Serum Gliadin Monitoring Extracts Patients with False Negative Results in Challenge Tests for the Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis

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ORIGINAL ARTICLE Serum Gliadin Monitoring Extracts Patients with False Negative Results in Challenge Tests for the Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis  doi:10.2332/allergolint.12-OA-0495 Kunie Kohno, Hiroaki Matsuo, Hitoshi Takahashi, Hiroyuki Niihara, Yuko Chinuki, Sakae Kaneko, Tsutomu Honjoh, Tatsuya Horikawa, Shoji Mihara and Eishin Morita [About this authors] ABSTRACT Background: Challenge testing with wheat plus exercise and/or aspirin is a gold standard for the diagnosis of wheat-dependent exercise-induced anaphylaxis (WDEIA); however, the test may often yield false-negative results. Our previous study suggested that an increase in serum wheat gliadin levels is required to induce allergic symptoms in patients with WDEIA. Based on this knowledge, we sought to extract the patients with false negative results in the challenge tests of WDEIA. Methods: Thirty-six patients with suspected WDEIA were enrolled. First, group categorizations -Group I, challenge tests were positive; Group II, challenge tests were negative and serum gliadin were undetectable; Group III, challenge tests were negative and serum gliadin were detectable -were given according to the results of wheat plus exercise and/or aspirin challenge testing and serum gliadin levels. Second, diagnoses were made using retests and/or dietary management in Group II and III. Results: Positive results for wheat plus exercise and/or aspirin challenge tests gave a diagnosis of definite WDEIA in 17 of 36 patients (Group I). Of the remaining 19 challenge negative patients, serum gliadin was undetectable in ten patients (Group II). Of the ten patients (Group II), three of them were diagnosed as definite WDEIA by retesting and six of them were diagnosed as probable WDEIA using a wheat elimination diet, whereas one patient was non-WDEIA. In the rest of the nine challenge negative patients, serum gliadin was detectable (Group III). No allergic episodes with a normal diet provided a diagnosis of non-WDEIA in seven of the nine patients, whereas the remaining two patients were probable WDEIA or had another food allergy because of repeated episodes. Conclusions: Our study revealed that serum gliadin monitoring during challenge testing is useful. KEY WORDS: challenge test, serum gliadin monitoring, wheat-dependent exercise-induced anaphylaxis, ω-5 gliadin ABBREVIATIONS: FDEIA, food-dependent exercise-induced anaphylaxis; HMW-glutenin, high-molecular-weight glutenin subunit; NSAIDs, non-steroidal anti-inflammatory drugs; WDEIA, wheat-dependent exercise-induced anaphylaxis. Received: 22 August 2012. Accepted: 20 December 2012. Allergology International : In Press [Full Text PDF (257k)]

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β2 agonist vilanterol

•  Volume 68, Issue 6
 
• > Article

Thorax 2013;68:513-520 doi:10.1136/thoraxjnl-2012-202606

• Asthma

• Original article

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β₂ agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial

1. William W Busse1, 
2. Paul M O'Byrne2, 
3. Eugene R Bleecker3, 
4. Jan Lötvall4, 
5. Ashley Woodcock5,
6. Leslie Andersen6, 
7. Wesley Hicks7, 
8. Jodie Crawford8, 
9. Loretta Jacques7, 
10. Ludovic Apoux9,
11. Eric D Bateman10

+Author Affiliations

1. ¹Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA
2. ²Michael G DeGroote School of Medicine, Hamilton, Ontario, Canada
3. ³Center for Genomics and Personalized Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
4. ⁴Krefting Research Centre, University of Gothenburg, Gothenburg, Sweden
5. ⁵Institute of Inflammation and Repair, University of Manchester, Manchester, UK
6. ⁶Respiratory Medicines Development Center, GlaxoSmithKline, Raleigh-Durham, North Carolina, USA
7. ⁷Respiratory Medicine Development Centre, GlaxoSmithKline, London, UK
8. ⁸Quantitative Sciences Division, GlaxoSmithKline, London, UK
9. ⁹Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, London, UK
10. ¹⁰Department of Medicine, University of Cape Town, Cape Town, South Africa

1. Correspondence toProfessor William W Busse, Department of Medicine, University of Wisconsin, K4/910 CSC, 600 Highland Avenue, Madison, WI 53792, USA; wwb@medicine.wisc.edu

• Received 21 August 2012
• Revised 2 January 2013
• Accepted 21 January 2013
• Published Online First 25 February 2013

Abstract

Background The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β₂ agonist vilanterol (VI) is in development for asthma and chronic obstructive pulmonary disease.

Objective To assess the safety and tolerability of FF/VI over 52 weeks in patients with asthma.

