Viral Respiratory Viral Respiratory Infections in theInfections in theMorbidity and MortalityMorbidity and Mortalityof Airway Diseases andof Airway Diseases and Immunocompromised Immunocompromised StatesStatesAcute and Chronic Bronchitis,Acute and Chronic Bronchitis,COPD, Asthma, Cystic Fibrosis,COPD, Asthma, Cystic Fibrosis,and Immunocompromisedand ImmunocompromisedCancer PatientsCancer Patients

Frequency, Seasonality, Frequency, Seasonality, and Characteristics of and Characteristics of Viral Respiratory Viral Respiratory Infections (VRIs)Infections (VRIs)

• Recognized for the last century as the most common infectious illness in humans

• Terminology has varied– Common respiratory infection– Common cold– Rhinosinusitis

• Rhinoviruses (RVs) cause a majority of these infections

Impact of VRIsImpact of VRIs

Monto AS et al. Clin Ther. 2001;1615.

• Adults average ~2 to 4 colds1,2 and children average 3 to 8 colds3 per year

• In 1996, colds were associated with ~148 million days restricted activity, 20 million days missed work, 22 million days missed school, 45 million days bedridden4

• In 1998, 25 million office visits to primary care providers for upper respiratory infections (URIs)5

• Costs associated with VRIs estimated at ~$25 billion annually6

1. Turner RB. Pediatr Ann. 1998;27:790. 2. Monto AS et al. Clin Ther. 2001;23:1615.3. Rosenstein N et al. Pediatrics. 1998;101:181 4. Adams PF et al. Vital Health Stat. 1999;10 (200). 5. Gonzales R et al. Clin Infect Dis. 2001;33:757.6. Fendrick AM et al. Value in Health. 2001;4:412.

Economic and Societal BurdenEconomic and Societal Burdenof VRIsof VRIs

Mea

n a

nn

ual

illn

ess

inci

den

ce

Reprinted from Monto AS, Ullman BM. JAMA. 1974;227:164.

Age group (yr)

7

6

5

4

3

2

1

0 1 1–2 3–4 5–9 10–14 15–19 20–24 25–29 30–39 40–49 50–59 60

Mean Annual Incidence of Respiratory Mean Annual Incidence of Respiratory Illnesses per Person-Year, Tecumseh, Illnesses per Person-Year, Tecumseh, Michigan, 1965–1971Michigan, 1965–1971

Females

Males

30

25

20

15

10

5

0

Per

cen

t

RV Parainfluenza viruses

Per

cen

t

Respiratory syncytial virus (RSV) Influenza virus30

25

20

15

10

5

0Jan Apr Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jan Apr Sep Oct Nov Dec Jan Feb Mar Apr May Jun

Reprinted from Br J Prev Soc Med, 1977;31:101-108, with permission from the BMJ Publishing Group.

Seasonality of Respiratory Agents: Proportion Seasonality of Respiratory Agents: Proportion Isolated in Each Calendar Month During Isolated in Each Calendar Month During 6 Years of Tecumseh, Michigan, Study6 Years of Tecumseh, Michigan, Study

• Transmission of viruses differs• Influenza

– Airborne transmission1

– Widespread outbreaks

• RVs– Closer contact required– Aerosol and direct2,3

– Households and schools are sites of transmission4

Transmission of Respiratory Transmission of Respiratory VirusesViruses

1. Goldman DA. Pediatr Infect Dis J. 2000;19(10 suppl):S97. 2. Gwaltney JM Jr, Hendley JO. Am J Epidemiol. 1982;116:828. 3. Dick EC et al. J Infect Dis. 1987;156:442. 4. Gwaltney JM Jr. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases.

5th ed. Philadelphia: Churchill Livingstone; 2000:1940.

Sore throatCoughActivity restrictionLower respiratory symptomsHeadache

Coryza

Per

cen

t

RV RSV Parainfluenza virus

Hemolyticstreptococci

Influenza A Influenza B

0

20

40

60

80

100

Characteristics of VRIs ofCharacteristics of VRIs ofKnown EtiologyKnown Etiology

Reprinted from Br J Prev Soc Med, 1977;31:101-108, with permission from the BMJ Publishing Group.

