Endogenous airway acidification, as assessed by pH in expired breath condensate, has been implicated in asthma pathophysiology. We measured pH in breath condensate of patients with inflammatory airway diseases in stable condition and examined its relationship with the inflammatory process (as assessed by differential cell counts in induced sputum), oxidative stress (as assessed by H₂O₂ and 8-isoprostane), and nitric oxide metabolism (as assessed by total nitrate/nitrite). We studied 40 patients with bronchial asthma (20 with moderate disease, forced expiratory volume in 1 second 60 [10]% SD predicted), 20 patients with bronchiectasis, 20 patients with chronic obstructive pulmonary disease (COPD), and 10 normal subjects. Mean (95% confidence intervals) pH values were significantly lower in patients with COPD and bronchiectasis compared with patients with asthma and control subjects (7.16, 7.09–7.23 and 7.11, 7.04–7.19 versus 7.43, 7.35–7.52 and 7.57, 7.51–7.64, respectively, p < 0.0001). Patients with moderate asthma had significantly lower values compared with mild and control subjects. In patients with COPD and bronchiectasis, the values of pH were significantly correlated with both sputum neutrophilia and oxidative stress. Respectively, in patients with moderate asthma, a significant correlation was observed between pH and sputum eosinophilia, total nitrate/nitrite, and oxidative stress. The pH of the expired breath condensate might be a simple, noninvasive, inexpensive, and easily repeatable procedure for the evaluation of the inflammatory process in airway diseases.

Introduction: International registries provide opportunities to describe use of biologics for treating severe asthma in current clinical practice. Our aims were to describe real-life global patterns of biologic use (continuation, switches, and discontinuations) for severe asthma, elucidate reasons underlying these patterns, and examine associated patient-level factors. Methods: This was a historical cohort study including adults with severe asthma enrolled into the International Severe Asthma Registry (ISAR; http://isaregistries.org, 2015– 2020) or the CHRONICLE Study (2018– 2020) and treated with a biologic. Eleven countries were included (Bulgaria, Canada, Denmark, Greece, Italy, Japan, Kuwait, South Korea, Spain, UK, and USA). Biologic utilization patterns were defined: 1) continuing initial biologic; 2) stopping biologic treatment; or 3) switching to another biologic. Reasons for discontinuation/switching were recorded and comparisons drawn between groups. Results: A total of 3531 patients were included. Omalizumab was the most common initial biologic in 2015 (88.2%) and benralizumab in 2019 (29.6%). Most patients (79%; 2791/3531) continued their first biologic; 10.2% (356/3531) stopped; 10.8% (384/3531) switched. The most frequent first switch was from omalizumab to an anti–IL-5/5R (49.6%; 187/377). The most common subsequent switch was from one anti–IL-5/5R to another (44.4%; 20/45). Insufficient efficacy and/or adverse effects were the most frequent reasons for stopping/switching. Patients who stopped/switched were more likely to have a higher baseline blood eosinophil count and exacerbation rate, lower lung function, and greater health care resource utilization. Conclusion: The description of real-life patterns of continuing, stopping, or switching biologics enhances our understanding of global biologic use. Prospective studies involving structured switching criteria could ascertain optimal strategies to identify patients who may benefit from switching.

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.