Correspondence

The Diagnosis and Treatment of Cough

N Engl J Med 2001; 344:1097-1098April 5, 2001

Article

To the Editor:

We share the concern of Irwin and Madison (Dec. 7 issue)1 about the unnecessary treatment of acute cough with antibiotics, which recent meta-analyses have shown has no clinically significant benefit.2-4 However, we disagree with the authors' terminology. Irwin and Madison avoid the diagnosis of bronchitis for patients with cough and production of phlegm, but there are compelling reasons to retain the term. “Acute bronchitis” is common in the medical literature and is familiar to patients and physicians alike. Unfortunately, the diagnosis of acute bronchitis has traditionally been used as justification for the administration of antibiotics and has even been described as “a cough that gets treated with antibiotics.” Instead of jettisoning the term, we favor educating both physicians and patients by informing them that antibiotics do not alter the course of acute bronchitis.

Several small studies have demonstrated the efficacy of β-agonists for decreasing the duration of acute cough. In one placebo-controlled trial,5 46 patients with acute bronchitis were randomly assigned, in a two-by-two factorial design, to erythromycin or placebo and albuterol or placebo. On day seven, 61 percent of the patients in the albuterol group were still coughing, as compared with 91 percent in the placebo group (P=0.02). The result was not influenced by the use of erythromycin.

Confirmatory studies are warranted, but the use of β-agonists makes biologic sense. Patients with acute bronchitis demonstrate obstruction on pulmonary-function testing.6 Albuterol allows physicians to prescribe effective therapy, satisfy patients, and avoid unnecessary antibiotics.

Jeffrey A. Linder, M.D.
Randall S. Stafford, M.D., Ph.D.
Massachusetts General Hospital, Boston, MA 02114

6 References

1
Irwin RS, Madison JM. The diagnosis and treatment of cough. N Engl J Med 2000;343:1715-1721
Full Text | Web of Science | Medline

2
Bent S, Saint S, Vittinghoff E, Grady D. Antibiotics in acute bronchitis: a meta-analysis. Am J Med 1999;107:62-67
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3
Smucny JJ, Becker LA, Glazier RH, McIsaac W. Are antibiotics effective treatment for acute bronchitis? A meta-analysis. J Fam Pract 1998;47:453-460
Web of Science | Medline

4
Fahey T, Stocks N, Thomas T. Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults. BMJ 1998;316:906-910
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5
Hueston WJ. Albuterol delivered by metered-dose inhaler to treat acute bronchitis. J Fam Pract 1994;39:437-440
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6
Williamson HA. Pulmonary function tests in acute bronchitis: evidence for reversible airway obstruction. J Fam Pract 1987;25:251-256
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To the Editor:

There is increasing evidence that in many cases of acute cough the cause is not the common cold or acute bronchitis. Two recent studies showed that acute bronchitis is often (in about one third of cases) the first manifestation of asthma, which becomes full-blown in the next several years.1,2 In nearly half of the patients presenting with a cough of at least two weeks' duration, there were signs of asthma or features of chronic obstructive pulmonary disease such as bronchial hyperresponsiveness (as measured with a methacholine challenge). Most patients could be classified correctly by history taking and physical examination only. Female sex, prolonged expiration, smoking, reports of wheezing and dyspnea, and symptoms elicited by allergens helped to predict the risk of asthma or chronic obstructive pulmonary disease.3 The physician must decide whether to proceed with further examination, referral to a respiratory specialist, or initiation of treatment with inhaled corticosteroids or bronchodilators.

Henk A. Thiadens, M.D., Ph.D.
Machiel P. Springer, M.D., Ph.D.
Leiden University Medical Center, Leiden 2301 CB, the Netherlands

Dirkje S. Postma, M.D., Ph.D.
University Hospital Groningen, Groningen 9700 AD, the Netherlands

3 References

1
Jonsson JS, Gislason T, Gislason D, Sigurdsson JA. Acute bronchitis and clinical outcome three years later: prospective cohort study. BMJ 1998;317:1433-1434
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2
Thiadens HA, Postma DS, De Bock GH, Huysman DAN, van Houwelingen HC, Springer MP. Asthma in adult patients presenting with symptoms of acute bronchitis in general practice. Scand J Prim Health Care 2000;18:188-192
CrossRef | Web of Science | Medline

3
Thiadens HA, de Bock GH, Dekker FW, et al. Identifying asthma and chronic obstructive pulmonary disease in patients with persistent cough presenting to general practitioners: descriptive study. BMJ 1998;316:1286-1290
CrossRef | Web of Science | Medline

To the Editor:

Irwin and Madison provide excellent guidelines for the management of cough in primary care but do not address the use of opioid antitussive medications. Among the many opioid preparations, some contain as little as 2.5 mg of codeine phosphate per dose or as much as 1 mg of hydromorphone per dose. At equivalent doses, the analgesic potency of hydromorphone is 130 times that of codeine. Preparations containing up to 5 mg of hydrocodone (which is approximately four times as potent as codeine) per dose are also available. For codeine, cough suppression has been shown to be dose related, and the analgesic potency of an opioid medication may also have a bearing on its antitussive properties.

