Chronic cough in the dog (Proceedings)

Chronic bronchial disease (CBD) is a general term used to describe a complex, progressive respiratory syndrome characterized by excessive mucous secretion within airways and thickening (hyperplasia of smooth muscle and epithelium) in the bronchial tree and frequent coughing. Cough is often described in the veterinary literature as one that persists at least "2 consecutive months" (cough duration is derived from the human literature and often extrapolated to veterinary medicine...not certain this is completely appropriate). The definition of chronic bronchitis implies that the coughing episodes occur exclusive of other bronchopulmonary disease, e.g., respiratory mycoses, neoplasia, and bacterial infection. In veterinary medicine, however, it is impossible to disregard the impact that secondary infections have on the progression and severity of clinical signs associated with chronic bronchial disease, particularly those associated with acquired bronchial and tracheal collapse. Interestingly, the literature on chronic bronchial disease in humans attributes the underlying cause to 3 factors: age, inhaled particulate material (especially smoke from tobacco), and bacteria. Clients willing to treat a pet with chronic bronchial disease must accept the premise that treatment is aimed at control, not cure.

Physical Findings

Chronic coughing is the hallmark clinical sign in dogs with bronchial disease. However, CBD can induce severe, acuteonset paroxysmal coughing episodes for which the patient is subsequently presented in respiratory distress. Collapse/syncope are occasionally reported by clients in acute episodes. In our experience (NCSU), acute respiratory distress associated with CBD is likely to be accompanied by acquired airway (not necessarily tracheal) collapse. Neither age nor gender seems to be predisposing factors to the development of CBD in dogs. While the disease is most common in dogs over 5 years of age, younger dogs can be (albeit rarely) affected. Among dogs, clinical signs associated with CBD appear to be most prevalent in small and toy breeds, particularly toy poodles, Pekingese, Yorkshire terriers, Chihuahuas, and Pomeranians. At least one author has suggested a hereditary predisposition to CBD in dogs. It is perhaps more appropriate to consider these breeds (uniquely?) at risk of developing severe clinical signs of bronchial disease, since CBD clearly occurs in mixed breed and large breed dogs as well as smaller breeds. Compromised airway integrity of toy dog breeds (chondrodysplasia), possibly an inherited problem, may further complicate the clinical course of CBD in the older dog. Obesity and advanced dental/periodontal disease are common, independent findings among small and toy dog breeds with CBD and are regarded as additional complicating (contributing??) factors in the clinical patient.

Detection of abnormal respiratory sounds during thoracic auscultation is not a consistently reliable indicator of CBD. Wheezing on expiration, if present, is considered a hallmark of sign of chronic bronchial disease. The ability to elicit coughing by simple manipulation of the cervical trachea is an inconsistent finding in dogs with CBD and an uncommon finding in affected cats. Crackles, when present, can be attributed to the presence of fluid, usually viscous respiratory secretions, in constricted airways.

Dogs with chronic small airway disease are predisposed to bronchial and intrathoracic tracheal collapse. Therefore, during coughing episodes, it is oftentimes possible to auscult airway collapse. Toward the end of expiration, particularly during cough, airway collapse is evident during thoracic auscultation as a loud, discrete thump, referred to as an endexpiratory click or "snap." The sound is generated as the main bronchi and intrathoracic trachea collapse abruptly. Tracheal collapse can culminate in respiratory distress and syncope in dogs during paroxysmal coughing episodes. It is possible for affected dogs to die subsequent to airway obstruction and respiratory arrest during an acute episode.

Laboratory Findings

Conventional hematology and biochemistry profiles are not likely to contribute to the diagnosis of CBD but are still indicated to rule out other underlying disease.

Trans-tracheal wash/aspiration (see below) is less likely than broncho-alveolar lavage (BAL) in revealing diagnostic information. Cytological evaluation of fluid recovered during BAL is expected to consist of predominantly of degenerate neutrophils with minimal or no bacteria. However, acute bacterial infection is a possible cause of acute exacerbation.

Diagnostic Confirmation

Thoracic Radiography: In the early, non-obstructive stages of CBD, a generalized interstitial lung pattern is usually present, although bronchial changes predominate. Thickening of bronchial walls, indicated by the "doughnut" appearance of endon bronchi, and "tram lines," the longitudinal shadows associated with thickened bronchi, can be seen. Bronchial calcification alone, commonly seen as a normal agerelated change in old dogs, should not be interpreted as bronchitis.

