Pulmonary hypertension during respiratory syncytial virus bronchiolitis: a risk factor for severity of illness.

BACKGROUND: Respiratory syncytial virus infection is the most frequent cause of acute lower respiratory tract disease in infants. A few reports have suggested that pulmonary hypertension is associated with increased severity of respiratory syncytial virus infection. We sought to determine the association between the pulmonary hypertension detected by echocardiography during respiratory syncytial virus bronchiolitis and clinical outcomes. METHODS: We retrospectively reviewed 154 children admitted with respiratory syncytial virus bronchiolitis who had an echocardiography performed during the admission. The association between pulmonary hypertension and clinical outcomes including mortality, intensive care unit (ICU) admission, prolonged ICU stay (>10 days), tracheal intubation, and need of high frequency oscillator ventilation was evaluated. RESULTS: Echocardiography detected pulmonary hypertension in 29 patients (18.7%). Pulmonary hypertension was observed more frequently in patients with congenital heart disease (CHD) (n = 11/33, 33%), chronic lung disease of infancy (n = 12/25, 48%), prematurity (<37 weeks gestational age, n = 17/59, 29%), and Down syndrome (n = 4/10, 40%). The presence of pulmonary hypertension was associated with morbidity (p < 0.001) and mortality (p = 0.02). However, in patients without these risk factors (n = 68), pulmonary hypertension was detected in five patients who presented with shock or poor perfusion. Chronic lung disease was associated with pulmonary hypertension (OR = 5.9, 95% CI 2.2-16.3, p = 0.0005). Multivariate logistic analysis demonstrated that pulmonary hypertension is associated with ICU admission (OR = 6.4, 95% CI 2.2-18.8, p = 0.0007), intubation (OR = 4.7, 95% CI 1.8-12.3, p = 0.002), high frequency oscillator ventilation (OR = 8.4, 95% CI 2.95-23.98, p < 0.0001), and prolonged ICU stay (OR = 4.9, 95% CI 2.0-11.7, p = 0.0004). CONCLUSIONS: Pulmonary hypertension detected by echocardiography during respiratory syncytial virus infection was associated with increased morbidity and mortality. Chronic lung disease was associated with pulmonary hypertension detected during respiratory syncytial virus bronchiolitis. Routine echocardiography is not warranted for previously healthy, haemodynamically stable patients with respiratory syncytial virus bronchiolitis.

Challenges establishing a multi-purpose fecal microbiota transplantation stool donor program in Toronto, Canada.

Background: The success of fecal microbiota transplantation (FMT) programs depends on maintaining suitable stool donors. We describe challenges recruiting and retaining universal donors in the first 2 years of an FMT clinical and research program in Toronto and identify opportunities for improvement. Methods: A four-stage screening process is used to identify suitable FMT donors in the Microbiota Therapeutics Outcomes Program. Donor screening follows Health Canada recommendations and excludes persons with history or risk for diseases associated with dysbiosis. Donors are rescreened microbiologically approximately every 1-3 months and answer ongoing health, exposure, and dietary questionnaires. Results: In the first 2 years of our program, 5 of 322 (1.6%) prospective stool donors passed initial screening, and only 2 (0.6%) were retained. Most prospective donors were excluded on telephone screening, at which point high BMI, medication use, and family history of relevant illness were common exclusions. No candidate was excluded because of a concerning physical examination. Microbiologic reasons for donor exclusion included carriage of Blastocystis hominis (n = 2), Helicobacter pylori (n = 2), extended spectrum beta-lactamase producing organisms (n = 1), Shiga-toxin producing Escherichia coli (n = 1), and sapovirus (n = 1). Universal donors were lost temporarily because of travel, antibiotic exposures, and transient carriage of antibiotic-resistant organisms. Conclusions: Recruiting and retaining suitable donors for FMT is challenging because of rigorous exclusions and labour-intensive screening processes. We present considerations for efficiency in donor screening, including targeting recruitment populations, expanded website self-screening, eliminating physical examinations, and streamlining post-travel risk assessment.

Historique: Le succès des programmes de transplantation de microbiote fécal (TMF) dépend de la rétention de donneurs fécaux appropriés. Les auteurs décrivent les difficultés à recruter et à conserver des donneurs universels dans les deux premières années d'un programme clinique et de recherche de TMF à Toronto ainsi qu'à déterminer les possibilités d'amélioration. Méthodologie: Un processus de sélection en quatre étapes permet de déterminer les donneurs de TMF appropriés au sein du programme de résultats thérapeutiques du microbiote. La sélection des donneurs suit les recommandations de Santé Canada et exclut les personnes ayant des antécédents ou un risque de maladies associés à la dysbiose. Les donneurs reprennent une sélection microbiologique environ tous les un à trois mois et répondent à des questionnaires sur la santé, l'exposition et le régime alimentaire. Résultats: Au cours de deux premières années du programme, cinq des 322 donneurs prospectifs de matière fécale (1,6 %) ont réussi la sélection initiale, et seulement deux (0,6 %) ont été retenus. La plupart des donneurs prospectifs ont été exclus à la sélection téléphonique; un IMC élevé, la prise de médicaments et des antécédents familiaux de maladie pertinente étaient des exclusions courantes. Aucun candidat n'a été exclu à cause d'un examen physique inquiétant. Les raisons microbiologiques d'exclure les donneurs incluaient le portage de Blastocystis hominis (n = 2), d'Helicobacter pylori (n = 2), d'organismes producteurs de bêta-lactamase à large spectre (n = 1), d'Escherichia coli producteur de la toxine de Shiga (n = 1) et du sapovirus (n = 1). Des donneurs temporaires étaient perdus temporairement à cause de voyages, d'exposition à des antibiotiques et de portage transitoire d'organismes antibiorésistants. Conclusions: Il est difficile de recruter et de retenir des donneurs appropriés de TMF en raison des exclusions rigoureuses et des processus de dépistage fastidieux. Les auteurs présentent des considérations d'efficacité pour le dépistage des donneurs, y compris le ciblage de populations à recruter, l'autodépistage élargi dans les sites Web, l'élimination des examens physiques et la rationalisation de l'évaluation du risque après le voyage.

