Recognition of the importance of cough in clinical medicine was the impetus for the original evidence-based consensus panel report on “Managing Cough as a Defense Mechanism and as a Symptom,” published in 1998,¹ and this updated revision. Compared to the original cough consensus statement, this revision (1) more narrowly focuses the guidelines on the diagnosis and treatment of cough, the symptom, in adult and pediatric populations, and minimizes the discussion of cough as a defense mechanism; (2) improves on the rigor of the evidence-based review and describes the methodology in a separate section; (3) updates and expands, when appropriate, all previous sections; and (4) adds new sections with topics that were not previously covered. These new sections include nonasthmatic eosinophilic bronchitis (NAEB); acute bronchitis; nonbronchiectatic suppurative airway diseases; cough due to aspiration secondary to oral/pharyngeal dysphagia; environmental/occupational causes of cough; tuberculosis (TB) and other infections; cough in the dialysis patient; uncommon causes of cough; unexplained cough, previously referred to as idiopathic cough; an empiric integrative approach to the management of cough; assessing cough severity and efficacy of therapy in clinical research; potential future therapies; and future directions for research.

The American College of Chest Physicians (ACCP) finds it imperative to include individuals who are experts in their respective fields on guideline development committees. Recommendations and publications that are the resulting products from these committees will have far-reaching significance that may affect multiple aspects of the practice of chest medicine throughout the world. Therefore, it is essential that the ACCP have full disclosure of outside interests from those individuals serving on policy development committees, including liaison representatives from outside organizations.

The impact of cough on health is substantial. It can (1) be an important defense mechanism that helps clear excessive secretions and foreign material from the airways; (2) be an important factor in the spread of infection; and (3) present as one of the most common symptoms for which patients seek medical attention and spend health-care dollars.¹

Objectives: To assemble a multidisciplinary, geographically diverse panel of experts in the diagnosis and treatment of cough with the intention of developing clinically relevant practice guidelines for pulmonary and primary care physicians, including recommendations covering many etiologies of cough, adult and pediatric evaluation and treatment, and empiric yet integrative algorithms for the management of the patient with cough.

Methods: The Duke University Center for Clinical Health Policy Research was selected to review and summarize the current evidence in this area. The expert panel established clinical recommendations and algorithms founded on the synthesis of this evidence.

Conclusions: This section describes the approach used to develop the guidelines, including identifying, evaluating, and synthesizing the evidence, assessing the strength of evidence pertinent to individual guidelines, and grading the guideline recommendations.

Objectives: To describe the anatomy and neurophysiology of the cough reflex.

Methods: A review of the literature was carried out using PubMed and the ISI Web of Knowledge from 1951 to 2004. Most of the referenced studies were carried out in animals

Conclusions: Studies carried out in animals provide suggestive but inconclusive evidence that C-fibers and rapidly adapting receptors (RARs) arising from the vagus nerves mediate coughing. Recent studies also have suggested that a vagal afferent nerve subtype that is not readily classified as a RAR or a C-fiber may play an important role in regulating cough. Afferent nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature also likely play a less essential but important accessory role in regulating cough. The responsiveness and morphology of the airway vagal afferent nerve subtypes and the extrapulmonary afferent nerves that regulate coughing are described.

Objective: The anatomy and neurophysiology of cough has been reviewed in the preceding section. The objective of this section is to describe how the varied anatomic components of the respiratory system work in concert to produce an effective cough.

Methods: This was accomplished by reviewing (1) the factors needed to produce effective cough pressures and gas velocity in the airways, and (2) the salient features of the interaction between the airflow generated during a cough and the mucus that lines the tracheobronchial tree. The MEDLINE database was searched for this review, and the search consisted of studies published in English between 1960 and April 2004. Search terms were “cough mechanics” and “cough physiology.”

Results: Inhaling to high lung volumes and glottic closure prior to the expiratory phase of cough facilitate the generation of high intrathoracic pressures. These high intrathoracic pressures (1) provide the driving force for airstream flow during cough and (2) dynamically compress the central airways, which further enhances the cough airstream velocity.

Conclusions: High intrathoracic pressures are needed to generate the requisite cough expiratory flows and airstream velocities. However, cough may be effective in individuals with mild-to-moderate degrees of respiratory muscle weakness, as only modest increases in intrathoracic pressure are needed to dynamically compress the large intrathoracic airways and increase cough flow velocity.

Objectives: To review the spectrum and frequency of complications associated with coughing.

Design/methodology: Ovid MEDLINE literature review (through March 2004) for all studies published in the English language, including case series and case reports, since 1966 using the MeSH terms “cough” and “complications.”

Results: The complications of cough appear to stem from physiologic events. The magnitude of pressures, velocities, and energy that is generated during vigorous coughing allow coughing to be an effective means of clearing the airways of excessive secretions and foreign material, and providing cardiopulmonary resuscitation; however, they can also cause a variety of profound physical and psychosocial complications. The adverse occurrences include cardiovascular, constitutional, GI, genitourinary, musculoskeletal, neurologic, ophthalmologic, psychosocial, respiratory, and skin complications, and a decrease in health-related quality of life.

Conclusions: Knowledge of the spectrum of complications should enable clinicians to appreciate (1) the impact of cough on patients, (2) why it is imperative to exhaust all possible diagnostic and therapeutic options to eliminate cough, and (3) why it is inappropriate to minimize a patient’s complaint of cough and/or advise him/her to “live with it.”

Objective: To review the literature on the most common causes of chronic cough.

Methods: MEDLINE was searched (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms “cough,” “causes of cough,” and “etiology of cough.” Case series and prospective descriptive clinical trials were selected for review. Also obtained were any references from these studies that were pertinent to the topic

Results: Upper airway cough syndrome (UACS) due to a variety of rhinosinus conditions, previously referred to as postnasal drip syndrome, asthma, nonasthmatic eosinophilic bronchitis (NAEB), and gastroesophageal reflux disease (GERD) are the most common causes of chronic cough. Each of these diagnoses may be present alone or in combination and may be clinically silent apart from the cough itself.

