JGIM i I I I I

PERSPECTIVES

The Common Cold Bennett Lorber, MD

T he common cold is the Rodney Dangerfield of infec-

t ious d iseases- - i t gets no respect. Although it is

among the most f requent and economically impor tant of

all infectious diseases, the cold is rarely discussed in

i medical school curricula, res idency training programs, or

even infectious diseases symposia.

: The common cold occupies an almost unique position

in infectious diseases, because everyone knows wha t it is

f r o m personal experience. As Supreme Court Jus t i ce Pot-

ter Stewart said about obscenity, "I know it when I see i t J

But, a l though we all know what the common cold is, it is

hard to define. In most definitions it is described as an

acute inf lammation of the m u c o u s membranes of the res-

piratory passages, part icularly of the nose, s inuses, and

throat, caused by viruses and characterized by sneezing,

rhinorrhea, coughing, and so forth.

HISTORY

C o l d s have been well known since antiquity, bu t cur ren t

unders tand ing really began in 1914 when Dr. Kruse in

Germany showed that nasal secret ions from persons with

colds could be made bacteria-free by Filtration, and tha t

these filtrates could be inoculated into the noses of recipi-

ents and cause colds. ~ He thus provided direct evidence of

the infectious na tu re of colds prior to the first isolation of

a respiratory virus. These initial experiments were refined

by Andrewes and Tyrrell at the Harvard Hospital in Salis-

bury, England. 2, 3 The Harvard Hospital was a prefabri-

cated hospital planned, constructed, and shipped to En-

gland by Harvard University and the American Red Cross

early in World War II "to help in the s tudy of the epidemic

disease tha t it was expected to follow intensive air attack."

Mercifully, epidemics did not occur, and it became a mili-

tary hospital. At the end of the war it was given to the

Ministry of Health, and a round 1946 it became the Com-

mon Cold Unit of the Medical Research Council. There,

From the Section of Infectious Diseases, Temple University School of Medicine and Hospital, Philadelphia, Pennsylvania.

Dr. Lorber is a Thomas M. Durant Professor of Medicine. Address correspondence and reprint requests to Dr. Lorber:

Section of Infectious Diseases, Temple University Hospital. Broad and Ontario Streets. Philadelphia, PA 19140.

over the next 30 years, Drs. Andrewes and Tyrrell per-

formed many impor tant s tudies on cold t ransmission. For

example, they showed that filtered nasal washings from

subjects with colds could be diluted 100-fold and still

produce disease; but only about 60% of those inoculated

developed symptoms. Remember, because viruses had

not yet been isolated, recipients could not be screened for

immunity.

In the 1940s Wade Hampton Frost along with Gover

studied the seasonal incidence of colds in six large Ameri-

can cities, and concluded that, dur ing the season of high

prevalence {September to March), colds occurred as a se-

ries of dist inct epidemics, each of several weeks duration,

suggesting multiple etiologic agents. Another epidemio-

logic s tudy was conducted in the 1950s by Dingle in the

so-called Cleveland Family Study. Again, he showed the

seasonal na ture of colds and tha t children had the high-

est annua l infection rates and were the most important

reservoir for cold viruses.

In the 1950s cell cul ture methods were used in the

s tudy of respiratory disease, and in 1956 and 1957 Pelon

and Price isolated the first cold viruses. i

In the 1970s investigators at the University of Vir-

ginia and the University of Wisconsin led by Drs. J a c k

Gwaltney and Elliott Dick, respectively, defined the modes

of cold t ransmission; and more recently, Hayden, Hend-

ley, and Gwaltney at the University of Virginia have inves-

tigated the pathogenesis as well as the t rea tment and pre-

vention of colds.

HOW COMMON IS THE COMMON COLD?

Young children typically have five to seven or more respi-

ratory il lnesses per year. The rate may be doubled in

those in day care. The frequency of colds decreases with

age, and in those under school age, boys have more colds

than girls, bu t later respiratory il lnesses are more com-

mon in women, part icularly dur ing childbearing years.

Colds are one of the most common h u m a n infections.