New mouse model of pulmonary hypertension induced by respiratory syncytial virus bronchiolitis.

Pulmonary hypertension (PH) has been observed in up to 75% of infants with moderate to severe respiratory syncytial virus (RSV) bronchiolitis and is associated with significant morbidity and mortality in infants with congenital heart disease. The purpose of the present study was to establish a mouse model of PH secondary to RSV bronchiolitis that mimics the disease etiology as it occurs in infants. Neonatal mice were infected with RSV at 5 days of age and then reinfected 4 wk later. Serum-free medium was administered to age-matched mice as a control. Echocardiography and right ventricular systolic pressure (RVSP) measurements via right jugular vein catheterization were conducted 5 and 6 days after the second infection, respectively. Peripheral capillary oxygen saturation monitoring did not indicate hypoxia at 2-4 days post-RSV infection, before reinfection, and at 2-7 days after reinfection. RSV-infected mice had significantly higher RVSP than control mice. Pulsed-wave Doppler recording of the pulmonary blood flow by echocardiogram demonstrated a significantly shortened pulmonary artery acceleration time and decreased pulmonary artery acceleration time-to-ejection time ratio in RSV-infected mice. Morphometry showed that RSV-infected mice exhibited a significantly higher pulmonary artery medial wall thickness and had an increased number of muscularized pulmonary arteries compared with control mice. These findings, confirmed by RVSP measurements, demonstrate the development of PH in the lungs of mice infected with RSV as neonates. This animal model can be used to study the pathogenesis of PH secondary to RSV bronchiolitis and to assess the effect of treatment interventions. NEW & NOTEWORTHY This is the first mouse model of respiratory syncytial virus-induced pulmonary hypertension, to our knowledge. This model will allow us to decipher molecular mechanisms responsible for the pathogenesis of pulmonary hypertension secondary to respiratory syncytial virus bronchiolitis with the use of knockout and/or transgenic animals and to monitor therapeutic effects with echocardiography.

Does consecutive influenza vaccination reduce protection against influenza: A systematic review and meta-analysis.

INTRODUCTION: Vaccination against influenza on an annual basis is widely recommended, yet recent studies suggest consecutive vaccination may reduce vaccine effectiveness (VE). PURPOSE: To assess whether when examining the entirety of existing data consecutive influenza vaccination reduces VE compared to current season influenza vaccination. DATA SOURCES: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 26, 2017; citations of included studies. STUDY SELECTION: Randomized, controlled trials (RCTs) and observational studies of children, adults and/or the elderly that reported laboratory-confirmed influenza infection over 2 or more consecutive influenza seasons were eligible. DATA EXTRACTION: Data related to study characteristics, participant demographics, cases of influenza infection by vaccination group and risk of bias assessment was extracted in duplicate. DATA SYNTHESIS: Five RCTs involving 11,987 participants did not show a significant reduction in VE when participants vaccinated in two consecutive seasons (VE 71%, 95% CI 62-78%) were compared to those vaccinated in the current season (VE 58%, 95% CI 48-66%) (odds ratio [OR] 0.88, 95% CI 0.62-1.26, p = 0.49, I2 = 39%). Twenty-eight observational studies involving 28,627 participants also did not show a reduction (VE for two consecutive seasons 41%, 95% CI 30-51% compared to VE for current season 47%, 95% CI 39-54%; OR 1.14, 95% CI 0.98-1.32, p = 0.09, I2 = 63%). Results from subgroup analyses by influenza type/subtype, vaccine type, age, vaccine match and co-morbidity support these findings; however, dose-response results were inconsistent. Certainty in the evidence was assessed to be very low due to unexplained heterogeneity and imprecision. LIMITATIONS: The inclusion of studies with relatively small sample sizes and low event rates contributed to the imprecision of summary VE and OR estimates, which were based on unadjusted data. CONCLUSION: Available evidence does not support a reduction in VE with consecutive influenza vaccination, but the possibility of reduced effectiveness cannot be ruled out due to very low certainty in this evidence. FUNDING SOURCE: CIHR Foundation Grant (PROSPERO: CRD42017059893).