Few data exist on the predictors of asthma remission by early adulthood in North America.
The predictors of adult asthma remission were determined in a multiethnic population of patients with ...mild-to-moderate persistent childhood asthma.
Asthma remission in early adulthood was measured by using 2 definitions: a clinical and a strict definition. Both included normal lung function and the absence of symptoms, exacerbations, and medication use. The strict definition also included normal airways responsiveness. Predictors were identified from 23 baseline measures by using multivariate logistic regression. The probability of remission was modeled by using decision tree analysis.
In 879 subjects the mean ± SD baseline age was 8.8 ± 2.1 years, 59.4% were male, and 68.7% were white. By adulthood, 229 (26.0%) of 879 participants were in clinical remission, and 111 (15.0%) of 741 participants were in strict remission. The degree of FEV1/forced vital capacity (FVC) ratio impairment was the largest predictor of asthma remission. More than half of boys and two thirds of girls with baseline FEV1/FVC ratios of 90% or greater were in remission at adulthood. Decreased airways responsiveness was also a predictor for both remission definitions (clinical remission odds ratio, 1.23 95% CI, 1.09-1.39; strict remission odds ratio, 1.52 95% CI, 1.26-1.84). The combination of normal FEV1/FVC ratio, airways responsiveness, and serum eosinophil count at baseline yielded greater than 80% probability of remission by adulthood.
A considerable minority of patients with persistent childhood asthma will have disease remission by adulthood. Clinical prognostic indicators of asthma remission, including baseline lung function, can be seen from an early age.
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Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular ...typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable for molecular typing; (2) to determine T. pallidum subtype distribution across geographic areas; and (3) to summarize available information on subtypes associated with neurosyphilis and macrolide resistance.
Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included "Treponema pallidum," or "syphilis," combined with the subject headings "molecular," "subtyping," "typing," "genotype," and "epidemiology." Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, χ(2) = 247.6, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, χ(2) = 102.3, p<0.001) compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited.
Primary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the relationship between clinical presentation and subtype, and further validation of ear lobe blood for obtaining T. pallidum DNA would be useful for future molecular studies of syphilis.
Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma ...pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels.
We sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA).
We identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels.
miRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels.
Previously, in the Childhood Asthma Management Program (CAMP), we used clinical variables to predict the remission of childhood asthma by early adulthood with high accuracy (area under the ...receiver-operating characteristic curve AUROC, 0.81) and found baseline FEV1 to forced vital capacity (FVC) ratio (FEV1/FVC) to be the greatest predictor of asthma remission.2 In addition, we previously used microRNA (miR, miRNA) networks to predict the remission of airway hyperresponsiveness in CAMP.3 miRNAs are small noncoding single-stranded RNAs with excellent noninvasive biomarker potential. The variables associated with loss to follow-up of the asthma remission outcome (ie, age, race, clinic site, income, exacerbations after exercise, exposure to tobacco smoke) and the differential acquisition of baseline miRNA data (ie, race, treatment group, clinic site) were controlled for in the subsequent multivariable logistic regression model.2 The clinical and miRNA variables statistically significant on univariable analyses were entered into a stepwise logistic regression model. The final model controlled for age, sex, race, treatment group, clinic, income, exposure to tobacco smoke, exercise-induced bronchospasm, pet ownership, batch effect, miR-96-5p, miR-199b-5p, miR-1307-3p, and miR-148-5p. Overall, integrating baseline clinical factors with miRNAs resulted in improved model fit (AIC, 194.1) and prediction performance (AUROC, 0.90; P = .001) of childhood asthma remission compared with using clinical variables alone (AIC, 752.1; AUROC, 0.81).2 Less severe baseline airway obstruction (ie, higher FEV1/FVC) and lower baseline miR-221-5p expression were independent long-term predictors of asthma remission by early adulthood.
Syphilis is prevalent among men who have sex with men (MSM) in China. Syphilis partner notification (PN) programs targeting MSM has been considered as one of effective strategies to prevention and ...control of the infection in the population. We examined willingness and preferences for PN among MSM to measure feasibility and optimize uptake.
Participation in a syphilis PN program was measured using a factorial survey from both the perspective of the index patient and the partner. Respondents were recruited from April-July 2011 using convenience sampling at two sites-a MSM sexually transmitted disease (STD) clinic and a MSM community based organization (CBO). Respondents first evaluated three factorial survey vignettes to measure probability of participation and then an anonymous sociodemographic questionnaire. A two-level mixed linear model was fitted for the factorial survey analysis.
In 372 respondents with mean age (± SD) 28.5 (± 6.0) years, most were single (82.0%) and closeted gays (66.7%). The Internet was the most frequent place to search for sex. Few (31.2%) had legal names for casual partners, but most had instant messenger (86.5%) and mobile phone numbers (77.7%). The mean probability of participation in a syphilis PN program was 64.5% (± 32.4%) for index patients and 63.7% (± 32.6%) for partners. Referral of the partner to a private clinic or MSM CBO for follow-up decreased participation compared to the local Center for Disease Control and Prevention (CDC) or public STD clinic.