During the first year of life, children have about 1.2 rhi-

novirus colds per year, and young adults have close to 1

rhinoxdrus cold per year. Several s tudies in households

indicate that infection with viral replication and shedding

may occur without symptoms, but 70% to 90% of t rans-

mitted infections are symptomatic. 4

Colds are virtually never fatal and rarely are compli- 229

230 Lorber, T h e C o m m o n Cold ]GIM

cated by more serious int~ctions, but they exact a t remen-

dous toll in morbidity and economic cost (Table 1). ~

EPIDEMIOLOGY

Colds occur worldwide, and antigenic types appear to cir-

culate randomly. Colds begin in early childhood and oc-

cur th roughout life, with illness being most common in

young children, bu t with peak antibody prevalence seen

in young adults, then declining with advancing age. In

temperate climates, colds peak in the fall and again in the

spring months .

WHAT CAUSES COLDS?

The agents responsible for colds are indicated in Table 2.

Rhinovirnses (rhino for nose} are the most important

causes and account for 30% to 40% of all colds. Rhinovi-

rns colds occur in the fall and the spl~ng. Another impor-

tan t cause of colds are the coronavirnses, which are most

prevalent during winter months.

In the Tecumseh Studies, Monto and his Michigan

colleagues s tudied respiratory infections in two 5-year pe-

riods, first in family groups and later in the community. 6, 7

They found tha t rhinoviruses were the single most impor-

tant cause of colds, account ing for more than a third, In

one 5-year period, 52 of the then-known 89 rhinovirus se-

rotypes were seen. Colds were most f requent in those less

than 5 years of age, and the median symptom durat ion in

adults was approximately 3 weeks. They noted that cold

t ransmiss ion intensified in September and again in May,

bu t occurred year- round in oscillating outbreaks.

Rhinoviruses are members of the Picornaviridae fam-

ily (pico for little--RNA). Other members of the family in-

clude enteroviruses like pollovirus and hepat i t is A virus.

Rhinoviruses are s ingle-stranded RNA viruses of 20 to 27

nm, without an envelope. They replicate well at 33 ° to

35°C bu t poorly at 37°C, which probably accounts for the

fact that these viruses cause upper respiratory tract in-

fections and not pneumonias . As there are approximately

100 antigenically dist inct types of rhinoviruses, one could

have a cold a year for life and never run out of new ones.

Rhinoviruses are hardy and remain infectious for at least

Table I . The Cost of Colds Annually in United States

No. of colds Days of restricted activity Visits to physicians Lost days of work Lost days of school Economic burden

In cold remedy sales In analgesic sales

100 million 250 million

22 million 30 million 30 million

5 billion dollars 1 billion dollars 1.5 billion dollars

*Adapted f r o m reference 5.

Table 2. Causes of the Common Cold*

Cause

No. of Antigenic

Types %Ot

Cases

Rhinovirus 100 Coronavirus 4 Respiratory syncytial virus 2 Adenovirus 47 Parainfluenza virus 4 Influenza virus 3 Other viruses 3 Unknown

t 30-40 10-15

10-15

5

25-40

*Adapted f r o m references 4. 6. and 7.

three hours after drying on hard surfaces such as stain-

less steel or formica, but do not last as long on porous

surfaces like paper tissues. Rhinoviruses are known to intact humans , ch impan-

zees, and gibbons. J a n e Goodall has described cold out-

breaks and their seasonal pat tern in her chimpanzee

studies. Research has been hindered by the fact tha t an inex-

pensive animal model of the common cold is not available.