Conclusion: In the absence of evidence for the presence of another disorder, an approach focused on detecting the presence of UACS, asthma, NAEB, or GERD, alone or in combination, is likely to have a far higher yield than routinely searching for relatively uncommon or obscure diagnoses.

Objective: To review the literature on postnasal drip syndrome (PNDS)-induced cough and the various causes of PNDS. Hereafter, PNDS will be referred to as upper airway cough syndrome (UACS).

Methods: MEDLINE search (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms “cough,” “causes of cough,” “etiology of cough,” “postnasal drip,” “allergic rhinitis,” “vasomotor rhinitis,” and “chronic sinusitis.” Case series and prospective descriptive clinical trials were selected for review. Also, any references from these studies that were pertinent to the topic were obtained.

Results: In multiple prospective, descriptive studies of adults, PNDS due to a variety of upper respiratory conditions has been shown either singly or in combination with other conditions, to be the most common cause of chronic cough. The symptoms and signs of PNDS are nonspecific, and a definitive diagnosis of PND-induced cough cannot be made from the medical history and physical examination findings alone. Furthermore, the absence of any of the usual clinical findings does not rule out a response to treatment that is usually effective for PND-induced cough. The differential diagnosis of PNDS-induced cough includes allergic rhinitis, perennial nonallergic rhinitis, postinfectious rhinitis, bacterial sinusitis, allergic fungal sinusitis, rhinitis due to anatomic abnormalities, rhinitis due to physical or chemical irritants, occupational rhinitis, rhinitis medicamentosa, and rhinitis of pregnancy. Because of a high prevalence of upper respiratory symptoms associated with gastroesophageal reflux disease (GERD), GERD may occasionally mimic PNDS. A crucial unanswered question is whether the conditions listed above actually produce cough through a final common pathway of PND or whether, in fact, in some circumstances they cause irritation or inflammation of upper airway structures that directly stimulate cough receptors and produce cough independently of or in addition to any associated PND.

Conclusion: PNDS (ie, UACS) secondary to a variety of rhinosinus conditions is the most common cause of chronic cough. Because it is unclear whether the mechanisms of cough are the PND itself or the direct irritation or inflammation of the cough receptors located in the upper airway, the guideline committee has decided that, pending further data that address this difficult question, the committee unanimously recommends that the term upper airway cough syndrome be used in preference to postnasal drip syndrome when discussing cough associated with upper airway conditions.

Objective: To review the literature on cough and the common cold.

Methods: MEDLINE was searched through May 2004 for studies published in the English language since 1980 on human subjects using the medical subject heading terms “cough” and “common cold.” Selected case series and prospective descriptive clinical trials were reviewed. Additional references from these studies that were pertinent to the topic were also reviewed.

Results: Based on extrapolation from epidemiologic data, the common cold is believed to be the single most common cause of acute cough. The most likely mechanism is the direct irritation of upper airway structures. It is also clear that viral infections of the upper respiratory tract that produce the common cold syndrome frequently produce a rhinosinusitis. In the setting of a cold, the presence of abnormalities seen on sinus roentgenograms or sinus CT scans are frequently due to the viral infection and are not diagnostic of bacterial sinus infection.

Conclusion: Cough due to the common cold is probably the most common cause of acute cough. In a significant subset of patients with “postinfectious” cough, the etiology is probably an inflammatory response triggered by a viral upper respiratory infection (ie, the common cold). The resultant subacute or chronic cough can be considered to be due to an upper airway cough syndrome, previously referred to as postnasal drip syndrome. This process can be self-perpetuating unless interrupted with active treatment.

Background: Asthma is among the most common causes of chronic cough in adult nonsmokers. Although cough usually accompanies dyspnea and wheezing, it may present in isolation as a precursor of typical asthmatic symptoms, or it may remain the predominant or sole symptom of asthma. The latter condition is known as cough-variant asthma (CVA).

Methods: Data for this review were obtained from a National Library of Medicine (PubMed) search, performed in April 2004, of the English language literature from 1975 to 2004, limited to human studies, using the search terms “cough” and “asthma.”

Results: The diagnosis of cough not associated with typical asthmatic symptoms (ie, CVA) presents a challenge, because physical examination and spirometry findings may be entirely normal. Methacholine inhalation challenge testing can demonstrate the presence of bronchial hyperresponsiveness; however, the diagnosis of cough due to asthma is only confirmed after the resolution of cough with antiasthmatic therapy. In general, the therapeutic approach to asthmatic cough is similar to that of the typical form of asthma. Most patients will respond to inhaled bronchodilators and inhaled corticosteroids. A subgroup of patients will require the addition of leukotriene receptor antagonists and/or a short course of oral corticosteroids.

Conclusions: Asthma should be considered as a potential etiology in any patient with chronic cough, because asthma is a common condition that is commonly associated with cough. Because the subgroup of asthmatic patients with CVA presents with no other symptoms of asthma, clinical suspicion must remain high. Cough due to asthma responds to standard antiasthmatic therapy.

Objectives: To critically review and summarize the literature on cough and gastroesophageal reflux disease (GERD), and to make evidence-based recommendations regarding the diagnosis and treatment of chronic cough due to GERD.

Design/methodology: Ovid MEDLINE literature review (through March 2004) for all studies published in the English language and selected articles published in other languages such as French since 1963 using the medical subject heading terms “cough,” “gastroesophageal reflux,” and “gastroesophageal reflux disease.”

