Treatment in LAF rooms also seemed to have comparable influence on interstitial pneumonitis after bone marrow transplantation.

  12. Cat-scratch disease. Subtle vertebral bone marrow abnormalities demonstrated by MR imaging and radionuclide bone scan.

    PubMed

    Wilson, J D; Castillo, M

    1995-01-01

    Cat-scratch disease (CSD) is a benign, self-limited cause of lymphadenitis occurring mainly in children and young adults. Its etiology is a delicate, small gram-negative pleomorphic bacillus. Less common manifestations of CSD are seen in 5% of patients and include Parinaud's oculoglandular syndrome (with enlargement of the preauricular nodes), parotid gland enlargement, encephalitis, radiculopathy, pneumonitis, erythema nodosum, thrombocytopenia, and lytic bone lesions. We describe a patient in whom magnetic resonance imaging initially detected subtle vertebral bone marrow abnormalities that correlated with the site of abnormality on a subsequent radionuclide bone scan.

  13. Paradoxical immune reconstitution inflammatory syndrome associated with previous Cryptococcus neoformans infection in an HIV-positive patient requiring neurosurgical intervention.

    PubMed

    Biagetti, Carlo; Nicola, Monica; Borderi, Marco; Pavoni, Michele; Tampellini, Livia; Verucchi, Gabriella; Chiodo, Francesco

    2009-04-01

    Immune reconstitution inflammatory syndrome (IRIS) in HIV-1-infected patients is associated with an exaggerated inflammatory response against an opportunistic infection during highly active antiretroviral therapy. The only review on IRIS associated with Criptococcus neoformans reported 21 episodes including lymphadenitis, necrotizing pneumonitis, breast and cutaneous abscess, and cryptococcomas. To our knowledge this is the first report of IRIS associated with previous meningeal criptococcal infection which required neurosurgical intervention with placement of a ventriculo-peritoneal shunt to drain a CSF cyst formed by exclusion of the temporal horn of the right lateral ventricle. We demonstrate that this procedure is possible without complications such as cryptococcal dissemination into the peritoneum.

  14. Severe hyperkalemia as a complication of timolol, a topically applied beta-adrenergic antagonist

    SciTech Connect

    Swenson, E.R.

    1986-06-01

    Severe hyperkalemia occurred in a patient with radiation pneumonitis and glaucoma shortly after beginning prednisone therapy. There was no evidence of renal failure, diabetes, acidosis, increased potassium intake, or significant tissue trauma. Medications having adverse effects on potassium metabolism were considered, and the patient's use of timolol maleate eyedrops was discontinued. His serum potassium level normalized despite continuation of the prednisone therapy. He became hyperkalemic on rechallenge with timolol and normokalemic following its withdrawal. This case indicates that the potential for beta-blocker-induced hyperkalemia exists even with topical appreciation.

  15. Thoracic perspective revisited in chronic liver disease.

    PubMed

    Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Kumar, Sachin; Arora, Ankur

    2015-08-01

    A variety of chest manifestations are seen in patients with chronic liver diseases, namely hepatopulmonary syndrome, portopulmonary hypertension, intrathoracic portosystemic collaterals, hepatic hydrothorax, infections, drug-induced changes, manifestations of hepatocellular carcinoma, gynecomastia, acute respiratory distress syndrome, autoimmune changes, aspiration pneumonitis and changes due to α1-antitrypsin deficiency. Gastroenterologists and radiologists should be aware of these entities; knowledge of the imaging findings specific to each condition is of prime importance for managing such patients. © The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

  16. Bone marrow transplantation in a patient with drug-induced aplastic anemia.

    PubMed

    Banerjee, T K; Band, P R; Pabst, H; Goldsand, G; Armstrong, W D; Brown, J; Hill, J R; Dossetor, J B

    1972-09-09

    A 23-year-old woman gravely ill with Pseudomonas septicemia secondary to presumed drug-induced bone marrow aplasia received marrow transplantation from two male HL-A identical sibling donors. She had a successful engraftment with excellent but temporary clinical improvement. Subsequently she succumbed to graft-versus-host disease manifested by Pseudomonas and Candida albicans septicemia, cytomegalovirus pneumonitis, three phases of dermatitis, nausea, vomiting, dysphagia, diarrhea, fever, edema and bone pain, with gradual but complete graft suppression by the 74th day after the transplantation. A second marrow transplant on the 70th day was unsuccessful.

  17. Plague studies*

    PubMed Central

    Pollitzer, R.

    1953-01-01

    In examining the control and prevention of plague, the author pays particular attention to the control of commensal rodents and their fleas. The various rat poisons in current use, their efficacy and practical application, and the dangers involved in their manipulation are described in great detail. The author also discusses other anti-rodent measures such as fumigation, rat-proofing, sanitation, protection of food, etc. The second part of the study deals with: vector control—the outstanding value of DDT application in rodent-flea control is emphasized—, the direct control of bubonic and pneumonic plague, and the control of the spread of plague at a distance. PMID:20603968

  18. WE-AB-202-01: Evaluating the Toxicity Reduction with CT-Ventilation Functional Avoidance Radiation Therapy

    SciTech Connect

    Vinogradskiy, Y; Miyasaka, Y; Kadoya, N

    Purpose: CT-ventilation is an exciting new imaging modality that uses 4DCTs to calculate lung ventilation. Studies have proposed to use 4DCT-ventilation imaging for functional avoidance radiotherapy which implies designing treatment plans to spare functional portions of the lung. Although retrospective studies have been performed to evaluate the dosimetric gains to functional lung; no work has been done to translate the dosimetric gains to an improvement in pulmonary toxicity. The purpose of our work was to evaluate the potential reduction in toxicity for 4DCT-ventilation based functional avoidance. Methods: 70 lung cancer patients with 4DCT imaging were used for the study. CT-ventilationmore » maps were calculated using the patient’s 4DCT, deformable image registrations, and a density-change-based algorithm. Radiation pneumonitis was graded using imaging and clinical information. Log-likelihood methods were used to fit a normal-tissue-complication-probability (NTCP) model predicting grade 2+ radiation pneumonitis as a function of doses (mean and V20) to functional lung (>15% ventilation). For 20 patients a functional plan was generated that reduced dose to functional lung while meeting RTOG 0617-based constraints. The NTCP model was applied to the functional plan to determine the reduction in toxicity with functional planning Results: The mean dose to functional lung was 16.8 and 17.7 Gy with the functional and clinical plans respectively. The corresponding grade 2+ pneumonitis probability was 26.9% with the clinically-used plan and 24.6% with the functional plan (8.5% reduction). The V20-based grade 2+ pneumonitis probability was 23.7% with the clinically-used plan and reduced to 19.6% with the functional plan (20.9% reduction). Conclusion: Our results revealed a reduction of 9–20% in complication probability with functional planning. To our knowledge this is the first study to apply complication probability to convert dosimetric results to toxicity

  19. Earthquakes and emergence

    NASA Astrophysics Data System (ADS)

    Earthquakes and emerging infections may not have a direct cause and effect relationship like tax evasion and jail, but new evidence suggests that there may be a link between the two human health hazards. Various media accounts have cited a massive 1993 earthquake in Maharashtra as a potential catalyst of the recent outbreak of plague in India that has claimed more than 50 lives and alarmed the world. The hypothesis is that the earthquake may have uprooted underground rat populations that carry the fleas infected with the bacterium that causes bubonic plague and can lead to the pneumonic form of the disease that is spread through the air.

  20. Recurrent massive pleural effusion due to pleural, pericardial, and epicardial fibrosis in histoplasmosis.

    PubMed

    Kilburn, C D; McKinsey, D S

    1991-12-01

    Acute histoplasmosis is generally a benign, self-limited pulmonary infection. Although Histoplasma capsulatum pneumonitis is common, pleural effusions associated with histoplasmosis are quite rare, and massive pleural effusions have not been reported. There have been several reports of pericardial fibrosis secondary to histoplasmosis, but epicardial fibrosis has not been described. We report a biopsy-proven case of histoplasmosis initially associated with recurrent massive pleural effusions and excessive pleural fibrosis causing a trapped lung. The patient later developed constrictive pericarditis. Despite pericardiectomy, severe cor pulmonale occurred, and the patient died. Necropsy demonstrated fibrosis of the epicardium.

  1. Toxoplasmosis with hemophagocytic syndrome after bone marrow transplantation: diagnosis at autopsy.

    PubMed

    Duband, S; Cornillon, J; Tavernier, E; Dumollard, J-M; Guyotat, D; Péoc'h, M

    2008-10-01

    Toxoplasmosis is a rare but well recognized opportunistic infection that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Besides encephalitis, other common presentations of Toxoplasma gondii infection are interstitial pneumonitis and myocarditis. Because of its non-specific clinical and biological signs and its lethal outcome, toxoplasmosis is often misdiagnosed and only revealed at autopsy. We report a case of a postmortem diagnosis of disseminated toxoplasmosis associated with hemophagocytic syndrome, which underlines the value of necropsy in cases of death after transplantation. We also discuss clinical presentations and risk factors that lead to toxoplasmosis in allo-HSCT recipients.

  2. Unique Case of Disseminated Plague With Multifocal Osteomyelitis.

    PubMed

    Tovar Padua, Leidy; Kamali, Amanda; Kim, Hannah; Green, Nicole M; Civen, Rachel; Schwartz, Benjamin; Krogstad, Paul; Deville, Jaime; Yeganeh, Nava; Lugo, Debra; Baker, Amira; Soni, Priya; Cho, Catherine; Svircic, Natalia; Dry, Sarah; Seeger, Leanne; Lloyd, Jessica; Deukmedjian, Grace; Bowen, Richard; Hale, Gillian; Zaki, Sherif R; Mead, Paul; Nielsen-Saines, Karin

    2017-09-01

    Plague is a disease caused by Yersinia pestis. Septicemic and pneumonic plague have a high mortality rate if untreated. Here we describe the challenges of accurately diagnosing a nonfatal pediatric case of septicemic plague with involvement of multiple organs; to our knowledge, the first documented case of multifocal plague osteomyelitis. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. [Comprehensive characteristics of the pulmonary syndrome in chronic liver diseases].

    PubMed

    Pashchenko, I G; Romanov, A A; Zhumanbaeva, R M; Osmolovskiĭ, V S; Faliushina, N V

    1988-01-01

    Combined investigations have shown that the pulmonary syndrome in chronic liver diseases is a group of changes (heterogeneous in their structure and origin), most of which are of intercurrent nature (chronic bronchitis and its complications, chronic pneumonia), the lesser part of them is related directly to an inflammatory liver process and constitutes the true pulmonary syndrome (interstitial pneumonitis, fibrosing alveolitis). In view of the fact that chronic liver pathology is attended by concomitant disorders of pulmonary ventilation, hemodynamics and immunologic homestasis, the authors propose that they should be regarded as a risk factor contributing to the development of respiratory diseases.

  4. Detection of notifiable diseases through surveillance for imported plague--New York, September-October 1994.

    PubMed

    1994-11-11

    Recent reports of bubonic and pneumonic plague outbreaks in India (1,2) prompted the New York City Department of Health (NYCDOH) and the New York State Department of Health (NYSDOH), in conjunction with CDC, to develop an emergency response plan to detect and manage suspected cases imported by international air travel. This report describes the surveillance system implemented by CDC on September 27 and supplemental efforts by NYC/NYSDOH to guide and inform physicians about the outbreak, and summarizes clinical findings for 11 travelers who had symptoms suggestive of plague.

  5. [The respiratory effects of smoking].

    PubMed

    Peiffer, G; Underner, M; Perriot, J

    2018-06-01

    A marked increase in the morbidity and mortality of a large number of broncho-pulmonary diseases has been documented in relation to smoking. The influence of tobacco smoking on various respiratory conditions. is discussed: incidence, severity or natural history modification of some respiratory illnesses: obstructive lung diseases (COPD, asthma), lung cancer, bacterial, viral respiratory infections, with the impact of smoking on tuberculosis. Finally, the relationship of tobacco with diffuse interstitial lung disease: protective role of smoking (controversial in sarcoidosis, real in hypersensitivity pneumonitis). The benefits of smoking cessation are described. Copyright © 2018. Published by Elsevier Masson SAS.

  6. Histopathological Analogies in Chronic Pulmonary Lesions between Cattle and Humans: Basis for an Alternative Animal Model

    PubMed Central

    Ramírez-Romero, Rafael; Nevárez-Garza, Alicia M.; Rodríguez-Tovar, Luis E.; Wong-González, Alfredo; Ledezma-Torres, Rogelio A.; Hernández-Vidal, Gustavo

    2012-01-01

    Most of the natural cases of pneumonia in feedlot cattle are characterized by a longer clinical course due to chronic lung lesions. Microscopically, these lesions include interstitial fibroplasia, bronchitis, bronchiectasis, bronchiolitis obliterans, and epithelial metaplasia of the airways. Herein, the aim was to review, under a medical perspective, the pathologic mechanisms operating in these chronic pneumonic lesions in calves. Based on the similarities of these changes to those reported in bronchiolitis obliterans/organising pneumonia (BO/OP) and chronic obstructive pulmonary disease (COPD) in human beings, calves are proposed as an alternative animal model. PMID:22629176

  7. [Adult-onset Still's disease with pulmonary and cardiac involvement and response to intravenous immunoglobulin].

    PubMed

    Neto, Nilton Salles Rosa; Waldrich, Leandro; de Carvalho, Jozélio Freire; Pereira, Rosa Maria Rodrigues

    2009-01-01

    Cardiopulmonary manifestations of adult-onset Still's disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

  8. Regulatory T Cells Contribute to the Inhibition of Radiation-Induced Acute Lung Inflammation via Bee Venom Phospholipase A2 in Mice

    PubMed Central

    Shin, Dasom; Lee, Gihyun; Sohn, Sung-Hwa; Park, Soojin; Jung, Kyung-Hwa; Lee, Ji Min; Yang, Jieun; Cho, Jaeho; Bae, Hyunsu

    2016-01-01

    Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase A2 (bvPLA2) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLA2 in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLA2 six times after radiation. To evaluate the level of inflammation, the number of immune cells, mRNA level of inflammatory cytokine, and histological changes in the lung were measured. BvPLA2 treatment reduced the accumulation of immune cells, such as macrophages, neutrophils, lymphocytes, and eosinophils. In addition, bvPLA2 treatment decreased inflammasome-, chemokine-, cytokine- and fibrosis-related genes’ mRNA expression. The histological results also demonstrated the attenuating effect of bvPLA2 on radiation-induced lung inflammation. Furthermore, regulatory T cell depletion abolished the therapeutic effects of bvPLA2 in radiation-induced pneumonitis, implicating the anti-inflammatory effects of bvPLA2 are dependent upon regulatory T cells. These results support the therapeutic potential of bvPLA2 in radiation pneumonitis and fibrosis treatments. PMID:27144583

  9. Efficacy of tilmicosin in the control of experimentally induced Actinobacillus pleuropneumoniae infection in swine

    PubMed Central

    2004-01-01

    Abstract The efficacy of tilmicosin administered in the feed to control Actinobacillus pleuropneumoniae infections in pigs was evaluated through a multisite, multitrial study. For each of 6 trials, 48 pigs (stratified by weight and sex) were randomly assigned to 6 to 8 pens. Medicated feed containing tilmicosin (200 g/t) and unmedicated feed were randomly assigned at the pen level and were provided ad libitum from day −7 to trial termination (day 14). Seeder pigs (inoculated intranasally with A. pleuropneumoniae serotype 1 and showing signs of clinical disease) were introduced to each pen on day 0. Rates of death, gross lesions, and culture of A. pleuropneumoniae at necropsy, clinical scores, average daily gain in weight, and average body temperature were compared between the medicated and unmedicated pigs. Compared with the unmedicated pigs, significantly fewer (P < 0.05) pigs given tilmicosin had lesions typical of A. pleuropneumoniae or had A. pleuropneumoniae isolated from their tissues at necropsy. Together with a significant reduction (P < 0.05) in the average percentage of pneumonic lung involvement (both visually and by weight), there were reductions in the numbers of pigs with moderate and severe pneumonic lung lesions and with A. pleuropneumoniae associated mortality. With tilmicosin treatment, the average daily weight gain, daily temperature, abdominal appearance, attitude, and respiration were also significantly better (P < 0.05). The results of this study demonstrate the in vivo effectiveness of tilmicosin (200 g/t) in controlling pleuropneumonia among swine experimentally infected with A. pleuropneumoniae. PMID:14979429

