Upper Respiratory Infections: Treatment Selection for Active Patients

Randall A. Swain, MD; Barbara Kaplan, PharmD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 26 - NO. 2 - FEBRUARY 98

In Brief: Moderate exercise may reduce the risk of upper respiratory tract infections, but intense training can increase that risk. Though the average cold does not appear to hinder athletic performance, short-term symptomatic treatment consisting of topical decongestants and/or nasal ipratropium bromide may be useful for active patients. Vitamin C and zinc lozenges may reduce the duration of cold symptoms. Antibiotics are appropriate for treating such complications as acute bacterial sinusitis, otitis media, or pneumonia but are ineffective against viral infection. Some drugs are banned by sports organizations, and others, such as first-generation antihistamines, may impair performance.

The US Centers for Disease Control and Prevention has estimated that the average annual incidence of upper respiratory tract infections (URIs) in the United States is 429 million episodes, resulting in more than $2.5 billion in direct and indirect healthcare costs. Most athletes have suffered through acute URIs that have interfered with competition or practice. In fact, a study (1) of Olympic athletes noted that such infections are the most common medical problem that occurs during Olympic competitions.

The problem of dealing with URIs raises a number of questions for physicians and active people. Among them are the effects of exertion on immunity (see "How Does Exercise Affect Immunity?" below) and the advisability of engaging in exercise or competition during the illness (see "URI Performance Effects and Risks in Athletes" below). For patients who continue to work out while ill with a URI, physicians need to choose a treatment that will not impair the patients' ability to exercise. In addition, athletes involved in high-level competition must avoid using medications that are banned by sports governing bodies.

A Horde of Viruses

The common cold is most often caused by one of several hundred rhinoviruses, but coronaviruses or the respiratory syncytial virus may also lead to infection. Other viruses, such as influenza, parainfluenza, and adenoviruses, may produce respiratory symptoms, but these are often associated with pneumonia, fever, or chills.

Colds occur in a seasonal pattern that usually begins in mid-September and concludes in late April to early May. The common cold is quite contagious and can be transmitted by either person-to-person contact or airborne droplets. Upper respiratory symptoms usually begin 1 to 2 days after exposure and generally last 1 to 2 weeks, even though viral shedding and contagion can continue for 2 to 3 more weeks (2). Symptoms may persist with the occurrence of complications such as sinusitis or lower respiratory involvement such as bronchitis or pneumonia.

Clinical Presentation

The common cold has a variety of overt symptoms, including malaise, nasal stuffiness, rhinorrhea, nonproductive cough, mild sore throat, and, in some cases, a low-grade fever. Because of the similarity of symptoms, a cold may be mistaken for perennial allergic rhinitis, but allergies can usually be ruled out because of the differences in chronicity.

On physical examination, the patient's nasal passages are congested and a clear discharge may be evident. The remaining exam is usually normal, and laboratory tests are generally unhelpful. A nasal smear result that includes eosinophils may indicate an allergic etiology rather than a URI. Further diagnostic tests—chest x-rays, sinus radiographs, limited computed tomography of the sinuses—should be reserved for patients whose physical findings suggest complications such as pneumonia or chronic sinusitis. Suspicious findings may include fever, crackles on lung auscultation, sinuses that are tender to palpation, and prolonged nasal symptoms with purulent discharge.

Assessing the Treatments

Treatments that attack the actual cause of the common cold are difficult to develop given the many serotypes of rhinovirus and others that cause similar illness. Vaccines have been considered but seem unlikely because of this heterogeneity, and agents such as alpha-interferon and specific antivirals have not been effective. No cure for the common cold exists, so preventing and reducing the impact of infection should be the goal of healthcare. The most effective prevention is frequent hand washing and avoiding contact with the mucous membranes and hands of infected persons.

If a patient presents with a viral URI, the spectrum of remedies is extensive. Since most of these infections are self-limiting, clinicians usually recommend rest and fluids, but other treatments include environmental and nutritional therapies, over-the-counter (OTC) and prescription decongestant and antihistamine products, new antihistamine and anticholinergic nasal formulations, and antibiotics. The following discussion of these modalities focuses on side effects that may adversely affect athletic performance. Table 1 lists commonly used cough and cold medications, their side effects, and special considerations for athletes.

