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Janet A Englund - One of the best experts on this subject based on the ideXlab platform.
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a multicenter consortium to define the epidemiology and outcomes of pediatric solid organ transplant recipients with inpatient Respiratory Virus infection
2019Co-Authors: Lara Danzigerisakov, Janet A Englund, William J Steinbach, Grant Paulsen, Flor M Munoz, Leigh R Sweet, Michael R Green, Marian G Michaels, Alastair Murray, Natasha B HalasaAbstract:BACKGROUND Respiratory Virus infection (RVI) in pediatric solid organ transplant (SOT) recipients poses a significant risk; however, the epidemiology and effects of an RVI after pediatric SOT in the era of current molecular diagnostic assays are unclear. METHODS A retrospective observational cohort of pediatric SOT recipients (January 2010 to June 2013) was assembled from 9 US pediatric transplant centers. Charts were reviewed for RVI events associated with hospitalization within 1 year after the transplant. An RVI diagnosis required Respiratory symptoms and detection of a Virus (ie, human rhinoVirus/enteroVirus, human metapneumoVirus, influenza Virus, parainfluenza Virus, coronaVirus, and/or Respiratory syncytial Virus). The incidence of RVI was calculated, and the association of baseline SOT factors with subsequent pulmonary complications and death was assessed. RESULTS Of 1096 pediatric SOT recipients (448 liver, 289 kidney, 251 heart, 66 lung, 42 intestine/multivisceral), 159 (14.5%) developed RVI associated with hospitalization within 12 months after their transplant. RVI occurred at the highest rates in intestine/abdominal multivisceral (38%), thoracic (heart/lung) (18.6%), and liver (15.6%) transplant recipients and a lower rate in kidney (5.5%) transplant recipients. RVI was associated with younger median age at transplant (1.72 vs 7.89 years; P < .001) and among liver or kidney transplant recipients with the receipt of a deceased-donor graft compared to a living donor (P = .01). The all-cause and attributable case-fatality rates within 3 months of RVI onset were 4% and 0%, respectively. Multivariable logistic regression models revealed that age was independently associated with increased risk for a pulmonary complication (odds ratio, 1.24 [95% confidence interval, 1.02-1.51]) and that receipt of an intestine/multivisceral transplant was associated with increased risk of all-cause death (odds ratio, 24.54 [95% confidence interval, 1.69-327.96]). CONCLUSIONS In this study, hospital-associated RVI was common in the first year after pediatric SOT and associated with younger age at transplant. All-cause death after RVI was rare, and no definitive attributable death occurred.
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clinical outcomes associated with Respiratory Virus detection before allogeneic hematopoietic stem cell transplant
2015Co-Authors: Angela P Campbell, Janet A Englund, Katherine A Guthrie, Robert M Farney, Elisa L MinerichAbstract:The decision to proceed with hematopoietic cell transplant (HCT) in patients with new upper Respiratory symptoms is challenging. Guidelines co-sponsored by national and international societies recommend delaying HCT in patients with pretransplant upper Respiratory tract infections (URTIs) [1, 2], although documentation of benefits of delaying is limited and the strength of evidence is low (BIII) [3]. Potential disadvantages of delay include progression of underlying disease and logistical issues regarding donor and patient availability. The benefit of delaying HCT may depend on specific Viruses and symptoms present. One retrospective analysis of pretransplant URTI caused by Respiratory syncytial Virus (RSV) found that delaying HCT reduced the risk of pneumonia after transplant [3]. Another study evaluating parainfluenza Virus (PIV) infections pre-HCT determined that complications were not increased after HCT [4]. Data in children are even more limited [5, 6]. Many transplant centers test symptomatic patients for Respiratory Viruses by polymerase chain reaction (PCR) before HCT and delay transplant, if possible, when Respiratory symptoms are present and Respiratory Viruses including influenza, PIV, RSV, or human metapneumoVirus (HMPV) are detected [2]. For the most prevalent and now readily detectable Viruses including human coronaViruses (HCoVs), human bocaVirus (HBoV), and human rhinoViruses (HRVs), uncertainty exists regarding proceeding to HCT as consequences of mild URTI due to these Viruses are unknown. For centers that collect screening pretransplant nasal specimens, the decision to proceed is problematic when asymptomatic viral shedding is detected. We evaluated clinical outcomes associated with pretransplant Respiratory Viruses in patients followed prospectively before and through 100 days after HCT. Multiplex PCR testing for Respiratory Viruses was performed on nasal washes (NWs) and on lower Respiratory tract samples, if available. We determined whether detection of a pretransplant Respiratory Virus, the type of Virus, or accompanying symptoms influenced patient outcomes during the first 100 days after HCT. Primary outcome measures included lower Respiratory tract disease requiring bronchoscopy, days alive and out of hospital, and overall mortality.
