The Experts below are selected from a list of 18951 Experts worldwide ranked by ideXlab platform
Marshall I. Hertz - One of the best experts on this subject based on the ideXlab platform.
-
Bronchiolitis obliterans after human lung transplantation.
American Journal of Respiratory and Critical Care Medicine, 2002Co-Authors: Marc Estenne, Marshall I. HertzAbstract:Over the last decade, improvements in surgical techniques, lung preservation, immunosuppression, and management of ischemia–reperfusion injury and infections have contributed to increase the 1-year patient survival after lung transplantation to 70–80% (1). However, long-term survival is threatened by Bronchiolitis obliterans, which is thought to be a form of chronic allograft rejection. Bronchiolitis obliterans after lung transplantation was first described in 1984 at Stanford University in heart–lung transplant recipients who showed a progressive decline in FEV 1 (2). Lung biopsies from these patients showed intraluminal polyps comprised of fibromyxoid granulation tissue and plaques of dense submucosal eosinophilic scar. Obliteration of the small airways by these lesions produces progressive airflow obstruction, often accompanied by recurrent lower respiratory tract infection. Bronchiolitis obliterans, and its clinical correlate Bronchiolitis obliterans syndrome, affect up to 50–60% of patients who survive 5 years after transplantation (3). In most patients, Bronchiolitis obliterans is a progressive process that responds poorly to augmented immunosuppression, and it accounts for more than 30% of all deaths occurring after the third postoperative year (1). Survival at 5 years after the onset of Bronchiolitis obliterans is only 30–40%, and survival at 5 years after transplantation is 20–40% lower in patients with than in patients without Bronchiolitis obliterans (4). In this review, we present current concepts regarding post-transplant Bronchiolitis obliterans, including: ( 1 ) the recently updated classification system for Bronchiolitis obliterans syndrome (BOS), ( 2 ) an overview of current concepts regarding its pathogenesis and risk factors, ( 3 ) potential surrogate markers that may contribute to early detection, and ( 4 ) approaches to the management of this devastating complication.
-
risk factors for the development of Bronchiolitis obliterans syndrome after lung transplantation
The Journal of Thoracic and Cardiovascular Surgery, 1997Co-Authors: Timothy J Kroshus, Marshall I. Hertz, Vibhu R Kshettry, Kay Savik, Ranjit John, Morton R BolmanAbstract:Abstract Objective: This study identifies specific clinical and immunologic factors in lung transplant recipients that influence the subsequent development of chronic allograft dysfunction. Methods: The study group consisted of 132 consecutive patients who received lung allografts (76 single, 25 bilateral single, and 31 heart-lung) and survived at least 90 days. One hundred twenty-one patients were used in the analysis that modeled time to development of histologic obliterative Bronchiolitis or Bronchiolitis obliterans syndrome. Results: Variables noted to have an effect on the time to development of Bronchiolitis obliterans syndrome included cytomegalovirus pneumonitis (RR = 3.2, p = 0.001), late acute rejection (RR = 1.3, p = 0.02), human leukocyte antigen mismatches at the A loci (RR = 1.8, p = 0.02), total human leukocyte antigen mismatches (RR = 1.4, p = 0.04), and absence of donor antigen–specific hyporeactivity (52% vs 100% survival free from Bronchiolitis obliterans syndrome at 2 years; p = 0.005). Cytomegalovirus pneumonitis had a significant effect on time to obliterative Bronchiolitis (RR = 3.6, p = 0.0005), as did donor antigen–specific hyporeactivity (52% vs 100% survival free from obliterative Bronchiolitis at 2 years; p = 0.01). In multivariate analysis, cytomegalovirus pneumonitis (RR = 3.2, p = 0.02), human leukocyte antigen mismatches at the A loci (RR = 2.4, p = 0.006), and late acute rejection (RR = 1.3, p = 0.02) were identified as predictors of Bronchiolitis obliterans syndrome. Cytomegalovirus pneumonitis was associated with time to development of histologic obliterative Bronchiolitis (RR = 2.3, p = 0.02). Conclusions: Several risk factors were associated with the development of chronic allograft dysfunction, which, in turn, had a significant impact on long-term survival. Early identification of lung allograft recipients with risk factors for the development of Bronchiolitis obliterans syndrome may allow modification in immunosuppression and antiviral therapy to potentially decrease the prevalence of this disorder. J Thorac Cardiovasc Surg 1997;114:195-202