Results: GERD, singly or in combination with other conditions, is one of the most common causes of chronic cough. In patients with normal chest radiographic findings, GERD most likely causes cough by stimulation of an esophageal-bronchial reflex. When GERD causes cough, there may be no GI symptoms up to 75% of the time. While 24-h esophageal pH monitoring is the most sensitive and specific test in linking GERD and cough in a cause-effect relationship, it has its limitations. In addition, there is no general agreement on how to best interpret the test, and it cannot detect non-acid reflux events. Therefore, when patients fit the clinical profile that has a high likelihood of predicting that GERD is the cause of cough, antireflux medical therapy should be empirically instituted. While some patients improve with minimal medical therapy, others require more intensive regimens. When empiric treatment fails, it cannot be assumed that GERD has been ruled out as a cause of chronic cough. Rather, an objective investigation for GERD is then recommended because the empiric therapy may not have been intensive enough or medical therapy may have failed. Surgery may be efficacious when intensive medical therapy has failed in selected patients who have undergone an extensive objective GERD evaluation.

Conclusions: Accurately diagnosing and successfully treating chronic cough due to GERD can be a major challenge.

Background: The purpose of this review is to present the evidence for the diagnosis and treatment of cough due to acute bronchitis and make recommendations that will be useful for clinical practice. Acute bronchitis is one of the most common diagnoses made by primary care clinicians and emergency department physicians. It is an acute respiratory infection with a normal chest radiograph that is manifested by cough with or without phlegm production that lasts for up to 3 weeks. Respiratory viruses appear to be the most common cause of acute bronchitis; however, the organism responsible is rarely identified in clinical practice because viral cultures and serologic assays are not routinely performed. Fewer than 10% of patients will have a bacterial infection diagnosed as the cause of bronchitis. The diagnosis of acute bronchitis should be made only when there is no clinical or radiographic evidence of pneumonia, and the common cold, acute asthma, or an exacerbation of COPD have been ruled out as the cause of cough. Acute bronchitis is a self-limited respiratory disorder, and when the cough persists for > 3 weeks, other diagnoses must be considered.

Methods: Recommendations for this review were obtained from data using a National Library of Medicine (PubMed) search dating back to 1950, which was performed in August 2004. The search was limited to literature published in the English language and human studies, using search terms such as “cough,” “acute bronchitis,” and “acute viral respiratory infection.”

Results: Unfortunately, most previous controlled trials guiding the treatment of acute bronchitis have not vigorously differentiated acute bronchitis and the common cold, and also have not distinguished between an acute exacerbation of chronic bronchitis and acute asthma as a cause of acute cough. For patients with the putative diagnosis of acute bronchitis, routine treatment with antibiotics is not justified and should not be offered. Antitussive agents are occasionally useful and can be offered as therapy for short-term symptomatic relief of coughing, but there is no role for inhaled bronchodilator or expectorant therapy. Children and adult patients with confirmed and probable whooping cough should receive a macrolide antibiotic and should be isolated for 5 days from the start of treatment; early treatment within the first few weeks will diminish the coughing paroxysms and prevent spread of the disease; the patient is unlikely to respond to treatment beyond this period.

Conclusion: Acute bronchitis is an acute respiratory infection that is manifested by cough and, at times, sputum production that lasts for no more than 3 weeks. This syndrome should be distinguished from the common cold, an acute exacerbation of chronic bronchitis, and acute asthma as the cause of acute cough. The widespread use of antibiotics for the treatment of acute bronchitis is not justified, and vigorous efforts to curtail their use should be encouraged.

Background: Chronic bronchitis is a disease of the bronchi that is manifested by cough and sputum expectoration occurring on most days for at least 3 months of the year and for at least 2 consecutive years when other respiratory or cardiac causes for the chronic productive cough are excluded. The disease is caused by an interaction between noxious inhaled agents (eg, cigarette smoke, industrial pollutants, and other environmental pollutants) and host factors (eg, genetic and respiratory infections) that results in chronic inflammation in the walls and lumen of the airways. As the disease advances, progressive airflow limitation occurs, usually in association with pathologic changes of emphysema. This condition is called COPD. When a stable patient experiences a sudden clinical deterioration with increased sputum volume, sputum purulence, and/or worsening of shortness of breath, this is referred to as an acute exacerbation of chronic bronchitis as long as conditions other than acute tracheobronchitis are ruled out. The purpose of this review is to present the evidence for the diagnosis and treatment of cough due to chronic bronchitis, and to make recommendations that will be useful for clinical practice.

Methods: Recommendations for this section of the review were obtained from data using a National Library of Medicine (PubMed) search dating back to 1950, performed in August 2004, of the literature published in the English language. The search was limited to human studies, using the search terms “cough,” “chronic bronchitis,” and “COPD.”

Results: The most effective way to reduce or eliminate cough in patients with chronic bronchitis and persistent exposure to respiratory irritants, such as personal tobacco use, passive smoke exposure, and workplace hazards is avoidance. Therapy with a short-acting inhaled β-agonist, inhaled ipratropium bromide, and oral theophylline, and a combined regimen of inhaled long-acting β-agonist and an inhaled corticosteroid may improve cough in patients with chronic bronchitis, but there is no proven benefit for the use of prophylactic antibiotics, oral corticosteroids, expectorants, postural drainage, or chest physiotherapy. For the treatment of an acute exacerbation of chronic bronchitis, there is evidence that inhaled bronchodilators, oral antibiotics, and oral corticosteroids (or in severe cases IV corticosteroids) are useful, but their effects on cough have not been systematically evaluated. Therapy with expectorants, postural drainage, chest physiotherapy, and theophylline is not recommended. Central cough suppressants such as codeine and dextromethorphan are recommended for short-term symptomatic relief of coughing.

Conclusions: Chronic bronchitis due to cigarette smoking or other exposures to inhaled noxious agents is one of the most common causes of chronic cough in the general population. The most effective way to eliminate cough is the avoidance of all respiratory irritants. When cough persists despite the removal of these inciting agents, there are effective agents to reduce or eliminate cough.

Objectives: Nonasthmatic eosinophilic bronchitis is a newly recognized cause of chronic cough. Our objective was to review the pathogenesis, natural history, diagnosis, and treatment of this condition.