Dr. Andrewes, on his "windswept hilltop j u s t outside Sal-

isbury in Southern England," failed in his a t tempts to in-

fect a variety of animals including mice, rats, guinea pigs,

hedgehogs, ferrets, kittens, pigs, monkeys, and baboons. 3

PATHOGENESIS

Rhinoviruses grow in the upper airway and a t tach and

gain entry to host cells by binding to an intercellular ad-

hesion molecule, so-called ICAM-1, as a receptor. The vi-

ral region that a t taches to ICAM-1 is in a cleft or canyon

on the viral shell, s, 9

Evidence indicates that infection begins in the ade-

noidal area and rapidly spreads to the ciliated epi thel ium

in the nose,l° The frequency of large airway involvement

remains unknown. In spite of everything my mother believes (father too},

drafts, cold temperature, and dampness have nothing to

do with cold acquisi t ion or severity. Andrewes addressed

this quest ion more than 40 years ago, and an excerpt

from one of his papers is most instructive:

We took three groups o f s ix volunteers. Three pairs re- ceived a dose o f virus so di luted that w e expec ted it to produce only a f e w colds. Three pairs were chilled; they s o a k e d in hot baths and then s tood about undr ied in bathing d r e s s e s in a p a s s a g e f o r a hat.l hour or a s long a s they could bear it. In addition, they wore w e t socks f o r some hours. Most s h o w e d a drop o f several degrees in body temperature, a n d f e l t rather chilly and u n h a p p y f o r a time. Finally. three other pairs received the dilute vi- n t s a n d the chilling treatment. The resul ts w e r e encour- aging. Chilling alone produced no colds. Dilute virus pro- duced mild colds in two subjects , and the combined treatments , colds in four, o f wh i ch two were rather good ones. W e were fool i sh enough to repeat this exper iment

JGIM V o l u m e I 1, Apri l 1 9 9 6 231

with a contrary result. Again, chiUing alone d id nothing but those wi th virus alone h a d on this occasion twice as m a n y colds a s those having the chilling t rea tment in ad- dition to vints. So w e have got to f i n d a better technique f o r lowering res is tance or e lse jo in the school o f thought that d i s m i s s e s the ef fects o f draughts and w e t socks a s mere superst i t ions. 3

Douglas and associates tried this again in the United

States, and reported their resul ts in the New England

J o u r n a l of Medicine in October 1968. u In these studies,

subjects were exposed in a 4°C room and were seated in a

32°C water bath. This was done at the t ime of inoculation,

du r ing incubation, dur ing maximal illness, and during re-

covery. There was no difference in infection rates, illness

severity, viral shedding, or antibody response in subjects

compared with controls.

Tiny amoun t s of virus will cause disease, and j u s t

one tenth of a t issue cul ture infecting doses0 (TCIDs0) can

cause illness. Virus is shed from the nose 24 hours after

inoculation, and shedding peaks on the second and third

day with large amount s of virus recoverable. Nasal biopsy

studies show epithelial damage is slight with little or no

inflammation; cuboidal epithelial ceils and some neutro-

phils are shed in these nasal secretions.

Several s tudies have examined the role of s t ress to

see if colds are more frequent or more severe in those un-

dergoing stress. One such study, reported in the New En-

gland J o u r n a l of Medicine in 1991, used experimental na-

sal inoculat ion in volunteers after they completed s tress

evaluat ion quest ionnaries . 12 The authors of this s tudy

found an increase in both infection rates and symptom-

atic colds with increases in psychological stress. This

s tudy controlled for age, gender, education, allergic sta-

tus, season, antibodies, smoking, alcohol, exercise, and

other factors. In another inoculat ion study conducted at

Stony Brook and reported the following year, infection

rates were the same, bu t clinical colds occurred more of-

ten in subjects with a higher number of "life events" in the

previous year. ~3

Nasal biopsy studies have shown little, if any, cell

damage or inflammatory infiltrate.. 14 Therefore recent

s tudies have examined the role of chemical mediators in

the pathogenesis of the common cold. Kinins, prostaglan-

dins, his tamine, inter leukins 1, 6, and 8, as well as t umor

necrosis factor (TNF) have all been implicated as potential

contr ibutors to cold symptoms. For example, high levels

of the potent vasoactive peptide bradykinin have been

found in nasa l secret ions of subjects with symptoms bu t

not in those shedding virus wi thout s y m p t o m s ) 5, 16

In a recent s tudy volunteers were inoculated with a

rhinovirus, and nasal lavage specimens were examined

daily to measure levels of inter leukin 1 (IL-1), kinins, and

albumin. 17 Resul ts showed tha t 24 hours after nasa l inoc-

ulat ion there is a striking increase in each of these fol-

lowed by rapid declines over the next 48 hours. IL- 1 levels

were not significantly increased in subjects who were in-

fected bu t asymptomatic , as had previously been shown

for kinins. IL-1 can increase the responsiveness of some

cells to bradykinin by up-regulat ing the expression of ki-

nin receptors. IL-1 increases vascular permeability, and

therefore could lead to increased p lasma t ransudat ion

and a consequent ia l increase in a lbumin in nasal secre-

tions.