  10. Efficacy of tilmicosin in the control of experimentally induced Actinobacillus pleuropneumoniae infection in swine.

    PubMed

    Paradis, Marie-Anne; Vessie, Gordon H; Merrill, John K; Dick, C Paul; Moore, Camille; Charbonneau, George; Gottschalk, M; MacInnes, Janet I; Higgins, Robert; Mittal, K R; Girard, C; Aramini, Jeffery J; Wilson, Jeffrey B

    2004-01-01

    The efficacy of tilmicosin administered in the feed to control Actinobacillus pleuropneumoniae infections in pigs was evaluated through a multisite, multitrial study. For each of 6 trials, 48 pigs (stratified by weight and sex) were randomly assigned to 6 to 8 pens. Medicated feed containing tilmicosin (200 g/t) and unmedicated feed were randomly assigned at the pen level and were provided ad libitum from day -7 to trial termination (day 14). Seeder pigs (inoculated intranasally with A. pleuropneumoniae serotype 1 and showing signs of clinical disease) were introduced to each pen on day 0. Rates of death, gross lesions, and culture of A. pleuropneumoniae at necropsy, clinical scores, average daily gain in weight, and average body temperature were compared between the medicated and unmedicated pigs. Compared with the unmedicated pigs, significantly fewer (P < 0.05) pigs given tilmicosin had lesions typical of A. pleuropneumoniae or had A. pleuropneumoniae isolated from their tissues at necropsy. Together with a significant reduction (P < 0.05) in the average percentage of pneumonic lung involvement (both visually and by weight), there were reductions in the numbers of pigs with moderate and severe pneumonic lung lesions and with A. pleuropneumoniae associated mortality. With tilmicosin treatment, the average daily weight gain, daily temperature, abdominal appearance, attitude, and respiration were also significantly better (P < 0.05). The results of this study demonstrate the in vivo effectiveness of tilmicosin (200 g/t) in controlling pleuropneumonia among swine experimentally infected with A. pleuropneumoniae.

  11. Plague.

    PubMed

    Lazarus, Angeline A; Decker, Catherine F

    2004-03-01

    In the United States, plague poses a threat to humans from the infected animals in the endemic areas of the Western states. Plague may also be used in the near future as an agent of warfare or terrorism. Although the presentation of bubonic plague may be less of a problem, the septicemic and pneumonic forms present challenges to early diagnosis and prompt treatment. The major threat of plague as an agent of terrorism will probably be through the inhalational route. which could result in many cases of the pneumonic form, requiring early recognition and initiation of appropriate therapy. In a mass-casualty scenario, the clinician should be aware of the potential agents of biowarfare and be familiar with the treatment and prophylaxis recommendations outlined by the CDC. It is also prudent to employ universal precautions and respiratory isolation when treating patients with any unknown exposure. In endemic areas, personal protective measures such as use of insecticides, insect repellants, and prompt prophylaxis in cases of exposure to plague are recommended for reducing the incidence of infection. The author also recommends review of CDC website on bioterrorism (http://www.bt.cdc.gov) to keep informed of plague updates.

  12. Epizootic pneumonia of bighorn sheep following experimental exposure to Mycoplasma ovipneumoniae.

    PubMed

    Besser, Thomas E; Cassirer, E Frances; Potter, Kathleen A; Lahmers, Kevin; Oaks, J Lindsay; Shanthalingam, Sudarvili; Srikumaran, Subramaniam; Foreyt, William J

    2014-01-01

    Bronchopneumonia is a population limiting disease of bighorn sheep (Ovis canadensis). The cause of this disease has been a subject of debate. Leukotoxin expressing Mannheimia haemolytica and Bibersteinia trehalosi produce acute pneumonia after experimental challenge but are infrequently isolated from animals in natural outbreaks. Mycoplasma ovipneumoniae, epidemiologically implicated in naturally occurring outbreaks, has received little experimental evaluation as a primary agent of bighorn sheep pneumonia. In two experiments, bighorn sheep housed in multiple pens 7.6 to 12 m apart were exposed to M. ovipneumoniae by introduction of a single infected or challenged animal to a single pen. Respiratory disease was monitored by observation of clinical signs and confirmed by necropsy. Bacterial involvement in the pneumonic lungs was evaluated by conventional aerobic bacteriology and by culture-independent methods. In both experiments the challenge strain of M. ovipneumoniae was transmitted to all animals both within and between pens and all infected bighorn sheep developed bronchopneumonia. In six bighorn sheep in which the disease was allowed to run its course, three died with bronchopneumonia 34, 65, and 109 days after M. ovipneumoniae introduction. Diverse bacterial populations, predominantly including multiple obligate anaerobic species, were present in pneumonic lung tissues at necropsy. Exposure to a single M. ovipneumoniae infected animal resulted in transmission of infection to all bighorn sheep both within the pen and in adjacent pens, and all infected sheep developed bronchopneumonia. The epidemiologic, pathologic and microbiologic findings in these experimental animals resembled those seen in naturally occurring pneumonia outbreaks in free ranging bighorn sheep.

  13. Bronchoalveolar carcinoma (adenocarcinoma) mimicking recurrent bacterial community-acquired pneumonia (CAP).

    PubMed

    Cunha, Burke A; Syed, Uzma; Mikail, Nardeen

    2012-01-01

    Depending on the community-acquired pneumonia (CAP) pathogen, host factors, and immune status, CAPs resolve on chest x-rays at different rates. CAPs that resolve more slowly than expected, or not at all, are termed "slowly or non-resolving CAPs." In contrast, recurrent CAPs may be due to host defense defects (eg, multiple myelomas) or post-obstructive bronchogenic carcinomas. There are a variety of noninfectious disorders that may mimic CAPs on chest x-ray: alveolar hemorrhage, pulmonary drug reactions, radiation pneumonitis, Wegener's granulomatosis, bronchiolitis obliterans organizing pneumonia, bronchogenic carcinomas, and lymphomas. Noninfectious mimics of recurrent CAPs include congestive heart failure, pulmonary emboli, infarctions, sarcoidosis, and systemic lupus erythematosus pneumonitis. We present the case of a middle-aged man who presented with recurrent right middle lobe and right lower lobe CAPs. Diagnostic bronchoscopy showed no bronchial obstruction, but open lung biopsy showed bronchoalveolar carcinoma (well-differentiated adenocarcinoma). Bronchoalveolar carcinomas presenting as post-obstructive or recurrent CAPs are rare because the spread is along tissue planes and not endobronchially. The case described demonstrates a rare cause of bronchogenic carcinoma mimicking recurrent CAP. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. PD-1 checkpoint inhibition: Toxicities and management.

    PubMed

    Hahn, Andrew W; Gill, David M; Agarwal, Neeraj; Maughan, Benjamin L

    2017-12-01

    With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others. In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. Then, we will discuss the specific management of the most common immune-mediated adverse events including colitis, hepatitis, pneumonitis, rash, endocrinopathies, nephritis, and neurologic toxicities. Immune-related adverse events are frequently treated with immunosuppressive medication such as steroids and mycofenolate mofetil. There are specific immune-related adverse events which are frequently seen by the treating oncologist from checkpoint inhibitors. It is essential to understand the recommended treatment options to minimize toxicity and mortality from this important class of anti-neoplastic therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Vaccination of calves using the BRSV nucleocapsid protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects the lungs against BRSV replication and pathology.

    PubMed

    Letellier, Carine; Boxus, Mathieu; Rosar, Laurent; Toussaint, Jean-François; Walravens, Karl; Roels, Stefan; Meyer, Gilles; Letesson, Jean-Jacques; Kerkhofs, Pierre

    2008-09-02

    Respiratory syncytial virus (RSV) is a major cause of respiratory disease in both cattle and young children. Despite the development of vaccines against bovine (B)RSV, incomplete protection and exacerbation of subsequent RSV disease have occurred. In order to circumvent these problems, calves were vaccinated with the nucleocapsid protein, known to be a major target of CD8(+) T cells in cattle. This was performed according to a DNA prime-protein boost strategy. The results showed that DNA vaccination primed a specific T-cell-mediated response, as indicated by both a lymphoproliferative response and IFN-gamma production. These responses were enhanced after protein boost. After challenge, mock-vaccinated calves displayed gross pneumonic lesions and viral replication in the lungs. In contrast, calves vaccinated by successive administrations of plasmid DNA and protein exhibited protection against the development of pneumonic lesions and the viral replication in the BAL fluids and the lungs. The protection correlated to the cell-mediated immunity and not to the antibody response.

  16. [Therapeutic effect of the association between pulmonary ventilation and aerosol--inhalation with sulphureous mineral water in the chronic bronchopneumopathies].

    PubMed

    Lopalco, M; Proia, A R; Fraioli, A; Serio, A; Cammarella, I; Petraccia, L; Grassi, M

    2004-04-01

    Our research evaluates the efficacy of the inalation therapy by mineral sulphureous water in patients suffering from cronic bronchopneumopathy. From August to October 2002, two groups of patients, randomly selected, suffering from cronic bronchopneumonopathy, were studied at spa center "Pompeo" in Ferentino (FR). Every patient was treated daily during a cycle of twelve days. The first group was treated by pneumonic mechanical ventilation associated to sulphureous water aerosolinalation, the second by mechanical pulmonary ventilation associated to sulphureous water aerosol-inalation medicated with flunisolide. Every patient carried out spirometry, before and after treatment, and the measurement of FEV1 was considered a good parameter to evaluate the respiratory function. All patients reported an improvement in symptoms as dyspnea and cough. Results obtained show a significant functional improvement of respiratory function in both groups, evaluated by FEV1. Equal efficacy treating the patients by medicated and not medicated treatments stress the therapeutic role of mineral sulphureous waters in chronic bronchopneumopathies. Our research points out the usefullness of pneumonic ventilation associated with sulphureous water aerosol-inalation in patients suffering from chronic bronchopneumopathies.

  17. Management of normal tissue toxicity associated with chemoradiation (primary skin, esophagus, and lung).

    PubMed

    Yazbeck, Victor Y; Villaruz, Liza; Haley, Marsha; Socinski, Mark A

    2013-01-01

    Nearly one quarter of patients with lung cancer present with locally advanced disease where concurrent chemoradiotherapy is the current standard of care for patients with good performance status. Cisplatin-based concurrent chemoradiotherapy consistently showed an improvement in survival compared with sequential chemoradiotherapy, at the expense of an increase in the toxicity profile. Over the past decades, several encouraging biomarkers such as transforming growth factor-beta and radioprotective agents such as amifostine were studied but without reaching approval for patient care. We reviewed the prevalence and risk factors for different adverse effects associated with the combined chemoradiotherapy modality, especially dermatitis, mucositis, esophagitis, and pneumonitis. These adverse effects can further be divided into acute, subacute, and chronic. Dermatitis is usually rare and responds well to topical steroids and usual skin care. Acute esophagitis occurs in 30% of patients and is treated with proton pump inhibitors, promotility agents, local anesthetic, and dietary changes. Radiation pneumonitis is a subacute complication seen in 15% of patients and is usually managed with steroids. Chronic adverse effects such as radiation fibrosis and esophageal stricture occur approximately 6 months after completion of radiation therapy and are usually permanent. In this review, complications of chemoradiotherapy for patients with locally advanced lung cancer are delineated, and approaches to their management are described. Given that treatment interruption is associated with a worse outcome, patients are aggressively treated with a curative intent. Therefore, planning for treatment adverse effects improves patient tolerance, compliance, and outcome.

  18. Radionuclide injury to the lung.

    PubMed Central

    Dagle, G E; Sanders, C L

    1984-01-01

    Radionuclide injury to the lung has been studied in rats, hamsters, dogs, mice and baboons. Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors. These changes are somewhat similar for different species. Their severity can be related to the absorbed radiation dose (measured in rads) produced by alpha, beta or gamma radiation emanating from various deposited radionuclides. The chemicophysical forms of radionuclides and spatial-temporal factors are also important variables. As with other forms of injury to the lung, repair attempts are highlighted by fibrosis and proliferation of pulmonary epithelium. Lung tumors are the principal late effect observed in experimental animals following pulmonary deposition of radionuclides at dose levels that do not result in early deaths from radiation pneumonitis or fibrosis. The predominant lung tumors described have been of epithelial origin and have been classified, in decreasing frequency of occurrence, as adenocarcinoma, bronchioloalveolar carcinoma, epidermoid carcinomas and combined epidermoid and adenocarcinoma. Mesothelioma and fibrosarcoma have been observed in rats, but less commonly in other species. Hemangiosarcomas were frequency observed in dogs exposed to beta-gamma emitters, and occasionally in rats exposed to alpha emitters. These morphologic changes in the lungs of experimental animals were reviewed and issues relevant to the prediction of human hazards discussed. PMID:6376095

  19. Comparison of experimental respiratory tularemia in three nonhuman primate species.

    PubMed

    Glynn, Audrey R; Alves, Derron A; Frick, Ondraya; Erwin-Cohen, Rebecca; Porter, Aimee; Norris, Sarah; Waag, David; Nalca, Aysegul

    2015-04-01

    Tularemia is a zoonotic disease caused by Francisella tularensis, which is transmitted to humans most commonly by contact with infected animals, tick bites, or inhalation of aerosolized bacteria. F. tularensis is highly infectious via the aerosol route; inhalation of as few as 10-50 organisms can cause pneumonic tularemia. Left untreated, the pneumonic form has more than >30% case-fatality rate but with early antibiotic intervention can be reduced to 3%. This study compared tularemia disease progression across three species of nonhuman primates [African green monkey (AGM), cynomolgus macaque (CM), and rhesus macaque (RM)] following aerosolized F. tularensis Schu S4 exposure. Groups of the animals exposed to various challenge doses were observed for clinical signs of infection and blood samples were analyzed to characterize the disease pathogenesis. Whereas the AGMs and CMs succumbed to disease following challenge doses of 40 and 32 colony forming units (CFU), respectively, the RM lethal dose was 276,667 CFU. Following all challenge doses that caused disease, the NHPs experienced weight loss, bacteremia, fever as early as 4 days post exposure, and tissue burden. Necrotizing-to-pyogranulomatous lesions were observed most commonly in the lung, lymph nodes, spleen, and bone marrow. Overall, the CM model consistently manifested pathological responses similar to those resulting from inhalation of F. tularensis in humans and thereby most closely emulates human tularemia disease. The RM model displayed a higher tolerance to infection and survived exposures of up to 15,593 CFU of aerosolized F. tularensis. Published by Elsevier Ltd.

