Background Perturbations in the intestinal microbiota may disrupt mechanisms involved in the development of immunologic tolerance. The present study aimed to examine the establishment of the infant ...microbiota and its association to the development of atopic dermatitis (AD). Methods Within a randomized, placebo-controlled trial on the prevention of AD by oral supplementation of a bacterial lysate between week 5 and the end of month 7, feces was collected at the ages of 5 weeks (n = 571), 13 weeks (n = 332), and 31 weeks (n = 499) and subjected to quantitative PCRs to detect bifidobacteria, bacteroides, lactobacilli, Escherichia coli , Clostridium difficile , and Clostridium cluster I. Results Birth mode, breast-feeding but also birth order had a strong effect on the microbiota composition. With increasing number of older siblings the colonization rates at age 5 weeks of lactobacilli ( P < .001) and bacteroides ( P = .02) increased, whereas rates of clostridia decreased ( P < .001). Colonization with clostridia, at the age of 5 and 13 weeks was also associated with an increased risk of developing AD in the subsequent 6 months of life (odds ratioadjusted = 2.35; 95% CI, 1.36-3.94 and 2.51; 1.30-4.86, respectively). Mediation analyses demonstrated that there was a statistically significant indirect effect via Clostridium cluster I colonization for both birth mode and birth order in association to AD. Conclusion The results of this study are supportive for a role of the microbiota in the development of AD. Moreover, the “beneficial” influence of older siblings on the microbiota composition suggests that this microbiota may be one of the biological mechanisms underlying the sibling effect.
Background Results from phase III clinical trials in adults and phase II clinical trials in children and adolescents demonstrate that tiotropium is an effective treatment when added to inhaled ...corticosteroid (ICS) maintenance therapy. Objective We sought to assess the efficacy and safety of once-daily tiotropium Respimat added to ICSs with or without a leukotriene receptor antagonist in a phase III trial in adolescent patients with moderate symptomatic asthma. Methods In this 48-week, double-blind, placebo-controlled, parallel-group study, 398 patients aged 12 to 17 years were randomized to receive 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg) of once-daily tiotropium or placebo (2 puffs) administered through the Respimat device every evening, each as add-on treatment to ICS background therapy, with or without a leukotriene receptor antagonist; long-acting β2 -agonist therapy was not permitted during the study. Results Improvement in peak FEV1 within 3 hours after dosing at 24 weeks (primary end point) was statistically significant with both tiotropium doses compared with placebo: 5 μg of tiotropium, 174 mL (95% CI, 76-272 mL); 2.5 μg of tiotropium, 134 mL (95% CI, 34-234 mL). Significant improvements in trough FEV1 at week 24 (a secondary end point) were observed with the 5-μg dose only. Trends for improvement in asthma control and health-related quality of life over the 48-week treatment period were observed. Conclusions Once-daily tiotropium significantly improved lung function and was safe and well tolerated when added to at least ICS maintenance therapy in adolescent patients with moderate symptomatic asthma. Larger responses were observed with the 5-μg tiotropium dose.
Background Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in ...patients with moderate or severe symptomatic asthma. Objective We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma. Methods In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy. Results Compared with placebo, tiotropium 5 μg, but not 2.5 μg, add-on therapy improved the primary end point, peak FEV1 within 3 hours after dosing (5 μg, 139 mL 95% CI, 75-203; P < .001; 2.5 μg, 35 mL 95% CI, −28 to 99; P = .27), and the key secondary end point, trough FEV1 (5 μg, 87 mL 95% CI, 19-154; P = .01; 2.5 μg, 18 mL 95% CI, −48 to 85; P = .59). The safety and tolerability of tiotropium were comparable with those of placebo. Conclusions Once-daily tiotropium Respimat 5 μg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma.
Background Threshold levels for peanut allergy determined by using oral challenges are important for the food industry with regard to allergen labeling. Moreover, the utility of biological markers in ...predicting threshold levels is uncertain. Objective We sought to use a modified oral food challenge regimen that might determine threshold levels for peanut allergy mimicking a more real-life exposure and to correlate the eliciting dose (ED) and severity of clinical reaction in children with peanut allergy with B-cell, T-cell, and effector cell markers. Methods A modified food challenge procedure with doses scheduled 2 hours apart was used in 63 children with peanut allergy. All children received a maximum of 8 semi-log increasing titration steps of roasted peanuts ranging from 3 to 4500 mg of peanut protein until objective allergic reactions occurred. Severity of symptoms was graded from I to V. Biological markers were measured before challenge. Results Forty-five of 63 patients showed objective symptoms after greater than 30 minutes, with a median latency of clinical reaction of 55 minutes. By using a log-normal dose-distribution model, the ED5 was calculated to be 1.95 mg of peanut protein. The ED was significantly and inversely correlated with peanut- and Ara h 2–specific IgE levels, skin prick test responses, basophil activation, and TH 2 cytokine production by PBMCs. Symptom severity did not correlate with any of the markers or the ED. Conclusion This modified food challenge procedure might better reflect threshold levels for peanut allergy than the standard procedure because most of the patients reacted at a time interval of greater than 30 minutes. By using this model, threshold levels, but not severity, could be correlated with biological markers.