Another recently reported s tudy of na tura l colds oc-

curr ing in children in day care showed an increase in na-

sal secretion levels of IL-1, IL-6, and IL-8 as well as TNF

levels associated with symptomatic coldsJ s There were no

differences in c ~o k in e responses in this s tudy in children

who did or did not receive antibiotics. Levels of TNF re-

mained elevated for a m u c h longer period than did the in-

ter leukin levels.

HOW DO WE CATCH COLDS?

Three major routes by which a virus could get from one

person to another have been extensively studied. 19, 20

These are airborne t ransmiss ion by small aerosolized par-

ticles, the so-called droplet nuclei, which may remain

suspended for prolonged periods of time and travel signif-

icant distances; t ransmiss ion by large aerosol particles

t h a t travel no more than a few feet; and direct contact.

Most of the data we have regarding t ransmiss ion of colds

come from experimental infection ra ther than na tura l in-

fection and may not completely reflect what happens in

the real world, bu t are probably a good, if not perfect, ap-

proximation. Drs. Gwaltney, Hendley, and colleagues at the Uni-

versity of Virginia have done beautiful s tudies of cold

t ransmission. One s tudy reported in 1978 addressed the

three potential routes. 2~ First they demonst ra ted that the

virus could easily be transferred from contaminated

hands of one person to another. A 10-second hand con-

tact led to viral t ransfer in 20 of 28 contacts. They then

demonst ra ted tha t hand- to -hand contact was an efficient

method of cold t ransmiss ion whereas large-particle aero-

sols rarely t ransmit ted infection and small-particle aero-

sols were ineffective in t ransmit t ing colds (Table 3).

Employing a clever device tha t enables volunteers to

sit at a table and play cards while prohibiting them from

touching their noses, Dr. Elliott Dick and his University of

Wisconsin colleagues have demonst ra ted tha t colds can

be t ransmit ted by large-particle aerosol. 22 However, this

means of t ransmiss ion is not efficient and requires pro-

longed exposure unlikely to occur in most na tura l set-

tings.23. 24 Transmiss ion by this route also appears to re-

Table 3. Transmissibility of Experimental Colds*

Method Exposed Infected

Hand-to-hand 15 11 Large-particle aerosol 12 1 Small-particle aerosol 10 0

*Adapted f f o m reference 21.

232 Lorber, The Common Cold IGIM

quire the presence of severe colds with cough as a

prominent symptom. Tyrrell showed in the 1960s tha t in-

fectious aerosols produced by coughing and sneezing

come primarily from the salivary pool in the mou th and

not from nasal secretions.

Studies of the risk of infection by site of initial inocu-

lation show tha t the amoun t of virus needed to produce

symptomat ic infection follox~_ng inoculat ion onto the na-

sal mucosa or inside the nares is 1 /10 ,000th the amoun t

necessary following inoculat ion on the nose outside of the

nares. 23 Other s tudies have shown the conjunct iva to be a

hospitable place for rhinoviruses, with t ransmiss ion effi-

ciencies approximat ing those of the nasal mocusa. Rhi-

novirus infection is not believed to occur in conjunctival

cells; rather, virus deposited in the eye is rapidly passed

down the tear duct into the nasal passages, The mouth is

not an efficient place for t ransmission, as has been dem-

onstrated by kissing studies. In 1984, the Wisconsin

group reported a s tudy in which donors kissed recipients

for 11/t2 minutes (two 45-second contacts). 2~ Subjects were

ins t ructed to "use the kissing technique most na tura l to

them." Only 8% of those kissed by infected donors got

symptomatic colds.

