Abstract
Asthma—chronic obstructive pulmonary disease (COPD) overlap, termed as ACO, is a complex heterogeneous disease characterised by persistent airflow limitation, which manifests features of both asthma and COPD. These patients have a worse prognosis, in terms of more frequent and severe exacerbations, more frequent symptoms, worse quality of life, increased comorbidities and a faster lung function decline. In absence of clear diagnostic or therapeutic guidelines, ACO presents as a challenge to clinicians. The present study aims to investigate whether ACO patients have a distinct exhaled breath condensate (EBC) metabolic profile in comparison to asthma and COPD. A total of 132 age and BMI matched male smokers were recruited in the exploratory phase which consisted of (i) controls = 33 (ii) asthma = 34 (iii) COPD = 30 and (iv) ACO = 35. Using nuclear magnetic resonance (NMR) metabolomics, 8 metabolites (fatty acid, propionate, isopropanol, lactate, acetone, valine, methanol and formate) were identified to be significantly dysregulated in ACO subjects when compared to both, asthma and COPD. The expression of these dysregulated metabolites were further validated in a fresh patient cohort consisting of (i) asthma = 32 (ii) COPD = 32 and (iii) ACO = 40, which exhibited a similar expression pattern. Multivariate receiver operating characteristic (ROC) curves generated using these metabolites provided a robust ACO classification model. The findings were also integrated with previously identified serum metabolites and inflammatory markers to develop a robust predictive model for differentiation of ACO. Our findings suggest that NMR metabolomics of EBC holds potential as a platform to identify robust, non-invasive biomarkers for differentiating ACO from asthma and COPD.
Highlights
As per the definition provided by the Global Initiative for Asthma (GINA), asthma is considered to be a heterogeneous disease, with characteristics of chronic airway inflammation, clinical history of wheezing, shortness of breath, chest tightness and cough, together with reversible airflow limitation[1]
asthma COPD overlap (ACO) patients have been excluded from randomised controlled trials (RCTs) till date and this population is poorly characterised in most mechanistic studies
Nuclear magnetic resonance (NMR) is characterized by inherent distinctive advantages, which include minimal sample preparation, rapid spectra acquisition time, and the possibility to perform an untargeted analysis limited to the chemical nature of metabolites
Summary
As per the definition provided by the Global Initiative for Asthma (GINA), asthma is considered to be a heterogeneous disease, with characteristics of chronic airway inflammation, clinical history of wheezing, shortness of breath, chest tightness and cough, together with reversible airflow limitation[1]. A significant proportion of older patients with chronic airflow limitation (i.e. not completely reversible after bronchodilation) have diagnosis and/or features of both asthma and COPD, amongst s mokers[4,5]. Such patients are termed as ‘overlap’ cases. NMR is characterized by inherent distinctive advantages, which include minimal sample preparation, rapid spectra acquisition time, and the possibility to perform an untargeted analysis limited to the chemical nature of metabolites These advantages have promoted NMR-based metabolomics of EBC to the rank of a valuable method for an efficient investigation of a variety of lung d iseases[13]. It is reported that NMR spectral signatures of EBC can be used for the discovery and characterization of different asthma e ndotypes[17]
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