Asthma is a heterogeneous disease with varying severity. Severe asthma is a subject of constant research because it greatly affects patients’ quality of life, and patients with severe asthma experience symptoms, exacerbations, and medication side effects. Eosinophils, although at first considered insignificant, were later specifically associated with features of the ongoing inflammatory process in asthma, particularly in the severe case. In this review, we discuss new insights into the pathogenesis of severe asthma related to eosinophilic inflammation and the pivotal role of cytokines in a spectrum that is usually referred to as “T2-high inflammation” that accounts for almost half of patients with severe asthma. Recent literature is summarized as to the role of eosinophils in asthmatic inflammation, airway remodeling, and airway hypersensitivity. Major advances in the management of severe asthma occurred the past few years due to the new targeted biological therapies. Novel biologics that are already widely used in severe eosinophilic asthma are discussed, focusing on the choice of the right treatment for the right patient. These monoclonal antibodies primarily led to a significant reduction of asthma exacerbations, as well as improvement of lung function and patient quality of life.

Asthma is a common airway disease, affecting millions of people worldwide. Although most asthma patients experience mild symptoms, it is characterized by variable airflow limitation, which can occasionally become life threatening in the case of a severe exacerbation. The commonest triggers of asthma exacerbations in both children and adults are viral infections. In this review article, we will try to investigate the most common viruses triggering asthma exacerbations and their role in asthma immunopathogenesis, since viral infections in young adults are thought to trigger the development of asthma either right away after the infection or at a later stage of their life. The commonest viral pathogens associated with asthma include the respiratory syncytial virus, rhinoviruses, influenza and parainfluenza virus, metapneumovirus and coronaviruses. All these viruses exploit different molecular pathways to infiltrate the host. Asthmatics are more prone to severe viral infections due to their unique inflammatory response, which is mostly characterized by T2 cytokines. Unlike the normal T1 high response to viral infection, asthmatics with T2 high inflammation are less potent in containing a viral infection. Inhaled and/or systematic corticosteroids and bronchodilators remain the cornerstone of asthma exacerbation treatment, and although many targeted therapies which block molecules that viruses use to infect the host have been used in a laboratory level, none has been yet approved for clinical use. Nevertheless, further understanding of the unique pathway that each virus follows to infect an individual may be crucial in the development of targeted therapies for the commonest viral pathogens to effectively prevent asthma exacerbations. Finally, biologic therapies resulted in a complete change of scenery in the treatment of severe asthma, especially with a T2 high phenotype. All available data suggest that monoclonal antibodies are safe and able to drastically reduce the rate of viral asthma exacerbations.

Chronic rhinosinusitis is a common disease worldwide and can be categorized into chronic rhinosinusitis with nasal polyps and chronic rhinosinusitis without nasal polyps. Chronic rhinosinusitis with nasal polyps is common in patients with asthma and, particularly, severe asthma. Severe asthma is effectively treated with biologics and the coexistence of severe asthma with chronic rhinosinusitis with nasal polyps presents a phenotype that is more likely to respond to such treatment. In this review, we focus on the link between asthma and nasal polyps, and we review the treatment effect of various monoclonal antibodies in patients with severe asthma and nasal polyps as well as in patients with nasal polyps without asthma or with mild-to-moderate asthma. With the enhancement of our armamentarium with new monoclonal antibodies the right choice of biologic becomes an important target and one that is difficult to achieve due to the lack of comparative head-to-head studies.

Introduction: Community-acquired pneumonia (CAP) presents high mortality rates and high healthcare costs worldwide. C-reactive protein (CRP) has been widely used as a biomarker for the management of CAP. We evaluated the performance of CRP threshold values and ΔCRP as predictors of CAP survival and length of hospital stay. Methods: A total of 173 adult patients with CAP were followed for up to 30 days. We measured serum CRP levels on days 1, 4, and 7 (D1, D4, and D7) of hospitalization, and their variations between different days were calculated (ΔCRP). A multivariate logistic regression model was created with CAP 30-day survival and length of hospital stay as dependent variables, and absolute CRP values and ΔCRP, age, sex, smoking habit (pack-years), pO2/FiO2 ratio on D1, WBC on D1, and CURB-65 score as independent variables. Results: A total of six patients with CAP died (30-day mortality 3.47%). No difference was found in CRP levels and ΔCRP between survivors and non-survivors. Using a cut-off level of 9 mg/dL, the AUC (95% CI) for the prediction of survival of CRP on D4 and D7 were 0.765 (0.538–0.992) and 0.784 (0.580–0.989), respectively. A correlation between CRP values on any day and length of hospital stay was found, with it being stronger for CRPD4 and CRPD7 (p < 0.0001 and p = 0.0024, respectively). A reduction of CRP > 50% from D1 to D4 was associated with 4.11 fewer days of hospitalization (p = 0.0308). Conclusions: CRP levels on D4 and D7, but not ΔCRP, could fairly predict CAP survival. A reduction of CRP > 50% by the fourth day of hospitalization could predict a shorter hospital stay.

Asthma is generally characterized by variable symptoms such as dyspnea and wheezing and variable airflow obstruction. This review focuses on a subset of patients suffering from asthma with persistent airflow limitation that is not fully reversible (asthma with fixed airflow obstruction, FAO). The pathophysiology, the risk factors and the clinical outcomes associated with FAO are presented, as well as the distinct clinical entity of severe asthma and its inflammatory subtypes (T2 and non-T2). The current strategies for the treatment of these endotypes and treatment of the distinct Asthma/COPD overlap (ACO) phenotype are described. Management and medical interventions in FAO and/or ACO patients demand a holistic approach, which is not yet clearly established in guidelines worldwide. Finally, a treatment algorithm that includes FAO/ACO management based on pharmacological and non-pharmacological treatment, guideline-based management for specific co-morbidities, and modification of the risk factors is proposed.

Severe asthma greatly affects patients’ quality of life. Major advances have occurred in the management of severe eosinophilic asthma the past few years due to the new targeted biological therapies. There are three anti-IL-5 mAbs, mepolizumab, reslizumab and benralizumab. Despite the different mechanism of blocking IL-5 the clinical effects are quite similar as randomized controlled trials and real-life studies have shown. Moreover, there are reports of responding to one after failing to respond to another anti-IL-5 therapy. Accordingly, it is challenging to explore the possible differences in the response to anti-IL-5 treatments. This might help us not only understand possible mechanisms that contribute to the resistance to treatment in this particular asthma endotype, but also to phenotype within severe eosinophilic asthma in order to treat our patients more efficiently.