Studies of the na tura l rate of secondary infection

have shown t ransmiss ion efficiencies ranging from 38% in

spouses in s tudies of marr ied couples to as high as 88%

in persons confined to a small closed envi ronment in Ant-

arctica. 25 The incubat ion period for secondary cases in

households has been shown to be 1 to 10 days with a me-

dian of 3 days. 26

Virus has been found on 40% of donor hands on a

single sampling and 909/o on repeat sampling. It is found

in only 10% of cough or sneeze samples. It survives on the

hands even when dry- for several hours. 27

So it appears that the major means of cold t ransmis-

sion is from the donor 's nose to the donor 's hand, arid

from there to the recipient 's hand, and hence from the re-

cipient 's fmger to his or her nose or eye. Fomites can

t ransmit colds. If a donor touches a cup handle or playing

cards and then leaves the room, an individual who subse-

quently handles these objects may develop a cold.

The quest ion of how often we place ourselves at r isk

for colds by put t ing our fingers to our noses or rubbing

our eyes has been answered by the Virginia group who

observed medical staff a t tending grand rounds presenta-

t ions as well as individuals in a Sunday School group. 28

The doctors rubbed their eyes and picked their noses

about once every two to three hours; Sunday School at-

tendees seated in a circle rubbed their eyes with equal fre-

quency but less often touched their fingers to their noses,

IMMUNITY

Even if immuni ty were complete, one could have a cold

every year and not use up all the antigenically dist inct

rhinoviruses. Neutralizing antibodies to rhinoviruses are

found in the se rum of only 40% to 85% of individuals with

symptomat ic infection depending on the type of virus. Im-

muni ty to coronaviruses appears to he short-lived, and

reinfections with the same immunotype do occur. Virtu-

ally nothing is known about the role of cellular immuni ty

in colds. However, there is evidence tha t rhinovirus colds

trigger a systemic cell-mediated response. 29' 3o

DIAGNOSIS

The diagnosis of a cold is not difficult--you know it when

you see it. The virus can be cul tured on h u m a n embry-

onic lung cell l ines such as WI-38, bu t this is rarely done

outside of investigational studies. Serology is not useful be-

cause there are too many serotypes and symptomat ic in-

dividuals do not always demonstrate a rise in antibody titer.

CLINICAL FEATURES

The common clinical features of the common cold are

shown in Table 4. Nasal symptoms including nasal stuffi-

ness, runny nose, and sneezing are the mos t common

symptoms, occurring in 45% to 75°/0 of patients. Scratchy

or sore throats are the next most common, occurr ing in

one third to one half of patients, and const i tut ional symp-

toms such as headache, feverishness, and myalgia are

less frequent, occurr ing in 10% to 40% of patients. A third

of pat ients experience cough or hoarseness or both.

Symptoms tend to peak on the second or third day of ill-

ness, and mos t symptoms resolve in roughly one week

with the exception of cough, which may linger. Smokers

have the same incidence of colds as nonsmokers , bu t the

symptoms are more severe, part icularly cough.

COMPLICATIONS

Complications of colds are uncommon. Clinical s inusit is

is seen in 0.5% of children with colds and otitis media in

2%. Rhinoviruses appear to interfere with the effective-

ness of antimicrobial therapy for bacterial otii:is media

Table 4. Clinical Features of the Common Cold

% Symptom or Sign . . . . . .

Nasal Discharge 75 Sneezing 60 Obstruction 45

Pharyngeal Sore throat 50 Scratchy throat 30

Lower respiratory Cough 40 Hoarseness 30

Constitutional Headache 40 Feverishness 15 Myalgia 15

JGIM Volume 11, April 1996 2 3 3

more than other viruses. 3l In adults , na tu ra l rhinovirus

colds are frequently associated with pronounced bu t t ran-

s ient increases in middle ear pressure. 32

Cold vi ruses have been shown to precipitate a s thma

attacks, and in children have been the most common in-

fectious agents associated with acute at tacks, tn experi-

menta l rhinovirus infection, forced expiratory volume in

one second {FEV1) is decreased, and some adul ts with

mild to moderate a s thma have been shown to have an in-

crease in h is tamine sensitivity dur ing rhinovirus infec-

tion. Most exacerbat ions of chronic obstructive pulmo-

nary disease are linked to viral ra ther than bacterial

infections; rhinoviruses can contr ibute to this morbidity,

bu t less frequently t h a n other respiratory viruses.

