Treatment of Acute and Subacute Cough: What Works, What Doesn't

Recently, the American College of Chest Physicians (ACCP) updated its guidelines on the management of cough.¹ Among the major changes to the original guidelines issued in 1998 are new recommendations for the treatment of coughs caused by colds and for the vaccination of adults against pertussis. The revised guidelines discuss the management of acute, subacute, and chronic cough.

Highlighted here are the recommendations for acute and subacute cough-the types most often seen in primary care (Table). With a few exceptions, this discussion focuses on cough in adults. 

ACUTE COUGH

A cough that lasts less than 3 weeks is considered acute. Causes include:

• Upper or lower respiratory tract infection.

• Exacerbation of a preexisting condition, such as asthma or chronic obstructive pulmonary disease (COPD).

• Environmental or occupational exposure.

The common cold. This is the most common cause of acute cough. The only agents recommended in the guidelines for treatment of cough in adults with upper respiratory tract infections (URTIs) are:

• Inhaled ipratropium.

• Older antihistamine/decongestants (brompheniramine and sustained-release pseudoephedrine).

• Naproxen.

Although newer ("non-drowsy") and older antihistamines both desiccate excess mucus, the newer agents work only on histamine-mediated congestion, which occurs in allergy, says Richard Irwin, MD, chair of the ACCP guidelines committee and professor of medicine at the University of Massachusetts Medical School. To dry up the mucus associated with a cold, an anticholinergic agent is needed; the older antihistamine/decongestants are effective because they have anticholinergic as well as antihistaminic properties. Ipratropium is also an anticholinergic.

Dr Irwin notes that naproxen was the only NSAID specified for treatment of cough associated with colds because it was the only NSAID studied in this setting. "There's no reason to believe that naproxen is the only NSAID that would work," he says.

Although the above agents were found effective in adults, none of them were recommended for children. In a significant departure from the original guidelines-which advocated a uniform approach for patients of all ages-the updated guidelines outline different management strategies for children (younger than 15 years) and adults. The recommendation that no pharmacologic therapy of any kind be used in children with cough associated with URTI is one of the key features of the new pediatric guidelines.

Over-the-counter cough and cold medications (with the exception of the older antihistamine/decongestants) were not found to be effective. Preparations in which zinc is the active ingredient also were not recommended. Even prescription central-acting cough suppressants, such as those that contain dextromethorphan or codeine, were found to be of limited efficacy in patients with cough associated with the common cold and were not recommended in this setting.

The new guidelines do not mention nonpharmacologic treatments for cough, such as steam inhalation, chest rubs, increased fluid intake, or demulcents. Dr Irwin notes that this omission resulted from stringent evidentiary requirements for non-disease-specific therapies; the guideline authors primarily looked at double-blind, randomized, placebo-controlled trials. Almost no studies of nonpharmacologic therapies met these standards.

Dr Irwin points out that in almost all studies of treatments for cough associated with the common cold, a placebo effect of 30% to 40% improvement is observed. If a practitioner wants to recommend a treatment to a patient in order to produce this placebo effect, he suggests a modality such as steam, which can do little harm in an adult patient, rather than any kind of medical therapy.

Acute bronchitis. This is another common cause of acute cough. In fact, acute bronchitis is among the illnesses most commonly diagnosed by primary care physicians. Clinical findings include cough that lasts up to 3 weeks, with or without production of phlegm. The diagnosis should only be made after other possible causes of cough, such as pneumonia, the common cold, acute asthma, or an acute exacerbation of COPD, have been ruled out.

Acute bronchitis is largely a clinical diagnosis. Routine use of viral cultures and similar procedures is not recommended because a caus- ative organism is rarely identified.

The most common cause of acute bronchitis seems to be respiratory viruses; a bacterial cause is identified in fewer than 10% of patients. Thus, the new guidelines stress that antibiotics have no role in the treatment of acute bronchitis. They even go so far as to urge "vigorous efforts to curtail their use" in this setting. Although Dr Irwin acknowledges the difficulty involved in implementing this change-because of the widespread expectation that antibiotics will be prescribed-the guideline authors recommend that physicians explain carefully to patients why these agents are not needed.

In contrast to cough associated with the common cold, in acute bronchitis, antitussive agents were found to be "occasionally useful" and are recommended for short-term symptomatic relief of coughing. Expectorants and, except under rare circumstances, bronchodilators are not recommended for patients with acute bronchitis.

SUBACUTE COUGH

Coughs that have lasted at least 3 weeks but not more than 8 are classified as "subacute." The first step in the workup of patients who present with subacute cough is to determine whether they have a postinfectious cough. If the cough began during or shortly after they experienced symptoms of an acute URTI, it may be postinfectious. If there was no antecedent URTI, the cough probably represents an early stage of chronic cough and should be worked up accordingly.

Postinfectious cough. The pathogenesis of this type of cough is not fully understood, and multiple factors may contribute to its development. These include postviral inflammation of the upper or lower airway, hypersecretion of mucus, and airway hyperresponsiveness (the latter 2 are associated most often with inflammation of the lower airway). In addition, prior problems with persistent inflammation of the nose and paranasal sinuses (called "upper airway cough syndrome" in the revised guidelines instead of "postnasal drip syndrome"), asthma, or gastroesophageal reflux disease may also play a role in the development of postinfectious cough. Although a specific causative agent is usually not identified, Dr Irwin nonetheless recommends considering the location of the original infection as well as 1 or more of the above mechanisms in decisions about therapy.