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self collection of foam nasal swabs for Respiratory Virus detection by pcr among immunocompetent subjects and hematopoietic cell transplant recipients
2013Co-Authors: Angela P Campbell, Jane Kuypers, Janet A Englund, Katherine A Guthrie, Lawrence Corey, Michael BoeckhAbstract:Self-collected foam nasal swabs (NS) obtained after instillation of saline spray were compared with nasal washes from immunocompetent subjects during 146 upper Respiratory infections (URIs); the sensitivities for reverse transcription (RT)-PCR Respiratory Virus detection were 95% and 88%, respectively (P = 0.06). The sensitivities from NS collected with and without saline spray during 142 URIs from immunocompetent subjects were 96% and 86% (P = 0.004), respectively, and those from 140 URI samples from hematopoietic cell transplantation recipients were 88% and 85% (P = 0.56), respectively.
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Respiratory Virus pneumonia after hematopoietic cell transplantation hct associations between viral load in bronchoalveolar lavage samples viral rna detection in serum samples and clinical outcomes of hct
2010Co-Authors: Angela P Campbell, Jason W Chien, Jane Kuypers, Janet A Englund, Anna Wald, Katherine A Guthrie, Lawrence Corey, Michael BoeckhAbstract:Background. Few data exist on Respiratory Virus quantitation in lower Respiratory samples and detection in serum from hematopoietic cell transplant (HCT) recipients with Respiratory Virus-associated pneumonia. Methods. We retrospectively identified HCT recipients with Respiratory syncytial Virus (RSV), parainfluenza Virus, influenza Virus, metapneumoVirus (MPV), and coronaVirus (CoV) detected in bronchoalveolar lavage (BAL) samples, and we tested stored BAL and/or serum samples by quantitative polymerase chain reaction. Results. In 85 BAL samples from 82 patients, median viral loads were as follows: for RSV (n = 35), 2.6 × 10 6 copies/mL; for parainfluenza Virus (n = 35), 4.9 × 10 7 copies/mL; for influenza Virus (n = 9), 6.8 × 10 5 copies/mL; for MPV (n = 7), 3.9 × 10 7 copies/mL; and for CoV (n = 4), 1.8 × 10 5 copies/mL. Quantitative viral load was not associated with mechanical ventilation or death. Viral RNA was detected in serum samples from 6 of 66 patients: 4 of 41 with RSV pneumonia, 1 with influenza B, and 1 with MPV/influenza A Virus/CoV coinfection (influenza A Virus and MPV RNA detected). RSV detection in serum was associated with high viral load in BAL samples (P = .05), and viral RNA detection in serum was significantly associated with death (adjusted rate ratio, 1.8; P = .02). Conclusion. Quantitative polymerase chain reaction detects high viral loads in BAL samples from HCT recipients with Respiratory Virus pneumonia. Viral RNA is also detectable in the serum of patients with RSV, influenza, and MPV pneumonia and may correlate with the severity of disease.
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Respiratory Virus infection among hematopoietic cell transplant recipients evidence for asymptomatic parainfluenza Virus infection
2007Co-Authors: Jane Kuypers, Janet A Englund, Katherine A Guthrie, Lawrence Corey, Angela J Peck, Rhoda Ashley Morrow, Robert C HackmanAbstract:The incidence of Respiratory Virus infection after hematopoietic cell transplantation (HCT) has probably been underestimated with conventional testing methods in symptomatic patients. This prospective study assessed viral infection episodes by testing weekly Respiratory samples collected from HCT recipients, with and without symptoms reported by questionnaire, for 100 days after HCT. Samples were tested by culture and direct fluorescent antibody testing for Respiratory syncytial Virus (RSV), parainfluenza Virus (PIV), and influenza A and B, and by quantitative reverse transcription–polymerase chain reaction for RSV, PIV, influenza A and B, and metapneumoVirus (MPV). Of 122 patients, 30 (25%) had 32 infection episodes caused by RSV (5), PIV (17), MPV (6), influenza (3), RSV, or influenza (1). PIV, with a cumulative incidence estimate of 17.9%, was the only Virus for which asymptomatic infection was detected. Lower Virus copy number in patients with no or one symptom compared with 2 or more symptoms was found for all Viruses in all patients (P < .001), with PIV infection having a similar Virus-specific comparison (P = .004). Subclinical infection with PIV may help explain why infection-control programs that emphasize symptoms are effective against RSV and influenza but often not against PIV.
Angela P Campbell - One of the best experts on this subject based on the ideXlab platform.
