Activity-Rest Circadian Rhythms in COPD

1. Activity-Rest Circadian Rhythms in COPD Kristina Leyden, RN, MSN, FNP-C The University of Texas Health Science Center at Houston 6901 Bertner Avenue Houston, TX 77030 Sandra K. Hanneman, PhD, RN, FAAN Cynthia McCarley, RN, DSN Nikhil S. Padhye, PhD Michael H. Smolensky, PhD

2. Background COPD – • Airway inflammation • Progressive dyspnea • Activity intolerance (Global Strategy for the Diagnosis, 2009) Persons active during day and sleep during night - Airway tone Airway inflammation (Clark & Hetzel, 1977)

3. Increased severity of COPD=Worsening Dyspnea Worsening dyspnea = Activity intolerance Increases (Watz, Waschki, Meyer, & Magnussen, 2009)

4. What we know • Circadian pacemaker synchronizes circadian rhythms to 24 hours by activity-rest routine coupled to light-dark cycle (Ancoli-Israel, Martin, Kripke, Marler, & Klauber, 2002; Van Someren, 2000) • Alterations in circadian rhythms, including activity-rest rhythm, occur with aging (Ancoli-Israel et al., 2002; Czeisler et al., 1992; Swaab, Fliers, & Partiman, 1985; Van Someren, 2000) • COPD primarily disease in adults over age of 65 (American Lung Association, December 2007)

5. Relationships • Little known about relationships among COPD symptoms and activity-rest circadian rhythm

6. Questions • Are there circadian rhythm profiles in activity-rest in patients living at home with COPD? • What are relationships among activity-rest, dyspnea, fatigue, and lung function circadian profiles?

7. Significance • Knowledge of activity-rest circadian rhythm profile in patients with COPD may suggest times during night and day when patients would benefit optimally from pharmacological and/or non-pharmacological intervention

8. Parent Study (McCarley et al., 2007) • 10 community-dwelling older men and women with moderate to severe COPD and without history of sleep disturbances • Daily self-assessments over 8 consecutive days in the home setting • Dyspnea • Fatigue • Lung function • Study participants wore actigraph for 8-day monitoring period

9. Parent Study Results (McCarley et al., 2007) • Significant circadian rhythms (p < .05): • Dyspnea (40%) • (Visual analog scale) • Fatigue (60%) • (Visual analog scale) • Lung function (60%) • (PEFR meter)

10. Parent Study Results (cont.) • Dyspnea and fatigue moderately correlated (r = .48; p < .01) • Dyspnea and lung function significantly negatively correlated (r = -.11; p < .05) • Fatigue and lung function significantly negatively correlated (r = -.15; p < .01) (McCarley, Hanneman, Padhye, & Smolensky, 2007)

11. Aim of Secondary Analysis • To describe circadian rhythm profiles of activity-rest routines and sleep patterns in patients with COPD • In participants from the previously reported study on circadian rhythm profiles of dyspnea, fatigue, and lung function

12. Hypotheses • Variable 24-hour activity-rest pattern explains variability in circadian rhythms of: • Dyspnea • Fatigue • Lung function • Increased sleep latency, night arousals, and daytime sleep contribute to variability in circadian rhythms

13. Methods • Secondary analysis • Actigraphy data that were collected prospectively from participants enrolled in parent study • Single-group • Time series

14. Methods • Approval from University of Texas Health Science Center-Houston IRB • All participants provided written informed consent

15. Sample • 9 older adults • 10 in parent study, data available for only 9 (90%)

16. Study Participant Characteristics

17. Study Participant Characteristics • Participants reported: • Diurnal activity • Nighttime sleep • Social routine • Clinically stable • No medication change or hospitalization in 6 weeks preceding data collection

18. Instrument • Basic Mini-Motionlogger(Ambulatory Monitoring, Inc., Ardsley, NY) • Measures activity counts through piezoelectric bimorph-ceramic cantilevered beam • Senses degree of motion • Elicits voltage in response to varying magnitudes of movement • Detects movement with sensitivity of 0.003g

19. Data Collection • Actigraph programmed for 1-minute epoch lengths • Non-dominant wrist at beginning of data collection and removed at end of study • Removed only for submersion of wrist in water

20. Data Analysis • Zero-crossing method • Action4 and Action-W, version 2 software (Ambulatory Monitoring, Inc.)

21. Data Analysis (cont.) • Data sets trimmed at 8 days for consistency of comparisons across participants • Activity counts reported as: • Minimum value • Maximum value • Median • Data not normally distributed

22. Data Analysis (cont.) • Activity-rest data fit to 24-hour cosinor model • Significant activity-rest circadian rhythm defined as p<.001 with zero-amplitude test • R2 used to evaluate goodness-of-fit of data to cosinor model • Statistical significance expected due to large number of data points • R2> .10 (Higher R2, stronger fit, stronger rhythm)

23. Results

24. Activity-rest Circadian Rhythm

25. Relations Among Dyspnea, Fatigue, Lung Function, and Activity-Rest Circadian Rhythms

26. Relations Among Dyspnea, Fatigue, Lung Function, and Activity-Rest Circadian Rhythms

27. Discussion • Peak timed activity near those found by others • (Brown, et al., 1990) • Correlate with phase advance of activity levels found in older population • (Brown et al., 1990; Kripke et al., 2005; Yoon, Kripke, Youngstedt, & Elliott, 2003) • Lower mesor and higher amplitude in activity counts in this population • (Kripke et al., 2005; Van Someren, 2000)

28. Limitations • Conflicting literature on best model to analyze actigraphy-rest circadian rhythms • Single cosinor used to compare parameters with literature • 5-parameter cosinor model, with alpha (width of rhythm) and beta (steepness of curve), may better explain activity-rest pattern (Ancoli-Israel et al., 2003)

29. Limitations (cont.) • Acrophase remained relatively constant across the subjects • No diaries or activity logs used • Fully described environment

30. Contribution to gaps and recommendations • Significant, robust activity-rest circadian rhythm in 7/9 (78%) • Further studies recommended to confirm findings and compare with older community-dwelling adults without COPD • Understanding patterns for better symptom management • Administration of medication when airway tone decreased may lead to better management

31. Conclusion • Lack of circadian rhythm in pulmonary variables suggestive AR did not synchronize circadian pacemaker • Further study needed to confirm or determine mechanism for the role of AR patterns as synchronizer