Reprinted with permission from Monto AS et al. J Infect Dis. 1987;156:43. ©1987 by The University of Chicago. All rights reserved.

Characteristics of RV-Associated Characteristics of RV-Associated IllnessesIllnesses

Illness with indicated syndrome (%) Percent with

Age group (years)

No. of isolates

Lower respiratory

Upper respiratory

Laryngo- pharyngeal Other

Medianduration(days)

Activity restriction

Physician consultation

0–4 61 14.8 83.6 1.6 — 12 0 16.4

5–19 39 5.1 74.4 15.4 5.1 7 56.4 15.4

20–39 59 33.9 59.3 6.8 — 13 11.9 15.3

40 17 64.7 29.4 5.9 — 20 35.3 35.3

Total 176 23.8 68.2 6.8 1.2 12 19.9 17.6

Adapted with permission from Arruda E et al. J Clin Microbiol. 1997;35:2864.

Clinical featureRV %

positive

First symptom (% of subjects) Sore throat Stuffy nose Runny nose Sneezing

391717

8

Most bothersome symptom (% of subjects) Runny nose Stuffy nose Sore throat Malaise

36201910

Median duration of symptoms (days) Cold episode Sleep disturbance Interference with daily activities

1147

Clinical Features and Duration of Clinical Features and Duration of Illness in Adults with RV ColdsIllness in Adults with RV Colds(n=276, RV confirmed by PCR or culture)(n=276, RV confirmed by PCR or culture)

Reproduced with permission from Pediatrics, Vol. 102, Pages 291-295, Table 2. Copyright 1998.

Virus

RV

RSV

HCV

Total positive

Middle ear fluid, *No. (%)

22 (24%)

17 (18%)

7 (8%)

44 (48%)

Nasopharyngeal aspirate, †No. (%)

28 (30%)

21 (23%)

14 (15%)

57 (62%)

Infectedchildren, No. (%)

32 (35%)

26 (28%)

16 (17%)

69 (75%)

Detection of Viruses by RT-PCR in MiddleDetection of Viruses by RT-PCR in MiddleEar Fluid and Nasopharyngeal AspiratesEar Fluid and Nasopharyngeal Aspiratesfrom 92 Children with Acute Otitis Mediafrom 92 Children with Acute Otitis Media

*2 samples had both HRV and RSV RNA; †2 aspirates had both HRV and RSV RNA, and 1 had both RSV and HCV RNA. RV=rhinovirus; RSV=respiratory syncytial virus; HCV=human coronavirus.

• Sinusitis is an extremely common part of the common cold syndrome

• RV has been detected in 50% of adult patients with sinusitis by RT-PCR of maxillary sinus brushings or nasal swabs1

• Frequency of association of RV infection with sinusitis suggests the common cold could be considered a rhinosinusitis2

RV in Acute SinusitisRV in Acute Sinusitis

1. Pitkäranta A et al. J Clin Microbial. 1997;35:1791.2. Gwaltney JM Jr. Clin Infect Dis. 1996;23:1209.

• Respiratory viruses are common pathogens in acute bronchitis1

• Respiratory virus infection associated with cough1

– Influenza virus: 75%–93% of cases– Adenovirus: 45%–90%– RVs: 32%–60%– Coronavirus: 10%–50%

• 40% of nonasthmatic patients with acutebronchitis had FEV1 80% of predicted2

• Bronchial reactivity remained increased up to 5 weeks after episode of acute bronchitis2,3

VRIs and Acute BronchitisVRIs and Acute Bronchitis

1. Gwaltney JM Jr. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed. Philadelphia: Churchill Livingstone; 2000:703.

2. Williamson HA Jr. J Fam Pract. 1987;25:251. 3. Hallett JS, Jacobs RL. Ann Allergy. 1985;55:568.

• In persons 60–90 years of age with RV infection, median duration of illness was16 days

• 19% were confined to bed; 26% had restriction of daily activities

• 63% had lower respiratory tract symptoms;43% consulted their physician

• Burden of RV infection in the elderly appears to exceed that of influenza

Nicholson KG et al. BMJ. 1996;313:1119.

