Cough is an explosive expiration that provides a normal protective mechanism for clearing the tracheobronchial tree of secretions and foreign material. When excessive or bothersome, it is also one of the most common symptoms for which patients seek medical attention. Reasons for this include discomfort from the cough itself, interference with normal lifestyle, and concern for the cause of the cough, especially fear of cancer.
Coughing may be initiated either voluntarily or reflexively. As a defensive reflex it has both afferent and efferent pathways. The afferent limb includes receptors within the sensory distribution of the trigeminal, glossopharyngeal, superior laryngeal, and vagus nerves. The efferent limb includes the recurrent laryngeal nerve and the spinal nerves. The cough starts with a deep inspiration followed by glottic closure, relaxation of the diaphragm, and muscle contraction against a closed glottis. The resulting markedly positive intrathoracic pressure causes narrowing of the trachea. Once the glottis opens, the large pressure differential between the airways and the atmosphere coupled with tracheal narrowing produces rapid flow rates through the trachea. The shearing forces that develop aid in the elimination of mucus and foreign materials.
Cough can be initiated by a variety of irritant triggers either from an exogenous source (smoke, dust, fumes, foreign bodies) or from an endogenous origin (upper airway secretions, gastric contents). These stimuli may affect receptors in the upper airway (especially the pharynx and larynx) or in the lower respiratory tract, following access to the tracheobronchial tree by inhalation or aspiration. When cough is triggered by upper airway secretions (as with postnasal drip) or gastric contents (as with gastroesophageal reflux), the initiating factor can go unrecognized and the cough may persist. Additionally, prolonged exposure to such irritants may initiate airway inflammation, which can itself precipitate cough and sensitize the airway to other irritants. Cough associated with gastroesophageal reflux is due only in part to irritation of upper airway receptors or to aspiration of gastric contents, as a vagally mediated reflex mechanism secondary to acid in the distal esophagus may also contribute.
Any disorder resulting in inflammation, constriction, infiltration, or compression of airways can be associated with cough. Inflammation commonly results from airway infections, ranging from viral or bacterial bronchitis to bronchiectasis. In viral bronchitis, airway inflammation sometimes persists long after resolution of the typical acute symptoms, thereby producing a prolonged cough that may last for weeks. Pertussis infection is also a possible cause of persistent cough in adults; however, diagnosis is generally made on clinical grounds. Asthma is a common cause of cough. Although the clinical setting commonly suggests when a cough is secondary to asthma, some patients present with cough in the absence of wheezing or dyspnea, thus making the diagnosis more subtle ("cough variant asthma"). A neoplasm infiltrating the airway wall, such as bronchogenic carcinoma or a carcinoid tumor, is commonly associated with cough. Airway infiltration with granulomas may also trigger a cough, as seen with endobronchial sarcoidosis or tuberculosis. Compression of airways results from extrinsic masses such as lymph nodes or mediastinal tumors, or rarely from an aortic aneurysm.
Examples of parenchymal lung disease potentially producing cough include interstitial lung disease, pneumonia, and lung abscess. Congestive heart failure may be associated with cough, probably as a consequence of interstitial as well as peribronchial edema. A nonproductive cough complicates the use of angiotensin-converting enzyme (ACE) inhibitors in 5–20% of patients taking these agents. Onset is usually within 1 week of starting the drug but can be delayed up to 6 months. Although the mechanism is not known with certainty, it may relate to accumulation of bradykinin or substance P, both of which are degraded by ACE. In contrast, angiotensin II receptor antagonists do not seem to increase cough, likely because these drugs do not significantly increase bradykinin levels.
The most common causes of cough can be categorized according to the duration of the cough. Acute cough (less than 3 weeks) is most often due to upper respiratory infection (especially the common cold, acute bacterial sinusitis, and pertussis), but more serious disorders, such as pneumonia, pulmonary embolus, and congestive heart failure, can also present in this fashion. Subacute cough (between 3 and 8 weeks) is commonly post-infectious, resulting from persistent airway inflammation and/or postnasal drip following viral infection, pertussis, or infection with Mycoplasma or Chlamydia. In the patient with subacute cough that is not clearly post-infectious, the varied causes of chronic cough should be considered. Chronic cough (more than 8 weeks) in a smoker raises the possibilities of chronic obstructive lung disease or bronchogenic carcinoma. In a nonsmoker who has a normal chest radiograph and is not taking an ACE inhibitor, the most common causes of chronic cough are postnasal drip (sometimes termed the upper airway cough syndrome), asthma, and gastroesophageal reflux. Eosinophilic bronchitis in the absence of asthma has also been recognized as a potential cause of chronic cough.
