1. COLDS

2. The COMMON Cold #1 REASON for visits to physicians, #3 for internists
27 million physician visits per year
23 million days of work missed
Average adult has 2-4 colds per year
$3 billion spent per year on OTC remedies
The common cold is unavoidable. It's the most common illness. One of the most common reasons people go to the doctor. As with the other topics covered this block, it is so common, we ought to be expert in dealing with it. As you can see, in the US more money is spent on OTC cold remedies than the GNP of many countries in the world
It can be a bore, but really it’s sort of a pure encounter; the illness is almost always self-limited; the patient almost always gets better. But the dynamics of the doctor-patient encounter, the battle over antibiotics, conflicts with patients’ beliefs about the illness are the same as with more serious diseases, but here they are in pure form.

3. Epidemiology September through May
Spread by hand-to-hand contact and aerosols
Reason for cold season not known - hypothesized at least in temperate climates that that’s when people are in school, indoors in large groups
Spread - experimental rhinovirus in healthy volunteers mostly through handtohand, other viruses causing cold may be different. Found in >40% of single swab samples from hands, <10% of coughs and sneezes. A study of natural colds found that handwashing with virucidal soap reduced transmission; rhinovirus transmission was zero. RSV requires close contact. Influenza transmission is mostly by small particle aerosol. Fomite transmission is possible, but in general concentrations on objects are low. Inserting virus into nasal cavity much lower innoculum than in the oral cavity. One study of experimental rhinovirus - 1/10000th the innoculum needed inside the nose as outside the nose. Kissing studies show the mouth not efficient. The conjunctiva is efficient - doesn’t infect - gets into the nares from the tear ducts.
Although commonness of cold you would expect a very efficient transmission rate, one study looking at transmission rates among married couples showed only 38% rhinovirus. Another study of experimentally induced rhinovirus infection showed 44% transmission after 150 donor/hours of exposure. Infection rate was only 10% with 3-36 hours exposure. Also adult physicians do not have higher frequency of colds.

4. _____________________________________
Microbiology
_____________________________________
Virus % of cases
Rhinovirus
Coronavirus
RSV
Influenza
Parainfluenza
Adenovirus
Unkown
Most colds are rhinoviruses of which there are over a 100 antigenic types, immunity to one does not usually convey immunity to another. Random patterns of spread.
Incubation period is 48-72h; viral shedding can last 1-2 weeks after symptoms go awayu.

5. Pathogenesis ICAM Rhinosinusitis
Histology of Nasal Epithelium is Normal
Increased vascular permeability and secretions
Components of Snot
Role of PMNs, Histamine, Kinins, IL
Rhinoviruses attach to intercellular adhesion molecule, gain entry into cells. They grow better at deg centidgrade, but multiple studies looking for association between infection and cold and wet haven’t shown a connection.
They impair the action of ciliated cells, perhaps acccounting for the rare complicaitons.
There is little cellular infiltrate or morphologic change in the intact epithelial cells
Snot is a combination of vascular leakage , increased mucus production, small amounts of shedding epithelial and immunoglobin
It’s probably the host immune response that increases rhinorrhea. WBC counts rise slightly. Increase IgG and IgA on third day of cold in snot. Histamine plays no role. Kinins appear to be the best candidate for mediator - major differences between infected/symptomatic and infected/non-symptomatic subjects in levels with appropriate time course. IL-1,6,8 similar.

6. Approach to the common cold ____________________________________ ____________________________________
H & P
Diagnosis - consider complications, flu allergy, strep
Ascertain Expectations
Reassure (but don’t minimize)
Express sympathy
Educate
Offer symptomatic relief

7. H & P Symptom Frequency Day Nasal 45 to 75% 1 - 2 Discharge Sneezing
Obstruction
Pharyngeal to 50%
Sore Throat
Scratch Throat
Cough to 80%
Hoarse to 30%
Constitutional
Feverish
Myalgia
Headache
The cold is usually not a difficult diagnosis to make. The usual course is onset of nasal symptoms, followed in a day or so by feverishness, weakness, scratchy throat, and cough. The fever is usually low-grade.
On exam, the patient is non-toxic. The temp is lowgrade or normal. Nares is inflamed equally with watery/snotty discharge, throat slightly erythemtatous, no LN, Chest CTA

