The authors have declared that no competing interests exist.
Practice of meditation or exercise may enhance health to protect against acute infectious illness.
To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness.
Randomized controlled prevention trial with three parallel groups.
Madison, Wisconsin, USA.
Community-recruited adults who did not regularly exercise or meditate.
1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed.
Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control.
Training in mindfulness meditation or exercise may help protect against ARI illness.
This trial was likely underpowered.
Clinicaltrials.gov
Acute respiratory infection (ARI), including common cold, influenza, and influenza-like-illness, is very common, and leads to substantive morbidity, mortality, and economic harms. Evidence suggests that psychological, social and behavioral factors influence susceptibility to ARI illness [
Given these associations, we designed the first MEPARI trial [
The MEPARI-2 trial was designed to replicate and extend findings from the first MEPARI trial. The primary aim was to evaluate potential preventive benefits of meditation or exercise training on the incidence, duration, and severity of all-cause ARI illness, along with ARI-related absenteeism, health care utilization, and medication use. Secondary aims included evaluation of: a) potential pro-inflammatory mediators, and b) psychosocial outcomes including depressive symptoms, general mental and physical health, mindful attention, perceived stress, positive and negative emotion, self-efficacy, sleep quality, and social support.
The MEPARI-2 trial was conducted in Madison, Wisconsin, USA, and was approved by the University of Wisconsin Institutional Review Board’s human subjects committee. Adults aged 30 to 69 years were recruited using a variety of community advertising techniques, screened by telephone interview, and then met twice in person for baseline assessment, written informed consent, and enrollment. Allocation to the 3 treatment groups was accomplished using sealed envelopes, based on randomization codes generated by an independent statistician using variable block sizes. While participants could not be blinded to interventions, investigators remained masked to group assignment until after the last participant exited.
To be eligible, prospective participants had to answer “Yes” to either “Have you had at least 2 colds in the last 12 months?” or “On average do you get at least 1 cold per year?” Prospective participants were excluded if they scored 14 or higher on the PHQ-9 depression screen [
Following procedures nearly identical to the first MEPARI trial [
The trial was conducted from 2012 to 2016, with 4 annual cohorts. Screening occurred in the summer, with enrollment and randomization in August, followed by MBSR or EX training in September and October. Participants were followed through May of the following year using computerized weekly self-report, periodic in-person visits, and close surveillance during ARI illness. Weekly self-reports included daily minutes of MBSR or EX practice. Exercise minutes were defined as moderate or vigorous following accepted criteria [
The primary outcome was global severity of ARI illness, defined as area-under-the-time-severity-curve. Daily self-reports on the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) [
Assessment included ARI-related absenteeism and health care utilization, virus identification, and inflammatory biomarker levels during ARI illness. Secondary outcomes also included several psychosocial domains assessed by validated self-report instruments at baseline, then 3 or 4 times after intervention. These assessed: general mental and physical health (SF-12) [
Blood and nasal wash samples were collected at baseline, 1 and 4 months after the 8-week interventions, and approximately 24–72 hours into each ARI episode. Biomarkers included: interleukin-6 (IL-6), interleukin-8 (IL-8), high sensitivity C-reactive protein (CRP), procalcitonin (PCT), and interferon-gamma-induced protein 10 (IP-10) [
Participants used a nasal swab at home as soon as ARI illness criteria were confirmed, and then came to the hospital lab for nasal lavage and blood draw. Polymorphonuclear (PMN) leukocytes in the nasal wash were counted using a standard hemocytometer and expressed as neutrophils per milliliter (PMN/mL). Viruses were identified from both swabs and nasal wash, using high-throughput multiplex PCR methods developed at the University of Wisconsin [
Data are presented in the manuscript as means with standard deviations (or 95% confidence intervals) for measurements with distributions consistent with normality. For skewed measurements, medians and interquartile ranges are reported. Nonparametric statistical tests are used to compare groups: the Kruskal-Wallis test using Wilcoxon scores for continuous variables and the Pearson chi-square test for categorical variables. Between-group contrasts of ARI outcomes include differences in means (for measures consistent with normal distribution) or shifts in location (using Hodges Lehmann estimation for skewed measures). Comparing intervention to control groups, the Wilcoxon signed rank test is used to for the highly skewed cytokine data, and the Wald chi-square test in negative binomial regression is used to compare the number of ARI illnesses per person. ARI outcomes are also portrayed as proportional differences in rates (equivalent to relative risk reduction). The control group is used as reference for all between-group comparisons.
