Chemokines and inflammation in the nasal passages of infants with respiratory syncytial virus bronchiolitis. (2002 Jul)
chemokines and inflammation in the nasal passages of infants with respiratory syncytial virus bronchiolitis . This study measured chemokines in nasal lavage fluids ( NLF ) from infants with respiratory syncytial virus ( RSV ) bronchiolitis , defined by lung hyperinflation and wheezing . comparison was made to RSV positive infants without bronchiolitis and RSV negative infants with acute respiratory illnesses . RSV positive illnesses were associated with increased epithelial shedding , increased rantes / protein ratios , and increased IL 8 / protein ratios in NLF compared to RSV negative illnesses . among RSV positive infants , bronchiolitics had greater total cell counts and percentage epithelial cells in NLF than nonbronchiolitics . bronchiolitics also had roughly twice the NLF rantes / IL 8 ratio than nonbronchiolitics ( P . 043 ) . semiquantitative reverse transcriptase polymerase chain reaction of nasal epithelium suggested similar rantes / IL 8 ratio increases among bronchiolitics . A more mildly affected , RSV positive outpatient population showed none of these differences . We conclude that RSV bronchiolitis is associated with a shift toward relatively more rantes in nasal secretions of infants sick enough to require hospitalization , and mucosal epithelium may contribute to this process . similar processes in the lower airways may enhance inflammation due to rantes responsive cell types and affect clinical manifestations .

The appearance of cell bound IgE in respiratory tract epithelium after respiratory syncytial virus infection. (1980 Dec)
The appearance of cell bound IgE in respiratory tract epithelium after respiratory syncytial virus infection . We studied the appearance of IgE in the respiratory tract in 42 infants and young children with various forms of respiratory illness after infection by respiratory syncytial virus ( RSV ) . IgE was bound to exfoliated nasopharyngeal epithelial cells in most patients with RSV infection during the acute phase of infection , regardless of the form of illness . however , the continued presence of cell bound IgE was more common in patients with RSV induced bronchiolitis or asthma than in patients with mild upper respiratory tract illness or pneumonia due to RSV . persistence of IgE was also apparently related to the incidence of previous episodes of wheezing in patients or their families . The production of IgE and the subsequent release of chemical mediators of bronchospasm may contribute to the pathogenesis of acute illness due to RSV ; persistence of IgE in the respiratory tract may explain the recurrent episodes of wheezing that occur in many patients after RSV induced bronchiolitis .

Combination treatment with fty720 and ctla4igg preserves the respiratory epithelium and prevents obliterative disease in a murine airway model. (2002 Jun)
combination treatment with fty720 and ctla4igg preserves the respiratory epithelium and prevents obliterative disease in a murine airway model . background : mouse heterotopic tracheal transplantation offers a reproducible model of obliterative bronchiolitis after lung transplantation . ctla4igg inhibits signaling of the CD28 / B7 pathway and induces antigen specific T cell unresponsiveness . fty720 induces T cell apoptosis and sequestration of circulating mature lymphocytes . We previously found that ctla4igg could prevent the development of obliterative airway disease but could not preserve the respiratory epithelium of grafted tracheae . We evaluated whether treatment with either fty720 or ctla4igg , or with combination fty720 and ctla4igg could preserve the respiratory epithelium and inhibit the development of obliterative airway disease . methods : tracheae with main bronchi from C3H / He mice were transplanted heterotopically into BALB / C mice and harvested on Day 35 . recipient mice received either no treatment or treatment with intraperitoneal fty720 , ctla4igg , or the combination of the 2 . results : either fty720 or ctla4igg alone significantly inhibited the development of obliterative airway disease . however , normal ciliated columnar respiratory epithelial cells were lost in the allografts . In contrast , combination therapy preserved the respiratory epithelium of the allografted tracheae . fty720 concentration in the tissue was very high ; treatment with fty720 inhibited mixed lymphocyte reactions and augmented T cell apoptosis . conclusion : combination treatment with fty720 and ctla4igg may prevent obliterative airway disease .

