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Abid Z.,Northwestern University | Oh S.S.,University of California at San Francisco | Hu D.,University of California at San Francisco | Sen S.,University of California at San Francisco | And 14 more authors.
Clinical and Experimental Allergy | Year: 2016

Background: Younger maternal age at birth is associated with increased risk of asthma in offspring in European descent populations, but has not been studied in Latino populations. Objectives: We sought to examine the relationship between maternal age at birth and prevalence of asthma in a nationwide study of Latino children. Methods: We included 3473 Latino children aged 8–21 years (1696 subjects with physician-diagnosed asthma and 1777 healthy controls) from five US centres and Puerto Rico recruited from July 2008 through November 2011. We used multiple logistic regression models to examine the effect of maternal age at birth on asthma in offspring overall and in analyses stratified by ethnic subgroup (Mexican American, Puerto Rican and other Latino). Secondary analyses evaluated the effects of siblings, acculturation and income on this relationship. Results: Maternal age < 20 years was significantly associated with decreased odds of asthma in offspring, independent of other risk factors (OR = 0.73, 95% CI: 0.57–0.93). In subgroup analyses, the protective effect of younger maternal age was observed only in Mexican Americans (OR = 0.53, 95% CI: 0.36, 0.79). In Puerto Ricans, older maternal age was associated with decreased odds of asthma (OR = 0.65, 95% CI: 0.44–0.97). In further stratified models, the protective effect of younger maternal age in Mexican Americans was seen only in children without older siblings (OR = 0.44, 95% CI: 0.23–0.81). Conclusion and Clinical Relevance: In contrast to European descent populations, younger maternal age was associated with decreased odds of asthma in offspring in Mexican American women. Asthma is common in urban minority populations but the factors underlying the varying prevalence among different Latino ethnicities in the United States is not well understood. Maternal age represents one factor that may help to explain this variability. © 2016 John Wiley & Sons Ltd

PubMed | Veterans Caribbean Health System, The Ann and Robert H Lurie Childrens Hospital of Chicago, Northwestern University, Baylor College of Medicine and 9 more.
Type: | Journal: eLife | Year: 2017

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.210

MacGinnitie A.J.,Boston Childrens Hospital | Rachid R.,Boston Childrens Hospital | Gragg H.,Boston Childrens Hospital | Little S.V.,Boston Childrens Hospital | And 20 more authors.
Journal of Allergy and Clinical Immunology | Year: 2016

Background: Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. Objective: We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. Methods: Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. Results: The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; . P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. Conclusion: Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach. © 2016 American Academy of Allergy, Asthma & Immunology.

Johnson S.,Great North Childrens Hospital | Stojanovic J.,Great North Childrens Hospital | Ariceta G.,Hospital Vall D Hebron Barcelona | Bitzan M.,McGill University | And 14 more authors.
Pediatric Nephrology | Year: 2014

Background: In 2009, the European Paediatric Study Group for Haemolytic Uraemic Syndrome (HUS) published a clinical practice guideline for the investigation and initial therapy of diarrhea-negative HUS (now more widely referred to as atypical HUS, aHUS). The therapeutic component of the guideline (comprising early, high-volume plasmapheresis) was derived from anecdotal evidence and expert consensus, and the authors committed to auditing outcome.Methods: Questionnaires were distributed to pediatric nephrologists across Europe, North America, and the Middle East, who were asked to complete one questionnaire per patient episode of aHUS between July 1, 2009 and December 31, 2010. Comprehensive, anonymous demographic and clinical data were collected.Results: Seventy-one children were reported with an episode of aHUS during the audit period. Six cases occurred on a background of influenza A H1N1 infection. Of 71 patients, 59 (83 %) received plasma therapy within the first 33 days, of whom ten received plasma infusion only. Complications of central venous catheters occurred in 16 out of 51 patients with a catheter in-situ (31 %). Median time to enter hematological remission was 11.5 days, and eight of 71 (11 %) patients did not enter hematological remission by day 33. Twelve patients (17 %) remained dialysis dependent at day 33.Conclusions: This audit provides a snapshot of the early outcome of a group of children with aHUS in the months prior to more widespread use of eculizumab. © 2014, IPNA.

Finer G.,Northwestern University | Price H.E.,Northwestern University | Shore R.M.,The Ann and Robert H Lurie Childrens Hospital of Chicago | White K.E.,Indiana University | Langman C.B.,Northwestern University
American Journal of Medical Genetics, Part A | Year: 2014

Hyperphosphatemic familial tumoral calcinosis (HFTC) is characterized by enhanced renal phosphate absorption, hyperphosphatemia, and tumor-like extraosseous calcifications due to inactivating mutations in FGF23 or associated proteins. Surgical excision is needed when low phosphate diet and phosphate binders are ineffective. Sporadic reports have supported acetazolamide use. We report on a 7-year-old African American boy who presented with severe HFTC requiring numerous surgical excisions. Tumors continued to appear and others reoccurred despite phosphate restriction and sevelamer carbonate. At the age of 9.5 years, acetazolamide (40mg/kg/day) was added and resulted in mild metabolic acidosis (bicarbonate 25.3mEq/L vs. 21.4mEq/L, P<0.001; serum pH 7.38 vs. 7.31, P=0.013, pre- and post-acetazolamide, respectively) but no change in tubular reabsorption of phosphate (TRP) (96.9% vs. 95.9%, P=0.34) or serum phosphate (6.6mg/dl vs. 6.9mg/dl, P=0.52 pre- and post-acetazolamide, respectively). Following the initiation of acetazolamide therapy, the patient experienced significant improvement in disease course as indicated by resolution of localized bone pain, cessation of tumor formation, and no tumor recurrence. Despite mild metabolic acidosis, our patient had improved linear growth and did not develop any other side effects related to therapy. Intact FGF23 remained abnormally low throughout disease course, while C-terminal FGF23 increased with acetazolamide. We conclude that acetazolamide can control severe HFTC by inducing mild metabolic acidosis despite no change in serum phosphate or TRP. This effect may be exerted though improved calcium-phosphate complex solubility and increased FGF23 locally. © 2014 Wiley Periodicals, Inc.

Keir L.S.,Northwestern University | Keir L.S.,The Ann and Robert H Lurie Childrens Hospital of Chicago | Langman C.B.,Northwestern University | Langman C.B.,The Ann and Robert H Lurie Childrens Hospital of Chicago
Transfusion and Apheresis Science | Year: 2016

Objectives: To review the role of complement in glomerular pathologies focusing on thrombotic microangiopathies (TMA) caused by Shiga toxin (Stx) and organ transplantation associated hemolytic uremic syndrome (HUS) as well as C3 glomerulopathy (C3G). Methods: Examination of literature discussing TMA associated with Stx HUS, transplantation related HUS and C3G. Results: There is an emerging role for complement biology in the renal glomerulus where its inappropriate over-activation is integral to several diseases. Stx HUS patients show evidence of complement activation and the toxin itself can activate complement and inhibit its normal regulation. However, therapeutic complement blockade has not yet proven effective in all circumstances. This may be partly related to late use and a clinical trial could be warranted. Organ transplantation associated HUS has carried a poor prognosis. While case reports supporting the use of complement inhibition exist, there has not been a formal trial. Complement activation in C3G is established but again treatment with complement inhibition has failed to be uniformly beneficial. Here, too, a clinical trial may help determine which subgroup of patients should be treated with these agents. Conclusion: Complement plays an important role in the glomerulus but more work is needed to fully understand how it contributes to normal function and pathology. This will help direct appropriate therapy in these diseases. © 2016 Elsevier Ltd.

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