Although the percentage of colds that are complicated

(sinus, ear, as thma, bronchitis), the absolute number of

cases of the complications is large because colds them-

selves are so common.

Recently publ ished studies of computed tomographic

imaging, 33 as well as magnet ic resonance imaging, a4 in

pat ients with uncomplicated colds have shown tha t s inus

abnormali t ies are extremely common and self-limited. A

cold is in reality a rhinosinusit is . The frequency of s inus

abnormali ty should not be used as a rat ionale for antibi-

otic t r ea tment of colds, as some have suggested, because

these s tudies show that s inus involvement is common

and self-limited.

TREATMENT

There is a great deal of irrational behavior regarding cold

t reatment . In Dr. Andrewes' words, "almost everyone has

his own foolproof technique for preventing or curing colds

• . . even the mos t eminent men of science a lmost invari-

ably lose all sense of critical j udgmen t when colds and es-

pecially their own colds are concerned." The great physi-

cian-educator, Sir William Osier, did not th ink m u c h of

the cold remedies of his day, and his own recommenda-

tion for cold managemen t is as follows: Go to bed. Hang

your ha t on a bedpost. Drhfl¢ whiskey unti l you see two

hats. In the morning you'll be m u c h better,

For the moment , cold t rea tment is primarily symp-

tomatic. There is no role for antibiotics in the typical cold.

Direct approaches to the virus include blocking agents to

prevent the virus from binding to ICAM-1 or to give solu-

ble ICAM-1 to bind virus before it reaches receptors.

Agents such as these are under investigation, as bu t none

are available.

Antiviral medicat ions have been studied including in-

terferon and other agents. Interferon does work. Studies

comparing interferon alfa with placebo show that inter-

feron-treated subjects have a diminished rate and dura-

tion of virus shedding and decreased nasal secretion

weights during the period of drug administrat ion. 36 The

problem with interferon alfa is tha t many subjects experi-

ence local adverse effects including nasa l dryness, crust-

ing, bleeding, and mucosa l ulceration, aT, 38

A n u m b e r of direct antiviral agents have shown good

ability to inactivate rhinovirus in vitro. One such agent,

pirodavir, was studied in a randomized double-blind pla-

cebo-controlled trial. 39 Those treated with in t ranasal piro-

davir had less virus recoverable from nasal washes, bu t

unfor tunate ly there was absolutely no impact of the anti-

viral on any of the usua l cold symptoms compared with

those of placebo-treated patients.

Another approach to t rea tment employs ant imedia-

tors because there is good evidence implicating kinins, cy-

tokines, and so forth, in pathogenesis of colds. To sum-

marize, data for these agents are not compelling, and

often conflicting. Agents that have been s tudied include

aspirin and other nonsteroidal ant i - inf lammatory agents,

both nasal and systemic steroids, ant ihis tamines, and ip-

ratropium, a parasympathet ic blocking agent.

In some studies, aspirin was shown to be bet ter than

placebo in decreasing cold symptoms, but one should

view these resul ts with caut ion since the major effect of

aspirin and nonsteroidal drugs is on headache and sore

throat and not on the nasal symptoms. In some s tudies

aspirin and other nonsteroidal drugs increase viral shed-

ding when compared with placebo. 4° Symptomatic im-

provement coupled with prolonged shedding could be bad

in te rms of the public heal th because pat ients who feel

bet ter are more likely to re turn to work or school and,

while shedding ~ - u s for a longer time, spread the infec-

tion to a greater n u m b e r of individuals. In 1992 the Vir-

ginia group reported on the use of naproxen in experi-

menta l colds, finding no alteration of viral shedding or

antibody responses bu t a beneficial effect on headache,

malaise, myalgia, and interestingly, cough. 41 There was

no effect on nasal symptoms. Nonsteroidal drugs are

prostaglandin inhibitors, and it has been shown that in-

t ranasal challenge with prostaglandin is a potent s t imu-

lus for cough in heal thy volunteers.