The new guidelines concede that the optimal therapy for postinfectious cough is not known. In adults, empiric treatment is recommended. A trial of inhaled ipratropium is suggested as a first-line treatment, which may be followed by inhaled corticosteroids if ipratropium fails to attenuate the cough. Centrally acting antitussive agents may be considered if other measures fail. The guidelines state that except in patients with bacterial sinusitis or early pertussis, antibiotic therapy has no role in the treatment of postinfectious cough.

In children with cough that lasts longer than 4 weeks, empiric treatment is discouraged. Instead, practitioners are urged to search diligently for clinical clues to the underlying diagnosis; if none are identified, a policy of watching and waiting is recommended. Either clues to a diagnosis will eventually appear-which can then guide therapy-or the cough is likely to abate spontaneously.

Pertussis. This is a very important diagnosis to consider in patients with subacute cough. One of the most notable changes in the updated guidelines is the expanded discussion of pertussis. The reason for the new emphasis, explains Dr Irwin, is the increasing incidence of pertussis among adults and adolescents. During the 1990s, both the number and the proportion of reported cases of pertussis among adults and adolescents more than doubled.² A recent estimation of the annual incidence in this population is 370 to 450 cases per 100,000 persons.²

Most cases of pertussis in adults are not suspected or detected.² "It's not on doctors' radar," says Dr Irwin.

Consider pertussis in patients with a progressively worsening cough that has lasted 2 weeks or longer, especially if it has followed acute upper airway symptoms that resemble those of a common cold. If the cough occurs in paroxysms or is accompanied by post-tussive vomiting or an inspiratory stridor or whooping sound, infection with Bordetella pertussis should be the working diagnosis. Although nasopharyngeal smears and cultures, if positive, will confirm the diagnosis, the yield of these tests is not particularly good. Often, the diagnosis must be made on clinical grounds and then confirmed by serology. Contact with a person with confirmed pertussis, in conjunction with a compatible clinical picture, is also regarded as confirmatory.

A classic case of pertussis has 3 phases:

• Catarrhal phase. This is characterized by coryza and gradual development of cough (primarily at night early in the illness); it lasts about 2 weeks.

• Paroxysmal phase. This is characterized by increasingly severe coughing that occurs in fits, produces large amounts of viscid mucus, and may be accompanied by post-tussive vomiting and the characteristic inspiratory whooping sound; it also lasts about 2 weeks.

• Convalescent phase. During this phase, symptoms gradually ameliorate; it lasts at least 3 weeks, sometimes much longer.

Macrolide antibiotics are effective against pertussis. However, their effectiveness extends only through about the first week of the paroxysmal phase. After that, the organism has largely been cleared by the body's own defenses, even though severe symptoms may remain. Nor are any other agents recommended as symptomatic treatment; long-acting b-agonists, antihistamines, corticosteroids, and pertussis immunoglobulin all failed to show benefit in patients with pertussis.

Dr Irwin speculates that antireflux therapy may be helpful when the cough that follows a B pertussis infection remains persistently troublesome. Although there are no da-ta to support such an approach, he says he feels comfortable suggesting it because cough that lasts 8 weeks or longer is considered a chronic cough and gastroesophageal reflux disease is one of the most common causes of chronic cough.

Thus, early diagnosis is critical. In addition to permitting the initiation of treatment that can diminish the severity of the coughing, timely diagnosis also helps stem the spread of the disease. Whenever pertussis is diagnosed early enough for a course of macrolide antibiotics to be effective, the patient should be isolated for 5 days after the start of treatment.

Unfortunately, the similarities between the early, catarrhal phase of pertussis and common URTIs make timely diagnosis difficult. Compounding this difficulty, notes Dr Irwin, is that adults with pertussis often do not have classic symptoms. "If you were to wait for cough accompanied by a 'whoop' or cough-vomit syndrome, you would miss a great deal of whooping cough," he says.

Dr Irwin notes that even if pertussis is diagnosed too late for antibiotic therapy to be of help to the patient, prophylaxis can still be profitably offered to his or her close contacts. The incubation for the disease ranges from 7 to 21 days. It is vitally important, he says, to report all cases of pertussis to the local health department, whatever the stage at the time of diagnosis. Health department officials can help with the screening of contacts and may be able to help prevent a large outbreak of the disease, something that has become a significant problem in schools, in the military, and wherever people live in close quarters in the wintertime.

The new guidelines underscore the importance of vaccinating children against pertussis through administration of a complete diphtheria, tetanus, acellular pertussis (DTaP) primary vaccination series, followed by a DTaP booster early in adolescence. In addition, the guideline authors recommend routine use of the new adult DTaP vaccine for all adults younger than 65 years. The vaccine should be given at 10-year intervals.

"This is a major, major advance," Dr Irwin says of the new vaccine-which he plans to offer to all his eligible adult patients.

References:

REFERENCES:

1.

Irwin RS, Baumann MH, Boulet LP, et al. Diagnosis and management of cough: executive summary. ACCP evidence-based clinical practice guidelines.

Chest

. 2006;129:1S-23S.

2.

Ward JI, Cherry JD, Chang SJ, et al. Efficacy of an acellular pertussis vaccine among adolescents and adults.

N Engl J Med

. 2005;353:1555-1563.