  20. Radiation exposure and lung disease in today's nuclear world.

    PubMed

    Deas, Steven D; Huprikar, Nikhil; Skabelund, Andrew

    2017-03-01

    Ionizing radiation poses important health risks. The per capita annual dose rate has increased in the United States and there is increasing concern for the risks posed by low-dose occupational exposure among workers in nuclear industries and healthcare. Recent nuclear accidents and concern for terrorism have heightened concern for catastrophic, high-dose ionizing radiation exposure. This review will highlight recent research into the risks to lung health posed by ionizing radiation exposure and into potential treatments. Angiotensin-converting enzyme inhibitors and some antioxidants have shown promise as mitigators, to decrease pneumonitis and fibrosis when given after exposure. Studies of survivors of nuclear catastrophes have shown increased risk for lung cancer, especially in nonsmokers. There is evidence for increased lung cancer risk in industrial radiation workers, especially those who process plutonium and may inhale radioactive particles. There does not seem to be an increased risk of lung cancer in healthcare workers who perform fluoroscopic procedures. High-dose ionizing radiation exposure causes pneumonitis and fibrosis, and more research is needed to develop mitigators to improve outcomes in nuclear catastrophes. Long-term, low-dose occupational radiation may increase lung cancer risk. More research to better define this risk could lead to improved safety protocols and screening programs.

  1. Sequence diversity of the leukotoxin (lktA) gene in caprine and ovine strains of Mannheimia haemolytica.

    PubMed

    Vougidou, C; Sandalakis, V; Psaroulaki, A; Petridou, E; Ekateriniadou, L

    2013-04-20

    Mannheimia haemolytica is the aetiological agent of pneumonic pasteurellosis in small ruminants. The primary virulence factor of the bacterium is a leukotoxin (LktA), which induces apoptosis in susceptible cells via mitochondrial targeting. It has been previously shown that certain lktA alleles are associated either with cattle or sheep. The objective of the present study was to investigate lktA sequence variation among ovine and caprine M haemolytica strains isolated from pneumonic lungs, revealing any potential adaptation for the caprine host, for which there is no available data. Furthermore, we investigated amino acid variation in the N-terminal part of the sequences and its effect on targeting mitochondria. Data analysis showed that the prevalent caprine genotype differed at a single non-synonymous site from a previously described uncommon bovine allele, whereas the ovine sequences represented new, distinct alleles. N-terminal sequence differences did not affect the mitochondrial targeting ability of the isolates; interestingly enough in one case, mitochondrial matrix targeting was indicated rather than membrane association, suggesting an alternative LktA trafficking pattern.

  2. Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions.

    PubMed

    Stauder, Michael C; Macdonald, O Kenneth; Olivier, Kenneth R; Call, Jason A; Lafata, Kyle; Mayo, Charles S; Miller, Robert C; Brown, Paul D; Bauer, Heather J; Garces, Yolanda I

    2011-05-01

    Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days. A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0. With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48Gy in 4 Fx, and most peripheral lesions with 54Gy in 3 Fx. The incidence of grade ≥ 2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy. Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Mitigation of lung injury after accidental exposure to radiation.

    PubMed

    Mahmood, J; Jelveh, S; Calveley, V; Zaidi, A; Doctrow, S R; Hill, R P

    2011-12-01

    There is a serious need to develop effective mitigators against accidental radiation exposures. In radiation accidents, many people may receive nonuniform whole-body or partial-body irradiation. The lung is one of the more radiosensitive organs, demonstrating pneumonitis and fibrosis that are believed to develop at least partially because of radiation-induced chronic inflammation. Here we addressed the crucial questions of how damage to the lung can be mitigated and whether the response is affected by irradiation to the rest of the body. We examined the widely used dietary supplement genistein given at two dietary levels (750 or 3750 mg/kg) to Fischer rats irradiated with 12 Gy to the lung or 8 Gy to the lung + 4 Gy to the whole body excluding the head and tail (whole torso). We found that genistein had promising mitigating effects on oxidative damage, pneumonitis and fibrosis even at late times (36 weeks) when drug treatment was initiated 1 week after irradiation and stopped at 28 weeks postirradiation. The higher dose of genistein showed no greater beneficial effect. Combined lung and whole-torso irradiation caused more lung-related severe morbidity resulting in euthanasia of the animals than lung irradiation alone.

  4. Early infectious complications in allogeneic marrow transplant recipients with acute leukemia: effects of prophylactic measures.

    PubMed

    Buckner, C D; Clift, R A; Thomas, E D; Hersman, J; Sanders, J E; Stewart, P S; Wade, J C; Murphy, M; Counts, G; Meyers, J D

    1983-01-01

    One hundred eighty-two patients with acute leukemia underwent allogeneic marrow transplantation and received one of two forms of infection prophylaxis: isolation and decontamination procedures in laminar air flow rooms (90 patients) or prophylactic granulocyte transfusion from a single family member (92 patients). Infection acquisition and survival were analyzed from the time of admission to 100 days posttransplant. There were 20 major local infections in the laminar air flow group and 16 in the prophylactic granulocyte group. Of the patients in the laminar air flow group, 24 (27%) had 27 episodes of bacteremia, while 23 (25%) of the prophylactic granulocyte group had 25 episodes of bacteremia. There were no significant differences in infection acquisition between the two groups during the period of granulocytopenia or after engraftment. The mortality during the first 100 days was 28% for the laminar air flow group and 35% for the prophylactic granulocyte group. Thirteen patients (14%) in the laminar air flow group and five (5%) in the prophylactic granulocyte group died with bacterial or fungal infections. There were no statistically significant differences between the two groups in overall incidence of or mortality from interstitial pneumonitis which was the predominant cause of death. However, the subset of patients who were seronegative for cytomegalovirus antibody at the time of transplant and received granulocytes from seropositive donors had a significantly higher incidence of and mortality from cytomegalovirus interstitial pneumonitis.

  5. Human ectoparasites and the spread of plague in Europe during the Second Pandemic.

    PubMed

    Dean, Katharine R; Krauer, Fabienne; Walløe, Lars; Lingjærde, Ole Christian; Bramanti, Barbara; Stenseth, Nils Chr; Schmid, Boris V

    2018-02-06

    Plague, caused by the bacterium Yersinia pestis , can spread through human populations by multiple transmission pathways. Today, most human plague cases are bubonic, caused by spillover of infected fleas from rodent epizootics, or pneumonic, caused by inhalation of infectious droplets. However, little is known about the historical spread of plague in Europe during the Second Pandemic (14-19th centuries), including the Black Death, which led to high mortality and recurrent epidemics for hundreds of years. Several studies have suggested that human ectoparasite vectors, such as human fleas ( Pulex irritans ) or body lice ( Pediculus humanus humanus ), caused the rapidly spreading epidemics. Here, we describe a compartmental model for plague transmission by a human ectoparasite vector. Using Bayesian inference, we found that this model fits mortality curves from nine outbreaks in Europe better than models for pneumonic or rodent transmission. Our results support that human ectoparasites were primary vectors for plague during the Second Pandemic, including the Black Death (1346-1353), ultimately challenging the assumption that plague in Europe was predominantly spread by rats. Copyright © 2018 the Author(s). Published by PNAS.

  6. Human ectoparasites and the spread of plague in Europe during the Second Pandemic

    PubMed Central

    Krauer, Fabienne; Walløe, Lars; Bramanti, Barbara; Stenseth, Nils Chr.; Schmid, Boris V.

    2018-01-01

    Plague, caused by the bacterium Yersinia pestis, can spread through human populations by multiple transmission pathways. Today, most human plague cases are bubonic, caused by spillover of infected fleas from rodent epizootics, or pneumonic, caused by inhalation of infectious droplets. However, little is known about the historical spread of plague in Europe during the Second Pandemic (14–19th centuries), including the Black Death, which led to high mortality and recurrent epidemics for hundreds of years. Several studies have suggested that human ectoparasite vectors, such as human fleas (Pulex irritans) or body lice (Pediculus humanus humanus), caused the rapidly spreading epidemics. Here, we describe a compartmental model for plague transmission by a human ectoparasite vector. Using Bayesian inference, we found that this model fits mortality curves from nine outbreaks in Europe better than models for pneumonic or rodent transmission. Our results support that human ectoparasites were primary vectors for plague during the Second Pandemic, including the Black Death (1346–1353), ultimately challenging the assumption that plague in Europe was predominantly spread by rats. PMID:29339508

  7. Plague pneumonia disease caused by Yersinia pestis.

    PubMed

    Cleri, D J; Vernaleo, J R; Lombardi, L J; Rabbat, M S; Mathew, A; Marton, R; Reyelt, M C

    1997-03-01

    Plague is a zoonotic infection caused by Yersina pesits, a pleomorphic, gram-negative non-spore-forming coccobacillus that is more accurately classified as a subspecies of Y pseudotuberculosis. Animal reservoirs include rodents, rabbits, and occasionally larger animals. Cats become ill and have spread pneumonic disease to man. Dogs may be a significant sentinel animal as well as a reservoir, although do not usually become ill. Flea bites commonly spread disease to man. Person to person spread has not been a recent feature until the purported outbreak of plague and plague pneumonia in India in 1994. Other factors that increase risk of infection in endemic areas are occupation-veterinarians and assistants, pet ownership, direct animal-reservoir contact especially during the hunting season, living in households with an index case, and, mild winters, cool moist springs, and early summers. Clinical presentations include subclinical plague (positive serology without disease); plague pharyngitis; pestis minor (abortive bubonic plague); bubonic plague; septicemic plague; pneumonic plague; and plague meningitis. Most prominent of plague's differential diagnosis are Reye's syndrome, other causes of lymphadenitis, bacterial pneumonias, tularemia, and acute surgical abdomen. Treatment has reduced mortality from 40-90% to 5-18%. The drug of choice (except for plague meningitis) is streptomycin, with tetracyclines being alternatives. Parenteral cholamphenicol is the treatment of choice for plague meningitis. A tetracycline should be administered as chemoprophylaxis to all contacts over the age of 8 years. Plague vaccine is available, but is only partially protective.

  8. Personalized medicine in interstitial lung diseases.

    PubMed

    Spagnolo, Paolo; Oldham, Justin M; Jones, Mark G; Lee, Joyce S

    2017-05-01

    A number of recent studies have explored the possibility to apply personalized medicine to interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), the most common and deadly of the idiopathic interstitial pneumonias. In our review, we summarize and discuss the most recent literature on personalized medicine in IPF as well as hypersensitivity pneumonitis and sarcoidosis, with emphasis on patient subgroups for which a personalized approach to disease prognostication and management may become a reality in the near future. Most of the studies that have explored the applicability of personalized medicine to ILDs have been conducted in patients with IPF. Such studies have suggested the existence of several distinct disease subgroups defined by similar genetic profiles, molecular pathways, exposures and individual lifestyles. Personalized medicine in hypersensitivity pneumonitis is in its infancy. The development and applicability of personalized medicine to sarcoidosis, on the other hand, remains problematic for several reasons, including the lack of a diagnostic gold standard, the highly variable and unpredictable disease course, particularly across patients of different ethnicities, the poor correlation between disease activity and disease severity and the lack of a validated management algorithm. A number of distinct patient subgroups have been identified in ILDs. Although available data need to be validated longitudinally, the possibility to study homogeneous groups of patients may allow prediction of disease behavior and response to treatment with dramatic clinical implications.

  9. Bronchopleural cutaneous fistula due to Eikenella corrodens.

    PubMed

    Wong, Kin-Sun; Huang, Yhu-Chering

    2005-01-01

    The aim of this paper is to review the subject and to report on and discuss a case of bronchopleural cutaneous fistula due to Eikenella corrodens. A 16-year-old girl was brought to our hospital with fever and blood-tinged sputum 2 weeks prior to her admission. She suffered from neurologic sequelae of herpetic encephalitis and had been bed-ridden since 5 years of age. A longitudinal paraspinal soft mass had been noted in the previous week by her mother. She had been given oral feeding despite frequent choking for the past few years. On palpation, the mass can be squeezed to follow the least resistance of subcutaneous space longitudinally extending to the lower thoracic region. Chest computed tomography scan revealed right lower lobe necrotizing pneumonitis and a pleuro-cutaneous fistula leading to the subcutaneous air locules. A protracted course of antibiotics was prescribed and subcutaneous air trapping decreased in size over 8 weeks. Eikenella corrodens has increasingly been implicated as a potential causative pathogen in pleuropulmonary infections. Pleuro-cutaneous fistula and abscess formation complicating empyema and necrotizing pneumonitis due to E. corrodens infection have not been reported. A bulging thoracic subcutaneous lesion waxes and wanes with respiration suggest the possibility of a pleruo-cutaneous fistula. Treatment of Eikenella empyema using antibiotics without surgical decortication requires a prolonged course of antibiotic therapy.

  10. Animal model of grain worker's lung.

    PubMed Central

    Stepner, N; Broder, I; Baumal, R

    1986-01-01

    We examined the light microscopic changes in the lungs of rabbits exposed to grain dust for variable periods of time, to determine whether an animal model of grain worker's lung could be developed. Experimental animals were exposed to grain dust at a concentration of 20 mg/m3 for 7 hr/day, 5 days/week, for up to 6 months. The lungs of these rabbits demonstrated a granulomatous interstitial pneumonitis associated with exudation of mononuclear cells into the alveoli and conducting airways. These changes appeared within 5 days of the onset of exposure and reached a peak at 3 weeks but were sustained through the longest exposure interval. No abnormalities were observed in the lungs of control rabbits. These results show three points of consistency with those obtained in epidemiologic studies of grain elevator workers. First, the rapid appearance of the experimental changes suggests that the mechanism of tissue injury may not be immunologic. Second, the occurrence of the histopathologic alterations in the interstitium, alveoli, and airways corresponds with the combined restrictive and obstructive ventilatory defect described in the human epidemiologic studies. Third, the absence of lung fibrosis in rabbits exposed to dust for 6 months suggests that the pneumonitis is reversible. Thus this experimental model shows promise of helping to clarify the nature and mechanism of the adverse pulmonary effects of grain dust. Images FIGURE 1. FIGURE 2. PMID:3709485

  11. Assessment of Workers' Exposure to Grain Dust and Bioaerosols During the Loading of Vessels' Hold: An Example at a Port in the Province of Québec.

    PubMed

    Marchand, Geneviève; Gardette, Marie; Nguyen, Kiet; Amano, Valérie; Neesham-Grenon, Eve; Debia, Maximilien

    2017-08-01

    Longshoremen are exposed to large amounts of grain dust while loading of grain into the holds of vessels. Grain dust inhalation has been linked to respiratory diseases such as chronic bronchitis, hypersensitivity, pneumonitis, and toxic pneumonitis. Our objective was to characterize the exposure of longshoremen to inhalable and total dust, endotoxins, and cultivable bacteria and fungi during the loading of grain in a vessel's hold at the Port of Montreal in order to assess the potential health risks. Sampling campaigns were conducted during the loading of two different types of grain (wheat and corn). Environmental samples of microorganisms (bacteria, fungus, and actinomycetes) were taken near the top opening of the ship's holds while personal breathing zone measurements of dust and endotoxins were sampled during the worker's 5-hour shifts. Our study show that all measurements are above the recommendations with concentration going up to 390 mg m-3 of total dust, 89 mg m-3 of inhalable fraction, 550 000 EU m-3 of endotoxins, 20 000 CFU m-3 of bacteria, 61 000 CFU m-3 of fungus and 2500 CFU m-3 of actinomycetes. In conclusion, longshoremen are exposed to very high levels of dust and of microorganisms and their components during grain loading work. Protective equipment needs to be enforced for all workers during such tasks in order to reduce their exposure. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  12. A Patient with Non-Hodgkin Lymphoma and Nonspecific Interstitial Pneumonia during Ibrutinib Therapy.