RV Infection in the ElderlyRV Infection in the Elderly

Reprinted from Wald TG et al. Ann Intern Med. 1995;123:588.

Upper respiratoryCoughCoryzaNasal or sinus congestionSore throat

TotalLower respiratory

Productive coughDyspneaHoarseness

TotalGastrointestinal

AnorexiaNausea, vomiting, or diarrhea

TotalSystemic

Malaise or fatigueMyalgiaSweating or chills

Total

34 (97)31 (89)21 (60)18 (51)

35 (100)

19 (54) 8 (23) 5 (14)23 (66)

11 (31) 4 (11)12 (34)

23 (66) 8 (23) 5 (14)25 (71)

Symptom No. of patients (%)

Symptoms of RV Infection in Symptoms of RV Infection in 35 Culture-Documented Illnesses 35 Culture-Documented Illnesses in a Long-Term Care Facilityin a Long-Term Care Facility

• VRIs are the most common infectious diseases worldwide

• RVs are predominant cause of VRIs in allage groups

• Transmission requires relatively close contact

• Family and school major sites of transmission• RV infections peak in autumn, with minor spring

peaks• RVs cause AOM, sinusitis, and bronchitis in

otherwise healthy people

SummarySummary

Role of VRIs in Asthma Role of VRIs in Asthma Exacerbations Exacerbations

• Poor underlying control

• Environmental factors– VRIs

– Allergen exposure

– Air pollution

– Bacterial infections

– Stress

– Exercise/cold air

– Occupational exposure

Causes of Asthma ExacerbationsCauses of Asthma Exacerbations

Reprinted from BMJ. 1995;310:1225-1229, with permission from the BMJ Publishing Group.

Virus

Picornaviruses 146 47 147

Coronavirus 17 14 21 38

Influenza viruses 14 10 20 21

Parainfluenza viruses 1, 2, and 3 6 6 18 21

RSV 6 6 12 12

Other 2 1 2 3

Method of detection

Viruses Detected During Asthma Viruses Detected During Asthma Exacerbations in ChildrenExacerbations in Children

*84 identified as RV on further testing.ELISA=enzyme-linked immunosorbent assay.

PCR CultureImmuno-

fluorescenceAntibody rise

by ELISA Total

*

Hospital admissions for asthma correlate with virus isolation peaks and school terms.

Adapted with permission from Johnston SL et al. Am J Respir Crit Care Med. 1996;154:654. Official Journalof the American Thoracic Society. ©American Lung Association.

VRIs and Hospitalizations VRIs and Hospitalizations for Asthmafor Asthma

Total pediatric andadult hospitalizations

School holidays

URIs

0

5

10

15

20

Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar

• Comparison of wheezing and nonwheezing (control) children– Age, atopic status, eosinophil markers

• In wheezing children <2 years old– Respiratory viruses detected in 82% (18/22)– RSV predominant, 68% (15/22)

• In wheezing children 2 years old– Respiratory viruses detected in 83% (40/48)– RV predominant, 71% (34/48)– +PCR for RV and nasal eosinophilia or elevated nasal

ECP, 48% (23/48)

Rakes GP et al. Am J Respir Crit Care Med. 1999;159:785.

Children with Wheezing Children with Wheezing Presenting to the ERPresenting to the ER

RV=rhinovirus; HCV=human coronavirus; RSV=respiratory syncytial virus.Nicholson KG et al. BMJ. 1993;307:982.

Pathogen

RVHCV OC43HCV 229EInfluenza BParainfluenzaRSVChlamydia psittaciDual infection

Number

76 21 15 2 5 2 3 5

Percent ofall episodes

33.2 9.2 6.6 0.9 2.2 0.9 1.3 2.2

Viruses Detected in 229 Viruses Detected in 229 Symptomatic Asthma Episodes Symptomatic Asthma Episodes in Adultsin Adults

Data from Teichtahl H et al. Chest. 1997;112:591.

