Proteomic analysis of serum and sputum analytes distinguishes controlled and poorly controlled asthmatics

Kasaian, Marion T.; Lee, J.; Brennan, Agnes; Danto, Spencer I.; Black, Kendall E.; Fitz, Lori; Dixon, Anne E.

doi:10.1111/cea.13151

Cited by 22 publications

(21 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…35 Proteomic analysis of sputum have shown a protein profile that can differentiate symptomatic from stable asthma, primarily by neutrophil markers and extracellular matrix degradation proteins. 36 Olfactomedin-like 3 and apoptosis inhibitor-5 were among the differentially expressed proteins with increased abundance in normal compared with metaplastic epithelium irrespective of symptom control status. Apoptosis inhibitor-5 is a protein with potent anti-apoptotic signaling in tumor cells and olfactomedin-like 3 has been found to have a proangiogenic effect within the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 93%

Comparison of Normal and Metaplastic Epithelium in Patients with Stable versus Persistently Symptomatic Severe Asthma Using Laser-Capture Microdissection and Data-Independent Acquisition–Mass Spectrometry

Weitoft

Müller

Åhrman

et al. 2019

The American Journal of Pathology

View full text Add to dashboard Cite

A proportion of patients with severe asthma (SA) show poor responses to traditional asthma medications; however, it remains unknown why some patients remain persistently symptomatic. Our objective was to explore the use of laser-capture microdissection of specific epithelial structures combined with quantitative data-independent acquisition mass spectrometry to elucidate differences in protein composition in patients with SA with varying symptom control. Unbiased label-free quantitative proteome analyses were performed on laser-captureemicrodissected areas of specific epithelial structures from patients with SA with varying degrees of symptom control. A total of 1993 stable SA and 1652 symptomatic SA proteins in normal epithelium and 1458 stable SA and 1647 symptomatic SA proteins in metaplastic epithelium were quantified. When comparing proteome profiles based on symptom control, 33 proteins in patients with stable SA (!twofold change; P 0.05) and 13 proteins in patients with persistently symptomatic SA (!twofold change; P 0.05) were enriched significantly. When comparing proteome profiles based on epithelial status, 21 proteins in normal epithelium (!twofold change; P 0.05) and 6 proteins in metaplastic epithelium (!twofold change; P 0.05) were enriched significantly. New treatment strategies are needed for patients with severe asthma and exploratory studies of unbiased nature such as this may help when searching for new mechanisms and potential targets involved in the disease pathology. (Am J Pathol 2019, 189: 2358e2365; https://doi.Asthma is a chronic inflammatory airway disorder characterized by variable airflow obstruction with an increasing prevalence worldwide. 1 Severe asthma (SA) is defined by the requirement of treatment with high-dose inhaled and/or systemic corticosteroids in combination with a second longterm controller medication, and represents approximately 5% to 10% of all asthma patients. 2 In addition, a proportion of patients with SA show poor responses to traditional

show abstract

Section: Discussionmentioning

confidence: 93%

Comparison of Normal and Metaplastic Epithelium in Patients with Stable versus Persistently Symptomatic Severe Asthma Using Laser-Capture Microdissection and Data-Independent Acquisition–Mass Spectrometry

Weitoft

Müller

Åhrman

et al. 2019

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…We also identified many novel asthma-related genes not previously implicated in GWAS or EWAS. For example, high expression of AZU1 , an inflammatory mediator that regulates neutrophils, is correlated with poor asthma control [ 42 ]. Additionally, DEGS2 is involved in sphingolipid metabolism, which has been implicated in respiratory outcomes [ 43 ] including asthma [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenome-wide association study of DNA methylation and adult asthma in the Agricultural Lung Health Study

Hoang

Sikdar

et al. 2020

Eur Respir J

View full text Add to dashboard Cite

Epigenome-wide studies of methylation in children support a role for epigenetic mechanisms in asthma. Studies in adults are rare, and few have examined non-atopic asthma. We conducted the largest epigenome-wide association study of blood DNA methylation in adults in relation to non-atopic and atopic asthma.We measured DNA methylation in blood using the Illumina MethylationEPIC array among 2286 participants in a case-control study of current adult asthma nested within a U.S. agricultural cohort. Atopy was defined by serum specific immunoglobulin E. Participants were categorised as atopy without asthma (n=185), non-atopic asthma (n=673), atopic asthma (n=271), or a reference group of neither atopy nor asthma (n=1157). Analyses were conducted using logistic regression.No associations were observed with atopy without asthma. Numerous CpGs were differentially methylated in non-atopic asthma (8 at family-wise error rate [FWER] p<9×10−8; 524 at False Discovery Rate [FDR]<0.05) and implicated 382 novel genes. More CpGs were identified in atopic asthma (181 at FWER; 1086 at FDR) and implicated 569 novel genes. 104 FDR CpGs overlapped. 35% of CpGs in non-atopic asthma and 91% in atopic asthma replicated in studies of whole blood, eosinophils, airway epithelium, or nasal epithelium. Implicated genes were enriched in pathways related to the nervous system or inflammation.We identified numerous, distinct differentially methylated CpGs in non-atopic and atopic asthma. Many CpGs from blood replicated in asthma-relevant tissues. These circulating biomarkers reflect risk and sequelae of disease and implicate novel genes associated with non-atopic and atopic asthma.

show abstract

“…This has enabled us to conduct studies at places far away from specialized laboratories (15) Examination of sputum continues to be a gold standard for non-invasive studies of airway pathology. New prospects have opened up with the continuously proposed many dozens tometry and different '-omics' approaches (17)(18)(19). However for the basic needs of distinguishing the major asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap, standard cell counts are the indispensable outcome.…”

Section: Discussionmentioning

confidence: 99%

Freezing of sputum as a way to improve the applicability of sputum studies

Popov

Petlichkovski²,

Mustakov

et al. 2018

Biomedical Reviews

View full text Add to dashboard Cite

Rationale: within 2 hours of their collection poses limitations to its wider applicability. A way to bypass this hurdle would be to freeze the sample at the time of collection and to examine it at a later stage. Methods and Subjects: We developed a protocol for freezing of sputum upon collection by adding dimethylsulfoxide to it. We tested the reproducibility of cell counts in frozen samples and in fresh portions from the same sputum specimens. We took sputum from 41 asthmatics (18 males) with different levels of control of their disease: 19 of the samples were spontaneously produced and 22 were induced with hypertonic saline. Results: neutrophils, eosinophils and macrophages in the paired fresh and frozen sputum samples. Cell viability in frozen sputum was had better reproducibility than the spontaneous ones. Conclusion: Examination of frozen sputum samples does not change total cell counts and differential cell counts, despite conbut one examined specimens.

show abstract

Proteomic analysis of serum and sputum analytes distinguishes controlled and poorly controlled asthmatics

Abstract: Proteomic profiles in serum and sputum distinguished controlled and poorly controlled asthmatics, and were maintained over time. Findings support a link between sputum neutrophil markers and loss of asthma control.

Cited by 22 publications

References 45 publications

Comparison of Normal and Metaplastic Epithelium in Patients with Stable versus Persistently Symptomatic Severe Asthma Using Laser-Capture Microdissection and Data-Independent Acquisition–Mass Spectrometry

Comparison of Normal and Metaplastic Epithelium in Patients with Stable versus Persistently Symptomatic Severe Asthma Using Laser-Capture Microdissection and Data-Independent Acquisition–Mass Spectrometry

Epigenome-wide association study of DNA methylation and adult asthma in the Agricultural Lung Health Study

Freezing of sputum as a way to improve the applicability of sputum studies

Contact Info

Product

Resources

About