Methods: The current literature was reviewed using an Ovid MEDLINE and PubMed literature review for all studies published in the English language from 1963 to December 2004 using the medical subject heading term “eosinophilic bronchitis.”

Results: Nonasthmatic eosinophilic bronchitis is a common cause of chronic cough. It is characterized by the presence of eosinophilic airway inflammation, similar to that seen in asthma. However, in contrast to asthma, nonasthmatic eosinophilic bronchitis is not associated with variable airflow limitation or airway hyperresponsiveness. The differences in functional association are related to differences in the localization of mast cells within the airway wall, with airway smooth muscle infiltration occurring in patients with asthma, and epithelial infiltration in patients with nonasthmatic eosinophilic bronchitis. Diagnosis is made by the confirmation of eosinophilic airway inflammation usually with induced sputum analysis after the exclusion of other causes for chronic cough on clinical, radiologic, and lung function assessment. The cough usually responds well to treatment with inhaled corticosteroids. The dose and duration of treatment differ between patients. The condition can be transient, episodic, or persistent unless treated, and occasionally patients may require long-term prednisone treatment.

Conclusions: Further study of this condition may improve our understanding of airway inflammation and airway responsiveness, leading to novel targets for therapeutic agents for the treatment of both asthma and nonasthmatic eosinophilic bronchitis.

Background: Bronchiectasis is a condition that is characterized by the permanent dilation of bronchi with destruction of elastic and muscular components of their walls, usually due to acute or chronic infection. The cardinal symptom is a chronic productive cough.

Methods: Review of articles cited in the systematic literature search, along with others found in Ovid MEDLINE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trial Register, and the Database of Abstracts of Reviews of Effectiveness) from 1966 through 2003.

Results/conclusions: High-resolution CT scanning of the chest is the preferred means of establishing the diagnosis of bronchiectasis. With the increasing use of antibiotics in the treatment of childhood infection in the last several decades, an increasing percentage of patients with bronchiectasis now have an underlying disorder that predisposes them to chronic or recurrent infection. These include cystic fibrosis, common variable immunodeficiency, HIV infection, primary ciliary dyskinesia, allergic bronchopulmonary aspergillosis, and chronic Mycobacterium avium complex infection. A variety of agents have been used to improve cough effectiveness and prevent infectious exacerbations in patients with bronchiectasis, with variable results. Chest physiotherapy offers a modest benefit in increasing sputum volume, but its long-term effectiveness is unknown. Selected patients with localized idiopathic bronchiectasis that causes intolerable symptoms despite maximal medical therapy should be offered treatment with surgery. Patients with exacerbations of bronchiectasis should be given antibiotics, with the choice of agents depending on the likely causative pathogens.

Objectives: To review the role of nonbronchiectatic suppurative airway disease (bronchiolitis) in the spectrum of causes of cough and its management.

Design/methodology: A MEDLINE search (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms “cough,” “causes of cough,” “etiology of cough,” “interstitial lung disease,” “bronchiolitis,” “bronchiolitis obliterans,” “diffuse panbronchiolitis,” and “inflammatory bowel disease” was performed. Case series and prospective descriptive clinical trials were selected for review. Any references from these studies that were pertinent to the topic were also obtained.

Results/conclusions: In patients with cough in whom other more common causes of cough have been excluded, incomplete or irreversible airflow limitation, small airways disease seen on high-resolution CT scan, or purulent secretions seen on bronchoscopy, should suggest nonbronchiectatic suppurative airways disease (bronchiolitis) as a potential primary cause. Successful management depends on the identification of the specific underlying disorder.

Background: Patients who complain of a persistent cough lasting > 3 weeks after experiencing the acute symptoms of an upper respiratory tract infection may have a postinfectious cough. Such patients are considered to have a subacute cough because the condition lasts for no > 8 weeks. The chest radiograph findings are normal, thus ruling out pneumonia, and the cough eventually resolves, usually on its own. The purpose of this review is to present the evidence for the diagnosis and treatment of postinfectious cough, including the most virulent form caused by Bordetella pertussis infection, and make recommendations that will be useful for clinical practice.

Methods: Recommendations for this section of the guideline were obtained from data using a National Library of Medicine (PubMed) search dating back to 1950, which was performed in August 2004, of the literature published in the English language. The search was limited to human studies, using the search terms “cough,” “postinfectious cough,” “postviral cough,” “Bordetella pertussis,” “pertussis infection,” and “whooping cough.”

Results: The pathogenesis of the postinfectious cough is not known, but it is thought to be due to the extensive inflammation and disruption of upper and/or lower airway epithelial integrity. When postinfectious cough emanates from the lower airway, this is often associated with the accumulation of an excessive amount of mucus hypersecretion and/or transient airway and cough receptor hyperresponsiveness; all may contribute to the subacute cough. In these patients, the optimal treatment is not known. Except for bacterial sinusitis or early on in a B pertussis infection, therapy with antibiotics has no role, as the cause is not bacterial infection. The use of inhaled ipratropium may be helpful. Other causes of postinfectious cough are persistent inflammation of the nose and paranasal sinuses, which leads to an upper airway cough syndrome (previously referred to as postnasal drip syndrome), and gastroesophageal reflux disease, which may be a complication of the vigorous coughing. One type of postinfectious cough that is particularly virulent is that caused by B pertussis infection. When the cough is accompanied by paroxysms of coughing, posttussive vomiting, and/or an inspiratory whooping sound, the diagnosis of a B pertussis infection should be made unless another diagnosis is proven. This infection is highly contagious but responds to antibiotic coverage with an oral macrolide when administered early in the course of the disease. A safe and effective vaccine to prevent B pertussis is now available for adults as well as children. It is recommended according to CDC guidelines.

Conclusions: In patients who have a cough lasting from 3 to 8 weeks with normal chest radiograph findings, consider the diagnosis of postinfectious cough. In most patients, a specific etiologic agent will not be identified, and empiric therapy may be helpful. A high degree of suspicion for cough due to B pertussis infection will lead to earlier diagnosis, patient isolation, and antibiotic treatment.

