# Exercise as it relates to Disease/Changes in Pulmonary Exercise Haemodynamics in Scleroderma

This is a critical analysis of the article "Changes in pulmonary exercise haemodynamics in scleroderma: a 4-year prospective study" by Gabor Kovacs, Alexander Avian, Nora Wutte, Franz Hafner, Florentine Moazedi-Fürst, Sonja Kielhauser, Elisabeth Aberer, Marianne Brodmann, Winfried Graninger, Vasile Foris, Andrea Olschewski and Horst Olschewski.

## Background

Scleroderma is an autoimmune disease which causes a thickening and tightening of a variety of soft tissues, there are different classifications based on how the body is affected. These classifications are broadly broken into limited and systemic scleroderma. Limited scleroderma mainly effects the skin of the extremities, causing limited movement and poor circulation. Systemic scleroderma (SSc) additionally affects the underlying soft tissues, including main organs such as the heart, lungs, and gastrointestinal tract. Because of the nature of SSc, it causes serious complications which are often not diagnosed until after death. Most SSc patients have a survival rate of up to 5 years from diagnosis; 14% of all deaths are caused by pulmonary arterial hypertension (PAH), with 87% of all deaths attributed to scleroderma caused by heart complications. Until recently there have been limited screening processes to detect possible PAH in SSc patients. However, techniques with increased sensitivity have been developed with the potential to detect abnormalities in cardiac function which can cause serious health issues, even death. Early diagnosis of cardiac involvement in SSc patients is important as it can lead to better therapy responses and may prevent life threatening complications for many years. The article "Changes in pulmonary exercise haemodynamics in scleroderma: a 4-year prospective study" is an important step in research as it looks at using exercise and non-invasive ways to screen for PAH.

## Where is this research from?

"Changes in pulmonary exercise haemodynamics in scleroderma: a 4-year prospective study" was conducted by Gabor Kovacs et al. and included in the European Respiratory Journal (ERJ), which was published online on the 13th of July 2017. The ERJ is the lead scientific journal of the European Respiratory Society (ERS) and publishes a wide array of reliable up to date, high quality peer reviewed articles and research.
The authors of this study have a wide variety of expertise in numerous disciplines such as pulmonology, statistics, angiology, rheumatology, and physiology. They are affiliated the Medical University of Graz, Graz, Austria and the Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.

## What kind of research was this?

The research is a 4-year prospective cohort study which is longitudinal in design, which provides information about the relationship between exposure and outcome. Prospective cohort studies have several advantages over other types of observational studies and are considered the gold standard within this area of study. When considering other forms of research designs such as meta-analysis and systematic reviews, prospective cohort studies sit in the middle.

## What did the research involve?

The research involved studying a sample of 99 individuals with systemic scleroderma to look for pulmonary arterial hypertension (PAH). Prior to commencing the study, written consent was obtained and the study was conducted in line with the Helsinki Declaration.These individuals had previously been screened and participated if they were determined not to have any pre-existing diagnosis of any heart conditions. Baseline rest and exercise data that looked at systolic pulmonary arterial pressure (sPAP), peak oxygen uptake, mean pulmonary arterial pressure, and heart rate was collected using exercise echocardiography, cardiopulmonary exercise testing and in a subgroup right heart catheter (RHC) insertion. The patients from this study where then followed up 4 years later on average, at this point data was collected again. To collect the exercise induced responses all patients were asked to perform a symptom-limited cardiopulmonary exercise test on a variable-load, half-recumbent, left sloping echocardiography cycle ergometer using a standard protocol with a 25 watt increment increase every 2 minutes.