Table 1. A Profile of Common Cough and Cold Medications, Including International Olympic Committee (IOC) and National Collegiate Athletic Association (NCAA) Policies Governing Their Use
Medication	Purpose	IOC Policy	NCAA Policy	Side Effects and Special Considerations
Aerosolized beta2 agonists (eg, albuterol)	Reverse postinflammatory bronchospasm	Physician's written consent required*	Permitted**	Raises heart rate and may cause tremor
Alcohol-based liquid combination products	Treat multiple symptoms	Depends on active ingredient	May lead to disqualification (if athlete is checked for alcohol use)	Potential drowsiness and coordination problems
Alpha1 agonists (oral) (eg, pseudoephedrine, phenylpropanolamine)	Decongestion	Banned	Permitted	May cause tachycardia, nervousness, transient stimulation, dizziness, drowsiness, elevation of blood pressure
Anticholinergic compounds:    Ipratropium bromide     (topical)	Drying	Permitted	Permitted	May cause nasal dryness and occasional epistaxis
Other anticholinergics    (eg, methscopolamine,    atropine, hyoscyamine)	Drying	Permitted unless combined with other banned ingredients	Permitted	May cause orthostasis, dysfunction of heat regulation, dry mouth, constipation
Antihistamines (oral) (eg, chlorpheniramine, diphenhydramine)	Drying	Banned for shooting events only	Permitted	Drowsiness, dry mouth, orthostatic hypertension
Benzonatate capsules	Cough suppression, local anesthesia	Permitted	Permitted	Chewing can numb the mouth; can cause sedation, dizziness
Codeine, hydrocodone	Cough suppression	Codeine permitted; hydrocodone banned	Permitted	Drowsiness, constipation, nausea
Dextromethorphan	Cough suppression	Permitted	Permitted	Drowsiness possible, but side effects uncommon
Guaifenesin	Promote expectoration (mucolysis)	Permitted unless combined with other banned ingredients	Permitted unless combined with alcohol	No side effects; must be taken with lots of water to improve efficacy
Topical decongestants (eg, oxymetazoline, phenylephrine)	Decongestion	Permitted	Permitted	Local burning; prolonged use may cause dependence
Zinc and vitamin C lozenges	Possible reduction in symptom severity and duration	Permitted	Permitted	Possible taste disturbance, increase of oxalate stones if susceptible
*Systemic forms banned. **Systemic forms permitted only with a physician's written consent.

General URI Medication

Antihistamines and decongestants. Clinicians often recommend the use of combination antihistamine/decongestant products for the treatment of the common cold, but these products must be used with caution in athletes. Antihistamines often cause sedation and dry mouth, and they may cause difficulties in sweating and temperature regulation that are likely to impair athletic performance. The use of alpha-1 agonist decongestants such as pseudoephedrine and phenylpropanolamine is banned by the International Olympic Committee (IOC) during competition because of possible ergogenic properties. However, research (3) has not shown that such decongestants improve an athlete's performance. In fact, the National Collegiate Athletic Association (NCAA) no longer bans decongestants during competition. (For the IOC and the NCAA policies on various cold-related medications, see table 1.)

Recent reviews on the subject confirm that oral and topical decongestants help relieve upper respiratory symptoms (4). Topical nasal decongestants work better and faster than oral agents, but, because of rebound congestion or tolerance, the topical products can be used for only 3 to 5 days. If they are used continuously for 1 to 2 weeks or more, rhinitis medicamentosus—chronic nasal stuffiness—can occur as a result of drug dependency.

Several first-generation antihistamines are available without prescription, including chlorpheniramine, brompheniramine, diphenhydramine, and clemastine. However, the success of antihistamines as a treatment for common colds appears to vary. Studies (5-8) have shown that chlorpheniramine use reduces sneezing, nasal mucous production, and overall symptoms from viral URI. However, Gaffey et al (8) found that diphenhydramine did not reduce cold symptoms any better than placebo. Another study (9) demonstrated that clemastine reduced nasal secretions up to 27% more than placebo.