Goals/objectives: To review the scientific evidence on cough associated with tumors in the lungs.

Methods: MEDLINE literature review (through March 2004) for all studies published in the English language, including case series and case reports, since 1966 using the medical subject heading terms “cough” and “lung neoplasms.”

Results: Primary bronchogenic carcinoma is the most common lethal neoplasm in the United States. Malignancies that arise in other organs will often metastasize to the lungs. Any form of cancer involving the lungs may be associated with cough. However, cough is far more likely to indicate involvement of the airways than the lung parenchyma because of the location of cough receptors. Cough is present in > 65% of patients at the time lung cancer is diagnosed, and productive cough is present in > 25% of patients. While cough as a presenting symptom of lung cancer is common, many studies have shown that lung cancer is the cause of chronic cough in ≤ 2% of all patients who present with a chronic cough.

Conclusions: Bronchoscopy is usually indicated when there is suspicion of airway involvement by a malignancy. Conversely, bronchoscopy usually should not be performed to assess a cough for the possibility of lung cancer when there is little risk for lung cancer (nonsmokers) and when there are normal findings on a plain chest radiograph. If the lung cancer can be removed surgically, cough will usually abate. Radiation therapy, chemotherapy (especially with gemcitabine), and endobronchial treatment methods likely will improve cough caused by lung cancer. Centrally acting narcotic antitussive agents are usually administered for the control of cough caused by lung cancer when other treatment methods fail.

Background: Cough may be an indicator of aspiration due to oral-pharyngeal dysphagia.

Methods: Relevant literature was identified by searching the Communication Sciences and Disorders Dome, the Cumulative Index to Nursing and Allied Health Literature, the Educational Resource Information Center, Health & Psychosocial Instruments, the American Psychological Association, and the National Library of Medicine databases from 1965 to 2004 using the terms “deglutition,” “aspiration,” and “cough.”

Results: Aspiration was observed on radiologic evaluation in over one third of acute stroke patients and in > 40% of patients undergoing cervical spine surgery. Cough while eating may indicate aspiration, but aspiration may be clinically silent. Subjective patient and caregiver reports of cough while eating are useful in identifying patients who are at risk for aspiration. Objective measures of voluntary cough and tussigenic challenges to inhaled irritants are under investigation to determine their capacity to predict the risk for aspiration and subsequent pneumonia. The treatment of dysphagic patients by a multidisciplinary team, including early evaluation by a speech-language pathologist, is associated with improved outcomes. Effective clinical interventions such as the use of compensatory swallowing strategies and the alteration of food consistencies can be based on the results of instrumental swallowing studies. The efficacy of swallowing exercises and electrical muscle stimulation is under study. Surgical interventions may be considered in selected patients, but studies proving efficacy are generally lacking.

Conclusions: Patients who are at risk for aspiration can be identified, and appropriate interventions can reduce its associated morbidity.

Background: A dry, persistent cough is a well-described class effect of the angiotensin-converting enzyme (ACE) inhibitor medications. The mechanism of ACE inhibitor-induced cough remains unresolved, but likely involves the protussive mediators bradykinin and substance P, agents that are degraded by ACE and therefore accumulate in the upper respiratory tract or lung when the enzyme is inhibited, and prostaglandins, the production of which may be stimulated by bradykinin.

Methods: Data for this review were obtained from a National Library of Medicine (PubMed) search, which was performed in May 2004, of the literature published in the English language from 1985 to 2004, using the search terms “angiotensin-converting enzyme,” “angiotensin converting enzyme inhibitors,” and “cough.”

Results: The incidence of ACE inhibitor-induced cough has been reported to be in the range of 5 to 35% among patients treated with these agents. However, a much lower incidence has been described in studies of patients presenting for the evaluation of chronic cough. The onset of ACE inhibitor-induced cough ranges from within hours of the first dose to months after the initiation of therapy. Resolution typically occurs within 1 to 4 weeks after the cessation of therapy, but cough may linger for up to 3 months. The only uniformly effective treatment for ACE inhibitor-induced cough is the cessation of treatment with the offending agent. The incidence of cough associated with therapy with angiotensin-receptor blockers appears to be similar to that of the control drug. In a minority of patients, cough will not recur after the reintroduction of ACE inhibitor therapy.

Conclusions: In a patient with chronic cough, ACE inhibitors should be considered as wholly or partially causative, regardless of the temporal relation between the initiation of ACE inhibitor therapy and the onset of cough. Although the cessation of therapy is the only uniformly effective treatment for ACE inhibitor-induced cough, some pharmacologic agents have been shown to attenuate the cough.

Objectives: To review the literature on habit, tic, and psychogenic cough, and to make evidence-based recommendations regarding diagnosis and treatment.

Design/methodology: For data on adults, an Ovid MEDLINE literature review (through February 2005) was performed for all studies published in the English language, including case series and case reports, since 1966 using the medical subject heading terms “habit cough,” “psychogenic cough,” “tic disorder,” “vocal tic,” “Tourette’s syndrome,” “honking cough,” and “barking cough.” For pediatric data, articles were identified dating from 1966 from searches of the Cochrane Library, PubMed, EMBASE, the list of references in relevant publications, and the authors’ collection of references with the last search performed in February 2005. The search terms used were “children” and “vocal tics” or “habit cough,” or “psychogenic cough” or “chronic cough.”