Background Lower prevalence of atopy was found in children with continuous exposure to livestock and thus to microbial compounds. In animal models exposure to endotoxin (LPS) decreases allergic ...sensitization and airway inflammation. Objective We sought to evaluate the effect of orally applied bacterial lysate in infancy on the prevalence of atopic dermatitis (AD) after the treatment phase at 7 months of age. Methods This randomized, placebo-controlled trial included 606 newborns with at least single heredity for atopy. From week 5 until the end of month 7, infants were treated orally with bacterial lysate containing heat-killed gram-negative Escherichia coli Symbio and gram-positive Enterococcus faecalis Symbio or its placebo. Children were followed until 3 years of age. Results There was no difference in the primary outcome between the active and placebo groups in the total study group. AD prevalence was significantly reduced at the end of the intervention phase (31 weeks of age) in the subgroup of infants with single heredity for atopy (relative risk, 0.52; 95% CI, 0.3-0.9). Ten percent (15/154) of infants in the active group had AD compared with 19% (27/145, P = .030) in the placebo group. This was more pronounced in the group of infants with paternal heredity for atopy (11% vs 32%, P = .004; relative risk, 0.34; 95% CI, 0.2-0.7). Conclusion Feeding of bacterial lysate might have prevented the development of AD, especially in children with paternal atopy, possibly indicating a preventive property only in subjects with a limited risk for atopy.
BackgroundFor therapy of severe asthma 5 monoclonal antibodies have been available in Germany up to November 2022, but no clear rules exist on choice of initial therapy, assessment of response, and ...switch.ObjectiveTo assess current practice on all aspects of biologic therapy by specialists in Germany.MethodsA questionnaire was created by specialists for severe asthma, which was tested and modified by further experts. We invited 119 pulmonologists of the German Asthma Net (GAN) to complete the survey and used SoSci Survey and SPSS for data collection and analysis.ResultsForty-seven pulmonologists took part in the survey with a median annual number of patients treated with biologics of 35, 55% worked in an outpatient practice, and 40% in a hospital. Exacerbations and oral steroid use were the most important factors for the decision to start a biologic therapy. Accordingly, these parameters were also the most relevant for assessment of response. Most participants considered type-2 inflammation biomarkers and comorbidities (foremost CRSwNP and AD) for choosing initial biologic. Asthma Control Test (ACT) was the most common instrument for assessing status of disease control. There was no consensus on thresholds for response of pulmonary function tests including FEV1, FVC, and RV. Eighty-five percent of participants distinguished between "responders", "partial responders" and "non-responders". Comorbidities played an important role for the decision to switch to another biologic, eg, when initial therapy had insufficient effectiveness on CRSwNP.ConclusionThis study provides a detailed insight into current opinions and practice of biologic use in severe asthma in Germany.
Looking into the future of Trichuris suis therapy Hepworth, Matthew R., PhD; Hamelmann, Eckard, MD; Lucius, Richard, PhD ...
Journal of allergy and clinical immunology,
03/2010, Letnik:
125, Številka:
3
Journal Article
Recenzirano
Odprti dostop
...timing of helminth exposure is clearly important because early infections with T trichiura in human subjects directly correlated with reduced skin test reactivity to 7 common allergens.6 Thus a ...study in which all patients received a consistent and high number of doses before allergen exposure might prove more efficacious.
Objective To test whether chronic bronchial inflammation may be a contributing risk factor for persistent airflow limitation in children born before 32 weeks of gestation in later life. Study design ...Thirty-six of 160 children born before 32 completed weeks of gestation who were born between 1988 and 1992 were recruited at a median age of 11 years. Eighteen age-matched children born at term were controls; 47% of the premature infants and 61% of the term born children produced sputum of sufficient quality for interleukin (IL)-8, cell numbers, and differential counts. Results Compared with term born children, sputum from the premature group had a higher proportion of neutrophils (62% vs 3.8%; P < .001) and higher IL-8/protein values (1.93 μg/g vs 0.64 μg/g; P = .008). Forced expiratory flow 25%-75% and forced expiratory volume in 1 second/vital capacitywere significantly lower (73.4 % vs 116% predicted, P = .002 and 97% vs 101%, P = .012, respectively). Lung function values and sputum indices did not correlate. IL-8/protein and neutrophil percentages correlated significantly with decreasing gestational age (Spearman rank coefficient = −0.58, P = .020 and −.70, P =.03 respectively). Conclusion A significant proportion of school children born very preterm demonstrate persistent peripheral airway obstruction that is accompanied by neutrophilic lower airway inflammation.
Rationale Once-daily tiotropium Respimat® (tioR) add-on to ICS maintenance therapy ± additional controllers improves lung function, exacerbations, and asthma control with demonstrated safety in ...adults with symptomatic asthma.
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