8. Consider Complications
Bronchitis
Sinusitis
Otitis Media
Pneumonia
Bronchospasm
In terms of the rate of complication, it is extremely low; less than 2%, probably less than 1%. But because the illness is so common, you do see a lot of cases of complicated cold.
Cough associated with nasal symptoms and other characterisitc symptoms usually due to throat clearing, postnasal drip. The cough associated with viral infection frequently lingers as well. There are multiple studies comparing the outcomes of patients with cough, phlegm (even purulent) and preceding or concomitant nasal symptoms. The abx make no difference in the outcome, rate of complication, time to improvement. They also have no prophylactic role.
Viral rhinosinusitis can be difficult to distinguish from bacterial - there are various studies, some well conducted for clinical algorithms for sinusitis. When purulent nasal discharge on inspection, maxillary toothache, colored rhinnorhea, history of poor response to OTC decongestant and antihistamine, and abnormal transillumniation are all present probability of sinusitis is 90%. In some studies facial pain when bending over is discriminating. The time course helps too. Sinus symptoms that come on with a cold and without any of these distinguishing features have a very low probability of sinusitis < 10%.

9. THE TRUE BLUE FLU Epidemiology
Usually peaks in January or later
20,000 deaths in a typical epidemic season
110,000 hospitalizations
10%-20% of population infected during typical season
When flu epidemic in region, high percentage of those with ILI have flu
During pandemics (three this century) attack rates have been higher than 50%. Biggest one was 1918, the spanish flu. More people died than in WWI. Last major pandemic was Hong Kong Flu of 1968.
Transmission is possible through aerosol and direct contact. Probably mostly aerosol, the epidemics move fast.
Incubation 1-7 days, usually 2-3. Viral shedding begins one day before onset of symptoms, peaks with severity; declines over 4-5 days. You could make a case for isolating these patients.

10. THE TRUE BLUE FLU Clinical Presentation
Classic Flu - sudden onset prostration, high fever, nasal stuffiness, sore throat, myalgia, cough and headache
Study Flu - usually fever + 2 symptoms
Illness resolves over four to five days
Cough, fatigue, malaise can linger 2-3 weeks
Complications - bacterial tracheobronchitis, sinsusitis, pneumonia
During pandemics (three this century) attack rates have been higher than 50%. Biggest one was 1918, the spanish flu. More people died than in WWI. Last major pandemic was Hong Kong Flu of 1968.
Transmission is possible through aerosol and direct contact. Probably mostly aerosol, the epidemics move fast.
Incubation 1-7 days, usually 2-3. Viral shedding begins one day before onset of symptoms, peaks with severity; declines over 4-5 days. You could make a case for isolating these patients.
Most deaths and complications are in the eldedly

11. DIAGNOSIS OF INFLUENZA Are there pathognomonic symptoms
DIAGNOSIS OF INFLUENZA Are there pathognomonic symptoms? Proportion of patients with symptom
Symptom
Fever (> 37.8)
Feverishness
Cough
Nasal congestion
Weakness
Loss of Appetite
Sore Throat
Headache
Myalgia
With flu Without flu
From “Clinical Signs and Symptoms Predicting Influenza Infection” Arch Int Med 160: 11/27/00
Looked at data from Zanamivir trials which documented flu infection carefully, mostly type A, some B
With flu more likely to have cough, fever; best multivariate predictor was combo of cough and fever. + predictive value went up with higher temp
Basically these numbers are so high that for any one patien, the symptom complex will not distinguish

12. DIAGNOSIS OF INFLUENZA Are there pathognomonic symptoms?
USE OF A CASE DEFINITION AS A DIAGNOSTIC TOOL
100 patients with a flu-like illness:
T > plus 2 of 4: cough, myalgia, sore throat, headache
Case Definition: T > 38 + cough during flu season
Positive Predictive Value 86.8%
Negative Predictive Value 39.3%
Sensitivity %
Specificity %
__________________________
“Predicting influenza infections during epidemics with use of a clinical case definition” Boivin et al Clinical Infect Dise 2000 nov
Most important was the season. Bundling symptoms by itself doesn’t help; spec and NPV are low.
Can rule in flu somewhat; avoid abx

