Allergen Immunotherapy: History and Future Developments

Allergen immunotherapy (AIT) was introduced in clinical practice more than 100 years ago. The clinical effectiveness in allergic rhinitis (and asthma) and in hymenoptera allergy was apparent early on but it was not until the mid-1900s that randomized placebo-controlled trials proved its efficacy. In the 1980s, sublingual immunotherapy (SLIT) was accepted in official guidelines. The availability of safer routes, such as SLIT, prompted increasing investigation of AIT for food allergy. The introduction of molecular-based diagnosis introduced the possibility of better targeted prescription of AIT. Other approaches are being explored, such as immunogenic peptides, recombinant allergens, and adjuvants

Local Nasal Specific Immunotherapy for Allergic Rhinitis

The possibility of producing local hyposensitization by administering allergens via mucosal routes was envisaged at the beginning of 1900, and local nasal immunotherapy has been extensively studied since the 1970s. Presently, there are 21 randomized controlled trials being conducted with the most common allergens, consistently showing the clinical efficacy of local nasal immunotherapy for rhinitis. Other advantages are that it has an optimal safety profile and can be self-administered at home by the patient. Moreover, there are several data from animal models and from humans that confirm the immunomodulatory effect of intranasally administered antigens. On the other hand, local nasal immunotherapy seems to be effective only on rhinitis symptoms and requires a particular technique of administration. For these reasons, its clinical use is progressively declining in favour of the sublingual route although nasal immunotherapy is validated in official documents and remains a viable alternative to injection

Impact of rhinitis on airway inflammation: biological and therapeutic implications

There is increasing evidence for a close link between the upper and the lower respiratory tracts and the fact that rhinitis has an important impact on asthma. Several clinical and experimental observations suggest a similar immunopathology between the upper and lower airways in allergic subjects. The common inflammatory process that develops in the respiratory tract explains some of the complex interactions among different clinical diseases such as rhinitis, sinusitis, asthma, bronchial hyperresponsiveness and viral infections. There are also non-inflammatory mechanisms that may contribute to the link between rhinitis and asthma. Moreover, the outcomes of various pharmacological treatments of rhinitis have recently provided further support for the hypothesis of the united airways. We discuss some of the recent observations on the nose-lung interaction and some of the novel therapeutic approaches used to treat rhinitis and asthma that arise from this

Anti-Interleukin 5 (IL-5) and IL-5Ra Biological Drugs: Efficacy, Safety, and Future Perspectives in Severe Eosinophilic Asthma

The definition of asthma has changed considerably in recent years, to the extent that asthma is no longer considered a single disease but a heterogeneous disorder that includes several phenotypes and, possibly, endotypes. A more detailed analysis of the immunological mechanisms underlying the pathogenesis of asthma shows interleukin 5 (IL-5) to be a crucial cytokine in several asthma phenotypes. In fact, IL-5 exerts selective action on eosinophils, which, in turn, sustain airway inflammation and worsen asthma symptoms and control. Clinical trials have shown drugs targeting IL-5 or its receptor alpha subunit (IL-5Ra) to be a promising therapeutic approach to severe asthma, whose characteristics render standard therapy of little use: systemic corticosteroids only partially control the disease and have well-known adverse effects, and omalizumab is used for allergic subtypes. Analysis of the design process of clinical trials reveals the importance of patient selection, taking into account both clinical data (e.g., exacerbations, lung function, and quality of life) and biomarkers (e.g., eosinophils, which are predictive of therapeutic response)

Allergen-driven HLA-G expression and secretion in peripheral blood mononuclear cells from allergic rhinitis patients

It has been reported that soluble HLA-G serum levels are increased in patients with pollen-induced allergic rhinitis and decrease after immunotherapy. However, no functional study has been conducted so far. The aim of this study was to evaluate the membrane expression and secretion of HLA-G molecules in peripheral blood mononuclear cells from allergic rhinitis patients after in vitro incubation with the causal allergen

Sublingual Immunotherapy: Recent Advances

ABSTRACT The practice of administering sublingual immunotherapy for respiratory allergy is gaining more and more diffusion worldwide as a consequence of the robust demonstration of clinical efficacy and safety provided by recent high-powered and well-designed studies, confirming for individual seasonal allergens the results of previous metanalyses in adult and pediatric populations. Preliminary evidence derives from recent rigorous trials on perennial allergens, like house dust mites, and specifically designed studies addressed the benefits on asthma. Emerging research suggests that SLIT may have a future role in other allergic conditions such as atopic dermatitis, food, latex and venom allergy. Efforts to develop a safer and more effective SLIT for inhalant allergens have led to the development of allergoids, recombinant allergens and formulations with adjuvants and substances targeting antigens to dendritic cells that possess a crucial role in initiating immune responses. The high degree of variation in the evaluation of clinical effects and immunological changes requires further studies to identify the candidate patients to SLIT and biomarkers of short and long term efficacy. Appropriate management strategies are urgently needed to overcome the barriers to SLIT compliance

The WEB-based Asthma Control: An intriguing connection or a dangerous hazard?

