N-acetylcysteine Treatment in Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis/Pre-COPD: Distinct Meta-analyses.

INTRODUCTION: N-acetylcysteine (NAC) is a mucolytic agent with antioxidant properties. Oxidative stress is a key pathogenic mechanism in chronic respiratory conditions such as COPD and chronic bronchitis (CB). In these meta-analyses we investigated the efficacy of NAC in subjects with COPD or CB, the latter being a potential pre-COPD condition (CB/pre-COPD). METHODS: The meta-analyses were conducted according to PRISMA guidelines. Exacerbations were assessed using total number of exacerbations. Improvement in patients' respiratory symptoms and/or patients quality of life (QoL) were measured by validated tools or assessed at the end of the study. RESULTS: Twenty studies were included, of which seven evaluated NAC in patients with symptoms of CB/pre-COPD as entry criterion. NAC treated patients showed a significant reduction of the incidence of exacerbations as compared to placebo both in COPD (IRR=0.76; 95% confidence interval (CI) 0.59-0.99) and CB/pre-COPD (IRR=0.81; 95% CI 0.69-0.95). Sensitivity analyses in studies with duration higher than 5 months, confirmed the overall results. CB/pre-COPD patients treated with NAC were significantly more likely to experience an improvement in symptoms and/or QoL compared to placebo (odds ratio (OR)=3.47; 95% CI 1.92-6.26). A similar trend was observed in the few COPD studies evaluable. Sensitivity analyses showed a significant association of NAC with improvement in symptoms and/or QoL both in CB/pre-COPD and COPD patients. CONCLUSIONS: These findings provide novel data of NAC on the improvement in symptoms and QoL in addition to prevention of exacerbations in COPD and CB/pre-COPD. PROSPERO registry no. CRD42023468154.

From treatable traits to GETomics in airway disease: moving towards clinical practice.

The treatable traits approach represents a strategy for patient management. It is based on the identification of characteristics susceptible to treatments or predictive of treatment response in each individual patient. With the objective of accelerating progress in research and clinical practice relating to such a treatable traits approach, the Portraits event was convened in Barcelona, Spain, in November 2022. Here, while reporting the key concepts that emerged from the discussions during the meeting, we review the current state of the art related to treatable traits and chronic respiratory diseases management, and we describe the possible actions that clinicians can take in clinical practice to implement the treatable traits framework. Furthermore, we explore the new concept of GETomics and the new models of research in the field of COPD.

Evaluating as-needed inhaled corticosteroid strategies in asthma: expanding the benefits to mild asthma.

INTRODUCTION: Adherence to regular anti-inflammatory treatment is commonly low, and short-acting ß2 agonist (SABA) overuse is common in patients with asthma, leading to an increased risk of asthma-related adverse events. AREAS COVERED: Given the pivotal role of inflammation in asthma, multiple as-needed inhaled corticosteroid (ICS)-containing therapies have been developed, leading to a reduction in asthma exacerbations and improvement in symptom control. Currently, as-needed ICS/formoterol is one of the most commonly available formulations; however, other combinations such as ICS/SABA have been shown to be superior to as-needed SABA alone. Therefore, we performed a comprehensive review of the available scientific literature to enhance the advantages and disadvantages of each combination in clinical practice. EXPERT OPINION: The future direction we foresee in asthma management consists in abandoning as-needed short-acting bronchodilators in favor of as-needed ICS-containing therapies. Each patient is unique and differs from others; consequently, a single option will not fit everyone. Patients' and physicians' awareness of this perspective can be reached through the development of multiple therapeutic options suitable for each condition that can be found in 'real life'.

Effects of anti-IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real-life multicentre study (BIONIGE).

Background: Mepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown. Objectives: To evaluate the change in total IgE levels at 4 ± 2 months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels. Methods: Observational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis. Results: Three-month treatment (on average) with mepolizumab (n = 104) or benralizumab (n = 82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (-35%, p < 0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig-E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control. Conclusion: Benralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti-IL5-pathway treatments.

Air Pollution Exposure Impairs Airway Epithelium IFN-ß Expression in Pre-School Children.

Introduction: Air pollution is a risk factor for respiratory infections and asthma exacerbations. We previously reported impaired Type-I and Type-III interferons (IFN-ß/λ) from airway epithelial cells of preschool children with asthma and/or atopy. In this study we analyzed the association between rhinovirus-induced IFN-ß/λ epithelial expression and acute exposure to the principal outdoor air pollutants in the same cohort. Methods: We studied 34 children (17asthmatics/17non-asthmatics) undergoing fiberoptic bronchoscopy for clinical indications. Bronchial epithelial cells were harvested by brushing, cultured and experimentally infected with Rhinovirus Type 16 (RV16). RV16-induced IFN-ß and λ expression was measured by quantitative real time PCR, as was RV16vRNA. The association between IFNs and the mean exposure to PM10, SO2 and NO2 in the day preceding bronchoscopy was evaluated using a Generalized Linear Model (GLM) with Gamma distribution. Results: Acute exposure to PM10 and NO2 was negatively associated to RV16-induced IFNß mRNA. For each increase of 1ug/m3 of NO2 we found a significative decrease of 2.3x103 IFN-ß mRNA copies and for each increase of 1ug/m3 of PM10 a significative decrease of 1x103 IFN-ß mRNA copies. No significant associations were detected between IFN-λ mRNA and NO2 nor PM10. Increasing levels of NO2 (but not PM10) were found to be associated to increased RV16 replication. Conclusions: Short-term exposure to high levels of NO2 and PM10 is associated to a reduced IFN-ß expression by the airway epithelium, which may lead to increased viral replication. These findings suggest a potential mechanism underlying the link between air pollution, viral infections and asthma exacerbations.