## What were the basic results?

The results showed that scleroderma patients without previously diagnosed cardiac diseases developed a mild but significant deterioration of pulmonary exercise haemodynamics and exercise capacity over a 4-year period indicating a progression of pulmonary vascular disease. Three out of the 99 patients developed RHC-confirmed PAH, however 41 patients did not complete the study. Exercise testing results showed that systemic pulmonary arterial pressure at 50 watts (sPAP50) increased, mean pulmonary vascular resistance increased significantly as well, indicating a possible stiffening of the pulmonary arteries which have been shown to be a predictor of PAH and is associated with decreased exercise capacity and poorer outcomes. There were significant decreases in peak oxygen uptake demonstrate a decrease in exercise capacity. At rest there was no significant change in resting systemic pulmonary arterial pressure or mean pulmonary vascular resistance, indicating that exercise can induce symptoms of pulmonary arterial pressure and a change in pulmonary haemodynamics earlier than at rest.

## What conclusions can we take from this research?

The study found that exercise induced pulmonary haemodynamics can be important for recognising pulmonary vascular disease in SSc. Currently RHC insertions represent the most reliable method to assess pulmonary haemodynamics, however this procedure is invasive and cannot be performed in a healthy population for ethical reasons. This study suggests that echocardiography, could be a reliable method to assess pulmonary haemodynamics in scleroderma patients. It cannot be assumed that echocardiography is a reliable and valid tool in determining rest and exercise pulmonary haemodynamics outside of this study. Additional research is required to attempt minimise some of the limitations of the study such as using a small sample size, loss to follow up, heavy presence of selection bias and enriching of the sample with healthier patients, the lack of a healthy control group and possible interference from medicines prescribed outside of the study.

## Practical advice

Using echocardiography as a screening tool can pick up on exercise pulmonary haemodynamics, and pulmonary arterial pressure which can indicate possible pulmonary arterial hypertension and the need to perform an RHC insertion. Further research could indicate the ability of using echocardiography as a diagnostic tool. New research should look at considering a broader population of SSc patients, the use of immunosuppressive medications and a healthy control group would benefit research on the use of non-invasive exercise induced PAH testing measures on SSc patients.

## Further information and resources

For further support and information on scleroderma please look at the following links:
Organisations and helpful information:
* https://sclerodermainfo.org/guide/
* https://www.scleroderma.org/site/SPageNavigator/patients_whatis.html
* https://www.hopkinsscleroderma.org/scleroderma/frequently-asked-questions/
* https://www.sclerodermaaustralia.com.au/
General information on exercising with scleroderma:
* https://www.hospitalhealth.com.au/content/aged-allied-health/article/is-it-safe-to-exercise-with-scleroderma--850099346#axzz6YAhsZ4lD
* https://www.selfmanagescleroderma.com/lessons/exercise-guidelines-for-general-fitness.html
* https://www.scleroderma.org/site/DocServer/Form_16c_low_res.pdf?docID=19809&AddInterest=1281

## References

* 1 2 3 4 CALLEJAS-RUBIO JL, MORENO-ESCOBAR E, de la FUENTE PM, PÉREZ LL, FERNÁNDEZ RR, SÁNCHEZ-CANO D, et al. Prevalence of Exercise Pulmonary Arterial Hypertension in Scleroderma. The Journal of Rheumatology. 2008;35(9):1812-6.
* 1 2 3 4 5 Krieg T, Meurer M. Systemic scleroderma: clinical and pathophysiologic aspects. Journal of the American Academy of Dermatology. 1988;18(3):457-81.
* 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Kovacs G, Avian A, Wutte N, Hafner F, Moazedi-Fürst F, Kielhauser S, et al. Changes in pulmonary exercise haemodynamics in scleroderma: a 4-year prospective study. European Respiratory Journal. 2017;50(1):1601708.
* ↑ Tyndall AJ, Bannert B, Vonk M, Airò P, Cozzi F, Carreira PE, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Annals of the Rheumatic Diseases. 2010;69(10):1809-15.
* ↑ Simonds AK, Reeves EL. ERJ Open Research: FAQs. European Respiratory Journal. 2015;46(2):318-20.
* 1 2 3 Hammoudeh S, Gadelhaq W, Janahi I. Prospective cohort studies in medical research. Cohort studies in health sciences Chile: IntechOpen. 2018:11-28.