Managing the coughing dog (Proceedings)

Coughing is a common presentation in small animal practice, which can be caused by either heart or respiratory tract disease. In order to optimally manage the coughing patient, clinicians need to decide whether cardiac or airway disease is the cause.

Pathophysiology

Coughing is a non-specific response to inflammation or stretch of the airways following a variety of insults, including viral, bacterial or other infections, allergic or hypersensitivity responses, foreign material, external compression, accumulation of edema fluid, structural abnormalities, or neoplasia. When the airways become inflamed, the clinical manifestations include erythema and hyperemia, mucosal edema, increased mucus production with proliferation of goblet and Clara cells, and infiltration of inflammatory cells. Normally, the mucociliary escalator, the alveolar macrophages, and the bronchus associated lymphoid tissue are the most important protective mechanisms of the lower airways. The cough reflex comes into play when these responses have been overwhelmed by an increased volume of edema, exudate or mucus, or by the presence of foreign material. The cough reflex may also be triggered by repeated local trauma or stretch, such as might occur in dogs with structural abnormalities such as collapsing trachea or compression of the left mainstem bronchus as a result of left atrial enlargement.

The cough reflex is triggered locally in the airways, and controlled by cough centers in the brainstem. A cough begins as a maximal inspiration, followed by initial forced exhalation against a closed glottis. Sudden opening of the glottis results in rapid expulsion of air under considerable pressure, which assists in removal of debris, foreign material, and mucus from the respiratory tract. This is further assisted by simultaneous contraction of the bronchial smooth muscle, which narrows the airways, further increasing the force with which material is expelled. Coughing may be defined as productive or non-productive. A productive cough occurs when material is expectorated from the trachea into the pharynx. In dogs and cats this material is usually swallowed, but it can occasionally be expectorated to the exterior. Clinically, a productive cough sounds moist and low-pitched, and the animal often swallows immediately afterwards. In contrast, non-productive coughing is usually harsh, high-pitched or even honking. Expectoration of mucus may occur occasionally, but is usually not a feature.

Dogs with heart disease may cough because of the presence of pulmonary edema fluid within the pulmonary airspaces if they are in congestive heart failure. Alternatively, they may not be in congestive heart failure, but may cough because an enlarged left atrium is pressing upwards against the left mainstem bronchus, directly compressing and irritating the airway.

Common causes of coughing in dogs

• Left-sided congestive heart failure, often mitral regurgitation

• Collapsing trachea

• Chronic bronchitis

• Compression of the left mainstem bronchus

• Bronchiectasis

• Chronic bronchopneumonia

• Tracheal or bronchial foreign bodies

• Tracheal or bronchial masses or neoplasms

• Pulmonary neoplasia such as bronchogenic carcinoma

• Parasitic infestations

• Heartworms (Dirofilaria immitis)

• Upper airway obstruction such as laryngeal paralysis or brachycephalic airway syndrome

• Fungal infections such as blastomycosis or aspergillosis

• Pulmonary inflammatory disorders eg pulmonary infiltrate with eosinophils

Distinguishing cardiac from pulmonary disease in coughing animals

History and physical exam

In dogs, coughing may be caused by either cardiac or airway disease. The signalment can provide useful information: coughing in older dogs can be caused by congestive heart failure or by inflammation in chronic bronchitis or collapsing trachea. Younger patients may be more likely to suffer from infectious or parasitic infestations, especially if they are in a high-stress environment. Breed predispositions exist for certain disorders such as collapsing trachea in Yorkshire Terriers and Miniature Poodles. A previous history of vomiting or regurgitation can indicate the presence of chronic aspiration pneumonia or systemic neoplasia. Chronic bronchitis may be a sequela of infectious tracheobronchitis or necrotizing tracheitis due to smoke inhalation. Recent travel to areas endemic for lungworms, heartworms or fungal infections may be of diagnostic significance.

