Publications by authors named "Andrew J MacGinnitie"

24 Publications

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TEMPORARY REMOVAL: Predicting outcomes of baked egg and baked milk oral food challenges by using a ratio of food-specific IgE to total IgE.

J Allergy Clin Immunol Pract 2020 Nov 17. Epub 2020 Nov 17.

Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass.

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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http://dx.doi.org/10.1016/j.jaip.2020.11.004DOI Listing
November 2020

Utility of measuring tryptase levels in children and young adults.

Ann Allergy Asthma Immunol 2019 10 7;123(4):398-399. Epub 2019 Aug 7.

Division of Immunology, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2019.07.030DOI Listing
October 2019

Immunoglobulin E blockade during food allergen ingestion enhances the induction of inhibitory immunoglobulin G antibodies.

Ann Allergy Asthma Immunol 2019 02 4;122(2):213-215. Epub 2018 Nov 4.

Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2018.10.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360101PMC
February 2019

The Role of Food Challenges in Clinical Practice.

J Allergy Clin Immunol Pract 2018 Mar - Apr;6(2):353-360

Division of Immunology, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass.

Food challenges are the criterion standard for establishing the presence or absence of food allergy. However, they remain underused because of their resource-intensive nature, inadequate reimbursement, and concern for the risk of anaphylaxis. Here, we review indications for performing food challenges, including scenarios of uncertain diagnosis, quality-of-life effects following food challenges, and the impact on office practice including coding and reimbursement issues. Demand for food challenges is likely to increase and allergists should be capable of providing this service to their patients when indicated.
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http://dx.doi.org/10.1016/j.jaip.2017.12.014DOI Listing
November 2019

Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy: Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial.

J Allergy Clin Immunol Pract 2018 Mar - Apr;6(2):476-485.e3. Epub 2017 Oct 31.

Department of Pediatrics, University of North Carolina, Chapel Hill, NC.

Background: Peanut oral immunotherapy, using a variety of approaches, has been previously shown to induce desensitization in peanut-allergic subjects, but no products have been approved for clinical use by regulatory agencies.

Objective: We performed the first phase 2 multicentered study to assess the safety and efficacy of AR101, a novel oral biologic drug product.

Methods: A randomized, double-blind, placebo-controlled trial was conducted at 8 US centers. Eligible subjects were 4 to 26 years old, sensitized to peanut, and had dose-limiting symptoms to ≤143 mg of peanut protein in a screening double-blind, placebo-controlled food challenge (DBPCFC). Subjects were randomized 1:1 to daily AR101 or placebo and gradually up-dosed from 0.5 to 300 mg/day. The primary endpoint was the proportion of subjects in each arm able to tolerate ≥443 mg (cumulative peanut protein) at exit DBPCFC with no or mild symptoms.

Results: Fifty-five subjects (29 AR101, 26 placebo) were enrolled. In the intention-to-treat analysis, 23 of 29 (79%) and 18 of 29 (62%) AR101 subjects tolerated ≥443 mg and 1043 mg at exit DBPCFC, respectively, versus 5 of 26 (19%) and 0 of 26 (0%) placebo subjects (both P < .0001). Compared with placebo, AR101 significantly reduced symptom severity during exit DBPCFCs and modulated peanut-specific cellular and humoral immune responses. Gastrointestinal (GI) symptoms were the most common treatment-related adverse events (AEs) in both groups, with 6 AR101 subjects (21%) withdrawing, 4 of those due primarily to recurrent GI AEs.

Conclusions: In this study, AR101 demonstrated an acceptable safety profile and demonstrated clinical activity as a potential immunomodulatory treatment option in peanut-allergic children over the age of 4, adolescents, and young adults.
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http://dx.doi.org/10.1016/j.jaip.2017.09.016DOI Listing
November 2019

Multicenter prevalence of anaphylaxis in clinic-based oral food challenges.

Ann Allergy Asthma Immunol 2017 10 7;119(4):339-348.e1. Epub 2017 Sep 7.