It is not clear when and how to use opioid antitussive medications. In fact, in a study involving an office-based population,1 codeine, dextromethorphan, and guaifenesin were all found to be equally effective. In addition, opioid agents have the potential for addiction. Perhaps a case can be made for the use of high-potency opioid antitussive medications in patients with lung cancer or those needing relief from a cough during radioimaging procedures.

Ram Kakaiya, M.D.
Jennifer Wamhoff, Pharm.D.
University of Illinois College of Medicine at Rockford, Rockton, IL 61072-0319

1 References

1
Croughan-Minihane MS, Petitti DB, Rodnick JE, Eliaser G. Clinical trial examining effectiveness of three cough syrups. J Am Board Fam Pract 1993;6:109-115
Medline

Author/Editor Response

The authors reply:

To the Editor: We avoid using the term “acute bronchitis” for patients with a syndrome of acute cough and phlegm, as noted by Linder and Stafford, because it is too often inaccurate. A diagnosis of acute bronchitis implies that the patient has an acute, noneosinophilic inflammatory condition of the lower airway, which is often not the case for those with acute cough and phlegm. For example, the common cold presents as a syndrome of acute cough and phlegm but is not associated with inflammation of the lower airway. In addition, patients with acute cough in the setting of unrecognized asthma or chronic obstructive pulmonary disease are also likely to have a misdiagnosis of acute bronchitis, as stressed by Thiadens et al. We use the term “acute bronchitis” only when there is objective evidence of noneosinophilic inflammation of the lower airway.1 If one splits rather than lumps diseases that present as a syndrome of acute cough and phlegm, patients with cough due to postnasal drip from an acute infection of the upper respiratory tract are more likely to be effectively treated,2 and one can hope that there will be less overprescription of antibiotics and more appropriate use of bronchodilators.

Although we agree with Thiadens et al. that patients with asthma and chronic obstructive pulmonary disease often present to generalists with acute (or subacute) cough, we are cautious in making a diagnosis of these conditions on the basis of clinical criteria or physiological testing alone, because these methods can be unreliable. With respect to asthma, a prospective study showed that only 54 percent of patients considered by pulmonologists to have symptomatic clinical asthma actually had it.2 In addition, the results of a methacholine challenge can falsely predict that cough is due to asthma.3 For these reasons, the definitive diagnosis of symptomatic asthma requires an appropriate clinical context (e.g., cough), compatible results of physiological testing (e.g., positive results on methacholine challenge), a favorable response to specific therapy, and a clinical course consistent with asthma during follow-up.3

As stressed in both our review and the evidence-based consensus panel report of the American College of Chest Physicians,4 there should be only a limited role for nonspecific therapy, and only with agents shown to be efficacious, such as opioid antitussive medications. Nonspecific antitussive therapy should be prescribed only when specific therapy will not work rapidly enough or is unavailable (e.g., for inoperable lung cancer, as suggested by Kakaiya and Wamhoff).

Richard S. Irwin, M.D.
J. Mark Madison, M.D.
University of Massachusetts Medical School, Worcester, MA 01655

4 References

1
Pizzichini E, Pizzichini MMM, Efthimiadis A, et al. Indices of air-way inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med 1996;154:308-317
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2
Pratter MR, Hingston DM, Irwin RS. Diagnosis of bronchial asthma by clinical evaluation: an unreliable method. Chest 1983;84:42-47
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3
Irwin RS, French CT, Smyrnios NA, Curley FJ. Interpretation of positive results of a methacholine inhalation challenge and 1 week of inhaled bronchodilator use in diagnosing and treating cough-variant asthma. Arch Intern Med 1997;157:1981-1987
CrossRef | Web of Science | Medline

4
Irwin RS, Boulet L-P, Cloutier MM, et al. Managing cough as a defense mechanism and as a symptom: a consensus panel report of the American College of Chest Physicians. Chest 1998;114:Suppl 2:133S-181S
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Citing Articles (1)