The Relationship Between Allergic Rhinitis, Asthma, and Cardiovascular Disease in the National Health Interview Surveys (NHIS), 1999-2018.

BACKGROUND: Atopic disease has been associated with immune dysregulation and chronic inflammation, but current practice guideline recommendations do not include the evaluation of inflammatory outcomes among patients with asthma and allergic rhinitis (AR). OBJECTIVE: This study investigates the relationship between asthma, AR, and cardiovascular disease (CVD) using data from the U.S. National Health Interview Survey (NHIS) between 1999 and 2018. METHODS: We used data from adults in the NHIS (n = 603,140, representing a population of 225,483,286). Exposures were physician-diagnosed asthma (lifetime/past-year) and AR (past-year). Outcomes were physician-diagnosed heart disease: coronary heart disease (CHD), angina, heart attack, and nonspecific "heart-condition" (all lifetime). We used survey-weighted descriptive analysis and logistic regression adjusting for demographic and socioeconomic factors. RESULTS: A total of 11.44% reported at least 1 heart condition, with CHD the most prevalent (4.27%) across 20 years of pooled data. Asthma and AR were associated with higher CVD in all bivariate analyses. Specifically, lifetime asthma was associated with increased odds of CHD, (odds ratio [OR] 1.36; 95% confidence interval [95% CI] 1.29-1.42), with stronger effects observed for a past-year asthma attack (OR 1.66; 95% CI 1.55-1.80). The strongest effect of all was observed in those with a past-year asthma attack having increased odds of angina (OR 2.42; 95% CI 2.24-2.63). Allergic rhinitis was independently associated with increased odds of CHD (OR 1.25; 95% CI 1.18-1.28). CONCLUSIONS: Asthma and AR are risk factors for all types of CVD in this nationally representative study covering a 2-decade period in the United States. Clinicians should consider screening patients with severe and/or uncontrolled asthma and AR early for CVD, particularly angina and CHD. Future studies are warranted to explore the immunological milieu in these patients and identify therapeutic targets.

Serum Immunoglobulin Levels as Potential Biomarkers of COVID-19 Pneumonia.

OBJECTIVE: Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) has been known to cause immune dysregulation. However, the association between specific immunoglobulins and clinical characteristics in COVID-19 remains poorly understood. This study investigated the relationship between immunoglobulins and clinical outcomes in adults hospitalized with COVID-19 pneumonia. METHODS: A retrospective chart analysis was performed (N=569, December 2020-April 2021). Information on demographics, clinical factors, and total serum immunoglobulin (IgG, IgA, IgM, and IgE) levels were collected (N=60). Clinical outcomes of interest included: symptom duration, comorbidities (Charlson 10-year-estimated-survival (C10YES) and comorbidity index (CCI), vital derangements upon presentation (NEWS-2-score), length of stay (LOS), and mortality. Spearman correlation, chi-square tests and linear regression were conducted. RESULTS: Serum IgM levels were positive predictors of C10YES (ß=0.104, p=0.023) and negative predictors of CCI (ß=-0.007, p=0.047). There was an association between higher serum IgG levels and longer LoS (ß=7.455, p=0.047). We found no significant associations between immunoglobulins and preadmission symptom duration, medication use, or mortality. CONCLUSIONS: Total IgM was associated with increased survival and decreased comorbidity, and total IgG was associated with length of hospitalization. IgM may predict the body's initial ability to produce humoral immune responses, and IgG may function as a possible signature of chronic antigenic responses and inflammation, associated with comorbidities that increase COVID-19 hospitalization. Evaluating total IgM and IgG as prognostic biomarkers in COVID-19 pneumonia patients may contribute to improved management and clinical outcomes.

Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19.