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clinical outcomes associated with Respiratory Virus detection before allogeneic hematopoietic stem cell transplant
2015Co-Authors: Angela P Campbell, Janet A Englund, Katherine A Guthrie, Robert M Farney, Elisa L MinerichAbstract:The decision to proceed with hematopoietic cell transplant (HCT) in patients with new upper Respiratory symptoms is challenging. Guidelines co-sponsored by national and international societies recommend delaying HCT in patients with pretransplant upper Respiratory tract infections (URTIs) [1, 2], although documentation of benefits of delaying is limited and the strength of evidence is low (BIII) [3]. Potential disadvantages of delay include progression of underlying disease and logistical issues regarding donor and patient availability. The benefit of delaying HCT may depend on specific Viruses and symptoms present. One retrospective analysis of pretransplant URTI caused by Respiratory syncytial Virus (RSV) found that delaying HCT reduced the risk of pneumonia after transplant [3]. Another study evaluating parainfluenza Virus (PIV) infections pre-HCT determined that complications were not increased after HCT [4]. Data in children are even more limited [5, 6]. Many transplant centers test symptomatic patients for Respiratory Viruses by polymerase chain reaction (PCR) before HCT and delay transplant, if possible, when Respiratory symptoms are present and Respiratory Viruses including influenza, PIV, RSV, or human metapneumoVirus (HMPV) are detected [2]. For the most prevalent and now readily detectable Viruses including human coronaViruses (HCoVs), human bocaVirus (HBoV), and human rhinoViruses (HRVs), uncertainty exists regarding proceeding to HCT as consequences of mild URTI due to these Viruses are unknown. For centers that collect screening pretransplant nasal specimens, the decision to proceed is problematic when asymptomatic viral shedding is detected. We evaluated clinical outcomes associated with pretransplant Respiratory Viruses in patients followed prospectively before and through 100 days after HCT. Multiplex PCR testing for Respiratory Viruses was performed on nasal washes (NWs) and on lower Respiratory tract samples, if available. We determined whether detection of a pretransplant Respiratory Virus, the type of Virus, or accompanying symptoms influenced patient outcomes during the first 100 days after HCT. Primary outcome measures included lower Respiratory tract disease requiring bronchoscopy, days alive and out of hospital, and overall mortality.
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a patient self collection method for longitudinal monitoring of Respiratory Virus infection in solid organ transplant recipients
2015Co-Authors: Carl M Preiksaitis, Angela P Campbell, Jane Kuypers, Cynthia E Fisher, Keith R Jerome, Meei Li HuangAbstract:Abstract Background Methods for the longitudinal study of Respiratory Virus infections are cumbersome and limit our understanding of the natural history of these infections in solid organ transplant (SOT) recipients. Objectives To assess the feasibility and patient acceptability of self-collected foam nasal swabs for detection of Respiratory Viruses in SOT recipients and to define the virologic and clinical course. Study design We prospectively monitored the course of symptomatic Respiratory Virus infection in 18 SOT patients (14 lung, 3 liver, and 1 kidney) using patient self-collected swabs. Results The initial study sample was positive in 15 patients with the following Respiratory Viruses: rhinoVirus (6), metapneumoVirus (1), coronaVirus (2), Respiratory syncytial Virus (2), parainfluenza Virus (2), and influenza A Virus (2). One hundred four weekly self-collected nasal swabs were obtained, with a median of 4 samples per patient (range 1–17). Median duration of viral detection was 21 days (range 4–77 days). Additional new Respiratory Viruses detected during follow-up of these 15 patients included rhinoVirus (3), metapneumoVirus (2), coronaVirus (1), Respiratory syncytial Virus (1), parainfluenza Virus (1), and adenoVirus (1). Specimen collection compliance was good; 16/18 (89%) patients collected all required specimens and 79/86 (92%) follow-up specimens were obtained within the 7 ± 3 day protocol-defined window. All participants agreed or strongly agreed that the procedure was comfortable, simple, and 13/14 (93%) were willing to participate in future studies using this procedure. Conclusion Self-collected nasal swabs provide a convenient, feasible, and patient-acceptable methodology for longitudinal monitoring of upper Respiratory Virus infection in SOT recipients.
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self collection of foam nasal swabs for Respiratory Virus detection by pcr among immunocompetent subjects and hematopoietic cell transplant recipients
2013Co-Authors: Angela P Campbell, Jane Kuypers, Janet A Englund, Katherine A Guthrie, Lawrence Corey, Michael BoeckhAbstract:Self-collected foam nasal swabs (NS) obtained after instillation of saline spray were compared with nasal washes from immunocompetent subjects during 146 upper Respiratory infections (URIs); the sensitivities for reverse transcription (RT)-PCR Respiratory Virus detection were 95% and 88%, respectively (P = 0.06). The sensitivities from NS collected with and without saline spray during 142 URIs from immunocompetent subjects were 96% and 86% (P = 0.004), respectively, and those from 140 URI samples from hematopoietic cell transplantation recipients were 88% and 85% (P = 0.56), respectively.