Viruses Detected in Adult Patients Viruses Detected in Adult Patients Hospitalized with AsthmaHospitalized with Asthma

54.5%

6.1%

27.3%

3% 3%Influenza AInfluenza BRVAdenovirusRSVHerpes

33 organisms isolated; 5 subjects had >1 virus detected and some viruses were detected by >1 test.

6.1%

2 episodes of “common cold” beforeage 1 yr decrease risk of asthma by age 7by ~50%

• Other viral infections—eg, herpes, varicella, measles—also protective

• Reported LRI with wheeze in the first 3 years of life increases risk of asthma

Illi S et al. BMJ. 2001;322:390.

Respiratory Infections in Respiratory Infections in Infancy May Protect Against Infancy May Protect Against Development of AsthmaDevelopment of Asthma

Children who had 2 older siblings or attended day care during first 6 mo of life had increased risk of wheeze early in life but decreased risk later.

Reprinted with permission from Ball TM et al. N Engl J Med. 2000;343:538. Copyright ©2000 Massachusetts Medical Society. All rights reserved.

P=0.01

P=0.03P=0.001

P<0.001P<0.001

2.7

1.0

0.4

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Ad

just

ed r

elat

ive

risk

of

freq

uen

t w

hee

zin

g

Age (yr)

0.1

Effect of Day Care in Infancy and Effect of Day Care in Infancy and Number of Older Siblings onNumber of Older Siblings onAsthma RiskAsthma Risk

• Viral infections (esp. RV) frequently cause exacerbations of asthma

• Possible mechanisms– Extension into the lower

airway1-3

– Inflammation2,3

Immunologic Mechanisms of VRI-Immunologic Mechanisms of VRI-Induced Asthma ExacerbationsInduced Asthma Exacerbations

1. Gern JE et al. Am J Respir Crit Care Med. 1997;155:1159.2. Gern JE, Busse WW. J Allergy Clin Immunol. 2000;106:201.3. Fraenkel DJ et al. Am J Respir Crit Care Med. 1995;151:879.

AirwayHyperresponsiveness

Plasmaleakage

Mucus hypersecretion

Inflammatorycell recruitmentand activation

Neural activation

Virus-infected epithelium

Adapted from Gern JE, Busse WW. J Allergy Clin Immunol. 2000;106:201.

RV-Induced Airway InflammationRV-Induced Airway Inflammation

• VRIs (especially RV infections in children >2 yr old) and atopy synergistically enhance the risk of wheezing1

– Antigen-specific IgE– Eosinophilic inflammation

• Cytokine production pattern is related to outcomes of experimental infection2

• High IFN-/IL-5 ratio=Th1-type (antiviral) response2

• Low IFN-/IL-5 ratio=Th2-type (allergic) response2

1. Rakes GP et al. Am J Respir Crit Care Med. 1999;159:785.2. Gern JE et al. Am J Respir Crit Care Med. 2000;162:2226.

What Is Different About VRIs in What Is Different About VRIs in Asthma?Asthma?

• PBMC IFN- secretion– Reduced peak viral

shedding

• Sputum IFN-/IL-5 mRNA ratio correlates with– Lower symptom scores– More rapid viral

clearance

Parry DE et al. J Allergy Clin Immunol. 2000;105:692.Reprinted from Gern JE et al. Am J Respir Crit Care Med. 2000;162:2226.

Immunologic Risk Factors for Immunologic Risk Factors for More Severe VRIsMore Severe VRIs

Virus detected at 14 days?No Yes

IFN/

IL-5

rat

io (

un

its)

100

101

102

103

104

Th1Th1

Th2Th2

• Viruses cause asthma exacerbations in adults and children

• RVs cause ~60% of virus-induced exacerbations of asthma

• RVs directly infect the bronchial airways

• The response to viral infection is shaped by the host’s antiviral response

• VRIs in early childhood may protect against the development of asthma

SummarySummary

Role of VRI and RV in Role of VRI and RV in Acute Exacerbations of Acute Exacerbations of Chronic Bronchitis Chronic Bronchitis

Cost of Acute Exacerbations of Cost of Acute Exacerbations of Chronic Bronchitis (AECB)Chronic Bronchitis (AECB)

• Hospitalization (500,000 episodes)– Total cost, $1.6 billion– Mean LOS, 6 days– Mean cost, $5500/patient

• Outpatient office visits 65 yr: 331,000, cost $24.9 million– <65 yr: 237,000, cost $15.1 million

• Indirect costs– Days lost from work– Lost productivity

.

