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Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα. In recent years, the important role of proinflammatory cytokines in the etiopathogenesis of various chronic diseases such as asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), chronic obstructive pulmonary diseases (COPDs), and chronic spontaneous urticaria has been studied. Although alarmins have been found to be mainly implicated in the mechanisms of type 2 inflammation, studies on monoclonal antibodies against TSLP demonstrate partial efficacy even in patients whose inflammation is not definable as T2 and the so-called low T2. Tezepelumab is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating the safety and efficacy of Tezepelumab in various inflammatory disorders. In this review, we will highlight major recent advances in understanding the functional role of TSLP, its involvement in Th2-related diseases, and its suitability as a target for biological therapies.

The recent advances in the knowledge of immunological aspects of many pulmonary diseases, allowed to identify cells, biological functions, cytokines, and receptors that are preferentially involved in each disease. This is the case of asthma, where IL-13 (together with IL-4) is recognized as a central mediator. The role of IL-13 is strictly related, via complex signaling pathways, to eosinophil recruitment and activation, to mucus secretion, periostin generation and to fibrogenic processes (which are part of the remodeling process). These peculiar roles of IL-13 have suggested the hypothesis of its role in Idiopathic Pulmonary Fibrosis, and consequently of its antagonists in the treatment of such disease. We review herein the immunological roles of IL-13 in asthma and IPF, and the currently ongoing attempts to treat IPF by IL-13 antagonism strategies., (Copyright © 2017. Published by Elsevier Ltd.)

Introduction: In the last two decades the knowledge of the mechanisms of the inflammatory processes underlying asthma rapidly evolved, several key mediators (cytokines and receptors) were identified, and the laboratory techniques have allowed us to synthesize monoclonal antibodies highly specific for those target molecules. Nowadays, many biological agents are investigated in asthma (with anti IgE being the only commercially available). The clinical efficacy of some biologics was demonstrated in many cases, however, the safety issue has progressively emerged and has been recognized as a crucial aspect., Areas Covered: We summarized the currently available knowledge on the safety and side effects of biologics in asthma, as derived by reviews, meta analyses and clinical trials. PubMed was searched with the terms anti IL-x [AND] safety [OR] side effects, within the categories "clinical trial", meta-analysis" and "review". Case reports were excluded. The authors collegially selected the relevant entries to be included., Expert Opinion: Overall, the safety of most of the investigated agents seems to be satisfactory, a certain risk of side effects remains present, and is variable for the different molecules. Thus caution must be paid in evaluating the risk to benefit ratio. Specific biomarkers to predict the response to each biological are urgently needed to improve the safety profile.

The use and role of allergen immunotherapy (AIT) in asthma is still a matter of debate, and no definite recommendation about this is made in guidelines, both for the subcutaneous and sublingual routes. This is essentially due to the fact that most controlled randomised trials were not specifically designed for asthma, and that objective measures of pulmonary function were only occasionally considered. Nonetheless, in many trials, favourable results in asthma (symptoms, medication usage, bronchial reactivity) were consistently reported. There are also several meta analyses in favour of AIT, although their validity is limited by a relevant methodological heterogeneity. In addition to the crude clinical effect, a disease modifying action of AIT (prevention of asthma onset and long-lasting effects) have been reported. The safety is an important aspect to consider in asthma. Fatalities were rare: in Europe no fatality was reported in the last three decades, as in the United States in the last 4 years. Based on previous surveys, and common sense, uncontrolled asthma is still recognized as the most important risk factor for severe adverse events. On the contrary, there is no evidence that AIT can worsen or induce asthma. According to the available evidence, AIT can be safely used as add-on treatment when asthma is associated with rhinitis (a frequent condition), provided that asthma is adequately controlled by pharmacotherapy. AIT cannot be recommended or suggested as single therapy. When asthma is the unique manifestation of respiratory allergy, its use should be evaluated case by case.

Background: Adverse reactions to drugs are common in the clinical practice. Many outpatients are frequently referred to allergists in order to determine which drugs they can safely take in the future., Objective: We set up an oral single-dose tolerance test procedure to find out for each patient one or more alternative drugs that can be taken when needed., Methods: 452 outpatients (130 male, 322 female) with well-documented reactions (urticaria/angioedema, respiratory symptoms, laryngeal edema, anaphylaxis, exfoliative skin diseases) underwent the challenge. All tests were preceded by a single-blind placebo: if a reaction occurred, a second placebo was administered. Otherwise, a single dose (1/10 of the therapeutic one) of an alternative drug was given blindly and the patient was then observed for 6 h. The drugs used were different in structure from those suspected of having caused the adverse reaction. The patients were followed up at 4- to 6-month intervals, in order to detect any reaction that may have occurred with the tested drugs., Results: 98 patients (89 women) had untoward reactions after the first placebo and 34 out of them reacted to the second placebo, too. During challenges the reaction rate ranged between 4.6 and 9.0%; these reactions were easily managed and none of them was severe. We followed up 407 patients: 87.2% of them were able to use one or more of the suggested drugs without reactions, 9.3% did not take the drugs and only 3.5% reported reactions to the previously tested drugs., Conclusion: The challenge procedure proved to be a simple tool for managing patients with adverse reactions to drugs. Its safety and reliability were validated by a long-term follow-up., (Copyright 2002 S. Karger AG, Basel)

Local routes for immunotherapy (IT) such as oral (OIT) and sublingual (SLIT) have the primary aim of avoiding or minimizing the risk of adverse events and of improving the compliance of the patients with IT itself. About the possible mechanisms of action, only few information are available since local IT has been deeply studied only in the last ten years. The current data about pharmacokinetics are controversial and not conclusive, since they are mostly derived from animal models. However, very recent studies have demonstrated that the sublingual/swallow modality is the most promising way of mucosal immunotherapy. Thus, SLIT could be shown to lead to systemic immunological effects and to a decreased responsiveness of target organs. Furthermore, no severe adverse events were reported in the SLIT-studies. Some studies indicate that SLIT is as effective as subcutaneous IT, whilst OIT is not recommended for the clinical practice. SLIT would appear particularly suitable for pediatric patients. Administration schedules include a build-up phase and a maintenance phase which can be administered either preseasonally or continuously, and rush schedules for preseasonal IT are also available. Furthermore, SLIT reduces time and money expenses usually required by SIT since it is self-administered.

Background: Cetirizine is an antihistamine used in the treatment of allergic rhinoconjunctivitis, that has antiallergic activity., Objective: The aim of this double-blind, placebo-controlled, parallel group study was to evaluate the clinical efficacy and the antiallergic activity of cetirizine, administered either continuously or on demand over a 4-week period of natural allergen exposure., Methods: Twenty patients, with allergic rhinoconjunctivitis due to grass and/or Parietaria pollen, were enrolled. They were randomized into 2 parallel groups: one group received the standard dose of 10 mg cetirizine daily and the other received placebo, all patients were allowed to take an additional daily dose of cetirizine when needed. Variables evaluated were clinical symptoms (recorded on diary cards), number of additional on demand cetirizine doses, nasal inflammatory cells, and pollen counts., Results: The results of the present study show that patients treated with continuous administration of cetirizine achieved significant symptomatic relief and inflammatory control (decreases in numbers of infiltrating neutrophils and eosinophils) in comparison to patients treated on demand., Conclusion: Continuous treatment with cetirizine is more effective than on demand treatment. Continuous treatment reduces clinical and inflammatory variables more than symptomatic treatment and the on demand therapy can determine acceptable clinical control, but does not reduce allergic inflammation.