Fexofenadine is Efficacious and Safe in Children (Aged 6-11 Years) with Seasonal Allergic Rhinitis

Background: This is the first prospective, randomized, doubleblind, placebo-controlled study showing statistical improvement of an H1-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. Objective: This randomized, placebo-controlled, parallelgroup,double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. Methods: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (±1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point

Increased Na+/Mg2+ Antiport in Erythrocytes of Patients with Cystic Fibrosis

Peer Reviewe

Myeloperoxidase and eosinophil cationic protein in serum and sputum during antibiotic treatment in cystic fibrosis patients with Pseudomonas aeruginosa infection

I order to study the time-course of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) as parameters for monitoring inflammation in cystic fibrosis (CF), we investigated ten patients during both a 14-day intravenous antibiotic treatment and a corresponding self control. Modified Shwachman-Kulczycki score improved significantly (p < 0.008), C-reactive protein (CRP) levels decreased significantly (p < 0.05) during antibiotic treatment, while in the control phase there were no significant differences. Lung function parameters did not change significantly during antibiotic treatment or control phase. Serum MPO concentration (p < 0.006) and peripheral blood neutrophil granulocyte counts (p < 0.04) decreased significantly during antibiotic treatment, but not during the control phase. Sentm ECP concentration showed a tendency to decrease during antibiotic treatment, but this failed to reach significance. In general, sputum concentrations of MPO and ECP Were 500- to 1000-fold higher than in serum. However, neither MPO nor ECP in sputum showed a significan variation over time during antibiotic treatment or control phase. From our data we conclude that: (1) measurements of MPO, neutrophils and CRP in peripheral blood do correlate with clinical parameters such as the modified Shwachman-Kulczycki score; (2) neutrophils and MPO seem to reflect inflammatory changes induced by antibiotic treatment; (3) eosinophils may play a role in CF by an enhanced ‘releasability’ and (4) Sputum measurements of mediators of inflammation cannot be recommended

Interleukin-4 (IL-4) enhances and soluble interleukin-4 receptor (sIL-4R) inhibits histamine release from peripheral blood basophils and mast cells in vitro and in vivo

The aim of the study was to analyse the effect of interleukin-4 (IL-4) on allergen and anti-IgE mediated histamine release from basophils and human skin mast cells and to assess whether soluble recombinant interleukin-4 receptor (sIL4R) can inhibit these effects. Anti-IgE stimulated histamine release from peripheral blood basophils and mast cells of atopic donors was enhanced after preincubation with IL-4, whereas after preincubation with sIL-4R it was inhibited. These effects were even more pronounced when samples were stimulated with a clinically relevant allergen. In IL-4 preincubated skin mast cells, there was a similar enhancement of anti-IgE stimulated histamine release, which could again be inhibited by sIL-4R. The effects of IL-4 and sIL4R were dose- and time-dependent. Mice sensitized to ovalbumin and treated with soluble recombinant murine sIL-4R showed significantly reduced immediate-type cutaneous hypersensitivity responses compared with untreated mice. These in vivo effects were IgE independent, since there were no significant differences in total and allergen specific IgE/IgG1 antibody titres between treated and untreated mice. This indicates that IL4 exerts priming effects on histamine release by effector cells of the allergic response and that these effects are potently antagonized by soluble IL-4R both in vitro and in vivo

Management of the polyallergic patient with allergy immunotherapy: A practice-based approach

Background: The great majority (60-80 %) of patients consulting specialist physicians for allergic respiratory disease are polysensitized and thus may be potentially clinically polyallergic. However, management approaches to allergen immunotherapy (AIT) in polysensitized and polyallergic patients are not standardized. Methods: An international group of clinicians with in-depth expertise in AIT product development, clinical trials and clinical practice met to generate up-to-date, unambiguous, pragmatic guidance on AIT in polysensitized and polyallergic patients. The guidance was developed after reviewing (1) the current stance of regulatory bodies and learned societies, (2) the literature data on single- and multi-AIT and (3) the members' confirmed clinical experience with polysensitized patients. Results: AIT is safe and effective in polysensitized and polyallergic patients, and should always be based on the identification of one or more clinically relevant allergens (based on the type and severity of symptoms, the duration of induced symptoms, the impact on quality of life and how difficult an allergen is to avoid). Single-AIT is recommended in polyallergic patients in whom one of the relevant allergens is nevertheless clearly responsible for the most intense and/or bothersome symptoms. Parallel 2-allergen immunotherapy or mixed 2-allergen immunotherapy is indicated in polyallergic patients in whom two causal relevant allergens have a marked clinical and QoL impact. In parallel 2-allergen immunotherapy (whether subcutaneous or sublingual), high-quality, standardized, single-allergen formulations must be administered with an interval of 30 min. Mixing of allergen extracts may be considered, as long as (1) the mixture is technically feasible, (2) the mixture is allowed from a regulatory standpoint, (3) the allergen doses are reduced in proportion to the number of components but are still at concentrations with demonstrated efficacy. Conclusions: Physicians can prescribe AIT (preferably with high-quality, standardized, single-allergen formulations) with confidence in polysensitized and polyallergic patients by focusing on clinical/QoL relevance and safety

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

ARIA 2016:Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease

ARIA-Versorgungspfade für die Allergenimmuntherapie 2019 = 2019 ARIA Care pathways for allergen immunotherapy

Allergen immunotherapy (MT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence- based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe MT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomaikers that can predict MT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate phannacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients

How Exposures to Biologics Influence the Induction and Incidence of Asthma

A number of environmental factors can affect the development and severity of allergy and asthma; however, it can be argued that the most significant inhaled agents that modulate the development of these conditions are biologics. Sensitization to environmental allergens is an important risk factor for the development of asthma. Innate immune responses are often mediated by receptors on mononuclear cells whose primary ligands arise from microorganisms. Many pathogens, especially viruses, target epithelial cells and affect the host immune response to those pathogens. The acquired immune response to an allergen is influenced by the nature of the innate immune system. Products of innate immune responses to microbes promote T(H)1-acquired responses. In the absence of T(H)1 responses, T(H)2 responses can dominate. Central to T(H)1/T(H)2 balance is the composition of contaminants that derive from microbes. In this review we examine the biology of the response to allergens, viruses, and bacterial products in the context of the development of allergy and asthma