Bronchitis

James Allen, MD

I. Acute Bronchitis

A. Epidemiology

1. 9th most common outpatient illness seen by physicians in the United States

2. the average adult has 3 - 5 viral infections of the upper respiratory tract per year

3. occur throughout the year except RSV, influenza, and parainfluenza which occur in epidemics in late fall through early spring

B. Clinical presentation

1. cough with or without sputum production

a) sputum can be purulent in either bacterial or non-bacterial bronchitis

b) many of the agents causing bronchitis also cause pneumonia

2. fever

3. concurrent pharyngitis or laryngitis is very common

4. occasionally: hoarseness, chest pain

5. exam: normal or coarse wheezes and coarse crackles

6. chest x-ray is normal

C. Differential diagnosis

1. pneumonia

2. lung abscess

3. asthma

4. post-nasal drip

5. gastroesophageal reflux disease

6. bronchiectasis

7. chronic bronchitis

8. airway obstruction

a) tumor

b) foreign body

D. Causative agents:

1. viruses (the most common etiology in normal adults)

a) myxoviruses

(1) influenza

(a) winter and early spring

(b) incubation period 1-4 days

(2) parainfluenza

(a) October and November

(b) causes croup in children, common cold symptoms more common than primary bronchitis in adults

(3) respiratory synctial virus

(a) January through March

(b) common cold symptoms more common than bronchitis in adults

(c) can resemble influenza

(d) often nosocomial in immunocompromised adults

b) rhinovirus

(1) usually early fall and late spring

(2) incubation period = 2 days

(3) common cold symptoms most common

c) adenovirus

(1) occurs throughout the year

(2) usual incubation period = 4-7 days

(3) conjunctivitis can be a helpful finding since it is not usually found with the other viral causes of bronchitis

d) coronaviruses

(1) winter and early spring

(2) usually causes common-cold symptoms

(3) incubation period is 2-4 days

(4) less systemic symptoms than influenza and adenovirus

e) herpes simplex

(1) unexplained new wheezing

(2) hemoptysis

(3) with or without labial herpetic lesions

(4) respiratory failure frequent

2. bacteria

a) Streptococcus pneumonia

b) Hemophilus influenza

c) Bordetella pertussis

(1) natural infection provides life-time immunity but vaccination only provides immunity for about 10 years

(2) most young adults in the U.S. are susceptible

(3) in adults, pertussis (whooping cough) lacks the typical "whoop" and is a much more indolent and mild infection than in children

(4) erythromycin may be effective early in the course; late in the course, bronchodilators or short courses of prednisone can sometimes be useful

(5) currently felt to be the cause of 25% of chronic cough in college-aged adults

(6) when Bordatella pertussis is suspected

(a) a nasopharyngeal swab on special medium can be performed; this medium must be made fresh and is not widely available; in central Ohio, Children's Hospital is the only lab performing this culture

(b) direct immunofluorescent antibody testing of sputum can be performed

(c) regular culture can be performed

(d) four-fold change in serum titers can be performed but this is usually not helpful in the acute setting when decisions regarding therapy must be made

3. other

a) mycoplasma pneumonia

(1) year round but more common in winter

(2) clusters in families

(3) incubation period = 9=21 days

(4) cough usually non-productive

(5) exanthems in 11-25%

(6) WBC usually normal

(7) diagnosis:

(a) cold agglutinins usually > 1:32

i) can also be seen in legionella, influenza, adenovirus and other conditions

(b) diagnosis can be confirmed serologically but this is usually unnecessary

i) single titer >1:64 suggestive

ii) four-fold rise in titer diagnostic

(c) culture for mycoplasma usually not done because of the long delay to obtaining positive cultures (Å 10 days)

(8) chest x-ray infiltrates (indicating pneumonia) are common and typically out of proportion to the physical findings

b) chlamydia pneumonia

(1) clinically similar to mycoplasma

(2) nearly as common in young adults as mycoplasma

(3) difficult to grow in culture

(4) diagnosis can be confirmed serologically but confirmation is usually unnecessary

(a) single titer > 1:16 (IgM) or > 1:512 (IgG)

(b) 4-fold titer rise after acute infection (check 2nd titer 4-6 weeks after acute specimen)

E. Laboratory investigation

1. in most patients - none

2. chest x-ray usually unnecessary but should be obtained if there is evidence of consolidation on physical examination or if the patient is particularly susceptible to pneumonia (elderly patients, immunocompromised patients, TB exposure, debilitated patients, patients with malignancy)

3. sputum stain only helpful if it is uncontaminated with oral secretions

4. sputum culture indicated if:

a) there is a local epidemic (pertussis, virus, mycoplasma, chlamydia)

b) you suspect HSV tracheobronchitis

c) the patient is unusually susceptible to infections (eg, immunocompromised patients; patients with marginal lung function)

d) patient does not respond to symptomatic or empiric therapy

e) pertussis is suspected and the diagnosis will change your clinical behavior (eg., isolation of patient, prophylaxis of susceptible family members, etc.)