Globally, an estimated 300 million people have asthma, presenting a considerable and increasing burden of disease for healthcare systems, families, and patients themselves. Despite two decades of guidelines, asthma seems to remain not optimally controlled in a substantial proportion of people. The achievement of asthma control is the result of the interaction among different variables concerning the disease pattern and patients' and physicians' knowledge and behavior. It is well known that adherence to treatment increases in parallel to patient education. There is now a growing interest in the use of digital information technologies to promote asthma control and improve outcomes. Mobile health, or mHealth, refers to mobile devices, medical sensors, and communication technologies that can enhance chronic disease care and monitoring. Aim of this review was to evaluate the web resources nowadays available and to analyze the published studies about the web-based instruments used to improve asthma knowledge, control asthma outcomes. In general, studies revealed that the technology is well accepted. Interactive asthma technology may be, in addition, of help in reaching populations difficult to reach, such as inner city populations. The number of tools and apps available continues to increase, and agencies such as the FDA, become involved in their regulation, thus the mHealth landscape will continue to evolve. Although asthma tools and apps have great potential to improve care for asthma, the proof of data reproducibility, the demonstration of effectiveness, and the privacy issues still represent the major technical problems

Pidotimod: The state of art

Despite the use of antibiotics and vaccines, the frequency of respiratory tract infections is still high and these infections interest a wide range of patients, from children to aged people, including in particular these extreme categories because of the deficiency of their immune system, due to immaturity in the former case and to "immunosenescence" in the latter. For that reason immunostimulant drugs are getting more important to prevent and to attenuate infections. Pidotimod (3-L-pyroglutamyl-L-thiazolidine-4carboxylic acid) is a synthetic dipeptide with immunomodulatory properties. We reviewed studies conducted on different categories of patients, with particular attention on children and senile patients suffering from recurrent respiratory tract infections, associated, or not, with asthma or COPD. The outcomes considered are both clinical and laboratory parameters. The common end-point of these studies is that Pidotimod has an immunomodulatory activity which is able both to improve the clinical conditions of patients and to enhance and stimulate their immunity cells (lymphocytes but not only) functions acting on adaptive and innate immunity. Pidotimod is also able to increase the concentration of salivary IgA directed against bacteria; furthermore, it can modulate airway epithelial cells functions up-regulating the expression of toll-like receptors and acting on adhesion molecules. According to studies conducted on patients with atopic asthma, it seems that Pidotimod could affect T-lymphocytes balance with a possible addictional anti-allergic activity. Furthermore, it has been demonstrated an improvement of FEV1 and PEF in asthmatic patients treated with Pidotimod. Main clinical outcomes are the reduction of the number of infectious episodes, lesser severity of signs and symptoms and, consequently, a reduction in use of antibiotics and symptomatic drugs, less working and school days lost, less mortality and morbidity. The studies considered give positive results, confirming Pidotimod's efficacy. Furthermore, many studies show a good safety profile of the drug, without recording serious adverse events and mutagenic potential, and a very low incidence of side effects. Pidotimod is also a more safe solution in patients subjected to vaccination, if compared to lyophilized polibacterial, which can't be administered for thirty days before vaccination

Psychological aspects in asthma: Do psychological factors affect asthma management?

open5noDespite the regular treatment with inhaled corticosteroids (ICS) or ICS plus long-acting beta2-agonists, permits to control de majority of asthmatics, a significant proportion of patients does not respond to this treatment. This review was aimed to explore the role of psychological factors associated to the unsuccessful fulfilment of optimal levels of asthma control, especially in patients suffering from severe asthma. The results of a Medline search were 5510 articles addressed to different psychological key concepts, constructs and variables. This review will highlight how some selected psychological factors may have a burden on asthma management. Evidences are now available about the link between asthma (in terms of severity and control), some psychological aspects (subjective perception, alexithymia, coping style) and mental health (anxiety, depression). Taking into account this most probably bidirectional influence, a screening of mental symptoms and psychological aspects related to asthma, could lead to plan appropriate interventions to better control asthma and to improve the patient's wellbeing.openBaiardini I.; Sicuro F.; Balbi F.; Canonica G.W.; Braido F.Baiardini, I.; Sicuro, F.; Balbi, F.; Canonica, G. W.; Braido, F