RESUMEN
BACKGROUND: Young children and older adults are susceptible for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Pneumococcal protein-specific antibodies play a protective role against IPD; however, not much is known about the pace of acquisition, maturation, and maintenance of these antibodies throughout life. METHODS: Immunoglobulin G (IgG) and IgA levels, avidity, and/or specificity to the pneumococcal proteome in serum and saliva from healthy young children, adults, and older adults, with known carriage status, were measured by enzyme-linked immunosorbent assay (ELISA) and 2-dimensional western blotting against ΔcpsTIGR4. RESULTS: Eleven-month-old children, the youngest age group tested, had the lowest pneumococcal proteome-specific IgG and IgA levels and avidity in serum and saliva, followed by 24-month-old children and were further elevated in adult groups. Among adult groups, the parents had the highest serum and saliva IgG and IgA antibody levels. In children, antibody levels and avidity correlated with daycare attendance and presence of siblings, posing as proxy for exposure and immunization. Immunodominance patterns slightly varied throughout life. CONCLUSIONS: Humoral immunity against the pneumococcal proteome is acquired through multiple episodes of pneumococcal exposure. Low-level and low-avidity antiproteome antibody profiles in young children may contribute to their IPD susceptibility, while in overall antiproteome antibody-proficient older adults other factors likely play a role.
RESUMEN
BACKGROUND & OBJECTIVES: Despite the availability of biologics for severe pediatric asthma, real-life studies reporting on drivers behind initiating biologics and their alignment with the Global Initiative for Asthma (GINA) recommendations are lacking. METHODS: We performed analysis within the pediatric asthma noninvasive diagnostic approaches study, a prospective cohort of 6- to 17-year-old children with severe asthma. Information was collected on demographic factors, symptom control, treatment, comorbidities, and diagnostic tests from medical records and questionnaires. We divided patients into "starters" or "nonstarters" based on the clinical decision to initiate biologics and performed multivariate logistic regression analysis to identify drivers behind initiating therapy. Additionally, we assessed patient suitability for biologics according to key factors in the GINA recommendations: Type 2 inflammation, frequency of exacerbations, and optimization of treatment adherence. RESULTS: In total, 72 children (mean age 11.5 ± 3.0 years, 65.3% male) were included (13 starters). Initiation of biologics was associated with a higher GINA treatment step (adjusted odds ratio's [aOR] = 5.0, 95%CI 1.33-18.76), steroid toxicity (aOR = 21.1, 95%CI 3.73-119.91), frequency of exacerbations (aOR = 1.6, 95%CI 1.10-2.39), improved therapy adherence (aOR = 1.7, 95%CI 1.10-2.46), Caucasian ethnicity (aOR = 0.20, 95%CI 0.05-0.80), ≥1 allergic sensitization (aOR = 0.06, 95%CI 0.004-0.97), and allergic rhinitis (aOR = 0.13, 95%CI 0.03-0.65). Furthermore, steroid toxicity was identified as an important factor for deviation from the current recommendations on biologic prescription. CONCLUSIONS: We identified multiple drivers and inhibitors for initiating biologics, and showed the clinical need for biologics in severe pediatric asthmatics suffering from steroid toxicity. These findings may help refine asthma management guidelines.