5. when Herpes simplex is suspected, bronchoscopy is diagnostic:

a) tracheobronchial ulcerations

b) typical inclusion bodies seen on tracheobronchial washings

c) growth of HSV from bronchial washings

F. Treatment

1. in usual clinical practice, the cause of bronchitis is usually not immediately apparent

a) there have been only 7 good randomized, placebo-controlled studies about antibiotic treatment for typical bronchitis in the outpatient clinic

(1) Howie (Lancet, 1970; 2:1099-1102)

(a) tetracycline vs. placebo

(b) n = 829

(c) no benefit

(2) Scott (BMJ, 1976; 2:556-9)

(a) doxycycline vs. placebo

(b) n = 212

(c) no benefit

(3) Franks (J Fam Pract 1984; 19:185-90)

(a) TMP-SMX vs. placebo

(b) n = 67

(c) TMP-SMX had a benefit

(4) Williamson (J Fam Pract 1984; 19:481-6)

(a) doxycycline vs. placebo

(b) n = 74

(c) no benefit

(5) Brickfield (J Fam Pract 1986; 23:119-22)

(a) erythromycin vs. placebo

(b) n = 52

(c) no benefit

(6) Dunlay (J Fam Pract 1987; 25:137-41)

(a) erythromycin vs. placebo

(b) n = 63

(c) erythromycin had a benefit

(7) Verhij (Br J Gen Pract 1994; 44:400-4)

(a) doxycycline vs. placebo

(b) n = 158

(c) no benefit for patients under 55; reduced days of cough for patients over 55 receiving doxycycline

b) for the unselected population of otherwise normal patients with acute bronchitis, the use and selection of specific antibiotics remains unclear

(1) if viral causes are suspected, antibiotics are not indicated except for:

(a) documented HSV

i) acyclovir: 8 mg/kg Q8 hours IV for 7-10 days

(b) documented RSV in the immunocompromised host or the severely ill (hospitalized) patient

i) ribavirin inhaled

(c) presumptive severe influenza during epidemics

i) amantidine (200 mg QD x 10 days) or rimantidine (200 - 300 mg QD x 10 days) for severe cases or for prophylaxis in high risk, unvaccinated patients

(2) If antibiotics are used, it seems prudent to use safe, inexpensive antibiotics which have been shown in at least one placebo-controlled study to be effective and which should in theory cover most of the common treatable causes of acute bronchitis (pertussis, mycoplasma, chamydia, pneumococcus)

(a) antibiotics are in general overused for treatment of acute bronchitis and in fact, albuterol is more likely to provide clinical benefit (see below)

(b) erythromycin probably fits best

(c) other agents (newer macrolides; quinolones) should be as effective or more effective than erythromycin but have not been well tested vs. placebo and are considerably more expensive. Their main role is in the erythromycin-intolerent patient

(d) SMX-TMP has been shown to be better than placebo but does not cover all of the theoretically typical causes well

2. usual viral bronchitis - supportive measures only

a) analgesics, antitussives (dextromethorphan, codeine)

b) antibiotics not necessary unless compounding bacterial infection occurs (as often happens with influenza

c) post-viral bronchospasm with cough and/or wheezing is common and can last for 1-2 months following viral bronchitis; beta agonist and steroid inhalers are beneficial; most patients do not develop asthma long term

(1) this appears to be especially common with C. pneumonia

(2) at least one analysis has suggested that if empiric therapy is to be given for acute bronchitis in otherwise healthy adults, that albuterol is more likely to provide relief than antibiotics (J Gen Med 1996; 11:557-62)

II. Chronic Bronchitis

A. Epidemiology

1. generally a disease of smokers and former smokers

B. Pathophysiology

1. diminished ability to clear bacteria due to:

a) ciliary dysfunction

b) excessive secretions produced by submucosal mucus glands

c) exudate from chronic inflammation

d) airway obstruction

(1) abundant, thick, exudative secretions

(2) increased bronchomotor tone

e) impaired phagocytosis by neutrophils

f) reduced IgA in airway secretions

2. increased colonization of bronchial epithelium by Hemophilus sp.