First-generation antihistamines appear to reduce sneezing and nasal discharge but have no effect on nasal stuffiness. Though their benefits are thought to be due to anticholinergic effects rather than to their effect on histamine, anticholinergic side effects such as orthostasis and disruption of thermoregulation can impair athletic performance. Newer, nonsedating antihistamines—loratidine, terfenadine, and astemizole—do not appear to improve symptoms of the common cold (10).

Ipratropium bromide. A nasal formulation of this topical anticholinergic drug was recently approved by the US Food and Drug Administration for the treatment of rhinorrhea associated with both allergies and URIs. The spray is available in two strengths, 0.03% and 0.06%; the stronger solution is usually used for treating URIs.

Two studies (11,12) examined the efficacy of ipratropium bromide in patients who had URIs. Patients were administered two sprays of the 0.06% solution in each nostril (42 micrograms per spray) four times daily. Treated patients had a reduction in nasal discharge of about 34% relative to untreated patients. The nasal spray was generally well tolerated; minor side effects included nasal dryness and an increase in blood-tinged nasal discharge. Intranasal ipratropium bromide may be considered for treating patients who have moderate to severe symptoms from URI.

Antitussives. A benign cough that results from postnasal drip or bronchospasm may be treated symptomatically, as long as there is no suspicion of acute bacterial pneumonia or bronchitis. Benzonatate capsules may provide relief for athletes with an acute cough. However, antitussives such as dextromethorphan and codeine have not been shown to be effective for treating cough in URI (4). The use of such agents may be of particular concern to elite athletes because the IOC has banned all narcotic cough suppressants. Furthermore, many of the liquid formulations contain alcohol, so their use may be problematic for college athletes since the NCAA occasionally tests for breath alcohol.

Guaifenesin, a commonly prescribed expectorant, appears to irritate gastric mucosa and stimulate respiratory tract secretions, theoretically resulting in increases in respiratory fluid volumes and decreased phlegm viscosity. Patients are instructed to take guaifenesin with plenty of water to ensure proper action. Research (4) has not proven guaifenesin clinically beneficial for URI, and many clinicians suggest that increased fluid intake alone can provide the desired expectorant effect.

Beta₂ agonists. The use of beta₂ agonists—such as an albuterol metered-dose inhaler—has been shown to be more beneficial than erythromycin in patients with persistent and productive coughs (13). This treatment is recommended for athletes with bronchospasm, but the use of a beta₂ agonist inhaler requires written consent during Olympic competition. Smokers and patients over 40 years old who have persistent, URI-related coughs may also benefit from treatment with a beta₂ agonist.

Vitamin C and Zinc Gluconate

Vitamins and minerals appear to be of some benefit to those who have colds. The first vitamin to be studied extensively was vitamin C. Linus Pauling is famous for his advocacy of vitamin C and its use to prevent the common cold, but true efficacy in cold prevention remains controversial. Although vitamin C may not actually prevent colds, some evidence (14) suggests that it may shorten the illness; though it may or may not be effective, the vitamin is innocuous because it is water soluble and thus easily excreted in urine.

More recently, zinc gluconate in the form of throat lozenges has been touted as effective for common cold management. Studies have demonstrated that the lozenges can reduce the duration of symptoms if started early in the illness. In a recent study (15) of 100 patients who had viral URIs, 50 subjects were given zinc gluconate lozenges (13.3 mg zinc per lozenge) and 50 were given a placebo every 2 hours until symptoms abated. The treated patients' symptoms persisted 4.4 days, vs 7.6 days for those of the controls. The zinc lozenges were well tolerated, and only mild taste disturbances were reported.

We believe that combination throat lozenges—containing vitamin C and zinc—may decrease the length of cold symptoms. Because such lozenges have no adverse effects on physical performance, they should be considered as a first-line treatment for athletes and active people.