13. DIAGNOSIS OF INFLUENZA INFLUENZA SURVEILLANCE www.cdc.gov
WHO - worldwide tracking of drift and shift
CDC, Influenza Branch
National Respiratory and Enteric Virus Surveillance System
122 Cities Mortality Reporting System
State and Territorial Epidemiologists Reports
US Influenza Sentinel Physicians Surveillance Network
Influenza Surveillance - given that the most important determinant of whether a syndrome is flu is the presence of the virus in the community, how do we know this?
WHO -elaborate international tracking of antigenic drift and shift of Hemagluttin and Neuramidase Drift and Shift; advises manufacturers what to stir into vaccines. Tracks worldwide progress of epidemic. Some guesswork to all of this. Strain emerges with enough change that people have no immunity
CDC - has a whole division devoted to flu. The NREVSS is a network of labs that report numbers of specimens sent in and tested. Types virus.
The 122 cities - vital statistics offices of the cities report total # of death certificates of pneumonia and/or flu listed.
State health departments report activity each week. "Sporadic" = flu or ILI but no outbreaks in schools or NHs. "Regional" - outbreaks in area less than <50% of state's pop. "Widespread" - > 50%
Sentinel physicians report # of patients seen, # with ILI.

14. DIAGNOSIS OF INFLUENZA
RAPID FLU TESTS
The FDA approved 3 new in-office test kits: FLU-OIA, QuickVue and Zstatflu - detect viral antigens via immunoassay, or neuramidase activity
Senstivity is low in adults with less severe illness - maybe 60%
But specificity is 95%.
They take about 1/2 hour to cook.
15-20$
The Reverse Transcriptase PCR is as sensitive as viral cx but not comercially available yet.
The characteristics of the test not that different from physician impression during epidemic. Therefore most useful at the the beginning and end of epidemics.
Because of the time frame for treatment, doesn't so much benefit the individual pt in terms of specific treatment; some value to confirmed diagnosis; can prophylax contacts; avoid abx

15. INFLUENZA Treatment Drug Trade Name Flu Type Cost Caveat
____________________________________________________
Amantidine Symmetrel A Resistance
Generic CNS
Rimantidine Flumadine A Resistance
Zanamivir Relenza A and B Bronchospasm
Oseltamivir Tamiflu A and B GI
All the drugs are only effective in the first 48 hours of the illness. In general they reduce the duration of symptoms by a day or two and reduce the severity. None definitively reduces the incidence of subsequent complications (pneumonia, sinusitis, bronchitis, OM. Consider treatment in someone at very high risk - old old, frail, COPD, marginal pulmonary reserve. Someone with a particularly severe case (pneumonia).
Rimantidine and Amantidine block an ion channel in the viral membrane and block a step in the entry of viral proteins into the cell.
Zanamivir and Oseltamivir are neuramidase inhibitors. Neuramidase is a viral protein that permits the virus to grab through mucus to the surfaces of cells. Neuramidase also active in the release of virus from infected cells.
All things considered, Zanamivir or Oseltamivir probably the best medicines for treatment of an individual case. They treat influenza B, there is no reported resistance as yet; there may be lower complication rates
If cost an issue, amant or rimant; CNS side effects in elderly; rimant may be better.

16. INFLUENZA Prophylaxis
VACCINATE
EXPOSURES
LONGTERM CARE FACILITIES
Just a side note:
Vaccination is still the most effective and safe means of prevention. 90% effective in healthy adults. Less so in the elderly. Associated with impressive reductions in hospitalizations (52%) for pneumonia and influenza.
Vaccination takes 14 days to work. Sometimes the vaccine is a poor antigenic match for the virus. In high risk, double barrel vax + drug may work. If it is a particularly bad flu that year, consider. Can use any of the antivirals - use of rimantidine as prophylaxis hasn’t been associated with resistance. Studies in healthy people showing neuramidase inhibitors work as prophylaxis.
Outbreaks in LTC facilities can involve high percentage of residents, most of whom are at high risk. Even when vaccinated. If an outbreak starts, antivirals should be given to all residents regardless of vax status until a week or two after the onset of the last confirmed case.