C. Differential diagnosis

1. alpha-1-antitrypsin deficiency

2. bronchiectasis

3. lung abscess

4. tuberculosis

5. lung cancer

D. Causative agents: 50% of acute exacerbations of chronic bronchitis are due to bacterial infections:

1. Streptococcus pneumonia

2. Hemophilus influenza

3. Moraxella catarrhalis

E. Clinical definition:

1. productive cough for 3 or more months in each of 2 consecutive years

2. sputum production usually does not exceed 60 ml in 24 hours

3. an exacerbation may be characterized by any or all of the following:

a) increased purulence

b) increased frequency of cough

c) increased dyspnea

d) chest discomfort

e) wheezing

f) hemoptysis

g) note: fever, rigors, and pleuritic chest pain suggest pneumonia

F. Laboratory investigation

1. chest x-ray not necessary unless the symptoms are decidedly new for the patient and lung cancer is considered or unless pneumonia is suspected

2. blood tests not necessary

3. sputum stain and culture not generally required but can help direct treatment, particularly in the patient allergic to the commonly used antibiotics or refractory to empiric treatment

G. Treatment

1. smoking cessation

2. antibiotics (see table)

a) reserve treatment for patients with 2 of the following:

(1) increased dyspnea

(2) increased sputum volume

(3) increased sputum purulence

b) first line (preferred because of cost - generally < $15 per course):

(1) TMP/SMX (DS BID x 7-10 days)

(a) my personal favorite because of low cost and BID dosing (ie, good compliance)

(2) doxycycline (100 mg BID x 7-10 days)

(a) my personal second favorite

(3) erythromycin (250-500 mg QID x 7-10 days)

(4) ampicillin (250-500 mg QID x 7-10 days) or amoxicillin (250-500 mg TID x 7-10 days

(a) there is increasing resistance of H. flu to ampicillin/amoxicillin

(b) M. catarrhalis is generally ampicillin-resistant

(5) tetracycline (250-500 mg QID x 7-10 days)

(a) there are increasing resistant strains of S. pneumonia

c) second line - if there is no response to a first line drug after 3-5 days (these drugs are much more expensive than the first line drugs and generally run $30 - $90 per course; consider checking sputum culture at this point):

(1) amoxicillin-clavulanate (Augmentin)

(2) ciprofloxacin (500-750 mg BID x 7-10 days)

(a) poor activity against S. pneumonia

(3) ofloxacin (400 mg BID x 7-10 days)

(4) cefuroxime (250-500 mg BID x 7-10 days)

(5) cefaclor (250 500 mg TID x 7-10 days)

(a) poor against H. influenza

(6) azithromycin (500 mg day 1; 250 mg days 2-5)

(7) clarithromycin (500 mg BID x 7-10 days)

3. bronchodilators (see table)

a) inhaled beta agonists

(1) there is little difference in the clinical efficacy of the various beta agonists

(2) some of the factors to consider in choosing a beta agonist:

(a) cost (the least expensive will vary from one pharmacy to another)

(b) which one is on a particular patient's insurance plan

(c) ease of use (pirbuterol [Maxair] autoinhaler has some advantages for patients who are not using a spacer because inhaler coordination is unnecessary)

(d) duration of action (salmeterol [Serevent] can be used as a Q12 hour dosing which gives particularly good coverage throughout the night)

(e) patients often develop a personal preference for one beta agonist over others - this can often be a significant factor

b) ipratropium bromide (Atrovent) may have some advantages over beta agonists for chronic use in this population of patients. The combined preparation, Combivent (ipratropium bromied + albuterol) is only slightly more expensive than Atrovent alone and provides both medications in a single cannister, thereby improving compliance

c) theophylline

(1) relatively weak bronchodilator compared to beta agonists

(2) this drug has increasingly fewer indications and should be reserved for patients who derive a clear benefit from it after maximum therapy with iprotropium, beta agonists, antibiotics, and steroids

(3) although it is relatively inexpensive, the necessity of blood levels frequently makes it's use relatively expensive

(4) it has a narrow therapeutic window and blood levels are adversely affected by a number of common acute factors:

(a) decreased clearance (increased blood levels):

i) smoking cessation

ii) ciprofloxacin

iii) erythromycin

iv) allopurinol

v) cimetidine

vi) CHF

vii) pneumonia

viii) liver disease

ix) viral infection

(b) increased clearance (decreased blood levels):

i) rifampin

ii) phenobarbitol

4. corticosteroids

a) moderate doses of oral steroids for 7-10 days are helpful in many patients, usually in conjunction with antibiotics