    PubMed

    Jungmann, Sven; Ludwig, Wolf-Dieter; Schönfeld, Nicolas; Blum, Torsten-Gerriet; Großwendt, Claudia; Boch, Christian; Rehbock, Beate; Griff, Sergej; Schmittel, Alexander; Bauer, Torsten T

    2017-01-01

    We present a 74-year-old male with nonspecific interstitial pneumonia (NSIP) during treatment with ibrutinib for mantle cell lymphoma. Previously, the patient had received six cycles of bendamustine and rituximab and six cycles of R-CHOP, followed by rituximab maintenance therapy. Respiratory tract complications of ibrutinib other than infectious pneumonia have not been mentioned in larger trials, but individual case reports hinted to a possible association with the development of pneumonitis. In our patient, the onset of alveolitis that progressed towards NSIP together with the onset of ibrutinib treatment suggests causality. One week after ibrutinib was discontinued, nasal symptoms resolved first. A follow-up CT showed a reduction in the reticular hyperdensities and ground-glass opacities, suggestive of restitution of the lung disease. To our knowledge, this is the first case showing a strong link between ibrutinib and interstitial lung disease, strengthening a previous report on subacute pneumonitis. Our findings have clinical implications because pulmonary side effects were reversible at this early stage. We, therefore, suggest close monitoring for respiratory side effects in patients receiving ibrutinib.

  13. Compartmental responses after thoracic irradiation of mice: Strain differences

    SciTech Connect

    Chiang, C.-S.; Liu, W.-C.; Jung, S.-M.

    2005-07-01

    Purpose: To examine and compare the molecular and cellular processes leading to radiation fibrosis and pneumonitis in C57BL/6J and C3H/HeN mice. Methods and Materials: At indicated times after various doses of thoracic irradiation, the cell populations obtained by bronchoalveolar lavage of C57BL/6J mice were differentially analyzed by cytology and assessed by RNase protection (RPA) assay for levels of cytokines and related genes. The molecular responses in bronchial alveolar lavage (BAL) populations were compared with those in whole lung of C57BL/6J mice and with those of C3H/HeN mice. The former strain develops late radiation fibrosis, whereas the latter develop subacute radiationmore » pneumonitis. Results: In C57BL/6J mice, a decrease in the total number of BAL cells was found 1 week after 6, 12, or 20 Gy thoracic irradiation with a subsequent dose-dependent increase up to 6 months. After 12 and 20 Gy, large, foamy macrophages and multinucleated cells became evident in BAL at 3 weeks, only to disappear at 4 months and reappear at 6 months. This biphasic response was mirrored by changes expression of mRNA for proinflammatory cytokines and the Mac-1 macrophage-associated antigen. As with BAL, whole lung tissue also showed biphasic cytokine and Mac-1 mRNA responses, but there were striking temporal differences between the two compartments, with changes in whole lung tissue correlating better than BAL with the onset of fibrosis in this strain. The radiation-induced proinflammatory mRNA responses had strain-dependent and strain-independent components. Thoracic irradiation of C3H/HeN induced similar increases in tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-1{alpha}/{beta}, and interferon (IFN)-{gamma} mRNA expression in lung as it did in C57BL/6J mice during the 'presymptom' phase at 1-2 months. However, immediately preceding and during the pneumonitic time period at 3-4 months, TNF-{alpha} and IL-1{alpha}/{beta} mRNAs were highly upregulated in C3H

  14. Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H1N1 pneumonia: primary influenza pneumonia versus concomitant/secondary bacterial pneumonia

    PubMed Central

    Song, Joon Y.; Cheong, Hee J.; Heo, Jung Y.; Noh, Ji Y.; Yong, Hwan S.; Kim, Yoon K.; Kang, Eun Y.; Choi, Won S.; Jo, Yu M.; Kim, Woo J.

    2011-01-01

    Please cite this paper as: Song et al. (2011). Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H1N1 pneumonia: primary influenza pneumonia versus concomitant/secondary bacterial pneumonia. Influenza and Other Respiratory Viruses 5(6), e535–e543. Background  Although influenza virus usually involves the upper respiratory tract, pneumonia was seen more frequently with the 2009 pandemic influenza A/H1N1 than with seasonal influenza. Methods  From September 1, 2009, to January 31, 2010, a specialized clinic for patients (aged ≥15 years) with ILI was operated in Korea University Guro Hospital. RT‐PCR assay was performed to diagnose 2009 pandemic influenza A/H1N1. A retrospective case–case–control study was performed to determine the predictive factors for influenza pneumonia and to discriminate concomitant/secondary bacterial pneumonia from primary influenza pneumonia during the 2009–2010 pandemic. Results  During the study period, the proportions of fatal cases and pneumonia development were 0·12% and 1·59%, respectively. Patients with pneumonic influenza were less likely to have nasal symptoms and extra‐pulmonary symptoms (myalgia, headache, and diarrhea) compared to patients with non‐pneumonic influenza. Crackle was audible in just about half of the patients with pneumonic influenza (38·5% of patients with primary influenza pneumonia and 53·3% of patients with concomitant/secondary bacterial pneumonia). Procalcitonin, C‐reactive protein (CRP), and lactate dehydrogenase were markedly increased in patients with influenza pneumonia. Furthermore, procalcitonin (cutoff value 0·35 ng/ml, sensitivity 81·8%, and specificity 66·7%) and CRP (cutoff value 86·5 mg/IU, sensitivity 81·8%, and specificity 59·3%) were discriminative between patients with concomitant/secondary bacterial pneumonia and patients with primary influenza pneumonia. Conclusions  Considering the subtle manifestations of 2009 pandemic

  15. Stereotactic Body Radiation Therapy for Re-irradiation of Persistent or Recurrent Non-Small Cell Lung Cancer

    SciTech Connect

    Trovo, Marco, E-mail: marcotrovo33@hotmail.com; Minatel, Emilio; Durofil, Elena

    2014-04-01

    Purpose: To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. Methods and Materials: The analysis was conducted in 17 patients with “in-field” recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose tomore » 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. Results: The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). Conclusions: Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern.« less

  16. Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial.

    PubMed

    Chun, Stephen G; Hu, Chen; Choy, Hak; Komaki, Ritsuko U; Timmerman, Robert D; Schild, Steven E; Bogart, Jeffrey A; Dobelbower, Michael C; Bosch, Walter; Galvin, James M; Kavadi, Vivek S; Narayan, Samir; Iyengar, Puneeth; Robinson, Clifford G; Wynn, Raymond B; Raben, Adam; Augspurger, Mark E; MacRae, Robert M; Paulus, Rebecca; Bradley, Jeffrey D

    2017-01-01

    Purpose Although intensity-modulated radiation therapy (IMRT) is increasingly used to treat locally advanced non-small-cell lung cancer (NSCLC), IMRT and three-dimensional conformal external beam radiation therapy (3D-CRT) have not been compared prospectively. This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospective clinical trial. Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617, in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab, and 60- versus 74-Gy radiation doses. Comparisons included 2-year overall survival (OS), progression-free survival, local failure, distant metastasis, and selected Common Terminology Criteria for Adverse Events (version 3) ≥ grade 3 toxicities. Results The median follow-up was 21.3 months. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The IMRT group had larger planning treatment volumes (median, 427 v 486 mL; P = .005); a larger planning treatment volume/volume of lung ratio (median, 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056). Two-year OS, progression-free survival, local failure, and distant metastasis-free survival were not different between IMRT and 3D-CRT. IMRT was associated with less ≥ grade 3 pneumonitis (7.9% v 3.5%, P = .039) and a reduced risk in adjusted analyses (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046). IMRT also produced lower heart doses ( P < .05), and the volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis ( P < .05). The lung V5 was not associated with any ≥ grade 3 toxicity, whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026). Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports

  17. SciTech Connect

    Rosenzweig, Kenneth E., E-mail: ken.rosenzweig@mountsinai.org; Zauderer, Marjorie G.; Laser, Benjamin

    Purpose: In patients with malignant pleural mesothelioma who are unable to undergo pneumonectomy, it is difficult to deliver tumoricidal radiation doses to the pleura without significant toxicity. We have implemented a technique of using intensity-modulated radiotherapy (IMRT) to treat these patients, and we report the feasibility and toxicity of this approach. Methods and Materials: Between 2005 and 2010, 36 patients with malignant pleural mesothelioma and two intact lungs (i.e., no previous pneumonectomy) were treated with pleural IMRT to the hemithorax (median dose, 46.8 Gy; range, 41.4-50.4) at Memorial Sloan-Kettering Cancer Center. Results: Of the 36 patients, 56% had right-sided tumors.more » The histologic type was epithelial in 78%, sarcomatoid in 6%, and mixed in 17%, and 6% had Stage I, 28% had Stage II, 33% had Stage III, and 33% had Stage IV. Thirty-two patients (89%) received induction chemotherapy (mostly cisplatin and pemetrexed); 56% underwent pleurectomy/decortication before IMRT and 44% did not undergo resection. Of the 36 patients evaluable for acute toxicity, 7 (20%) had Grade 3 or worse pneumonitis (including 1 death) and 2 had Grade 3 fatigue. In 30 patients assessable for late toxicity, 5 had continuing Grade 3 pneumonitis. For patients treated with surgery, the 1- and 2-year survival rate was 75% and 53%, and the median survival was 26 months. For patients who did not undergo surgical resection, the 1- and 2-year survival rate was 69% and 28%, and the median survival was 17 months. Conclusions: Treating the intact lung with pleural IMRT in patients with malignant pleural mesothelioma is a safe and feasible treatment option with an acceptable rate of pneumonitis. Additionally, the survival rates were encouraging in our retrospective series, particularly for the patients who underwent pleurectomy/decortication. We have initiated a Phase II trial of induction chemotherapy with pemetrexed and cisplatin with or without pleurectomy

  18. Mutated and Bacteriophage T4 Nanoparticle Arrayed F1-V Immunogens from Yersinia pestis as Next Generation Plague Vaccines

    PubMed Central

    Tao, Pan; Mahalingam, Marthandan; Kirtley, Michelle L.; van Lier, Christina J.; Sha, Jian; Yeager, Linsey A.; Chopra, Ashok K.; Rao, Venigalla B.

    2013-01-01

    Pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism Yersinia pestis poses a serious threat for deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine against plague. The polymeric bacterial capsular protein F1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response V antigen, has high propensity to aggregate, thus affecting its purification and vaccine efficacy. We used two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, to construct new plague vaccines that provided complete protection against pneumonic plague. The NH2-terminal β-strand of F1 was transplanted to the COOH-terminus and the sequence flanking the β-strand was duplicated to eliminate polymerization but to retain the T cell epitopes. The mutated F1 was fused to the V antigen, a key virulence factor that forms the tip of the type three secretion system (T3SS). The F1mut-V protein showed a dramatic switch in solubility, producing a completely soluble monomer. The F1mut-V was then arrayed on phage T4 nanoparticle via the small outer capsid protein, Soc. The F1mut-V monomer was robustly immunogenic and the T4-decorated F1mut-V without any adjuvant induced balanced TH1 and TH2 responses in mice. Inclusion of an oligomerization-deficient YscF, another component of the T3SS, showed a slight enhancement in the potency of F1-V vaccine, while deletion of the putative immunomodulatory sequence of the V antigen did not improve the vaccine efficacy. Both the soluble (purified F1mut-V mixed with alhydrogel) and T4 decorated F1mut-V (no adjuvant) provided 100% protection to mice and rats against pneumonic plague evoked by high doses of Y. pestis CO92. These novel platforms might lead to efficacious and easily manufacturable next generation plague vaccines. PMID:23853602

  19. Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

    PubMed Central

    Sha, Jian; Kirtley, Michelle L.; van Lier, Christina J.; Wang, Shaofei; Erova, Tatiana E.; Kozlova, Elena V.; Cao, Anthony; Cong, Yingzi; Fitts, Eric C.; Rosenzweig, Jason A.

    2013-01-01

    Braun (murein) lipoprotein (Lpp) and lipopolysaccharide (LPS) are major components of the outer membranes of Enterobacteriaceae family members that are capable of triggering inflammatory immune responses by activating Toll-like receptors 2 and 4, respectively. Expanding on earlier studies that demonstrated a role played by Lpp in Yersinia pestis virulence in mouse models of bubonic and pneumonic plague, we characterized an msbB in-frame deletion mutant incapable of producing an acyltransferase that is responsible for the addition of lauric acid to the lipid A moiety of LPS, as well as a Δlpp ΔmsbB double mutant of the highly virulent Y. pestis CO92 strain. Although the ΔmsbB single mutant was minimally attenuated, the Δlpp single mutant and the Δlpp ΔmsbB double mutant were significantly more attenuated than the isogenic wild-type (WT) bacterium in bubonic and pneumonic animal models (mouse and rat) of plague. These data correlated with greatly reduced survivability of the aforementioned mutants in murine macrophages. Furthermore, the Δlpp ΔmsbB double mutant was grossly compromised in its ability to disseminate to distal organs in mice and in evoking cytokines/chemokines in infected animal tissues. Importantly, mice that survived challenge with the Δlpp ΔmsbB double mutant, but not the Δlpp or ΔmsbB single mutant, in a pneumonic plague model were significantly protected against a subsequent lethal WT CO92 rechallenge. These data were substantiated by the fact that the Δlpp ΔmsbB double mutant maintained an immunogenicity comparable to that of the WT strain and induced long-lasting T-cell responses against heat-killed WT CO92 antigens. Taken together, the data indicate that deletion of the msbB gene augmented the attenuation of the Δlpp mutant by crippling the spread of the double mutant to the peripheral organs of animals and by inducing cytokine/chemokine responses. Thus, the Δlpp ΔmsbB double mutant could provide a new live-attenuated background

  20. Effect of Normal Lung Definition on Lung Dosimetry and Lung Toxicity Prediction in Radiation Therapy Treatment Planning

    SciTech Connect

    Wang, Weili; Department of Radiation Oncology, the Fourth Affiliated Hospital, China Medical University, Shenyang; Xu, Yaping

    2013-08-01

    Purpose: This study aimed to compare lung dose–volume histogram (DVH) parameters such as mean lung dose (MLD) and the lung volume receiving ≥20 Gy (V20) of commonly used definitions of normal lung in terms of tumor/target subtraction and to determine to what extent they differ in predicting radiation pneumonitis (RP). Methods and Materials: One hundred lung cancer patients treated with definitive radiation therapy were assessed. The gross tumor volume (GTV) and clinical planning target volume (PTV{sub c}) were defined by the treating physician and dosimetrist. For this study, the clinical target volume (CTV) was defined as GTV with 8-mm uniformmore » expansion, and the PTV was defined as CTV with an 8-mm uniform expansion. Lung DVHs were generated with exclusion of targets: (1) GTV (DVH{sub G}); (2) CTV (DVH{sub C}); (3) PTV (DVH{sub P}); and (4) PTV{sub c} (DVH{sub Pc}). The lung DVHs, V20s, and MLDs from each of the 4 methods were compared, as was their significance in predicting radiation pneumonitis of grade 2 or greater (RP2). Results: There are significant differences in dosimetric parameters among the various definition methods (all Ps<.05). The mean and maximum differences in V20 are 4.4% and 12.6% (95% confidence interval 3.6%-5.1%), respectively. The mean and maximum differences in MLD are 3.3 Gy and 7.5 Gy (95% confidence interval, 1.7-4.8 Gy), respectively. MLDs of all methods are highly correlated with each other and significantly correlated with clinical RP2, although V20s are not. For RP2 prediction, on the receiver operating characteristic curve, MLD from DVH{sub G} (MLD{sub G}) has a greater area under curve of than MLD from DVH{sub C} (MLD{sub C}) or DVH{sub P} (MLD{sub P}). Limiting RP2 to 30%, the threshold is 22.4, 20.6, and 18.8 Gy, for MLD{sub G}, MLD{sub C}, and MLD{sub P}, respectively. Conclusions: The differences in MLD and V20 from various lung definitions are significant. MLD from the GTV exclusion method may be more accurate in

  1. [Consequences of short term fluctuations of the environmental temperatures in calves--Part 2: Effects on the health status of animals within three weeks after exposure].

