Viruses are the most common infectious agents affecting humans, and some investigators contend that viral upper respiratory illness (URI) causes more frequent acute disability among athletes than all other diseases combined (32). Disease patterns among summer and winter Olympic athletes are remarkably consistent, with respiratory infections heading the list, followed by gastrointestinal disorders and skin infections (17). In the 1992 Winter Olympics, some of the world's greatest athletes were unable to compete or did not perform strongly because of a URI (25). The average adult has from one to six colds each year (3), with rhinoviruses accounting for about 40% of these infections (10). Rhinovirus infections, most prevalent in the fall and spring months (6), are associated with major socioeconomic expense in the United States, costing 5 billion dollars annually due to truancy from work and school, physician expenses, and over-the-counter medications (35).
Athletes and exercise enthusiasts commonly continue to participate in competitive and recreational sports during a URI. Although moderate exercise may decrease the risk of acquiring a URI (25), research has not demonstrated conclusively whether exercise training during a URI may prolong or intensify the illness. Is there a dose-response phenomenon with respect to the severity and duration of a URI and the extent of physical activity during a URI? A recent review by Weidner (36) offers the assumption that if strenuous exercise can compromise the immune response in healthy subjects, it would seem plausible for exercise to further compromise the immune system during an illness; however, the extent to which this compromise may affect the course of a URI has not been determined and warrants investigation. The purpose of this study was to determine both the acute (immediately postexercise) and chronic (10-d period) effects of exercise training on the symptom severity and duration of a rhinovirus-caused URI. We hypothesized that even moderate exercise during a URI may prolong the severity and duration of the illness.
Student volunteers (ages 19-29) were solicited from classes in the School of Physical Education at Ball State University. An initial screening consisted of a health history questionnaire including information regarding acute and chronic diseases, asthma, bronchitis, chronic colds, allergies (including penicillin), pregnancy, immune deficiency, medications, and physical activity level. All volunteers were moderately fit, indicated by having a maximal oxygen uptake value corresponding to > the 40th percentile for age and gender (men > 41 mL·kg−1·min−1; women > 33 mL·kg−1·min−1). These values were determined using data collected at the Cooper Clinic and established by the Institute of Aerobics Research (Dallas, TX, 1989). Subjects were also apparently healthy according to the criteria of the American College of Sports Medicine (1). All subjects agreed to refrain from self-treating their colds (e.g., no over-the-counter medications). Each subject signed an informed consent form approved by the Institutional Review Board. Subjects who completed the study received modest remuneration for their efforts.
Fifty subjects who tested negative to the HRV 16 antibody were randomly assigned to the exercise (EX) group or the nonexercise (NEX) group. Thirty-four subjects (M = 17, F = 17) were assigned to the EX (experimental) group, and 16 subjects (M = 7, F = 9) were assigned to the NEX (control) group. The split for the number of subjects assigned to the EX and NEX groups was a compromise designed to have passable statistical power for the analyses of only the EX group, and for the analyses comparing the EX and NEX groups.
Experimental design. Subjects testing negative for the HRV 16 antibody completed a graded exercise test to volitional fatigue, and 70% of HR reserve was determined for exercise training purposes. The graded exercise test also served to confirm that each subject was moderately fit. The EX group was assigned to supervised exercise training sessions, whereas the NEX group was instructed to be sedentary throughout the study. Obvious exceptions for activity were granted for both subject groups (e.g., walking to class, working part-time jobs), although subjects received excused absences from participation in any physical activity class. Repeated verbal encouragement was given to persuade the NEX group to remain sedentary and the EX group to refrain from any additional physical activity other than what was assigned.
All subjects were inoculated with RV 16 on 2 consecutive days. EX group subjects were requested to exercise the morning of their first day of inoculation while NEX group subjects were instructed not to exercise for a ten day period beginning the day of inoculation. Additionally, EX subjects reported for supervised exercise within 18 h of the first inoculation and again within 18 h of the second inoculation the following day. After these 2 consecutive days of exercise, EX subjects abstained from exercise for 1 d and then exercised every other day for 8 d (total of six exercise sessions in a 10-d period, five sessions in which subjects had URI symptoms). All subjects reported to the laboratory every 12 h for 10 consecutive days. Beginning on day 2 (the day of the second inoculation), all subjects completed a 13-item symptom severity checklist for each reporting period. EX group subjects also completed this symptom severity checklist immediately after exercise. All subjects completed an activity log for each evening reporting period. New, preweighed Ziploc bags and facial tissues of known weight were distributed; used tissues were then collected for each reporting period. These used facial tissues were weighed and counted, and nasal discharge weights were computed.