Respiratory syncytial virus infection of human primary nasal and bronchial epithelial cell cultures and bronchoalveolar macrophages. (1992 Apr)
respiratory syncytial virus infection of human primary nasal and bronchial epithelial cell cultures and bronchoalveolar macrophages . In adults , clinical symptoms caused by respiratory syncytial virus ( RSV ) are usually confined to the upper respiratory tract , whereas RSV infection in infants frequently causes bronchiolitis and pneumonia . The preferential localization of RSV infection to the upper airways may partially be due to protective immunity , but may also depend on a difference in susceptibility of epithelial cells from upper and lower airways , or on antiviral activities of bronchoalveolar macrophages ( AM ) . In this study , we have compared the susceptibility of primary adult human nasal epithelium , primary adult human bronchial epithelium , a human bronchial epithelial cell line ( BEAS 2B ) , and adult human AM to infection with RSV . The cell cultures were infected with multiplicities of infection ( moi ) of 1 and 0 . 1 . virus release into the supernatants was assayed at days 1 , 2 , 4 , and 7 , and the percentage of virus positive cells determined by immunofluorescence at the same time points . similar proportions of nasal epithelial cells ( NE ) and bronchial epithelial cells ( BE ) were infected with RSV . approximately 50 to 75 ( with moi 1 ) and 2 to 10 ( with moi 0 . 1 ) of the cells were infected by 24 h ; almost all the cells were RSV positive by …

Intranasal infection of ferrets ( mustela putorius furo ) with canine parainfluenza virus. (1992 Mar)
intranasal infection of ferrets ( mustela putorius furo ) with canine parainfluenza virus . immunocompetent and cyclophosphamide immunosuppressed ferrets were intranasally infected with canine parainfluenza virus ( CPIV ) and observed for clinical signs , histopathologic lesions , the immunocytochemical demonstration of CPIV antigen in the respiratory tract and scanning electron microscopic alterations of the tracheal epithelium until 36 days post infection ( p . i . ) . In both groups , clinical signs were minimal , restricted to the upper respiratory tract and consisted of cough elicited by tracheal compression between 3 and 7 days p . i . microscopically , inflammatory and degenerative lesions were observed in the trachea and less frequently in the nasal cavity ; bronchiolitis or interstitial pneumonia was not demonstrated . By immunocytochemistry , CPIV antigen was demonstrated in tracheal epithelial cells , whereas nasal cavity , bronchi , bronchioles and lung were devoid of viral antigen . ferrets given CPIV alone developed a minimal lymphocytic tracheitis with minimal loss of cilia and CPIV antigen was observed only 4 days p . i . 17 days p . i . , normal epithelial organization and ciliary reappearance was reestablished . ferrets treated with cyclophosphamide and infected with CPIV exhibited mild to moderate histological lesions as above with similar scanning electron microscopic changes until 36 p . i . tracheal lesions consisted of intraepithelial and submucosal infiltration of lymphocytes and macrophages , focal epithelial hyperplasia and multifocal loss of cilia . In addition , …

Detection of respiratory syncytial virus RNA in blood of neonates by polymerase chain reaction. (1998 May)
detection of respiratory syncytial virus RNA in blood of neonates by polymerase chain reaction . during the winter season of 1994 / 1995 , nasopharyngeal aspirates and blood samples of neonates who were admitted to the neonatal intensive Care Unit ( NICU ) ( group 1 ) and infants with respiratory tract disease ( group 2 ) were examined prospectively for the presence of respiratory syncytial virus ( RSV ) . examination of nasal washes were done by antigen detection and blood samples were tested by nested reverse transcription and polymerase chain reaction ( RT PCR ) . The results of the 41 neonates studied were as follows : 14 / 41 were positive for RSV antigen in nasal washes and for RSV RNA in blood , 5 / 41 were only RSV antigen positive , 13 / 41 neonates had negative nasal washes ; 6 had positive RT PCR results in blood . In 9 / 41 cases only blood samples were available . Five of these were positive by RT PCR testing . group 2 included 20 infants hospitalized with respiratory tract disease , e . g . , pneumonia , bronchiolitis , or upper respiratory tract infection ( URTI ) . eleven out of twenty were positive for RSV antigen in nasal washes and 6 / 20 were also positive for RSV RNA in blood . The conclusion is that viremia may be a frequent occurrence in neonates and young children .