Steam

Although steam has been advocated as a URI treatment for many years, thorough research on its efficacy was not done until recently. Before the 1990s, researchers not only believed that steam relieved symptoms, but also thought it might inhibit viral replication (viral shedding). However, Forstall et al (16) found that the cold symptoms of 32 subjects treated with steam were not significantly different from those of 36 controls. Furthermore, Hendley et al (17) showed that steam treatment had no effect on viral shedding. As a result, we do not recommend steam for the treatment of patients who have a common cold.

Antibiotics

As the number of resistant bacterial pathogens increases, the medical community has begun to scrutinize the use of antibiotics to treat URIs. A recent study (18) examined the antibiotic prescribing patterns of over 1,500 physicians during more than 28,000 patient visits in an ambulatory care setting. Antibiotics were prescribed for 51% of the patients diagnosed as having colds (acute nasopharyngitis) and 66% of those who had bronchitis. Antibiotic treatment of probable viral illness accounted for 21% of all antibiotic prescriptions written.

The cause of such overuse may lie with both patients and physicians. Some patients who have a URI believe that they need antibiotics to recover, and busy physicians may choose to save time by writing a prescription rather than discussing drug resistance and efficacy. However, we have found that most patients, if they receive a short, factual explanation, understand that antibiotic overuse may lead to increasing bacterial resistance and that antibiotic treatment does not cure a viral infection and may cause side effects.

So when should antibiotics be prescribed? A critical review of the many studies on antibiotic use in common cold patients who are otherwise healthy reveals many methodological flaws. Nevertheless, it is clear that antibiotics are effective and appropriate for the treatment of acute bacterial sinusitis, acute otitis media, and bacterial pneumonia, which are often complications of the common cold. Most clinicians also agree that purulent productive coughs in smokers should be treated with antibiotics. But the use of antibiotics in healthy, young athletes and adult nonsmokers who have purulent, productive coughs has not been proven effective (19).

A subpopulation of otherwise healthy patients who have purulent nasal discharge may benefit from antibiotics. One study (20) showed that the use of amoxicillin-clavulanate for patients who had nasopharyngeal swab cultures that demonstrated growth of bacterial respiratory pathogens shortened the duration of symptoms. Unfortunately, obtaining nasopharyngeal swab cultures on all patients would be too expensive and impractical. Furthermore, the patients who responded to antibiotics may have done so because of subclinical sinusitis.

In summary, antibiotics are overused in the treatment of URI. More rigorous patient selection and education regarding URI etiology can help reduce the continued misuse of antibiotics and the risk of increasing antibiotic resistance in the United States.

No Miracle Cure

Active patients will inevitably contract colds. Those who want to continue to exercise or compete, especially competitive athletes, may be desperate for a miracle cure. Unfortunately, physicians can only offer therapies that reduce symptoms or, at best, shorten their duration (table 2).

Table 2. Recommended Treatments for Common Cold Symptoms
Symptom	Recommended Therapy
Acute nonproductive cough	None, or dextromethorphan products without alcohol or benzonatate if symptoms are severe and patient desires treatment
Acute purulent cough in an otherwise healthy individual	As with acute nonproductive cough, no medical therapy or symptomatic treatment
Persistent cough	Albuterol or other beta2 agonist inhalers, 1-2 wk
General cold symptoms	Vitamin C and zinc gluconate lozenges started within 24 to 48 hr of onset
Nasal congestion	Topical decongestants (maximum use of 3-5 dy)
Rhinorrhea	Topical anticholinergic spray as needed
Sinusitis, otitis media, or pneumonia	Appropriate antibiotic therapy

In the face of this challenge, we recommend that symptomatic patients who desire therapy use ipratropium bromide nasal spray and topical decongestants for up to 5 days, as needed. Zinc gluconate lozenges—with or without vitamin C—are safe for athletes and appear to decrease the duration of cold symptoms when initiated at the onset of symptoms. To prevent athletes from being disqualified from competition, clinicians need to be aware of OTC and prescription medications that are banned by sports organizations.

Antibiotics should be reserved for patients who have bacterial complications of URIs. For patients who have persistent, purulent rhinorrhea, no clinical signs or symptoms of sinusitis, and a positive nasopharyngeal culture, antibiotics may be warranted, but further study in this area is needed. Albuterol inhalers may adequately treat patients who have persistent cough and no evidence of bacterial pneumonia.