Virus detection and quantification. Just before HRV 16 inoculation, a preinoculation nasal wash was taken from all subjects. This nasopharyngeal sample, designed to detect most subclinical or incubating respiratory viruses, allowed us to eliminate previously infected subjects from the experiment. The cultures were examined by microscope approximately every other day; other standard techniques were used for detection and identification of viruses (e.g., hemadsorption for myxo- and paramyxoviruses, acid lability for rhinoviruses, etc.) (16,19). These cell cultures could not detect all possible viruses (e.g., most coronavirus infections and many coxsackie A viruses). Beginning the day after inoculation (day 2), nasal washings were obtained, and virus specimens were quantitated for HRV 16.
Inoculation and clinical evaluation of URI. As outlined by Dick et al. (11,13), each subject was inoculated intranasally by aerosol (office atomizer) and by pipette with about 1000 infectious particles of safety-tested HRV 16. This inoculation was repeated the next day (day 2). Ordinarily, about 50% of the inoculated subjects will develop moderate/severe colds. Subjects typically develop a slight sore throat the evening of day 2, and symptoms will become fully developed over the next 2 d (days 3 and 4). Symptoms often diminish rapidly thereafter, and the subjects are well in a week. The colds are very ordinary with nasal stuffiness, rhinorrhea, cough (usually after day 3), and some malaise. About 1-2% will have a fever over 100°F.
Before infection, each subject completed a previously validated symptom checklist (11-13). Subjects rated (0 = not present, 1 = mild, 2 = moderate, 3 = severe) the severity of 13 common cold symptoms. A cold with a total score of less than 7 is considered mild; 7-11, moderate; 12 or greater, severe.
Beginning on day 1 (day of first inoculation), subjects were given a box of Kleenex brand facial tissues and a Ziploc bag, both of known weights. All subjects were required to collect every used facial tissue, placing them into the bags and carefully resealing them. Tissues were weighed and counted and subsequent mucous weights computed and recorded within 2 h of collection. These weights served as an objective measure of symptom severity.
Physical activity profile. All subjects were required to complete a physical activity log each evening reporting period (7:00 p.m.) beginning the second day of inoculation (day 2). The activity log was simply intended to recognize if or when a subject engaged in activity beyond what was assigned or absolutely necessary. The quantity of the subjects' recreational or physical activity was determined through self-report and included total minutes of walking and cycling (transportation), hours of work, and participation in recreational activity. None of the previously validated physical activity measurement instruments reported in the literature (20) was appropriate for this purpose, because none required daily physical activity reports.
Graded exercise testing. Body fat was measured (30,33), and subjects were prepared for the exercise electrocardiogram (ECG) using a CM-5 configuration, during which time the Borg rating of perceived exertion (RPE) scale (4) and instructions for the test were explained. The ECG was monitored continuously during the exercise test using a Physio-Control Lifepak 7 (Redmond, WA).
A Sensormedics 2900 Metabolic Measuring Cart (Yorba Linda, CA) was utilized for all metabolic measurements with a Hans Rudolph 2700 series one-way nonrebreathing valve (Kansas City, MO) and mouthpiece. Expired air was analyzed breath-by-breath, and the data were expressed using a five-breath average for each subject tested. The ventilatory threshold was calculated using the V-slope technique (2).
Two standardized incremental treadmill protocols, one for men and one for women, were used in this study. Both protocols consisted of 1-min stages (1-MET increments) and began with 5-6 min of graded walking and then progressed to running speeds. All subjects were encouraged to give a maximal effort and were provided with strong verbal prompts throughout the testing sessions. HR and RPE were recorded during the last 10 s of each stage.
Exercise training. Within 18 h of the first inoculation, EX subjects began the supervised exercise training program previously described. Subjects were scheduled for one of two possible exercise times, either morning or evening. Subjects who were assigned to exercise in the morning were expected to exercise at the same time for the entire 6 d of training; likewise, subjects assigned to exercise in the evening did so regularly. Exercise consisted of training at 70% of HR reserve for 40 min, with the mode of exercise designed to match each subject's regular form of workout. Choices included cycling on either the Air-Dyne bicycle (Schwinn Bicycle Co., Chicago, IL) or Cybex MET 100 cycle (Cybex Metabolic Systems, Ronkonkoma, NY); walking or jogging on a treadmill (Trotter, Millis, MA) or at an indoor track; or stair climbing on the Stepmill (StairMaster Sports and Medical Products, Kirkland, WA). All subjects performed the same mode for each training session. HR was monitored continuously via Polar HR telemetry units; rating of perceived exertion via the Borg 6-20 RPE scale was recorded twice per training session.