-
obliterative Bronchiolitis after lung transplantation a fibroproliferative disorder associated with platelet derived growth factor
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Marshall I. Hertz, Craig A Henke, Raouf E Nakhleh, Keith R Harmon, William A Marinelli, J M K Fox, Spencer H Kubo, Sara J Shumway, R M Bolman, Peter B BittermanAbstract:Abstract Fibroproliferative disorders are characterized by accumulations of mesenchymal cells and connective tissue in critical locations, leading to organ dysfunction. We examined the role of platelet-derived growth factor (PDGF) in the pathogenesis of obliterative Bronchiolitis, a fibroproliferative process that occurs after lung transplantation and results in small airway occlusion. Bronchoalveolar lavage fluid from obliterative Bronchiolitis patients significantly stimulated fibroblast migration, whereas fluid from patient controls did not. Quantitation by radioligand binding assay demonstrated increased concentrations of PDGF in lavage fluid from obliterative Bronchiolitis patients (patients, 104 +/- 26.9 pM; controls, 8.4 +/- 6.9 pM; P < 0.01). Heparin affinity, gel filtration, and Western blot analysis confirmed the presence of PDGF in lavage fluid. Immunohistochemical and in situ hybridization studies of histologic sections and bronchoalveolar lavage cells suggest that alveolar macrophages are one cellular source. Prospective evaluation of sequential bronchoalveolar lavage samples from a patient who developed obliterative Bronchiolitis demonstrated markedly increased PDGF concentrations before the onset of irreversible airflow obstruction. These findings are consistent with a role for PDGF in the fibroproliferative changes observed in obliterative Bronchiolitis.
Pedro A Piedra - One of the best experts on this subject based on the ideXlab platform.
-
robust cytokine and chemokine response in nasopharyngeal secretions association with decreased severity in children with physician diagnosed Bronchiolitis
The Journal of Infectious Diseases, 2016Co-Authors: Erin G Nicholson, Chelsea Schlegel, Roberto P Garofalo, Reena Mehta, Margaret Scheffler, Minghua Mei, Pedro A PiedraAbstract:BACKGROUND Bronchiolitis causes substantial disease in young children. Previous findings had indicated that a robust innate immune response was not associated with a poor clinical outcome in Bronchiolitis. This study tested the hypothesis that increased concentrations of cytokines and chemokines in nasal wash specimens were associated with decreased severity in Bronchiolitis. METHODS Children <24 months old who presented to the emergency department with signs and symptoms of Bronchiolitis were eligible for enrollment. Nasal wash specimens were analyzed for viral pathogens and cytokine/chemokine concentrations. These results were evaluated with regard to disposition. RESULTS One hundred eleven children with Bronchiolitis were enrolled. A viral pathogen was identified in 91.9% of patients (respiratory syncytial virus in 51.4%, human rhinovirus in 11.7%). Higher levels of cytokines and chemokines (interferon [IFN] γ; interleukin [IL] 4, 15, and 17; CXCL10; and eotaxin) were significantly associated with a decreased risk of hospitalization. IL-17, IL-4, IFN-γ, and IFN-γ-inducible protein 10 (CXCL10 or IP-10) remained statistically significant in the multivariate analyses. CONCLUSIONS The cytokines and chemokines significantly associated with decreased Bronchiolitis severity are classified in a wide range of functional groups (T-helper 1 and 2, regulatory, and chemoattractant). The involvement of these functional groups suggest that a broadly overlapping cytokine/chemokine response is required for control of virus-mediated respiratory disease in young children.