Approach to the Patient: Cough
A detailed history frequently provides the most valuable clues for the etiology of the cough. Particularly important questions include:
- Is the cough acute, subacute, or chronic?
- At its onset, were there associated symptoms suggestive of a respiratory infection?
- Is it seasonal or associated with wheezing?
- Is it associated with symptoms suggestive of postnasal drip (nasal discharge, frequent throat clearing, a "tickle in the throat") or gastroesophageal reflux (heartburn or sensation of regurgitation)? However, the absence of such suggestive symptoms does not exclude either of these diagnoses.
- Is it associated with fever or sputum? If sputum is present, what is its character?
- Does the patient have any associated diseases or risk factors for disease (e.g., cigarette smoking, risk factors for infection with HIV, environmental exposures)?
- Is the patient taking an ACE inhibitor?
The general physical examination may point to a systemic or nonpulmonary cause of cough, such as heart failure or primary nonpulmonary neoplasm. Examination of the oropharynx may provide suggestive evidence for postnasal drip, including oropharyngeal mucus or erythema, or a "cobblestone" appearance to the mucosa. Auscultation of the chest may demonstrate inspiratory stridor (indicative of upper airway disease), rhonchi or expiratory wheezing (indicative of lower airway disease), or inspiratory crackles (suggestive of a process involving the pulmonary parenchyma, such as interstitial lung disease, pneumonia, or pulmonary edema).
Chest radiography may be particularly helpful in suggesting or confirming the cause of the cough. Important potential findings include the presence of an intrathoracic mass lesion, localized pulmonary parenchymal opacification, or diffuse interstitial or alveolar disease. An area of honeycombing or cyst formation may suggest bronchiectasis, while symmetric bilateral hilar adenopathy may suggest sarcoidosis.
Pulmonary function testing is useful for assessing the functional abnormalities that accompany certain disorders producing cough. Measurement of forced expiratory flow rates can demonstrate reversible airflow obstruction characteristic of asthma. When asthma is considered but flow rates are normal, bronchoprovocation testing with methacholine or cold-air inhalation can demonstrate hyperreactivity of the airways to a bronchoconstrictive stimulus. Measurement of lung volumes and diffusing capacity is useful primarily for demonstration of a restrictive pattern, often seen with any of the diffuse interstitial lung diseases.
If sputum is produced, gross and microscopic examination may provide useful information. Purulent sputum suggests chronic bronchitis, bronchiectasis, pneumonia, or lung abscess. Blood in the sputum may be seen in the same disorders, but its presence also raises the question of an endobronchial tumor. Greater than 3% eosinophils seen on staining of induced sputum in a patient without asthma suggests the possibility of eosinophilic bronchitis. Gram and acid-fast stains and cultures may demonstrate a particular infectious pathogen, while sputum cytology may provide a diagnosis of a pulmonary malignancy.
More specialized studies are helpful in specific circumstances. Fiberoptic bronchoscopy is the procedure of choice for visualizing an endobronchial tumor and collecting cytologic and histologic specimens. Inspection of the tracheobronchial mucosa can demonstrate endobronchial granulomas often seen in sarcoidosis, and endobronchial biopsy of such lesions or transbronchial biopsy of the lung interstitium can confirm the diagnosis. Inspection of the airway mucosa by bronchoscopy may also demonstrate the characteristic appearance of endobronchial Kaposi's sarcoma in patients with AIDS. High-resolution computed tomography (HRCT) can confirm the presence of interstitial lung disease and frequently suggests a diagnosis based on the specific abnormal pattern. It is the procedure of choice for demonstrating dilated airways and confirming the diagnosis of bronchiectasis.
A diagnostic algorithm for evaluation of subacute and chronic cough is presented in Fig. 34-1.
Common complications of coughing include chest and abdominal wall soreness, urinary incontinence, and exhaustion. On occasion, paroxysms of coughing may precipitate syncope (cough syncope), consequent to markedly positive intrathoracic and alveolar pressures, diminished venous return, and decreased cardiac output. Although cough fractures of the ribs may occur in otherwise normal patients, their occurrence should at least raise the possibility of pathologic fractures, which are seen with multiple myeloma, osteoporosis, and osteolytic metastases.
