key: cord-007385-xcx4ic0s authors: Spector, Sheldon L. title: The common cold: Current therapy and natural history()()() date: 2005-11-30 journal: J Allergy Clin Immunol DOI: 10.1016/s0091-6749(95)70218-0 sha: doc_id: 7385 cord_uid: xcx4ic0s Despite its prevalence, the common cold is complicated and can be difficult to treat, even symptomatically. There is still no cure for the myriad of viruses that cause the common cold. Many of the most popular remedies are either ineffective or counterproductive. This paper reviews the causes and course of upper respiratory infections, and discusses treatment options, including a new anticholinergic aqueous formulation for controlling rhinorrhea. (J ALLERGY CLIN IMMUNOL 1995;95:1133-8.) As new data emerge regarding the pathophysiology of upper respiratory infections (URIs), we continue to gain new insight into their treatment and possible complications. It has been estimated that the average preschool child experiences six to ten URIs, or "colds," per year; the average adult has two to four? The effects of the common cold can be uncommonly disruptive, forcing otherwise normal individuals to miss work, school, or other important activities. Individuals who are at increased risk, such as those with bronchitis or asthma, may also experience a life-threatening exacerbation of their underlying conditions. The average annual expenditure for various cold treatments exceeds $2 billion in the United States. This statistic becomes even more provocative when we consider that one of every three individuals with a confirmed infection has no apparent symptoms of a cold. Viruses that cause colds can be spread through contact with inanimate surfaces, 2 as well as by hand-to-hand contact? Seasonal variations in cold patterns have long been recognized. Generally there are fewer colds in the warm summer months and more colds during periods of crowding, particularly the fall. Upper respirato~ infection seem to be a significant factor in cold epidemiology. Folklore is somewhat at odds with modern science over this issue; there are many cultures where youngsters who have a "cold" are dressed sufficiently to keep them warm on the coldest winter night, even when the outside temperature is tropical. Colds are caused by a wide variety, of viruses (Table I) . The rhinoviruses, which account for more than 30% of colds in adults, have more than 100 antigenically different types. Coronaviruses also appea r to be responsible for a large percentage of colds, but precisely what that percentage is compared with parainfluenza or respiratory syncytial viruses has not yet been well established. Certain viruses appear to be more common in children than adults, but in general, viruses appear in roughly the same proportions in both populations. Some viruses may be associated with more severe symptoms than others, for example, the exacerbation of asthma seen with respiratory syncytial virus. However, the most significant factor in the severity of a viral infection seems to be the incubation period. 4 Various factors are thought to increase susceptibility to URIs. There seems to be a relationship between colds and stress. In assessing the differences between symptomatic and asymptomatic individuals with confirmed viral infections, Stone 6 found an association similar to a dose-response between psychologic stress and increased risk of acute infectious respiratory illness; the risk involved increased rates of infections rather than frequency of symptoms after infection. Smokers are at greater risk than nonsmokers to develop both infections and symptoms after infection. 6 It also appears that certain drugs may increase susceptibility to colds. Aspirin and acetaminophen suppress sero-neutralizing antibody response (p < 0.05) and are associated with increased nasal symptoms and signs. There is a trend towards longer duration of virus shedding with both of these medications. 7 Common cold viruses characteristically cause an infection that is self-limited and of short duration. Although shedding of rhinovirus has been shown to last 3 weeks in young adults with experimentally induced colds, s, 9 rhinoinfections with coronavirus are usually detected for only a few days. Most colds are not associated with cell necrosis or significant mucosal damage, but there may be some sloughing of columnar epithelial cells. 1° Initially there is an increase in vascular permeability, ~1 followed later by glandular secretions, both of which may have implications with regard to the timing and effectiveness of treatment. The constituents of the glandular secretions provide clues to their origins. 11, i2 There is an elaboration of inflammatory mediators such as kinins. When these mediators accumulate along with polymorphonuclear cells, there is an increase in nasal symptoms. 13 Since bradykinin is a likely mediator, 14 (Table II) . Although Doyle et al. 24 reported no increase in nasal responsiveness to an infectious trigger in allergic compared with nonallergic individuals, Bardin et al. 25 found that patients with allergic rhinitis had more severe colds independent of preinnoculation anti-body. There is also an increased twitchiness of the tracheal bronchial tree following colds. 26 Sir William Osler has been quoted as saying, "There is just one way to treat a cold, i.e., with contempt." We seem to have made some progress in the treatment of URIs since this statement was made, due largely to a better understanding of the pathophysiology of colds, although there is certainly still room for improvement. Some treatments used today are better choices than others in terms of pathophysiology. As mentioned previously, both aspirin and acetaminophen may have a detrimental effect on cold treatment, neutralizing antibodies and increasing nasal symptoms. 27 In a 1136 Spector J ALLERGY CLIN IMMUNOL MAY 1995 study by Sperber et al., 28 naproxen did not alter virus shedding or serum neutralizing antibody in experimental rhinovirus cold, but it had a beneficial effect on such symptoms as headache, malaise, myalgia, and cough. Oral o~-agonists relieve congestion in many individuals, although their effect is not dramatic. 29, 3o Topical decongestants may also help; unfortunately, if they are overused they may also be associated with rebound congestion or worsening of symptoms. The role of antihistamines in the treatment of the common cold has been debated. Some antihistamines do not seem to be very effective, 31 whereas others may provide mild benefit. Antihistamine/ decongestants do not appear to be effective in the treatment of URIs in children. 32, 33 Cromolyn sodium and nedocromil have both been studied; they do not cause a worsening of symptoms, but neither do they seem to provide any significant improvement. 