Nitric oxide (NO) is a short-lived gas molecule which has been studied for its role as a signaling molecule in the vasculature and later, in a broader view, as a cellular messenger in many other biological processes such as immunity and inflammation, cell survival, apoptosis, and aging. Fractional exhaled nitric oxide (FeNO) is a convenient, easy-to-obtain, and non-invasive method for assessing active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid the diagnosis and monitoring of several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory and/or immunological conditions, including allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, atopic dermatitis, eosinophilic esophagitis, and food allergy. In this review, we aim to provide an extensive overview of the current state of knowledge about FeNO as a biomarker in type 2 inflammation, outlining past and recent data on the application of its measurement in patients affected by a broad variety of atopic/allergic disorders.

Eosinophils play a key role in airway inflammation in many diseases, such as allergic and non-allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic obstructive pulmonary disease. In these chronic disabling conditions, eosinophils contribute to tissue damage, repair, remodeling, and disease persistence through the production a variety of mediators. With the introduction of biological drugs for the treatment of these respiratory diseases, the classification of patients based on clinical characteristics (phenotype) and pathobiological mechanisms (endotype) has become mandatory. This need is particularly evident in severe asthma, where, despite the great scientific efforts to understand the immunological pathways underlying clinical phenotypes, the identification of specific biomarkers defining endotypes or predicting pharmacological response remains unsatisfied. In addition, a significant heterogeneity also exists among patients with other airway diseases. In this review, we describe some of the immunological differences in eosinophilic airway inflammation associated with severe asthma and other airway diseases and how these factors might influence the clinical presentation, with the aim of clarifying when eosinophils play a key pathogenic role and, therefore, represent the preferred therapeutic target.

Background:Hereditary angioedema (HAE) is caused by mutations in the C1 inhibitor (C1-INH) gene Serpin Family G Member 1(SERPING1), which results in either the decreased synthesis of normal C1-INH (C1-INH‐HAE type I) or expression of unfunctional C1-INH (C1-INH‐HAE type II). In recent studies, emotional stress was reported by patients as the most common trigger factor for C1-INH‐HAE attacks. Moreover, patients reported considerable distress over the significant variability and uncertainty with which the disease manifests, in addition to the impact of physical symptoms on their overall quality of life.Objective:We did a systematic review of the literature to shed light on the advancements made in the study of how stress and psychological processes impact C1-INH‐HAE.Methods:All of the articles on C1-INH‐HAE were analyzed up to December 2019. Both medical data bases and psychological data bases were examined. The keywords (KWs) used for searching the medical and psychological data bases were the following: “hereditary angioedema,” “psychology,” “stress,” “anxiety,” and “depression.”Results:Of a total of 2549 articles on C1-INH‐HAE, 113 articles were retrieved from the literature search by using the related KWs. Twenty-one of these articles were retrieved, examined, and classified.Conclusion:Although the literature confirmed that stress may induce various physical diseases, it also warned against making simplistic statements about its incidence that did not take into account the complexity and multicausality of factors that contribute to C1-INH‐HAE expression.

Adiponectin (Acrp30) is an adipokine widely studied for its beneficial metabolic properties. It circulates as low molecular weight (LMW), medium molecular weight (MMW) and high molecular weight (HMW) oligomers. The latter exert the most potent biological effects. Acrp30 attracted renewed interest with the finding that it was associated with the development and progression of immune disorders. The mechanisms underlying this association and the role of Acrp30 in the pathophysiology of immune-mediated conditions remain unknown. Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by chronic activation of the immune system, impaired antibody production and imbalanced cytokine production. In the attempt to shed light on the expression of Acrp30 in CVID we: a) investigated total Acrp30 and its oligomerization state in CVID patients undergoing maintenance Ig replacement therapy; b) assessed the effects of Ig replacement therapy on Acrp30 expression in treatment-naïve CVID patients, namely, patients not treated before diagnosis, before and after the first Ig administration; and c) evaluated the correlation between Acrp30 levels and clinical phenotypes of the disease. As controls, we analyzed healthy subjects and patients affected by a non-immunodeficiency chronic inflammatory demyelinating polyneuropathy (CIDP), before and after Ig infusion. We found that total Acrp30 and HMW oligomers were decreased in CVID but not in CIDP patients versus controls. Moreover, Acrp30 levels were correlated with IgA levels and were associated with two CVID phenotypes, namely, autoimmune cytopenia and enteropathy. Receiver operating characteristic curve analysis indicated that Acrp30 modulation is specific for CVID patients. Acrp30 and HMW levels quickly and dramatically increased after Ig infusion only in eight treatment-naïve CVID patients but not in five CIDP patients. This finding indicates that Ig administration per se is not able to induce an increase of Acrp30, but the specific cellular and/or molecular background proper of CVID seems to be essential. In conclusion, our data indicate that Acrp30 is specifically related to CVID activity. Further studies are required to understand the biological role of Acrp30 and its possible use as disease biomarker in CVID.

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES—Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.