Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalized management approach can be provided. We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum. Partition-around-medoids clustering was applied to a training set of 266 asthmatic participants from the European Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) adult cohort using 8 prespecified clinic-physiologic variables. This was repeated in a separate validation set of 152 asthmatic patients. The clusters were compared based on sputum proteomics and transcriptomics data. Four reproducible and stable clusters of asthmatic patients were identified. The training set cluster T1 consists of patients with well-controlled moderate-to-severe asthma, whereas cluster T2 is a group of patients with late-onset severe asthma with a history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chronic airflow obstruction but is composed of nonsmokers. Cluster T4 is predominantly composed of obese female patients with uncontrolled severe asthma with increased exacerbations but with normal lung function. The validation set exhibited similar clusters, demonstrating reproducibility of the classification. There were significant differences in sputum proteomics and transcriptomics between the clusters. The severe asthma clusters (T2, T3, and T4) had higher sputum eosinophilia than cluster T1, with no differences in sputum neutrophil counts and exhaled nitric oxide and serum IgE levels. Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.

Cells constantly produce oxidizing species because of their metabolic activity, which is counteracted by the continuous production of antioxidant species to maintain the homeostasis of the redox balance. A deviation from the metabolic steady state leads to a condition of oxidative stress. The source of oxidative species can be endogenous or exogenous. A major exogenous source of these species is tobacco smoking. Oxidative damage can be induced in cells by chemical species contained in smoke through the generation of pro-inflammatory compounds and the modulation of intracellular pro-inflammatory pathways, resulting in a pathological condition. Cessation of smoking reduces the morbidity and mortality associated with cigarette use. Next-generation products (NGPs), as alternatives to combustible cigarettes, such as electronic cigarettes (e-cig) and tobacco heating products (THPs), have been proposed as a harm reduction strategy to reduce the deleterious impacts of cigarette smoking. In this review, we examine the impact of tobacco smoke and MRPs on oxidative stress in different pathologies, including respiratory and cardiovascular diseases and tumors. The impact of tobacco cigarette smoke on oxidative stress signaling in human health is well established, whereas the safety profile of MRPs seems to be higher than tobacco cigarettes, but further, well-conceived, studies are needed to better understand the oxidative effects of these products with long-term exposure.

Asthma is a chronic inflammatory condition involving the airways with varying pathophysiological mechanisms, clinical symptoms and outcomes, generally controlled by conventional therapies including inhaled corticosteroids and long-acting β₂ agonists. However, these therapies are unable to successfully control symptoms in about 5–10% of severe asthma patients. Atopic asthma, characterized by high immunoglobulin (Ig)E or eosinophilia, represents about 50% of asthmatic patients. Interleukin (IL)-5 is the main cytokine responsible of activation of eosinophils, hence therapeutic strategies have been investigated and developed for clinical use. Biologics targeting IL-5 and its receptor (first mepolizumab and subsequently, reslizumab and benralizumab), have been recently approved and used as add-on therapy for severe eosinophilic asthma resulting in a reduction in the circulating eosinophil count, improvement in lung function and exacerbation reduction in asthma patients. Despite these biologics having been approved for stratified severe asthma patients that remain uncontrolled with high doses of conventional therapy, a number of patients may be eligible for more than one biologic. Presently, the lack of head-to-head studies comparing the biological agents among themselves and with conventional therapy make the choice of optimal therapy for each patient a challenge for clinicians. Moreover, discontinuation of these treatments, implications for efficacy or adverse events, in particular in long-term treatment, and needs for useful biomarkers are still matters of debate. In this review we evaluate to date, the evidence on mepolizumab that seems to demonstrate it is a well-tolerated and efficacious regimen for use in severe eosinophilic asthma, though more studies are still required.

Background: People who smoke and who face challenges trying to quit or wish to continue to smoke may benefit by switching from traditional cigarettes to noncombustible nicotine delivery alternatives, such as heated tobacco products (HTPs) and electronic cigarettes (ECs). HTPs and ECs are being increasingly used to quit smoking, but there are limited data about their effectiveness. Objective: We conducted the first randomized controlled trial comparing quit rates between HTPs and ECs among people who smoke and do not intend to quit. Methods: We conducted a 12-week randomized noninferiority switching trial to compare effectiveness, tolerability, and product satisfaction between HTPs (IQOS 2.4 Plus) and refillable ECs (JustFog Q16) among people who do not intend to quit. The cessation intervention included motivational counseling. The primary endpoint of the study was the carbon monoxide–confirmed continuous abstinence rate from week 4 to week 12 (CAR weeks 4-12). The secondary endpoints included the continuous self-reported ≥50% reduction in cigarette consumption rate (continuous reduction rate) from week 4 to week 12 (CRR weeks 4-12) and 7-day point prevalence of smoking abstinence. Results: A total of 211 participants completed the study. High quit rates (CAR weeks 4-12) of 39.1% (43/110) and 30.8% (33/107) were observed for IQOS-HTP and JustFog-EC, respectively. The between-group difference for the CAR weeks 4-12 was not significant (P=.20). The CRR weeks 4-12 values for IQOS-HTP and JustFog-EC were 46.4% (51/110) and 39.3% (42/107), respectively, and the between-group difference was not significant (P=.24). At week 12, the 7-day point prevalence of smoking abstinence values for IQOS-HTP and JustFog-EC were 54.5% (60/110) and 41.1% (44/107), respectively. The most frequent adverse events were cough and reduced physical fitness. Both study products elicited a moderately pleasant user experience, and the between-group difference was not significant. A clinically relevant improvement in exercise tolerance was observed after switching to the combustion-free products under investigation. Risk perception for conventional cigarettes was consistently higher than that for the combustion-free study products under investigation. Conclusions: Switching to HTPs elicited a marked reduction in cigarette consumption among people who smoke and do not intend to quit, which was comparable to refillable ECs. User experience and risk perception were similar between the HTPs and ECs under investigation. HTPs may be a useful addition to the arsenal of reduced-risk alternatives for tobacco cigarettes and may contribute to smoking cessation. However, longer follow-up studies are required to confirm significant and prolonged abstinence from smoking and to determine whether our results can be generalized outside smoking cessation services offering high levels of support. Trial Registration: ClinicalTrials.gov NCT03569748; https://clinicaltrials.gov/ct2/show/NCT03569748

We provide an extensive review of 17 independent and industry-funded studies targeting carbonyls in aerosol emissions of Heated Tobacco Products (HTPs), focusing on quality criteria based on the reproducibility of experiments, appropriate analytic methods, and puffing regimes. Most revised studies complied with these requirements, but some were unreproducible, while others failed to consider analytical variables that may have affected the results and/or produced unrealistic comparisons. We also provide a review of the literature on the physicochemical properties of heated tobacco and HTP aerosols, as well as the evaluation of HTPs by regulatory agencies, addressing various critiques of their relative safety profile. The outcomes from the revised studies and regulatory evaluations tend to agree with and converge to a general consensus that HTP aerosols expose users to significantly lower levels of toxicity than tobacco smoke.