Methods Patients (aged ≥12 years; on inhaled corticosteroid) were randomised (2:2:1) to FF/VI 100/25 µg or FF/VI 200/25 µg once daily in the evening, or fluticasone propionate (FP) 500 µg twice daily. Safety evaluations included adverse events (AEs), non-fasting glucose, potassium, 24-h urinary cortisol excretion, ophthalmic assessments, heart rate and pulse rate.

Results On-treatment AEs were similar across groups (FF/VI 66–69%; 73% FP). Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (6–7%) than FP (3%). Twelve serious AEs were reported; one (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p≤0.006), but not at Week 52 (ratios to FP were 1.05 [0.83 to 1.33] for FF/VI 100/25 µg and 1.09 [0.87 to 1.38] for FF/VI 200/25 µg). No clinically important changes in non-fasting glucose, potassium, QT interval corrected using Fridericia's formula (QTc[F]) or ophthalmic assessments were reported. Pulse rate (10 min post dose [T_max], Week 52) was significantly increased with FF/VI versus FP (3.4 bpm, 95% CI 1.3 to 5.6; p=0.002 [FF/VI 100/25 µg]; 3.4 bpm, 95% CI 1.2 to 5.6; p=0.003 [FF/VI 200/25 µg]). Mean heart rate (24-h Holter monitoring) decreased from screening values in all groups (0.2–1.1 bpm FF/VI vs 5 bpm FP; Week 52).

Conclusions FF/VI (100/25 µg or 200/25 µg) administered once daily over 52 weeks was well tolerated by patients aged ≥12 years with asthma. The overall safety profile of FF/VI did not reveal any findings of significant clinical concern.

ClinicalTrials.gov NCT01018186

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Role of exhaled nitric oxide as a predictor of atopy

Research

Role of exhaled nitric oxide as a predictor of atopy

Karina M Romero, Colin L Robinson, Lauren M Baumann, Robert H Gilman, Robert G Hamilton, Nadia N Hansel andWilliam Checkley

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Respiratory Research 2013, 14:48 doi:10.1186/1465-9921-14-48

Published: 2 May 2013

Abstract (provisional)

Background

The fractional exhaled nitric oxide (FeNO) is a quantitative, noninvasive and safe measure of airways inflammation that may complement the assessment of asthma. Elevations of FeNO have recently been found to correlate with allergic sensitization. Therefore, FeNO may be a useful predictor of atopy in the general population. We sought to determine the diagnostic accuracy of FeNO in predicting atopy in a population-based study.

Methods

We conducted a cross-sectional study in an age- and sex- stratified random sample of 13 to 15 year-olds in two communities in Peru. We asked participants about asthma symptoms, environmental exposures and sociodemographics, and underwent spirometry, assessment of FeNO and an allergy skin test. We used multivariable logistic regression to model the odds of atopy as a function of FeNO, and calculated area-under-the-curves (AUC) to determine the diagnostic accuracy of FeNO as a predictor of atopy.

Results

Of 1441 recruited participants, 1119 (83%) completed all evaluations. Mean FeNO was 17.6 ppb (SD=0.6) in atopics and 11.6 ppb (SD=0.8) in non-atopics (p<0 .001="" a="" analyses="" feno="" in="" multivariable="">20 ppb was associated with an increase in the odds of atopy in non-asthmatics (OR=5.3, 95% CI 3.3 to 8.5) and asthmatics (OR=16.2, 95% CI 3.4 to 77.5). A FeNO>20 ppb was the best predictor for atopy with an AUC of 68% (95% CI 64% to 69%). Stratified by asthma, the AUC was 65% (95% CI, 61% to 69%) in non-asthmatics and 82% (95% CI, 71% to 91%) in asthmatics.

Conclusions

FeNO had limited accuracy to identify atopy among the general population; however, it may be a useful indicator of atopic phenotype among asthmatics.

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Skin Test–Positive Immediate Hypersensitivity Reaction to Iodinated Contrast Media: The Role of Controlled Challenge Testing

A Prieto-García, M Tomás, R Pineda, P Tornero, T Herrero, V Fuentes, L Zapatero, M de Barrio. Skin Test–Positive Immediate Hypersensitivity Reaction to Iodinated Contrast Media: The Role of Controlled Challenge Testing