As CBD progresses, there is a tendency for the small airways, bronchi and, eventually, the intrathoracic trachea to collapse during exhalation, particularly during the expiratory phase of cough. The prevalence and severity of tracheal collapse appears to be most severe in adult, miniature, and toy dog breeds. Although chondrodysplasia and trachealis muscle dysfunction have been implicated in the pathogenesis of tracheal collapse, the functional diameter of the small airways in dogs with chronic bronchitis is also an important cause of bronchial and tracheal collapse, particularly in older dogs. Acquired airway collapse is a significant and complicating factor in dogs (especially small breeds) with CBD. Acquired changes in intra-thoracic airway aerodynamics lead to lower intra-thoracic airway pressure during exhalation (cough) and can lead to rapid, intermittent, but total, collapse of the airway, especially at the level of the carina (tracheal bifurcation). These can be heard during auscultation as the expiratory phase of cough (end-expiratory 'snap') is abruptly interrupted. (video of acquired airway collapse will be shown during the presentation)

Bronchoalveolar Lavage and Culture: Cytology of specimens collected during BAL may contain only mucous and normal respiratory epithelium in spite of the severity of the patient's clinical signs. Neutrophils, eosinophils, macrophages, lymphocytes, goblet cells, and even bacteria may be seen. However, in our hands, the diagnostic value of cytologic examination of tracheobronchial washings collected during tracheal aspiration or bronchoalveolar lavage is limited.

Bronchoscopic Exam: In the dog, direct visualization of the trachea and right and left main bronchi using a flexible endoscope is a valuable, although underutilized, diagnostic procedure. Compared to the lower airways of normal dogs, the primary and secondary bronchi appear to have an irregular contour, are mottled white and pink in color, and usually contain accumulations of thick mucous that cling to the bronchial walls and trachea. Oftentimes thin strands of tenacious mucous can be seen traversing the bronchial lumen.

Treatment of Chronic Bronchial Disease

      The Acute Exacerbation

It is possible for dogs with CBD to present with respiratory distress, cyanosis, and syncope following a severe, acuteonset coughing episode. Affected dogs characteristically have complete bronchial and intra-thoracic tracheal collapse. Oxygen administered by face mask should be administered immediately, and an intravenous catheter is placed in any available vein. Sedation with morphine (dogs only-0.5 mg/kg, SQ or IM) or diazepam (dogs @ 5 to 20 mg IV or cats @ 5 mg maximum, IV) is indicated in the conscious, anxious patient. The patient is given a single dose of methylprednisolone (12 mg/kg, IV). It may be safer to actually anesthetize particularly anxious patients with an ultrashortacting barbiturate, intubate, then administer oxygen through an endotracheal tube. When the patient has been stabilized, thoracic radiographs should be obtained as soon as possible to determine the integrity of the lungs and airways. Even in extreme cases, it has not been necessary to suction mucous from the airways. Restriction to airflow in comatose patients is attributable to airway thickening and collapse rather than mucous accumulation.

      Long-Term Management

Corticosteroids. Dogs with CBD derive significant benefit from the shortterm administration of antiinflammatory doses of corticosteroids. Orally administered corticosteroids not only have a rapid, anti-inflammatory effect, they are a potent antitussive. Rapid resolution of cough is expected following onset of corticosteroids. This is true in patients with acute and chronic disease. Even when evidence of tracheobronchial collapse and/or pneumonia exists, shortterm corticosteroids (up to 5-7 days) have an important role in managing the affected patient. Oral prednisolone is given at doses ranging from 0.2 to 0.5 mg/kg, twice daily in both dogs and cats. Once stable, most dogs can be effectively managed with a single dose given on alternate days.

The goal of corticosteroid therapy is not long-term management. The clinician should strive to administer the least effective dose possible for the shortest period of time needed to control the clinical signs. Exacerbation of cough is expected in the future. Therefore, it is preferred that steroids be administered selectively in these patients. I prefer to use steroid therapy in these patients as short-term rescue treatment.

(administration of corticosteroids via the respiratory tract can be accomplished with a Metered-Dose Inhaler [MDI]. MDI's have been modified for use in dogs as well as cats. Treatment with an MDI can be difficult. I see little benefit over oral administration).

Antimicrobials. The role of long-term antimicrobial therapy may be underappreciated in managing patients with CBD. Although bacterial infection (pneumonia) is seldom recognized as a co-factor in dogs with CBD, many pulmonologists do consider "low-grade" bacterial colonization within the small airways to be a key factor in CBD. Although relatively uncommon, opportunistic infections (pneumonia) involving normal respiratory flora can become lifethreatening in dogs with significantly compromised respiratory defense mechanisms, particularly tracheobronchial collapse and diminished mucociliary transport. The role of B. bronchiseptica as a complicating factor in the pathogenesis of CBD must not be underestimated. When in vitro culture and sensitivity results are not immediately available, the clinician is justified in prescribing antimicrobial. In the author's experience, antimicrobial therapy plays a critical role in the long-term management of CBD in dogs.

