Activity-Rest Circadian Rhythms in COPD

Kristina Leyden, RN, MSN, FNP-CThe University of Texas Health Science Center at Houston 6901 Bertner AvenueHouston, TX 77030Sandra K. Hanneman, PhD, RN, FAANCynthia McCarley, RN, DSNNikhil S. Padhye, PhDMichael H. Smolensky, PhD

Background

COPD – Airway inflammationProgressive dyspneaActivity intolerance

(Global Strategy for the Diagnosis, 2009)

Persons active during day and sleep during night -Airway tone Airway inflammation

(Clark & Hetzel, 1977)

Increased severity of COPD=Worsening Dyspnea

Worsening dyspnea = Activity intolerance Increases

(Watz, Waschki, Meyer, & Magnussen, 2009)

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)

Relationships

Little known about relationships among COPD symptoms and activity-rest circadian rhythm

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?

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

Parent Study (McCarley et al., 2007)

10 community-dwelling older men and women with moderate to severe COPD and without history of sleep disturbancesDaily self-assessments over 8 consecutive days in the home setting

DyspneaFatigueLung function

Study participants wore actigraph for 8-day monitoring period

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)

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)

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

Hypotheses

1. Variable 24-hour activity-rest pattern explains variability in circadian rhythms of:

a. Dyspneab. Fatiguec. Lung function

2. Increased sleep latency, night arousals, and daytime sleep contribute to variability in circadian rhythms

Methods

Secondary analysisActigraphy data that were collected prospectively from participants enrolled in parent study

Single-groupTime series

Methods

Approval from University of Texas Health Science Center-Houston IRBAll participants provided written informed consent

Sample

9 older adults10 in parent study, data available for only 9 (90%)

Study Participant CharacteristicsCharacteristics of the Study Participants (N=9)

ParticipantAge in Years Gender

Home O2 Use Study dates

1 64 F 24 HR 11/01/02-11/09/02

2 79 F 24 HR 06/19/02-06/28/02

3 64 F NO 07/25/02-08/02/02

4 61 F NO 11/18/02-11/27/02

5 77 F SLEEP 01/23/03-02/01/03

6 57 M SLEEP 01/24/03-02/01/03

7 81 M NO 01/27/03-02/09/03

8 77 M 24 HR 02/21/03-03/01/03

9 64 F SLEEP 03/02/03-03/10/03

Mean+SD* 69+9     

*SD, Standard Deviation; 02, Oxygen

Study Participant Characteristics

Participants reported:Diurnal activityNighttime sleepSocial routineClinically stable

No medication change or hospitalization in 6 weeks preceding data collection

Instrument

Basic Mini-Motionlogger (Ambulatory Monitoring, Inc., Ardsley, NY)

Measures activity counts through piezoelectric bimorph-ceramic cantilevered beam Senses degree of motionElicits voltage in response to varying magnitudes of movementDetects movement with sensitivity of 0.003g

Data Collection

Actigraph programmed for 1-minute epoch lengthsNon-dominant wrist at beginning of data collection and removed at end of studyRemoved only for submersion of wrist in water

Data Analysis

Zero-crossing methodAction4 and Action-W, version 2 software (Ambulatory Monitoring, Inc.)

Data Analysis (cont.)

Data sets trimmed at 8 days for consistency of comparisons across participantsActivity counts reported as:

Minimum valueMaximum valueMedian

Data not normally distributed

Data Analysis (cont.)

Activity-rest data fit to 24-hour cosinor modelSignificant activity-rest circadian rhythm defined as p<.001 with zero-amplitude testR2 used to evaluate goodness-of-fit of data to cosinor model

Statistical significance expected due to large number of data pointsR2 > .10 (Higher R2, stronger fit, stronger rhythm)

ResultsMinimum, maximum, and median 8-day activity counts (N=9)

Participant Minimum Maximum Median1 0 6703 6862 0 6756 10443 0 7892 10934 280 10290 17605 17 6754 9876 0 8200 16657 1106 8297 21008 0 6319 14649 7 7478 1060

Group median 0 7478 1318

Activity-rest Circadian RhythmMean 8-day Activity-rest Cosinor Parameters (N=9)

Participant Mesor Amplitude Acrophase* R2 p

1 111 1317 14:38 0.41 0.000

2 148 64 12:54 0.17 0.000

3 138 84 14:26 0.36 0.000

4 129 73 12:43 0.25 0.000

5 95 38 11:39 0.09 0.000

6 138 72 17:07 0.24 0.000

7 98 81 14:21 0.54 0.000

8 141 24 18:41 0.06 0.242

9 96 58 12:53 0.18 0.000Group mean 122 201 14:22 0.26 0.027

SD 22 419 2:15 0.16 0.081

*Acrophase reported in military time

SD standard deviation

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

Rhythm Characteristics of Dyspnea, Fatigue, PEFR, and Activity-rest by Single Cosinor Analysis a

Dyspnea Fatigue PEFR Activity-restParticipant Mesor Ampb Acroc R2d pe   Mesor Ampb Acroc R2d pe   MesorAmpb Acroc R2d pe   Mesor Ampb Acroc R2d pe