Observation of the patient at rest can provide vital information. Most patients with mild to moderate chronic bronchitis, collapsing trachea, or airway compression/obstruction are normal at rest between paroxysms of coughing. In contrast, patients with severe airway disease or congestive heart failure often have increased respiratory rate and effort at rest. They may have a considerable abdominal component to their respiration, with nasal flare and postural adaptation. The most severely affected patients have paradoxical respiration and signs of respiratory muscle fatigue. The whole airway, particularly the cervical trachea, should be carefully palpated. Attention should be paid to the presence of any kind of compressive mass lesion in the neck or thoracic inlet. The trachea itself should be palpated and compressed to induce coughing. In normal dogs and cats, the trachea is cylindrical and the dorsal membrane can only be palpated with difficulty. Dogs with collapsing trachea may have obvious softening of the tracheal cartilage and airway deformity (rings become C-shaped). A brief, dry cough can be induced in most normal dogs and cats when the trachea is compressed. In contrast, paroxysms of coughing and wheezing may be precipitated in patients with pre-existing inflammation caused by tracheal collapse, chronic bronchitis or feline asthma. Induction of a moist or productive cough should prompt suspicions of bronchiectasis, bronchopneumonia, or other serious lung disease. The jugular veins should be evaluated for excessive distention or jugular pulses, which can indicate right-sided heart disease.

Auscultation is a vital part of the evaluation of any patient with a cough. The first important question, particularly in dogs, is whether or not there is evidence of heart disease. The heart must be carefully ausculted to detect any evidence of a murmur or arrhythmia. Coughing can be an early sign of left-sided congestive heart failure in dogs with mitral regurgitation or dilated cardiomyopathy. It is important to recognize that the mere presence of a murmur is not enough to prompt a diagnosis of congestive heart failure. Many patients that are actually suffering from chronic bronchitis or collapsing trachea also have some degree of mild mitral endocardiosis, but are not actually in heart failure. Therapy for heart disease in such patients will not result in resolution of the cough, which instead should be treated with anti-tussives and bronchodilators. Some patients with mitral regurgitation may have significant enlargement of the left atrium due to regurgitant flow. In this instance, compression of the left mainstem bronchus may result in coughing that is unrelated to heart failure. Next, all lung fields and the cervical trachea should be carefully ausculted for the presence of abnormal sounds. The most common finding is increased upper airway sounds, particularly in patients with chronic bronchitis, collapsing trachea, or airway obstruction. In patients with tracheal obstruction, the sounds are loudest when the bell of the stethoscope is placed over the cervical trachea. Wheezes (musical sounds produced by movement of air through narrowed airways) are often ausculted in cats with feline asthma. Dull areas may indicate the presence of collapsed or consolidated lung lobes, masses, or pleural effusion. Soft crackles are a serious finding, suggesting the presence of fluid such as cardiogenic edema or pneumonia. Dogs with chronic end-stage bronchial or lung disease may also have generalized coarse crackles which are probably caused by early closure and opening of small bronchi.

A complete physical examination, paying particular attention to abdominal palpation, should be performed. Abdominal distention attributable to hepatomegaly can contribute to coughing due to craniad pressure on the diaphragm by abdominal contents. A fluid wave may indicate ascites and right-sided heart failure.

Diagnostic testing

Every patient that has been coughing for more than 2 months deserves at least a basic workup to determine the best course of management, and to attempt to prevent progression of the disease. Many of these disorders, whether they are cardiac or respiratory in origin, are slowly progressive and most do not resolve spontaneously. Early treatment is often the most important tool to delay progression and minimize morbidity. In particular, management of disorders such as collapsing trachea, chronic bronchitis, and congestive heart failure can be extremely frustrating for both owner and veterinarian. Before committing to life-long therapy for these chronic illnesses it is vital that a correct diagnosis is made, and that reversible or curable disorders are ruled out.

A basic clinical workup should include a complete blood count, chemistry panel, urinalysis, and heartworm testing. The intent is to determine the presence of organic or systemic disease that may be contributing to chronic cough. For example, patients with fungal pneumonia may have eosinophilia or increased white blood cell count, and those with neoplasia or hyperadrenocorticism may have increased liver enzymes. If therapy with drugs such as corticosteroids, angiotensin-converting enzyme inhibitors, or digoxin is to be considered, then knowledge of liver and kidney function, and electrolyte status, is vital.

Thoracic and possibly also cervical radiographs are vital in evaluation of patients with chronic coughing. If the patient has a heart murmur, the radiographs should be carefully screened to rule out any evidence of pulmonary venous distention or alveolar disease caused by pulmonary edema. If there is evidence of pulmonary edema or pulmonary venous distention, then congestive heart failure is likely to be contributing to the coughing in a dog. The cardiac silhouette should be checked for enlargement, which could be global or only of one chamber, usually the left atrium. If the left atrium is enlarged and pressing dorsally against the left mainstem bronchus, this can be a cause of coughing that relates to the heart disease, but is not congestive heart failure.