The primary efficacy analysis was done using the same zero-inflated multivariate regression model employed in the first MEPARI trial [
SAS version 9.4 was used for data cleanup and most statistical analyses (unless otherwise specified). Stata was used for zero-inflated models and missing-at-random evaluations. When data was found to satisfy the missing-completely-at-random criteria [
Of 1197 persons screened, 413 were randomized, and 390 completed the trial (
Sample, N | 137 | 138 | 138 |
Age (years), mean ± SD | 49.1 ± 11.4 | 49.2 ± 11.2 | 50.7 ± 12.1 |
Female, n (%) | 107 (78.1) | 105 (76.1) | 101 (73.2) |
Current Smoker, n (%) | 9 (6.6) | 6 (4.3) | 11 (8.0) |
Race, n (%) | |||
White/Caucasian | 105 (76.6) | 121 (88.3) | 123 (89.1) |
Black/African American | 14 (10.2) | 5 (3.6) | 6 (4.3) |
Asian | 8 (5.8) | 5 (3.6) | 3 (2.2) |
Other/More Than One Race | 10 (7.3) | 6 (4.4) | 6 (4.3) |
Hispanic Ethnicity, n (%) | 5 (3.8) | 11 (8.1) | 8 (6.0) |
BMI (kg/m2), mean ± SD | 29.3 ± 7.0 | 29.8 ± 7.8 | 29.0 ± 6.6 |
College Graduate or Higher, n (%) | 108 (78.8) | 106 (76.8) | 102 (73.9) |
Income > $50,000, n (%) | 79 (58.1) | 85 (63.4) | 85 (62.5) |
Systolic BP (mmHg), mean ± SD | 122 ± 15 | 120 ± 16 | 124 ± 17 |
Diastolic BP (mmHg), mean ± SD | 75 ± 9 | 74 ± 8 | 76 ± 9 |
Instruments, mean ± SD | |||
BFI: Agreeableness | 37.4 ± 5.5 | 37.4 ± 5 | 37.7 ± 5.4 |
BFI: Conscientiousness | 36.1 ± 5.6 | 36.3 ± 5.3 | 35.6 ± 5.8 |
BFI: Openness | 40.4 ± 5.3 | 40.1 ± 5.4 | 39.2 ± 6.3 |
BFI: Extraversion | 27.1 ± 6.9 | 27.4 ± 6.2 | 26.8 ± 5.9 |
BFI: Neuroticism | 20.6 ± 6.3 | 20.3 ± 5.9 | 20.8 ± 5.7 |
SF12: Physical Health | 51.4 ± 8.4 | 51.2 ± 8 | 51.4 ± 8.3 |
SF12: Mental Health | 47.9 ± 10.4 | 48.0 ± 10 | 47.6 ± 9.9 |
SPS Social Support | 83.2 ± 9.8 | 83.5 ± 10.1 | 83.3 ± 9.3 |
SNI: Network Diversity | 6.3 ± 2 | 6.3 ± 1.8 | 6.3 ± 1.8 |
SNI: Potential Contacts | 24.2 ± 9.8 | 23.6 ± 8.9 | 23.6 ± 8.1 |