1 90 3314:5

9 0.17 0.04 98 3220:5

0 0.55 <.01 98 7 15:42 0.16 0.05 111 1317 14:38 0.41 0.000

2 100 3 11:26 0.06 0.31 148 64 12:54 0.17 0.000

3 113 44 4:28 0.25 0.01 119 61 4:16 0.46 <.01 100 7 20:06 0.18 0.03 138 84 14:26 0.36 0.000

4 98 1519:4

1 0.02 0.66 101 5721:4

5 0.48 <.01 100 7 9:52 0.67 <.01 129 73 12:43 0.25 0.000

5 105 3522:4

1 0.27 <.01 107 4423:0

5 0.49 <.01 97 11 13:51 0.52 <.01 95 38 11:39 0.09 0.000

6 102 14 6:19 0.28 <.01 102 11 5:58 0.17 0.03 98 18 18:29 0.39 <.01 138 72 17:07 0.24 0.000

7 99 6 19:12 0.10 0.11 98 81 14:21 0.54 0.000

8 100 214:5

5 0.02 0.77 100 3 9:49 0.05 0.39 100 2 14:36 0.02 0.72 141 24 18:41 0.06 0.241

9 99 1019:1

3 0.03 0.59 95 2517:5

8 0.08 0.23 100 3 9:23 0.09 0.16

10 97 1117:0

7 0.04 0.52   97 1919:3

8 0.21 0.02   99 5 15:19 0.41<.01   96 58 12:53 0.18 0.000

Mean 101 2114:5

5 0.14 0.32   102 3215:2

4 0.31 0.08   99 4 14:47 0.33 0.14   1815 779 14:22 0.29 0.027Note: Participants 2 and 7 did not consistently report dyspnea and fatigue. Participant 9 did not have retrievable actigraph data. Participant 9 has corrected acrophase for PEFR of 1829. All means corrected. P <.05 for Dyspnea, Fatigue, PEFR. P <.001 for Activity-rest.aModified from McCarley, et al. (2007)bAmplitudecAcrophasedGoodness of fit/strength of rhythmeSignificance level

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

Rhythm Characteristics of Dyspnea, Fatigue, PEFR, and Activity-rest by Single Cosinor Analysis a

Dyspnea Fatigue PEFR Activity-restParticipant Mesor Ampb Acroc R2d pe   Mesor Ampb Acroc R2d pe   MesorAmpb Acroc R2d pe   Mesor Ampb Acroc R2d pe

1 90 3314:5

9 0.17 0.04 98 3220:5

0 0.55 <.01 98 7 15:42 0.16 0.05 111 1317 14:38 0.41 0.000

2 100 3 11:26 0.06 0.31 148 64 12:54 0.17 0.000

3 113 44 4:28 0.25 0.01 119 61 4:16 0.46 <.01 100 7 20:06 0.18 0.03 138 84 14:26 0.36 0.000

4 98 1519:4

1 0.02 0.66 101 5721:4

5 0.48 <.01 100 7 9:52 0.67 <.01 129 73 12:43 0.25 0.000

5 105 3522:4

1 0.27 <.01 107 4423:0

5 0.49 <.01 97 11 13:51 0.52 <.01 95 38 11:39 0.09 0.000

6 102 14 6:19 0.28 <.01 102 11 5:58 0.17 0.03 98 18 18:29 0.39 <.01 138 72 17:07 0.24 0.000

7 99 6 19:12 0.10 0.11 98 81 14:21 0.54 0.000

8 100 214:5

5 0.02 0.77 100 3 9:49 0.05 0.39 100 2 14:36 0.02 0.72 141 24 18:41 0.06 0.241

9 99 1019:1

3 0.03 0.59 95 2517:5

8 0.08 0.23 100 3 9:23 0.09 0.16

10 97 1117:0

7 0.04 0.52   97 1919:3

8 0.21 0.02   99 5 15:19 0.41<.01   96 58 12:53 0.18 0.000

Mean 101 2114:5

5 0.14 0.32   102 3215:2

4 0.31 0.08   99 4 14:47 0.33 0.14   1815 779 14:22 0.29 0.027Note: Participants 2 and 7 did not consistently report dyspnea and fatigue. Participant 9 did not have retrievable actigraph data. Participant 9 has corrected acrophase for PEFR of 1829. All means corrected. P <.05 for Dyspnea, Fatigue, PEFR. P <.001 for Activity-rest.aModified from McCarley, et al. (2007)bAmplitudecAcrophasedGoodness of fit/strength of rhythmeSignificance level

DiscussionPeak 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)

Limitations

Conflicting literature on best model to analyze actigraphy-rest circadian rhythms

Single cosinor used to compare parameters with literature5-parameter cosinor model, with alpha (width of rhythm) and beta (steepness of curve), may better explain activity-rest pattern (Ancoli-Israel et al., 2003)

Limitations (cont.)

Acrophase remained relatively constant across the subjectsNo diaries or activity logs usedFully described environment

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 COPDUnderstanding patterns for better symptom managementAdministration of medication when airway tone decreased may lead to better management

Conclusion

Lack of circadian rhythm in pulmonary variables suggestive AR did not synchronize circadian pacemakerFurther study needed to confirm or determine mechanism for the role of AR patterns as synchronizer