All respiratory disease-related deaths
The estimated effects of exercise energy expenditure on all respiratory disease-related deaths were also not significantly different between walking and running (P = 0.10). Table 3 shows that for running and walking combined, the risk for all respiratory disease-related deaths decreased 7.3% per MET-hour per day, which persisted when adjusted for BMI, and was significant in both males and females separately (Table 3). Forty-nine percent of the respiratory disease deaths had CVD listed as a contributing cause, a mortality end point known to decrease with running (30,31). However, the reduction in the risk for all respiratory disease-related deaths persisted when all CVD-related deaths were excluded (Table 3). Only two-thirds of the potential risk reduction was achieved by meeting the current exercise guidelines (Fig. 1). Exceeding the current exercise guidelines was associated with a significantly greater decrease in all respiratory disease-related deaths than merely satisfying the guidelines (i.e., >1.8 vs 1.07 to 1.8 MET·h·d−1; HR, 0.79; 95% CI, 0.63–0.98; P = 0.04 for all respiratory disease-related deaths).
Pneumonia as the underlying cause
The risk for pneumonia decreased 13.1% per MET-hour per day run or walked, and was significant both with and without adjustment for BMI and when the analyses were restricted to women (Table 3, P = 0.07 for men). Compared with not achieving the current exercise recommendation, the risk for pneumonia as an underlying cause of death decreased 21% for meeting the guidelines, 31% by exceeding the guidelines by one- to twofold, 35% by exceeding the guidelines by two- to threefold, and 37% by exceeding the guidelines by threefold or more when all CVD-related deaths were excluded (not displayed).
All pneumonia-related deaths
The risk for all pneumonia-related deaths decreased 10.5% per MET-hour per day run or walked, and was significant both with and without adjustment for BMI and when the analyses were restricted to men and women. Compared with not achieving the current exercise recommendation, the risk for all pneumonia-related deaths decreased 36.2% for meeting the guidelines, 50.6% by exceeding the guidelines by one- to twofold, 55.9% by exceeding the guidelines by two- to threefold, and 54.0% by exceeding the guidelines by threefold or more (Fig. 1, middle). The reductions in risk for all pneumonia-related mortality were somewhat weakened by excluding CVD-related deaths but remained significant except for merely meeting the guidelines.
Aspiration pneumonia as the underlying cause.
There was no difference in the per MET-hour per day reduction in aspiration pneumonia mortality between running and walking (P = 0.89). Its risk decreased 19.9% per MET-hour per day run or walked before adjustment for BMI and 19.1% after adjustment. Figure 1 (bottom) shows that aspiration pneumonia was less likely to occur in those that exceeded 1.8 MET·h·d−1 run or walked (i.e., exceeded the current recommendations).
Other respiratory disease-related deaths
The remaining 441 deaths included 180 respiratory failures of an unspecified nature and 261 deaths involving other respiratory causes. Neither the respiratory failures (HR, 0.985; 95% CI, 0.924–1.045; P = 0.62) nor the other respiratory causes (HR, 0.943; 95% CI, 0.885–1.002; P = 0.06) were significantly related to MET-hours per day run or walked.
These analyses show that the risks for respiratory diseases and pneumonia as underlying and contributing causes of mortality decreased significantly in association with greater baseline exercise energy expenditure (MET·h·d−1), and it did not differ significantly between running (a vigorously intense exercise) and walking (a moderately intense exercise). Exceeding physical activity recommendations beyond that currently recommended appeared to produce substantial reductions in risk. Aspiration pneumonia mortality also decreased significantly with greater METs run or walked, with those who exceeded the recommendations having ≥60% lower risk for aspiration pneumonia as those who fell short of the recommendations.
The current results substantially strengthen the evidence linking pneumonia risk to physical activity in women. Specifically, the women’s risk for pneumonia as an underlying cause decreased significantly per MET-hour per day both before (Table 3) and after adjustment for BMI (HR, 0.644; 95% CI, 0.420–0.916; P = 0.01). At best, prior reports suggest a weak association that loses its statistical significance when adjusted for BMI. In particular, a 2-yr follow-up of 78,062 women who participated in the Nurses’ Health Study showed that the risk for community-acquired pneumonia decreased 6% for the second, 21% for the third, 26% for the fourth, and 34% for the fifth quintile of recreational or leisure-time physical activity relative to the least active quintile (1). This trend was significant when adjusted for age, smoking, and alcohol intake (P = 0.02), but not when further adjusted for BMI. Subsequent 12-yr follow-up of this cohort (N = 83,185) showed that nurses in the highest activity quintile had 28% lower risk of nonfatal community-acquired pneumonia compared with those in the lowest quintile when adjusted for age, smoking, and alcohol use (P < 0.0001 for trend), but again, not when adjusted for BMI (17). The highest quintile of walking had 18% lower risk of community-acquired pneumonia compared with the lowest quintile, but there was no significant trend across quintiles. Running or jogging >2 h·wk−1 had 54% lower risk than a woman who neither ran nor jogged (17). The effects of BMI adjustment on the walking, jogging, or running associations were not reported.