Definitive treatment of cough depends on determining the underlying cause and then initiating specific therapy. Elimination of an exogenous inciting agent (cigarette smoke, ACE inhibitors) or an endogenous trigger (postnasal drip, gastroesophageal reflux) is usually effective when such a precipitant can be identified. Other important management considerations are treatment of specific respiratory tract infections, bronchodilators for potentially reversible airflow obstruction, inhaled glucocorticoids for eosinophilic bronchitis, chest physiotherapy and other methods to enhance clearance of secretions in patients with bronchiectasis, and treatment of endobronchial tumors or interstitial lung disease when such therapy is available and appropriate. In patients with chronic, unexplained cough, an empirical approach to treatment is often used for both diagnostic and therapeutic purposes, starting with an antihistamine-decongestant combination, nasal glucocorticoids, or nasal ipratropium spray to treat unrecognized postnasal drip. If ineffective, this may be followed sequentially by empirical treatment for asthma, nonasthmatic eosinophilic bronchitis, and gastroesophageal reflux.
Symptomatic or nonspecific therapy of cough should be considered when: (1) the cause of the cough is not known or specific treatment is not possible, and (2) the cough performs no useful function or causes marked discomfort or sleep disturbance. An irritative, nonproductive cough may be suppressed by an antitussive agent, which increases the latency or threshold of the cough center. Such agents include codeine (15 mg qid) or nonnarcotics such as dextromethorphan (15 mg qid). These drugs provide symptomatic relief by interrupting prolonged, self-perpetuating paroxysms. However, a cough productive of significant quantities of sputum should usually not be suppressed, since retention of sputum in the tracheobronchial tree may interfere with the distribution of alveolar ventilation and the ability of the lung to resist infection.
Hemoptysis is defined as the expectoration of blood from the respiratory tract, a spectrum that varies from blood-streaking of sputum to coughing up large amounts of pure blood. Massive hemoptysis is variably defined as the expectoration of more than 100–600 mL over a 24-h period, although the patient's estimation of the amount of blood is notoriously unreliable. Expectoration of even relatively small amounts of blood is a frightening symptom and may be a marker for potentially serious disease, such as bronchogenic carcinoma. Massive hemoptysis, on the other hand, can represent an acutely life-threatening problem. Blood can fill the airways and the alveolar spaces, not only seriously disturbing gas exchange but potentially causing asphyxiation.
Because blood originating from the nasopharynx or the gastrointestinal tract can mimic blood coming from the lower respiratory tract, it is important to determine initially that the blood is not coming from one of these alternative sites. Clues that the blood is originating from the gastrointestinal tract include a dark red appearance and an acidic pH, in contrast to the typical bright red appearance and alkaline pH of true hemoptysis.
An etiologic classification of hemoptysis can be based on the site of origin within the lungs (Table 34-1). The most common site of bleeding is the tracheobronchial tree, which can be affected by inflammation (acute or chronic bronchitis, bronchiectasis) or by neoplasm (bronchogenic carcinoma, endobronchial metastatic carcinoma, or bronchial carcinoid tumor). The bronchial arteries, which originate either from the aorta or from intercostal arteries and are therefore part of the high-pressure systemic circulation, are the source of bleeding in bronchitis or bronchiectasis or with endobronchial tumors. Blood originating from the pulmonary parenchyma can be either from a localized source, such as an infection (pneumonia, lung abscess, tuberculosis), or from a process diffusely affecting the parenchyma (as with a coagulopathy or with an autoimmune process such as Goodpasture's syndrome). Disorders primarily affecting the pulmonary vasculature include pulmonary embolic disease and those conditions associated with elevated pulmonary venous and capillary pressures, such as mitral stenosis or left ventricular failure.
Although the relative frequency of the different etiologies of hemoptysis varies from series to series, most recent studies indicate that bronchitis and bronchogenic carcinoma are the two most common causes in the United States. Despite the lower frequency of tuberculosis and bronchiectasis seen in recent compared to older series, these two disorders still represent the most common causes of massive hemoptysis in several series, especially worldwide. Even after extensive evaluation, a sizable proportion of patients (up to 30% in some series) have no identifiable etiology for their hemoptysis. These patients are classified as having idiopathic or cryptogenic hemoptysis, and subtle airway or parenchymal disease is presumably responsible for the bleeding.
Approach to the Patient: Hemoptysis
The history is extremely valuable. Hemoptysis that is described as blood-streaking of mucopurulent or purulent sputum often suggests bronchitis. Chronic production of sputum with a recent change in quantity or appearance favors an acute exacerbation of chronic bronchitis. Fever or chills accompanying blood-streaked purulent sputum suggests pneumonia, whereas a putrid smell to the sputum raises the possibility of lung abscess. When sputum production has been chronic and copious, the diagnosis of bronchiectasis should be considered. Hemoptysis following the acute onset of pleuritic chest pain and dyspnea is suggestive of pulmonary embolism.