Expression of MHC antigens in normal human lungs and transplanted lungs with obliterative bronchiolitis. (1989 Oct)
expression of MHC antigens in normal human lungs and transplanted lungs with obliterative bronchiolitis . immunocytochemical techniques have been used to investigate the expression of common determinants of class I , common determinants of class II and DR , DP , and DQ antigens on frozen sections from twenty normal donor lungs , three lungs resected due to carcinoma and nine lungs removed from heart / lung recipients who were undergoing retransplant due to obliterative bronchiolitis . In all lungs , alveolar macrophages expressed common determinants of class I and class II , as well as DR , DP and DQ antigens . In normal lung , class I was expressed on all vascular endothelium , all tracheal epithelium and most , but not all , bronchiolar epithelium . class II was always expressed on tracheal epithelium , but expression on bronchiolar epithelium and vascular endothelium was variable and sometimes absent . In lungs from transplant patients with severe obliterative bronchiolitis , vascular endothelium , in addition to expressing class I , now consistently expressed class II . epithelium from trachea , bronchioles , and alveoli also consistently expressed class I and class II . To conclude , there is enhanced expression of class II antigens on endothelial and epithelial cells from lungs with obliterative bronchiolitis .

Popcorn worker s lung : in vitro exposure to diacetyl , an ingredient in microwave popcorn butter flavoring , increases … (2006 Aug)
popcorn worker s lung : in vitro exposure to diacetyl , an ingredient in microwave popcorn butter flavoring , increases reactivity to methacholine . workers who inhale microwave popcorn butter flavorings experience decrements in lung function and can develop clinical bronchiolitis obliterans , i . e . , popcorn worker s lung ( kreiss , K . , gomaa , A . , kullman , G . , fedan , K . , simoes , E . J . , enright , P . L . , 2002 . clinical bronchiolitis obliterans in workers at a microwave popcorn plant . N . Engl . J . Med . 347 , 330 338 . ) . In a rat inhalation model , vapors of an artificial butter flavoring damaged the epithelium of the upper and lower airways ( hubbs , A . F . , battelli , L . A . , goldsmith , W . T . , porter , D . W . , frazer , D . , friend , S . , schwegler berry , D . , mercer , R . R . , reynolds , J . S . , grote , A . , castranova , V . , kullman , G . , fedan , J . S . , dowdy , J . , jones , W . G . , 2002 . necrosis of nasal and airway epithelium in rats inhaling vapors of artificial butter flavoring . toxicol . Appl . …

Evaluation of immunoglobulin E specific antibodies and viral antigens in nasopharyngeal secretions of children with respiratory syncytial virus infections. (1993 May)
evaluation of immunoglobulin E specific antibodies and viral antigens in nasopharyngeal secretions of children with respiratory syncytial virus infections . enzyme immunoassays were developed to detect the presence of specific immunoglobulin E ( IgE ) antibodies and respiratory syncytial ( RS ) virus structural proteins in nasopharyngeal secretions in order to improve the knowledge on some aspects of the pathogenesis of severe acute lower respiratory tract infections caused by RS virus . these assays were used to analyze clinical specimens from children with RS virus associated infections ( bronchiolitis and pneumonia ) , and the findings were correlated with the patients clinical symptoms . The results indicate the presence of specific IgE against the two external glycoproteins ( G and F ) and the absence of detectable IgE levels for the internal viral antigens . there was a correlation between the levels of IgE specific antibodies and the amount of viral protein F in the secretions , indicating that the IgE response against the viral glycoproteins might be related to the antigen load . In addition , a correlation was found between higher levels of both viral protein F specific IgE and F antigen with higher respiratory rates in children with pneumonia . these findings may be relevant because they suggest an association between the virus load and the immune response in the pathogenesis of RS virus infections .