SNI: Number of Roles | 7.3 ± 1.9 | 7.5 ± 1.8 | 7.2 ± 1.8 |
PANAS Positive | 35.4 ± 6.7 | 35.1 ± 7 | 33.9 ± 7.5 |
PANAS Negative | 18.6 ± 6.8 | 18.2 ± 6.2 | 18.6 ± 6.7 |
PSS10 Perceived Stress | 13.3 ± 6.6 | 13.1 ± 6.4 | 12.4 ± 5.9 |
PHQ9 Depressive Symptoms | 2.9 ± 2.9 | 2.4 ± 2.4 | 2.9 ± 3.1 |
PSQI Sleep Quality | 6.2 ± 3.6 | 5.8 ± 3.3 | 5.7 ± 3.3 |
MAAS Mindful Attention | 4.3 ± 0.8 | 4.1 ± 0.8 | 4.3 ± 0.7 |
MSES Mindful Self-Efficacy | 97.3 ± 14.7 | 97.6 ± 15.7 | 96.8 ± 14.6 |
ESES Exercise Self-Efficacy | 112.4 ± 38.6 | 112.5 ± 38.3 | 116.0 ± 38.8 |
Stanford Presenteeism | 20.3 ± 5.3 | 20.4 ± 5.4 | 20.1 ± 5.2 |
Instruments, median (IQR) | |||
Feeling Loved Score | 365 (340–385) | 369 (333–389) | 370 (340–389) |
GPAQ (MET-hrs/wk) | 560 (160–1320) | 730 (240–1940) | 1020 (320–2400) |
SIC Comorbidity Score | 2.0 (1.0–4.0) | 2.0 (1.0–4.0) | 3.0 (1.0–4.0) |
Biomarkers, median (IQR) | |||
IL-6 (serum) (pg/mL) | 1.8 (1.1–2.9) | 1.6 (1.0–2.8) | 1.7 (1.0–2.9) |
IL-6 (nasal) (pg/mL) | 1.0 (0.6–2.1) | 1.3 (0.8–2.2) | 1.1 (0.5–2.3) |
IL-8 (pg/mL) | 157 (79–271) | 167 (86–313) | 194 (87–352) |
IP-10 (pg/mL) | 156 (126–198) | 141 (117–183) | 152 (127–198) |
hsCRP (pg/mL) | 1.4 (0.6–3.9) | 1.6 (0.7–4.5) | 1.5 (0.7–4.8) |
HbA1c (pg/mL) | 5.6 (5.3–5.8) | 5.5 (5.2–5.7) | 5.6 (5.3–5.8) |
Abbreviations: SD = standard deviation, IQR = interquartile range, BP = blood pressure, BFI = big five inventory, SF12 = medical outcomes study short form, SPS = social provisions scale, SNI = social network index, PANAS = positive and negative affect schedule, PSS = perceived stress scale, PSQI = Pittsburg sleep quality index, MAAS = mindfulness attention awareness scale, MSES = mindfulness self-efficacy scale, ESES = exercise self-efficacy scale, GPAQ = global physical activity questionnaire, SIC = Seattle index of comorbidity, HbA1c = hemoglobin A1c, hsCRP = high sensitivity C-reactive protein, IL = interleukin, IP = interferon gamma-induced protein.