Results/conclusions: The methodologies used and rigor of the diagnostic and therapeutic interventions reported in the literature are inconsistent. The putative clinical characteristics of habit cough and psychogenic cough, for the most part, have not been prospectively or systematically studied. Therefore, on the basis of expert opinion, the diagnoses of habit cough or psychogenic cough can be made only after an extensive evaluation is performed that includes ruling out tic disorders and uncommon causes of chronic cough, and when cough improves with behavior modification or psychiatric therapy. In adult patients with chronic cough that remains persistently troublesome despite an extensive and thorough evidence-based evaluation, and after behavior modification and/or psychiatric therapy have failed, unexplained cough should be diagnosed rather than habit cough or psychogenic cough. In children, the depth of investigations to rule out uncommon causes must be individualized as some investigations and/or treatment may increase morbidity. In adult and pediatric patients with chronic cough that is associated with troublesome psychological manifestations, psychological counseling or psychiatric intervention should be encouraged after other causes have been ruled out.

Objectives: To review the role of chronic interstitial pulmonary disease in the spectrum of causes of cough and its management.

Design/methodology: A MEDLINE search (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms “cough,” “causes of cough,” “etiology of cough,” “interstitial lung disease,” “idiopathic pulmonary fibrosis,” “sarcoidosis,” and “hypersensitivity pneumonitis” was performed. Case series and prospective descriptive clinical trials were selected for review. Any references from these studies that were pertinent to the topic were also obtained.

Results/conclusions: In patients with cough, chronic interstitial pulmonary disease should be considered as a primary cause only after more common causes, such as upper airway cough syndrome and gastroesophageal reflux, have been excluded. Successful management depends on identification of the specific disorder.

Objectives: This section of the guideline aims to review the role of occupational and environmental factors in causing and contributing to cough. It also aims to indicate when such causes should be considered in a clinical setting, and a general approach to assessment and management.

Methods: A review was performed of published data between 1985 and 2004 using PubMed. The search terms used included “air pollution,” “sick building syndrome,” “occupational asthma,” “occupational lung disease,” “hypersensitivity pneumonitis” (HP), “cigarette smoke,” and “asthma.” Selected articles were chosen when meeting the objectives, but the extent of articles available and the limited space for this section does not permit a fully comprehensive review of all of these areas, for which the reader is referred to other sections of this clinical practice guideline, the published literature, textbooks of occupational lung disease, or more specific review articles.

Results/conclusions: Almost any patient presenting with cough may have an occupational or environmental cause of or contribution to their cough. The importance of this is that recognition and intervention may result in full or partial improvement of the cough, may limit the need for medication/symptomatic treatment, and may improve the long-term prognosis. Nonoccupational environmental contributing factors for upper and lower airway causes of cough include indoor irritant and allergenic agents such as cigarette smoke, cooking fumes, animals, dust mites, fungi, and cockroaches. Causes of HP indoors include birds and fungal antigens. Outdoor pollutants and allergens also contribute to upper and lower airway causes of cough. Occupational exposures can cause hypersensitivity responses leading to rhinitis and upper airway cough syndrome, previously referred to as postnasal drip syndrome, as well as asthma, HP, chronic beryllium disease, and hard metal disease, as well as irritant or toxic responses. The diagnosis is only reached by initially considering possible occupational and environmental factors, and by obtaining an appropriate medical history to determine relevant exposures, followed by objective investigations. This may require referral to a center of expertise.

Background: Although tuberculosis (TB) and other lung infections are common throughout the developing world, they are not among the most common causes of chronic cough.

Methods: Articles were selected from a MEDLINE search from 1966 through 2003 (using medical subject heading words “cough,” “tuberculosis,” and “lung infection”), and World Health Organization and Centers for Disease Control and Prevention web sites.

Results: Because of the contagious nature of TB and its potential for devastating morbidity and mortality for individual patients and society, TB should be considered early on in the workup of patients with chronic cough when the likelihood of active TB is high. On a worldwide basis, many cases of chronic cough are caused by infection including TB, and endemic fungi and parasites are important causes of cough in specific geographic regions. The convergence of the AIDS epidemic with the high prevalence of TB in the developing world has fueled the marked increase in cases of TB. Persons who live and work in facilities like prisons and nursing homes are also susceptible to tuberculous infection, and they spread it to others. Infection with endemic fungi and parasites should be considered in patients with chronic cough who live, or have lived, in these areas.

Conclusion: Patients with unexplained chronic cough who have resided in areas having endemic infection with TB, fungi, or parasites should undergo diagnostic evaluation for these pathogens when more common causes of cough have been ruled out.

Objective: To review the clinical associations between peritoneal dialysis (PD) and cough.

Methodology: A literature review was performed on PubMed for articles published between 1983 and 2004 using the search terms “dialysis” and “cough.”

Results/conclusions: Patients receiving PD are more likely to develop a cough than other patients with end-stage renal disease who are receiving hemodialysis. Although both groups of patients frequently receive medications, such as angiotensin-converting enzyme inhibitors and β-adrenergic blocking agents, that can trigger cough and both may be at increased risk for fluid overload and pulmonary edema, the increased risk associated with PD appears to relate to gastroesophageal reflux, likely from the peritoneal dialysate.

Background: Patients with compromised immune systems often complain of chronic cough. While these patients are susceptible to opportunistic infections that should be considered in the evaluation, common causes should also be investigated.

Methods: MEDLINE search using the terms “cough,” “immunocompromise,” “HIV,” “AIDS,” “neutropenia,” and “corticosteroids,” from 1966 through the end of 2003.

Results: Patients with compromised immune systems and chronic cough usually have the same disorders causing cough as in the general population. However, depending on the nature and severity of the immune defect, they may also have a variety of infections not usually encountered in immunocompetent hosts.

Conclusion: In immunocompromised patients presenting with cough, the initial diagnostic evaluation should be the same as that for healthy hosts. However, when these diagnoses have been excluded, opportunistic infections should be considered.

Objectives: To describe the uncommon causes of cough.

Design/methodology: An English language literature search by MEDLINE citations from 1975 through 2004 was used to identify publications on uncommon pulmonary and nonpulmonary disorders in which cough was present as the major or presenting symptom in > 50% of those persons affected by the uncommon diseases.

