Acoustic biomarkers in asthma: a systematic review.

OBJECTIVE: Current monitoring methods of asthma, such as peak expiratory flow testing, have important limitations. The emergence of automated acoustic sound analysis, capturing cough, wheeze, and inhaler use, offers a promising avenue for improving asthma diagnosis and monitoring. This systematic review evaluated the validity of acoustic biomarkers in supporting the diagnosis of asthma and its monitoring. DATA SOURCES: A search was performed using two databases (PubMed and Embase) for all relevant studies published before November 2023. STUDY SELECTION: 27 studies were included for analysis. Eligible studies focused on acoustic signals as digital biomarkers in asthma, utilizing recording devices to register or analyze sound. RESULTS: Various respiratory acoustic signal types were analyzed, with cough and wheeze being predominant. Data collection methods included smartphones, custom sensors and digital stethoscopes. Across all studies, automated acoustic algorithms achieved average accuracy of cough and wheeze detection of 88.7% (range: 61.0 - 100.0%) with a median of 92.0%. The sensitivity of sound detection ranged from 54.0 to 100.0%, with a median of 90.3%; specificity ranged from 67.0 to 99.7%, with a median of 95.0%. Moreover, 70.4% (19/27) studies had a risk of bias identified. CONCLUSIONS: This systematic review establishes the promising role of acoustic biomarkers, particularly cough and wheeze, in supporting the diagnosis of asthma and monitoring. The evidence suggests the potential for clinical integration of acoustic biomarkers, emphasizing the need for further validation in larger, clinically-diverse populations.

ERS statement: a core outcome set for clinical trials evaluating the management of COPD exacerbations.

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use.

Obese, non-eosinophilic asthma: frequent exacerbators in a real-world setting.

OBJECTIVE: In the UK, asthma deaths are at their highest level this century. Increased recognition of at-risk patients is needed. This study phenotyped frequent asthma exacerbators and used machine learning to predict frequent exacerbators. METHODS: Patients admitted to a district general hospital with an asthma exacerbation between 1st March 2018 and 1st March 2020 were included. Patients were organized into two groups: "Infrequent Exacerbators" (1 admission in the previous 12 months) and "Frequent Exacerbators" (≥2 admissions in the previous 12 months). Patient data were retrospectively collected from hospital and primary care records. Machine learning models were used to predict frequent exacerbators. RESULTS: 200 patients admitted for asthma exacerbations were randomly selected (73% female; mean age 47.8 years). Peripheral eosinophilia was uncommon in either group (21% vs 19%). More frequent exacerbators were being treated with high-dose ICS than infrequent exacerbators (46.5% vs 23.2%; P < 0.001), and frequent exacerbators used more SABA inhalers (10.9 vs 7.40; P = 0.01) in the year preceding the current admission. BMI was raised in both groups (34.2 vs 30.9). Logistic regression was the most accurate machine learning model for predicting frequent exacerbators (AUC = 0.80). CONCLUSIONS: Patients admitted for asthma are predominately female, obese and non-eosinophilic. Patients who require multiple admissions per year have poorer asthma control at baseline. Machine learning algorithms can predict frequent exacerbators using clinical data available in primary care. Instead of simply increasing the dose of corticosteroids, multidisciplinary management targeting Th2-low inflammation should be considered for these patients.

Recurrent Severe Preschool Wheeze: From Prespecified Diagnostic Labels to Underlying Endotypes.

Rationale: Preschool wheezing is heterogeneous, but the underlying mechanisms are poorly understood.Objectives: To investigate lower airway inflammation and infection in preschool children with different clinical diagnoses undergoing elective bronchoscopy and BAL.Methods: We recruited 136 children aged 1-5 years (105 with recurrent severe wheeze [RSW]; 31 with nonwheezing respiratory disease [NWRD]). Children with RSW were assigned as having episodic viral wheeze (EVW) or multiple-trigger wheeze (MTW). We compared lower airway inflammation and infection in different clinical diagnoses and undertook data-driven analyses to determine clusters of pathophysiological features, and we investigated their relationships with prespecified diagnostic labels.Measurements and Main Results: Blood eosinophil counts and percentages and allergic sensitization were significantly higher in children with RSW than in children with a NWRD. Blood neutrophil counts and percentages, BAL eosinophil and neutrophil percentages, and positive bacterial culture and virus detection rates were similar between groups. However, pathogen distribution differed significantly, with higher detection of rhinovirus in children with RSW and higher detection of Moraxella in sensitized children with RSW. Children with EVW and children with MTW did not differ in terms of blood or BAL-sample inflammation, or bacteria or virus detection. The Partition around Medoids algorithm revealed four clusters of pathophysiological features: 1) atopic (17.9%), 2) nonatopic with a low infection rate and high use of inhaled corticosteroids (31.3%), 3) nonatopic with a high infection rate (23.1%), and 4) nonatopic with a low infection rate and no use of inhaled corticosteroids (27.6%). Cluster allocation differed significantly between the RSW and NWRD groups (RSW was evenly distributed across clusters, and 60% of the NWRD group was assigned to cluster 4; P < 0.001). There was no difference in cluster membership between the EVW and MTW groups. Cluster 1 was dominated by Moraxella detection (P = 0.04), and cluster 3 was dominated by Haemophilus or Staphylococcus or Streptococcus detection (P = 0.02).Conclusions: We identified four clusters of severe preschool wheeze, which were distinguished by using sensitization, peripheral eosinophilia, lower airway neutrophilia, and bacteriology.

