Asthma is a very frequent chronic airway disease that includes many different clinical phenotypes and inflammatory patterns. In particular, eosinophilic bronchial inflammation is often associated with allergic as well as nonallergic asthma. The most important cytokine involved in the induction, maintenance, and amplification of airway eosinophilia in asthma is interleukin-5 (IL-5), released by both T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2). Hence, IL-5 and its receptor are suitable targets for selective biologic drugs which can play a key role in add-on treatment of severe eosinophilic asthma refractory to corticosteroids. Within such a context, the anti-IL-5 monoclonal antibodies mepolizumab and reslizumab have been developed and approved for biological therapy of uncontrolled eosinophilic asthma. In this regard, on the basis of several successful randomized controlled trials, the anti-IL-5 receptor benralizumab has also recently obtained the approval from US Food and Drug Administration (FDA).

Among the various members of the mitogen-activated protein kinase (MAPK) family, p38 MAPK subgroup is the most involved in airway and lung inflammation underlying asthma and chronic obstructive pulmonary disease (COPD). In particular, several environmental agents including aeroallergens, cigarette smoke, airborne pollutants, viral and bacterial pathogens activate the p38α isoform which in turn up-regulates the expression of multiple proinflammatory cytokines and chemokines, as well as the production of some fibrogenic factors. Therefore, p38 MAPK-induced bronchial inflammation and remodelling significantly contribute to the development, persistence and amplification of airflow limitation, which is the hallmark of asthma and COPD. Such advances in our understanding of p38 role in the pathobiology of the above widespread, chronic obstructive respiratory diseases, have led to consider p38 MAPK as a suitable molecular target for novel treatment strategies. Indeed, many studies have been carried out in both animal and clinical settings, with the aim of evaluating the potential therapeutic effects of p38 MAPK inhibitors in both asthma and COPD.

Introduction: Patient–ventilator asynchrony may occur with modes of partial ventilatory support. Because this problem is associated with worsened outcomes, identifying and managing asynchronies has been recognized as a relevant clinical problem during both invasive and noninvasive (NIV) mechanical ventilation. Areas covered: In this review article, we first describe the different forms of patient–ventilator asynchrony and how they are classified and quantified. Then, we show how these asynchronies can be recognized, considering the techniques used to properly detect asynchronies, by either ventilator waveform observation, or through systems based on more complexes mathematical algorithms, by means of adjunctive signals, such as the electrical activity of the diaphragm or esophageal pressure. Finally, we describe the actions that can be undertaken in order to limit the rate of asynchronies during both invasive ventilation and NIV mechanical ventilation, such as modifications of the ventilator mode and/or settings, variation of the sedation regimen (type and doses), and other technical pitfalls. Expert commentary: Detection of asynchronies is crucial in order to reduce their incidence, adopting adjustments of the ventilator settings, sedation regimen, and other technical pitfalls. It remains to be clarified whether the relationship between high incidence of asynchrony and worsened outcome is causative or just associative.

Chronic rhinosinusitis is a common inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion, and hyposmia. The genetic predisposition or the exposure to irritants can sustain the inflammatory response and the development of nasal polyposis. Nasal polyps are benign and teardrop-shaped growths that project in the nasal cavities, and originate from the ethmoid sinuses. This inflammatory process is associated with high expression of IL-4, IL-5 and IL-13 and IgE. Antibodies targeting these cytokines or receptors represent a therapeutic strategy in the treatment of nasal polyposis in combination with corticosteroids. The molecular pathogenesis of nasal polyps in chronic rhinosinusitis (CRS) patients is associated with remodeling transition, a process in which epithelial cells lose their typical phenotype, acquiring a mesenchymal-like aspect. TGFβ/SMAD, ERK, and Wnt/β-catenin pathways are altered during the nasal tissue remodeling. miRNA and inhibitor molecules targeting these signaling pathways are able to interfere with the process; which could lead to alternative therapies. Nasal polyps are an alternative source of mesenchymal stem cells, which can be isolated from surgical biopsies. A molecular understanding of the biology of PO-MSCs will contribute to the delineating inflammatory process underlying the development of nasal polyps.

Asthma and nasal polyposis often coexist and are frequently intertwined by tight pathogenic links, mainly consisting of the cellular and molecular pathways underpinning type 2 airway inflammation. The latter is characterized by a structural and functional impairment of the epithelial barrier, associated with the eosinophilic infiltration of both the lower and upper airways, which can be driven by either allergic or non-allergic mechanisms. Type 2 inflammatory changes are predominantly due to the biological actions exerted by interleukins 4 (IL-4), 13 (IL-13), and 5 (IL-5), produced by T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2). In addition to the above cytokines, other proinflammatory mediators involved in the pathobiology of asthma and nasal polyposis include prostaglandin D₂ and cysteinyl leukotrienes. Within this context of ‘united airway diseases’, nasal polyposis encompasses several nosological entities such as chronic rhinosinusitis with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD). Because of the common pathogenic origins of asthma and nasal polyposis, it is not surprising that the more severe forms of both these disorders can be successfully treated by the same biologic drugs, targeting many molecular components (IgE, IL-5 and its receptor, IL-4/IL-13 receptors) of the type 2 inflammatory trait.