    PubMed

    Reinhold, P; Elmer, S

    2002-04-01

    The aim of the present study was to examine consequences of sudden changes in ambient temperature over a 4-hour period (see part 1 [ELMER & REINHOLD, 2002]) on respiratory health in clinically healthy calves. Therefore, the relationship between short-term changes in ambient temperature and the occurrence of clinical respiratory disease was checked over a period of 3 weeks after exposure in 10 calves exposed to 5 degrees C, in 9 calves exposed to 35 degrees C and in 8 control calves (kept at 18-20 degrees C). Within the period beginning 3 days before exposure and lasting until up to 21 days after exposure, each calf was examined clinically. Rectal temperature and respiratory rate were measured daily. All calves were euthanised on day 21 after exposure. Macroscopically visible pneumonic lesions were evaluated using a semiquantitative system. Tissue samples from tonsils, bronchi, trachea, lung and mediastinal lymph nodes were examined bacteriologically. In contrast to non-exposed control calves, severe respiratory illness was observed in individual calves of both exposed groups (5 degrees C, 35 degrees C). Significant increases in body temperature, respiratory rate and animal losses (2 calves died in the group exposed to 5 degrees C, one calf died in the group exposed to 35 degrees C) were the main clinical findings. At necropsy (3 weeks after exposure), no pneumonic lesions were observed in control calves--despite the fact that this group had the highest microbiological colonisation rates in tonsils and in large airways, i.e. trachea and bronchi, within all groups. However, variable pneumonic lung lesions were seen in remaining calves exposed to cold or warm air (5 degrees C, 35 degrees C). The microbiological examination confirmed that mainly Mycoplasma spp. were identified in the lung tissue of calves exposed to 5 degrees C while Pasteurella multocida and/or Mannheimia haemolytica were the only germs found in the lung tissue of calves exposed to 35 degrees C. The

  2. Risk factors in surgical management of thoracic empyema in elderly patients.

    PubMed

    Hsieh, Ming-Ju; Liu, Yun-Hen; Chao, Yin-Kai; Lu, Ming-Shian; Liu, Hui-Ping; Wu, Yi-Cheng; Lu, Hung-I; Chu, Yen

    2008-06-01

    Although elderly patients with thoracic disease were considered to be poor candidates for thoracotomy before, recent advances in preoperative and postoperative care as well as surgical techniques have improved outcomes of thoracotomies in this patient group. The aim of this study was to investigate surgical risk factors and results in elderly patients (aged > or =70 years) with thoracic empyema. Seventy-one elderly patients with empyema thoracis were enrolled and evaluated from July 2000 to April 2003. The following characteristics and clinical data were analysed: age, sex, aetiology of empyema, comorbid diseases, preoperative conditions, postoperative days of intubation, length of hospital stay after surgery, complications and mortality. Surgical intervention, including total pneumonolysis and evacuation of the pleura empyema cavity, was carried out in all patients. Possible influent risk factors on the outcome were analysed. The sample group included 54 men and 17 women with an average age of 76.8 years. The causes of empyema included parapneumonic effusion (n = 43), lung abscess (n = 8), necrotizing pneumonitis (n = 8), malignancy (n = 5), cirrhosis (n = 2), oesophageal perforation (n = 2), post-traumatic empyema (n = 2) and post-thoracotomy complication (n = 1). The 30-day mortality rate was 11.3% and the in-hospital mortality rate was 18.3% (13 of 71). Mean follow up was 9.4 months and mean duration of postoperative hospitalization was 35.8 days. Analysis of risk factors showed that patients with necrotizing pneumonitis or abscess had the highest mortality rate (10 of 18, 62.6%). The second highest risk factor was preoperative intubation or ventilator-dependency (8 of 18, 44.4%). This study presents the clinical features and outcomes of 71 elderly patients with empyema thoracis who underwent surgical treatment. The 30-day surgical mortality rate was 11.3%. Significant risk factors in elderly patients with empyema thoracis were necrotizing pneumonitis, abscess

  3. Differential diagnosis of granulomatous lung disease: clues and pitfalls: Number 4 in the Series "Pathology for the clinician" Edited by Peter Dorfmüller and Alberto Cavazza.

    PubMed

    Ohshimo, Shinichiro; Guzman, Josune; Costabel, Ulrich; Bonella, Francesco

    2017-09-30

    Granulomatous lung diseases are a heterogeneous group of disorders that have a wide spectrum of pathologies with variable clinical manifestations and outcomes. Precise clinical evaluation, laboratory testing, pulmonary function testing, radiological imaging including high-resolution computed tomography and often histopathological assessment contribute to make a confident diagnosis of granulomatous lung diseases. Differential diagnosis is challenging, and includes both infectious (mycobacteria and fungi) and noninfectious lung diseases (sarcoidosis, necrotising sarcoid granulomatosis, hypersensitivity pneumonitis, hot tub lung, berylliosis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, rheumatoid nodules, talc granulomatosis, Langerhans cell histiocytosis and bronchocentric granulomatosis). Bronchoalveolar lavage, endobronchial ultrasound-guided transbronchial needle aspiration, transbronchial cryobiopsy, positron emission tomography and genetic evaluation are potential candidates to improve the diagnostic accuracy for granulomatous lung diseases. As granuloma alone is a nonspecific histopathological finding, the multidisciplinary approach is important for a confident diagnosis. Copyright ©ERS 2017.

  4. I-131 Radiation-Induced Myelosuppression in Differentiated Thyroid Cancer Therapy.

    PubMed

    Probst, Stephan; Abikhzer, Gad; Chaussé, Guillaume; Tamilia, Michael

    2018-06-07

    Radioactive iodine (RAI) treatment of differentiated thyroid cancer has been used in clinical practice for almost 60 years and is generally accepted to be a safe and efficacious treatment. Severe toxicity in the form of radiation pneumonitis, sometimes progressing to fibrosis, and bone marrow suppression are reported but remain rare. We present a case of severe myelosuppression requiring hospitalization and transfusion support in an otherwise well, young female patient who had received 175 mCi I-131 for low-volume micronodular lung disease one month prior, with a cumulative lifetime administered activity of 575 mCi. The most important risk factors for myelosuppression following RAI are the activity received, the amount of functioning thyroid tissue present, and the lifetime cumulative activity received.

  5. Acute mercury vapor poisoning in a 3-month-old infant: A case report.

    PubMed

    Gao, Zhenyan; Ying, Xiaolan; Yan, Jin; Wang, Ju; Cai, Shizhong; Yan, Chonghuai

    2017-02-01

    We investigated the clinical characteristics of a 3-month-old infant with acute mercury vapor poisoning. Clinical symptoms of acute mercury poisoning in infants include acute onset, rapid progression, severe illness with respiratory symptoms that may result in pneumothoraces and aspiration pneumonias. A 3-month-old girl presented with pneumothoraces and respiratory failure to the hospital. Two days before hospitalization, the girl had stayed in a room containing mercury vapor for several hours. She was hospitalized for acute mercury poisoning. We used sodium dimercaptosulphonate (DMPS) for treatment. Pulmonary disease was mainly induced by the inhalation of mercury vapor. The disease was characterized by acute respiratory distress, pneumothorax and acute chemical pneumonitis. It responded to chelation therapy with the agent DMPS. Copyright © 2016. Published by Elsevier B.V.

  6. Toxicology of oxides of nitrogen. I. Toxic concentrations

    SciTech Connect

    La Towsky, L.W.; MacQuiddy, E.L.; Tollman, J.P.

    1941-01-01

    One hundred twelve rabbits, cats, guinea pigs, rats, and mice were exposed to 30 to 1000 ppM NO/sub 2/. Average time to produce death was: 30 ppM - none in 3 hr, 100 ppM - 318 min, 150 ppM - 90 min, 400 ppM - 58 min, 600 ppM - 32 min, 800 ppM - 29 min, 1000 ppM - 19 min. Rats and mice were more sensitive, sometimes exhibiting delayed effects (e.g., 2 to 3 hr at 55 ppM). Cats were most sensitive in that they thrash excitedly, thus breathing more. Methemoglobin was frequently seen in blood during exposure.more » Death was from edema (most common), asphyxia, or pneumonitis (secondary).« less

  7. [Interrelationship among "NANDA, NOC and NIC". A pilot study and an evaluation of a nursing document].

    PubMed

    Gomez de Segura Navarro, Carlota; Esain Larrambe, Ainhoa; Tina Majuelo, Pilar; Guembe Ibáñez, Irene; Fernández Perea, Laura; Narvaiza Solís, M Jesús

    2006-01-01

    (a) to determine the effectiveness of a nursing document which integrates nursing diagnoses, nursing treatments/actions (NIC), and results (NOC); (b) to verify the application of the aforementioned document in a hospitalization unit. A descriptive, transversal and observational study. Nursing documents (NANDA, NIC and NOC taxonomies). PHASES: 1st: analysis of the content in the nursing documentation for 23 pneumonic patients: Selection of nursing diagnoses and the most frequent interdependent problems. 2nd: Selection of results and nursing treatment/actions. 3rd: Elaboration of the document and a description of the Likert scales to define the state of the indicators for each result. 4th: A pilot study of the document applied to 12 patients. the application of the document permits one to identify the real status of a patient; to establish specific objectives; to improve the recording of data; to observe the effectiveness of treatment; to include educational activities; to give greater continuity and quality to a treatment plan.

  8. Advances in the Management of Meconium Aspiration Syndrome

    PubMed Central

    Swarnam, Kamala; Soraisham, Amuchou S.; Sivanandan, Sindhu

    2012-01-01

    Meconium aspiration syndrome (MAS) is a common cause of severe respiratory distress in term infants, with an associated highly variable morbidity and mortality. MAS results from aspiration of meconium during intrauterine gasping or during the first few breaths. The pathophysiology of MAS is multifactorial and includes acute airway obstruction, surfactant dysfunction or inactivation, chemical pneumonitis with release of vasoconstrictive and inflammatory mediators, and persistent pulmonary hypertension of newborn (PPHN). This disorder can be life threatening, often complicated by respiratory failure, pulmonary air leaks, and PPHN. Approaches to the prevention of MAS have changed over time with collaboration between obstetricians and pediatricians forming the foundations for care. The use of surfactant and inhaled nitric oxide (iNO) has led to the decreased mortality and the need for extracorporeal membrane oxygenation (ECMO) use. In this paper, we review the current understanding of the pathophysiology and management of MAS. PMID:22164183

  9. Fatal pulmonary co-infection with pneumocystis and cytomegalovirus in a patient with acquired immunodeficiency syndrome.

    PubMed

    Chuganji, Eri; Abe, Toshikazu; Kobayashi, Hiroyuki; Nakano, Noriyuki; Kanai, Takao; Ohara, Gen; Takayashiki, Norio; Noguchi, Masayuki; Morishita, Yukio; Aoki, Makoto; Tokuda, Yasuharu

    2014-01-01

    A 33-year-old homosexual Japanese man who admitted to having sex with men presented with a two-week history of dyspnea and fever. Chest imaging showed diffuse pulmonary frosted-glass-like shadows. A blood test revealed positive HIV antibodies with a CD4 cell count of 66/μL. Bronchoalveolar lavage identified pneumocystis. Although the patient exhibited a transient response to anti-pneumocystis treatment and mega-dose steroid pulse therapy, he eventually died from respiratory failure. An autopsy suggested massive cytomegalovirus and pneumocystis pneumonitis. The pulmonary co-infection with cytomegalovirus may have been worsened by the use of mega-dose steroids, and such therapy should be avoided in patients with a high HIV viral load and low CD4 count.

  10. Pulmonary health effects of agriculture.

    PubMed

    Nordgren, Tara M; Bailey, Kristina L

    2016-03-01

    Occupational exposures in the agricultural industry are associated with numerous lung diseases, including chronic obstructive pulmonary disease, asthma, hypersensitivity pneumonitis, lung cancer, and interstitial lung diseases. Efforts are ongoing to ascertain contributing factors to these negative respiratory outcomes and improve monitoring of environmental factors leading to disease. In this review, recently published studies investigating the deleterious effects of occupational exposures in the agricultural industry are discussed. Occupational exposures to numerous agricultural environment aerosols, including pesticides, fungi, and bacteria are associated with impaired respiratory function and disease. Increases in certain farming practices, including mushroom and greenhouse farming, present new occupational exposure concerns. Improved detection methods may provide opportunities to better monitor safe exposure levels to known lung irritants. In the agricultural industry, occupational exposures to organic and inorganic aerosols lead to increased risk for lung disease among workers. Increased awareness of respiratory risks and improved monitoring of agricultural environments are necessary to limit pulmonary health risks to exposed populations.

  11. Applications of Machine Learning for Radiation Therapy.

    PubMed

    Arimura, Hidetaka; Nakamoto, Takahiro

    2016-01-01

    Radiation therapy has been highly advanced as image guided radiation therapy (IGRT) by making advantage of image engineering technologies. Recently, novel frameworks based on image engineering technologies as well as machine learning technologies have been studied for sophisticating the radiation therapy. In this review paper, the author introduces several researches of applications of machine learning for radiation therapy. For examples, a method to determine the threshold values for standardized uptake value (SUV) for estimation of gross tumor volume (GTV) in positron emission tomography (PET) images, an approach to estimate the multileaf collimator (MLC) position errors between treatment plans and radiation delivery time, and prediction frameworks for esophageal stenosis and radiation pneumonitis risk after radiation therapy are described. Finally, the author introduces seven issues that one should consider when applying machine learning models to radiation therapy.

  12. Endobronchial occlusive disease: Nd:YAG or PDT?

    NASA Astrophysics Data System (ADS)

    Regal, Anne-Marie; Takita, Hiroshi

    1991-06-01

    Patients with endobronchial occlusion commonly experience dyspnea, cough, hemoptysis, pneumonitis, and atelectasis. If luminal patency is not re-established, obstructive symptoms may progress to sepsis and death. Although the overall survival of patients with lung cancer may not be altered by relief of airway obstruction, the prognosis for this subset of patients may be improved by eliminating the septic complications of bronchial occlusion. Techniques to treat occluded bronchi include electro-fulguration, cryotherapy, brachytherapy, laser (CO2, Nd-YAG) therapy, and photodynamic therapy (PDT). These represent local forms of treatment and are intended to be palliative. Nd-YAG and PDT are the modalities more frequently utilized in this setting. Comparison of the two treatment forms may furnish insight regarding the appropriate role for each as individual therapies and as part of the armamentarium of cancer therapies.

  13. Handling a community-acquired methicillin-resistant Staphylococcus aureus outbreak: emerging data.

    PubMed

    Elston, Dirk M

    2008-08-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CAMRSA) strains continue to emerge as important causes of sepsis, folliculitis, skin abscesses, necrotizing pneumonitis, empyema, and bone and joint infections. Community-acquired methicillin-resistant S aureus often affects young, previously healthy individuals, including athletes and children in day care. Drainage remains the most important intervention for an abscess. The most common CAMRSA strains in the United States, Canada, and Europe remain sensitive to sulfonamides and tetracycline. Rates of clindamycin resistance vary widely geographically, and physicians should be familiar with their local antibiogram data. Multidrug-resistant strains of CAMRSA are emerging, and the routine addition of antibiotics such as tetracycline to animal feed is contributing to the emergence of resistance. Recurrence and spread of infection can be reduced by addressing the carrier state. Strategies for treatment and elimination of staphylococcal carriage are discussed.

  14. The natural history and incidence of Yersinia pestis and prospects for vaccination.

    PubMed

    Williamson, E D; Oyston, P C F

    2012-07-01

    Plague is an ancient, serious, infectious disease which is still endemic in regions of the modern world and is a potential biothreat agent. This paper discusses the natural history of the bacterium and its evolution into a flea-vectored bacterium able to transmit bubonic plague. It reviews the incidence of plague in the modern world and charts the history of vaccines which have been used to protect against the flea-vectored disease, which erupts as bubonic plague. Current approaches to vaccine development to protect against pneumonic, as well as bubonic, plague are also reviewed. The considerable challenges in achieving a vaccine which is licensed for human use and which will comprehensively protect against this serious human pathogen are assessed.