In a recent s tudy of in t ranasal and systemic steroids

(inhibitors of IL-1 production) before and after inoculation

with virus, the steroid-treated group shed virus for a

longer period than those receiving placebo, bu t there was

no difference in infection rates. 42 These data and those

from earlier s tudies showing that pat ients on steroids do

not seem to have worse colds or more complications are

comforting because many individuals use nasal steroids

for seasonal allergies. Data on ant ih is tamines are also conflicting. Chlor-

pheni ramine was superior to placebo in a mul t icenter trial. 43 Studies of terfenadine showed no benefit. 44- 45 A

more recent s tudy employing the ant ih is tamine clemas-

tine fumarate , which has anticholinergic and H 1 blocking

actions, showed a 35% to 50% reduct ion in sneezing and

nasal discharge wi thout impact on other s3n-nptoms in-

cluding nasal obstruction, sore throat, cough, headache,

a n d m a l a i s e . 46

The nasal secret ions of colds have been reduced by

using nasa l ipratropium, a parasympathotyt ic agent. 47

Vasoconstrictors such as phenylphrine, ephedrine, or o x y -

234 Lorber, The C o m m o n Cold JGIM

metazoline in the form of drops or spray do provide symp-

tomatic relief of obstruction, but the relief is short-lived,

and after a couple of days use rebound is a problem. 4s A

combination of antihistamine plus pseudoephedrine was re-

portedly effective. 49 Gwaltney has recommended a multiple-

agent approach, combining an antiviral agent with other

compounds that block selected inflammatory pathways. 5°

There is a common belief that milk produces mucus. An

Austral ian s tudy showed tha t milk did not produce higher

levels of nasal secretions dur ing rhinovirus infection, a~

Tonsil lectomy does not decrease the incidence of colds.

Other t rea tment approaches include inhalat ion of

warm moist hea t (chicken soup equivalent), along with

zinc and vi tamin C. Studies have both supported the effi-

cacy of these remedies and shown no beneficial effect.

Ty~ tell at the Harvard Hospital showed tha t nasal h}~er-

thermia, in the form of inhaled moist heat when used at

the beginning of a cold, reduced symptoms by more than

40%. 52 More recent s tudies from the Cleveland Clinic in

pat ients with na tura l colds showed that raising in t ranasal

tempera ture to 43°C by s team inhalat ion was no bet ter

than placebo with regard to nasal congestion, drainage, sneezing, and nasal resistance. 53, 54

There was some early en thus ia sm for zinc gluconate

(zinc inhibits viral polypeptide cleavage). Two randomized

controlled trials of zinc gluconate lozenges tas te -matched

with placebo (unlike earlier studies) were performed by

the Virginia group in the late 1980s and showed no effi-

cacy. 55 A similar negative resul t with zinc acetate was re-

ported from Australia; in fact, illness lasted longer in the

zinc-treated group, s6 A 1992 s tudy of zinc gluconate from

the Dar tmouth College Health Service showed a 500/0 re-

duct ion in the durat ion of symptoms if the medicat ion

was star ted within one day of the onset of symptoms;

tas te -match ing was not optimal in this s t u d y Y

There is no clear therapeut ic effect of vi tamin C. as Re-

garding t reatment , the late, renowned spor tscas ter Red

Barber, when asked one day in 1986 if he had any reme-

dies for the cold, said: 'q'he best t rea tment I know for a

cold is a pair of clean sheets." Or as the old adage says:

With proper t rea tment a cold can be ended in seven days;

otherwise, it lasts a week. These s ta tements are unduly

pessimistic. Some s tandard remedies do seem to give re-

lief. Among these are decongestants (oral preferred) for

nasal obstruction, dext romethophan and codeine (possi-

ble naproxen and ibuprofen) for cough, first-generation

ant ih is tamines for reducing sneezing and rhinorrhea,

warm gargles for sore throat, nonsteroidal ant i - inf iamma-

tory drugs for headache and sore throat, and petrolatum-

based oin tments for raw and macera ted skin a round the

nose and upper lip.