Dogs with chronic bronchitis or collapsing trachea usually have normal radiographs or a peribronchial pattern. Sometimes a collapsing trachea can be demonstrated by radiographs obtained during inspiration and during exhalation, or by using flexed and extended neck views. Caution should be exerted in interpretation of these views, however. Patients with chronic tracheal collapse or bronchitis usually do not have evidence of pulmonary alveolar disease. If there are any signs of alveolar disease, other disorders such as bronchopneumonia, neoplasia, or congestive heart failure should be considered. Bronchiectasis can be evident as a cylindrical dilation of bronchi as they extend to the periphery of the lung lobes, rather than their usual tapering. Masses may be evident in lung lobes or compressing the airways. Radio-opaque foreign bodies may be seen. Lastly, intraluminal masses, abscesses, parasitic nodules or foreign bodies may be outlined by the negative contrast of air in the major airways.

Fluoroscopy is a very useful additional modality to confirm a diagnosis of collapsing trachea or mainstem bronchus. Bronchoscopy is a very useful tool for evaluation of the chronically coughing dog. Dynamic collapse of the airways can be easily seen, and bronchoscopy is the "gold standard" for diagnosis of collapsing trachea. Foreign bodies may be visualized and even removed. The airways can be evaluated for the presence of inflammation and exudate, and samples can be obtained directly from affected areas. Bronchoalveolar lavage is a useful technique which can provide diagnostic information in the presence of fungal or neoplastic lung disease. Bronchoscopy can only be carried out under general anesthesia, which limits its use to the stable patient. Left-sided congestive heart failure may require evaluation with echocardiography and electrocardiography. Some dogs or cats with chronic coughing may have mass lesions in the lung, which may require surgical exploration and resection. Some of these patients may also benefit from additional imaging modalities such as computed tomography or magnetic resonance of the thorax.

Management

Diuretics and vasodilators

Dogs that are coughing because of congestive heart failure often respond favorably to therapy with diuretics and vasodilators that effectively reduce cardiac preload. Reduction of cardiac preload decreases the hydrostatic pressure in the pulmonary capillary bed, thereby reducing the rate of formation of pulmonary edema fluid. The fluid that has already formed can then drain away through the pulmonary lymphatics. Side effects of excessive dehydration, electrolyte abnormalities, and pre-renal azotemia must be carefully monitored.

Anti-tussives

Anti-tussive agents are especially important when the cough is non-productive, especially when it is caused by airway compression by the left mainstem bronchus, chronic bronchitis, or collapsing trachea. They are often of considerable benefit when long-term coughing is interfering with the patient's ability to exercise and even to sleep. In such cases, the continued airway irritation caused by coughing can lead to more coughing, and thus can perpetuate a vicious cycle, which can be temporarily broken by anti-tussive agents. The primary drugs effective as anti-tussives are centrally acting opiate derivatives, which act on the cough center of the brain to depress its response to cough stimuli. Hydrocodone bitartrate (1.25-5 mg PO up to QID) is effective and widely used. Other drugs, such as butorphanol tartrate (0.05-0.1 mg/kg PO, BID-QID) are also effective, with less central nervous system depression.

Bronchodilators

Two classes of bronchodilators are widely used: methylxanthine derivatives and beta 2 agonists. Methylxanthine derivatives such as aminophylline (4-5.5 mg/kg PO TID) are well absorbed from the gastrointestinal tract. They are phosphodiesterase inhibitors that cause bronchodilation by decreasing the intracellular breakdown of cAMP. They also act at the level of the diaphragm to increase its contractility and to render it less susceptible to fatigue. Thus, these agents may also prove useful in cases of chronic respiratory tract disease for reasons other than bronchodilation. The beta 2 agonists such as terbutaline sulfate (1.25-5 mg BID-TID) and albuterol (50 mg/kg PO BID-TID) activate adenylate cyclase and therefore increase intracellular camp, thus inducing bronchodilation.

Corticosteroids

Corticosteroids play an important role in therapy, but considering their negative side-effects, their use should be undertaken with caution. Anti-inflammatory doses of prednisone (0.5 mg/kg SID) can be beneficial in patients with collapsing trachea or chronic bronchitis. This dose can be effective in decreasing the inflammatory response, leading to reduction of secretions, and decreases in mucosal edema, airway thickening and bronchospasm. This results in clinical improvement in many patients, with decreased coughing and better exercise tolerance.

References available on request