BACKGROUND: WHO has established a Global Clinical Platform for the clinical characterisation of COVID-19 among hospitalised individuals. We assessed whether people living with HIV hospitalised with COVID-19 had increased odds of severe presentation and of in-hospital mortality compared with individuals who were HIV-negative and associated risk factors. METHODS: Between Jan 1, 2020, and July 1, 2021, anonymised individual-level data from 338 566 patients in 38 countries were reported to WHO. Using the Platform pooled dataset, we performed descriptive statistics and regression analyses to compare outcomes in the two populations and identify risk factors. FINDINGS: Of 197 479 patients reporting HIV status, 16 955 (8·6%) were people living with HIV. 16 283 (96.0%) of the 16 955 people living with HIV were from Africa; 10 603 (62·9%) were female and 6271 (37·1%) were male; the mean age was 45·5 years (SD 13·7); 6339 (38·3%) were admitted to hospital with severe illness; and 3913 (24·3%) died in hospital. Of the 10 166 people living with HIV with known antiretroviral therapy (ART) status, 9302 (91·5%) were on ART. Compared with individuals without HIV, people living with HIV had 15% increased odds of severe presentation with COVID-19 (aOR 1·15, 95% CI 1·10-1·20) and were 38% more likely to die in hospital (aHR 1·38, 1·34-1·41). Among people living with HIV, male sex, age 45-75 years, and having chronic cardiac disease or hypertension increased the odds of severe COVID-19; male sex, age older than 18 years, having diabetes, hypertension, malignancy, tuberculosis, or chronic kidney disease increased the risk of in-hospital mortality. The use of ART or viral load suppression were associated with a reduced risk of poor outcomes; however, HIV infection remained a risk factor for severity and mortality regardless of ART and viral load suppression status. INTERPRETATION: In this sample of hospitalised people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was an independent risk factor for both severe COVID-19 at admission and in-hospital mortality. These findings have informed WHO immunisation policy that prioritises vaccination for people living with HIV. As the results mostly reflect the data contribution from Africa, this analysis will be updated as more data from other regions become available. FUNDING: None. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Recurrent reactive infectious mucocutaneous eruption (RIME): Insights from a child with three episodes.

Reactive infectious mucocutaneous eruption (RIME) was recently proposed to replace the term Mycoplasma pneumoniae (MP)-induced rash and mucositis to account for the fact that non-MP pathogens may also cause rash and mucositis. In this report, we describe a unique case of recurrent RIME featuring a total of three episodes. As two of the episodes demonstrated contemporaneous infection with MP and group A streptococcus or influenza B, this case lends further support to use of the term RIME. In addition, although RIME typically involves at least two mucous membranes, this case shows that recurrent episodes may fall into the rare exception in which mucositis is limited to one site.

In-hospital mortality of hematopoietic stem cell transplantation among children with nonmalignancies: A nationwide study in the United States from 2000 to 2012.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) can cure or alleviate a wide range of nonmalignant childhood conditions. However, few studies have examined longitudinal national trends of frequency or short-term complications of HSCT before 2006 when an HSCT became a reportable procedure by US law. By using a US nationally representative database, we conducted nationwide longitudinal analyses on demographics, in-hospital mortality, and short-term complications in nonmalignant HSCT from 2000 to 2012. PROCEDURE: We analyzed 2504 admissions for children < 20 years old who underwent an allogeneic HSCT for a nonmalignant condition by using the Kids' Inpatient Database for the years 2000, 2003, 2006, 2009, and 2012. Changes in in-hospital mortality and other outcomes were assessed over the study period using weighted analyses, which enabled generation of national estimates in each year. RESULTS: The number of admissions for HSCT increased from 334 to 667 from 2000 to 2012, respectively; among them, the use of bone marrow decreased (66.5% to 34.1%, P < 0.001). In-hospital mortality declined (13.4% to 7.1%, P = 0.04), as did bacteremia (28.7% to 10.1%, P < 0.001) and vascular catheter infections (18.8% to 8.7%, P = 0.006), but cytomegalovirus infections increased (4.9% to 15.9%, P < 0.001), as did adenovirus infections (1.8% to 6.9%, P < 0.001) from 2000 to 2012. CONCLUSION: Population-based analyses demonstrated a substantial expansion of the utilization of HSCT occurred for pediatric nonmalignancies from 2000 to 2012 in the United States, whereas the in-hospital mortality declined by approximately a half. Further research is needed to identify distinct contributing factors.

Allergic sensitization and clinical outcomes in urban children with asthma, 2013-2016.