Statistical analysis. Symptom severity scores from the cold symptom checklist were summed. Three statistical analysis were performed. A two group by nine measure (2 × 9) repeated measures ANOVA procedure was used to compare the symptom questionnaire mean z-value scores and the mucous weights for days 2-10. A subject's values obtained during the a.m. and p.m. testing were averaged to arrive at a subject's value for a day. The statistical power for comparing the differences between the EX and NEX groups over the 9 d (P < 0.05) was 0.96 for Cohen's (7) medium-sized effect (Eta = 0.25) and 0.99 for his large effect (Eta = 0.37). Preliminary analyses of the questionnaire and mucous data suggested an alternative to the usual ANOVA procedure was desirable. The alternative procedure employed for these data was the assignment of ranks to the data values, normalizing the ranks (obtaining normal distribution z-values for percentiles of the ranks), and evaluating the data via conventional ANOVA procedures and F-tests (8,9,18). The other two statistical procedures were a two by five (2 × 5) repeated measures ANOVA for differences between the EX pre- and post-exercise cold symptom scores, and a one-way ANOVA for differences between the quantity of recreational physical activity performed by the EX and NEX groups. The statistical power for the EX group prepost differences (P < 0.05) was 0.67 for Cohen's (7) medium-sized effect (Eta = 0.25) and 0.97 for his large effect (Eta = 0.37). The SPSS MANOVA program (SPSS, Inc., Chicago, IL) was used for these analyses.
Symptom severity. The statistical tests yielded by the ANOVA evaluating the (main) effect of the exercise treatment for days 2-10 indicated no difference between the overall (combined for days 2-10) EX and NEX cold symptom score mean (rank) z-values, a difference (main effect) among the combined EX and NEX group cold symptom score means for days 2-10, and no divergence in the difference between the EX and NEX mean z-values for particular days (no group by day interaction). Essentially, the only systematic variation among the EX and NEX groups for the 9 d were the differences among the days. The mean z-values are shown in Figure 1. The combined EX and NEX group means for the 9 d illustrate a typical reaction to HRV 16, with highest number of symptoms being reported on days 3 and 4 after inoculation.
Pre/post-exercise cold symptom severity scores. The statistical tests yielded by the ANOVA evaluating the differences between the EX group pre- and post-cold symptom score means for the 5 exercise condition days indicated no overall difference between pre- and post-means (combined for the 5 exercise days) and no divergence in the difference between the pre- and post-means for particular exercise days. In short, exercising did not have an immediate effect on the reporting of cold symptoms. The EX group pre- and post-means are shown in Figure 2.
Mucous weight measurements. The statistical tests yielded by the ANOVA evaluating the effect of the exercise treatment on the mucous weights for days 2-10 indicated no difference between the mean z-values of the EX and NEX groups, a difference (main effect) among the combined EX and NEX group mean weights for days 2-10, and no divergence in the difference between the EX and NEX mean weights for particular days (no group by day interaction). The distribution of the mean mucous weights, considered in this study as an objective measure of cold symptoms, exhibited the same pattern for the nine days as did the mean cold symptom score values. As shown in Figure 3, the mucous mean weights (mean z-values) were highest for days 3 and 4.
Physical activity profiles. Total minutes of walking and cycling (i.e., transportation purposes), hours of work, and participation in recreational activity were determined from reviewing physical activity logs completed by the subjects for each evening reporting period.
There was no significant difference in physical activity levels between groups with respect to minutes of transportation or hours of work. Additionally, none of the subjects reported participation in recreational fitness activity, other than what was assigned for the EX group.
Although the present study did not examine specific immune responses to exercise during an URI, (e.g., neutrophil killing capacity, T-cell proliferation), it attempted to evaluate the impact of exercise training during a URI on subsequent symptom severity and duration. In the context that URI symptomatology may partially indicate the extent and effect of exercise on immune system responses during a URI, results of the present study do not appear to support Weidner's (36) assumption that exercise could further compromise the immune response during a URI. For instance, symptom severity on day 3, as indicated by mean cold symptom score, for the EX group was 5.7 ± 0.94 as compared with 8.1 ± 1.43 for the NEX group. Although the mean score reported by the NEX group indicated a moderate/severe illness (score > 7) and the EX group mean score for the same day was indicative of a subclinical/mild illness (score < 7), there was no statistically significant difference between these two mean scores.