Eosinophil degranulation in the respiratory tract during naturally acquired respiratory syncytial virus infection. (1992 Feb)
eosinophil degranulation in the respiratory tract during naturally acquired respiratory syncytial virus infection . eosinophil cationic protein ( ECP ) , a cytotoxic protein contained in the granules of eosinophils , has been suggested as having an important role in the pathogenesis of asthma . To determine whether ECP plays a similar role in bronchiolitis , we tested samples of nasopharyngeal secretions , obtained from a group of 47 children with various forms of illness related to respiratory syncytial virus ( RSV ) and from 26 children with non RSV upper respiratory tract illness or bacterial pneumonia , for the presence of ECP by means of a double antibody radioimmunoassay . concentrations of ECP in children with RSV bronchiolitis were significantly higher ( 166 . 8 ng / ml ) than the mean concentration of ECP in both groups of children with RSV upper respiratory tract illness ( 43 . 5 ng / ml , p less than 0 . 002 ) and RSV lower respiratory tract disease without wheezing ( 29 . 1 ng / ml ; p less than 0 . 0002 ) . children with non RSV upper respiratory tract illness or bacterial pneumonia had levels of ECP in nasopharyngeal secretions similar to those of children with RSV upper respiratory tract illness or RSV pneumonia . High ECP levels in nasopharyngeal secretions ( greater than 50 ng / ml ) were predictive of the development of bronchiolitis at the time of RSV infection ( p less than …

Experimental infection of calves with respiratory syncytial virus. (1975 Sep)
experimental infection of calves with respiratory syncytial virus . three bovine isolates and one human isolate of RS virus were given intranasally to gnotobiotic , colostrum deprived and conventional calves . All isolates produced a biphasic pyrexia associated with a serous nasal discharge . virus was recovered from nasal secretions 4 10 days after inoculation from nasal , tracheal and bronchial mucosae and lung of animals killed 7 13 days after inoculation . infection did not produce any macroscopic lesions , but histologically there was a focal degenerative rhinitis and a catarrhal bronchiolitis with the occasional formation of syncytia in bronchioles and alveoli .

Obliterative airway disease after heterotopic tracheal xenotransplantation : pathogenesis and prevention using new immunosuppressive agents. (1997 Sep)
obliterative airway disease after heterotopic tracheal xenotransplantation : pathogenesis and prevention using new immunosuppressive agents . background : The purpose of this study was to investigate whether obliterative bronchiolitis might occur after xenogenic pulmonary transplantation . A model for obliterative airway disease ( OAD ) after tracheal allograft transplantation in the rat undergoes tracheal obliteration with histologic features characteristic of obliterative bronchiolitis in human lung transplant recipients . using this model , the pathogenesis of OAD and its prevention with immunosuppressive drugs was studied in rat recipients of hamster tracheal grafts . methods : tracheae from 30 hamsters ( xenografts ) or 23 brown norway rats ( allografts ) were implanted and wrapped in the greater omentum of untreated lewis rats . The grafts were removed on day 1 , 3 , 7 , 14 , 21 , or 28 after transplantation and stained with hematoxylin and eosin and masson s trichrome and by immunohistochemistry and immunofluorescence ( IFL ) techniques . In addition , 25 recipients were treated with cyclosporine ( CsA , 10 mg / kg p . o . ) , leflunomide ( LFM , 20 mg / kg p . o . ) , or rapamycin ( RPM , 6 mg / kg i . p . ) for 14 or 21 days ( 5 animals per treatment group ) . visual and morphometric analyses were used to evaluate the extent of airway obliteration , luminal coverage by respiratory or flattened cuboidal epithelium , and extent …

Response of the macaque nasal epithelium to ambient levels of ozone. (1987 Aug)
response of the macaque nasal epithelium to ambient levels of ozone . A morphologic and morphometric study of the transitional and respiratory epithelium . although ozone ( O3 ) induced bronchiolitis has been morphologically characterized , effects of O3 on the upper respiratory tract have not been thoroughly investigated . The purpose of this study was to determine whether exposures to ambient levels of O3 induce lesions in the nasal mucosa . bonnet monkeys were exposed to 0 . 00 , 0 . 15 , or 0 . 30 ppm O3 for 6 or 90 days , 8 hours / day . after exposure , nasal mucosa was processed for light and electron microscopy . quantitative changes were evident in the nasal transitional and respiratory epithelium . At 6 or 90 days of exposure to 0 . 15 or 0 . 30 ppm O3 lesions consisted of ciliated cell necrosis , shortened cilia , and secretory cell hyperplasia . inflammatory cell influx was only present at 6 days of exposure . ultrastructural changes in goblet cells were evident at 90 days . ambient levels of O3 can induce significant nasal epithelial lesions , which may compromise upper respiratory defense mechanisms .