PREVENTION

Vaccines are not likely to be useful, as there are more

than 100 antigenically dist inct rhinoviruses, several coro-

naviruses, 47 adenovinlses , and so on.

Interferon and, before that, interferon inducers have

been shown to prevent colds in home contacts. An early

s tudy used intranasal poly-I:C, an inducer of interferon,

with beneficial effects, 59 In later studies, postexposure

prophylaxis with interferon alfa reduced respiratory infec-

tion by 40% and almost el iminated colds due to rhinovi-

ruses.60. 61 Long-term interferon use caused m u c h nasal

irritation and produced bloody discharge and nasal ulcer-

ations 37. 38 but shor t - term use (5 days of prophylaxis)

would probably be sufficient and would avoid local side

effects. In another postexposure s tudy in families employ-

ing in t ranasal interferon alfa-2b, no benefit was seen. 62

Interferon beta is as active in vitro as interferon alfa and

appeared to be bet ter tolerated. Unfortunately, in a s tudy

of na tura l colds in early au tumn, colds occurred in 5% of

the placebo-treated group and 6% of those receiving inter-

feron beta. 63

Unfortunately, Linus Pauling notwithstanding, the

weight of the evidence is that v i tamin C is minimally help-

ful, if at all, in the prevention of colds. 64 Many studies of

vi tamin C suffer from a placebo effect since subjects tak-

ing vi tamin C were able to detect tile bitter taste. Coule-

han and colleagues showed a beneficial effect of vi tamin C

prophylaxis in a Navajo boarding school. 65 Those taking

vi tamin C prophylaxis had fewer days of respiratory infec-

tion morbidity. Disappointingly, 2 years later, the same

group performed a double-blind, placebo-controlled s tudy

of vi tamin C prophylaxis in Navajo school children in

which no benefit was shown. 6e In fact, children with high

blood levels of vi tamin C had a longer mean durat ion of

illness than others. What can work to prevent colds are efforts to block

transmission. Paper t issues do decrease cold t ransmis-

sion, especially if impregnated with a virucidal agent. 67, as

But even without such agents, t i ssues mechanical ly block

virus t ransmiss ion if used and disposed of promptly after

use. Studies in households show tha t mothers of children

with colds did not catch colds if they dipped their hands

in virucidal baths, tZates were reduced from 40 to 13

colds per 1,000 days of exposure. Iodine in a 2% solution

is highly effective but stains the skin. A 1984 publicat ion

showed that a lotion containing glutaric acid worked for

some, bu t not all, s t rains of rhinoviruses. 69

Handwashing is a good idea, as is remember ing to

keep one 's fingers away from the eyes and nose.

Finally, the great humoris t Robert Benchely provided

some advice about avoiding colds in a 1947 essay. I'd like

to share some of his wisdom.

Don't breathe through your mouth or your nose. These

two orifices have been called "the twin roads to germ- ville" and, on a busy day, present a picture to the micro- scope similar to that of the Boston Turnpike. So long as people use their mouths and their noses to breathe

through, we're going to have epidemics, plagues and the

eventual disintegration of the human race. Eat a balanced diet. No proteins, no starches, no

carbohydrates. Jus t a good s teak with lyonnaise pota-

]GI~II V o l u m e 11, Apri l 1 9 9 6 235

toes a n d asparagus . R e m e m b e r the old adage: "S tu~ a cold a n d s t u f f a fever ."

No exercise. This is all-important. Exercise j u s t s t irs up the po isons in the s y s t e m and m a k e s you a hot-bed q]" d i sease . Sit, or lie. a s still a s possible.

I f you th ink you have caught a cold, call in a good doctor. Call in three good doctors and p lay bridge. 7°

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