A history of previous or coexisting disorders should be sought, such as renal disease (seen with Goodpasture's syndrome or Wegener's granulomatosis), lupus erythematosus (with associated pulmonary hemorrhage from lupus pneumonitis), or a previous malignancy (either recurrent lung cancer or endobronchial metastasis from a nonpulmonary primary tumor) or treatment for malignancy (with recent chemotherapy or a bone marrow transplant). In a patient with AIDS, endobronchial or pulmonary parenchymal Kaposi's sarcoma should be considered. Risk factors for bronchogenic carcinoma, particularly smoking and asbestos exposure, should be sought. Patients should be questioned about previous bleeding disorders, treatment with anticoagulants, or use of drugs that can be associated with thrombocytopenia.
The physical examination may also provide helpful clues to the diagnosis. For example, examination of the lungs may demonstrate a pleural friction rub (pulmonary embolism), localized or diffuse crackles (parenchymal bleeding or an underlying parenchymal process associated with bleeding), evidence of airflow obstruction (chronic bronchitis), or prominent rhonchi, with or without wheezing or crackles (bronchiectasis). Cardiac examination may demonstrate findings of pulmonary arterial hypertension, mitral stenosis, or heart failure. Skin and mucosal examination may reveal Kaposi's sarcoma, arteriovenous malformations of Osler-Rendu-Weber disease, or lesions suggestive of systemic lupus erythematosus.
Diagnostic evaluation of hemoptysis starts with a chest radiograph (often followed by a CT scan) to look for a mass lesion, findings suggestive of bronchiectasis, or focal or diffuse parenchymal disease (representing either focal or diffuse bleeding or a focal area of pneumonitis). Additional initial screening evaluation often includes a complete blood count, a coagulation profile, and assessment for renal disease with a urinalysis and measurement of blood urea nitrogen and creatinine levels. When sputum is present, examination by Gram and acid-fast stains (along with the corresponding cultures) is indicated.
Fiberoptic bronchoscopy is particularly useful for localizing the site of bleeding and for visualization of endobronchial lesions. When bleeding is massive, rigid bronchoscopy is often preferable to fiberoptic bronchoscopy because of better airway control and greater suction capability. In patients with suspected bronchiectasis, HRCT is the diagnostic procedure of choice.
A diagnostic algorithm for evaluation of nonmassive hemoptysis is presented in Fig. 34-2.
The rapidity of bleeding and its effect on gas exchange determine the urgency of management. When the bleeding is confined to either blood-streaking of sputum or production of small amounts of pure blood, gas exchange is usually preserved; establishing a diagnosis is the first priority. When hemoptysis is massive, maintaining adequate gas exchange, preventing blood from spilling into unaffected areas of lung, and avoiding asphyxiation are the highest priorities. Keeping the patient at rest and partially suppressing cough may help the bleeding to subside. If the origin of the blood is known and is limited to one lung, the bleeding lung should be placed in the dependent position, so that blood is not aspirated into the unaffected lung.
With massive bleeding, the need to control the airway and maintain adequate gas exchange may necessitate endotracheal intubation and mechanical ventilation. In patients in danger of flooding the lung contralateral to the side of hemorrhage despite proper positioning, isolation of the right and left mainstem bronchi from each other can be achieved by selectively intubating the nonbleeding lung (often with bronchoscopic guidance) or by using specially designed double-lumen endotracheal tubes. Another option involves inserting a balloon catheter through a bronchoscope by direct visualization and inflating the balloon to occlude the bronchus leading to the bleeding site. This technique not only prevents aspiration of blood into unaffected areas but also may promote tamponade of the bleeding site and cessation of bleeding.
Other available techniques for control of significant bleeding include laser phototherapy, electrocautery, bronchial artery embolization, and surgical resection of the involved area of lung. With bleeding from an endobronchial tumor, argon plasma coagulation or the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser can often achieve at least temporary hemostasis by coagulating the bleeding site. Electrocautery, which uses an electric current for thermal destruction of tissue, can be used similarly for management of bleeding from an endobronchial tumor. Bronchial artery embolization involves an arteriographic procedure in which a vessel proximal to the bleeding site is cannulated, and a material such as Gelfoam is injected to occlude the bleeding vessel. Surgical resection is a therapeutic option either for the emergent therapy of life-threatening hemoptysis that fails to respond to other measures or for the elective but definitive management of localized disease subject to recurrent bleeding.