Detection of respiratory syncytial virus in nasopharyngeal secretions by 24 well plate precentrifugation assay using a monoclonal antibody against F … (2000 May)
detection of respiratory syncytial virus in nasopharyngeal secretions by 24 well plate precentrifugation assay using a monoclonal antibody against F protein . background : respiratory syncytial virus ( RSV ) is responsible for 50 of all bronchiolitis and 25 of pneumonia cases during the first month of life . detection of the RSV antigen by immunofluorescence in exfoliated nasal epithelium or by other methods in nasopharyngeal swabs is useful in the potentially infected patient because results are available within a few hours . In contrast , RSV antigen detection in cell culture may require as much as 3 weeks . methods : three methods for detection of respiratory syncytial virus in 131 clinical respiratory specimens from patients with acute respiratory disease and bronchiolitis were compared utilizing the following : a precentrifugation immunofluorescence assay using Hep 2 cells , indirect immunofluorescence assay , and conventional tube cell culture using Hep 2 cells . results : respiratory syncytial virus was identified in 36 specimens by the three methods previously described . The virus was recovered in 41 ( 31 . 3 ) samples by precentrifugation immunofluorescence assay , 40 ( 30 . 5 ) were identified by the immunofluorescence technique , and 38 ( 29 . 0 ) cases were positive by conventional cell culture . The sensitivity of the precentrifugation assay in relation to the immunofluorescence technique was 90 , the specificity 94 . 5 , and the agreement , 96 . 2 . A positive predictive value of 90 . …

Experimental bovine respiratory syncytial virus infection in conventional calves : light microscopic lesions , microbiology , and studies on lavaged … (1985 Jun)
experimental bovine respiratory syncytial virus infection in conventional calves : light microscopic lesions , microbiology , and studies on lavaged lung cells . conventionally raised male holstein calves , 1 month of age , were infected by intranasal and intratracheal inoculation with bovine respiratory syncytial virus . viral antigen was identified by fluorescence microscopy most commonly in the cytoplasm of tracheal and bronchial epithelial cells 3 to 5 days after inoculation . cytoplasmic viral antigen was identified also in nasal , nasopharyngeal , bronchiolar , and alveolar epithelial cells and in alveolar macrophages . bronchitis and tracheitis , characterized in part by epithelial necrosis , formation of syncytial epithelial cells and epithelial hyperplasia , were the most common lesions observed histologically . rhinitis , bronchiolitis , and interstitial pneumonia were observed less frequently . alterations were not detected in the numbers of cells recovered by bronchoalveolar lavage after inoculation . An increase in the phagocytic rate of latex beads occurred in macrophages 5 days after inoculation . viral induced lesions were resolved by 30 days after inoculation . The results indicated that bovine respiratory syncytial virus inoculation of calves results in reversible alterations in airway epithelial structure and in the phagocytic function of alveolar macrophages .

RSV induced bronchiolitis but not upper respiratory tract infection is accompanied by an increased nasal IL 18 response. (2003 Aug)
RSV induced bronchiolitis but not upper respiratory tract infection is accompanied by an increased nasal IL 18 response . The aim of this study was to investigate potential differences in the local nasal immune response between bronchiolitis and upper respiratory tract infection induced by respiratory syncytial virus ( RSV ) . nasal brush samples were obtained from 14 infants with RSV bronchiolitis and from 8 infants with RSV upper respiratory tract infection . The samples were taken during infection ( acute phase ) and 2 4 weeks later ( convalescent phase ) . cytospin preparations were stained immunohistochemically for T cells , macrophages , and eosinophils . staining also took place for intercellular adhesion molecule 1 ( ICAM 1 ) , T helper 1 ( Th1 ) like ( interleukin 12 IL 12 , interferon gamma IFN gamma ) , Th2 like ( IL 4 , IL 10 ) , and proinflammatory cytokines ( IL 6 , IL 8 , IL 18 ) . during both RSV induced bronchiolitis and upper respiratory tract infection , cellular inflammation was observed . This was characterised by an increase in the numbers of nasal macrophages , which tended to be higher in bronchiolitis than in upper respiratory tract infection . numbers of T lymphocytes and ICAM 1 positive cells increased during both bronchiolitis and upper respiratory tract infection . there were no differences between numbers in the groups . interestingly , a distinct nasal proinflammatory cytokine response was observed in RSV induced bronchiolitis …

