Early preschool wheeze trajectories are predominantly non-allergic with distinct biologic and microbiome traits.

Background: Disentangling preschool wheezing heterogeneity in terms of clinical traits, temporal patterns, and collective healthcare burden is critical for precise and effective interventions.

Objective: We aimed to collectively define contributions and distinct characteristics of respiratory phenotypes based on longitudinal wheeze and atopic sensitization patterns in the first 5 years of life.

Methods: Group-based trajectory analysis was performed in the CHILD Cohort study to identify distinct wheeze and allergic sensitization trajectories.

Exploring the potential mediating role of systemic antibiotics in the association between early-life lower respiratory tract infections and asthma at age 5 in the CHILD study.

Objective: Lower respiratory tract infections (LRTIs) in early life are one of the strongest risk factors for childhood asthma and are often treated with systemic antibiotics (IV or oral). We aimed to explore the association between early-life LRTIs and systemic antibiotics on asthma development and the potential mediating role of antibiotics in this relationship.

Methods: Data were collected as part of the longitudinal, general Canadian population CHILD Study.

Reduce, reinforce, and replenish: safeguarding the early-life microbiota to reduce intergenerational health disparities.

Socioeconomic (SE) disparity and health inequity are closely intertwined and associated with cross-generational increases in the rates of multiple chronic non-communicable diseases (NCDs) in North America and beyond. Coinciding with this social trend is an observed loss of biodiversity within the community of colonizing microbes that live in and on our bodies. Researchers have rightfully pointed to the microbiota as a key modifiable factor with the potential to ease existing health inequities.

Antibiotics taken within the first year of life are linked to infant gut microbiome disruption and elevated atopic dermatitis risk.

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in both pediatric and adult populations. The development of AD has been linked to antibiotic usage, which causes perturbation of the microbiome and has been associated with abnormal immune system function. However, imbalances in the gut microbiome itself associated with antibiotic usage have been inconsistently linked to AD.

Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease.

Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e.

Breastfeeding enrichment of B. longum subsp. infantis mitigates the effect of antibiotics on the microbiota and childhood asthma risk.

Background: Early antibiotic exposure is linked to persistent disruption of the infant gut microbiome and subsequent elevated pediatric asthma risk. Breastfeeding acts as a primary modulator of the gut microbiome during early life, but its effect on asthma development has remained unclear.

Methods: We harnessed the CHILD cohort to interrogate the influence of breastfeeding on antibiotic-associated asthma risk in a subset of children (n = 2,521).

Longitudinal body mass index trajectories at preschool age: children with rapid growth have differential composition of the gut microbiota in the first year of life.

Background/objective: The steep rise in childhood obesity has emerged as a worldwide public health problem. The first 4 years of life are a critical window where long-term developmental patterns of body mass index (BMI) are established and a critical period for microbiota maturation. Understanding how the early-life microbiota relate to preschool growth may be useful for identifying preventive interventions for childhood obesity.

Early-life cytomegalovirus infection is associated with gut microbiota perturbations and increased risk of atopy.

Background: The "old friends" hypothesis posits that reduced exposure to previously ubiquitous microorganisms is one factor involved in the increased rates of allergic diseases. Cytomegalovirus (CMV) may be one of the "old friends" hypothesized to help prevent allergic diseases. We sought to elucidate whether early-life CMV infection is associated with childhood atopy via perturbations of the gut microbiota.

A rich meconium metabolome in human infants is associated with early-life gut microbiota composition and reduced allergic sensitization.

Microbiota maturation and immune development occur in parallel with, and are implicated in, allergic diseases, and research has begun to demonstrate the importance of prenatal influencers on both. Here, we investigate the meconium metabolome, a critical link between prenatal exposures and both early microbiota and immune development, to identify components of the neonatal gut niche that contribute to allergic sensitization. Our analysis reveals that newborns who develop immunoglobulin E (IgE)-mediated allergic sensitization (atopy) by 1 year of age have a less-diverse gut metabolome at birth, and specific metabolic clusters are associated with both protection against atopy and the abundance of key taxa driving microbiota maturation.

HEARTBiT: A Transcriptomic Signature for Excluding Acute Cellular Rejection in Adult Heart Allograft Patients.

Background: Nine mRNA transcripts associated with acute cellular rejection (ACR) in previous microarray studies were ported to the clinically amenable NanoString nCounter platform. Here we report the diagnostic performance of the resulting blood test to exclude ACR in heart allograft recipients: HEARTBiT.

Methods: Blood samples for transcriptomic profiling were collected during routine post-transplantation monitoring in 8 Canadian transplant centres participating in the Biomarkers in Transplantation initiative, a large (n = 1622) prospective observational study conducted between 2009 and 2014.

Decreasing antibiotic use, the gut microbiota, and asthma incidence in children: evidence from population-based and prospective cohort studies.

