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Pilot study investigating diagnostic utility of serum MMP-1 and TGF-β1 in asthma in ‘real world’ clinical practice in India
  1. Aswani Prabha1,
  2. Komarla Sundararaja Lokesh1,
  3. S K Chaya1,
  4. B S Jayaraj1,
  5. Sowmya Malamardi1,
  6. M V S S T Subbarao2,
  7. Sarah C Beck3,
  8. Mamidipudi Thirumala Krishna3,4,
  9. Padukudru Anand Mahesh1,5
  1. 1Department of Respiratory Medicine, JSS Medical College, JSS Academy of Higher Education & Research (JSSAHER), Mysore, Karnataka, India
  2. 2Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSSAHER), Mysore, Karnataka, India
  3. 3Department of Allergy and Immunology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  4. 4Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
  5. 5Special Interest Group - Environment and Respiratory Diseases, JSS Academy of Higher Education & Research (JSSAHER), Mysore, Karnataka, India
  1. Correspondence to Dr Padukudru Anand Mahesh, JSS Medical College, Mysore, Karnataka 570015, India; mahesh1971in{at}yahoo.com

Abstract

Aims At a tissue level, matrix metalloproteinase-1 (MMP-1) and transforming growth factor-beta 1 (TGF-β1) contribute to allergic airway inflammation, tissue remodelling and disease severity in asthma via different pathways. Their peripheral blood levels and role in diagnosis and therapeutic monitoring has not been adequately explored. We investigated the association between MMP-1 and TGF-β in moderate and severe persistent asthma and evaluated their performance characteristics by constructing receiver operating characteristic curves.

Methods Serum MMP-1 and TGF-β1 were measured using ELISA in 75 adults; moderate persistent asthma (n=25), severe persistent asthma (n=25) and healthy community controls (n=25). Severity of asthma was determined as per Global Initiative for Asthma guidelines. Subjects were followed up for 3 months and treatment responsiveness was assessed by spirometry and symptom response.

Results Serum MMP-1 and TGF-β1 were significantly elevated in asthmatics compared with controls (p<0.0001 and p<0.01). While serum MMP-1 was elevated in severe asthma compared with moderate asthma (p<0.05), TGF-β1 was lower in severe asthma compared with moderate asthma (p<0.05). The performance characteristics of serum MMP-1 and TGF-β1 were promising in this cohort with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 82%, 100%, 100% and 99% and 62%, 100%, 100% and 97.8%, respectively; sensitivity of MMP-1 being superior.

Conclusion This pilot study showed that serum MMP-1 and TGF-β1 levels are elevated in chronic asthma and may serve as a useful adjunct in differentiating moderate from severe asthma. A large multicentre study in well characterised cohort of asthmatics is warranted to investigate their role in diagnosis and therapeutic monitoring.

  • asthma
  • inflammation
  • cytokines
  • allergy and immunology

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Footnotes

  • Handling editor Stephen R A Jolles.

  • Contributors Study conception, design and data collection was done by PAM, AP, BSJ, KSL, SKC, MVSSTS, SM. All authors contributed towards material preparation, data analysis, drafting of manuscript and all authors have read and commented on the manuscript. All authors have read and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests MTK’s department received funding from Thermo Fisher, ALK Abello, MEDA and other pharmaceutical companies over the years for PracticAllergy course. MTK has received funds from ALK Abello to attend an international conference.

  • Patient consent for publication Not required.

  • Ethics approval The study was reviewed by the Institutional Ethics Committee (IEC) of JSS Medical College, Mysuru, India (Letter No. JSSMC/PG/4007/2017-18 dated 04 November 2017). All the study subjects were enrolled into study after informed consent process.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data is not freely available, but can be provided upon reasonable request.

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