Metabolomic Analysis by Nuclear Magnetic Resonance Spectroscopy as a New Approach to Understanding Inflammation and Monitoring of Pharmacological Therapy in Children and Young Adults With Cystic Fibrosis

Montuschi, Paolo; Lucidi, Vincenzina; Paris, Debora; Montemitro, Enza; Shohreh, Rugia; Mores, Nadia; Melck, Dominique; Santini, Giuseppe; Motta, Andréa

doi:10.3389/fphar.2018.00595

Cited by 15 publications

(8 citation statements)

References 66 publications

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“…Altered levels of fatty acids in EBC are extensively reported 16 , 35 – 37 . Fatty acid levels in ACO are significantly dysregulated with an expression pattern similar to that of serum observed in these patients 19 .…”

Section: Discussionmentioning

confidence: 99%

Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease

Ghosh

Choudhury

Bhattacharyya³

et al. 2021

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 99%

Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease

Ghosh

Choudhury

Bhattacharyya³

et al. 2021

Sci Rep

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“…A few studies evaluated the effect of initiation and withdrawal of inhalation medication on breathprints. Two studies found significant changes in breathprint after start of inhalation therapy [ 44 , 50 ]. A designed multidimensional model, combining eNose technology with spirometry, gave a better indication of treatment response (AUC 0.857) than spirometry only (AUC 0.561) [ 50 ].…”

Section: Current Clinical Applicationmentioning

confidence: 99%

The smell of lung disease: a review of the current status of electronic nose technology

et al. 2021

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There is a need for timely, accurate diagnosis, and personalised management in lung diseases. Exhaled breath reflects inflammatory and metabolic processes in the human body, especially in the lungs. The analysis of exhaled breath using electronic nose (eNose) technology has gained increasing attention in the past years. This technique has great potential to be used in clinical practice as a real-time non-invasive diagnostic tool, and for monitoring disease course and therapeutic effects. To date, multiple eNoses have been developed and evaluated in clinical studies across a wide spectrum of lung diseases, mainly for diagnostic purposes. Heterogeneity in study design, analysis techniques, and differences between eNose devices currently hamper generalization and comparison of study results. Moreover, many pilot studies have been performed, while validation and implementation studies are scarce. These studies are needed before implementation in clinical practice can be realised. This review summarises the technical aspects of available eNose devices and the available evidence for clinical application of eNose technology in different lung diseases. Furthermore, recommendations for future research to pave the way for clinical implementation of eNose technology are provided.

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“…Another unique and non-invasive tool to explore inter-individual pharmacokinetic variability is exhaled breath metabolomics. Nuclear magnetic resonance-based metabolomics of exhaled breath condensate which has successfully been employed to recognize biomarkers of respiratory diseases such as asthma or chronic obstructive pulmonary disease could furthermore contribute to the individual tailoring of treatment for CF ( Montuschi et al, 2014 ; Montuschi et al, 2018 ). In order to illustrate a personalized medicine approach, clinical and genetic biomarkers need to be identified and PK/PD model that express the dynamic behaviour of the CFTR drug effect need to be developed in patients that are classified as non-/poor and normal responders ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

Insights Into Patient Variability During Ivacaftor-Lumacaftor Therapy in Cystic Fibrosis

et al. 2021

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Background: The advent of cystic fibrosis transmembrane conductance regulator protein (CFTR) modulators like ivacaftor have revolutionised the treatment of cystic fibrosis (CF). However, due to the plethora of variances in disease manifestations in CF, there are inherent challenges in unified responses under CFTR modulator treatment arising from variability in patient outcomes. The pharmacokinetic (PK) data available for ivacaftor-lumacaftor cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator drug combination is limited.Methods: Secondary objectives were to identify (1) patient characteristics and (2) the interactions between ivacaftor-lumacaftor responsible for interindividual variability (IIV).Results: Peak plasma concentrations (Cmax) of ivacaftor - lumacaftor were >10 fold lower than expected compared to label information. The one-way ANOVA indicated that the patient site had an effect on Cmax values of ivacaftor metabolites ivacaftor-M1, ivacaftor-M6, and lumacaftor (p < 0.001, p < 0.001, and p < 0.001, respectively). The Spearman’s rho test indicated that patient weight and age have an effect on the Cmax of lumacaftor (p = 0.003 and p < 0.001, respectively) and ivacaftor metabolite M1 (p = 0.020 and p < 0.001, respectively). Age (p < 0.001) was found to effect on Cmax of ivacaftor M6 and on Tmax of ivacaftor M1 (p = 0.026). A large impact of patient characteristics on the IIV of PK parameters Cmax and Tmax, was observed among the CF patients.Conclusion: Understanding the many sources of variability can help reduce this individual patient variability and ensure consistent patient outcomes.

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Metabolomic Analysis by Nuclear Magnetic Resonance Spectroscopy as a New Approach to Understanding Inflammation and Monitoring of Pharmacological Therapy in Children and Young Adults With Cystic Fibrosis

Cited by 15 publications

References 66 publications

Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease

Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease

The smell of lung disease: a review of the current status of electronic nose technology

Insights Into Patient Variability During Ivacaftor-Lumacaftor Therapy in Cystic Fibrosis

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