Johannes Schulze

Beekeepers anaphylaxis: successful immunotherapy covered by omalizumab

been reported as an allergen up till now. To our knowledge, there have only been six studies in which cases of allergy to lychee were reported. In one of these (1) a 16 kDa profilin (Lit c 1) was identified, which cross-react with that of Compositae plants, including sunflower seed. Niggemann et al. (2) described a case of cross-reactivity between lychee and latex by CAP inhibition but without identifying the responsible allergen. In the other four cases published (3–6) only a description of the reactions which occurred after lychee ingestion was given but no mention was made of the allergenic proteins responsible for these.

Methacholine challenge--comparison of an ATS protocol to a new rapid single concentration technique.

Bronchial methacholine challenge is well established in asthma diagnostics and research. ATS guidelines propose a five step standard dosimeter (SDM) protocol with incremental concentrations of methacholine to calculate the concentration causing a 20% drop in FEV(1) in an individual (PC(20)FEV(1)). In contrast, the aerosol provocation system (APS) by Viasys automatically determines the administered dose of methacholine by measuring the effective nebulisation time and referring it to drug concentration and nebuliser power. Therefore, it offers a feasible and less time-consuming provocation procedure by applying incremental doses (PD(20)) of methacholine using a single concentration (16mg/mL methacholine, APS-SC). In this study we compared these two methods in 52 young adults (25+/-5.8 years). Following a screening visit, subjects were randomly assigned to undergo either SDM or APS-SC followed by the other method within 1 week. A close correlation between concentration and dosage causing a 20% fall of FEV(1) was found (r=0.69, p<0.001). Using the ATS categorisation of bronchial responsiveness we interpreted the results of the APS-SC method as follows: PD(20) methacholine<0.3mg as moderate to severe BHR, 0.3 - 0.6mg as mild BHR, 0.6 - 1.0mg as borderline BHR, and>1.0mg as normal bronchial response. We conclude that the five-step APS-SC is a suitable method, providing reliable results. In clinical practice the APS-SC is a timesaving procedure and less prone to errors since only one dilution of methacholine is necessary compared to the SDM.

Methacholine challenge in young children as evaluated by spirometry and impulse oscillometry.

BACKGROUNDnIn young children, it is difficult to obtain a reproducible flow-volume curve throughout all stages of bronchial challenge. The forced oscillation technique (FOT) is especially established in paediatrics because this method does not require forced or maximal manoeuvres and is less cooperation-dependent than conventional spirometry.nnnOBJECTIVESnTo evaluate the association of spirometric and impulse oscillometric (IOS) indices in a short protocol for methacholine provocation.nnnMETHODSnThe primary endpoint was the methacholine dose that caused a 20% decrease in FEV(1) (PD(-20)FEV(1)) compared to baseline. Changes in respiratory resistance (Rrs5) and reactance (Xrs5) acquired by IOS were compared with FEV(1).nnnRESULTSnForty-eight children (5.3xa0±xa00.9 years) were challenged. The mean maximal reduction in FEV(1) was 29.8%xa0±xa014.7 (pxa0<xa00.0001), the mean increase in Rsr5 was 55.3%xa0±xa031.7, and the mean decrease in Xrs5 was 0.37xa0kPaxa0sxa0L(-1)xa0±xa00.23 (pxa0<xa00.001). An increase in Rrs5 of 45.2% and a decrease in Xrs5 of 0.69xa0kPaxa0sxa0L(-1) showed the optimal combination of sensitivity and specificity to detect a 20% reduction in FEV(1) (0.72 and 0.73; 0.80 and 0.76, respectively), and the area under the ROC curve was 0.76 and 0.81, respectively (pxa0<xa00.005). In 28 patients with significant changes in FEV(1) and Rsr5, the PD(-20)FEV(1) was 0.48xa0mg methacholine ±0.59 and the PD(+40)Rrs5 was 0.28xa0mg methacholine ±0.45 (pxa0=xa00.03).nnnCONCLUSIONSnA short protocol for methacholine challenge testing is feasible in young children. IOS detected 70-80% of patients who responded in spirometry. During the challenge, the Rrs5 response preceded the FEV(1) response.

Severe isolated pulmonary Langerhans cell histiocytosis in a 6-year-old girl

Langerhans cell histiocytosis (LCH) usually affects different organs or bones. Isolated pulmonary disease is rare in childhood. We report about a 6-year-old girl with progressive pulmonary insufficiency, onset of clubbing at 4 years of age and honeycombing lung infiltrations on X-ray films. The radiological suspicion of primary pulmonary LCH was confirmed by the presence of CD1a positive cells in the bronchoalveolar lavage fluid. Other organs were not involved. The girl was treated according to the LCH—III International Study Protocol with a good response. Follow-up showed no reactivation of LCH but a reduced vital capacity and signs of interstitial pulmonary involvement on a CT scan. Conclusion:Langerhans cell histiocytosis should be considered in the aetiology of cystic lung diseases. Early responders to treatment have a high likelihood of becoming free of disease. However, pulmonary fibrosis is an important mechanism of lung remodelling in pulmonary Langerhans cell histiocytosis and the long-term prognosis is unclear.

