Chronic obstructive pulmonary disease (COPD) inflammatory subtypes: an interview with Dr Vanessa McDonald, University of Newcastle, Australia

Vanessa McDonald ARTICLE IMAGE

Please could you give an introduction to chronic obstructive pulmonary disease (COPD)?

COPD is defined as a preventable and treatable disease associated with significant extrapulmonary consequences that may contribute to severity.

The pulmonary component of COPD is characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive with an abnormal inflammatory response of the lungs to noxious particles (GOLD Strategy Document). Airflow obstruction in COPD is not highly variable and largely irreversible.

COPD can be characterised pathologically by emphysema, chronic bronchitis and bronchiolitis or the coexistence of these conditions.

The airflow limitation is caused by damage to the small airways as a result of the airway inflammation by remodelling seen in chronic bronchitis and by parenchymal destruction as a result of loss of alveolar attachments and decrease in elastic recoil, the features of emphysema.

For the patient these pathological changes result in the characteristic symptoms of progressive dyspnea, cough and sputum production.

What is known about the causes of COPD?

The most common cause of COPD is cigarette smoking, however infection and occupation and environmental exposures may also play a role in the development of the disease.

How many people suffer from COPD?

COPD is a common condition associated with a significant disease burden in Australia and worldwide(1, 2).

COPD is now Australia’s 4th leading cause of mortality and 3rd leading cause of disease burden(3) and by 2020 it is predicted that COPD will emerge as the 3rd leading cause of death and 5th leading cause of disability worldwide(4, 5).

Of all Australians over 40 years, moderate to severe COPD affects 7.5%, and the prevalence rises rapidly with increasing age; 29% of Australians over 75 have COPD(6).

Why is COPD a leading cause of hospital admissions?

Patients are usually admitted to hospital with an acute exacerbation of COPD; this is a common occurrence in people who have COPD and all people with COPD are at risk.

The frequency of exacerbation is associated with poor disease trajectory with an accelerated decline in lung function(7) and in health status(8), and increased mortality(9).

Furthermore recent evidence indicates that exacerbations cluster together in time and that after one exacerbation patients are at a heightened risk of a second(10).

Underreporting of exacerbations is common as is delayed management and these factors lead to hospitalisation.

You have recently received a Ramaciotti Establishment Grant to study inflammatory phenotypes in COPD. What is currently known about the different inflammatory subtypes of COPD?

Airway and systemic inflammation in COPD is both common and heterogeneous, and since any one person can exhibit more than one inflammatory process, any individual may require more than one therapeutic approach(11).

For example, targeting neutrophilic inflammation alone will treat 57% of people with COPD.(12) Targeting eosinophilic inflammation will treat a further 34%, and targeting systemic inflammation will manage this problem in 59% of the COPD group.

In COPD neutrophilic inflammation is thought to be typical. However there is now increasing recognition of the heterogeneity of airway inflammation in COPD.

Please could you describe how you plan to use the Ramaciotti Establishment Grant?

The funding from the Ramaciotti Establishment grant will be used to support a laboratory technical officer to provide sample analysis in a randomised controlled trial of inflammometry guided treatment in patients with COPD.

We will conduct a double blind, parallel group randomised controlled trial with participants with stable COPD. The study aims to determine the efficacy of an inflammometry treatment algorithm in the management of COPD, on the outcomes of quality of life and COPD exacerbations, and to determine the responsiveness of a panel of serum biomarkers to inflammometry based treatment in COPD.

What impact do you think this research will have?

This study will test a new and clinically feasible approach to the management of COPD. It has the potential to lead to major improvements in health status and to significantly reduce exacerbations.

A positive trial will provide a rational method to manage the multiple disease components of COPD, leading to reduced health care burden and improved treatment guidelines for COPD.

Furthermore this study will define the role of serum biomarkers in the assessment and management of COPD, the translation of a simple blood biomarker into clinical practice will significantly advance COPD management for primary and tertiary care providers and patients.

These are highly relevant clinical issues due to the impact of COPD on patients and the health care system. We will publish these results in international respiratory or medicine journals and will translate the evidence by informing clinical practice guidelines for COPD.

Would you like to make any further comments?

I would like to take that opportunity to thank the Ramaciotti Foundation for their generous support not only for the benefit of my research but for their ongoing support of early career biomedical researcher in Australia.

Where can readers find more information?

For further information on the Ramaciotti Awards: http://www.perpetual.com.au/ramaciotti/

About Dr Vanessa McDonald

Vanessa McDonald BIG IMAGEDoctor Vanessa McDonald is a senior lecturer in the School of Nursing and Midwifery and holds a Conjoint Senior Lecturer appointment in the School of Medicine and Public Health. Vanessa is a post-doctoral fellow in the HMRI’s VIVA programme and the Priority Research Centre for Asthma and Respiratory Disease.

