# Exercise as it relates to Disease/HIIT - a new method for improving exercise capacity in adults with Cystic Fibrosis

This is a critique of the article by Wolfgang Gruber, David Orenstein, Klaus Braumann and Ralph Beneke; Interval exercise training in Cystic Fibrosis - effects on exercise capacity in severely affected adults, from the Journal of Cystic Fibrosis. This is written for assessment in the Health, Disease and Exercise unit at the University of Canberra.

## What is the background to this research?

Cystic Fibrosis (CF) is a chronic autosomal disease affecting approximately 3500 people in Australia. Many bodily systems are impacted, however the lungs are the major factor limiting exercise tolerance. Previous research, mainly focused on low to moderate intensity aerobic exercise, demonstrated the importance of physical activity and exercise in slowing disease progression and reducing disease severity. Gruber investigated whether high intensity interval training (HIIT) was a reasonable alternative, and if it produced worthwhile adaptations compared to standard low to moderate intensity exercise programs (SEP) for individuals severely affected with CF.
HIIT combines vigorous bursts of activity with periods of low intensity or passive recovery. Small volumes of HIIT induce changes similar to that seen in longer bouts of endurance training. Adaptations have been recorded in healthy and some diseased populations, however little research has been done in individuals with CF, particularly in adults. HIIT is proposed to be a better alternative for these individuals than prolonged lower intensity activities as it produces similar adaptations in less time. In a case study of an adolescent, HIIT improved exercise tolerance and capacity, and aided in mucus clearance. This study hoped to see similar results in adult participants. HIIT research in individuals with CF is important in enabling everyone to participate in exercise and acquire adaptations.

## Where is the research from?

Lead authors, Gruber and Orenstein, have extensive backgrounds in researching CF with some focus on exercise, particularly by Gruber. The two authors combined have over 150 publications on CF, and therefore a wide knowledge of the field. Studies by Orenstein and Gruber have been cited over 5000 and 200 times respectively in journal publications, indicating good credibility with other researchers.

## What kind of research was this?

The study was a quasi-randomised control trial, involving 43 adults severely affected by CF, who volunteered for the 6-week study. Participants were split into the HIIT and SEP groups via a specific selection criteria regarding oxygen saturation (SpO$_2$) levels. Participants with low SpO$_2$ at rest or low power outputs were put into the HIIT group, and those with higher SpO$_2$ were placed in the SEP group. As a result, improvements in the HIIT group could be impacted, as participants may be unable to exercise, or continue exercising, at the high intensities needed to produce adaptations. This could skew the results in favour of the SEP group.
Quasi-random sampling techniques have implications for suggesting causation in research as there is less control over the independent variable, potential selection bias and a lack of internal validity. Selection bias may be present with the SpO$_2$ criteria, which could affect the reliability of the results.

## What did the research involve?

| | HIIT Group | SEP Group |
| Activity | Treadmill walking at 3-4 km/h | Various activities including resistance training and ball games |
| Duration | 16 minutes | 45 minutes |
| Frequency | 5 days/week | 5 days/week |
| Intensity | 20-30 second high-intensity intervals (by adjusting treadmill grade) | Low-moderate |
| Rest | 60 seconds active recovery | Unknown |
It is unknown whether participants in the SEP group completed the same exercises, and the specific exercises included. More detail is needed to increase the reliability of the results.
The HIIT group were given supplemental oxygen during exercise, which has implications for the real world applications of this research. Supplemental oxygen may not be available for all individuals during exercise, therefore the positive adaptations may be unattainable. An additional study in less severe cases without supplemental oxygen may be required to determine if this is possible.

## What were the basic results?

Results showed significant increases in maximal and sub-maximal VO$_2$, power and O$_2$-pulse. Adaptations from the HIIT program were largest during sub-maximal exercise, with a 24.4% increase in VO$_2$, compared with a 12.4% increase from the SEP. During maximal exercise, increases in VO$_{2peak}$ were larger in the SEP group than the HIIT group, with 15.5% and 12.0% improvements respectively. However, increases in O$_2$-pulse were greater in the SEP for both maximal and sub-maximal exercise by 6.6% and 5.0% respectively. No improvements in lung function were recorded for either group.
Table 1: Percentage increase of exercise parameters from test one to test two in the HIIT and SEP groups
| Intensity | Exercise Parameters | HIIT group | SEP group |
| Maximal | VO$_{2PEAK}$ (mL/kg/min) | 12.0% | 15.5% |
| Maximal | Power$_{PEAK}$ (Watt) | 19.5% | 16.1% |
| Maximal | O$_2$-pulse$_{PEAK}$ (mL/beat) | 8.5% | 15.1% |
| Sub-maximal | VO$_2$ (mL/kg/min) | 24.4% | 12.4% |
| Sub-maximal | Power (Watt) | 19.3% | 18.6% |
| Sub-maximal | O$_2$-pulse (mL/beat) | 10.8% | 15.8% |
The authors reported individuals felt HIIT was less strenuous than the SEP, however, it was not stated how this was measured. These participants also only completed the HIIT program, and cannot accurately compare its difficulty to the SEP.