Niederman MS et al. Clin Ther. 1999;21:576-591

• Infectious, 80%– Bacterial pathogens, 40%–50%– Viruses, 30%–40%– Atypical bacteria, 5%–10%

• Noninfectious, 20% – Environmental factors– Noncompliance with medical therapy

Sethi S. Chest. 2000;117(suppl):380S.

AECB: EtiologyAECB: Etiology

Data from Greenberg SB et al. Am J Respir Crit Care Med. 2000;162:167.

Viral AECB: PathogensViral AECB: Pathogens

0

5

10

15

20

25

30

35

Picorna-viruses

Para-influenzaviruses

Corona-viruses

Influenzaviruses

RSV Adeno-viruses

Control

FEV1 50%

FEV1 <50%

% o

f to

tal i

den

tifi

ed

Virus-Associated Illness in Virus-Associated Illness in Controls and COPD PatientsControls and COPD Patients

2600% LRT symptoms alone

0.520.380.54No. VRIs/yr

31.81.4No. respiratory illnesses/yr

323055No. patients

FEV1 <50%FEV1 50%Controls

LRT = lower respiratory tract.Data from Greenberg SB et al. Am J Respir Crit Care Med. 2000;162:167.

• FEV1<50% predicted – 52 hospitalizations

in 12 patients – 82% acute

exacerbations,22% pneumonia

– 5 of 6 deaths were COPD related

ER=emergency room.Data from Greenberg SB et al. Am J Respir Crit Care Med. 2000;162:167.

Viral AECB: Medical Resource Viral AECB: Medical Resource UtilizationUtilization

% V

RI

0

10

20

30

40

50

60

70

80

Office ER Hospital

Control

FEV1 50% predicted

FEV1 <50% predicted

100

• AECB manifestations– Increased dyspnea, 76%– Increased sputum volume, 62% – Increased sputum purulence, 39%

• Anthonisen type– Type 1 (all 3 of above symptoms), 20%– Type 2 (2 of above symptoms), 46%– Type 3 (1 of above symptoms), 34%

• 64% of AECB associated with prior cold (18 days)

Seemungal T et al. Am J Respir Crit Care Med. 2001;164:1618.

Viral AECB: Clinical PresentationViral AECB: Clinical Presentation

• 39.2% of AECB associated with viral infection

• Cold, increased dyspnea with cold, and sore throat associated with viral isolation

Data from Seemungal T et al. Am J Respir Crit Care Med. 2001;164:1618.

0

5

10

15

20

25

% o

f re

po

rted

exa

cerb

atio

ns

RV Corona Infl A Infl B Parainfl Adeno RSV

AECB: Viral Detection and AECB: Viral Detection and SymptomsSymptoms

• AECB are associated with considerable morbidity, mortality, and health care costs

• VRIs are an important cause of AECB• RVs are frequently detected in the airway

secretions of patients with AECB

SummarySummary

VRIs in Patients with VRIs in Patients with Cystic FibrosisCystic Fibrosis

• Cause exacerbations and LRIs• Contribute to long-term pulmonary

deterioration, morbidity, mortality• Strongly associated with every measure of

CF disease progression1

• Contribute to initial bacterial colonization2

1. Wang EEL et al. N Engl J Med. 1984;311:1653.2. Armstrong et al. Pediatr Pulmonol. 1998;26:371.

Cystic Fibrosis (CF): Respiratory Cystic Fibrosis (CF): Respiratory VirusesViruses

• Infection of epithelial cells– Release of proinflammatory mediators

– Attraction and activation of inflammatory cells

– Neutrophil release of prostaglandins and oxygen radicals

• Altered endothelial permeability

• Promotion of edema, enhanced cell recruitment

• Stimulation of mucus secretion

• Airway smooth muscle contraction

Prober CG. Clin Rev Allergy. 1991;9:87.