ERS International Congress 2023: highlights from the Basic and Translational Sciences Assembly.

Early career members of Assembly 3 (Basic and Translational Sciences) of the European Respiratory Society (ERS) summarise the key messages discussed during six selected sessions that took place at the ERS International Congress 2023 in Milan, Italy. Aligned with the theme of the congress, the first session covered is "Micro- and macro-environments and respiratory health", which is followed by a summary of the "Scientific year in review" session. Next, recent advances in experimental methodologies and new technologies are discussed from the "Tissue modelling and remodelling" session and a summary provided of the translational science session, "What did you always want to know about omics analyses for clinical practice?", which was organised as part of the ERS Translational Science initiative's aims. The "Lost in translation: new insights into cell-to-cell crosstalk in lung disease" session highlighted how next-generation sequencing can be integrated with laboratory methods, and a final summary of studies is presented from the "From the transcriptome landscape to innovative preclinical models in lung diseases" session, which links the transcriptome landscape with innovative preclinical models. The wide range of topics covered in the selected sessions and the high quality of the research discussed demonstrate the strength of the basic and translational science being presented at the international respiratory conference organised by the ERS.

ERS International Congress 2022: highlights from the Airway Diseases Assembly.

The European Respiratory Society (ERS) celebrated the return of an in-person meeting in Barcelona, Spain, after 2 years of virtual congresses. The ERS Congress 2022 programme was replete with symposia, skills workshops and abstract presentations from all 14 assemblies, encompassing over 3000 abstracts presented in the form of thematic poster discussion and oral presentations. In this article, highlights from the ERS Congress 2022 (including from thematic poster sessions, oral presentations and symposia from keynote speakers), presented by Assembly 5 (Airway diseases, asthma, COPD and chronic cough), are reviewed by Early Career Members and experts in the field, with the aim of presenting key recent findings in the field.

Prevalence and clinical implications of respiratory viruses in asthma during stable disease state and acute attacks: Protocol for a meta-analysis.

INTRODUCTION: Viruses are detected in over 50% of acute asthma attacks and in a notable proportion of patients with asthma during stable disease state They are associated with worse outcomes. We will conduct a series of systematic reviews and meta-analyses to quantify the prevalence and clinical burden of various respiratory viruses in stable asthma and acute asthma attacks. In addition, we will assess the viral loads of respiratory viruses during stable and acute asthma, to explore whether viral load could differentiate attacks triggered by viruses versus those where viruses are present as "innocent bystanders". MATERIALS AND METHODS: Based on a prospectively registered protocol (PROSPERO, ID: CRD42023375108) and following standard methodology recommended by Cochrane, we will systematically search Medline/PubMed, EMBASE, the Cochrane Library and relevant conference proceedings for studies assessing the prevalence or clinical burden of respiratory viruses in asthma. Methodological rigour of the included studies will be appraised using a tool specific for prevalence studies and the Newcastle-Ottawa Scale respectively. In anticipation of significant clinical and methodological heterogeneity, we will conduct random effect meta-analyses. For evaluating the prevalence of viruses, we will perform meta-analyses of proportions using the inverse variance method, and the Freeman-Tukey transformation. We will conduct meta-regression analyses for exploring heterogeneity. CONCLUSION: We envisage that these systematic reviews and meta-analyses will quantify the prevalence and burden of respiratory viruses in stable and acute asthma and will drive future research and clinical practice.

Sleep apps: current limitations and challenges.

Sleep app ownership is increasing exponentially, due to their accessibility and ease-of-use. However, there are several concerns regarding the use of sleep apps. Few sleep apps demonstrate empirical evidence to support their claims, and if they do, this evidence can be based on significant methodological limitations. In addition, there are data privacy concerns with regards to sleep apps, which share sensitive user data with business and marketing partners, unbeknownst to their users. Moreover, sleep apps may increase engagement with healthcare professionals, which may place additional strain on under-pressure sleep services. This would be compounded by the fact that some sleep apps produce many false positives, and clinicians would need more time to analyze the data provided by these apps. In the future, sleep apps must undergo rigorous validation studies and grant more autonomy to their users over how their data is shared.

Assessing Treatment Success or Failure as an Outcome in Randomised Clinical Trials of COPD Exacerbations. A Meta-Epidemiological Study.

A recently published ERS core outcome set recommends that all trials of COPD exacerbation management should assess the treatment success (or "cure" of the exacerbation), defined as a dichotomous measure of the overall outcome of an exacerbation. This methodological systematic review describes and compares the instruments that were used to assess treatment success or failure in 54 such RCTs, published between 2006-2020. Twenty-three RCTs used composite measures consisting of several undesirable outcomes of an exacerbation, together defining an overall unfavourable outcome, to define treatment failure. Thirty-four RCTs used descriptive instruments that used qualitative or semi-quantitative descriptions to define cure, marked improvement, improvement of the exacerbation, or treatment failure. Treatment success and failure rates among patients receiving guidelines-directed treatments at different settings and timepoints are described and could be used to inform power calculations in future trials. Descriptive instruments appeared more sensitive to treatment effects compared to composite instruments. Further methodological studies are needed to optimise the evaluation of treatment success/failure. In the meantime, based on the findings of this systematic review, the ERS core outcome set recommends that cure should be defined as sufficient improvement of the signs and symptoms of the exacerbation such that no additional systemic treatments are required.