Experimental sendai virus infection in laboratory rats. (1987 Nov)
experimental sendai virus infection in laboratory rats . II . pathology and immunohistochemistry . intranasal inoculation of 5 to 8 week old specific pathogen free sprague dawley rats with 5 X 10 ( 3 ) egg infectious doses of sendai virus resulted in severe rhinitis , bronchiolitis and alveolitis . The most severe rhinitis occurred on postinoculation ( PI ) days 4 6 , and pneumonia on day 4 . rhinitis and pneumonia persisted to PI day 21 , with peribronchial lymphoid infiltration detectable at PI day 42 . immunohistochemical studies showed that sendai virus antigens were present primarily in columnar epithelial cells of the respiratory mucosa of the nasal cavity and in bronchiolar and alveolar epithelium . antigen was first detectable at PI day 1 , was most prominent at days 3 4 and was undetectable after day 7 . More antigen could be seen in the nasal mucosa than in the lung at any stage in the infection . these studies show that sendai virus by itself is capable of evoking severe , although transient , rhinitis and pneumonia in laboratory rats free of other significant pathogens .

Chest X ray appearances in pneumonia and bronchiolitis. (1990 May)
chest X ray appearances in pneumonia and bronchiolitis . correlation to virological diagnosis and secretory bacterial findings . chest X ray findings were related to virus diagnosis , age and secretory bacterial findings in 128 infants and children under 7 years of age with clinical pneumonia and bronchiolitis . They belonged to a cohort examined in connection with the introduction of rapid methods for virological diagnosis . seventy six children had a virus infection diagnosed by examination of nasopharyngeal secretion and / or by serological methods . thirty seven of these children were classified as having pathogenic bacteria of importance in the respiratory tract . Four groups were compared : virus infected children with or without bacteria in the secretion and the corresponding virus negative groups . The X rays were normal significantly more often in the virus positive / bacteria negative group compared with the other groups . alveolar pneumonia appearing as lobar or segmental consolidations ( lobar pneumonia ) was observed with equal frequency and without relation to bacterial findings in the virus positive and the virus negative groups . But it was more often observed in the respiratory syncytial virus ( RSV ) infected children under 6 months of age compared with the older RSV children . In comparison disperse alveolar infiltrations ( bronchopneumonia ) mostly appeared in the virus positive group . interstitial pneumonia and peribronchitis were often present together in children over 6 months of age . there was no significant difference in the X …

Macrophage inflammatory protein 1alpha ( not T helper type 2 cytokines ) is associated with severe forms of respiratory syncytial … (2001 Jul)
macrophage inflammatory protein 1alpha ( not T helper type 2 cytokines ) is associated with severe forms of respiratory syncytial virus bronchiolitis . It has been suggested that the pathogenesis of respiratory syncytial virus ( RSV ) infection is related to the development of T helper ( Th ) type 2 cytokine responses . The presence of Th1 and Th2 cytokines and the chemokines macrophage inflammatory protein ( MIP ) 1alpha and monocyte chemotactic protein ( MCP ) 1 were assessed by elisa in nasopharyngeal secretions of infants with RSV infection . infants with mild bronchiolitis had increased Th1 cytokines and reduced Th2 cytokines , compared with infants with upper respiratory tract illness alone . severe bronchiolitis was characterized by a more balanced Th1 Th2 response that did not differ from that of infants with upper respiratory tract illness alone . In contrast , MIP 1alpha was markedly increased in infants with severe bronchiolitis . MIP 1alpha and MCP 1 levels also were inversely related to oxygen saturation ( P . 005 ) . Thus , the severity of RSV bronchiolitis appears to be related more to chemokine release than to Th2 cytokine production .