Immunology, Allergy, and Rheumatology Section, Texas Children's Hospital, Houston, Texas; Department of Pediatrics, Baylor College of Medicine, Houston, Texas. Electronic address:

Background: Although previous single-center studies report the rate of anaphylaxis for oral food challenges (OFCs) as 9% to 11%, little is known regarding the epidemiology of clinical OFCs across multiple centers in the United States.

Objective: To examine the epidemiology, symptoms, and treatment of clinical low-risk OFCs in the nonresearch setting.

Methods: Data were obtained from 2008 to 2013 through a physician survey in 5 food allergy centers geographically distributed across the United States. Allergic reaction rates and the association of reaction rates with year, hospital, and demographics were determined using a linear mixed model. Meta-analysis was used to pool the proportion of reactions and anaphylaxis with inverse-variance weights using a random-effects model with exact confidence intervals (CIs).

Results: A total of 6,377 OFCs were performed, and the pooled estimate of anaphylaxis was 2% (95% CI, 1%-3%). The rate of allergic reactions was 14% (95% CI, 13%-16%) and was consistent during the study period (P = .40). Reaction rates ranged from 13% to 33%. Males reacted 16% more frequently than females (95% CI, 4%-37.5%; P = .04). Foods challenged in 2013 varied geographically, with peanut as the most challenged food in the Northeast, Midwest, and West and egg as the most challenged in the South.

Conclusion: As the largest national survey of allergic reactions of clinical open OFCs in a nonresearch setting in the United States, this study found that performing clinical nonresearch open low-risk OFCs results in few allergic reactions, with 86% of challenges resulting in no reactions and 98% without anaphylaxis.
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http://dx.doi.org/10.1016/j.anai.2017.07.028DOI Listing
October 2017

Omalizumab facilitates rapid oral desensitization for peanut allergy.

J Allergy Clin Immunol 2017 Mar 5;139(3):873-881.e8. Epub 2016 Sep 5.

Division of Immunology, Boston Children's Hospital, Boston, Mass. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jaci.2016.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369605PMC
March 2017

Implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) for Food Challenges.

J Allergy Clin Immunol Pract 2017 Mar - Apr;5(2):335-344.e3. Epub 2016 Jun 30.

Division of Immunology, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address:

Background: Oral food challenges (OFCs) are routinely used to confirm ongoing food allergy. Serum-specific IgE (sIgE) and skin prick testing (SPT) are imperfect predictors of which patients will pass OFCs.

Objective: The objective of this study was to describe the design and implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) to study and iteratively improve sIgE and SPT thresholds to determine when and where to conduct OFCs for patients.

Methods: Allergists consulted recommended sIgE and SPT thresholds when ordering challenges although diversions were permitted. Criteria were iteratively improved after periodic analyses of challenge outcome and diversions.

Results: Over 3 years, allergists ordered 2368 food challenges for 1580 patients with histories of IgE-mediated reactions to food: 1386 in an outpatient clinic and 945 in a higher resource infusion center. Reactions to challenge were observed in 13% of clinic and 23% of infusion center challenges. Six patients challenged in clinic required treatment with epinephrine compared with 22 in the infusion center. The need for epinephrine was more common in patients with asthma-5% of asthmatic patients required epinephrine compared with 1% of nonasthmatic patients (P < .01). Recommended sIgE and SPT thresholds were incrementally changed and, using the control chart methodology, a significant decrease was noted in the proportion of challenges ordered in the higher resource location.

Conclusions: By setting and continually refining sIgE and SPT recommendations using the SCAMP method, allergists can better determine the risk of severe reaction and triage patients to the appropriate setting for an OFC.
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http://dx.doi.org/10.1016/j.jaip.2016.05.021DOI Listing
November 2017

Plasma-derived C1-INH for managing hereditary angioedema in pediatric patients: A systematic review.

Pediatr Allergy Immunol 2015 Sep;26(6):537-44

Department of Medicine and Pediatrics, Penn State University, Hershey, PA, USA.