  15. Plague.

    PubMed

    Prentice, Michael B; Rahalison, Lila

    2007-04-07

    Bubonic plague is an often fulminant systemic zoonosis, caused by Yersinia pestis. Conventional microbiology, bacterial population genetics, and genome sequence data, all suggest that Y pestis is a recently evolved clone of the enteric pathogen Yersinia pseudotuberculosis. The genetic basis of this organism's rapid adaptation to its insect vector (the flea) with transmission between mammalian hosts by novel subcutaneous and pneumonic routes of infection is becoming clearer. This transition provides a paradigm for the way in which new pathogens could emerge. Plague in humans is controlled by suppression of rodent reservoir hosts and their fleas and by early detection and treatment of cases of disease. Detection systems for plague in non-endemic regions might now be needed because of a bioterrorism threat. Rapid diagnostic tests are available and a subunit vaccine is in clinical trials.

  16. Yersinia pestis caf1 variants and the limits of plague vaccine protection.

    PubMed

    Quenee, Lauriane E; Cornelius, Claire A; Ciletti, Nancy A; Elli, Derek; Schneewind, Olaf

    2008-05-01

    Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains.

  17. Oral immunisation with live aroA attenuated Salmonella enterica serovar Typhimurium expressing the Yersinia pestis V antigen protects mice against plague.

    PubMed

    Garmory, Helen S; Griffin, Kate F; Brown, Katherine A; Titball, Richard W

    2003-06-20

    Bubonic and pneumonic plague are caused by the bacterium Yersinia pestis. The V antigen of Y. pestis is a protective antigen against plague. In this study, an aroA attenuated strain of Salmonella enterica serovar Typhimurium (SL3261) has been used to deliver the Y. pestis V antigen as a candidate oral plague vaccine. SL3261 was transformed with the expression plasmid pTrc-LcrV, containing the lcrV gene encoding V antigen. Immunoblot analysis showed V antigen expression in SL3261 in vitro and intragastric immunisation of mice with the recombinant Salmonella resulted in the induction of V antigen-specific serum antibody responses and afforded protection against Y. pestis challenge. However, the antibody responses induced by the recombinant Salmonella did not correlate with the protection afforded, indicating that immune responses other than antibody may play a role in the protection afforded against plague by this candidate vaccine.

  18. Plague.

    PubMed

    Cobbs, C Glenn; Chansolme, David H

    2004-07-01

    Plague is a disease that has been present for thousands of years and described since the earliest medical accounts. It occurs today worldwide, and may present in a variety of clinical forms. Bubonic disease, pneumonic plague, and septicemic plague are seen in addition to a number of other less common manifestations. As an agent of bioterrorism,Yersinia pestis could pose an extreme threat if released in the appropriate form and in the appropriate environment. Presumptive diagnosis may be made with readily available techniques, but laboratory handling of specimens requires special care. When there is a strong suspicion of plague, treatment should be instituted immediately, as delaying therapy will result in increased morbidity and mortality.

  19. Anthrax in transit; practical experience and intellectual exchange.

    PubMed

    Jones, Susan D; Teigen, Philip M

    2008-09-01

    Focusing on three Anglo-American outbreaks of industrial anthrax, this essay engages the question of how local circumstances influenced the transmission of scientific knowledge in the late nineteenth century. Walpole (Massachusetts), Glasgow, and Bradford (Yorkshire) served as important nodes of transnational investigation into anthrax. Knowledge about the morphology and behavior of Bacillus anthracis changed little while in transit between these nodes, even during complex debates about the nature of bacterial morphology, disease causation, and spontaneous generation. Working independently of their more famous counterparts (Robert Koch and Louis Pasteur), Anglo-American anthrax investigators used visual representations of anthrax bacilli to persuade their peers that a specific, identifiable cause produced all forms of anthrax-malignant pustule (cutaneous anthrax), intestinal anthrax, and woolsorter's disease (pneumonic anthrax). By the late 1870s, this point of view also supported what we would today call an ecological notion of the disease's origins in the interactions of people, animals, and microorganisms in the context of global commerce.

  20. Disseminated talc granulomatosis. An unusual finding in a patient with acquired immunodeficiency syndrome and fatal cytomegalovirus infection.

    PubMed

    Lewis, J H; Sundeen, J T; Simon, G L; Schulof, R S; Wand, G S; Gelfand, R L; Miller, H; Garrett, C T; Jannotta, F S; Orenstein, J M

    1985-02-01

    The association of disseminated magnesium silicate talc granulomatosis and acquired immunodeficiency syndrome is reported in a male homosexual who used intravenous drugs and who died of overwhelming cytomegalovirus (CMV) infection. Autopsy findings included widespread deposition of talc crystals in the lungs, liver, lymph nodes, bone marrow, and spleen. Typical CMV inclusions were seen in the lungs, kidneys, adrenal glands, gastrointestinal tract, and right eye. There was no evidence of malignancy. Analysis of peripheral blood neutrophil function revealed impaired chemotaxis and chemokinesis, but opsonophagocytosis had remained normal. The CMV infection in the small bowel was extensive and resulted in severe destruction of the muscularis propria and neural plexi, leading to marked dilatation and persistent diarrhea. The terminal course was marked by intractable hypotension, pneumonitis, and malnutrition, which could be attributed respectively to CMV involvement of the adrenal glands, lungs, and small bowel. The etiology and possible role of systemic talc granulomatosis in the development of immunosuppressive illness is reported herein.

  1. B cell receptor inhibition as a target for CLL therapy.

    PubMed

    Jeyakumar, Deepa; O'Brien, Susan

    2016-03-01

    Inhibitors of the B cell receptor (BCR) represent an attractive therapeutic option for patients with chronic lymphocytic leukemia. Recently approved inhibitors of Bruton's tyrosine kinase (ibrutinib) and phosphatidylinositol 3-kinase (idelalisib), are promising agents because they are generally well tolerated and highly effective. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and infections) associated with chemoimmunotherapy. As a class of medications, BCR inhibitors have some unique side effects including redistribution lymphocytosis. Ibrutinib has specific toxicities including increased risk for bleeding and atrial fibrillation. Idelalisib also has some unique toxicities consisting of transaminitis, diarrhea and pneumonitis. Ongoing clinical trials are evaluating these agents in combination with antibodies, chemotherapy and other small molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. SciTech Connect

    Adelstein, D.J.; Padhya, T.; Tomashefski, J.F. Jr.

    We describe a patient with recurrent small cell undifferentiated lung carcinoma after chemotherapy and mediastinal radiation therapy who presented with peripheral pulmonary infiltrates on chest radiograph. At autopsy the patient was found to have carcinomatous pneumonia confined to the radiographically abnormal lung. The descriptive term reverse radiation pneumonitis is applied in view of the striking nonsegmental distribution of these pulmonary infiltrates, which occurred only outside the irradiated field. In this patient, radiation therapy successfully controlled disease in the treated lung parenchyma, thus accounting for this unusual radiologic and histologic picture. Pneumonia carcinomatosa, occurring after lung irradiation, can therefore be addedmore » to the differential diagnosis of radiographic peripheral pulmonary infiltrates.« less

  3. CHANGES IN LUNG PARENCHYMA WITH PREOPERATIVE Co$sup 60$-IRRADIATION OF BRONCHIAL CARCINOMA

    SciTech Connect

    Widow, W.

    1959-01-01

    Histologic studies were made of resected lung tissue of 24 patients subjected to radiotherapy. Radiation pneumonitis with incipient fibrosis was observed in 14 cases. In only five of these cases could the histologic findings be confirmed radiologically. The histologic changes included swelling of alveolar septa, interstitial edema, increase of connective tissue components, giant cell formation, exfoliation of alveolar cells, intra-alveolar edema, depositio of cellular debris in small bronchi with apparent injury to the ciliated epithelial and mucous cells, and swelling of the peribronchial and perivascular tissue and pleura. Only a sparse inflammatory cell infiltrate was noted. These responses could notmore » be closely correlated with the radiation dose. The radiation reaction was most marked in the vicinity of old tuberculous lesions. No permanent impairment of pulmonary function would be expected from the observed histologic changes. (H.H.D.)« less

  4. ON THE RADIATION REACTION IN THE REGION OF CICATRIZED LUNG PROCESSES

    SciTech Connect

    Widow, W.; Huber, R.

    1961-03-30

    The effect of radiotherapy on old tuberculous lung scars was investigated in 23 persons undergoing treatment for lung cancer. In most cases total Co/sup 60/ x-ray doses of 2000 to 4000 r were given over a 2- to 3-week period, after which time cancer-bearing portions of the lung were surgically removed. Sections of the lung were examined histologically to determine particularly whether irradiation reactivated old tuberculous lesions. In 20 of the 23 cases, marked histologic changes, reflecting radiation pneumonitis, were observed, and in 8 cases tuberculous scar tissue was noted. Findings in these cases are described in detail. Except formore » one case, there was no evidence that irradiation exacerbated the tuberculous process; on the other hand, the radiation reaction appeared to be intensified in the vicinity of tubercles. (H.H.D.)« less

  5. Interstitial pneumonia associated to peginterferon alpha-2a: A focus on lung function

    PubMed Central

    Cortés-Telles, Arturo

    2016-01-01

    Pulmonary toxicity related to the use of pegylated interferon alpha-2a during treatment of hepatitis C infections is rare; nonetheless, some cases with fatal outcomes have been reported. Evaluating patients’ pulmonary function is a key to diagnosis, follow-up and prognosis of several respiratory diseases, but case reports of respiratory manifestations related to the use of pegylated interferon alpha-2a have limited their findings to only baseline measurements. This paper examines the case of a 65-year-old woman with chronic hepatitis C virus infection who developed interstitial pneumonitis associated with pegylated interferon alpha-2a. Initial lung function evaluation revealed a marked reduction compared to an earlier assessment; the results were consistent with a moderate restricted pattern. Fortunately, over the ensuing 8 weeks of follow-up after discontinuing the drug, the patient recovered her lung function and experienced an overall improvement in her respiratory symptoms. PMID:27051119

  6. Ice hockey lung – a case of mass nitrogen dioxide poisoning in the Czech Republic

    PubMed Central

    Brat, Kristian; Merta, Zdenek; Plutinsky, Marek; Skrickova, Jana; Ing, Miroslav Stanek

    2013-01-01

    Nitrogen dioxide (NO2) is a toxic gas, a product of combustion in malfunctioning ice-resurfacing machines. NO2 poisoning is rare but potentially lethal. The authors report a case of mass NO2 poisoning involving 15 amateur ice hockey players in the Czech Republic. All players were treated in the Department of Respiratory Diseases at Brno University Hospital in November 2010 – three as inpatients because they developed pneumonitis. All patients were followed-up until November 2011. Complete recovery in all but one patient was achieved by December 2010. None of the 15 patients developed asthma-like disease or chronic cough. Corticosteroids appeared to be useful in treatment. Electric-powered ice-resurfacing machines are preferable in indoor ice skating arenas. PMID:24032121

  7. Treatment for Radiation-Induced Pulmonary Late Effects: Spoiled for Choice or Looking in the Wrong Direction?

    PubMed Central

    Williams, Jacqueline P.; Johnston, Carl J.; Finkelstein, Jacob N.

    2010-01-01

    Due to the radiosensitivity of the lung, toxic endpoints, in the form of radiation pneumonitis and pulmonary fibrosis, are relatively frequent outcomes following radiation treatment of thoracic neoplasms. Because of the potential lethal nature of these normal tissue reactions, they not only lead to quality-of-life issues in survivors, but also are deemed dose-limiting and thereby compromise treatment. The mitigation and treatment of lung normal tissue late effects has therefore been the goal of many investigations; however, the complexity of both the organ itself and its response to injury has resulted in little success. Nonetheless, current technology allows us to propose likely targets that are either currently being researched or should be considered in future studies. PMID:20583979

  8. Melioidosis: reactivation during radiation therapy

    SciTech Connect

    Jegasothy, B.V.; Goslen, J.B.; Salvatore, M.A.

    1980-05-01

    Melioidosis is caused by Pseudomonas pseudomallei, a gram-negative, motile bacillus which is a naturally occurring soil saprophyte. The organism is endemic in Southeast Asia, the Philippines, Australia, and parts of Central and South America. Most human disease occurs from infection acquired in these countries. Infection with P pseudomallei may produce no apparent clinical disease. Acute pneumonitis or septicemia may result from inhalation of the organism, and inoculation into sites of trauma may cause localized skin abscesses, or the disease may remain latent and be reactivated months or years later by trauma, burns, or pneumococcal pneumonia, diabetic ketoacidosis, influenza, or bronchogenicmore » carcinoma. The last is probably the commonest form of melioidosis seen in the United States. We present the first case of reactivation of melioidosis after radiation therapy for carcinoma of the lung, again emphasizing the need to consider melioidosis in a septic patient with a history of travel, especially to Southeast Asia.« less

  9. Protective environment for marrow transplant recipients. A prospective study

    SciTech Connect

    Buckner, C.D.; Clift, R.A.; Sanders, J.E.

    1978-12-01

    Laminar air flow isolation and decontamination procedures were evaluated in a prospective randomized study in patients with aplastic anemia or acute leukemia undergoing marrow transplantation from HLA-matched siblings. Patients transplanted in the laminar air flow group had significantly less septicemia and major local infections than did patients in the control group. Nineteen of 46 laminar air flow patients and six of 44 control patients are alive at present. In patients with aplastic anemia the survival was 13 of 17 in the laminar air flow group compared with four of 17 in the control group. In patients with acute leukemia themore » survival was six of 29 in the laminar air flow group versus two of 27 in the control group. These differences were not statistically significant. Death in both the laminar air flow and control groups was predominantly due to interstitial pneumonitis or recurrent leukemia, which were unaffected by isolation and decontamination.« less

  10. [Epidemics in the news in Portugal: cholera, plague, typhus, influenza and smallpox, 1854-1918].

    PubMed

    de Almeida, Maria Antónia Pires

    2014-01-01

    In severe health crisis like those of 1854-1856, 1899 and 1918, especially in Porto, where cholera morbus, the bubonic plague, typhus fever, pneumonic influenza and smallpox killed high percentages of the population, the images of the epidemics in the press enable us to identify the scientific knowledge in a country considered peripheral, but which had studies and personnel specialized at the most advanced levels for the time. A database of 6,700 news items and announcements reveals the medical and pharmaceutical knowledge of the second half of the nineteenth and early twentieth centuries, the way it was transmitted and disclosed to the public and the solutions offered by the health authorities. Hygiene was consistently highlighted in the news and announcements.

  11. CT in the diagnosis of interstitial lung disease

    SciTech Connect

    Bergin, C.J.; Mueller, N.L.