-
multicenter study of viral etiology and relapse in hospitalized children with Bronchiolitis
Pediatric Infectious Disease Journal, 2014Co-Authors: Kohei Hasegawa, Pedro A Piedra, Jonathan M Mansbach, Stephen J Teach, Erin Stucky Fisher, Daniel Hershey, Joyce Y Koh, Sunday Clark, Ashley F Sullivan, Carlos A CamargoAbstract:BACKGROUND It is unclear whether the infectious etiology of severe Bronchiolitis affects short-term outcomes, such as posthospitalization relapse. We tested the hypothesis that children hospitalized with rhinovirus (RV) Bronchiolitis, either as a sole pathogen or in combination with respiratory syncytial virus (RSV), are at increased risk of relapse. METHODS We performed a 16-center, prospective cohort study of hospitalized children age <2 years with Bronchiolitis. During the winters of 2007-2010, researchers collected clinical data and nasopharyngeal aspirates from study participants; the aspirates were tested using real-time polymerase chain reaction. The primary outcome was Bronchiolitis relapse (urgent Bronchiolitis visit or scheduled visit at which additions to the Bronchiolitis medications were made) during the 2 weeks after hospital discharge. RESULTS Among 1836 enrolled children with 2-week, follow-up data, the median age was 4 months and 60% were male. Overall, 48% had sole RSV infection, 8% had sole RV infection, and 13% had RSV/RV coinfection. Compared with children with sole RSV infection, and adjusting for 10 demographic and clinical characteristics and clustering of patients within hospitals, children with sole RV infection did not differ in their likelihood of relapse (odds ratio: 0.99; 95% confidence interval: 0.52-1.90; P = 0.98), whereas those with RSV/RV coinfection were more likely to have relapse (odds ratio: 1.54; 95% confidence interval: 1.03-2.30; P = 0.03). CONCLUSIONS In this prospective, multicenter, multiyear study of children hospitalized with Bronchiolitis, we found that RSV/RV coinfection was independently associated with a higher likelihood of Bronchiolitis relapse. Present data support the concept that the infectious etiology of severe Bronchiolitis affects short-term outcomes.
-
immunopathogenesis of respiratory syncytial virus Bronchiolitis
The Journal of Infectious Diseases, 2007Co-Authors: Berkeley L Bennett, Roberto P Garofalo, Stanley G Cron, Yashoda M Hosakote, Robert L Atmar, Charles G Macias, Pedro A PiedraAbstract:BACKGROUND The objective of this study was to elucidate the relation between respiratory syncytial virus (RSV) infection and cytokine/chemokine concentrations, as well as the impact that these factors have on the severity of Bronchiolitis. METHODS Children <24 months old who presented to the emergency department with clinical symptoms of Bronchiolitis were prospectively enrolled in the study. Nasal-wash samples were analyzed to identify viral pathogens and to quantify RSV and cytokine/chemokine concentrations. Severe cases of disease were defined as those requiring hospitalization, and severity was further determined on the basis of the duration of supplemental-oxygen and/or intravenous-fluid therapy. RESULTS A total of 101 children were enrolled, 63 of whom were infected with RSV and 13 of whom were infected with other respiratory viruses; in 22 children, no virus was detected. RSV Bronchiolitis was associated with a greater inflammatory response than was non-RSV Bronchiolitis, although RSV infection was not associated with more-severe disease. Levels of interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-gamma, and macrophage inflammatory protein (MIP)-1beta were significantly inversely correlated with the duration of supplemental-oxygen therapy. CONCLUSION The robust inflammatory response associated with RSV infection does not contribute to the severity of RSV Bronchiolitis any more than it contributes to the severity of non-RSV Bronchiolitis. Elevated levels of proinflammatory mediators IL-6, IL-8, IFN-gamma, and MIP-1beta, as well as of the regulatory cytokine IL-10, may be protective against hypoxia in Bronchiolitis.
Ricardo M Fernandes - One of the best experts on this subject based on the ideXlab platform.
-
cpap and high flow nasal cannula oxygen in Bronchiolitis
Chest, 2015Co-Authors: Ian Sinha, Antonia Mcbride, Rachel Smith, Ricardo M FernandesAbstract:Severe respiratory failure develops in some infants with Bronchiolitis because of a complex pathophysiologic process involving increased airways resistance, alveolar atelectasis, muscle fatigue, and hypoxemia due to mismatch between ventilation and perfusion. Nasal CPAP and high-flow nasal cannula (HFNC) oxygen may improve the work of breathing and oxygenation. Although the mechanisms behind these noninvasive modalities of respiratory support are not well understood, they may help infants by way of distending pressure and delivery of high concentrations of warmed and humidified oxygen. Observational studies of varying quality have suggested that CPAP and HFNC may confer direct physiologic benefits to infants with Bronchiolitis and that their use has reduced the need for intubation. No trials to our knowledge, however, have compared CPAP with HFNC in Bronchiolitis. Two randomized trials compared CPAP with oxygen delivered by low-flow nasal cannula or face mask and found some improvements in blood gas results and some physiologic parameters, but these trials were unable to demonstrate a reduction in the need for intubation. Two trials evaluated HFNC in Bronchiolitis (one comparing it with headbox oxygen, the other with nebulized hypertonic saline), with the results not seeming to suggest important clinical or physiologic benefits. In this article, we review the pathophysiology of respiratory failure in Bronchiolitis, discuss these trials in detail, and consider how future research studies may be designed to best evaluate CPAP and HFNC in Bronchiolitis.