CF: Proposed Mechanisms ofCF: Proposed Mechanisms ofVirus-Induced ExacerbationVirus-Induced Exacerbation

• VRIs are associated with clinical exacerbations of CF with disease progression

• Inflammatory response most likely mechanism by which VRIs exacerbate CF

• Viruses predispose to bacterial colonization and infection

SummarySummary

VRIs in VRIs in Immunosuppressed Immunosuppressed Cancer PatientsCancer Patients

Impairments in Viral ImmunityImpairments in Viral Immunityin BMT Recipients with Cancerin BMT Recipients with Cancer

• B lymphocytes– Reduced response to stimulatory cytokines (IL-4)– Reduced serum immunoglobulins– Depressed primary and secondary responses to antigens

• T lymphocytes– Reduced CD4 lymphocyte numbers– Reduced helper cell activity– Increased suppressor cell activity– Reduced proliferative responses– Reduced CD8 lymphocyte cytotoxic function

• Mucositis• Reduced IgA secretion

Couch RB et al. Am J Med. 1997;102(suppl 3A):2.

• Allogeneic transplant

• Hematologic malignancy

• Graft-vs-host disease

• Corticosteroid therapy

• ? Conditioning regimen

• Lymphopenia (<200/mL)

• Age >65 years

• <100 days post-transplant

Risk Factors Associated withRisk Factors Associated withSerious Morbidity from VRIs inSerious Morbidity from VRIs inBMT RecipientsBMT Recipients

Sable CA, Donowitz GR. Clin Infect Dis. 1994;18:273.

Important Features of VRIs in Important Features of VRIs in Immunocompromised PatientsImmunocompromised Patients

• High potential for nosocomial acquisition1 • Prolonged shedding of virus, even with

treatment2

• High frequency of pneumonia and death1

• Viral pneumonia often associated with other infections1

• Outbreaks can occur in absence of community epidemic1

1. Couch RB et al. Am J Med. 1997;102(suppl 3A):2.2. Bodey GP. Am J Med. 1997;102(suppl 3A):77.

1. Data from Couch RB et al. Am J Med. 1997;102(suppl 3A):2.2. Data from Ghosh et al. Clin Infect Dis. 1999;29:528.

No. of infections leading to pneumonia

Pneumonia(% of infections)

Death (% of those

with pneumonia)*

LeukemiaBMT

BMT

2233

5961

3236

2720

7870

3325

945

6758

4422

22 32 100

Progression of VRIs inProgression of VRIs inLeukemia and BMTLeukemia and BMT

RSV1

Influenza

Parainfluenza

RV2

LeukemiaBMT

LeukemiaBMT

*Other pulmonary infections often present.

• VRIs are an important cause of morbidity and mortality in immunosuppressed cancer patients

• Underlying disease and immunosuppressive therapy contribute to the high mortality rate in BMT patients with VRIs

SummarySummary

Acute Respiratory Acute Respiratory Infections and Antibiotic Infections and Antibiotic Use: A Primary Care andUse: A Primary Care andHealth Services Health Services Research PerspectiveResearch Perspective

Reprinted from Gonzales R et al. Clin Infect Dis. 2001;33:757.

Off

ice

visi

ts (

1000

)

0

5000

10,000

15,000

20,000

25,000

Office visits

Antibiotic prescription

Bacterial prevalence

Acute Respiratory Infections (ARIs):Acute Respiratory Infections (ARIs):PrimaryPrimary Care Office Visits, Antibiotic Use, Care Office Visits, Antibiotic Use, and Bacterial Prevalence in US, 1998and Bacterial Prevalence in US, 1998

30%

76%

70%

62%

59%

URI Otitis media Sinusitis Pharyngitis Bronchitis0

20

40

60

80

100

An

tibio

tic Rx an

d estim

atedb

acterial prevalen

ce (% o

f visits)

Adapted from Gonzales R et al. Clin Infect Dis. 2001;33:757.

Estimated 55% of prescriptions (22.6 million) for ARIs are unnecessary, at a cost of $726 million.

