Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary disease

Singh, Brajesh Kumar; Jana, Saikat Kumar; Ghosh, Nilanjana; Das, Soumen; Bhattacharyya, Parthasarathi; Chaudhury, Koel

doi:10.1016/j.jpba.2016.09.034

Cited by 18 publications

(20 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The levels of sphingosine, sphingosine 1-phosphate, and lysophospholipids, biomarkers of lung tissue regeneration [19], were normalized after liver growth factor treatment in emphysema patients [20]. Another metabolomic study indicated doxycycline coupled with standard therapy might improve inflammatory response by downregulating the levels of fatty acids and lactate in COPD patients more significantly, compared to standard treatment alone [21].…”

Section: Copd-associated Biomarkers In Different Sample Types and mentioning

confidence: 99%

An Updated Overview of Metabolomic Profile Changes in Chronic Obstructive Pulmonary Disease

Ran

Pang

et al. 2019

Metabolites

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD), a common and heterogeneous respiratory disease, is characterized by persistent and incompletely reversible airflow limitation. Metabolomics is applied to analyze the difference of metabolic profile based on the low-molecular-weight metabolites (<1 kDa). Emerging metabolomic analysis may provide insights into the pathogenesis and diagnosis of COPD. This review aims to summarize the alteration of metabolites in blood/serum/plasma, urine, exhaled breath condensate, lung tissue samples, etc. from COPD individuals, thereby uncovering the potential pathogenesis of COPD according to the perturbed metabolic pathways. Metabolomic researches have indicated that the dysfunctions of amino acid metabolism, lipid metabolism, energy production pathways, and the imbalance of oxidations and antioxidations might lead to local and systematic inflammation by activating the Nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway and releasing inflammatory cytokines, like interleutin-6 (IL-6), tumor necrosis factor-α, and IL-8. In addition, they might cause protein malnutrition and oxidative stress and contribute to the development and exacerbation of COPD.

show abstract

Section: Copd-associated Biomarkers In Different Sample Types and mentioning

confidence: 99%

An Updated Overview of Metabolomic Profile Changes in Chronic Obstructive Pulmonary Disease

Ran

Pang

et al. 2019

Metabolites

View full text Add to dashboard Cite

show abstract

“…These findings in sputum are consistent with the lower serum spermine levels at resolution of exacerbation seen here. Changes in polyamines are not specific to CF as enhanced arginine synthesis/availability was seen in patients with COPD after addition of doxycycline as an anti-inflammatory agent [ 58 ]. Lower polyamine levels at resolution of CF exacerbation may be also related to lower cell proliferation rates and decreased oxidative stress as polyamines are elevated in diseases with increased cell turn-over e.g.…”

Section: Resultsmentioning

confidence: 99%

Metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation

et al. 2019

View full text Add to dashboard Cite

Background Cystic fibrosis lung disease is characterized by chronic bacterial infections in the setting of mucus abnormalities. Patients experience periodic exacerbations that manifest with increased respiratory symptoms that require intensification of therapy with enhanced airway clearance and intravenous (IV) antibiotics. Objectives In an observational study we tested if the profile of metabolites in serum distinguished the pre-from post-exacerbation state and which systemically measurable pathways were affected during the process to recovery. Methods Serum collected within 48 h of start and completion, respectively of IV antibiotics was collected from people with CF ages 6–30 years. Three day food records were collected prior to each sample. To reduce variation between subjects only subjects who had pancreatic insufficiency, had similar CF mutations, and did not have CF liver disease or diabetes were included. Metabolomic profiling was conducted by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy with metabolites being identified based on retention time/index, mass to charge ratio and comparison to known compounds. Biostatistical analyses used paired t -test with correction for multiple comparisons and orthogonal partial least square discriminant analysis. Results Thirty subjects (20 male) with a mean ± SEM age of 15.3 ± 1.2 years participated, 17 of whom had matched food-records. Lung function was significantly improved post-therapy compared to pre-therapy, (mean ± SEM) 75 ± 4% vs. 68 ± 4% predicted (n = 26). Serum metabonomics showed distinction of the pre-vs. post-therapy groups with 123 compounds contributing to the differentiation pre-versus post-antibiotics by multiple biostatistical analyses. Compounds and pathways affected included bile acids and microbial derived amino acid metabolites, increases in lipid classes of the glycerophospholipid, glycerolipids, cholesterol, phopsholipids, and most pronounced, the class of sphingolipids. Changes in n6/n3 fatty acids, decreased polyamines but increased metabolites in the nitric oxide pathway, and changes in the tryptophan-kynurenine pathway indicated decreased inflammation at resolution of exacerbation. Conclusions Changes in serum metabolites that distinguished CF pulmonary exacerbation vs. resolution of symptoms showed evidence of decreased inflammation and improvement from a catabolic state.

show abstract

“…Metabolomics may have several potential roles in COPD pharmacogenomics research, beyond increasing our understanding of disease mechanisms, pathways, and drug targets. Metabolomics studies may identify biomarkers predictive of drug response or demonstrate drug effects through analysis of downstream metabolites [98]. Since commonly used metabolomics panels measure levels of multiple xenobiotic molecules including some medications, these large studies may provide the ability to assess inter-individual variation in drug levels, which could be integrated with genetic data for consideration as a pharmacogenomics phenotype.…”

Section: Other Omics Technologies In Copd Pharmacogenomicsmentioning

confidence: 99%

Pharmacogenomics of chronic obstructive pulmonary disease

Hersh

2019

Expert Review of Respiratory Medicine

View full text Add to dashboard Cite

Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, which presents the opportunity for precision therapy based on genetics or other biomarkers. Areas covered: Alpha-1 antitrypsin deficiency, a genetic form of emphysema, provides an example of this precision approach to diagnosis and therapy. To date, research in COPD pharmacogenomics has been limited by small sample sizes, lack of accessible target tissue, failure to consider COPD subtypes, and different outcomes relevant for various medications. There have been several published genome-wide association studies and other omics studies in COPD pharmacogenomics; however, clinical implementation remains far away. There is a growing evidence base for precision prescription of inhaled corticosteroids in COPD, based on clinical phenotypes and blood biomarkers, but not yet based on pharmacogenomics. Expert opinion: At this time, there is insufficient evidence for clinical implementation of COPD pharmacogenomics. Additional genome-wide studies will be required to discover predictors of drug response and to identify genomic biomarkers of COPD subtypes, which could be targeted with subtype-directed therapies.

show abstract

Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary disease

Cited by 18 publications

References 29 publications

An Updated Overview of Metabolomic Profile Changes in Chronic Obstructive Pulmonary Disease

An Updated Overview of Metabolomic Profile Changes in Chronic Obstructive Pulmonary Disease

Metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation

Pharmacogenomics of chronic obstructive pulmonary disease

Contact Info

Product

Resources

About