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Cough, Cold and Flu… Who Knew?

Ralph Gonzales, MD, MSPH

Professor of Medicine; Epidemiology & BiostatisticsUniversity of California, San Francisco

18 February 2010

Outline

� Acute Cough Illness� Acute bronchitis

• Influenza• Pertussis

� Sinusitis� Pharyngitis

� Fusobacterium necrophorum

General Approach

� Diagnosis� Excluding Serious Illness� Testing?

� Treatment� Symptomatic Therapy� Antimicrobial Therapy

� Prognosis� When to Return for Work; Evaluation

Management Principles for Uncomplicated Acute Bronchitis

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Bronchitis-CDC; ACP; AAFP; IDSA… 2001

“The evaluation of adults with acute cough illness… should focus on ruling out serious illness, particularly pneumonia”

� In healthy, nonelderly adults, pneumonia is uncommon in the absence of vital sign abnormalities or asymmetrical lung sounds, and CXR is usually not indicated.

� When cough>3 weeks, CXR may be warranted in absence of other known causes.

Gonzales et al, 2001

Pneumonia Probabilities

8

6

8

10

0

20

0 10 20 30 40 50 60 70 80 90 100

Probability of Pneumonia

Tachycardia

Fever

Crackles

Dullness to Percussion

Cough + Nl Vital Signs

Cough, Fever, Tachycardia and Crackles

Metlay et al. JAMA. 1997;278:1440-1445.

PreTest Prob

Acute Bronchitis-Therapeutic Objectives

Symptoms Pathophysiology Treatment�Cough -bronchial RAD -bronchodilators

-mucus production -decongestants-post-nasal drip -sinus therapy-acid reflux -H2B; PPI

-cough suppressants

�Wheezing/SOB -bronchial RAD -bronchodilators

Resolution of Acute Bronchitis

0

20

40

60

80

100

0 2 4 6 8 10 12 14 16 18

Days with cough

% P

atie

nts

No Antibiotic

(+) Antibiotic

Stott, BMJ 1976

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Uncomplicated Acute Bronchitis-azithromycin vs. vitamin C (Lancet 2002;359;1648-54)

Return to Usual Activities

Microbiology of Acute Cough Illness in Adults-Louie JK et al. Clin Infect Diseases 2005;41:811-8

Microbiology of Acute Cough Illness in Adults-Louie JK et al. Clin Infect Diseases 2005;41:811-8

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H1N1-International

� The 2009 H1N1 influenza virus is the predominant influenza virus in circulation worldwide.

� Majority of 2009 H1N1 influenza isolates tested worldwide remain sensitive to oseltamivir (source: WHO) � 199 isolates tested worldwide have been found to be

resistant to oseltamivir – 52 of these isolates were detected US

H1N1 Epidemiology

� Incubation period: 1-7 days� Infectious period: -1 day until sx resolve

� 10% still shedding virus at 10 days � Immunosuppressed may shed for weeks

� Median age: 12-17 years

� Hospitalized H1N1� Median age 32 years (Canada)� 30% of deaths associated with bacterial pneumonia

Symptoms: H1N1 = seasonal flu

NYC high school outbreak (44 cases)� cough (98%)� fever (96%)

� headache (82%)

� sore throat (82%)� rhinorrhea (82%)

� muscle aches (80%)

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High Risk H1N1 Complications

� Children < 5 yrs (esp. < 2 yrs)� Adults >65 yrs

� Pregnant women� Chronic medical conditions� Immunosuppressed

� Adolescents (age<19 yrs) on chronic aspirin therapy� Reyes syndrome

Treatment of H1N1

CDC Quick Facts … 11/09� It’s not too late after 48 hrs

� No risk factors does not mean no treatment

� Treatment shouldn’t wait for laboratory confirmation

� Capsules can ease oseltamivir shortage

Are we out of the woods?

� How long do strains usually persist?

� Antigenic shift and virulence

� Oseltamivir resistance

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Acute Bronchitis:-bronchial hyperresponsiveness

Airflow obstruction in acute bronchitis without underlying lung disease

020406080

100

<=80 >80

FEV1, % predictedEur Resp J 1994;7:1239

Acute cough illness treatment-bronchodilator treatment

Melbye bronchitis 73 fenoterol aerosol Decrease symptoms1991 Improved FEV1

Hueston bronchitis 34 oral albuterol vs. Decrease cough @ 1 week1991 erythromycin (41% vs. 82%)

Hueston bronchitis 46 albuterol aerosol vs. Decrease cough @ 1 week1994 (placebo + erythro) (61% vs. 91%)

Littenberg nonspecific 104 albuterol aerosol No benefit1996 cough

Randomized, placebo controlled trials

OTC Cough Therapies-Cochrane Review, 2004

� Antitussives� codeine: 2 trials; no differences� dextromethorphan: 2 of 3 trials show benefit

� Expectorants (guaifenesin): 1 of 2 trials benefit� Mucolytics: 1 trial inconsistent benefit

� Antihistamine-Decongestant Combinations� 1 of 2 trials show benefit

� Dextro-salbutamol: reduced nocturnal cough only

Acute Cough Illnesswith or w/o phlegm Patient Characteristics

ElderlyImmunosuppression

COPD or CHFVital Sign Abnormalities

HR > 100 bpmRR > 24 br/min, or

T > 38o C

Is Influenza Likely?