Bronchial allergen provocation: A useful method to assess the efficacy of specific immunotherapy in children

The clinical efficacy of subcutaneous allergen‐specific immunotherapy (SCIT) varies between patients. New preparations are under development, and an objective tool with which to evaluate their efficacies in individual patients has become necessary. Our primary research question is whether bronchial allergen provocation (BAP) can be used to assess the efficacy of SCIT.

Bronchial allergen challenges in children – safety and predictors

In allergic asthma, the diagnosis of house dust mite (HDM) allergy is mainly based on the patients history, allergy testing by the skin prick test (SPT) or the levels of allergen‐specific IgE. We retrospectively analysed data from 350 bronchial provocations with HDM and related it to the following parameters: specific IgE, bronchial hyperresponsiveness (BHR) to methacholine testing (MCT) and exhaled NO (eNO).

Airway inflammation in children and adolescents with bronchiolitis obliterans

BACKGROUNDnAirway inflammation plays a major role in the progression of chronic lung diseases. The features of airway inflammation are not well defined among patients with cases of bronchiolitis obliterans (BO) that began in childhood.nnnOBJECTIVESnTo investigate the sputum cell and cytokine profiles of stable cases of BO regarding lung function and the involvement of small airway disease (SAD).nnnMETHODSnTwenty patients with BO (median age=14.5, range=7-23years) and 22 healthy controls (median age=16.5years, range=7-24years) were investigated. Lung function parameters and bronchial reversibility testing as well as sputum cell and cytokine profiles (IL-1β, IL-6, IL-8, TNF-α, IL-5, IFN-γ, and NFκB regulation) were analysed using quantitative RT-PCR and cytometric bead assay (CBA) in induced sputum.nnnRESULTSnPatients with BO had significantly lower lung function values, including FVC, forced expiratory volume (FEV1), the Tiffeneau index (FEV1/VC), and MEF25, but increased functional residual capacity (RV/TLC) values. Bronchial reversibility was found in five patients (25%). Moreover, airway inflammation (as indicated by total cells, neutrophils, IL-1β, IL-6, IL-8, TNF-α, and NFκB) was significantly increased among patients with BO compared with controls.nnnCONCLUSIONSnBO is predominantly a neutrophilic disease of the small bronchioles featuring elevated levels of pro-inflammatory cytokines leading to tissue remodelling and fibrosis of the small airways. Future therapies for patients with BO should more efficiently target the small airways.

Omalizumab effectively protects against early- and late allergic responses in asthma after 4 weeks

Omalizumab is licensed for therapy in severe allergic asthma with an effect demonstrated after 8 weeks or longer treatment. As new applications for omalizumab demand precise knowledge of the onset of effects, the objective of this study was to determine the time course of the early (EAR) and late allergic reaction (LAR).

Long-term effect of monophosphoryl lipid A adjuvanted specific immunotherapy in patients with grass pollen allergy

BACKGROUNDnUltra-short course pollen immunotherapy adjuvanted with monophosphoryl lipid A (MPL) is attractive to conventional allergen-specific immunotherapy (AIT). Long term efficacy of MPL-AIT has not been evaluated.nnnMETHODSn68 patients (age 16.75xa0±xa05.3 years) with allergic rhinitis to grass pollen were investigated. Group 1: 21 controls; Group 2: 19 after complete AIT, and Group 3: 28 with AIT and treatment cessation: 4 years range 3-6 years ago.nnnRESULTSnThe clinical symptoms (running nose, sneezing, conjunctivitis and the weekly overall score) were significantly reduced in patients group 2 and 3 compared with controls without AIT pxa0<xa00.0001. T-regulatory cells and TH1/TH2 cytokine pattern did not differ between patient groups.nnnCONCLUSIONnThe patients in our trial with grass pollen allergy exhibited significant and long-lasting improvements after MPL-AIT, however larger trials are needed to support this finding.

Comparison of two different assays and the predictive value of allergen components in house dust mite allergy

AIMnIn house dust mite (HDM) allergy diagnostics, the IMMULITE, ImmunoCAP and assays for allergen components (nDer p 1 and rDer p 2) are available.nnnMETHODSnSerum sIgE levels were compared and the predictive values for the detection of an early asthmatic response (EAR) were calculated with receiver operating characteristics and a log-logistic regression model.nnnRESULTSnsIgE levels of IMMULITE and ImmunoCAP were similar (Dermatophagoides pteronyssinus [D. pter.]xa047.3xa0±xa035.7 and 42.9xa0±xa034.4xa0kU.l-1;xa0pxa0=xa00.23). ImmunoCAP slgEs exhibited similar accuracy in detecting an EAR, area under the curves (AUCs): D. pter. (0.76);xa0Dermatophagoides farinae (0.79); nDer p 1 (0.69); and rDer p 2 (0.72). At low sIgE concentrations (3.5xa0kU.l-1), rDer p 2 was more specific and better predicted an EAR (probability rDer p 2: 62%;xa0D. pter.: 19%).