Results: A substantial number of uncommon or rare pulmonary and nonpulmonary disorders were identified. The uncommon occurrence of these diseases made it difficult to develop a meaningful evidence-based guideline to the diagnosis and therapy of many of the uncommon causes of cough. As cough was the major or presenting symptom, it was usually initially attributed to common respiratory diseases (eg, asthma or bronchitis). As a result, a substantial time lag existed from the onset of cough to the diagnosis of the etiologic entity. Diagnostic tests limited to the respiratory system did not always provide clues to the diagnosis of uncommon causes of cough.

Conclusions: Cough is the major or presenting symptom in many uncommon pulmonary and nonpulmonary disorders. A strong index of suspicion is essential to consider and diagnose the uncommon causes of cough. The diagnosis and management of cough in patients with uncommon causes of cough is dependent on the underlying etiology.

Objective: To review the literature on unexplained cough, previously referred to as idiopathic cough.

Methods: Search of MEDLINE (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms “cough,” “unexplained cough,” and “idiopathic cough.” We selected case series and prospective descriptive clinical trials. We also obtained any references from these studies that were pertinent to the topic.

Results: The diagnosis of unexplained (idiopathic) cough should only be considered after a thorough diagnostic and treatment approach for the most common causes of cough has been completed and uncommon causes have been adequately evaluated Unless this is done, it is likely that many patients with a definable cause of cough will be misdiagnosed as having “unexplained cough.”

Conclusion: The diagnosis of unexplained cough is probably made too often based on an inadequate diagnostic workup or treatment course to determine the specific cause of cough. Nevertheless, there may be a group of patients in whom none of the usual explanations for cough may be present. For this group, the committee unanimously recommends using the diagnostic term unexplained cough, rather than idiopathic cough.

Objective: Review the literature to provide a comprehensive approach, including algorithms for the clinician to follow in evaluating and treating the patient with acute, subacute, and chronic cough.

Methods: We searched MEDLINE (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms “cough,” “treatment of cough,” and “empiric treatment of cough.” We selected case series and prospective descriptive clinical trials. We also obtained any references from these studies that were pertinent to the topic.

Results: The relative frequency of the disorders (alone and in combination) that can cause cough as well as the sensitivity and specificity of many but not all diagnostic tests in predicting the cause of cough are known. An effective approach to successfully manage chronic cough is to sequentially evaluate and treat for the common causes of cough using a combination of selected diagnostic tests and empiric therapy. Sequential and additive therapy is often crucial because more than one cause of cough is frequently present.

Conclusion: Algorithms that provide a “road map” that the clinician can follow are useful and are presented for acute, subacute, and chronic cough.

Objectives: To review the literature on identifying cough and to make evidence-based recommendations for assessing the efficacy of cough-modifying agents in clinical research.

Design/methodology: Ovid MEDLINE literature review (through March 2004) for all studies published in the English language since 1953 using the medical subject heading terms “assessing the impact of cough,” “assessing the efficacy of cough treatments,” “tussigenic challenges,” “cough counting,” “character and timing of cough,” “visual analog scales,” “cough scoring systems,” “health related quality of life instruments,” “cough-specific health-related quality of life instruments,” “citric acid challenge,” “capsaicin challenge,” “flow-volume loops,” “assessing airway inflammation,” “lipid laden macrophages in sputum,” and “exhaled nitric oxide.”

Results/conclusions: To optimally evaluate the efficacy of cough-modifying agents, investigators should use both subjective and objective methods, because they have the potential to measure different things. A patient’s subjective response is likely the only one that measures the impact of the intensity of cough. With respect to subjective methods, it is recommended that a cough-specific health-related quality-of-life instrument be utilized because valid and reliable instruments exist. Even though visual analog scales have not been psychometrically tested, they are recommended because they are commonly used and valid, and they are likely to yield different but complementary results. Because there are cough-specific health-related quality-of-life instruments that have been fully psychometrically tested, and the same cannot be said for visual analog scales, this is a reason to use cough-specific health-related quality-of-life instruments as the primary, subjective outcome measure of choice. With respect to objective methods, tussigenic challenges can be used before and after the intervention to assess the effect of therapy on cough sensitivity. They are most likely to be helpful in disease states in which cough reflex sensitivity is known to be heightened. Because the act of coughing has the potential to traumatize the upper airway (eg, vocal cords), assessing the presence of upper airway edema before and after therapy with flow-volume loops may be useful. Investigators must be cautious and not assume that observing changes suggestive of inflammation and edema of upper airway structures is specific for any particular disease. Cough counting is recommended with a computerized methodology that is reliable and accurate, noninvasive and portable, and easy to use in unattended, ambulatory real-life settings within a subject’s home environment when it can be done over a 24-h period of time.

Background: Cough-suppressant therapy, previously termed nonspecific antitussive therapy, incorporates the use of pharmacologic agents with mucolytic effects and/or inhibitory effects on the cough reflex itself. The intent of this type of therapy is to reduce the frequency and/or intensity of coughing on a short-term basis.

Methods: Data for this review were obtained from several National Library of Medicine (PubMed) searches (from 1960 to 2004), which were performed between May and September 2004, of the literature published in the English language, limited to human studies, using combinations of the search terms “cough,” “double-blind placebo-controlled,” “antitussive,” “mucolytic,” “cough clearance,” “common cold,” “protussive,” “guaifenesin,” “glycerol,” and “zinc.”

Results: Mucolytic agents are not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Peripheral and central antitussive agents can be useful in patients with chronic bronchitis, but can have little efficacy in patients with cough due to upper respiratory infection. Some protussive agents are effective in increasing cough clearance, but their long-term effectiveness has not been established. DNase is not effective as a protussive agent in patients with cystic fibrosis. Inhaled mannitol is acutely effective in this patient population, but its therapeutic potential must be investigated further.

Conclusions: These findings suggest that suppressant therapy is most effective when used for the short-term reduction of coughing. Relatively few drugs are effective as cough suppressants.