34, 35 Apparently menthol cannot be positively demonstrated to provide a beneficial effect? 6 Interferon has been used in various studies with negative results. 3739 Either intranasal or systemic steroids may suppress inflammation during the first days of infection, and would seem to merit further investigation. 4° Among the many nonpharmacologic therapies, steam has been shown by various authors to provide no beneficial effect; 41, 42 however, with proper timing, local hyperthermia 43 or sauna 44 may decrease the incidence of colds or provide slight relief. In general, the use of zinc has been disappointing and is associated with side effects. 45 Godfrey et al. 46 commented on the poor bioavailability of the older zinc products and found a statistically significant decrease in the duration of colds with their nonchelated formulations. Vitamin C may decrease the duration of cold symptoms.47, 48 Of course, chicken soup is well known to provide benefit in the common cold (as long as it is one's mother's). In answer to the cynics who doubt such an assertion, chicken soup has been demonstrated to improve mucociliary clearance. 49 There are new pharmacologic therapies on the horizon that may prove useful to the physician in the treatment of the common cold. Ipratropium bromide nasal spray, an anticholinergic therapy, has the unique property of specifically controlling rhinorrhea in URIs, as has been demonstrated in many studies9 ,51 A novel attempt at antiviral therapy includes blockade of the receptor where the virus attaches. 52 Such a treatment may be useful against rhinoviruses that affect one or two common receptors but may not be applicable to less specific viruses. Modern research has demonstrated that URIs have myriad causes and complex effects. Although some time-honored treatments might have limited usefulness, novel attempts at ameliorating the symptoms of a common cold, such as the use of ipratropium bromide nasal spray or specific antiviral receptor therapy, might represent a significant advance. They are based on a better understanding of the pathophysiology of URIs. Ineffectiveness of recombinant interferon-beta serine nasal drops for prophylaxis of natural colds Chemical disinfection interrupt transfer rhinovirus type 14 from environmental surfaces to hands Potential role of hands in the spread of respiratory viral infections: studies with human parainfluenza virus 3 and rhinovirus 14 Signs and symptoms in common colds Development of common cold symptoms following experimental rhinovirus infection is related to prior stressful life events Smoking, alcohol consumption, and susceptibility to the common cold Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers Studies with rhinoviruses in volunteers: production of illness, effect of naturally acquired antibody, and demonstration of a protective effect not associated with serum antibody Sites of rhinovirus recovery after point inoculation of the upper airway Human ciliated epithelial cells in nasal secretions Analysis of nasal secretions during experimental rhinovirus upper respiratory infections Microvascular exudative hyperresponsiveness in human coronavirus-induced common cold Fireside conference 11. Common cold Kinins are generated in nasal secretions during natural rhinovirus colds A study of the efficacy of the bradykinin antogonist, NPC 567, in rhinovirus infections in human volunteers Peripheral blood mononuclear cell interleukin-2 and interferon-gamma production, cytotoxicity, and antigenstimulated blastogenesis during experimental rhinovirus infection Effect of rhinovirus 39 infection on cellular immune parameters in allergic and nonallergic subjects Increased levels of interleukin-1 are detected in nasal secretions of volunteers during experimental rhinovirus colds Chemotherapy of rhinovirus colds Respiratory viruses and exacerbations of asthma in adults Computed tomographic study of the common cold Physiologic abnormalities in the paranasal sinuses during experimental rhinovirus colds Middle ear abnormalities during natural rhinovirus colds in adults Effect of experimental rhinovirus 39 infection on the nasal response to histamine and cold air challenges in allergic and nonallergic subjects Amplified rhinovirus colds in atopic subjects Factors affecting the long-term variability of bronchial responsiveness in an adult general practice population Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers Effects of naproxen on experimental rhinovirus colds: a randomized, double-blind, controlled trial Pathophysiology and pharmacotherapy of common upper respiratory diseases Evaluation of an alpha agonist alone and in combination with a nonsteroidal antiinflammatory agent in the treatment of experimental rhinovirus colds Evaluation of oral terfenadine for treatment of the common cold Effectiveness of an antihistamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial Over-the-counter cold medications: a critical review of clinical trials between 1950 and 1991 The effect of intranasal nedocromil sodium on viral upper respiratory tract infections in human volunteers Intranasal sodium cromoglycate in post-catarrhal hyperreactive rhinosinusitis: a double-blind placebo controlled trial The effects of menthol on reaction time and nasal sensation of airflow in subjects suffering from the common cold Ineffectiveness of recombinant interferon-beta serine nasal drops for prophylaxis of natural colds Ineffectiveness of postexposurc prophylaxis of rhinovirus infection with lowdose intranasal alpha 2b interferon in families Recombinant human interferon-gamma as prophylaxis against rhinovirus colds in volunteers A randomized controlled trial of glucocorticoid prophylaxis against experimental rhinovirus infection Effect of inhaling heated vapor on symptoms of the common cold Effect of inhaling heated vapor on symptoms of the common cold Local hyperthermia benefits natural and experimental common colds Regular sauna bathing and the incidence of common colds Zinc gluconate lozenges for common cold: a double-blind clinical trial Zinc gluconate and the common cold: a controlled clinical study Vitamin C and the common cold Does vitamin C alleviate the symptoms of the common cold?: a review of current evidence Effects of drinking hot water, cold water, and chicken soup on nasal ¢,~ ~pec'~or ~ucus velocity and nasal airflow resistance Therapeutic effects of an anticboinergic-sympathomimetic combination in induced rhinovirus colds A double-blind, placebo-controlled study of the safety and efficacy of ipratropium bromide nasal spray versus placebo in patients with the common cold Modification of experimental rhinovirus colds by receptor blockade