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Respiratory Virus pneumonia after hematopoietic cell transplantation hct associations between viral load in bronchoalveolar lavage samples viral rna detection in serum samples and clinical outcomes of hct
2010Co-Authors: Angela P Campbell, Jason W Chien, Jane Kuypers, Janet A Englund, Anna Wald, Katherine A Guthrie, Lawrence Corey, Michael BoeckhAbstract:Background. Few data exist on Respiratory Virus quantitation in lower Respiratory samples and detection in serum from hematopoietic cell transplant (HCT) recipients with Respiratory Virus-associated pneumonia. Methods. We retrospectively identified HCT recipients with Respiratory syncytial Virus (RSV), parainfluenza Virus, influenza Virus, metapneumoVirus (MPV), and coronaVirus (CoV) detected in bronchoalveolar lavage (BAL) samples, and we tested stored BAL and/or serum samples by quantitative polymerase chain reaction. Results. In 85 BAL samples from 82 patients, median viral loads were as follows: for RSV (n = 35), 2.6 × 10 6 copies/mL; for parainfluenza Virus (n = 35), 4.9 × 10 7 copies/mL; for influenza Virus (n = 9), 6.8 × 10 5 copies/mL; for MPV (n = 7), 3.9 × 10 7 copies/mL; and for CoV (n = 4), 1.8 × 10 5 copies/mL. Quantitative viral load was not associated with mechanical ventilation or death. Viral RNA was detected in serum samples from 6 of 66 patients: 4 of 41 with RSV pneumonia, 1 with influenza B, and 1 with MPV/influenza A Virus/CoV coinfection (influenza A Virus and MPV RNA detected). RSV detection in serum was associated with high viral load in BAL samples (P = .05), and viral RNA detection in serum was significantly associated with death (adjusted rate ratio, 1.8; P = .02). Conclusion. Quantitative polymerase chain reaction detects high viral loads in BAL samples from HCT recipients with Respiratory Virus pneumonia. Viral RNA is also detectable in the serum of patients with RSV, influenza, and MPV pneumonia and may correlate with the severity of disease.
David L Woodland - One of the best experts on this subject based on the ideXlab platform.
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type i interferons regulate cytolytic activity of memory cd8 t cells in the lung airways during Respiratory Virus challenge
2010Co-Authors: Jacob E Kohlmeier, Alan D Roberts, Tres Cookenham, Shannon C Miller, David L WoodlandAbstract:Memory CD8(+) T cells in the lung airways provide protection from secondary Respiratory Virus challenge by limiting early viral replication. Here, we demonstrate that although airway-resident memory CD8(+) T cells were poorly cytolytic, memory CD8(+) T cells recruited to the airways early during a recall response showed markedly enhanced cytolytic ability. This enhanced lytic activity did not require cognate antigen stimulation, but rather was dependent on STAT1 transcription factor signaling through the interferon-alpha receptor (Ifnar1), resulting in the antigen-independent expression of granzyme B protein in both murine and human Virus-specific T cells. Signaling through Ifnar1 was required for the enhanced lytic activity and control of early viral replication by memory CD8(+) T cells in the lung airways. These findings demonstrate that innate inflammatory signals act directly on memory T cells, enabling them to rapidly destroy infected host cells once they enter infected tissues.
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the route of priming influences the ability of Respiratory Virus specific memory cd8 t cells to be activated by residual antigen
2010Co-Authors: Shiki Takamura, Alan D Roberts, Jacob E Kohlmeier, Dawn M Jelleygibbs, Susan Wittmer, David L WoodlandAbstract:After Respiratory Virus infections, memory CD8+ T cells are maintained in the lung airways by a process of continual recruitment. Previous studies have suggested that this process is controlled, at least in the initial weeks after Virus clearance, by residual antigen in the lung-draining mediastinal lymph nodes (MLNs). We used mouse models of influenza and parainfluenza Virus infection to show that intranasally (i.n.) primed memory CD8+ T cells possess a unique ability to be reactivated by residual antigen in the MLN compared with intraperitoneally (i.p.) primed CD8+ T cells, resulting in the preferential recruitment of i.n.-primed memory CD8+ T cells to the lung airways. Furthermore, we demonstrate that the inability of i.p.-primed memory CD8+ T cells to access residual antigen can be corrected by a subsequent i.n. Virus infection. Thus, two independent factors, initial CD8+ T cell priming in the MLN and prolonged presentation of residual antigen in the MLN, are required to maintain large numbers of antigen-specific memory CD8+ T cells in the lung airways.