(1) solumedrol comes in a 6 day tapering package (Medrol dosepak) which is convenient for prescribing since all you have to write for is "Medrol dosepak, take as directed on package" (4 mg pills: day 1 = 6 ; day 2 = 5; day 3 = 4; day 4 = 3; day 5 =2; day 6 =1)

(2) prednisone also comes in a 6 day tapering package (5 or 10 mg pills: day 1 = 6 ; day 2 = 5; day 3 = 4; day 4 = 3; day 5 =2; day 6 =1)

b) inhaled corticosteroids - can often allow reduction in daily dose of oral steroids in patients requiring maintenance steroids; especially useful in patients who respond to a course of oral steroids

(1) there are little clinical differences in the various steroid inhalers

(2) best used chronically in conjunction with a spacer to prevent thrush, especially when using more puffs than recommended on the package insert

(3) beclomethasone (Beclovent; Vanceril) is often the least expensive

(4) flunisolide (Aerobid) tastes the worst

(5) triamcinolone (Azmacort) comes with an attached spacer

(6) fluticasone (Flovent) is reportedly the most potent

5. expectorants

a) ?iodinated glycerol (2 tablets QID; occasionally helpful; may precipitate hypothyroidism in borderline hypothyroid patients)

b) ?DNAse (under investigation for chronic bronchitis)

6. oxygen may be required for 1 or 2 weeks in patients with borderline hypoxemia who become severely hypoxemic during exacerbations

 

III. Questions:

 

A. A 30 year old develops a non-productive cough in conjunction with low grade fever and pharyngitis in November. He does not seek medical attention until January when he presents with a persistent cough and normal chest exam. The most prudent next step would be:

1. sputum culture

2. nasopharyngeal swab for pertussis

3. beta agonist inhaler

4. bronchoscopy

5. ciprofloxacin

 

B. A 50 year old smoker with frequent recurrent episodes of acute on chronic bronchitis presents with a one week increase in cough frequency and sputum purulence. His pulmonary examination is notable only for a few diffuse coarse wheezes. The best initial step should be:

1. sputum culture

2. chest x-ray

3. trimethoprim-sulfamethoxazole

4. azithromycin

5. add theophylline

 

C. A 45 year old non-smoking man with end stage renal disease is admitted with a 3 day history of new cough, wheezing, and hemoptysis. His chest x-ray is clear but he is severely dyspneic with hypoxemia. Sputum stains show neutrophils but no bacteria. The next step should be:

1. bronchoscopy

2. nasopharyngeal culture for pertussis

3. methylprednisolone, 40 mg per day

4. chest CT

5. trimethoprim-sulfmethoxazole

 

D. A 23 year old college student presents to your office with a 2 day history of non-productive cough, pharyngitis, and otitis. Three of her housemates have had illnesses characterized by cough, low grade fever, and pharyngitis in the past 2 weeks. If you choose to prescribe an antibiotic, the best choice for antibiotic treatment is:

1. amoxicillin, 500 mg QID for 10 days

2. azithromycin, 500 mg followed by 250 mg QD for 5 days

3. ciprofloxacin, 500 mg BID for 10 days

4. erythromycin, 500 mg QID for 10 days

5. trimethoprim-sulfamethoxazole, double strength BID for 10 days

 

IV. Answers:

 

A. (3) Beta agonist inhaler; he most likely has post-infectious bronchospasm. It is too far from the original infection for bronchoscopy, antibiotics, or a sputum culture to be of use. Although pertussis was a possibility for the original infection, cultures are usually negative after a week or so of symptoms (usually about the time a patient presents to the physician)

 

B. (3) Trimethoprim-sulfamethoxazole; he has an acute exacerbation of chronic bronchitis. This is really a clinical diagnosis and for most patients, a sputum culture and a chest x-ray are just a waste of money. Theophylline may be of some marginal benefit chronically but is unlikely to be of much use acutely. Azithromycin would work fine but the patient would be broke.

 

C. (1) Bronchoscopy; he may very likely have herpes tracheobronchitis and would thus require a course of IV acyclovir. At 45, he was a child before pertussis vaccination was available and likely had pertussis as a child which would give him lifetime immunity; besides, pertussis usually causes a non-productive cough without hemoptysis or wheezing - typically the cough will occur in bouts, often severe enough to cause vomiting and often awakening from sleep. Steroids are not indicated in acute bronchitis in a non-smoker without asthma. A chest CT would be a waste of $700 dollars.

 

D. (4) Erythromycin; she most likely has mycoplasma or chamydia. Amoxicillin and TMP-SMX do not cover these organisms. Azithromycin and ciprofloxacin would work fine but she would spend all of her laundry money for next quarter on the prescription.

 

last updated September 8, 1997