PEx Findings

Consolidation, or Pleural Effusion

Treatment Options*Consider CXR

Treat Pneumonia

YesNo

Yes

No

Positive

Negative

Acute cough illness: evaluationsummary

Yes

No

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When to consider zebras…

� Cough > 3 weeks and normal CXR� Meds, asthma, GERD, postnasal drip,

pertussis

� Nocturnal Cough� GERD/postnasal drip, cough-variant

asthma, CHF

Pertussis…not just for children anymore

Pertussis…not just for children anymore

� DPT-related immunity wanes as early as 3 years… and absent after 10-12 years

� attack rates as high as 100%

� 10-15% adults seeking care for persistent cough (>3 wks) have evidence of pertussis

� No clinical features distinguish pertussis in previously immunized adults

Resolution of Acute Bronchitis

0

20

40

60

80

100

0 2 4 6 8 10 12 14 16 18

Days with cough

% P

atie

nts

No Antibiotic

(+) Antibiotic

Stott, BMJ 1976

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Pertussis� Diagnosis

� Dacron nasopharyngeal swab or nasal saline wash

� PCR is now standard…• No FDA-licensed tests yet…

� Coordinate with public health dept� Treatment

� Macrolides; trimethoprim-sulfa� Probably won’t help cough duration if started

after 10 days of illness� Reasonable to provide empirical Abx treatment

to contacts with cough, and close contacts/household members as prophylaxis.

PREVENTION: Pertussis Boosters-ACIP 2007 Recs (MMWR 2006;55:RR-17)

� Routine� Single Tdap instead of dT at age 11-18� Tdap (instead of dT) in adults 18-64 if > 10

years since dT

� Tdap when dT within 2-10 years� Adult contacts of infants < 12 months

• Women prior to pregnancy; else post-partum

� Healthcare workers (all staff)� Rare Adverse Events

• Arthus Reaction• Extensive Limb Swelling

Rhinosinusitis: Diagnosis

“The clinical diagnosis of acute bacterialrhinosinusitis should be reserved for…”

(1) rhinosinusitis symptoms > 7 days

+(2) purulent nasal secretions

+

(3) maxillary pain/tenderness in face/teeth

Rhinosinusitis: Diagnosis

“…rarely some patients with acute bacterial rhinosinusitis present with dramatic symptoms of severe unilateral maxillary pain, swelling and fever”

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Bacterial Sinusitis? Tough Call

0 20 40 60 80 100

sinus symptoms

high clinical suspicion

Xray (b)

CT scan (a)

purulent sinus aspirate

Cx (+) sinus aspirate

Bacterial Sinusitis, %

(a) CT scan criteria of air-fluid level or complete opacification.(b) Xray criteria of mucosal thickening, air-fluid level or complete opacification.

Rhinosinusitis: Rx Studies

Author Pat ien tSe lec t ion

TreatmentArms

Ant ibio t i c Rx* Placebo Rx*

L indbaek , 1996 c l in ica l susp ic ion+

CT Scan Dx

amox ic i l l i n ;pen ic i l l i n V ;p l acebo

D1086% 57%

van Buchem1997

c l in ica l susp ic ion+

Xray Dx

amox ic i l l i n ;p l acebo

D1483% 77%

Sta lman , 1997 c l in ica l c r i te r i a doxycyc l ine ;p l acebo

D1085% 85%

Bucher , 2003 c l in ica l c r i te r i a(on ly 32% Sx > 7

days )

amox-c lavu lanat e ;p l acebo

D1475% 75%

Merens te in,2005

c l in ica l c r i te r i a(100% Sx > 7

days )

amox ic i l l i n ;p l acebo

D1448% 37%

*Percent improved or cured

RCT: Abx +/- nasal steroids--Williamson, JAMA 2008

Abx + steroid Abx + placebo steroid + placebo placebo + placeboNo. of Sx days (n = 51) (n = 60) (n=63) (n=61)median (IQR) 7 (4-14) 7 (4-10) 7 (4-14) 7 (5-14)