Allergy Service, Hospital General Universitario Gregorio Marañón, Madrid, Spain

J Investig Allergol Clin Immunol 2013; Vol. 23(3): 183-189 Abstract Background: Immediate hypersensitivity reactions (IHR) to iodinated contrast media (ICM) have traditionally been considered nonallergic; however, the increasingly frequent reporting of positive skin test and basophil activation test results suggests a specific allergic mechanism in some patients. Skin tests have been proposed as a useful tool for diagnosis, although their sensitivity and predictive values remain to be determined. The role of controlled challenge testing has not been assessed. Objective: We aimed to evaluate the role of controlled challenge testing in skin test–positive IHR to ICM. Patients and Methods: We evaluated 106 patients with IHR to ICM by performing skin tests with the agent that caused the reaction. Patients with a positive result were selected. Skin tests were extended to a series of 8 ICMs; 5 patients underwent controlled challenge test with an alternative skin test–negative ICM; a further 2 patients underwent computed tomography with an alternative skin test–negative ICM. No premedication was administered. Results: Intradermal test results were positive to the ICM that caused the reaction in 11 out of 106 patients (10.4%). Five of the 11 patients tolerated a controlled challenge test with an alternative skin test–negative ICM. The 2 patients who underwent computed tomography with an alternative skin test–negative ICM tolerated the medium. Conclusions: Skin tests are useful for the diagnostic workup in patients with an allergic IHR to ICM. Since ICM cannot be avoided in many patients because they are irreplaceable in some diagnostic or therapeutic techniques, an alternative safe ICM should be investigated for future procedures. We propose the use of controlled challenge tests based on skin test results to address this need in skin test–positive reactions in order to identify an alternative non–cross-reactive ICM. Key words: Controlled challenge test. Allergic immediate hypersensitivity reactions. Iodinated contrast media. Skin tests.

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Stem cell factor-dependent mast cell proliferation, maturation and activity can be regulated by inhibitory receptors

Ewa Brzezińska-Błaszczyk, Edyta Bąbolewska (Centr Eur J Immunol 2013; 38 (1): 134-140) DOI (digital object identifier): 10.5114/ceji.2013.34371 view full text   Mast cells play an important role in many physiological and pathological processes. That is why, the factors and the mechanisms regulating mast cell development, maturation, proliferation, and activity within tissues are of special importance. More and more data indicate that mast cells express inhibitory receptors. Furthermore, there are findings that inhibitory receptors can modulate IgE-dependent mast cell activity, thereby influencing the intensity of allergic processes. Bearing in mind that c-kit (CD117)-specific stem cell factor (SCF) not only affects mast cell activity but also strongly promotes mast  cell development and proliferation, it is extremely interesting whether inhibitory receptors modulate SCF-mediated mast cell response. Nowadays, certain data suggest that some inhibitory receptors, such as FcγRIIB, CD72 molecule, paired immunoglobulin-like receptor B (PIR-B), CD300a molecule, and gp49B1 glycoprotein, can affect CD117-dependent mast cell activity and proliferation. keywords: mast cells, inhibitory receptors, mast cell development, stem cell factor

Specific antibody deficiency in children with recurrent respiratory infections: a controlled study with follow-up

1. 
   O. Ruuskanen^1,*, 
2. A. Nurkka⁴, 
3. M. Helminen³, 
4. M. K. Viljanen², 
5. H. Käyhty⁴,
6. L. Kainulainen¹

Article first published online: 10 APR 2013

DOI: 10.1111/cei.12053

© 2012 British Society for Immunology

Clinical & Experimental Immunology

Special Issue: Review series on Adoptive Cell Therapy. Immunology in the clinic: diabetes therapies and biomarkers

Volume 172, Issue 2, pages 238–244, May 2013

• Article
• References
• Cited By

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Keywords:

• CVID;
• immunodeficiency;
• pneumococcal vaccine;
• recurrent infections;
• specific antibody deficiency

Summary

Specific antibody deficiency (SAD) to unconjugated pneumococcal vaccine (PPV) is an established primary B cell immunodeficiency. The occurrence and natural history of SAD in children is unclear. We conducted an observational study to identify SAD in children with recurrent respiratory infections. Ninety-nine children, mean age 5·9 (range 2–16) years, with recurrent or severe infections were vaccinated with PPV; serum antibody concentrations for serotypes 4, 6B, 9V, 14, 18C, 19F and 23F were measured before and 2 weeks after vaccination with enzyme immunoassay. The retrospective control group consisted of 89 healthy children matched for age and gender. No children had received previous conjugated pneumococcal vaccine (PCV) or PPV. The structured history of infectious diseases of all participants was collected. Ten of 91 (11%) children (eight excluded due to immunoglobulin G subclass deficiency) with recurrent respiratory infections had SAD. In the control group, three children (3%) responded inadequately to PPV (P = 0·05). Most children with SAD also had many other minor immune defects. After 0·5–5 years (medium 3·8), eight children with SAD were revaccinated with PPV; five responded adequately and three inadequately. Two SAD children were revaccinated with PCV, one developed an adequate and one an inadequate response. Two children with SAD received treatment with intravenous immunoglobulin; the remaining eight children recovered without replacement therapy during the follow-up. SAD is common in young children with recurrent respiratory infections, but it is often transient and resolves itself within a few years without specific treatment.

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