A possible reason for this lack of difference may be that the prescribed intensity of exercise (70% of HRR) for the EX group was not challenging enough to elicit deleterious changes in immune responses and subsequently effect symptom severity and duration. According to current immunological literature (21,26,29), only high intensity exercise (e.g., marathon training/competition) has been associated with immune system changes that may subsequently alter immunocompetence. Several epidemiological studies (22,27,28) have also supported this finding, suggesting that athletes engaging in heavy training have a higher incidence of URI.
Essentially, the RV 16 cold appeared to produce a milder URI than some other naturally occurring viruses. Although mucous production served as a more objective measure of symptom severity, volume of mucous production was not significantly different between the EX and NEX groups for any given day. On day 3, for instance, the EX group mean mucous weight was 1.64 ± 0.39, whereas the NEX group mean was 1.63 ± 0.39.
A significant finding with respect to time was observed in symptom duration across days. Illness severity decreased by 27% for the EX group from day 4 (peak illness) to day 10 (last day of investigation). The NEX group exhibited similar findings in that illness severity decreased by 44% from day 4-10. No significant differences were observed between groups regarding symptom duration. Therefore, the trend observed across days within each group, although significant, does not appear to suggest immunological or physiological compromise during exercise with a rhinoviruscaused URI. Early work on animal models noted that prior exercise training enhances resistance to experimental illness, whereas exercise introduced at the time of infection impairs resistance to infection (23). Responsible mechanisms have not yet been elucidated. Research in this area may add to the growing body of literature on regulation of immune function (23).
Exercise participation during a URI should be considered carefully. Several guidelines pertaining to exercise participation during a URI have been reported (15,19,31). These guidelines indicate that if an individual is not experiencing extreme tiredness, malaise, fever, or swollen lymph glands, participation in mild intensity activity may be safely resumed. Furthermore, Eichner (14) recommends performing a "neck check" before exercise: assessing cold symptoms and subsequently classifying them as either above or below the neck. If illness symptoms are "above the neck" (e.g., runny nose, sneezing, or scratchy throat), individuals may exercise at a lower intensity. If these symptoms clear after a few minutes of exercise, intensity may be increased accordingly. Exercise is not recommended for those individuals experiencing "below the neck" symptoms (e.g. fever, aching muscles, productive cough, vomiting, or diarrhea). The results of the present study with rhinovirus-caused URI seem to support the "above-the-neck" recommendations mentioned above. There was no significant difference between the EX and NEX groups in chronic (10-d period) symptom severity and duration responses or in the EX group acute (pre- and post-exercise) symptom severity responses. Moderate exercise training with "above-the-neck" symptoms caused by a rhinovirus-caused URI does not appear to extend the length of or exacerbate the severity of the illness.
The present study was the first attempt to examine the influence of exercise training on the symptom severity and duration of a rhinovirus-caused URI. Investigations with other cold viruses (e.g., coronavirus) that may have different symptom profiles (i.e., variation in symptoms and their severity) and may cause different immunological and physiological responses, which also have not yet been examined, warrant investigation. Coronaviruses are considered to be the major cause of winter colds (6). Because rhinoviruses are responsible for only 40% of URI (10), many other viruses could be examined. However, subject safety dictates that these studies be restricted to those viruses that primarily cause "above the neck" symptoms only. Of particular significance here are the enteroviruses, usually occurring during summer and autumn months; these viruses, however, are probably not common causes of acute adult respiratory tract illness (24). The chief importance of enterovirus infection for the athlete lies in the association of some ECHO virus and Coxsackie virus strains with myocarditis and aseptic meningitis (32). Exercise may increase the risk of developing enterovirus cardiomyopathy (5,34).
Alternate patterns of exercise prescription (i.e., athletic vs fitness/recreational) including various intensities (>70% HRR), frequencies (every day vs every other day, >6 d), durations (>40 min), and modes (anaerobic vs aerobic) would help determine if and to what extent these patterns influence symptom severity and duration.
The course of cold symptom severity and duration during exercise among an older (>29 yr) and younger (<18 yr) population also warrants further investigation. As well, there is a need to investigate this response in individuals of varying fitness levels (e.g., sedentary, highly fit).
Results from this investigation suggest that moderate exercise training during a rhinovirus-caused URI under the conditions of this study design do not appear to affect illness symptom severity or duration. This finding is important for athletes and fitness enthusiasts alike who are interested in maintenance of their fitness levels during a rhinoviruscaused URI. Similar studies with other viruses (e.g., coronavirus), other forms of exercise (e.g., anaerobic), other exercise intensities (e.g., mild, heavy), other populations (e.g., young and old, laborers), and other fitness levels (e.g., sedentary, highly fit) warrant further investigation.
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