Rhinosinusitis: Diagnosis

“The clinical diagnosis of acute bacterialrhinosinusitis should be reserved for…” [B]

(1) rhinosinusitis symptoms > 7 days+

(2) purulent nasal secretions

+(3) maxillary pain/tenderness in face/teeth

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Abx for Sinusitis—Meta-analysis--Young, Lancet 2008

� Meta-analysis of clinical criteria-based RCTs of antibiotics for acute sinusitis� UNIQUE: aggregated patient-level data;

therefore able to examine specific signs/Sx

� Results:� “Duration of illness or severity of symptoms

did not predict antibiotic benefit”� “Purulent nasal discharge marginally

significant”

Odds Ratio for Cure with Antibiotic Rx for Acute Sinusitis

Young J et al, Lancet 2008

Rhinosinusitis: Diagnosis

“The clinical diagnosis of acute bacterialrhinosinusitis should be reserved for…” [B]

(1) rhinosinusitis symptoms > 7 days+

(2) purulent nasal secretions

+(3) maxillary pain/tenderness in face/teeth

Rhinosinusitis: Abx Rx

� “Acute rhinosinusitis resolves without antibiotic treatment in most cases” [A]� Antibiotic treatment should be

reserved for patients with moderately severe symptoms who meet criteria for clinical diagnosis of acute bacterial rhinosinusitis and for those with severe symptoms…regardless of duration of illness.

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Acute Sinusitis-Therapeutic Objectives

Symptoms Pathophysiology Treatment� Pain -increased sinus pressure due -↑ sinus drainage

inflammation & obstruction -nasal saline wash-nasal decongestant

-if >7-10 days of Sx -NSAIDs-↑ bacterial infection risk -Antibiotics

� Congestion -increased mucus production -oral decongestants-infection; recurrent; allergic -nasal steroids

Pharyngitis: Diagnosis

� “Clinically screen all adult patients with pharyngitis for the presence of 4 criteria:”

� history of fever� tonsillar exudates

� tender anterior cervical LAN

� absence of cough

� “Do not test or treat patients with none or only 1 of these criteria…”

Accuracy of Rapid Strep Test--Spectrum Bias

Sensitivity of RATPediatrics Adults

Centor Score0 47 61*1 65 61*2 82 763 90* 904 90* 97

*groups combined in studyPeds Ref: Hall MC et al. Pediatrics 2004;114:182Adult Ref: Dimatteo LA et al. Ann Emerg Med 2001;38:648

Pharyngitis: Abx Rx

� “Test patients with 2-4 criteria using a rapid antigen test, and limit Abx to patients with positive test results”, OR

� “Test patients with 2 or 3 criteria, and limit Abx to patients with positive test results or patients with 4 criteria”, OR

� “Do not use any diagnostic tests, and limit Abx to patients with 3 or 4 criteria”

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GAS Rapid negative, but patient Sxworsen… possibilities?

� False-negative rapid GAS test� Infectious mononucleosis

� Non-group A streptococcal infection� Group C, Group D

� Gonorrhea� Acute HIV

� Peritonsillar abscess

� Lemierre’s syndrome (septic thrombophlebitis)

Fusobacterium necrophorum-Centor RM. Ann Intern Med 2009;151:812-5

� Gram negative anaerobe.� Causative agent in Lemierre syndrome

� In 15-30 yo, causes 10% of cases (about same % as group A strep)

� Not responsive to macrolides

� Suspect in adolescent/young adult with worsening Sx and neck swelling

More relevant than Strep?? Streptococcal Pharyngitis-Therapeutic Objectives

Symptoms Pathophysiology Treatmentsore throat -inflammation -NSAIDs

-infection -antibiotics

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Therapeutic Windows for Antimicrobial ARI Treatments

� Influenza Sx 2 days

� GAS pharyngitis Sx 2 days� To prevent ARF 10 days

� Pertussis cough 7-10 days

How to help patients say “no” to antibiotics for viral ARIs

� Illness labeling: use “chest cold”, not “bronchitis”� Validate illness severity; focus on symptom relief� Provide a contingency plan� Discuss downside of unnecessary antibiotic use

� risk of carriage/spread of antibiotic-resistant bacteria

� Patient-physician communication� Explain the illness� Spend “enough” time� Treat with respect

Gracias CDC/ACP/AAFP/IDSA-Antibiotic Principles for ARIs

• Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JH, Hoffman JR, Sande MA. Principles of appropriate antibiotic use for treatm ent of acute respiratory tract infections in adults: Back ground, Specific Aims and Methods. Ann Intern Med 2001;134:479-86.