In the MBSR group, there were 112 ARI episodes and 1045 days of ARI illness, compared to 120 episodes and 1010 illness days in the EX group, and 134 episodes with 1210 days of ARI illness for controls (
Outcome | Exercise (n = 137) | Meditation (n = 138) | Control (n = 138) | Control vs Exercise |
Control vs Meditation |
---|---|---|---|---|---|
120 | 112 | 134 | |||
0.88 |
0.81 |
0.97 |
0.10 |
0.16 |
|
1.2 |
1.1 |
1.3 |
0.08 |
0.15 |
|
84 |
74 |
82 |
-0.03 |
0.10 |
|
1010 | 1045 | 1210 | |||
7.4 |
7.6 |
8.8 |
1.4 |
1.2 |
|
224 |
256 |
326 |
102 |
70 |
|
81 | 73 | 105 | |||
3.8 |
4.0 |
5.0 |
1.2 |
1.0 |
|
21 | 22 | 24 | |||
|
11 | 9 | 19 | ||
|
1 | 4 | 2 | ||
|
4 | 9 | 2 | ||
|
4 | 0 | 1 | ||
|
0 | 0 | 0 | ||
|
266 | 300 | 381 | ||
|
0.1 |
0.2 |
0.2 |
0.12 |
0.04 |
|
2.1 |
2.6 |
2.7 |
0.6 |
0.1 |
|
2.2 |
2.8 |
2.9 |
0.7 |
0.1 |
|
$119 |
$140 |
$163 |
$44 |
$23 |
91 | 90 | 119 | |||
|
4.2 |
5.7 |
4.2 |
-0.1 |
-0.1 |
|
6.0 |
4.0 |
8.0 |
0.0 |
1.0 |
|
2.8 |
3.5 |
2.7 |
-0.2 |
-0.5 |
|
25 |
29 |
16 |
-3.7 |
-3.0 |
|
728 |
472 |
551 |
-95 |
104 |
|
257 |
298 |
232 |
-25 |
-40 |
|
91 (76%) | 88 (79%) | 118 (88%) | ||
64 (70%) | 63 (72%) | 72 (61%) | -0.09 |
-0.11 |
|
68 | 65 | 76 | |||
|
1 (1.1%) | 1 (1.4%) | 2 (1.7%) | ||
|
12 (13%) | 15 (17%) | 16 (14%) | ||
|
43 (47%) | 28 (32%) | 41 (35%) | ||
|
1 (1%) | 10 (11.4%) | 9 (7.6%) | ||
|
11 (12.1%) | 11(12.5%) | 8 (6.8%) |
IQR = interquartile range, CI = confidence interval, AUC = area under the curve, ARI = acute respiratory infection, hsCRP = high sensitivity C-reactive protein, IL = interleukin, IP = interferon gamma-induced protein, OTC = over the counter, MPV = human metapneumovirus, RSV = respiratory syncytial virus, PIV = human parainfluenza virus.
1 Between-group comparison p-values comes from: a) Wald Chi-Square test in negative binomial regression for # of ARIs per person; b) Kruskal-Wallis test comparing nonparametric Wilcoxon scores for continuous outcomes (ARI duration, global severity); and c) Wald Chi-square test in logistic regression (for any ARI and any virus).
2 Between group differences are computed as control group minus treatment group with 95% confidence intervals.
3 Economic costs were calculated by summing the estimated salary lost from missing work, cost of medical provider visits, and cost of medications used.
4 Lab visits were within first 72 hours of ARI. Reasons for missing data include: lab closed on weekends, participant unable to get in, etc.
5 Comparisons are for between group change from baseline (reference group: Control). Neutrophils were not collected at baseline, so no change from baseline could be computed. See
6 Hodges-Lehmann estimation for shift in location, with 95% CIs.
7 More than one virus was identified in 10 separate ARIs. In the EX group, one ARI yielded both BoV and CoV, two ARIs had CoV and HRV, and one ARI had EV/HRV and PIV. In the MBSR group, one ARI yielded EV/HRV and CoV, and one ARI had EV/HRV and PIV (parainfluenza virus). In the control group, one ARI yielded HRV and BoV, one ARI had MPV (metapneumovirus) and CoV, one ARI had RSV (respiratory syncytial virus) and HRV, and one ARI yielded CoV and BoV.
There were 73 ARI-related days-of-missed-work and 22 ARI-related health care visits in the MBSR group, 81 days and 21 visits for EX, and 105 days and 24 visits for control. Mean ARI-related economic costs (including the cost of absenteeism) were $140 ($83, $197) for MBSR, $119 ($62, $175) for EX, and $163 ($95, $231) for control. Trends towards reduced absenteeism and ARI-related costs for both EX and MBSR were not statistically significant. On average, controls used 2.9 (2.6, 3.2) medications per ARI episode, similar to 2.8 (2.3, 3.2) medications for those in the MBSR condition. Exercisers used fewer medications than controls during ARI episodes (2.2 vs. 2.9; p = 0.001). Total ARI-related economic costs were slightly lower in both EX and MBSR groups compared to control.