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cxcr3 directs antigen specific effector cd4 t cell migration to the lung during parainfluenza Virus infection
2009Co-Authors: Jacob E Kohlmeier, Tres Cookenham, Shannon C Miller, Alan Roberts, Jan Pravsgaard Christensen, Allan Randrup Thomsen, David L WoodlandAbstract:Effector T cells are a crucial component of the adaptive immune response to Respiratory Virus infections. Although it was previously reported that the chemokine receptors CCR5 and CXCR3 affect trafficking of Respiratory Virus-specific CD8+ T cells, it is unclear whether these receptors govern effector CD4+ T cell migration to the lungs. To assess the role of CCR5 and CXCR3 in vivo, we directly compared the migration of Ag-specific wild-type and chemokine receptor-deficient effector T cells in mixed bone marrow chimeric mice during a parainfluenza Virus infection. CXCR3-deficient effector CD4+ T cells were 5- to 10-fold less efficient at migrating to the lung compared with wild-type cells, whereas CCR5-deficient effector T cells were not impaired in their migration to the lung. In contrast to its role in trafficking, CXCR3 had no impact on effector CD4+ T cell proliferation, phenotype, or function in any of the tissues examined. These findings demonstrate that CXCR3 controls Virus-specific effector CD4+ T cell migration in vivo, and suggest that blocking CXCR3-mediated recruitment may limit T cell-induced immunopathology during Respiratory Virus infections.
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protection from Respiratory Virus infections can be mediated by antigen specific cd4 t cells that persist in the lungs
2001Co-Authors: Robert J Hogan, Edward J Usherwood, Weimin Zhong, Alan D Roberts, Tres Cookenham, David L WoodlandAbstract:Although CD4+ T cells have been shown to mediate protective cellular immunity against Respiratory Virus infections, the underlying mechanisms are poorly understood. For example, although phenotypically distinct populations of memory CD4+ T cells have been identified in different secondary lymphoid tissues, it is not known which subpopulations mediate protective cellular immunity. In this report, we demonstrate that Virus-specific CD4+ T cells persist in the lung tissues and airways for several months after Sendai Virus infection of C57BL/6 mice. A large proportion of these cells possess a highly activated phenotype (CD44hi, CD62Llo, CD43hi, and CD25hi) and express immediate effector function as indicated by the production of interferon γ after a 5-h restimulation in vitro. Furthermore, intratracheal adoptive transfer of lung memory cells into β2m-deficient mice demonstrated that lung-resident Virus-specific CD4+ T cells mediated a substantial degree of protection against secondary Virus infection. Taken together, these data demonstrate that activated memory CD4+ T cells persisting at mucosal sites play a critical role in mediating protective cellular immunity.
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activated antigen specific cd8 t cells persist in the lungs following recovery from Respiratory Virus infections
2001Co-Authors: Robert J Hogan, Edward J Usherwood, Weimin Zhong, Alan D Roberts, Richard W Dutton, Allen G Harmsen, David L WoodlandAbstract:The poor correlation between cellular immunity to Respiratory Virus infections and the numbers of memory CD8 + T cells in the secondary lymphoid organs suggests that there may be additional reservoirs of T cell memory to this class of infection. Here we identify a substantial population of Ag-specific T cells in the lung that persist for several months after recovery from an influenza or Sendai Virus infection. These cells are present in high numbers in both the airways and lung parenchyma and can be distinguished from memory cell populations in the spleen and peripheral lymph nodes in terms of the relative frequencies among CD8 + T cells, activation status, and kinetics of persistence. In addition, these cells are functional in terms of their ability to proliferate, express cytolytic activity, and secrete cytokines, although they do not express constitutive cytolytic activity. Adoptive transfer experiments demonstrated that the long-term establishment of activated T cells in the lung did not require infection in the lung by a pathogen carrying the inducing Ag. The kinetics of persistence of Ag-specific CD8 + T cells in the lung suggests that they play a key role in protective cellular immunity to Respiratory Virus infections.
Michael Boeckh - One of the best experts on this subject based on the ideXlab platform.