Several antimicrobial agents are available for use. Those most commonly prescribed are listed below:

     • DOXYCYCLINE (3 to 5 mg/kg, orally, q12 h);

     • AZITHROMYCIN (5 mg/kg, orally, once daily...recommended for compliance);

     • ENROFLOXACIN (2.5 to 5.0 mg/kg, orally, once daily) caution when using with methyxanthine (aminophylline or theophylline) bronchodilators. ...see below.

Administration: For example, azithromycin would be prescribed for 14 to 21 days (5.0 mg/kg, once daily) for a patient with CBD. Following treatment, it is not uncommon for the patient's clinical signs to resolve for several weeks, or even months, followed by a gradual redevelopment of cough. In this case, the treatment regimen with azithromycin can be repeated with similar results expected. If an individual patient does become less responsive to therapy, another antimicrobial can be selected and administered in the same way.

Bronchodilators. The methylxanthine bronchodilators, theophylline and aminophylline (theophylline ethylenediamine), are often described as the preferred treatment for longterm management in dogs (extended-release theophylline, initially 5.0 mg/kg, orally, q12h; with gradual increase up to 10 mg/kg). NOTE: USE OF THEOPHYLLINE WITH ENROFLOXIN CAN CULMINATE IN TOXIC ACCUMULATION OF THEOPHYLLINE...it is therefore recommended to reduce the theophylline dose by 30% if used concurrently with a fluoroquinolone). Alternatively, beta-adrenergic bronchodilators (terbutaline and albuterol) can be used (small dogs: 0.625 to 1.25 mg [total dose] orally, q12h) (larger dogs: up to 2.5 to 5.0 mg/kg, orally, q12h). In my experience, the long-term benefit derived from bronchodilator therapy varies considerably among individual patients.

Antitussives. Cough suppressant therapy has limited value as a firstline drug in the management of CBD. Overthecounter products (e.g., dextromethorphan) are simply not effective. Narcotic cough suppressants such as hydrocodone are frequently prescribed for used in dogs. Clearly these agents should not be used alone in the management of CBD.

Aerosol Therapy. The greatest benefits to aerosol therapy are derived in patients with acute onset signs, an excessive accumulation of bronchial and tracheal secretions, and those with secondary bronchial infections. Treatment, if needed, entails aerosolization of 5 to 7 mL of sterile saline (with or without antibiotics added to the solution) at least 3 to 4 times daily. Each treatment requires 15 to 20 minutes.

      Prognosis

In the stabilized, non-acute dog with documented CBD, even when airway collapse is determined to involve both bronchi and the entire intrathoracic trachea, the client should understand that, although the prognosis is fair to good, the goals of treatment are control and longterm management, not cure. Left untreated, CBD could progress to bronchiectasis and, although uncommon in dogs, emphysema (chronic obstructive pulmonary disease or COPD). The objective of therapy, therefore is to delay progression of the underlying respiratory disease. Treatment is life-long. However, the results can be rewarding and excellent quality of life can be achieved for years.

Vaccination. Administration of intranasal vaccine containing Bordetella bronchiseptica antigen has no role in the treatment of chronic cough in the dog. Vaccine is appropriate only when used to mitigate the consequence of exposure to B. bronchiseptica and/or parainfluenza virus and should only be administered to healthy dogs. There are no studies to support therapeutic administration of either the intranasal or the parenteral vaccine.

However, vaccination of dogs with CBD against B. bronchiseptica is indicated for any patient at risk of exposure to populations of dogs. However, it is my recommendation that, in the event B. bronchiseptica vaccination is indicated, intranasal vaccination should be avoided in patients with CBD. Reason: Intranasal vaccines are attenuated live bacterial vaccine, usually in combination with a modified live parainfluenza virus vaccine. Post-vaccination replication of the vaccine antigens on the respiratory mucosa could exacerbate an acute respiratory event.

Additional Reading

Ford RB. Canine infectious tracheobronchitis. In Greene, CE, ed. Infectious Diseases of the Dog and Cat. 3rd ed. 2006. Saunders-Elsevier, St. Louis. pp. 54-61.

Johnson LR. Chronic bronchitis in dogs. Chapt 146, in JD Bonagura & DC Twedt (eds): Kirk's Current Veterinary Therapy XIV. Saunders-Elsevier. pp. 642-645, 2009.

Kuehn NF: Chronic Bronchitis in Dogs. In King, LG (ed): Textbook of Respiratory Disease in Dogs and Cats. Elsevier, St. Louis. pp. 379-387, 2004.