    1985-09-01

    The computed tomographic (CT) appearance of interstitial lung disease was assessed in 23 patients with known interstitial disease. These included seven patients with fibrosing alveolitis, six with silicosis, two with hypersensitivity pneumonitis, three with lymphangitic spread of tumor, two with sarcoidosis, one with rheumatoid lung disease, and two with neurofibromatosis. The CT appearance of the interstitial changes in the different disease entities was assessed. Nodules were a prominent CT feature in silicosis, sarcoidosis, and lymphangitic spread of malignancy. Distribution of nodules and associated interlobular septal thickening provided further distinguishing features in these diseases. Reticular densities were the predominant CT changemore » in fibrosing alveolitis, rheumatoid lung disease, and extrinsic allergic alveolitis. CT can be useful in the investigation of selected instances of interstitial pulmonary disease.« less

  12. Hunting for tularaemia - a review of cases in North Carolina.

    PubMed

    Rimawi, R H; Shah, K B; Chowdhary, R A; Cook, P P

    2015-05-01

    Human infections with Francisella tularensis can be acquired via numerous routes, including ingestion, inhalation, arthropod bite or direct contact with infected animals. Since 1991, there have been 25 reported cases of tularaemia in North Carolina, most of which were associated with rabbit hunting or cat bites. We present two adults cases of pulmonary and oropharyngeal tularaemia and review the reported cases since 1991-2013. We also present the fifth case of pulmonary empyema. While cavitary pneumonias are primarily treated with drainage, we illustrate a case of cavitary pneumonia associated with tularaemia successfully treated with oral ciprofloxacin after drainage. Tularaemia should be considered in patients with a perplexing radiographic image, animal exposure and lack of response to conventional empiric broad-spectrum antibiotics. Even in serious cases of pneumonic tularaemia, fluoroquinolones may provide a suitable alternative to aminoglycosides. © 2014 Blackwell Verlag GmbH.

  13. A rare cause of abdominal lymphadenopathy--tularemia: report of two pediatric cases.

    PubMed

    Gülhan, Belgin; Tezer, Hasan; Kanık-Yüksek, Saliha; Kılıç, Selçuk; Senel, Emrah

    2014-01-01

    Tularemia caused by Francisella tularensis occurs worldwide in the northern hemisphere, with great variation in geographic and temporal occurrence. It generally presents as an acute febrile disease with the major clinical presentations including the six classic forms of tularemia: ulceroglandular, glandular, oculoglandular, oropharyngeal, typhoidal, and pneumonic. In contrast to European countries, where the ulceroglandular form is more prominent, the oropharyngeal form is the most common presentation in Turkey. We present rare cases of oropharyngeal tularemia in a 16-year-old boy and nine-year-old girl. To the best of our knowledge, these are the firstly described abdominal lymphadenopathy cases from Turkey. The second case was admitted with erythema nodosum, and abdominal lymphadenopathy was detected during the investigation. Excisional lymph node biopsy revealed abdominal tularemia. It is necessary to consider tularemia in the differential diagnosis of abdominal lymphadenopathy in tularemia regions. We also conclude that oropharyngeal tularemia can cause lymphadenopathy in any part of the gastrointestinal tract.

  14. Kikuchi-Fujimoto disease: an unusual association with acute renal failure.

    PubMed

    Silva, Amanda Feliciano da; Focaccia, Roberto; Oliveira, Allan Constantino de; Sementilli, Angelo; Reis, Gelvana Flávio Barreto

    2010-01-01

    Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis of unknown etiopathogenesis, is a self-limited disease which frequently appears as feverish lymphadenomegaly, thus creating the need for differential diagnosis with lymphoma, systemic lupus erythematosus (SLE), infectious mononucleosis, cat-scratch disease, and toxoplasmosis with lymphonodal impairment. However, there are cases in which it may evolve with complications such as aseptic meningitis, cerebellar ataxia, and aseptic myocarditis. We are presenting a case of a 24-year-old man who had an initial picture of arthralgia, evening fever and adenomegaly. Kikuchi disease was diagnosed through lymph node biopsy with immunohistochemistry and evolves with severe systemic manifestations, such as pericarditis with cardiac tamponade, pneumonitis, hepatitis, and acute kidney failure - the latter has not been reported in literature yet. There was significant improvement of the clinical picture with prednisone.

  15. Middle lobe syndrome in children today.

    PubMed

    Romagnoli, Vittorio; Priftis, Kostas N; de Benedictis, Fernando M

    2014-06-01

    Middle lobe syndrome in children is a distinct clinical and radiographic entity that has been well described in the pediatric literature. However, issues regarding its etiology, clinical presentation, and management continue to puzzle the clinical practitioner. Pathophysiologically, there are two forms of middle lobe syndrome, namely obstructive and nonobstructive. Middle lobe syndrome may present as symptomatic or asymptomatic, as persistent or recurrent atelectasis, or as pneumonitis or bronchiectasis of the middle lobe and/or lingula. A lower threshold of performing a chest radiograph is warranted in children with persistent or recurrent nonspecific respiratory symptoms, particularly if there is clinical deterioration, in order to detect middle lobe syndrome and to initiate a further diagnostic and therapeutic workup. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

    SciTech Connect

    Chuong, Michael D.; Hallemeier, Christopher L.; Jabbour, Salma K.

    Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with protonmore » beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.« less

  17. The indoor air we breathe.

    PubMed Central

    Oliver, L C; Shackleton, B W

    1998-01-01

    Increasingly recognized as a potential public health problem since the outbreak of Legionnaire's disease in Philadelphia in 1976, polluted indoor air has been associated with health problems that include asthma, sick building syndrome, multiple chemical sensitivity, and hypersensitivity pneumonitis. Symptoms are often nonspecific and include headache, eye and throat irritation, chest tightness and shortness of breath, and fatigue. Air-borne contaminants include commonly used chemicals, vehicular exhaust, microbial organisms, fibrous glass particles, and dust. Identified causes include defective building design and construction, aging of buildings and their ventilation systems, poor climate control, inattention to building maintenance. A major contributory factor is the explosion in the use of chemicals in building construction and furnishing materials over the past four decades. Organizational issues and psychological variables often contribute to the problem and hinder its resolution. This article describes the health problems related to poor indoor air quality and offers solutions. Images p398-a p399-a PMID:9769764

  18. Cysticercal encephalitis presenting with a "starry sky" appearance on neuroimaging.

    PubMed

    Patil, Tushar B; Gulhane, Ragini V

    2015-01-01

    A lady in her early forties was brought to our hospital in an unconscious state with history of generalized tonic-clonic seizures for last 6 h. She had multiple episodes of seizures in last 4 months, but did not receive any treatment. Relatives also gave a history of fever, headache, and vomiting for last 1 week. Her seizures were controlled with intravenous lorazepam and valproate. Clinical examination revealed a delirious patient with bilateral papilledema, brisk deep tendon reflexes, and extensor plantars. She had aspirated and had bilateral coarse crepitations on chest auscultation. Computed tomography (CT) of brain showed multiple small hyperdense calcific lesions extending throughout both the cerebral hemispheres leading to a "starry sky" appearance, suggestive of cysticercal encephalitis. The patient succumbed to progressive aspiration pneumonitis on the 6(th) day after hospitalization.

  19. Radiation-Related Treatment Effects across the Age Spectrum: Differences and Similarities or What The Old and Young Can Learn From Each Other

    PubMed Central

    Krasin, Matthew J.; Constine, Louis S.; Friedman, Debra; Marks, Lawrence B.

    2010-01-01

    Radiation related effects in children and adults limit the delivery of effective radiation doses and result in long-term morbidity affecting function and quality of life. Improvements in our understanding of the etiology and biology of these effects, including the influence of clinical variables, dosimetric factors, and the underlying biologic processes has made treatment safer and more efficacious. However, the approach to studying and understanding these effects differs between children and adults. By using the pulmonary and skeletal organ systems as examples, comparisons are made across the age spectrum for radiation related effects including pneumonitis, pulmonary fibrosis, osteonecrosis and fracture. Methods for dosimetric analysis, incorporation of imaging and biology as well a length of follow-up are compared, contrasted and discussed for both organ systems in children and adults. Better understanding of each age specific approach and how it differs may improve our ability to study late effects of radiation across the ages PMID:19959028

  20. Severe acute respiratory distress syndrome caused by unintentional sewing machine lubricant ingestion: A case report.

    PubMed

    Kishore, Sunil; Chandelia, Sudha; Patharia, Neha; Swarnim

    2016-11-01

    Sewing machine oil ingestion is rare but is possible due to its availability at home. Chemically, it belongs to hydrocarbon family which is toxic if aspirated, owing to their physical properties such as high volatility and low viscosity. On the contrary, sewing machine lubricant has high viscosity and low volatility which makes it aspiration less likely. The main danger of hydrocarbon ingestion is chemical pneumonitis which may be as severe as acute respiratory distress syndrome (ARDS). We report a case of a 5-year-old girl with accidental ingestion of sewing machine lubricant oil, who subsequently developed ARDS refractory to mechanical ventilation. There was much improvement with airway pressure release ventilation mode of ventilation, but the child succumbed to death due to pulmonary hemorrhage.

  1. Severe acute respiratory distress syndrome caused by unintentional sewing machine lubricant ingestion: A case report

    PubMed Central

    Kishore, Sunil; Chandelia, Sudha; Patharia, Neha; Swarnim

    2016-01-01

    Sewing machine oil ingestion is rare but is possible due to its availability at home. Chemically, it belongs to hydrocarbon family which is toxic if aspirated, owing to their physical properties such as high volatility and low viscosity. On the contrary, sewing machine lubricant has high viscosity and low volatility which makes it aspiration less likely. The main danger of hydrocarbon ingestion is chemical pneumonitis which may be as severe as acute respiratory distress syndrome (ARDS). We report a case of a 5-year-old girl with accidental ingestion of sewing machine lubricant oil, who subsequently developed ARDS refractory to mechanical ventilation. There was much improvement with airway pressure release ventilation mode of ventilation, but the child succumbed to death due to pulmonary hemorrhage. PMID:27994384

  2. yadBC of Yersinia pestis, a new virulence determinant for bubonic plague.

    PubMed

    Forman, Stanislav; Wulff, Christine R; Myers-Morales, Tanya; Cowan, Clarissa; Perry, Robert D; Straley, Susan C

    2008-02-01

    In all Yersinia pestis strains examined, the adhesin/invasin yadA gene is a pseudogene, yet Y. pestis is invasive for epithelial cells. To identify potential surface proteins that are structurally and functionally similar to YadA, we searched the Y. pestis genome for open reading frames with homology to yadA and found three: the bicistronic operon yadBC (YPO1387 and YPO1388 of Y. pestis CO92; y2786 and y2785 of Y. pestis KIM5), which encodes two putative surface proteins, and YPO0902, which lacks a signal sequence and likely is nonfunctional. In this study we characterized yadBC regulation and tested the importance of this operon for Y. pestis adherence, invasion, and virulence. We found that loss of yadBC caused a modest loss of invasiveness for epithelioid cells and a large decrease in virulence for bubonic plague but not for pneumonic plague in mice.

  3. Plague: Clinics, Diagnosis and Treatment.

    PubMed

    Nikiforov, Vladimir V; Gao, He; Zhou, Lei; Anisimov, Andrey

    2016-01-01

    Plague still poses a significant threat to human health and as a reemerging infection is unfamiliar to the majority of the modern medical doctors. In this chapter, the plague is described according to Dr. Nikiforov's experiences in the diagnosis and treatment of patients, and also a review of the relevant literature on this subject is provided. The main modern methods and criteria for laboratory diagnosis of plague are briefly described. The clinical presentations include the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Early diagnosis and the prompt initiation of treatment reduce the mortality rate associated with bubonic plague and septicemic plague to 5-50 %; although a delay of more than 24 h in the administration of antibiotics and antishock treatment can be fatal for plague patients. Most human cases can successfully be treated with antibiotics.

  4. Ecologic Features of Plague Outbreak Areas, Democratic Republic of the Congo, 2004–2014

    PubMed Central

    Shako, Jean-Christophe; Gaudart, Jean; Sudre, Bertrand; Ilunga, Benoit Kebela; Shamamba, Stomy Karhemere Bi; Diatta, Georges; Davoust, Bernard; Tamfum, Jean-Jacques Muyembe; Piarroux, Renaud; Piarroux, Martine

    2018-01-01

    During 2004–2014, the Democratic Republic of the Congo (DRC) declared 54% of plague cases worldwide. Using national data, we characterized the epidemiology of human plague in DRC for this period. All 4,630 suspected human plague cases and 349 deaths recorded in DRC came from Orientale Province. Pneumonic plague cases (8.8% of total) occurred during 2 major outbreaks in mining camps in the equatorial forest, and some limited outbreaks occurred in the Ituri highlands. Epidemics originated in 5 health zones clustered in Ituri, where sporadic bubonic cases were recorded throughout every year. Classification and regression tree characterized this cluster by the dominance of ecosystem 40 (mountain tropical climate). In conclusion, a small, stable, endemic focus of plague in the highlands of the Ituri tropical region persisted, acting as a source of outbreaks in DRC. PMID:29350136

  5. Respiratory tract disease from thermosetting resins. Study of an outbreak in rubber tire workers.

    PubMed

    doPico, G A; Rankin, J; Chosy, L W; Reddan, W G; Barbee, R A; Gee, B; Dickie, H A

    1975-08-01

    An outbreak of upper and lower respiratory tract inflammatory disease and conjunctivitis among synthetic rubber tire workers occurred. The outbreak began after the introduction of a new thermosetting resin, containing resorcinol and a trimere of methylene aminoacetronitrile, into the rubber tire carcass stock formulation. Two hundred ten workers were affected. Characteristically, symptoms improved during periods of sick leave or vacation, recurring upon the workers' return to the plant. Chest radiograms disclosed pneumonic infiltrates in about one fourth of the cases. Pulmonary function studies detected abnormal airways dynamics as well as abnormal diffusing capacity in more than one third of the workers tested. Lung biopsy showed evidence of focal interstitial fibrosis and peribronchiolar and perivascular chronic inflammatory reaction. The illness was ascribed to volatile products released during the manufacture of synthetic rubber tires. The exact chemical nature of these products is unknown.

  6. Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

    PubMed

    Chuong, Michael D; Hallemeier, Christopher L; Jabbour, Salma K; Yu, Jen; Badiyan, Shahed; Merrell, Kenneth W; Mishra, Mark V; Li, Heng; Verma, Vivek; Lin, Steven H

    2016-05-01

    Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Toxic alveolitis after inhalation of a water repellent.

    PubMed

    Epping, Guido; Van Baarlen, Joop; Van Der Valk, Paul D L P M

    2011-12-01

    Inhalation of fluorocarbon polymers can cause pulmonary toxicity. Although multiple cases of lung injury have been reported, cellular characterization of the associated alveolitis occurring acutely after inhalation is limited. We report the case of a previously healthy woman who presented at our Emergency Department with an acute pneumonitis following inhalation of a fluorocarbon polymer-based rain-proofing spray. Bronchoalveolar lavage (BAL) performed shortly after the presentation showed an elevated total cell count, with a high proportion of neutrophils (58%) and eosinophils (9%). In addition, a lipid stain (Oil-Red-O-stain) showed a high level of lipid laden macrophages, a marker that could reflect a direct toxic effect of the spray on alveolar cells. The patient made a full recovery after four days of in-hospital observation with supportive care.

  8. The cause of death in smallpox: an examination of the pathology record.

    PubMed

    Martin, David Barrett

    2002-07-01

    Because the cause of death in smallpox remains controversial, the human pathology record was examined. The surviving case series of smallpox pathology in humans as well as other review articles from English language journals written during the last 200 years were reviewed. The skin lesions in smallpox developed as a result of viral damage and inflammation. Secondary bacterial infection did not occur until the scabs started shedding. During the papular stage of skin eruption, a secondary viremia caused focal lesions in the pharynx, larynx, tongue, trachea, and esophagus in descending frequency. The virus also caused potentially lethal interstitial pneumonitis as well as tubulointerstitial nephritis. The cytopathic effects of smallpox cause death. The data did not support previously promulgated theories attributing death to a bacterial sepsis syndrome seeded from the pustules or immune complex deposition. In a future outbreak, antibiotic therapy would minimally influence mortality.

  9. "Diesel siphoner's lung": Exogenous lipoid pneumonia following hydrocarbon aspiration.