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symptomatic Respiratory Virus infection and chronic lung allograft dysfunction
2016Co-Authors: Cynthia E Fisher, Michael Boeckh, Carl M Preiksaitis, Erika D Lease, Jeffrey D Edelman, Katharine A Kirby, Wendy M Leisenring, Ganesh Raghu, Ajit P LimayeAbstract:BACKGROUND Chronic lung allograft dysfunction (CLAD) is a major cause of allograft loss post-lung transplantation. Prior studies have examined the association between Respiratory Virus infection (RVI) and CLAD were limited by older diagnostic techniques, study design, and case numbers. We examined the association between symptomatic RVI and CLAD using modern diagnostic techniques in a large contemporary cohort of lung transplant recipients (LTRs). METHODS We retrospectively assessed clinical variables including acute rejection, cytomegaloVirus pneumonia, upper and lower RVI, and the primary endpoint of CLAD (determined by 2 independent reviewers) in 250 LTRs in a single university transplantation program. Univariate and multivariate Cox models were used to analyze the relationship between RVI and CLAD in a time-dependent manner, incorporating different periods of risk following RVI diagnosis. RESULTS Fifty patients (20%) were diagnosed with CLAD at a median of 95 weeks post-transplantation, and 79 (32%) had 114 episodes of RVI. In multivariate analysis, rejection and RVI were independently associated with CLAD (adjusted hazard ratio [95% confidence interval]) 2.2 (1.2-3.9), P = .01 and 1.9 (1.1-3.5), P = .03, respectively. The association of RVI with CLAD was stronger the more proximate the RVI episode: 4.8 (1.9-11.6), P < .01; 3.4 (1.5-7.5), P < .01; and 2.4 (1.2-5.0), P = .02 in multivariate analysis for 3, 6, and 12 months following RVI, respectively. CONCLUSIONS Symptomatic RVI is independently associated with development of CLAD, with increased risk at shorter time periods following RVI. Prospective studies to characterize the virologic determinants of CLAD and define the underlying mechanisms are warranted.
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self collection of foam nasal swabs for Respiratory Virus detection by pcr among immunocompetent subjects and hematopoietic cell transplant recipients
2013Co-Authors: Angela P Campbell, Jane Kuypers, Janet A Englund, Katherine A Guthrie, Lawrence Corey, Michael BoeckhAbstract:Self-collected foam nasal swabs (NS) obtained after instillation of saline spray were compared with nasal washes from immunocompetent subjects during 146 upper Respiratory infections (URIs); the sensitivities for reverse transcription (RT)-PCR Respiratory Virus detection were 95% and 88%, respectively (P = 0.06). The sensitivities from NS collected with and without saline spray during 142 URIs from immunocompetent subjects were 96% and 86% (P = 0.004), respectively, and those from 140 URI samples from hematopoietic cell transplantation recipients were 88% and 85% (P = 0.56), respectively.
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Respiratory Virus pneumonia after hematopoietic cell transplantation hct associations between viral load in bronchoalveolar lavage samples viral rna detection in serum samples and clinical outcomes of hct
2010Co-Authors: Angela P Campbell, Jason W Chien, Jane Kuypers, Janet A Englund, Anna Wald, Katherine A Guthrie, Lawrence Corey, Michael BoeckhAbstract:Background. Few data exist on Respiratory Virus quantitation in lower Respiratory samples and detection in serum from hematopoietic cell transplant (HCT) recipients with Respiratory Virus-associated pneumonia. Methods. We retrospectively identified HCT recipients with Respiratory syncytial Virus (RSV), parainfluenza Virus, influenza Virus, metapneumoVirus (MPV), and coronaVirus (CoV) detected in bronchoalveolar lavage (BAL) samples, and we tested stored BAL and/or serum samples by quantitative polymerase chain reaction. Results. In 85 BAL samples from 82 patients, median viral loads were as follows: for RSV (n = 35), 2.6 × 10 6 copies/mL; for parainfluenza Virus (n = 35), 4.9 × 10 7 copies/mL; for influenza Virus (n = 9), 6.8 × 10 5 copies/mL; for MPV (n = 7), 3.9 × 10 7 copies/mL; and for CoV (n = 4), 1.8 × 10 5 copies/mL. Quantitative viral load was not associated with mechanical ventilation or death. Viral RNA was detected in serum samples from 6 of 66 patients: 4 of 41 with RSV pneumonia, 1 with influenza B, and 1 with MPV/influenza A Virus/CoV coinfection (influenza A Virus and MPV RNA detected). RSV detection in serum was associated with high viral load in BAL samples (P = .05), and viral RNA detection in serum was significantly associated with death (adjusted rate ratio, 1.8; P = .02). Conclusion. Quantitative polymerase chain reaction detects high viral loads in BAL samples from HCT recipients with Respiratory Virus pneumonia. Viral RNA is also detectable in the serum of patients with RSV, influenza, and MPV pneumonia and may correlate with the severity of disease.