Background: Airway clearance may be impaired in disorders associated with abnormal cough mechanics, altered mucus rheology, altered mucociliary clearance, or structural airway defects. A variety of interventions are used to enhance airway clearance with the goal of improving lung mechanics and gas exchange, and preventing atelectasis and infection.

Method: A formal systematic review of nonpharmacologic protussive therapies was performed and constitutes the basis for this section of the guideline. In addition, the articles reviewed were found using the same methodology but were not limited to those that focused only on cough as a symptom. The MEDLINE database was searched for this review and consisted of studies published in the English language between 1960 and April 2004. The search terms used were “chest physiotherapy,” “forced expiratory technique,” “positive expiratory pressure,” “high frequency chest compression,” “insufflation,” and “exsufflation.”

Results: In general, studies of nonpharmacologic methods of improving cough clearance are limited by methodological constraints, and most were conducted only in patients with cystic fibrosis. Chest physiotherapy, including postural drainage, chest wall percussion and vibration, and a forced expiration technique (called huffing), increase airway clearance as assessed by sputum characteristics (ie, volume, weight, and viscosity) and clearance of the radioaerosol from the lung, but the long-term efficacy of these techniques compared with unassisted cough alone is unknown. Other devices that allow patients to achieve the same benefits derived from chest physiotherapy without the assistance of a caregiver appear to be as effective as chest physiotherapy in increasing sputum production.

Conclusions: Some nonpharmacologic therapies are effective in increasing sputum production, but their long-term efficacy in improving outcomes compared with unassisted cough alone is unknown.

Objectives: To review relevant literature and present evidence-based guidelines to assist general and specialist medical practitioners in the evaluation and management of children who present with chronic cough.

Methodology: The Cochrane, MEDLINE, and EMBASE databases, review articles, and reference lists of relevant articles were searched and reviewed by a single author. The date of the last comprehensive search was December 5, 2003, and that of the Cochrane database was November 7, 2004. The authors’ own databases and expertise identified additional articles.

Results/conclusions: Pediatric chronic cough (ie, cough in children aged < 15 years) is defined as a daily cough lasting for > 4 weeks. This time frame was chosen based on the natural history of URTIs in children and differs from the definition of chronic cough in adults. In this guideline, only chronic cough will be discussed. Chronic cough is subdivided into specific cough (ie, cough associated with other symptoms and signs suggestive of an associated or underlying problem) and nonspecific cough (ie, dry cough in the absence of an identifiable respiratory disease of known etiology). The majority of this section focuses on nonspecific cough, as specific cough encompasses the entire spectrum of pediatric pulmonology. A review of the literature revealed few randomized controlled trials for treatment of nonspecific cough. Management guidelines are summarized in two pathways. Recommendations are derived from a systematic review of the literature and were integrated with expert opinion. They are a general guideline only, do not substitute for sound clinical judgment, and are not intended to be used as a protocol for the management of all children with a coughing illness. Children (aged < 15 years) with cough should be managed according to child-specific guidelines, which differ from those for adults as the etiologic factors and treatments for children are sometimes different from those for adults. Cough in children should be treated based on etiology, and there is no evidence for using medications for the symptomatic relief of cough. If medications are used, it is imperative that the children are followed up and therapy with the medications stopped if there is no effect on the cough within an expected time frame. An evaluation of the time to response is important. Irrespective of diagnosis, environmental influences and parental expectations should be discussed and managed accordingly. Cough often impacts the quality of life of both children and parents, and the exploration of parental expectations and fears is often valuable in the management of cough in children.

Background: When the etiology of a patient’s chronic cough is established, specific antitussive therapy that is aimed at a particular cause of cough is highly effective. Nevertheless, in certain situations, therapy with cough suppressants, which previously were classified as nonspecific antitussive therapy, and which aim at suppressing the cough reflex regardless of the cause of cough, will be necessary.

Methodology: The data for this review were obtained with the aid of a National Library of Medicine (PubMed) search, which was performed in June 2004, of literature published in the English language from 1966 to 2004, using the search terms “cough,” “antitussive,” “pharmacotherapy,” “future therapies, ” and “potential therapies.”

Results/conclusions: Currently available cough-suppressant therapy is severely limited by a dearth of effective agents and/or their unacceptable side effects. Several classes of pharmacologic agents are currently under investigation in an attempt to develop clinically useful cough suppressants.

Objectives: To impart a call for further research into the identified domains of particular interest in the etiology, management, and treatment of cough.

Design/methodology: A literature review was performed using the search term “cough” in PubMed between 1983 and 2004. The final draft of this guideline was reviewed, in addition to recent studies on cough, and suggestions provided by the authors were collated into a definitive inventory of specific areas in which the lack of quality evidence encumbered the development of clinically relevant evidence-based recommendations.

Results/conclusions: Although our understanding of the causes and optimal management of chronic cough have significantly increased over the past 25 years, further research remains to be done on this common symptom. This is reflected by the generally low level of evidence for many of the recommendations in these guidelines. Research is particularly needed on the optimal treatment of postinfectious cough, how to distinguish acute bronchitis from other conditions, how to reliably diagnose and treat cough due to gastroesophageal reflux disease, clearly identifying a role for nonpharmacologic protussive treatment modalities in diseases associated with an increased production of bronchial secretions, determining how often cough in patients with interstitial lung disease is due to conditions other than these, establishing the spectrum and frequency of causes of chronic cough in the immunocompromised hosts, and better characterizing psychogenic cough. Further studies are also needed on methods for the assessment of cough, in particular, noninvasive measures of airway inflammation, and pharmacotherapy. It should be determined how often unexplained cough (previously referred to as idiopathic cough) is due to the use of non-evidence-based guidelines or to environmental causes, and assessed whether an empiric, integrative approach of diagnosing chronic cough leads to better outcomes, including cost-effectiveness, than routine testing. While much work has been done on chronic cough, we need studies on the spectrum and frequency of acute and subacute coughs.