BACKGROUND: The aim of this study was to examine if food and/or aeroallergen sensitization was associated with worse asthma, pulmonary function tests (PFT), and laboratory markers. METHODS: At our institution, 386 children with asthma were divided into allergic and nonallergic groups based on allergen-specific immunoglobulin E (IgE) testing classes 1-6 versus 0. Asthma severity and/or control, IgE level, eosinophil counts and/or percentages, forced vital capacity (FVC), forced expiratory volume in the first second of expiration (FEV1), and FEV1/FVC, were compared by using bivariate, regression, and subgroup analyses for children who were highly allergic (≥4 allergens). RESULTS: A total of 291 subjects with asthma were allergic, significantly older, and had higher mean IgE levels and eosinophil counts and percentages (all p < 0.001). A total of 203 subjects who were highly allergic had worse obstruction on PFTs. Increasing age predicted allergen sensitization after confounder adjustment, odds ratio (OR) 1.54 (95% confidence interval [CI], 1.18-2.02). Similarly, PFT obstruction was associated with multiple allergen sensitization (OR 0.97 [95% CI, 0.93-1.02]). CONCLUSION: Increasing age predicted allergic sensitization and multiple allergen sensitization. Worse obstruction on PFT also predicted multiple allergen sensitization. Continued surveillance of aeroallergen sensitization and PFT results may be beneficial in asthma management, particularly in older urban children.

Pubertal assessment: targeted educational intervention for pediatric trainees.

Background Timely and periodic pubertal assessment in children is vital to identify puberty related disorders. Pediatricians need to have working knowledge of puberty time and tempo. Pediatric residency is an important platform to acquire physical examination skills including pubertal assessment. Objective An educational intervention for teaching pubertal assessment was piloted on pediatric residents at our institution. Methods The intervention comprised of interactive lecture series, ID badge size Tanner stage cards and Tanner posters placed in residents' continuity clinics. Pre-intervention, post-intervention and 3 months post-intervention surveys for participating trainees were administered to determine the effectiveness of the intervention. Attitudes, practices, knowledge scores, and barriers to Tanner staging conduct were analyzed. Results Forty-three residents participated in the intervention. Knowledge scores of PGY1 (5.95 ± 1.6 vs. 7.47 ± 1.4, p < 0.01) improved right after the intervention, as did self-reported clinical practices of all trainees 3 months post- intervention with regards to conducting external genital examination and performing pubertal assessment. Confidence levels of pediatric trainees in conducting pubertal assessment and comfort levels in assessing the need for endocrine referral based on abnormal Tanner staging improved after the intervention, although the effect was not statistically significant. Conclusion Our intervention is a worthwhile technique for teaching pubertal assessment to residents as it is simple to conduct, easily reproducible, provides baseline knowledge needed for recognition of normal pubertal development and puberty related conditions, and instills confidence in residents.

Family Consumer Behaviors, Adolescent Prediabetes and Diabetes in the National Health and Nutrition Examination Survey (2007-2010).

BACKGROUND: Prediabetes or diabetes (characterized by hemoglobin A1c [HbA1c] levels ≥ 5.7 gm%) has been associated with numerous long-term complications. Family consumer behaviors are important risk factors that lead to impaired glucose tolerance or diabetes. However, few studies have studied the association between the family consumer environment and prediabetes and diabetes in adolescents. OBJECTIVE: The aim of this study was to examine the association between family consumer behaviors (healthy food availability and supermarket spending) and adolescent prediabetes and diabetes (ClinicalTrials.gov identifier #NCT03136289.) Methods: Data from a nationwide survey conducted by the Centers for Disease Control and Prevention (National Health and Nutrition Examination Survey [NHANES] 2007-2010 data) were used for these analyses. Adolescents aged 12-19 years were selected for this study. Bivariate analyses and logistic regression models assessed the relationship between family consumer behaviors and the prevalence of adolescent prediabetes and diabetes. Multivariable models adjusted for age, gender, ethnicity, physical activity, education, income, and household size. RESULTS: A total of 2520 adolescents were eligible for this study. Adolescents with healthier household food availability had negative odds (odds ratio [OR] = 0.74, 95% confidence interval [CI], 0.55-1.00), as did higher log supermarket spending (OR = 0.69; 95% CI, 0.57-0.85). Interaction models demonstrated that adolescent females had more negative odds of prediabetes/diabetes for both healthier food availability (OR = 0.79, 95% CI, 0.39-1.29) and for greater log supermarket spending (OR = 0.69, 95% CI, 0.57-0.85). CONCLUSION: This study shows that both healthy food availability and an increase in supermarket spending were associated with a decreased adjusted prevalence of prediabetes and diabetes in adolescents, with a greater effect in females. These results suggest the need for policy and dietary interventions targeting the consumer environment.

Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress-Related Pathogenesis and Current Challenges in Biomarker Development.

HPA axis genes implicated in glucocorticoid regulation play an important role in regulating the physiological impact of social and environmental stress, and have become a focal point for investigating the role of glucocorticoid regulation in the etiology of disease. We conducted a systematic review to critically assess the full range of clinical associations that have been reported in relation to DNA methylation of CRH, CRH-R1/2, CRH-BP, AVP, POMC, ACTH, ACTH-R, NR3C1, FKBP5, and HSD11ß1/2 genes in adults. A total of 32 studies were identified. There is prospective evidence for an association between HSD11ß2 methylation and hypertension, and functional evidence of an association between NR3C1 methylation and both small cell lung cancer (SCLC) and breast cancer. Strong associations have been reported between FKBP5 and NR3C1 methylation and PTSD, and biologically-plausible associations have been reported between FKBP5 methylation and Alzheimer's Disease. Mixed associations between NR3C1 methylation and mental health outcomes have been reported according to different social and environmental exposures, and according to varying gene regions investigated. We conclude by highlighting key challenges and future research directions that will need to be addressed in order to develop both clinically meaningful prognostic biomarkers and an evidence base that can inform public policy practice.

Adverse maternal exposures, methylation of glucocorticoid-related genes and perinatal outcomes: a systematic review.

AIM: Maternal environmental exposures affect perinatal outcomes through epigenetic placental changes. We examine the literature addressing associations between adverse maternal exposures, perinatal outcomes and methylation of key genes regulating placental cortisol metabolism. METHODS: We searched three databases for studies that examined NR3C1 and HSD11ß1/HSD11 ß 2 methylation with maternal exposures or perinatal outcomes. Nineteen studies remained after screening. We followed Cochrane's PRISMA reporting guidelines (2009). RESULTS: NR3C1 and HSD11 ß methylation were associated with adverse infant neurobehavior, stress response, blood pressure and physical development. In utero exposure to maternal stress, nutrition, preeclampsia, smoking and diabetes were associated with altered NR3C1 and HSD11 ß methylation. CONCLUSION: NR3C1 and HSD11 ß methylation are useful biomarkers of specific environmental stressors associated with important perinatal outcomes that determine pediatric and adult disease risk.

Clinical characteristics and dose-volume histogram parameters associated with the development of pleural effusions in non-small cell lung cancer patients treated with chemoradiation therapy.

BACKGROUND: To investigate descriptive characteristics and dose metric (DM) parameters associated with development of pleural effusions (PlEf) in non-small cell lung cancer (NSCLC) treated with definitive chemoradiation therapy (CRT). MATERIALS AND METHODS: We retrospectively assessed treatment records and follow-up imaging of 66 NSCLC patients to identify PlEf formation after CRT. PlEf association between mean heart dose (MHD), mean lung dose (MLD), heart V5-V60 (HV), and lung V5-V60 (LV) were evaluated using Cox Proportional Hazard Models. RESULTS: A total of 52% (34 of 66 patients) of our population developed PlEf and the actuarial rates at 6 months, 12 months, and 18 months were 7%, 30%, and 42%, respectively. Median time to diagnosis was five months (range 0.06-27 months). The majority of PlEfs were grade one (67%) and developed at a median of four (0.06-13) months, followed by grade two (15%) at a median 11 (5-12) months, and grade three (18%) at a median of 11 (3-27) months. On multivariate analysis, increasing HV5-HV50, LV5-LV50, MHD, and MLD were associated with greater risk of PlEf. Higher grade PlEf was also associated with higher doses of radiation to the heart, while lung DM parameters were not significantly associated with higher PlEf grades. At five-months post-CRT, MHD of 25 Gy was associated with a 100% chance of grade one PlEf, an 82% risk of grade two PlEf, and a 19% risk of grade three PlEf. CONCLUSIONS: Post-CRT PlEf is common in NSCLC with the majority being grade one. Increasing heart and lung irradiation was associated with increased risk of PlEf. Increasing heart irradiation also correlated with development of increasing grades of PlEf. The impact of potential cardiopulmonary toxicity and resultant PlEfs after CRT requires additional study.