The current results provide the only evidence linking pneumonia risk to physical activity in men. A 6-yr follow-up of 26,429 men age 44 to 79 in the Health Professionals Follow-up Study showed no significant risk reduction for community-acquired pneumonia from the lowest quintile of recreational or leisure-time physical activity to the second (7% increase), third (31% decrease), fourth (20% decrease), and fifth quintiles of activity (4% decrease) (1). Although Paffenbarger et al. (18) reported that lower physical activity predicted a 3.9-fold increased risk of deaths due to pneumonia in their 22-yr follow-up of 3686 San Francisco longshoremen, the increased risk was not statistically significant. In addition, moderate and heavy physical activities were not found to decrease the incidence of hospital-treated pneumonia in 50- to 69-yr-old male smokers participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (5).
The effects of running and walking we observed on pneumonia risk are consistent with other research, suggesting that exercise may improve immune function (3,11,35) and attenuate its decline with age (8). Regular exercise in adults has been associated with higher amounts of antiinfluenza IgG and IgM after immunization (7) and attenuates the decline in natural killer cell activity with age (37). Chronic resistance training is reported to improve natural killer cell activity in older women (12).
The reduction respiratory disease and pneumonia risk per MET-hours per day run or walked remained significant when CVD-related deaths were excluded. Over one-half of older community-acquired pneumonia patients have preexisting chronic cardiac conditions, and acute infections such as pneumonia can precipitate acute cardiac events (2). Although running reduces the risk for CHD (31) and stroke (30), our results suggest that the reductions respiratory disease and pneumonia risk were not simply the consequence of lowered CVD risk due to running or walking.
Whether obesity increases the risk for infectious pneumonia is controversial (10). Contrary to the Nurses Health Study (1), we did not find BMI was related to increased risk for pneumonia, but this might be explained by the study differences, e.g., our focus on fatal rather than nonfatal pneumonia and our lack of specificity on the origin of the infections (community vs hospital acquired). Our cohort was also leaner than either the men of the Health Professionals’ Follow-up Study (mean BMI, 24.2 kg·m−2 for our males vs 25.5 kg·m−2) or the women of the Nurses’ Health Study (mean BMI, 21.7 kg·m−2 for our females vs 24.45 kg·m−2), and it included fewer obese subjects (3.5% obese males vs 8.2% for the Health Professionals Follow-up Study; 1.5% obese females vs 12.1% in the Nurses’ Health Study), and therefore, many have included too few subjects at risk for their obesity.
We considered all respiratory-related and all pneumonia-related deaths in addition to deaths due to respiratory disease and pneumonia as underlying causes to increase statistical power. Concurrent infections, and the contraction of hospital-acquired pneumonia while being treated for other conditions, are examples of pneumonia’s contribution to mortality without necessarily being listed as the underlying cause. Moreover, the mechanism by which physical activity reduces mortality may not simply involve its effect on pneumonia as the underlying cause, but also by affecting whether pneumonia contributes to the fatal consequence of other underlying causes.
Finally, we hypothesize that the observed reduction of aspiration pneumonia with increased exercise may represent a lower risk for stroke or conditions requiring general anesthesia, less loss of vitality with aging, or the sustained ability to cough or otherwise prevent the aspiration of food or vomit. We have previously demonstrated that the risk for stroke decreases with greater running mileage (30). Greater running may also be associated with reduced susceptibility to lung inflammation when food or vomit is aspirated. The association was unexpected and requires confirmation.
There are important limitations to these analyses. Running, walking, and other baseline variables were self-reported from the participants’ baseline questionnaires. Exercise levels and other subject characteristics could have changed before infection. Our use of mortality is both a strength and weakness—a strength in its ease of ascertainment, lack of subjectivity, and broad importance to patients and the critical care community, and a weakness in that it is not known whether the risk reduction is due to a lower risk of infection, a lower risk of mortality among those infected, or both. Another important limitation of these analyses is the lack of information on the circumstances of the infections. Death certificate diagnoses do not distinguish pneumonias acquired in the community, nursing homes, and health care facilities. Almost all of the diagnoses were pneumonia, unspecified (ICD9: 486, ICD10: J18.9). Differential mortality could represent differences in susceptibility to infection and well as the adequacy, timeliness, and response to antibiotic treatment (23). Additional studies are required that track incidence, circumstances of infection, and treatment to determine whether the relationships observed are affected by patient physiology, behavior, or access to quality treatment in addition to exercise. Vital status is known only from the National Death Index, and therefore, some subjects who have died are likely to be misclassified as alive. Finally, we caution with regard to implying cause and effect in that individuals with greater susceptibility to respiratory disease may choose to exercise less.
In conclusion, the current results provide strong evidence that greater levels of physical activity may reduce the risk for respiratory disease-related deaths in a dose-dependent manner, including pneumonia and aspiration pneumonia. These effects appear to be independent of the effects of exercise on CVD risk.
This research was supported by grant HL094717 from the National Heart, Lung, and Blood Institute and was conducted at the Ernest Orlando Lawrence Berkeley National Laboratory (Department of Energy DE-AC03-76SF00098 to the University of California). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The authors have declared that no competing interests exist.
The results of the present study do not constitute endorsement by the American College of Sports Medicine.
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Keywords:© 2014 American College of Sports Medicine
PHYSICAL ACTIVITY; PNEUMONIA; PREVENTION; COHORT