Scores on the self-report questionnaires suggested improvements in mental health for both intervention groups, as shown in
Exercise | Meditation | Control | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
November/December | January | February/March | April/Exit |
November/December | January | February/March | April/Exit |
November/December | January | February/March | April/Exit |
|
4.4 |
4.4 |
4.5 |
4.5 |
4.3 |
4.4 |
4.4 |
4.4 |
4.2 | 4.2 | 4.3 | 4.3 | |
(2.6, 5.8) | (2.6, 5.8) | (2.7, 6.0) | (2.6, 6.0) | (2.9, 5.6) | (2.8, 5.6) | (2.8, 5.9) | (2.8, 5.9) | (2.7, 5.7) | (2.6, 5.8) | (2.7, 6.0) | (2.7, 5.9) | |
51.7 | 51.7 | 51.6 | 51.9 | 51.2 | 51.6 | 51.4 | 50.5 | 52.0 | 51.6 | 50.8 | 51.5 | |
(34.8, 69.2) | (33.5, 69.8) | (31.4, 70.2) | (32.2, 70.9) | (34.8, 69.3) | (35.7, 67.5) | (35.3, 66.4) | (31.4, 71.7) | (36.0, 68.1) | (34.1, 69.2) | (33.2, 68.4) | (33.9, 69.2) | |
47.6 | 47.7 | 47.6 | 47.8 | 48.0 | 49.2 |
49.3 |
49.7 |
45.5 | 45.5 | 46.2 | 45.9 | |
(23.5, 67.5) | (24.5, 66.6) | (24.8, 67.7) | (26.2, 65.6) | (27.7, 63.3) | (29.0, 62.1) | (28.0, 64.5) | (25.2, 66.5) | (24.5, 66.4) | (24.8, 66.2) | (25.6, 66.9) | (25.1, 66.6) | |
82.4 | 82.1 | 83.8 | 83.1 | 82.5 | 82.8 | 83.6 | 83.8 | 81.4 | 81.6 | 82.2 | 82.6 | |
(60.8, 101.9) | (61.7, 101.4) | (61.2, 103.2) | (62.2, 103.1) | (60.1, 102.6) | (60.4, 102.7) | (60.8, 103.7) | (61.5, 103.7) | (59.3, 103.5) | (61.6, 101.5) | (60.9, 103.5) | (62.6, 102.7) | |
13.0 |
12.3 |
12.4 |
13.3 | 13.0 |
12.4 |
12.3 |
11.6 |
14.0 | 13.8 | 13.6 | 13.4 | |
(0.6, 27.5) | (0.2, 27.3) | (0.5, 26.8) | (-0.5, 27.4) | (2.5, 25.5) | (2.6, 24.9) | (1.3, 25.9) | (0.8, 26.0) | (1.6, 26.5) | (1.0, 26.5) | (1.1, 26.2) | (0.6, 26.2) | |
5.4 |
5.5 |
5.4 |
5.3 |
5.5 | 4.9 | 5.2 | 5.1 | 6.0 | 5.8 | 5.6 | 5.8 | |
(-0.2, 12.2) | (-0.5, 12.0) | (-0.9, 12.2) | (-0.4, 12.0) | (-0.3, 12.4) | (-0.9, 12.4) | (-1.2, 12.5) | (-0.1,11.8) | (-0.6, 12.6) | (-0.7, 12.2) | (-0.7, 12.0) | (-1.3, 13.0) | |
1560 |
1380 |
1210 |
1440 |
700 | 480 | 680 | 980 | 670 | 540 | 600 | 1080 | |
(860, 2770) | (600, 2320) | (600, 2210) | (640, 2940) | (120, 1692) | (0, 1260) | (180, 1560) | (240, 2460) | (160, 1560) | (40, 1560) | (4, 1740) | (360, 2740) | |
99.0 |
99.0 |
99.9 |
100.7 |
101.4 |
102.6 |
94.8 | 94.8 | 95.1 | ||||
(63.3, 126.4) | (63.8, 125.8) | (66.6, 123.6) | (65.3, 124.3) | (65.4, 124.1) | (63.8, 126.5) | (64.5, 125.1) | (62.0, 127.5) | (63.0, 127.3) | ||||
104.6 |
104.3 |
104.4 |
92.7 | 96.3 |
94.3 |
86.0 | 84.3 | 84.6 | ||||