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community Respiratory Virus infections in immunocompromised patients hematopoietic stem cell and solid organ transplant recipients and individuals with human immunodeficiency Virus infection
2007Co-Authors: Michael Boeckh, Janet A EnglundAbstract:Abstract Infection is the leading cause of morbidity and mortality in immunocompromised patients such as hematopoietic/solid organ transplant recipients and individuals with human immunodeficiency Virus. Community Respiratory Virus infections are increasingly recognized as a significant threat to these patients. This article reviews current information in the clinical field of community Respiratory Viruses, including several newly discovered Respiratory Viruses. Respiratory syncytial Virus, influenza Viruses, parainfluenza Viruses, and adenoViruses cause the most serious disease in immunocompromised hosts, but other Respiratory Viruses are becoming increasingly appreciated as a cause of both upper and lower Respiratory tract disease. The clinical impact of these new Viruses, including human metapneumoVirus, non-SARS human coronaViruses, and human bocaVirus, is not yet clear. Modern molecular technology has made the discovery of new Viruses possible; the use of these new technologies in direct patient care is not yet standard but is becoming increasingly utilized. Clinicians should appreciate the potential for the development of antiviral resistance to influenza antivirals in immunocompromised patients.
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airflow decline after myeloablative allogeneic hematopoietic cell transplantation the role of community Respiratory Viruses
2006Co-Authors: Veronique Erard, Jason W Chien, Lawrence Corey, Hyung W Kim, Garrett W Nichols, Mary E D Flowers, Paul J Martin, Michael BoeckhAbstract:We conducted a 12-year retrospective study to determine the effects that the community Respiratory-Virus species and the localization of Respiratory-tract Virus infection have on severe airflow decline, a serious and fatal complication occurring after hematopoietic cell transplantation (HCT). Of 132 HCT recipients with Respiratory-tract Virus infection during the initial 100 days after HCT, 50 (38%) developed airflow decline < or =1 year after HCT. Lower-Respiratory-tract infection with parainfluenza (odds ratio [OR], 17.9 [95% confidence interval {CI}, 2.0-160]; P=.01) and Respiratory syncytial Virus (OR, 3.6 [95% CI, 1.0-13]; P=.05) independently increased the risk of development of airflow decline < or =1 year after HCT. The airflow decline was immediately detectable after infection and was strongest for lower-Respiratory-tract infection with parainfluenza Virus; it stabilized during the months after the Respiratory-tract Virus infection, but, at < or =1 year after HCT, the initial lung function was not restored. Thus, community Respiratory Virus-associated airflow decline seems to be specific to viral species and infection localization.
Jacob E Kohlmeier - One of the best experts on this subject based on the ideXlab platform.
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Establishment and Maintenance of Conventional and Circulation-Driven Lung-Resident Memory CD8+ T Cells Following Respiratory Virus Infections
2019Co-Authors: Shiki Takamura, Jacob E KohlmeierAbstract:Antigen-specific CD8+ tissue-resident memory T cells (TRM cells) persist in the lung following resolution of a Respiratory Virus infection and provide first-line defense against reinfection. In contrast to other memory T cell populations, such as central memory T cells that circulate between lymph and blood, and effector memory T cells (TEM cells) that circulate between blood and peripheral tissues, TRM cells are best defined by their permanent residency in the tissues and their independence from circulatory T cell populations. Consistent with this, we recently demonstrated that CD8+ TRM cells primarily reside within specific niches in the lung (Repair-Associated Memory Depots; RAMD) that normally exclude CD8+ TEM cells. However, it has also been reported that circulating CD8+ TEM cells continuously convert into CD8+ TRM cells in the lung interstitium, helping to sustain TRM numbers. The relative contributions of these two mechanisms of CD8+ TRM cells maintenance in the lung has been the source of vigorous debate. Here we propose a model in which the majority of CD8+ TRM cells are maintained within RAMD (conventional TRM) whereas a small fraction of TRM are derived from circulating CD8+ TEM cells and maintained in the interstitium. The numbers of both types of TRM cells wane over time due to declines in both RAMD availability and the overall number of TEM in the circulation. This model is consistent with most published reports and has important implications for the development of vaccines designed to elicit protective T cell memory in the lung
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airway resident memory cd8 t cells provide antigen specific protection against Respiratory Virus challenge through rapid ifn γ production
2015Co-Authors: Sean R Mcmaster, Jarad J Wilson, Hong Wang, Jacob E KohlmeierAbstract:CD8 airway resident memory T (TRM) cells are a distinctive TRM population with a high turnover rate and a unique phenotype influenced by their localization within the airways. Their role in mediating protective immunity to Respiratory pathogens, although suggested by many studies, has not been directly proven. This study provides definitive evidence that airway CD8 TRM cells are sufficient to mediate protection against Respiratory Virus challenge. Despite being poorly cytolytic in vivo and failing to expand after encountering Ag, airway CD8 TRM cells rapidly express effector cytokines, with IFN-γ being produced most robustly. Notably, established airway CD8 TRM cells possess the ability to produce IFN-γ faster than systemic effector memory CD8 T cells. Furthermore, naive mice receiving intratracheal transfer of airway CD8 TRM cells lacking the ability to produce IFN-γ were less effective at controlling pathogen load upon heterologous challenge. This direct evidence of airway CD8 TRM cell–mediated protection demonstrates the importance of these cells as a first line of defense for optimal immunity against Respiratory pathogens and suggests they should be considered in the development of future cell-mediated vaccines.