Presently, medications approved for children with Hereditary Angioedema (HAE) are extremely limited. This is especially the case for children under 12 years of age. For this reason we reviewed and summarized the data on treatment of children with HAE. Available data indicate that plasma derived C1-inhibitor is a safe, effective treatment option for HAE in pediatric patients, including those below 12 years of age. Other therapies are also appear safe for the under 12 year of age, but less data are available. Importantly, home-based treatment of HAE in this age group appears to be safe and effective and can improve quality of life. These findings support current HAE consensus guidelines which strongly recommend the use of plasma derived C1-inhibitor as a first-line treatment in children and encourage home and self-treatment.
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http://dx.doi.org/10.1111/pai.12425DOI Listing
September 2015

Characterization of anaphylaxis after ecallantide treatment of hereditary angioedema attacks.

J Allergy Clin Immunol Pract 2015 Mar-Apr;3(2):206-212.e4. Epub 2014 Oct 29.

Dyax Corp., Burlington, Mass.

Background: Ecallantide is a human plasma kallikrein inhibitor indicated for treatment of acute attacks of hereditary angioedema for patients 12 years of age and older. Ecallantide is produced in Pichia pastoris yeast cells by recombinant DNA technology. Use of ecallantide has been associated with a risk of hypersensitivity reactions, including anaphylaxis.

Objective: The objective of this detailed retrospective data review was to characterize anaphylaxis cases within the ecallantide clinical trials database.

Methods: Potential cases of hypersensitivity reactions in the ecallantide clinical development program were identified by examining reported adverse events. The National Institute of Allergy and Infectious Disease criteria were used to identify those events that were consistent with anaphylaxis; these cases were then reviewed in detail. Results from investigational antibody testing also were examined.

Results: Among patients who received subcutaneous ecallantide (n = 230 patients; 1045 doses of 30 mg ecallantide), 8 patients (3.5%) had reactions that met the National Institute of Allergy and Infectious Disease criteria for anaphylaxis; none occurred on first exposure to the drug. All 8 reactions had symptom onset within 1 hour of exposure and cutaneous manifestations commonly observed in type I hypersensitivity reactions. All the reactions responded to standard management of type I hypersensitivity reactions and resolved without fatal outcomes. IgE antibody testing to ecallantide or P pastoris was not consistently positive in patients who experienced apparent type I hypersensitivity reactions.

Conclusion: Anaphylaxis episodes after subcutaneous ecallantide exposure have clinical features suggestive of type I hypersensitivity reactions. However, anti-ecallantide or anti-P pastoris IgE antibody status was not found to be reliably associated with anaphylaxis.
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http://dx.doi.org/10.1016/j.jaip.2014.09.001DOI Listing
December 2015

Pediatric hereditary angioedema.

Pediatr Allergy Immunol 2014 Aug 9;25(5):420-7. Epub 2013 Dec 9.

Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Hereditary angioedema (HAE) is a lifelong illness characterized by recurrent swelling of the skin, intestinal tract, and, ominously, the upper airway. It is caused by inadequate activity of the protein C1-inhibitor, with dysfunction in the kallikrein/bradykinin pathway underlying the clinical symptoms. In addition to the physical symptoms, patients experience significant decrements in vocational and school achievement as well as in overall quality of life. Symptoms often begin in childhood and occur by age 20 in most patients, but life-threatening attacks are uncommon in the pediatric population. The availability of new therapies has transformed the management of HAE.
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http://dx.doi.org/10.1111/pai.12168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282351PMC
August 2014

Use of ecallantide in pediatric hereditary angioedema.

Pediatrics 2013 Aug 22;132(2):e490-7. Epub 2013 Jul 22.

Division of Immunology, Boston Children’s Hospital, Boston, Massachusetts 02115, USA.