17. Approach to the common cold ____________________________________ ____________________________________
H & P
Diagnosis - consider flu, bacterial complications, allergy, strep
Ascertain Expectations
Reassure (but don’t minimize)
Express sympathy
Educate
Offer symptomatic relief

19. Patients’ Understanding of the Common Cold
* 87% of people do not seek care for their colds
* In a survey of young adults 94% said it was not necessary to go to a doctor for a cold.
On the other hand
* Of patients in a clinic for other reasons, 61% said they would seek care for 5days rhinorrhea, cough, sore throat; if the discharge were discolored, 79% would seek care.
* 87% of a sample in England thought antibiotics were beneficial for a cold. a

20. Patients’ Understanding of the Common Cold
What Causes a Cold?
Virus 43.5%
Virus and Bacteria 41.9%
Bacteria %
Don’t Know 6.7%
Antibiotics are helpful for colds
Strongly Agree 18.2%
Agree %
Disagree 17.2%
Strongly Disagree 31.4%
Don’t know % aa
Study from year Healthy suburbanites seeking care for the common cold, 506 people who’d been to dr.
Conducted as an “update” to previous studies - some of which they allude to from the late 70’s and early 80’s. A startling 87% in the uK believed abx helped.
Kind of a crappy study

21. Factors Correlating with a Desire for Antibiotics
Previous Rx for Antibiotic for URI
Belief they work
Purulent secretions
Medicaid
From a country where abx are OTC
Couldn’t’ find studies looking at comparison of paying, non-paying

22. Why not give antibiotics?
Biggest Risk Factor for developing resistant S.pneumonia is previous exposure to abx
Good studies show that when overall antibiotic prescribing is reduced, the prevalence of resistant strains drops.
About 30% of all the antibiotics prescribed in the US are for outpatient colds. In many studies, patients with clear cut colds are Rxed abx 50-60% of the time.
They don’t work a

23. A Multidimensional Intervention to Reducing Rxs For Antibiotics
For “Bronchitis”
Preliminary study found that clinicians code according to Rx given, not symptoms. The dx of “chest cold” rather than “bronchitis” lowered expectations for abx
Patient and clinician education
Reduced Rxs for bronchitis from 74% to 48%

24. Symptomatic Treatment
Symptom Treatments
Congestion Topical Decongestant
Oral Decongestant
Rhinorrhea Anticholinergic
Sneezing Antihistamine
Cough Suppressant
Tx for Rhinorrhea
Constitutional Acetaminophen
ASA, NSAID
Sore Throat Gargles, Lozenges
Analgesia a
There are over 800 different OTC remedies; slightly different forumulations. For the number of $ and Rxs written it's remarkable how few good studies there are on this. It's all marketing.Almost all the treatment effects if they've been shown at all are minimal - 20%. You have to look at the different formulations to see what's really in it.
What makes the most sense is this:
Congestion - stop the vascular permeability with decongestant. They have been shown superior to placebo in reducing symptoms. no head to head. Antihistamines have shown no effect on congestion
Rhinorrhea - profuse discharge responds somewhat to decongestant. Also responds to decrease in cholinergic stimulus to secretion. Either thru side effect of first gen antihistamine (not second!) or through atrovent nasal.
Sneezing - antihistamines work unknown mechanism
Cough - only studies done of combo of dexbromphenaramine and sudafed and naproxen. Suppressants haven't been well studied. Pt's like codeine - more nausea with DM and more sedation with codeine. Makes sense if there's prominenet PND to treat nose. Prolonged cough r/o wheeze, sinusitis, tx PND

25. Remedies
Zinc Gluconate
Vitamin C
Chicken Soup
Vapors

26. You’ve got the worst cold I’ve seen all day

27. Are you miserable? You look miserable.

28. I wish we had better treatments for bad colds

29. but as you know there’s no cure yet

30. Your cold comes from a viral infection.

31. Unfortunately,
Antibiotics don’t kill viruses; they only work for bacterial infections. I would give you an Rx if I thought it would help in any way.

32. And furthermore,
Taking antibiotics can put you at risk for resistant infections. When you take them, you can select the bacteria that are resistant to them, that can survive them, and there’s a chance that if you needed them later, they might not work as well or at all.

33. YOUR body will fight this off just like it’s always done.

34. Your body’s immune system works best when you give it plenty of rest
And fluids

35. In the meantime, let’s see if we can treat the symptoms so you’re not suffering so much.

36. If it’s helping, keep taking the oil of newt

37. If you get worse,

38. I HOPE YOU FEEL BETTER SOON

39. bye

40. NO I AM NOT JUST GOING TO GIVE YOU THE ANTIBIOTICS

41. Approach to the common cold ____________________________________ ____________________________________
H & P
Diagnosis - consider flu, bacterial complications, allergy, strep
Ascertain Expectations
Reassure (but don’t minimize)
Express sympathy
Educate
Offer symptomatic relief