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Absence of evidence that respiratory viral infections influence pediatric lung transplantation outcomes: Results of the CTOTC-03 study.

ABSTRACT: Based on reports in adult lung transplant recipients, we hypothesized that community-acquired respiratory viral infections (CARVs) would be a risk factor for poor outcome after pediatric lung transplant. We followed 61 pediatric lung transplant recipients for 2+ years or until they met a composite primary endpoint including bronchiolitis obliterans syndrome/obliterative bronchiolitis, retransplant, or death. Blood, bronchoalveolar lavage, and nasopharyngeal specimens were obtained with standard of care visits. Nasopharyngeal specimens were obtained from recipients with respiratory viral symptoms. Respiratory specimens were interrogated for respiratory viruses by using multiplex polymerase chain reaction. Donor-specific HLA antibodies, self-antigens, and ELISPOT reactivity were also evaluated. Survival was 84% (1 year) and 68% (3 years). Bronchiolitis obliterans syndrome incidence was 20% (1 year) and 38% (3 years). The primary endpoint was met in 46% of patients. CARV was detected in 156 patient visits (74% enterovirus/rhinovirus). We did not find a relationship between CARV recovery from respiratory specimens and the primary endpoint (hazard ratio 0.64 [95% confidence interval: 0.25-1.59], P = .335) or between CARV and the development of alloimmune or autoimmune humoral or cellular responses. These findings raise the possibility that the immunologic impact of CARV following pediatric lung transplant is different than that observed in adults.

SUBMITTER: Sweet SC

PROVIDER: S-EPMC6883118 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Absence of evidence that respiratory viral infections influence pediatric lung transplantation outcomes: Results of the CTOTC-03 study.

Sweet Stuart C SC Chin Hyunsook H Conrad Carol C Hayes Don D Heeger Peter S PS Faro Albert A Goldfarb Samuel S Melicoff-Portillo Ernestina E Mohanakumar Thalachallour T Odim Jonah J Schecter Marc M Storch Gregory A GA Visner Gary G Williams Nikki M NM Kesler Karen K Danziger-Isakov Lara L

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20190725 12

Based on reports in adult lung transplant recipients, we hypothesized that community-acquired respiratory viral infections (CARVs) would be a risk factor for poor outcome after pediatric lung transplant. We followed 61 pediatric lung transplant recipients for 2+ years or until they met a composite primary endpoint including bronchiolitis obliterans syndrome/obliterative bronchiolitis, retransplant, or death. Blood, bronchoalveolar lavage, and nasopharyngeal specimens were obtained with standard ...[more]

PMID: 31216376

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Project description:With the global over 60-year-old population predicted to more than double over the next 35 years, caring for this aging population has become a major global healthcare challenge. In 2016 there were over 1 million deaths in >70 year olds due to lower respiratory tract infections; 13-31% of these have been reported to be caused by viruses. Since then, there has been a global COVID-19 pandemic, which has caused over 2.3 million deaths so far; increased age has been shown to be the biggest risk factor for morbidity and mortality. Thus, the burden of respiratory viral infections in the elderly is becoming an increasing unmet clinical need. Particular challenges are faced due to the interplay of a variety of factors including complex multimorbidities, decreased physiological reserve and an aging immune system. Moreover, their atypical presentation of symptoms may lead to delayed necessary care, prescription of additional drugs and prolonged hospital stay. This leads to morbidity and mortality and further nosocomial spread. Clinicians currently have limited access to sensitive detection methods. Furthermore, a lack of effective antiviral treatments means there is little incentive to diagnose and record specific non-COVID-19 viral infections. To meet this unmet clinical need, it is first essential to fully understand the burden of respiratory viruses in the elderly. Doing this through prospective screening research studies for all respiratory viruses will help guide preventative policies and clinical trials for emerging therapeutics. The implementation of multiplex point-of-care diagnostics as a mainstay in all healthcare settings will be essential to understand the burden of respiratory viruses, diagnose patients and monitor outbreaks. The further development of novel targeted vaccinations as well as anti-viral therapeutics and new ways to augment the aging immune system is now also essential.The reviews of this paper are available via the supplemental material section.

Project description:INTRODUCTION:The differentiation of viral from bacterial pneumonia is important in determining whether antibiotics are appropriate for treatment of these infections. Advances in diagnostic technologies such as respiratory panels (RP) utilizing polymerase chain reactions to detect viruses and determination of procalcitonin (PCT) concentrations may aid in this differentiation. However, some studies have shown limited impact for this purpose and thus continuation of antibiotics despite results suggesting viral infection. Our objective was to characterize clinician-prescribing behavior at our institution once RP and/or PCT results were known and suggestive of a viral respiratory infection. METHODS:This retrospective analysis was based upon records of hospitalized patients in whom proven or possible respiratory infections as indicated by RP testing, respiratory bacterial culture or International Statistical Classification of Diseases and Related Health Problems 9th revision codes for acute infectious respiratory illness was documented. Patients evaluated were required to have a RP or PCT within the first 72 h of presentation. Drug orders were evaluated for discontinuation of antibiotic therapy within 48 h of a procalcitonin of <0.25 μg/mL, a positive viral RP result, or both. RESULTS:Of 4869 patients with PCT and/or RP results, 2031 were included. PCT and RP testing were obtained in 503 and 1823 patients, respectively, with 295 patients having both. Results of these tests suggested 789 patients were potential candidates for antibiotic avoidance. These included 219 with a PCT <0.25 μg/mL, 601 with a positive viral RP result, and 31 with both. Antibiotics were administered to 307 patients (39%) within the first 72 h. In these, antibiotics were discontinued within 48 h of laboratory results availability. CONCLUSION:These results suggest that positive viral RP and low PCT results are infrequently associated with discontinuation of antibiotic therapy in proven or possible respiratory infections at our institution. Direct interventions with clinicians are likely needed to correct this behavior and decrease unnecessary antibiotic use.

Dataset Information

Absence of evidence that respiratory viral infections influence pediatric lung transplantation outcomes: Results of the CTOTC-03 study.

Publications

Absence of evidence that respiratory viral infections influence pediatric lung transplantation outcomes: Results of the CTOTC-03 study.

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