(13.8, 158.2) | (11.2, 157.4) | (13.4, 155.8) | (14.8, 157.3) | (12.6, 156.0) | (8.9, 160.2) | (17.8, 154.3) | (11.2, 157.4) | (13.3, 155.9) | ||||
34.8 | 34.5 | 34.9 | 35.1 | 34.8 | 35.8 | 33.6 | 32.7 | 33.2 | ||||
(17.9, 49.3) | (17.5, 47.9) | (17.6, 48.7) | (18.8, 48.4) | (20.3, 45.1) | (20.1, 46.2) | (18.6, 48.5) | (18.1, 47.3) | (18.2, 48.1) | ||||
17.9 | 17.7 | 17.9 | 17.7 | 17.5 | 17.4 | 18.7 | 19.0 | 17.9 | ||||
(5.8, 31.6) | (6.4, 31.6) | (5.6, 30.3) | (8.2, 29.3) | (7.9, 30.1) | (7.1, 28.8) | (7.5, 30.0) | (6.5, 31.4) | (7.2, 28.7) | ||||
4.3* | 4.1 |
4.1 | 4.4 | 3.9 | 3.6 | 5.3 | 4.9 | 4.5 | ||||
(-2.2, 12.8) | (-2.8, 12.5) | (-2.2, 11.2) | (-2.2, 12.8) | (-2.7, 12.4) | (-2.9, 12.0) | (-3.2, 13.7) | (-3.2, 12.9) | (-3.2, 12.2) | ||||
24.1 | 24.3 | 24.2 | 23.8 | 23.8 | 24.0 | 23.1 | 23.0 | 23.6 | ||||
(13.2, 32.9) | (13.9, 32.2) | (14.0, 33.3) | (13.5, 32.6) | (14.6, 31.4) | (14.4, 32.9) | (13.7, 32.4) | (13.8, 32.2) | (15.2, 32.1) | ||||
366.5 | 363.0 | 370.0 | 377.0 | 372.5 | 380.0 | 365.0 | 362.0 | 361.0 | ||||
(338.5, 389.5) | (339.0, 387.0) | (342.0, 388.0) | (342.0, 390.0) | (345.0, 390.0) | (350.0, 390.0) | (330.0, 381.0) | (340.0, 385.0) | (340.0, 385.0) | ||||
29.3* | 29.3 | 29.2 | 29.7 | 29.7 | 29.2 | 28.9 | 29.1 | |||||
(15.1, 43.3) | (14.6, 43.3) | (14.6, 43.6) | (14.0, 44.4) | (14.0, 44.4) | (16.1, 42.3) | (16.3, 41.6) | (15.9, 42.3) | |||||
124 (99, 157) /122 (95, 157) | 120 | 121 | 122 | 122 | 126 | 124 | 125 | |||||
(97, 152) | (95, 154) | (93, 159) | (93, 159) | (98, 154) | (93, 156) | (93, 157) | ||||||
77 (61, 96) / 75 (58, 95) | 76 | 76 | 75 | 75 | 77 | 77 | 77 | |||||
(61, 93) | (62, 93) | (58, 95) | (58, 95) | (60, 93) | (61, 92) | (61, 93) | ||||||
1.7 | 1.6 | 1.6 | 1.7 | 1.5 | 1. | |||||||
(1.0, 3.0) | (0.9, 2.5) | (0.9, 3.2) | (0.9, 2.6) | (1.0, 2.6) | (1.1, 3.0) | |||||||
1.8 | 1.6 |
1.7 |
1.6 |
1.3 |
1.6 |
|||||||
(0.8, 2.9) | (0.8, 2.8) | (0.8, 3.9) | (0.9, 2.6) | (0.6, 2.8) | (0.8, 3.6) | |||||||
214 |
227 |
238 |
258 |
255 |
248 |
|||||||
(127, 354) | (158, 414) | (144, 356) | (157, 424) | (140, 446) | (155, 390) | |||||||
139 |
145 |
140 | 149 | 148 | 147 | |||||||
(116, 172) | (111, 190) | (116, 183) | (114, 192) | (121, 205) | (123, 192) | |||||||
1.7 | 1.3 | 1.7 | 1.3 |
1.6 | 1.4 | |||||||
(0.7, 3.3) | (0.6, 3.2) | (0.8, 4.8) | (0.7, 3.3) | (0.7, 4.4) | (0.6, 3.9) | |||||||
5.5 | 5.5 | 5.6 |
5.5 | 5.6 |
5.5 | |||||||
(5.3, 5.8) | (5.3, 5.9) | (5.3, 5.8) | (5.2, 5.8) | (5.4, 5.9) | (5.3, 5.8) |
Mean (95% confidence interval) unless otherwise noted.