Enhanced PN services may be feasible among MSM in South China. Internet and mobile phone PN may contact partners untraceable by traditional PN. Referral of partners to the local CDC or public STD clinic may maximize PN participation.
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Piwi-interacting RNAs (piRNAs), comprising the largest noncoding RNA group, regulate transcriptional processes. Whether piRNAs are associated with type 2 (T2)-high asthma is unknown.
...We sought to investigate the association between piRNAs and T2-high asthma in childhood asthma.
We sequenced plasma samples from 462 subjects in the Childhood Asthma Management Program (CAMP) as the discovery cohort and 1165 subjects in the Genetics of Asthma in Costa Rica Study (GACRS) as a replication cohort. Sequencing reads were filtered first, and piRNA reads were annotated and normalized. Linear regression was used for the association analysis of piRNAs and peripheral blood eosinophil count, total serum IgE level, and long-term asthma exacerbation in children with asthma. Mediation analysis was performed to investigate the effect direction. We then ascertained if the circulating piRNAs were present in asthmatic airway epithelial cells in a Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo) public data set.
Fifteen piRNAs were significantly associated with eosinophil count in CAMP (P ≤ .05), and 3 were successfully replicated in GACRS. Eleven piRNAs were associated with total IgE in CAMP, and one of these was replicated in GACRS. All 22 significant piRNAs were identified in epithelial cells in vitro, and 6 of these were differentially expressed between subjects with asthma and healthy controls. Fourteen piRNAs were associated with long-term asthma exacerbation, and effect of piRNAs on long-term asthma exacerbation are mediated through eosinophil count and serum IgE level.
piRNAs are associated with peripheral blood eosinophils and total serum IgE in childhood asthma and may play important roles in T2-high asthma.
Older adults have the greatest burden of asthma and poorest outcomes. The pharmacogenetics of inhaled corticosteroid (ICS) treatment response is not well studied in older adults.
A genome-wide ...association study of ICS response was performed in asthmatics of European ancestry in Genetic Epidemiology Research on Adult Health and Aging (GERA) by fitting Cox proportional hazards regression models, followed by validation in the Mass General Brigham (MGB) Biobank and Rotterdam Study. ICS response was measured using two definitions in asthmatics on ICS treatment: (1) absence of oral corticosteroid (OCS) bursts using prescription records and (2) absence of asthma-related exacerbations using diagnosis codes. A fixed-effect meta-analysis was performed for each outcome. The validated single-nucleotide polymorphisms (SNPs) were functionally annotated to standard databases.
In 5710 subjects in GERA, 676 subjects in MGB Biobank, and 465 subjects in the Rotterdam Study, four novel SNPs on chromosome six near
validated across all cohorts and met genome-wide significance on meta-analysis for the OCS burst outcome. In 4541 subjects in GERA and 505 subjects in MGB Biobank, 152 SNPs with p<5 × 10
were validated across these two cohorts for the asthma-related exacerbation outcome. The validated SNPs included methylation and expression quantitative trait loci for
,
and
for the OCS burst outcome and
,
,
,
, and
for the asthma-related exacerbation outcome.
Multiple novel SNPs associated with ICS response were identified in older adult asthmatics. Several SNPs annotated to genes previously associated with asthma and other airway or allergic diseases, including
.
Hypersensitivity reactions (HSRs) to platinum-based chemotherapies are increasingly being recognized. The authors developed a novel risk-stratification protocol that was used successfully in a small ...number of patients with carboplatin-induced HSRs.
To describe the utility of this protocol in a large number of patients with carboplatin- or oxaliplatin-induced HSRs.
A 5-year retrospective review of patients referred to Massachusetts General Hospital with carboplatin- or oxaliplatin-induced HSR was performed. Patients were managed using a risk-stratification protocol using 3 repeat skin tests (STs) with intervening desensitizations. If the repeat ST result remained negative 3 times, patients received subsequent infusions without desensitization.
From 2008 to 2012, 142 patients (92 treated with carboplatin, 50 treated with oxaliplatin) completed 574 desensitizations. Most patients were women (84.5%, mean ± SD 58.1 ± 9.3 years). Patients with carboplatin-induced HSRs were classified as having positive (n = 32, 34.8%), negative (n = 38, 41.3%), or converted (n = 22, 23.9%) ST reactions when the initial negative ST reaction converted to positive at repeat ST. Of those with oxaliplatin-induced HSRs, 22 (44%) had positive, 25 (50%) had negative, and 3 (6%) had converted ST reactions. Of the patients with negative ST reactions, 17 with carboplatin-induced HSRs and 16 with oxaliplatin-induced HSRs safely completed 59 and 95 outpatient infusions, respectively, without desensitizations. For carboplatin and oxaliplatin, ST conversion was associated with an interval of at least 6 months from the HSR to the initial ST (carboplatin, P = .002; oxaliplatin, P = .045).
This risk-stratification protocol for presumed carboplatin- and oxaliplatin-induced HSRs safely identifies false-negative ST reactions and nonallergic patients who can receive infusions without desensitizations. This leads to fewer unnecessary desensitizations and improved patient care.
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