    PubMed

    Venkatnarayan, Kavitha; Madan, Karan; Walia, Ritika; Kumar, Jaya; Jain, Deepali; Guleria, Randeep

    2014-01-01

    Lipoid pneumonia is an unusual and uncommon form of pneumonia caused by aspiration of fatty substances. Hydrocarbon pneumonitis following aspiration of diesel is a form of exogenous lipoid pneumonia wherein, aspirated diesel reaches the alveoli rapidly without evoking any significant cough, but initiates an intense inflammatory reaction in the pulmonary parenchyma. This is a rarely described clinical scenario, although the practice of diesel siphonage from automobiles is a common practice in developing countries. We herein describe a 40-year-old male patient, in whom the diagnosis of lipoid pneumonia was delayed for a long duration and highlight the importance of taking a detailed occupational exposure history in patients with non-resolving pneumonia to rule out the underlying possibility of this rare clinical entity.

  10. Toxoplasmosis as a travel risk.

    PubMed

    Sepúlveda-Arias, Juan C; Gómez-Marin, Jorge E; Bobić, Branko; Naranjo-Galvis, Carlos A; Djurković-Djaković, Olgica

    2014-01-01

    Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects more than one third of the global population. Primary infection in immunocompetent individuals is usually asymptomatic; however, different organs can be affected in immunocompromised individuals leading to the development of encephalitis, myocarditis or pneumonitis. The prevalence of infection with Toxoplasma as well as its genetic structure varies geographically and for that reason travel may be considered as a risk factor to acquire the infection. As toxoplasmosis is a foodborne disease, health care providers should give health education on prevention measures to all prospective travelers in order to decrease the risk of infection in endemic areas. This review presents an overview of the infection with T. gondii with some considerations for travelers to and from endemic zones. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Plague studies*

    PubMed Central

    Pollitzer, R.

    1953-01-01

    The author examines in detail the symptomatology, diagnosis, and treatment of plague, and outlines the problem of the length of the incubation period. The clinical features commonly met with in all severely-affected plague patients, regardless of the primary localization of the infection, are described. The author then deals with the symptomatology and manifestations of bubonic plague as compared to those of primary pneumonic plague. The importance of a clinical diagnosis, from the point of view of prevention, is stressed, and the differential diagnosis of various forms of the disease is described. The study contains a detailed discussion of the respective merits of antibiotic treatment, serotherapy, and sulfonamide treatment. The author points out that the outstanding success of streptomycin and some other antibiotics will probably relegate the sulfonamides to the second rank in the treatment of bubonic plague. PMID:13082390

  12. Recurrent Aspiration in a Patient With Gastric Band Undergoing Electroconvulsive Therapy.

    PubMed

    Lubit, Elana B; Fetterman, Tammy Cohen; Ying, Patrick

    2016-06-01

    We report a case of a 33-year-old woman with depression and suicidal ideation, treated successfully with electroconvulsive therapy (ECT) in the past. Since her previous course of ECT, she underwent gastric banding, a bariatric surgical procedure associated with increased risk of gastric regurgitation. Despite increasingly stringent measures to minimize the risk of regurgitation and aspiration during ECT, she had several episodes of regurgitation, the last of which precipitated an acute illness consistent with aspiration pneumonitis. We took additional precautions after each event, until she had no further episodes of regurgitation. We discuss the risk posed by the gastric band, the measures we implemented to minimize that risk, and our recommendations for assessment and management of post-gastric banding patients who present for ECT.

  13. Immunological changes with kinase inhibitor therapy for chronic lymphocytic leukemia.

    PubMed

    Pleyer, Christopher; Wiestner, Adrian; Sun, Clare

    2018-05-15

    Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib. While opportunistic infections and viral reactivations occur with both ibrutinib and idelalisib, these complications are less common and less severe with ibrutinib, especially when used as monotherapy without additional immunosuppressive agents. This review discusses the impact of ibrutinib and idelalisib on the immune system, including infectious and auto-immune complications as well as their specific effects on the B-cell, T-cell, and myeloid compartment.

  14. Dose mapping: validation in 4D dosimetry with measurements and application in radiotherapy follow-up evaluation.

    PubMed

    Zhang, Geoffrey G; Huang, Tzung-Chi; Forster, Ken M; Lin, Kang-Ping; Stevens, Craig; Harris, Eleanor; Guerrero, Thomas

    2008-04-01

    The purpose of this paper is to validate a dose mapping program using optical flow method (OFM), and to demonstrate application of the program in radiotherapy follow-up evaluation. For the purpose of validation, the deformation matrices between four-dimensional (4D) CT data of different simulated respiration phases of a phantom were calculated using OFM. The matrices were then used to map doses of all phases to a single-phase image, and summed in equal time weighting. The calculated dose should closely represent the dose delivered to the moving phantom if the deformation matrices are accurately calculated. The measured point doses agreed with the OFM calculations better than 2% at isocenters, and dose distributions better than 1mm for the 50% isodose line. To demonstrate proof-of-concept for the use of deformable image registration in dose mapping for treatment evaluation, the treatment-planning CT was registered with the post-treatment CT image from the positron emission tomography (PET)/CT resulting in a deformation matrix. The dose distribution from the treatment plan was then mapped onto the restaging PET/CT using the deformation matrix. Two cases in which patients had thoracic malignancies are presented. Each patient had CT-based treatment planning for radiotherapy and restaging fluorodeoxy glucose (FDG)-PET/CT imaging 4-6 weeks after completion of treatments. Areas of pneumonitis and recurrence were identified radiographically on both PET and CT restaging images. Local dose and standard uptake values for pneumonitis and recurrence were studied as a demonstration of this method. By comparing the deformable mapped dose to measurement, the treatment evaluation method which is introduced in this manuscript proved to be accurate. It thus provides a more accurate analysis than other rigid or linear dose-image registration when used in studying treatment outcome versus dose.

  15. SciTech Connect

    Ghosh, Swarajit N., E-mail: snghosh@mcw.ed; Zhang Rong; Department of Pharmacology, Harbin Medical University College of Pharmacy, Harbin

    Purpose: To find the mitigators of pneumonitis induced by moderate doses of thoracic radiation (10-15 Gy). Methods and Materials: Unanesthetized WAG/RijCmcr female rats received a single dose of X-irradiation (10, 12, or 15 Gy at 1.615 Gy/min) to the thorax. Captopril (an angiotensin-converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in the drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating the breathing rate, ex vivo vascular reactivity, and histopathologic findings. Survival analysis was undertaken on all animals, except those scheduled for death. Results: Survival after amore » dose of 10 Gy to the thorax was not different from that of unirradiated rats for <=1 year. Survival decreased to <50% by 45 weeks after 12 Gy and by 8-9 weeks after 15 Gy. Captopril (17-56mg/kg/d) improved survival and reduced radiation-induced increases in breathing rate, changes in vascular reactivity, and histopathologic evidence of injury. Radiation-induced increases in the breathing rate were prevented even if captopril was started 1 week after irradiation or if it was discontinued after 5 weeks. Losartan, although effective in reducing mortality, was not as efficacious as captopril in mitigating radiation-induced increases in the breathing rate or altered vasoreactivity. Conclusion: In rats, a moderate thoracic radiation dose induced pneumonitis and morbidity. These injuries were mitigated by captopril even when it was begun 1 week after radiation or if discontinued 5 weeks after exposure. Losartan was less effective in protecting against radiation-induced changes in vascular reactivity or tachypnea.« less

  16. Weighing up the benefits and harms of a new anti-cancer drug: a survey of Australian oncologists.

    PubMed

    Chim, L; Salkeld, G; Stockler, M R; Mileshkin, L

    2015-08-01

    Little is known about the relative importance that oncologists attribute to the benefits and harms of anti-cancer drugs when considering treatment options with their patients. To quantify the trade-offs made between overall survival, progression-free survival and adverse effects. A web-based survey elicited importance weights for the benefits and harms of bevacizumab or everolimus. Combining the importance weights with trial-based probabilities produced a score and ranking for each treatment option. A total of 40 responses was received for the bevacizumab scenario and 32 for the everolimus scenario. All respondents regarded overall survival and progression-free survival as the most important attributes - more important than avoiding the potential harms regardless of drugs. Among the potential harms, respondents allocated the highest mean importance weight to gastrointestinal (GI) perforation and rated absolute improvement in overall survival as 1.6 times and 2.3 times as important as avoiding GI perforation in the two versions of the bevacizumab scenario respectively. For the everolimus scenario, stomatitis and pneumonitis were allocated the highest mean importance weights with absolute improvement in overall survival rated as 2.2 times as important as avoiding stomatitis/pneumonitis. All 40 respondents (100%) favoured treatment option with bevacizumab to no bevacizumab based on respondents' determined weights for treatment attributes. The converse was found for everolimus with 22 (69%) of respondents preferring the 'no everolimus' option. Oncologists' preferences over the benefits and harms of treatment do, when combined with evidence of effect, influence treatment decisions for anti-cancer drugs. © 2015 Royal Australasian College of Physicians.

  17. Alternative diagnosis in the putative ventilator-associated pneumonia patient not meeting lavage-based diagnostic criteria.

    PubMed

    Schoemakers, Rik J; Schnabel, Ronny; Oudhuis, Guy J; Linssen, Catharina F M; van Mook, Walther N K A; Verbon, Annelies; Bergmans, Dennis C J J

    2014-12-01

    The clinical picture of ventilator-associated pneumonia (VAP) can be mimicked by other infectious and non-infectious diseases. The aim of this study was to determine the alternative diagnoses and to develop a diagnostic flow chart for patients suspected of having VAP not meeting the diagnostic broncho-alveolar lavage (BAL) criteria. Adult intensive care patients with a clinical suspicion of VAP and negative BAL results were included. The clinical suspicion of VAP was based on the combination of clinical, radiological, and microbiological criteria. BAL was considered positive if cell differentiation revealed ≥ 2% cells with intracellular organisms and/or quantitative culture results of ≥ 10(4) cfu/ml. The most likely alternative diagnosis of fever and pulmonary densities was retrospectively determined by two authors independently. In all, 110 of 207 patients with suspected VAP did not meet the diagnostic BAL criteria and required further diagnostic evaluation. In 67 patients an alternative diagnosis for fever could be found. In 51 patients an alternative diagnosis of both fever and pulmonary densities could be established. In almost 40% of patients no alternative diagnosis could be provided. Non-bacterial pneumonia was diagnosed in 10 patients with Herpes simplex virus 1 (HSV-1) as the most common pathogen. In eight patients non-infectious pneumonitis was diagnosed. Due to the wide range of alternative diagnoses and applied tests the diagnostic work-up proved to be necessarily individualized and guided by repeated clinical assessment. The most frequently found alternative diagnoses were viral pneumonia and non-infectious pneumonitis.

  18. Clinical Significance of Non-neutropenic Fever in the Management of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Comparison with Febrile Neutropenia and Risk Factor Analysis.

    PubMed

    Park, Silvia; Kang, Cheol-In; Chung, Doo Ryeon; Peck, Kyong Ran; Kim, Won Seog; Kim, Seok Jin

    2015-07-01

    Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard chemotherapy in diffuse large B-cell lymphoma (DLBCL) patients. Although febrile neutropenia (FN) is the major toxicity of this regimen, non-neutropenic fever (NNF) becomes an emerging issue. We analyzed clinical features and outcomes of febrile complications from 397 patients with newly diagnosed DLBCL who were registered in the prospective cohort study. They had completed R-CHOP between September 2008 and January 2013. Thirty-nine patients (9.8%) had NNF whereas 160 patients (40.3%) had FN. Among them, 24 patients (6.0%) had both during their treatment. Compared to frequent occurrence of initial FN after the first cycle (> 50% of total events), more than 80% of NNF cases occurred after the third cycle. Interstitial pneumonitis comprised the highest proportion of NNF cases (54.8%), although the causative organism was not identified in the majority of cases. Thus, pathogen was identified in a limited number of patients (n=9), and Pneumocystis jiroveci pneumonia (PJP) was the most common. Considering that interstitial pneumonitis without documented pathogen could be clinically diagnosed with PJP, the overall rate of PJP including probable cases was 4.5% (18 cases from 397 patients). The NNF-related mortality rate was 10.3% (four deaths from 39 patients with NNF) while the FN-related mortality rate was only 1.3%. NNF was observed with incidence of 10% during R-CHOP treatment, and showed different clinical manifestations with respect to the time of initial episode and causes.

  19. MyD88-Dependent Recruitment of Monocytes and Dendritic Cells Required for Protection from Pulmonary Burkholderia mallei Infection

    PubMed Central

    Goodyear, Andrew; Troyer, Ryan; Bielefeldt-Ohmann, Helle

    2012-01-01

    The Gram-negative bacterium Burkholderia mallei causes rapidly fatal illness in equines and humans when contracted by inhalation and also has the potential to be used as a bioweapon. However, little is known regarding the early innate immune responses and signaling mechanisms required to generate protection from pneumonic B. mallei infection. We showed previously that monocyte chemoattractant protein 1 (MCP-1) was a critical chemokine required for protection from pneumonic B. mallei infection. We have now extended those studies to identify key Toll-like receptor (TLR) signaling pathways, effector cells, and cytokines required for protection from respiratory B. mallei infection. We found that MyD88−/− mice were highly susceptible to pulmonary challenge with B. mallei and had significantly short survival times, increased bacterial burdens, and severe organ pathology compared to wild-type mice. Notably, MyD88−/− mice had significantly fewer monocytes and dendritic cells (DCs) in lung tissues and airways than infected wild-type mice despite markedly higher bacterial burdens. The MyD88−/− mice were also completely unable to produce gamma interferon (IFN-γ) at any time points following infection. In wild-type mice, NK cells were the primary cells producing IFN-γ in the lungs following B. mallei infection, while DCs and monocytes were the primary cellular sources of interleukin-12 (IL-12) production. Treatment with recombinant IFN-γ (rIFN-γ) was able to significantly restore protective immunity in MyD88−/− mice. Thus, we conclude that the MyD88-dependent recruitment of inflammatory monocytes and DCs to the lungs and the local production of IL-12, followed by NK cell production of IFN-γ, are the key initial cellular responses required for early protection from B. mallei infection. PMID:22025508

  20. MyD88-dependent recruitment of monocytes and dendritic cells required for protection from pulmonary Burkholderia mallei infection.

    PubMed

    Goodyear, Andrew; Troyer, Ryan; Bielefeldt-Ohmann, Helle; Dow, Steven

    2012-01-01

    The Gram-negative bacterium Burkholderia mallei causes rapidly fatal illness in equines and humans when contracted by inhalation and also has the potential to be used as a bioweapon. However, little is known regarding the early innate immune responses and signaling mechanisms required to generate protection from pneumonic B. mallei infection. We showed previously that monocyte chemoattractant protein 1 (MCP-1) was a critical chemokine required for protection from pneumonic B. mallei infection. We have now extended those studies to identify key Toll-like receptor (TLR) signaling pathways, effector cells, and cytokines required for protection from respiratory B. mallei infection. We found that MyD88-/- mice were highly susceptible to pulmonary challenge with B. mallei and had significantly short survival times, increased bacterial burdens, and severe organ pathology compared to wild-type mice. Notably, MyD88-/- mice had significantly fewer monocytes and dendritic cells (DCs) in lung tissues and airways than infected wild-type mice despite markedly higher bacterial burdens. The MyD88-/- mice were also completely unable to produce gamma interferon (IFN-γ) at any time points following infection. In wild-type mice, NK cells were the primary cells producing IFN-γ in the lungs following B. mallei infection, while DCs and monocytes were the primary cellular sources of interleukin-12 (IL-12) production. Treatment with recombinant IFN-γ (rIFN-γ) was able to significantly restore protective immunity in MyD88-/- mice. Thus, we conclude that the MyD88-dependent recruitment of inflammatory monocytes and DCs to the lungs and the local production of IL-12, followed by NK cell production of IFN-γ, are the key initial cellular responses required for early protection from B. mallei infection.