Sarcoidosis is a multiorgan granulomatous disorder thought to be triggered and influenced by gene–environment interactions. Sarcoidosis affects 45–300/100 000 individuals in the USA and has an increasing mortality rate. The greatest gap in knowledge about sarcoidosis pathobiology is a lack of understanding about the underlying immunological mechanisms driving progressive pulmonary disease. The objective of this study is to define the lung-specific and blood-specific longitudinal changes in the adaptive immune response and their relationship to progressive and non-progressive pulmonary outcomes in patients with recently diagnosed sarcoidosis.
The BRonchoscopy at Initial sarcoidosis diagnosis Targeting longitudinal Endpoints study is a US-based, NIH-sponsored longitudinal blood and bronchoscopy study. Enrolment will occur over four centres with a target sample size of 80 eligible participants within 18 months of tissue diagnosis. Participants will undergo six study visits over 18 months. In addition to serial measurement of lung function, symptom surveys and chest X-rays, participants will undergo collection of blood and two bronchoscopies with bronchoalveolar lavage separated by 6 months. Freshly processed samples will be stained and flow-sorted for isolation of CD4 +T helper (Th1, Th17.0 and Th17.1) and T regulatory cell immune populations, followed by next-generation RNA sequencing. We will construct bioinformatic tools using this gene expression to define sarcoidosis endotypes that associate with progressive and non-progressive pulmonary disease outcomes and validate the tools using an independent cohort.
The study protocol has been approved by the Institutional Review Boards at National Jewish Hospital (IRB# HS-3118), University of Iowa (IRB# 201801750), Johns Hopkins University (IRB# 00149513) and University of California, San Francisco (IRB# 17-23432). All participants will be required to provide written informed consent. Findings will be disseminated via journal publications, scientific conferences, patient advocacy group online content and social media platforms.
The objective of this rapid scoping review was to identify studies of dose-sparing strategies for administration of intramuscular seasonal influenza vaccines in healthy individuals of all ages.
Comprehensive literature searches were executed in MEDLINE, Embase and the Cochrane library. The grey literature was searched via international clinical trial registries for relevant studies published in English in the last 20 years. We included studies in healthy humans of any age that used any dose-sparing strategy to administer intramuscular seasonal influenza vaccines. Title/abstract and full-text screening were carried out by pairs of reviewers independently. Data extraction was conducted by a single reviewer and verified by a second reviewer. Our outcomes were influenza infections, intensive care unit admission, pneumonia, hospitalisations, adverse events and mortality. Results were summarised descriptively.
A total of 13 studies with 10 351 participants were included in the review and all studies were randomised controlled trials (RCTs) conducted between 2006 and 2019. The most common interventions were the trivalent influenza vaccine (n=10), followed by the quadrivalent influenza vaccine (n=4). Nine studies included infants/toddlers 6–36 months old and one of these studies also included children and adolescents. In these nine studies, no clinical effectiveness outcomes were reported. Of the four adult studies (≥18 years), two studies reported on effectiveness outcomes, however, only one RCT reported on laboratory-confirmed influenza.
Due to the low number of studies in healthy adults and the lack of studies assessing confirmed influenza and influenza-like illness, there remains a need for further evaluation.