Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma.

Thymic stromal lymphopoietin (TSLP) is an innate cytokine, belonging to the group of alarmins, which plays a key pathogenic role in asthma by acting as an upstream activator of cellular and molecular pathways leading to type 2 (T2-high) airway inflammation. Released from airway epithelial cells upon tissue damage induced by several noxious agents including allergens, viruses, bacteria, and airborne pollutants, TSLP activates dendritic cells and group 2 innate lymphoid cells involved in the pathobiology of T2-high asthma. Tezepelumab is a fully human monoclonal antibody that binds to TSLP, thereby preventing its interaction with the TSLP receptor complex. Preliminary results of randomized clinical trials suggest that tezepelumab is characterized by a good safety and efficacy profile in patients with severe, uncontrolled asthma.

Benralizumab: From the Basic Mechanism of Action to the Potential Use in the Biological Therapy of Severe Eosinophilic Asthma.

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).

[Thunderstorm and asthma outbreaks during pollen season]. / Temporali e attacchi d'asma durante le stagioni polliniche.

An increasing body of evidence shows the occurrence of asthma epidemics, sometimes also severe, during thunderstorms in the pollen season in various geographical zones. The main hypothesis explaining association between thunderstorms and asthma claims that thunderstorms can concentrate pollen grains at ground level; these grains may then release allergenic particles of respirable size in the atmosphere after their rupture by osmotic shock. During the first 20-30 minutes of a thunderstorm, patients suffering from pollen allergy may inhale a high concentration of the allergenic material dispersed into the atmosphere, which can, in turn, induce asthmatic reactions, often severe. Subjects without asthma symptoms but affected by seasonal rhinitis can also experience an asthma attack. All subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe bronchial obstruction. Considering this background, it is useful to predict thunderstorms during pollen season and, thus, to prevent thunderstorm-related clinical event. However, it is also important to focus on therapy, and it is not sufficient that subjects at risk of asthma follow a correct therapy with bronchodilators, but they also need to inhale corticosteroids, using both in case of emergency.

Pharmacologic rationale underlying the therapeutic effects of tiotropium/olodaterol in COPD.

Bronchodilators are the most important drugs used for the treatment of chronic obstructive pulmonary disease (COPD). In particular, these therapeutic agents are mostly long-acting compounds utilized via inhalation, and include LAMA (long-acting muscarinic receptor antagonists) and LABA (long-acting ß2-adrenoceptor agonists). Because LAMA and LABA induce bronchodilation by distinct mechanisms of action, LABA/LAMA combinations provide a reciprocal potentiation of the pharmacological effects caused by each component. Hence, many COPD patients who do not achieve a satisfactory control of their symptoms using a single, either LAMA or LABA bronchodilator, can experience relevant benefits with the use of LAMA/LABA fixed combinations. Many different LAMA/LABA combinations have been recently developed and evaluated in randomized clinical trials. In this context, our review focuses on the pharmacological mechanisms underpinning the bronchodilation elicited by the LAMA tiotropium bromide and the LABA olodaterol. We also discuss the results of the most important clinical studies carried out in COPD patients to assess the efficacy and safety of tiotropium/olodaterol combinations.

Comparative effects of a two-week treatment with nebivolol and nifedipine in hypertensive patients suffering from COPD.

BACKGROUND: It has been suggested that the antihypertensive agent nebivolol, a beta1-adrenoceptor-blocking agent that modulates the endogenous production of nitric oxide, is preferable to 'conventional' beta1-blockers in hypertensive patients with airway dysfunction. OBJECTIVES: Since beta1-blockade by nebivolol is larger after repeated dosing than after a single oral intake, we have explored its effect on pulmonary function after a 2-week treatment in hypertensive patients with mild to moderate COPD. METHODS: A single-blind crossover design was used. Twenty patients with COPD as selected above and with a diastolic blood pressure of 95-110 mm Hg after 1 week of placebo run-in were entered into the two 2-week active treatment periods with either 5 mg nebivolol (n = 10) or 30 mg nifedipine gastrointestinal-transport-system (GITS) (n = 10) taken for a period of 2 weeks. After a further 1-week washout, subjects were crossed-over to receive the other drug for 2 additional weeks. At each visit, changes in spirometric indexes and the interaction with the bronchodilator effect of salbutamol were investigated. Moreover, systolic and diastolic blood pressure (BP) together with heart rate were manually measured in order to evaluate the cardiovascular effects of the different treatments. Throughout the study, patients recorded symptoms. RESULTS: Similar and significant reductions in systolic and diastolic BP were observed with both treatments. The impact of nifedipine on FEV1 was not significant (p > 0.05), while that of nebivolol was slight. The maximum response to salbutamol was slightly decreased with either nebivolol or nifedipine GITS. Day-to-day airway obstruction control, interpreted from patient recordings of symptom scores and inhaler use, was similar with both treatments. CONCLUSIONS: Our pilot study suggests that the use of nebivolol in hypertensive patients with stable mild to moderate COPD was safe during a 2-week trial. Evaluation of longer time periods, larger patient numbers with more severe COPD or during exacerbations is warranted.