See
Abbreviations: SPS = social provisions scale, PANAS = positive and negative affect schedule, PSS = perceived stress scale, PSQI = Pittsburg sleep quality index, MAAS = mindfulness attention awareness scale, MSES = mindfulness self-efficacy scale, ESES = exercise self-efficacy scale, GPAQ = global physical activity questionnaire, BP = blood pressure, HbA1c = hemoglobin A1c, hsCRP = high sensitivity C-reactive protein, IL = interleukin, IP = interferon gamma-induced protein.
1Exit visits occurred late May or early June.
2Median (interquartile range).
3 Blood pressures were collected in November at the flu shot visit and at the December in-clinic follow-up visit. All other measures were collected at only one month out of the two months listed.
Between group change from baseline comparison for that visit (reference group: Control group change from baseline):
* < 0.05,
** < 0.01 (nonparametric Wilcoxon scores in the Kruskal-Wallis test).
Biomarkers Only: Within treatment group change from baseline comparison for that visit (reference group: baseline for that treatment group):
# < 0.05,
## < 0.01 (nonparametric Wilcoxon Signed Rank Test.
Inflammatory biomarkers from nasal wash and blood collected during ARI illness are shown in
Comparing the two MEPARI trials, it is apparent that the magnitude of observed ARI reduction was larger in the first trial (
ARI-Related Outcome | MEPARI (n = 154) | MEPARI-2 (n = 413) | Pooled MEPARI and MEPARI-2 (n = 562) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTL | MBSR | %DR |
EX | %DR |
CTL | MBSR | %DR |
EX | %DR |
CTL | MBSR | %DR |
EX | %DR |
|
n | 51 | 51 | 47 | 138 | 138 | 137 | 189 | 189 | 184 | ||||||
Had a ARI (n) | 28 | 21 | 25 | 17 | 34 | 82 | 74 | 10 | 84 | -3 | 110 | 95 | 14 | 101 | 6 |
Total # ARIs | 40 | 27 | 33 | 26 | 29 | 134 | 112 | 16 | 120 | 10 | 174 | 139 | 20 | 146 | 14 |
Total Days with ARI | 453 | 257 | 43 | 241 | 42 | 1210 | 1045 | 14 | 1010 | 16 | 1663 | 1302 | 22 | 1241 | 23 |
# Viruses identified | 20 | 16 | 20 | 8 | 57 | 76 | 65 | 14 | 65 | 14 | 96 | 81 | 16 | 74 | 21 |
Mean ARI Global Severity (AUC) (per person) |
358 | 144 | 60 | 248 | 31 | 326 | 256 | 21 | 224 | 31 | 334 | 225 | 33 | 230 | 31 |
Mean ARI Global Severity (AUC) (per ARI) |
456 | 271 | 41 | 449 | 1.5 | 336 | 315 | 6 | 256 | 24 | 363 | 306 | 16 | 290 | 20 |
Total Days of Missed Work due to ARI | 67 | 16 | 76 | 32 | 48 | 105 | 73 | 30 | 82 | 21 | 172 | 89 | 48 | 114 | 32 |
Total # of ARI-Related Healthcare Visits | 16 | 10 | 38 | 15 | -2 | 24 | 22 | 8 | 21 | 12 | 40 | 32 | 20 | 36 | 5 |
ARI = acute respiratory infection; CTL = control; MBSR = mindfulness-based stress reduction; EX = exercise;
Global severity = area under curve, y-axis WURSS-24 daily score, x-axis ARI illness duration
1%DR = Percent Difference in Rate, calculated as (control rate–intervention rate) / (control rate) *100 (equivalent to relative risk reduction for incidence)
2 per person with zeros if the participant did not have an ARI. %DR = Percent Difference, calculated as (control-intervention)/control*100
3 per ARI (no zeros). %D = Percent Difference, calculated as (control-intervention)/control*100.