Objective: Hereditary angioedema (HAE) due to C1-inhibitor deficiency is a rare autosomal dominant disease that manifests as sudden unpredictable attacks of subcutaneous or submucosal edema affecting the skin, intestine, and upper airway. Ecallantide is a plasma kallikrein inhibitor indicated for treatment of HAE attacks in patients aged 16 years and older. This analysis examines safety and efficacy of ecallantide for treatment of HAE attacks in patients <18 years of age.

Methods: Data for patients aged 9 to 17 years treated subcutaneously with 30 mg ecallantide or placebo were pooled from 4 clinical studies (2 double-blind, placebo-controlled and 2 open-label). Efficacy end points included 2 HAE-specific patient-reported outcome measures: mean symptom complex severity (MSCS) score and treatment outcome score (TOS). Times to initial improvement, sustained improvement, and complete or near-complete symptom resolution were calculated. Treatment-emergent adverse events were examined.

Results: Overall, 29 pediatric patients were included; 25 of them received ecallantide for 62 total HAE attacks, and 10 received placebo for 10 total attacks. Ecallantide-treated attacks revealed clinically relevant reduction in symptom severity at 4 hours postdosing based on mean change in MSCS score (-1.4 ± 0.9 ecallantide versus -0.9 ± 0.6 placebo) and TOS (73.9 ± 35.50 ecallantide versus 45.0 ± 43.78 placebo). Patients treated with ecallantide showed rapid improvement in symptoms (median time to complete or near-complete symptom resolution: 181 minutes). No serious adverse events related to treatment were observed.

Conclusions: Ecallantide appears effective for HAE attacks in adolescents, with rapid symptom improvement. No unexpected safety issues were identified.
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http://dx.doi.org/10.1542/peds.2013-0646DOI Listing
August 2013

Outcomes after ecallantide treatment of laryngeal hereditary angioedema attacks.

Ann Allergy Asthma Immunol 2013 Mar 5;110(3):184-188.e2. Epub 2013 Jan 5.

Brigham and Women's Hospital, Boston, MA 02467, USA.

Background: Hereditary angioedema (HAE) is a rare disorder associated with episodic attacks of well-demarcated angioedema. Attacks that affect the larynx can result in life-threatening airway obstruction.

Objectives: To examine efficacy and safety of ecallantide treatment for laryngeal HAE attacks.

Methods: Data were combined from 4 clinical studies (EDEMA2, EDEMA3, EDEMA4, and DX-88/19) evaluating 30 mg of subcutaneous ecallantide for treatment of acute HAE attacks. Efficacy was assessed using 2 validated, HAE-specific, patient-reported outcome measures. The change in Mean Symptom Complex Severity (MSCS) score indicates change in symptom severity; a negative score indicates improvement. The calculated minimally important difference (MID) for change in severity is -0.30. The Treatment Outcome Score (TOS) measures treatment response. A positive score indicates improvement; the calculated MID is 30.

Results: Overall, 98 patients received ecallantide for 220 laryngeal attacks. The mean ± SD change in MSCS score was -1.1 ± 0.73 and -1.6 ± 0.68 at 4 and 24 hours, respectively. The mean ± SD TOS was 73.5 ± 35.8 and 85.5 ± 27.8 at 4 and 24 hours, respectively. Median time to significant improvement was 185 minutes (95% confidence interval, 167-226). One attack required intubation. Four treatment-emergent serious adverse events were reported, including 2 HAE attacks that resulted in hospitalization and 2 anaphylactic reactions. One of these reactions required treatment with epinephrine, but both patients recovered fully. There were no deaths.

Conclusion: In this large attack series, ecallantide was effective for treatment of laryngeal HAE attacks. There is a risk of hypersensitivity, including anaphylaxis, consistent with product labeling. As such, ecallantide should be administered under the supervision of a health care professional.

Trial Registration: clinicaltrials.gov Identifiers: not applicable for EDEMA2 (trial was conducted before implementation of registration requirements); NCT00262080 for EDEMA3, NCT00457015 for EDEMA4, and NCT00456508 for DX-88/19.
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http://dx.doi.org/10.1016/j.anai.2012.12.007DOI Listing
March 2013

Analysis of hereditary angioedema attacks requiring a second dose of ecallantide.