Simon B Drysdale - One of the best experts on this subject based on the ideXlab platform.
-
Management of Respiratory Syncytial Virus Bronchiolitis: 2015 Survey of Members of the European Society for Paediatric Infectious Diseases
2020Co-Authors: Elliott J Carande, Andrew J Pollard, Simon B DrysdaleAbstract:In 1995, the European Society for Paediatric Infectious Diseases (ESPID) carried out a survey of its members to assess the variation in management of respiratory syncytial virus (RSV) Bronchiolitis. The aim of the current study was to carry out a similar survey 20 years later to assess how the management had changed. An electronic, structured, English language survey, based on the United Kingdom National Institute for Health and Care Excellence (NICE) Bronchiolitis draft guideline, was sent to ESPID members in March 2015. Questions asked included information on treatment practices of infants with Bronchiolitis and doctor demographics. We received responses from 135 doctors (14% of the ESPID members) who worked in 115 hospitals. 56% of the doctors used a written guideline to manage bronchiolitic infants. All doctors stated that they isolated individually or in cohorts all hospitalised Bronchiolitis infants. The level of oxygen saturation suggested as an indication to administer supplemental oxygen varied between <89% and <95%. We found significant reductions in the use of ribavirin, bronchodilators, and corticosteroids from 1995 to 2015 (ribavirin 57% to 13%, < 0.0001; bronchodilators 95% to 82%, = 0.0024; corticosteroids 81% to 45%, < 0.0001). Although variability in management remains high, encouragingly significantly fewer doctors are prescribing ribavirin, bronchodilators, and corticosteroids compared to 20 years ago
-
viral Bronchiolitis management in hospitals in the uk
Journal of Clinical Virology, 2018Co-Authors: Elliott J Carande, Andrew J Pollard, Eva P Galiza, Alecia Nickless, Simon B DrysdaleAbstract:Abstract Background Viral Bronchiolitis is the leading cause of hospitalisation in infants less than a year old. The United Kingdom (UK) National Institute for Health and Care Excellence (NICE) published a guideline for the management of viral Bronchiolitis in June 2015. Objectives This study aimed to prospectively survey the management of viral Bronchiolitis in hospital Trusts in the UK to provide a baseline of practice prior to the publication of the 2015 NICE Bronchiolitis guideline against which future practice can be assessed. Study design An electronic, structured questionnaire was sent to hospital paediatricians in the UK prior to the publication of the NICE Bronchiolitis guideline via the Royal College of Paediatrics and Child Health e-portfolio system to assess the quality of Trust’s viral Bronchiolitis management guidelines. Results Paediatricians from 111 (65% of all) UK Trusts completed an electronic questionnaire. 91% of Trusts had a Bronchiolitis guideline. Overall only 18% of Trusts would be fully compliant with the NICE guideline. Between 43–100% of Trusts would be compliant with different sections of the guideline. There was variation in hospital admission criteria with respect to the need for supplemental oxygen (oxygen saturations Conclusions There was wide variation in the management of infants with Bronchiolitis in Trusts. Most bronchiolitic infants are not managed optimally in hospitals. Future guidelines should include advice on virus testing and isolation/cohorting.