References

1. Hanley DF: Medical care of the US Olympic team. JAMA 1976;236(2):147-148
2. Winther B, Gwaltney JM Jr, Mygind N, et al: Sites of recovery after point inoculation of the upper airway. JAMA 1986;256(13):1763-1767
3. Swain R, Harsha D, Baenziger J, et al: Do pseudoephedrine or phenlypropanolamine improve maximum oxygen uptake and time to exhaustion? Clin J Sports Med 1997;7(3):168-173
4. Smith MBH, Feldman W: Over-the-counter cold medications. JAMA 1993;269(17):2258-2263
5. Howard JC, Kantner TR, Lilenfield LS, et al: Effectiveness of antihistamines in the symptomatic management of common cold. JAMA 1979;242(22):2414-2417
6. Crutcher JE, Kantner TR: The effectiveness of antihistamines in the common cold. J Clin Pharmacol 1981;21(1):9-15
7. Doyle WJ, McBride TP, Skoner DP, et al: A double-blind, placebo controlled clinical trial of chlorpheniramine on the response of the nasal airway, middle ear and eustachian tube to provocative rhinovirus challenge. Pediatric Infect Dis J 1988;7(3):229-238
8. Gaffey MJ, Gwaltney JM, Sastre A, et al: Intranasally and orally administered antihistamine treatment of experimental rhinovirus colds. Am Rev Respir Dis 1987;136(3):556-560
9. Gwaltney JM Jr, Park J, Paul RA, et al: Randomized controlled trial of clemastine fumarate for treatment of experimental rhinovirus colds. Clin Infect Dis 1996;22(4):656-662
10. Berkowitz RB, Tinkelman DG: Evaluation of oral terfenadine for treatment of common cold symptoms. Ann Allergy 1991;67(6):593-597
11. Diamond L, Dockom RJ, Grossman J, et al: A dose-response study of the efficacy and safety of ipratropium bromide nasal spray in the treatment of the common cold. J Allergy Clin Immunol 1995;95(5 pt 2):1139-1146
12. Hayden FG, Diamond L, Wood PB, et al: Effectiveness and safety of intranasal ipratropium bromide in common colds. Ann Intern Med 1996;125(2):89-97
13. Hueston WJ: Albuterol delivered by metered-dose inhaler to treat acute bronchitis. J Fam Pract 1994;39(5):437-440
14. Hemila H: Does vitamin C alleviate the symptoms of the common cold? A review of current evidence. Scand J Infect Dis 1994;26(1):1-6
15. Mossad SB, Macknin ML, Medendorp SV, et al: Zinc gluconate lozenges for treating the common cold. Ann Intern Med 1996;125(2):81-88
16. Forstall GJ, Macknin ML, Yen-Lieberman BR, et al: Effect of inhaling heated vapor on symptoms of the common cold. JAMA 1994;271(14):1109-1111
17. Hendley JO, Aboft RD, Beasley PP, et al: Effect of inhalation of hot humidified air on experimental rhinovirus infection. JAMA 1994;271(14):1112-1113
18. Gonzales R, Steiner JF, Sande MA: Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. JAMA 1997;278(11):901-904
19. Orr PH, Scherer K, Macdonald A, et al: Randomized placebo-controlled trials of antibiotics for acute bronchitis: a critical review of the literature. J Fam Pract 1993;36(5):507-512
20. Kaiser L, Lew D, Hirschel B, et al: Effects of antibiotic treatment in the subset of common cold patients who have bacteria in nasopharyngeal secretions. Lancet 1996;347(9014):1507-1510

How Does Exercise Affect Immunity?

There is evidence (1-3) that regular, moderate aerobic exercise decreases the incidence of upper respiratory tract infections (URIs), but that more intense regimens can increase the risk. Nieman (1) describes several studies that have confirmed that runners of marathon or ultramarathon races are at the highest risk of contracting a URI during the 2 weeks after a race.