Ann Allergy Asthma Immunol 2013 Mar 8;110(3):168-72. Epub 2013 Jan 8.

Institute for Asthma and Allergy, Wheaton, MD 20902, USA.

Background: Effective treatment of acute attacks is critical in managing hereditary angioedema (HAE). Ecallantide, a plasma kallikrein inhibitor, is approved for the treatment of HAE attacks. Occasionally, a second dose is needed when treating attacks of HAE.

Objective: To evaluate the characteristics of HAE attacks requiring a second dose (dose B) of ecallantide.

Methods: Data from all ecallantide clinical trials (EDEMA2, EDEMA4, and DX-88/19) that allowed an open-label dose B were included in this analysis. Patient and attack characteristics potentially predictive of dose B after ecallantide were analyzed by logistic regression. A multivariate model was built using a backward selection process, incorporating variables from the univariate model with P < .20 and removing factors with the highest P value until only significant (P < .05) factors remained.

Results: The analysis included 732 ecallantide-treated HAE attacks in 179 patients. Dose B was required in 88 attacks (12.0%), most (80.5%) for incomplete response. By attack location, 31 of 325 abdominal attacks (9.5%), 17 of 158 laryngeal attacks (10.8%), and 40 of 242 peripheral attacks (16.5%) required dose B. On the basis of the univariate analysis, baseline severity (odds ratio = 1.33, P = .15) and peripheral attack (odds ratio = 1.80, P = .01) were identified as potential predictive factors; abdominal attacks had an inverse correlation (odds ratio = 0.64, P = .055). However, the multivariate analysis identified only peripheral attacks as statistically significantly correlated (P < .05) with dose B requirement.

Conclusion: A single, 30-mg dose of ecallantide was effective for most HAE attacks (88.0%). Patients with peripheral attacks of HAE were more likely to require a second dose of ecallantide after 4 hours.

Trial Registration: clinicaltrials.gov Identifiers: not applicable for EDEMA2 (trial was conducted before registration requirements were implemented), NCT00457015 for EDEMA4, and NCT00456508 for DX-88/19.
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http://dx.doi.org/10.1016/j.anai.2012.12.004DOI Listing
March 2013

Efficacy and safety of ecallantide in treatment of recurrent attacks of hereditary angioedema: open-label continuation study.

Allergy Asthma Proc 2013 Mar-Apr;34(2):155-61

Allergy & Asthma Specialists, Dallas, Texas, USA.

Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of potentially life-threatening edema. The plasma kallikrein inhibitor ecallantide is approved for treatment of acute HAE attacks. This study evaluates the efficacy and safety of ecallantide for treatment of multiple HAE episodes in the DX-88/19 (continuation) study. Patients received 30 mg of subcutaneous ecallantide for acute HAE attack symptoms, with no limit on number of episodes treated. Primary end point was change in patient-reported mean symptom complex severity (MSCS) score at 4 hours. Additional end points included change in MSCS score at 24 hours, treatment outcome score (TOS) at 4 and 24 hours, and time to response. Safety parameters included adverse events. Statistical analyses were conducted on qualifying treatment episodes (those with ≥12 patients). One hundred forty-seven patients received treatment for 625 episodes; analyses were conducted through 13 treatment episodes. Across 13 episodes at 4 hours, mean change in MSCS score ranged from -1.04 to -1.36, and mean TOSs ranged from 56.2 to 79.8. Median time to onset of sustained improvement ranged from 59 to 113 minutes. There was no indication of reduced efficacy with repeated ecallantide use. No new safety signals were detected. Eight patients (5.4%) reported potential hypersensitivity reactions, six of whom met the definition of anaphylaxis based on National Institute of Allergy and Infectious Diseases criteria. Ecallantide is effective for acute recurrent HAE attacks and maintains its efficacy and safety during multiple treatment episodes in patients with HAE. Potential hypersensitivity reactions were consistent with prior reports.
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http://dx.doi.org/10.2500/aap.2013.34.3653DOI Listing
August 2013

Long-acting beta-agonists and the risk of intensive care unit admission in children.