-
change in viral Bronchiolitis management in hospitals in the uk after the publication of nice guideline
Journal of Clinical Virology, 2018Co-Authors: Rachael Barr, Andrew J Pollard, Elliott J Carande, Simon B DrysdaleAbstract:Abstract Background Viral Bronchiolitis is one of the most common causes of hospitalisation in young infants. It has previously been shown that many United Kingdom (UK) hospital Trusts were not compliant with many aspects of the National Institute for Health and Care Excellence (NICE) Bronchiolitis guideline prior to its publication. Objectives This study aimed to investigate changes in the management of Bronchiolitis by hospital Trusts between 2015 (before NICE guideline publication) and 2017, after publication. Study design We prospectively surveyed paediatricians at UK hospital Trusts on the management of Bronchiolitis before (March to May 2015) and after (January to May 2017) the NICE Bronchiolitis guideline publication in June 2015, using an electronic, structured questionnaire. Results In 2015 111 Trusts were represented and in 2017 100 Trusts. Significant improvements were seen in the use of nebulised bronchodilators and hypertonic saline and provision of parental written guidance. However, full compliance with the guideline did not change with 18% of Trusts compliant before publication of the guideline in 2015 and 19% fully compliant with the guideline in 2017. Conclusions Overall there were modest but important improvements in the reported management of Bronchiolitis after the publication of the NICE guideline.
Louis Bont - One of the best experts on this subject based on the ideXlab platform.
-
increased risk of wheeze and decreased lung function after respiratory syncytial virus infection
PLOS ONE, 2014Co-Authors: Kim Zomerkooijker, Marieke J J Ermers, Cuno S P M Uiterwaal, Maroeska M Rovers, Louis BontAbstract:Background A relationship between hospitalization for respiratory syncytial virus (RSV) Bronchiolitis and asthma development has been suggested in case-control studies. Objective The aim of this study was to assess the risk of current wheeze, asthma, and lung function at school age in infants previously hospitalized for RSV Bronchiolitis compared to non-hospitalized children. Methods For this study, data from a prospective birth cohort of unselected, term-born infants (n = 553), of whom 4 (0.7%) were hospitalized for RSV Bronchiolitis, and a prospective patient cohort of 155 term infants hospitalized for RSV Bronchiolitis were used. Respiratory outcomes at age 6 in children hospitalized for RSV Bronchiolitis were compared to non-hospitalized children. Results The risk of current wheeze was higher in hospitalized patients (n = 159) compared to non-hospitalized children (n = 549) (adjusted odds ratio (OR) 3.2 (95% CI 1.2–8.1). Similarly, the risk of current asthma, defined as a doctor’s diagnosis of asthma plus current symptoms or medication use, was higher in hospitalized patients (adjusted OR 3.1 (95% CI 1.3–7.5). Compared to non-hospitalized children, RSV Bronchiolitis hospitalization was associated with lower lung function (mean difference FEV1% predicted −6.8 l (95% CI (−10.2 to −3.4). Conclusions and Clinical Relevance This is the first study showing that hospitalization for RSV Bronchiolitis during infancy is associated with increased risk of wheezing, current asthma, and impaired lung function as compared to an unselected birth cohort at age 6.
-
influence of promoter variants of interleukin 10 interleukin 9 and tumor necrosis factor α genes on respiratory syncytial virus Bronchiolitis
The Journal of Infectious Diseases, 2004Co-Authors: Barbara Hoebee, Louis Bont, Edwin Rietveld, Marijke Van Oosten, Hennie M Hodemaekers, Nico J D Nagelkerke, H J Neijens, Jan L L Kimpen, Tjeerd G KimmanAbstract:Previously, we reported genetic associations between severe respiratory syncytial virus (RSV) Bronchiolitis in infants and polymorphisms in the interleukin (IL)-4 and IL-4 receptor alpha (IL-4Ralpha) genes, providing evidence for involvement of T helper type 2 cytokines in the pathogenesis of RSV Bronchiolitis. We expanded our studies to polymorphisms in genes encoding IL-9, IL-10, and tumor necrosis factor (TNF)-alpha, using both a transmission/disequilibrium test and a case-control approach. Children homozygous for the IL-10 -592C or -592A allele had a higher risk of hospitalization for RSV Bronchiolitis than did heterozygous carriers (odds ratio [OR], 1.73 vs. 2.55; 95% confidence interval [CI], 1.13-2.66 vs. 1.21-5.39). In children hospitalized at < or =6 months of age, a significant association between RSV Bronchiolitis and the IL-10 -592C allele was found (OR, 1.61; 95% CI, 1.10-2.35). No significant associations of TNF-alpha and IL-9 polymorphisms with RSV Bronchiolitis were observed. We also explored the interactions between different polymorphisms and found an interaction between the IL-4Ralpha Q551R and IL-10 C-592A polymorphisms.