Background: Childhood asthma incidence is decreasing in some parts of Europe and North America. Antibiotic use in infancy has been associated with increased asthma risk. In the present study, we tested the hypothesis that decreases in asthma incidence are linked to reduced antibiotic prescribing and mediated by changes in the gut bacterial community.

Ensembling Electrical and Proteogenomics Biomarkers for Improved Prediction of Cardiac-Related 3-Month Hospitalizations: A Pilot Study.

Background: Many risk models for predicting mortality, hospitalizations, or both in patients with heart failure have been developed but do not have sufficient discriminatory ability. The purpose of this study was to identify predictive biomarkers of hospitalizations in heart failure patients using omics-based technologies applied to blood and electrical monitoring of the heart.

Methods: Blood samples were collected from 58 heart failure patients during enrollment into this study.

Development and Validation of Apolipoprotein AI-Associated Lipoprotein Proteome Panel for the Prediction of Cholesterol Efflux Capacity and Coronary Artery Disease.

Background: Cholesterol efflux capacity (CEC) is a measure of HDL function that, in cell-based studies, has demonstrated an inverse association with cardiovascular disease. The cell-based measure of CEC is complex and low-throughput. We hypothesized that assessment of the lipoprotein proteome would allow for precise, high-throughput CEC prediction.

Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy.

Background: Prostate cancer patients who have a detectable prostate-specific antigen (PSA) postprostatectomy may harbor pre-existing metastatic disease. To our knowledge, none of the commercially available genomic biomarkers have been investigated in such men.

Objective: To evaluate if a 22-gene genomic classifier can independently predict development of metastasis in men with PSA persistence postoperatively.

Multiple reaction monitoring mass spectrometry to identify novel plasma protein biomarkers of treatment response in cystic fibrosis pulmonary exacerbations.

Background: Systemic inflammation decreases with IV antibiotics during the treatment of CF pulmonary exacerbations (PEx). We used multiple reaction monitoring mass spectrometry and immunoassays to monitor blood proteins during PEx treatment to determine if early changes could be used to predict PEx outcomes following treatment.

Methods: Blood samples from 25 PEx (22 unique adults) were collected within 24h of admission, day 5, day 10, and at IV antibiotic completion.

Circulating biomarker responses to medical management vs. mechanical circulatory support in severe inotrope-dependent acute heart failure.

Background: Severe inotrope-dependent acute heart failure (AHF) is associated with poor clinical outcomes. There are currently no well-defined blood biomarkers of response to treatment that can guide management or identify recovery in this patient population. In the present study, we characterized the levels of novel and emerging circulating biomarkers of heart failure in patients with AHF over the first 30 days of medical management or mechanical circulatory support (MCS).

Airway hyperresponsiveness in chronic obstructive pulmonary disease: A marker of asthma-chronic obstructive pulmonary disease overlap syndrome?

Background: The impact of airway hyperreactivity (AHR) on respiratory mortality and systemic inflammation among patients with chronic obstructive pulmonary disease (COPD) is largely unknown. We used data from 2 large studies to determine the relationship between AHR and FEV decline, respiratory mortality, and systemic inflammation.

Objectives: We sought to determine the relationship of AHR with FEV decline, respiratory mortality, and systemic inflammatory burden in patients with COPD in the Lung Health Study (LHS) and the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study.

Discovery of novel plasma protein biomarkers to predict imminent cystic fibrosis pulmonary exacerbations using multiple reaction monitoring mass spectrometry.

Background: Despite the significant morbidity and mortality related to pulmonary exacerbations in cystic fibrosis (CF), there remains no reliable predictor of imminent exacerbation.

Objective: To identify blood-based biomarkers to predict imminent (<4 months from stable blood draw) CF pulmonary exacerbations using targeted proteomics.

Methods: 104 subjects provided plasma samples when clinically stable and were randomly split into discovery (n=70) and replication (n=34) cohorts.

Serum proteomics in multiple sclerosis disease progression.

Unlabelled: Multiple sclerosis (MS) is associated with chronic degeneration of the central nervous system and may cause permanent neurological problems and considerable disability. While its causes remain unclear, its extensive phenotypic variability makes its prognosis and treatment difficult. The identification of serum proteomic biomarkers of MS progression could further our understanding of the molecular mechanisms related to MS disease processes.

Gender-specific plasma proteomic biomarkers in patients with Anderson-Fabry disease.

Aims: Anderson-Fabry disease (AFD) is an important X-linked metabolic disease resulting in progressive end-organ involvement, with cardiac disease being the dominant determinant of survival in a gender-dependent manner. Recent epidemiological screening for AFD suggests the prevalence is much higher than previously recognized, with estimates of 1:3000. Our aim was to discover novel plasma biomarker signatures in adult patients with AFD.