• Cooper RJ, Hoffman JR, Bartlett JG, Besser RE, Gonzales R, Hickner JH, Sande MA. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med 2001;134:509-17

• Hickner JH, Bartlett JG, Besser RE, Gonzales R, Hoffman JR, Sande MA. Principles of appropriate antibiotic use for acute rhinosinusitis in adults: background. Ann Intern Med 2001;134:498-505.

• Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JH, Hoffman JR, Sande MA. Principles of appropriate antibiotic use for treatm ent of uncomplicated acute bronchitis: background. Ann Intern Med2001;134:521-29.

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Bronchitis References• Stott NC, West RR. Randomised controlled trial of antibiotics in patie nts with

cough and purulent sputum. BMJ. 1976;2(6035):556-9. • Melbye H, et al. Reversible airflow limitation in adults with respir atory infection . Eur

Respir J. 1994;7:1239-45.• Gonzales R et al. Decreasing antibiotic use in ambulatory practice: i mpact of a

multidimensional intervention on the treatment of u ncomplicated acute bronchitis in adults. JAMA. 1999;281:1512-9.

• Evans AT, et al. Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial. Lancet. 2002;359(9318):1648-54).

• Schroeder K, Fahey T. Over-the-counter medications for acute cough in chi ldren and adults in ambulatory settings. Cochrane Database Syst Rev. 2004(4):CD001831.

• Nennig ME, et al. Prevalence and incidence of adult pertussis in an u rban population. JAMA 1996;275:1672-4.

• Metlay JP, Fine MJ. Testing strategies in the initial management of pat ients with community-acquired pneumonia. Ann Intern Med. 2003;138:109-18.

• Preventing Tetanus, Diphtheria, and Pertussis Among Adults: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Per tussis Vaccine: Recommendations of the Advisory Committee on Immuni zation Practices (ACIP).MMWR 2006;55:RR-17.

• Pawar S, et al. Treatment of postnasal drip with proton pump inhibi tors: a prospective, randomized, placebo-controlled study. Am J Rhinol 2007;21:695-701.

Acute Rhinosinusitis Refs• Lindbaek M, et al. Randomized, double blind, placebo controlled trial o f penicillin V and

amoxycillin in treatment of acute sinus infections i n adults. BMJ 1996;313(7053):325-9.

• Stalman W, et al. The end of antibiotic treatment in adults with acut e sinusitis-like complaints in general practice? A placebo-controll ed double-blind randomized doxycycline trial. Br J Gen Pract 1997;47(425):794-9.

• van Buchem FL, et al. Primary-care-based randomized placebo-controlled tri al of antibiotic treatment in acute maxillary sinusitis. Lancet 1997;349(9053):683-7.

• Bucher HC, et al. Effect of amoxicillin-clavulanate in clinically diag nosed acute rhinosinusitis: a placebo-controlled, double-blind, randomized trial in general practice.Arch Intern Med. 2003;163:1793-8.

• Merenstein D, et al. Are antibiotics beneficial for patients with sinusi tis complaints? A randomized double-blind clinical trial. J Fam Pract 2005;54:144-51.

• Williamson et al. Antibiotics and topical nasal steroid for treatment of acute maxillary sinusitis: a randomized controlled trial. JAMA 2007;298:2487-96.

• Young et al. Antibiotics for adults with clinically diagnosed ac ute rhinosinusitis: a meta-analysis of individual patient data. Lancet 2008; 371(9616):874-6

Acute Pharyngitis Refs• Centor RM, Witherspoon JM, Dalton HP, et al. The diagnosis of strep throat in

adults in the emergency room. Med Decis Making 1981; 1:239-246.

• Zwart S, Sachs APE, Ruijs GJHM, et al. Penicillin for acute sore throat: randomised double blind trial of seven days versus three days treatment or placebo in adults. BMJ 2000; 320:150-154.

• DiMatteo L, Lowenstein SR, Brimhall B, et al. The relationship between the clinical features of pharyngitis and the sensitivity of a rapid antigen test: evidence of spectrum bias. Ann Emerg Med. 2001;38:648-52.

• Bulloch B, Kabani A, Tenenbein M. Oral dexamethasone for the treatment of pain in children with acute pharyngitis: a randomized, d ouble-blind, placebo-controlled trial. Ann Emerg Med. 2003;41:601-8.

• Kiderman A, Yaphe J, Bregman J, Zemel T, Furst AL. Adjuvant prednisone therapy in pharyngitis: a randomised controlled tri al from general practice. Br J Gen Pract 2005;55:218.

• Shah M, et al. Severe acute pharyngitis caused by group C streptoc occus. J Gen Intern Med 2007;22:272-74.

• Centor RM. Expand the pharyngitis paradigm for adolescents and young adults. Ann Intern Med 2009;151:812-5.