## What conclusions can we take from this research?

This research showed that HIIT induced cardiorespiratory adaptations in individuals with severe CF. HIIT was more effective for adaptations at sub-maximal intensity, and may be less appropriate for adaptations at maximal intensity. O$_2$-pulse showed a greater increase in the SEP group at both intensities, indicating improvement in the hearts ability to pump blood and oxygen. This is likely due to a strengthening of the heart muscle from the aerobic-based activity. There was less of an improvement in the HIIT group. Unfortunately, neither program significantly improved lung function or mucus clearance. Ultimately, both exercise programs provided beneficial adaptations and could be implemented to improve exercise capacity for individuals with CF. Research to compare these further and distinguish if either is more advantageous would be beneficial.
This study paved the way for other researchers to investigate further. A randomised control trial (RCT) by Sawyer in 2020 supported these findings, showing similar improvements in cardiorespiratory fitness after 8-weeks of low-volume HIIT. Sawyer reported the exercise was tolerated well without supplemental oxygen. Additional information provided by recent studies have made the introduction of HIIT into CF exercise programs more feasible.

## Practical advice

Knowledge of HIIT for CF is continually evolving with new research, however, there are still many gaps. Determining the mechanisms and effectiveness of HIIT programs for CF, whilst building on previous research is important in further understanding this field. Perhaps future research could compare adaptations produced by HIIT and resistance training; or HIIT and another form on anaerobic exercise. In addition, studies comparing variations of HIIT could determine what type provides more beneficial adaptations. This could include comparing different durations, types of HIIT activities (cycling vs running) and frequency. There are many avenues for continued research; studies now have only scratched the surface.

## Further information/resources

2020 HIIT and CF, RCT: https://link.springer.com/article/10.1186/s13102-020-0159-z
2020 HIIT and CF, case study: https://www.sciencedirect.com/science/article/pii/S2213007120303877

## References

* 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1. Gruber W, Orenstein DM, Braumann KM, Beneke R. Interval exercise training in cystic fibrosis—effects on exercise capacity in severely affected adults. J. Cyst. Fibros [Internet]. 2014 Jan [cited 2021 Aug 26];13(1):86-91. Available from: https://www.sciencedirect.com/science/article/pii/S1569199313001100
* ↑ Better health [Internet]. Victoria: Victoria State Governmnent; 2019. Cystic fibrosis (CF); 2019 Apr 16 [cited 2021 Aug 31]; [about 7 screens]. Available from: https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/cystic-fibrosis-cf#frequency-of-cystic-fibrosis
* 1 2 Radtke T, Nevitt SJ, Hebestreit H, Kriemler S. Physical exercise training for cystic fibrosis. Cochrane Database Syst. Rev [Internet]. 2017 Nov 1 [cited 2021 Aug 26](11). Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002768.pub4/abstract
* ↑ Moorcroft A, Dodd M, et al. Individualised unsupervised exercise training in adults with cystic fibrosis: a 1 year randomised controlled trial. Thorax [Internet]. 2004 [cited 2021 Aug 26];59(12):1074-80. Available from: https://thorax.bmj.com/content/59/12/1074.short
* 1 2 3 Gibala MJ, Little JP, et al. Physiological adaptations to low‐volume, high‐intensity interval training in health and disease. J. Physiol [Internet]. 2012 Jan 30 [cited 2021 Aug 31];590(5):1077-84. Available from: https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/jphysiol.2011.224725
* ↑ Hulzebos H, Snieder H, van der Et J, Helders P, Takken T. High-intensity interval training in an adolescent with cystic fibrosis: a physiological perspective. Physiother. Theory Pract [Internet]. 2011 [cited 2021 Sep 8];27(3):231-7. Available from: https://www.tandfonline.com/doi/full/10.3109/09593985.2010.483266
* 1 2 3 ResearchGate [Internet]. Unknown: ResearchGate; 2021. Wolfgang Gruber; 2021 [cited 2021 Aug 31]; [about 10 screens]. Available from: https://www.researchgate.net/profile/Wolfgang-Gruber
* 1 2 3 ResearchGate [Internet]. Unknown: ResearchGate; 2021. David Orenstein; 2021 [cited 2021 Aug 31]; [about 10 screens]. Available from: https://www.researchgate.net/profile/David-Orenstein-2
* 1 2 Sawyer A, Cavalheri V, et al. High-Intensity Interval Training Is Effective at Increasing Exercise Endurance Capacity and Is Well Tolerated by Adults with Cystic Fibrosis. J. Clin. Med [Internet]. 2020 Sep 25 [cited 2021 Aug 31];9(10):3098. Available from: https://www.mdpi.com/2077-0383/9/10/3098