No. of prescriptions Cost estimate

ARI diagnosis (millions) (millions)

Otitis media 9.6 $280

Pharyngitis 8.7 $215

URI 7.4 $227

Sinusitis 7.9 $310

Bronchitis 7.8 $289

Total 41.4 $1322

Estimated Annual Cost of Antibiotic Estimated Annual Cost of Antibiotic Use for ARIs in US, 1998Use for ARIs in US, 1998

Adapted from Stone S et al. Ann Emerg Med. 2000;36:320.

Emergency Department Visits and Emergency Department Visits and Antibiotic Use for ARIs in US, 1996Antibiotic Use for ARIs in US, 1996

Condition Visits (millions) Antibiotic use

URIs, all 2.0 26%

URIs only* 1.6 24%

Bronchitis, all 2.1 42%

Bronchitis only* 1.2 42%

Otitis media 2.7 55%

Pharyngitis 1.5 52%

Total ARIs 8.1 44.5%

*Excludes patients with additional diagnoses of asthma, COPD, chronic bronchitis, pneumonia, otitis, pharyngitis, sinusitis, HIV.

• Patients who expect antibiotics receive them more often1-3

• Strongest predictor of receipt of antibiotics for ARI isMD perception of patient expectation1,3

• Patient satisfaction more closely related to quality of communication (explanations, contingency plans) than receipt of antibiotics1,3,4

• Public beliefs about antibiotic effectiveness5

– Useful for VRI: 55%– Useful for bacterial but not viral illness: 21%

1. Hamm RM et al. J Fam Pract. 1996;43:56. 2. Bauchner H et al. Pediatrics. 1999;103:395. 3. Mangione-Smith R et al. Pediatrics. 1999;103:711. 4. Mangione-Smith R et al. Arch Pediatr Adolesc Med. 2001;155:800. 5. Wilson AA et al. J Gen Intern Med. 1999;14:658.

Use of Antibiotics: Patient Use of Antibiotics: Patient Expectations, Physician Perceptions, Expectations, Physician Perceptions, Public BeliefsPublic Beliefs

• Pre-, post-intervention trial to decrease antibiotic use in acute, uncomplicated bronchitis in HMO sites

• Full intervention: household and office-based patient-education materials; clinician education, profiling, and academic detailing

• Limited intervention: office-based patient education materials

• Antibiotic use declined from 74% to 48% only at site with full intervention

• No differences in revisits, other prescriptions, other diagnosesGonzales R et al. JAMA. 1999;281:1512.

Decreasing Antibiotic OveruseDecreasing Antibiotic OveruseIs Hard But PossibleIs Hard But Possible

• “Just Say No” to unnecessary antibiotics for ARI– Community and patient education– Office-based interventions– Clinician-oriented interventions

• Better technology for rapid diagnostic testing to identify bacterial vs viral illness

• Possible development of antiviral medications

SummarySummary

• VRIs are an important cause of morbidity and increased health care costs

• RVs are the most common cause of VRIs

• RVs are also an important cause of morbidity in patients with asthma, COPD, and CF, and in immunocompromised patients

• In immunocompromised cancer patients, VRIs increase mortality and morbidity from pneumonia

• The mechanism of exacerbation of asthma, chronic bronchitis, and CF is related to the host inflammatory response

• Patients with VRIs are often prescribed antibiotics

Program SummaryProgram Summary

ContributorsContributors

Gerald P. Bodey, Sr., MDThe University of Texas M. D. Anderson Cancer CenterHouston

Ethan A. Halm, MD, MPHMount Sinai School of MedicineNew York

James E. Gern, MDUniversity of WisconsinMadison

Sebastian L. Johnston, MDImperial College of Science, Technology and MedicineLondon, UK

Sanjay Sethi, MDState University of New YorkBuffalo

Homer A. Boushey, Jr., MD, EditorUniversity of CaliforniaSan Francisco

Arnold S. Monto, MDUniversity of Michigan School of Public HealthAnn Arbor

Harley A. Rotbart, MDUniversity of Colorado Health Sciences CenterDenver