Biography - Vanessa was awarded her PhD in February 2011. During her candidature she advanced a new project area of immense importance to patients and clinicians alike. She developed a novel multidimensional assessment to comprehensively describe the symptoms, pathology, psychological status, educational and self-management needs of older people with obstructive airway diseases (OAD) and designed a treatment approach that significantly improved health status and biological outcomes. During her PhD Vanessa was supported with an NHMRC Centre for Respiratory and Sleep Medicine PhD Scholarship. She also received several other competitive PhD scholarships to support her work; these included the Cooperative Research Centre (CRC) for asthma and airways PhD scholarship, the University of Newcastle’s Barker PhD award and the HMRI PhD support grant. Vanessa is now continuing to build a research programme in respiratory medicine. Her ongoing work investigates the management of obstructive airway diseases including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Vanessa has also sought training in evidence based medicine as a Cochrane systematic review author.

Despite having only very recently been awarded her PhD, she has already established a track record as an early career researcher. To date she has published over 27 peer reviewed journal articles ( over 50% as first author), two book chapters (first author), an economic impact national report, multimedia resources, 60 peer reviewed abstracts from national and international meetings, and national patient education publications. She has published in high impact journals including the Lancet, the AJRCCM and the European Respiratory Journal.

As an early career researcher she has also established a successful track record in grant funding from a number of different sources including the NHMRC (APP1045230 - $717,071) and the Ramaciotti Foundation. She has obtained project or equipment grants totaling over $125,0000, of these she is the CIA on over 75% of the successful applications.

Leadership – Vanessa has successfully developed a national reputation in respiratory research and education. She is a representative on several peak bodies including The Australian Lung Foundations (ALF) National COPD Coordinating Committee. She is Deputy Convenor of the TSANZ COPD special interest group and a member of the TSANZ Research Subcommittee. Vanessa is a consultant and working party member to redevelop the 2012 Australian Asthma Management Handbook and was a representative on the working party which developed the national guidelines for the management of COPD [COPD-X]. She is regularly invited to speak at national and state meetings. Vanessa regularly acts as a reviewer for several international journals including the European Respiratory Journal, Thorax, Respiratory Medicine and Cochrane.

References

  1. Access Economics, Allan H, Clift B, Crockett A, Darbishire W, Frith P, et al. Economic impact of COPD and cost effective solutions. Brisbane: The Australian Lung Foundation, 2008.
  2. Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global Strategy for the Diagnosis, Management, and Prevention of COPD 2006 Update Am J Respir Crit Care Med 2007;176:532-55.
  3. Mathers C VT, Stephenson C. The Burden of Disease and Injury in Australia. ISBN 1-74024-019-7. AIWH Cat. No. PHE-17 1999.
  4. Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 1997;349 1269–76.
  5. Michaud CM, Murray CJ, Bloom BR. Burden of disease – implications for future research. JAMA 2001;285:535–39.
  6. Toelle BG, Xuan W, Bird TE. Respiratory symptoms and illness in older Australians: the Burden of Obstructive Lung Disease (BOLD) study. MJA 2013;198:144-48.
  7. Kanner RE, Anthonisen NR, Connett JE, Lung Health Study Research Group. Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study. Am J Respir Crit Care Med 2001;164:358-64.
  8. Seemungal TA, Donaldson GC, Paul EA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1418-22.
  9. Soler-Cataluna J, Martinez-Garcia M, Roman Sanchez P, et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:925-31.
  10. Hurst JR, Donaldson GC, Quint JK, et al. Temporal clustering of exacerbations in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009;179(5):369-74.
  11. McDonald VM, Higgins I, Wood LG, Gibson PG. Multidimensional assessment and tailored interventions for COPD. Thorax 2012;Revisions Invited September 2012.
  12. McDonald VM, Simpson JL, Higgins I, Gibson PG. Multidimensional Assessment of Older People with Asthma & COPD: Clinical Management and Health Status. Age Ageing 2011;40(1):42-49.
April Cashin-Garbutt

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April Cashin-Garbutt

April graduated with a first-class honours degree in Natural Sciences from Pembroke College, University of Cambridge. During her time as Editor-in-Chief, News-Medical (2012-2017), she kickstarted the content production process and helped to grow the website readership to over 60 million visitors per year. Through interviewing global thought leaders in medicine and life sciences, including Nobel laureates, April developed a passion for neuroscience and now works at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour, located within UCL.

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