J Asthma 2012 Jun 30;49(5):450-5. Epub 2012 Apr 30.

Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.

Objective: A possible association between long-acting beta-agonists (LABA) and severe asthma exacerbations including death remains controversial. We examined whether LABA in the setting of combination therapy with inhaled corticosteroids (ICS) increase the risk of near-fatal asthma in children using a case-control study design.

Methods: Medical records from admissions for asthma exacerbations in children 4-18 years of age during the 2005 calendar year at Children's Hospital of Pittsburgh of UPMC were reviewed. Cases and controls were determined by pediatric intensive care unit (PICU) and floor admission, respectively. Exposure was defined by LABA use in combination with ICS versus ICS alone.

Results: Records from 85 PICU and 96 pediatric floor admissions were reviewed. LABA use in combination with ICS did not increase the risk of PICU admission (odds ratio 1.07, 95% CI 0.46-2.52) compared to ICS only without LABA. After adjusting for demographics, asthma severity, history of PICU admissions, and concurrent infection, LABA/ICS use still did not increase the risk of PICU admission (adjusted odds ratio 0.84, 95% CI 0.26-2.76) compared to ICS alone. There were no deaths and five intubations within the study period.

Conclusions: The combination of LABA and ICS did not appear to increase the risk of near-fatal asthma in children.
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http://dx.doi.org/10.3109/02770903.2012.677894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676306PMC
June 2012

Ecallantide for treatment of acute hereditary angioedema attacks: analysis of efficacy by patient characteristics.

Allergy Asthma Proc 2012 Mar-Apr;33(2):178-85

Division of Immunology, Children's Hospital Boston, Massachusetts, USA.

Hereditary angioedema (HAE) is characterized by episodic attacks of edema. HAE is caused by low levels of the protein C1 esterase inhibitor, which inhibits plasma kallikrein, the enzyme responsible for converting high-molecular-weight kininogen to bradykinin. Unregulated production of bradykinin leads to the characteristic clinical symptoms of swelling and pain. Ecallantide is a novel plasma kallikrein inhibitor effective for treatment of acute HAE attacks. This study was designed to analyze the efficacy of ecallantide for treating HAE attacks by attack location, attack severity, patient gender, and body mass index (BMI). An analysis of integrated data from two double-blind, placebo-controlled trials of ecallantide for treatment of acute HAE attacks was undertaken. For the purpose of analysis, symptoms were classified by anatomic location and, for each location, by the patient-assessed severity of the attack. Efficacy versus placebo was examined using two validated patient-reported outcomes: treatment outcome score and mean symptom complex severity score. One hundred forty-three attacks were analyzed (73 ecallantide and 70 placebo). Ecallantide was equally effective in both male and female subjects. Ecallantide had decreased efficacy for patients with BMI > 30 kg/m(2). Ecallantide showed efficacy for treatment of severe and moderate attacks, and was effective for abdominal, internal head and neck, external head and neck, and cutaneous locations. In summary, ecallantide is effective for treatment of acute HAE attacks of different symptom locations and severity; outcomes were similar for men and women. However, the standard dose was less effective for obese patients.
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http://dx.doi.org/10.2500/aap.2012.33.3528DOI Listing
August 2012

Indoor allergen sensitization and the risk of asthma and eczema in children in Pittsburgh.

Allergy Asthma Proc 2011 Sep-Oct;32(5):372-6

Division of Pulmonary Medicine, Allergy and Immunology, Children's Hospital of Pittsburgh of UPMC, Department of Pediatrics, University of Pittsburgh School of Medicine, Pennsylvania, USA.