Asthma, oculonasal symptoms, and skin test sensitivity across National Health and Nutrition Examination Surveys.

BACKGROUND: The increasing prevalence of allergies and asthma has been reported. However, the progression of the prevalence of allergy (the "allergic diathesis progression") has not been examined over time from skin test positivity to oculonasal symptoms to the development of asthma. OBJECTIVE: To investigate the change in the prevalences and associations of positive skin test reactions, oculonasal symptoms, and asthma during the Second and Third National Health and Nutrition Examination Surveys (NHANES II and NHANES III, respectively). METHODS: Data collected during NHANES II and III were used. The prevalence and associations of positive skin test reactions, oculonasal symptoms, and asthma and the linear trend of oculonasal symptoms and asthma prevalence across different cumulative positive skin test reactions were calculated for each NHANES period. RESULTS: From NHANES II to NHANES III, the prevalence of asthma doubled (2 times) and increased for positive skin test reactions (2.2 times), oculonasal symptoms (3.3 times), and concurrence of asthma, oculonasal symptoms, and positive skin test reactions (5.3 times). People were sensitive to an increasing number of allergens. Positive skin test reactions increased from 0.2% (NHANES II) to 2.7% (NHANES III) for people allergic to all 6 allergens. CONCLUSION: Despite some methodologic differences in skin tests across NHANES II and III, this study demonstrated significant increases in allergen sensitivities (prevalence and number of allergens), oculonasal symptoms, and asthma over a 20-year course, indicating that increased sensitivity led to increased allergic symptoms and asthma during the 20 years from NHANES II to NHANES III.

Early vs. Late Chemoradiation Therapy and the Postoperative Interval to Adjuvant Therapy Do Not Correspond to Local Recurrence in Resected Pancreatic Cancer.

OBJECTIVE: Standard postoperative therapy for pancreatic cancer consists of both chemotherapy alone and chemoradiation. We sought to investigate whether the sequence of chemotherapy and chemoradiation and overall time to initiation of adjuvant therapy would impact local vs. distant recurrence. METHODS: After Institutional Review Board approval, resected pancreas cancer patient charts were evaluated for medical background, surgical, pathological, chemoradiation (CRT), and follow-up. Local recurrence (LR) was defined as failures occurring in the postoperative bed and regional lymph nodes. Early vs. late CRT was defined by whether CRT was given early (within 1-2 cycles of adjuvant chemotherapy) or late in the course of adjuvant chemotherapy (after the 3rd cycle of chemotherapy). The postoperative interval variance was compared to LR factors such as progression-free survival (PFS) and overall survival (OS). RESULTS: Of the 34 eligible patients, 47% (n=16) underwent early CRT and 41% (n=14) underwent late CRT. 12% (n=14) did not undergo any induction chemotherapy. At median follow-up of 22 months, 53% (n=18) had metastases, 24% (n=8) had LR, and 24% (n=8) were disease free. Kaplan-Meier curves revealed that early vs. late CRT did not appear to significantly impact OS (p=0.63), PFS (p=0.085) or LR (p=0.19). Postoperative interval did not affect PFS (p=0.42) or OS (p=0.93). CONCLUSIONS: Early vs. late CRT and the time to initiation of adjuvant therapy were not significantly associated with LR in patients with resected pancreatic cancer. Future prospective studies are required to determine if sequencing of chemotherapy, CRT, or the postoperative interval impact survival and patterns of recurrence.