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type i interferons regulate cytolytic activity of memory cd8 t cells in the lung airways during Respiratory Virus challenge
2010Co-Authors: Jacob E Kohlmeier, Alan D Roberts, Tres Cookenham, Shannon C Miller, David L WoodlandAbstract:Memory CD8(+) T cells in the lung airways provide protection from secondary Respiratory Virus challenge by limiting early viral replication. Here, we demonstrate that although airway-resident memory CD8(+) T cells were poorly cytolytic, memory CD8(+) T cells recruited to the airways early during a recall response showed markedly enhanced cytolytic ability. This enhanced lytic activity did not require cognate antigen stimulation, but rather was dependent on STAT1 transcription factor signaling through the interferon-alpha receptor (Ifnar1), resulting in the antigen-independent expression of granzyme B protein in both murine and human Virus-specific T cells. Signaling through Ifnar1 was required for the enhanced lytic activity and control of early viral replication by memory CD8(+) T cells in the lung airways. These findings demonstrate that innate inflammatory signals act directly on memory T cells, enabling them to rapidly destroy infected host cells once they enter infected tissues.
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the route of priming influences the ability of Respiratory Virus specific memory cd8 t cells to be activated by residual antigen
2010Co-Authors: Shiki Takamura, Alan D Roberts, Jacob E Kohlmeier, Dawn M Jelleygibbs, Susan Wittmer, David L WoodlandAbstract:After Respiratory Virus infections, memory CD8+ T cells are maintained in the lung airways by a process of continual recruitment. Previous studies have suggested that this process is controlled, at least in the initial weeks after Virus clearance, by residual antigen in the lung-draining mediastinal lymph nodes (MLNs). We used mouse models of influenza and parainfluenza Virus infection to show that intranasally (i.n.) primed memory CD8+ T cells possess a unique ability to be reactivated by residual antigen in the MLN compared with intraperitoneally (i.p.) primed CD8+ T cells, resulting in the preferential recruitment of i.n.-primed memory CD8+ T cells to the lung airways. Furthermore, we demonstrate that the inability of i.p.-primed memory CD8+ T cells to access residual antigen can be corrected by a subsequent i.n. Virus infection. Thus, two independent factors, initial CD8+ T cell priming in the MLN and prolonged presentation of residual antigen in the MLN, are required to maintain large numbers of antigen-specific memory CD8+ T cells in the lung airways.
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cxcr3 directs antigen specific effector cd4 t cell migration to the lung during parainfluenza Virus infection
2009Co-Authors: Jacob E Kohlmeier, Tres Cookenham, Shannon C Miller, Alan Roberts, Jan Pravsgaard Christensen, Allan Randrup Thomsen, David L WoodlandAbstract:Effector T cells are a crucial component of the adaptive immune response to Respiratory Virus infections. Although it was previously reported that the chemokine receptors CCR5 and CXCR3 affect trafficking of Respiratory Virus-specific CD8+ T cells, it is unclear whether these receptors govern effector CD4+ T cell migration to the lungs. To assess the role of CCR5 and CXCR3 in vivo, we directly compared the migration of Ag-specific wild-type and chemokine receptor-deficient effector T cells in mixed bone marrow chimeric mice during a parainfluenza Virus infection. CXCR3-deficient effector CD4+ T cells were 5- to 10-fold less efficient at migrating to the lung compared with wild-type cells, whereas CCR5-deficient effector T cells were not impaired in their migration to the lung. In contrast to its role in trafficking, CXCR3 had no impact on effector CD4+ T cell proliferation, phenotype, or function in any of the tissues examined. These findings demonstrate that CXCR3 controls Virus-specific effector CD4+ T cell migration in vivo, and suggest that blocking CXCR3-mediated recruitment may limit T cell-induced immunopathology during Respiratory Virus infections.