The first MEPARI trial found statistically and clinically significant reductions in ARI illness for participants randomly assigned to 8 weeks of MBSR training, compared to observational controls [
The question of clinical significance is more complex and nuanced than that for statistical significance. Much of this complexity lies in the fact that different people value potential benefits and harms differently, resulting in a range of benchmark values for “minimal important difference” [
Comparison to influenza vaccination (flu shots) may help put MEPARI results in perspective. Flu shots are known to reduce influenza, with published estimates of proportional reductions in symptomatic illness, medical visits, and absenteeism ranging from 13% to 70% [
While flu shots confer protection only against influenza, the evidence presented here suggests that mindfulness and exercise training may reduce ARI illness in general, regardless of etiological agent. In the two MEPARI trials, representing five cold-and-flu seasons, only 22 of 253 viral identifications (8.8%) were influenza. Other studies concur that while upwards of 50% of people may experience an ARI illness in a given year, the risk of influenza-specific illness is generally less than 10% [
The main limitations of this study are related to sample selection, sample size, and heterogeneity of outcomes assessed. As with all randomized trials, the sample was comprised of people who were willing to take part in all aspects of the study regardless of group assignment, drawing in participants who may not be fully representative of those at most risk for ARI illness in general. The target sample size was determined using the results of the first MEPARI trial, which had observed 29% to 60% proportional reductions in the incidence, duration and overall severity of ARI illness. Thus, this follow-up phase 2 trial was not statistically powered to detect the smaller 10% to 30% proportional reductions actually observed. Lastly, the assessment of ARI prevention is complicated by the large amount of annual variation in ARI illness, in terms of etiological agents circulating, and in terms of the incidence, duration and severity of symptomatic illnesses resulting.
A final important consideration relates to health impacts beyond ARI illness. Exercise is known to benefit people with diabetes and cardiovascular disease [
In summary, the evidence from the MEPARI-2 trial is consistent with modest reduction in ARI illness attributable to both MBSR and EX training. The magnitude of observed benefit is similar to that from accepted medical interventions such as influenza vaccination and should be considered in light of potential health benefits beyond ARI. Additional research into the benefits of exercise and meditation is certainly warranted, perhaps in higher risk or sicker populations, where there are more health benefits to gain. Until that research is accomplished, we feel it justifiable to advocate for both mindfulness and exercise, as benefits appear likely, and risks minimal.
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The data presented are from MEPARI-2 (Meditation or Exercise for Preventing Acute Respiratory Infection), a randomized controlled trial sponsored by the National Center for Complementary and Integrative Health (NCCIH) at the U.S. National Institutes of Health (R01AT006970). The trial was registered at ClinicalTrials.gov (NCT01654289) on 19 July 2012, before the first participant was enrolled 1 August 2012. During the trial and writing of this paper Bruce Barrett was supported by a mid-career research and mentoring grant from NCCIH (K24AT006543); Supriya Hayer received support from a research training grant from NCCIH (T32AT006956) directed by Dr. Barrett. MEPARI-2 received some support from a Clinical and Translational Science Award (CTSA) through the National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427, which also provided research career development support to Elisa Torres (KL2TR000428). We wish to thank Amber Schemmel and Joseph Chase for assisting with data collection, the UW Integrative Health MBSR instructors, the UW Sports Medicine exercise instructors, and the 413 research participants.