Several studies have shown that sensitization to cockroach and mouse allergens is correlated with presence and severity of asthma, especially among children living in inner cities. This study evaluated the prevalence of positive skin testing to indoor allergens in the Pittsburgh area and the association with asthma and eczema. A retrospective analysis was performed of 540 children from the Pittsburgh area who underwent skin testing to indoor allergens. Presence of asthma and eczema were determined by parent and/or physician report. Asthma and eczema are not significantly more frequent among children who had positive skin testing to cockroaches or mice. However, asthma was more common among children who had positive skin testing to dogs (odds ratio [OR], 1.4; 95% CI, 1.23-1.65), cats (OR, 1.4; 95% CI, 1.21-1.58), and dust mites (OR, 1.2; 95% CI, 1.03-1.37). Eczema was more common in children who had positive skin testing to cats (OR, 1.5; 95% CI, 1.14-2.02). Both asthma (OR, 1.4; 95% CI, 1.18-1.58) and eczema (OR, 1.4; 95% CI, 1.07-1.92) were more prevalent among children with any positive skin test. We did not find that sensitization to cockroaches or mice was correlated with the diagnosis or asthma or eczema in the Pittsburgh area. However, sensitization to any allergen, and to cats and/or dogs specifically, was associated with diagnosis of both asthma and eczema. Our result suggests that allergic sensitization is associated with these diseases, but the implicated allergens may vary.
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http://dx.doi.org/10.2500/aap.2011.32.3456DOI Listing
April 2012

Infant with unusual food reactions.

Acta Paediatr 2011 Oct;100(10):1289, 1394-5

University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1111/j.1651-2227.2011.02316.xDOI Listing
October 2011

Chronic granulomatous disease in an adolescent with recurrent impetigo and cholecystectomy.

Pediatr Infect Dis J 2009 Mar;28(3):255-7

Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Chronic granulomatous disease is a rare primary immunodeficiency disorder resulting from a defect in the microbicidal activity of phagocytes. Patients are susceptible to certain bacterial and fungal infections, as well as other inflammatory complications. We report the case of a 12-year-old girl with recurrent impetigo whose history of cholecystitis triggered an evaluation that revealed chronic granulomatous disease.
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http://dx.doi.org/10.1097/INF.0b013e31818dd99fDOI Listing
March 2009

Management of an anaphylactoid reaction to methotrexate with a stepwise graded challenge.

Pediatr Allergy Immunol 2003 Oct;14(5):409-11

Division of Allergy/Immunology, Children's Hospital, Boston, MA 02446, USA.

We report the management of a 15-year-old boy with an anaphylactic or anaphylactoid response to his first dose of methotrexate during induction therapy for acute lymphoblastic leukemia (ALL). Because weekly methotrexate therapy is an important component of continuation chemotherapy for pediatric ALL, a stepwise graded challenge was employed to achieve drug tolerance.
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http://dx.doi.org/10.1034/j.1399-3038.2003.00073.xDOI Listing
October 2003

X-linked lymphoproliferative disease: genetic lesions and clinical consequences.

Curr Allergy Asthma Rep 2002 Sep;2(5):361-7

Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.

X-linked lymphoproliferative disorder (XLP) was first described almost 30 years ago; remarkably, the three major manifestations of XLP, fulminant infectious mononucleosis (FIM), lymphoma, and dysgammaglobulinemia, are all described in the report of the initial kindred. Subsequent establishment of an XLP registry has led to recognition of more unusual phenotypes in affected males; concurrently, much progress has been made in caring for boys with XLP, including treatment for the three major phenotypes, and curative bone marrow transplantation (BMT). The immunologic and genetic mechanisms resulting in XLP have also been intensively studied. Several years ago, the gene defective in XLP was identified as SAP (SLAM-associated protein), and recent data suggest that SAP plays a broad role in immune signaling. Here, we review the clinical manifestations and therapy of XLP, and briefly summarize recent research into the structure and function of SAP.
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http://dx.doi.org/10.1007/s11882-002-0068-0DOI Listing
September 2002