Denise C. Babineau

Temporal and racial differences associated with atopic dermatitis Staphylococcus aureus and encoded virulence factors

Monitoring pathogen emergence provides insight into how pathogens adapt in the human population. Secreted virulence factors, important contributors to infections, may differ in a manner dependent on the strain and host. Temporal changes of Staphylococcus aureus toxigenic potential, for example, in encoding toxic shock syndrome toxin 1 (TSST-1), contributed to an epidemic of TSS with significant health impact. This study monitored changes in atopic dermatitis (AD) S. aureus isolates and demonstrated both temporal and host infection differences according to host race based on secreted superantigen potential. The current temporal increase in enterotoxin gene cluster superantigen prevalence and lack of the gene encoding TSST-1 in AAs predict differences in infection types and presentations. ABSTRACT Atopic dermatitis (AD) is an inflammatory skin condition strongly associated with Staphylococcus aureus colonization and infection. S. aureus strains shift in populations in ~10-year intervals depending on virulence factors. Shifts in S. aureus virulence factors may in part explain the racial differences observed in the levels of prevalence and severity of AD. AD S. aureus isolates collected from 2011 to 2014 (103 isolates) and in 2008 (100 isolates) were examined for the prevalence of genes encoding superantigens (SAgs). The strains from 2011 to 2014 were obtained from AD patients as a part of the National Institute of Allergy and Infectious Diseases (NIAID) Atopic Dermatitis Research Network (ADRN). The prevalence of SAg genes was investigated temporally and racially. The enterotoxin gene cluster (EGC) was more prevalent in the 2011–2014 AD isolates than in the 2008 AD isolates. The prevalences of virulence factor genes were similar in European American (EA) and Mexican American (MA) patients but differed in 6 of 22 SAg genes between EA and African American (AA) or MA and AA isolates; notably, AA isolates lacked tstH, the gene encoding toxic shock syndrome toxin 1 (TSST-1). The presence of tstH and sel-p (enterotoxin-like P) was associated with decreased clinical severity and increased blood eosinophils, respectively. The EGC is becoming more prevalent, consistent with the previously observed 10 years of cycling of S. aureus strains. Race-specific S. aureus selection may account for differences in virulence factor profiles. The lack of TSST-1-positive (TSST-1+) AD S. aureus in AA is consistent with the lack of AAs acquiring TSST-1-associated menstrual toxic shock syndrome (TSS). IMPORTANCE Monitoring pathogen emergence provides insight into how pathogens adapt in the human population. Secreted virulence factors, important contributors to infections, may differ in a manner dependent on the strain and host. Temporal changes of Staphylococcus aureus toxigenic potential, for example, in encoding toxic shock syndrome toxin 1 (TSST-1), contributed to an epidemic of TSS with significant health impact. This study monitored changes in atopic dermatitis (AD) S. aureus isolates and demonstrated both temporal and host infection differences according to host race based on secreted superantigen potential. The current temporal increase in enterotoxin gene cluster superantigen prevalence and lack of the gene encoding TSST-1 in AAs predict differences in infection types and presentations.

Expression of corticosteroid-regulated genes by PBMCs in children with asthma

Background Variability in response to inhaled corticosteroids (ICSs) can result in less than optimal asthma control. Development of biomarkers assessing the therapeutic efficacy of corticosteroids is important. Objective We sought to examine whether in vitro PBMC responses to corticosteroids relate to the clinical ICS response. Methods PBMCs were collected from 125 children with asthma (6‐17 years) at enrollment (visit 0 [V0]) and after 1 year of bimonthly guidelines‐based management visits (visit 6 [V6]). Difficult‐to‐control and easy‐to‐control asthma were defined as requiring daily therapy with 500 &mgr;g or more of fluticasone propionate (FLU) with or without a long‐acting &bgr;‐agonist versus 100 &mgr;g or less of FLU in at least 4 visits. mRNA levels of glucocorticoid receptor &agr; and corticosteroid transactivation (FK506‐binding protein 5) and transrepression markers (IL‐8 and TNF‐&agr;) were measured by using RT‐PCR in freshly isolated cells and in response to 10−8 mol/L FLU. Results Compared with PBMCs from patients with easy‐to‐control asthma, PBMCs from those with difficult‐to‐control asthma had significantly lower glucocorticoid receptor &agr; levels at V0 (P = .05). A 30% increase in IL‐8 suppression by FLU (P = .04) and a trend for increased TNF‐&agr; suppression by FLU between V0 and V6 (P = .07) were observed in patients with easy‐to‐control asthma. In contrast, no changes between V0 and V6 in IL‐8 and TNF‐&agr; suppression by FLU were observed in patients with difficult‐to‐control asthma. Corticosteroid‐mediated transactivation (FK506‐binding protein 5 induction by FLU) increased in the PBMCs of patients with difficult‐to‐control and easy‐to‐control asthma between V0 and V6 (P = .05 and P = .03, respectively). Conclusions PBMCs of children with difficult‐to‐control asthma treated with guidelines‐based therapy and requiring high‐dose ICSs had reduced in vitro responsiveness to corticosteroids.

Rhinitis in children and adolescents with asthma: Ubiquitous, difficult to control, and associated with asthma outcomes

Background Rhinitis and asthma are linked, but substantial knowledge gaps in this relationship exist. Objective We sought to determine the prevalence of rhinitis and its phenotypes in children and adolescents with asthma, assess symptom severity and medication requirements for rhinitis control, and investigate associations between rhinitis and asthma. Methods Seven hundred forty‐nine children with asthma participating in the Asthma Phenotypes in the Inner‐City study received baseline evaluations and were managed for 1 year with algorithm‐based treatments for rhinitis and asthma. Rhinitis was diagnosed by using a questionnaire focusing on individual symptoms, and predefined phenotypes were determined by combining symptom patterns with skin tests and measurement of serum specific IgE levels. Results Analyses were done on 619 children with asthma who completed at least 4 of 6 visits. Rhinitis was present in 93.5%, and phenotypes identified at baseline were confirmed during the observation/management year. Perennial allergic rhinitis with seasonal exacerbations was most common (34.2%) and severe. Nonallergic rhinitis was least common (11.3%) and least severe. The majority of children remained symptomatic despite use of nasal corticosteroids with or without oral antihistamines. Rhinitis was worse in patients with difficult‐to‐control versus easy‐to‐control asthma, and its seasonal patterns partially corresponded to those of difficult–to‐control asthma. Conclusion Rhinitis is almost ubiquitous in urban children with asthma, and its activity tracks that of lower airway disease. Perennial allergic rhinitis with seasonal exacerbations is the most severe phenotype and most likely to be associated with difficult‐to‐control asthma. This study offers strong support to the concept that rhinitis and asthma represent the manifestations of 1 disease in 2 parts of the airways.