Two randomized, controlled studies (2,3) have shown that moderate exercise may prevent or limit common cold symptoms. One study of 36 women (mean age, 35) who had a URI showed that those who walked for 45 minutes 5 days per week suffered cold symptoms only half as long as sedentary controls. The other study demonstrated that the incidence of URIs among elderly women (65 to 85 years old) was inversely related to the amount of their physical exercise; colds were the least frequent among 12 highly conditioned endurance competitors, the most frequent among those who did mild calesthenic exercises, and of intermediate frequency among those who walked 40 minutes per day 5 days a week.

Science has not provided a definitive explanation for this phenomenon, but moderate acute and chronic exercise appears to elicit the release of natural killer cells, as well as other complex changes, which are related to increases in circulating epinephrine and cortisol. However, during intense or prolonged exercise the high demands made on the body may overstress these adaptations. Thus athletes may be more susceptible to URIs and also have more severe and longer-lasting symptoms after engaging in long, difficult workouts or events.

References

1. Nieman DC: Exercise, upper respiratory infection, and the immune system. Med Sci Sports Exerc 1994;26(2):128-139
2. Nieman DC, Nehlsen-Cannarella SL, Markoff PA, et al: The effects of moderate exercise training on natural killer cells and acute respiratory infections. Int J Sports Med 1990;11(6):467-473
3. Nieman DC, Henson DA, Gusewitch G, et al: Physical activity and immune function in elderly women. Med Sci Sports Exerc 1993;25(7):823-831

URI Performance Effects and Risks in Athletes

Many athletes contend that upper respiratory infections (URIs) hurt their performance. But many athletes keep playing while ill, and URIs may actually have little effect on their level of play.

Weidner (1) asked 45 college athletes to appraise their physical performance while they had a URI. Only 17.8% of the athletes reported that they missed practice because of their illness, and only 5.1% of the athletes actually missed an athletic event.

More objective data on the physiologic effects of URI on exercise were obtained in a study (2) of 45 male and female athletes who were inoculated with the rhinovirus. The athletes underwent a resting pulmonary function test and a submaximal exercise test while healthy and again at the peak of their illness. The illness caused no significant impairment of pulmonary function, maximum oxygen consumption, maximum heart rate, or rating of perceived exertion. Such findings suggest that an "average" cold does not significantly impair these parameters of athletic performance, even though subjects may believe it does.

Athletes and their physicians, however, should be aware that the literature cites a risk for myocarditis from vigorous exercise during viremia. In a recent report (3) of sports-related sudden death, 2 of 34 subjects were found to have viral myocarditis at autopsy. The general consensus is that the coxsackie virus may have a particular affinity for heart muscle, and this virus is an uncommon cause of the common cold. Sports medicine physicians usually instruct athletes and recreational exercisers who have any systemic symptoms, such as a fever (measured without any antipyretics), myalgias, productive cough, or any symptoms below the neck to refrain from vigorous workouts until symptoms resolve.

References

1. Weidner TG: Reporting behaviors and activity levels of intercollegiate athletes with an URI. Med Sci Sports Exerc 1994;26(1):22-26
2. Weidner TG, Anderson BN, Kaminisky LA, et al: Effect of a rhinovirus caused upper respiratory illness on pulmonary function test and exercise responses. Med Sci Sports Exerc 1997;29(5):604-609
3. Burke AP, Farb A, Virmani R, et al: Sports-related and nonsports-related sudden cardiac death in young adults. Am Heart J 1991;121(2 pt 1):568-575

Dr Swain is an associate professor of family and sports medicine at West Virginia University School of Medicine in Charleston. He is the founder of the Charleston Sports Medicine Associates and a charter member of the American Medical Society for Sports Medicine. Dr Kaplan is an assistant professor of clinical pharmacy and a clinical assistant professor of family medicine at West Virginia University Schools of Pharmacy and Medicine in Charleston. Address correspondence to Randall A. Swain, MD, Associate Professor of Family & Sports Medicine, West Virginia University School of Medicine, 1201 Washington St, Suite 108, Charleston, WV 25301; address e-mail to randall.swain@camcare.com.