Background 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. Objectives We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum. Methods 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. Results 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. Conclusion Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.
Non‐T2 asthma is traditionally defined as asthma without features of T2 asthma. The definition is arbitrary and is generally based on the presence of neutrophils in sputum, or the absence (or normal ...levels) of eosinophils or other T2 markers in sputum (paucigranulocytic), airway biopsies or in blood. This definition may be imprecise as we gain more knowledge from applying transcriptomics and proteomics to blood and airway samples. The prevalence of non‐T2 asthma is also difficult to estimate as most studies are cross‐sectional and influenced by concomitant treatment with glucocorticosteroids, and by the presence of recognized or unrecognized airway infections. No specific therapies have shown any clinical benefits in patients with asthma that is associated with a non‐T2 inflammatory process. It remains to be seen if such an endotype truly exists and to identify treatments to target that endotype. Meanwhile, identifying intense airway neutrophilia as an indicator of airway infection and airway hyperresponsiveness as an indicator of smooth muscle dysfunction, and treating them appropriately, and not increasing glucocorticosteroids in patients who do not have obvious T2 inflammation, seem reasonable.
Microplastic pollution is an emerging environmental problem, and little research has focused on its impact on the human body. Based on retrospective case series, the study required participants to ...fill out a questionnaire and provide sputum samples in order to investigate the presence of microplastics in human sputum and determine whether humans involuntarily inhale them. A total of 22 patients suffering from different respiratory diseases were recruited. We used an Agilent 8700 laser infrared imaging spectrometer and Fourier-transform infrared microscope to analyze sputum samples and evaluate microplastics in the respiratory tract. Remarkably, the size range of the method for detecting microplastics in our study is 20–500 μm. The results showed that 21 types of microplastics were identified, and polyurethane was dominant, followed by polyester, chlorinated polyethylene, and alkyd varnish, accounting for 78.36% of the total microplastics. Most of the aspirated microplastics detected are smaller than 500 μm in size (median: 75.43 μm; interquartile range: 44.67–210.64 μm). Microplastics are ubiquitous in all sputum, indicating that inhalation is a potential way for plastics to enter the human body. Additionally, the quantities of microplastic types in the respiratory tract are related to smoking, invasive examination, etc. (P < 0.05). This study sheds new light on microplastic exposure, which provides basic data for the risk assessment of microplastics to human health.
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.
We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD ...exacerbations.
Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center. Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation. Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.
The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.
A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD. The sputum mediator and microbiome profiles were distinct between clusters.
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MUPPITS-2 was a randomized, placebo-controlled clinical trial that demonstrated mepolizumab (anti-IL-5) reduced exacerbations and blood and airway eosinophils in urban children with ...severe eosinophilic asthma. Despite this reduction in eosinophilia, exacerbation risk persisted in certain patients treated with mepolizumab. This raises the possibility that subpopulations of airway eosinophils exist that contribute to breakthrough exacerbations.
We aimed to determine the effect of mepolizumab on airway eosinophils in childhood asthma.
Sputum samples were obtained from 53 MUPPITS-2 participants. Airway eosinophils were characterized using mass cytometry and grouped into subpopulations using unsupervised clustering analyses of 38 surface and intracellular markers. Differences in frequency and immunophenotype of sputum eosinophil subpopulations were assessed based on treatment arm and frequency of exacerbations.
Median sputum eosinophils were significantly lower among participants treated with mepolizumab compared with placebo (58% lower, 0.35% difference 95% CI 0.01, 0.74, P = .04). Clustering analysis identified 3 subpopulations of sputum eosinophils with varied expression of CD62L. CD62Lint and CD62Lhi eosinophils exhibited significantly elevated activation marker and eosinophil peroxidase expression, respectively. In mepolizumab-treated participants, CD62Lint and CD62Lhi eosinophils were more abundant in participants who experienced exacerbations than in those who did not (100% higher for CD62Lint, 0.04% difference 95% CI 0.0, 0.13, P = .04; 93% higher for CD62Lhi, 0.21% difference 95% CI 0.0, 0.77, P = .04).
Children with eosinophilic asthma treated with mepolizumab had significantly lower sputum eosinophils. However, CD62Lint and CD62Lhi eosinophils were significantly elevated in children on mepolizumab who had exacerbations, suggesting that eosinophil subpopulations exist that contribute to exacerbations despite anti-IL-5 treatment.
COVID-19 is the shocking viral pandemics of this year which affected the health, economy, communications, and all aspects of social activities all over the world. Early diagnosis of this viral ...disease is very important since it can prevent lots of mortalities and care consumption.
The functional similarities between COVID-19 and COVID-2 in inducing acute respiratory syndrome lightened our mind to find a diagnostic mechanism based on early traces of mitochondrial ROS overproduction as lung cells’ dysfunctions induced by the virus. We designed a simple electrochemical sensor to selectively detect the intensity of ROS in the sputum sample (with a volume of less than 500 μl). Comparing the results of the sensor with clinical diagnostics of more than 140 normal and involved cases resulted in a response calibration with accuracy and sensitivity both 97%. Testing the sensor in more than 4 hospitals shed promising lights in ROS based real-time tracing of COVID-19 from the sputum sample.
•A novel electrotechnical diagnosis system for fast screening of COVID-19 was developed.•It has been based on early tracing of reactive oxygen species (ROS) overproduction.•MWCNTs have a crucial role in selective detection of released ROS induced by the virus.•These impressive results were achieved while the sensor declared diagnosis in less than 30 s.
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