The Importance of Subclinical Inflammation in Canine & Feline Lower Airway Disease
ACVIM 2008
Carol Norris Reinero, DVM, DACVIM, PhD
Columbia, MO, USA

Introduction

Inflammatory bronchial diseases are among the most common chronic respiratory diseases of dogs and cats. Management focuses on anti-inflammatory therapy to decrease inflammation thus preventing permanent airway damage and a subsequent decline in pulmonary function. Traditionally, the intensity and duration of anti-inflammatory therapy has been based on a belief that resolution of clinical signs and radiographic abnormalities correspond with resolution of inflammation. However, in humans resolution of clinical signs and improvement of abnormalities on thoracic radiography are poor predictors of airway inflammation. Since suppression of inflammation is crucial to prevent irreversible damage and functional decline, it is important to investigate if subclinical inflammation can occur in dogs and cats with naturally developing lower airway disease.

Canine and Feline Lower Airway Disease: Overview

Inflammatory bronchial diseases (chronic bronchitis and feline asthma) are commonly diagnosed in dogs and cats, and are characterized by some or all of the following: cellular infiltration of bronchial mucosa, squamous metaplasia of the tracheobronchial epithelium, goblet cell hyperplasia, glandular hypertrophy, smooth muscle hypertrophy, mucosal edema and loss of ciliated epithelial cells.1-3 Clinical signs can range from mild to severe cough, exercise intolerance, wheeze, respiratory distress, cyanosis, and in rare instances, death. Definitive diagnosis is reached based on appropriate clinical signs, characteristic thoracic radiographic changes, and airway cytology demonstrating increased neutrophils, eosinophils, or both. Management in large part has focused on suppressing airway inflammation to minimize chronic airway changes and a subsequent decline in pulmonary function. Glucocorticoids administered by injection, orally or via inhalation are potent anti-inflammatory drugs that can lead to often dramatic improvement or resolution of clinical signs. However, administration of glucocorticoids (especially long term or in high doses) can lead to adverse local and systemic effects. The goal is to taper glucocorticoid therapy to the lowest effective dose that will control airway inflammation.

The dose and duration of anti-inflammatory therapy has classically been based on monitoring clinical signs. The thought has been that complete or nearly complete resolution of clinical signs corresponds with resolution of inflammation and thus a decreased need for anti-inflammatory medication. Resolution of thoracic radiographic abnormalities have also been advocated to provide additional evidence of treatment success. Since they are minimally invasive, inexpensive and readily available, the use of clinical signs and radiographic findings are ideal monitoring tools for inflammatory bronchial diseases. However, there are no clinical studies assessing if airway inflammation is adequately suppressed in dogs or cats with inflammatory bronchial disease in clinical and/or radiographic remission.

Effects of Subclinical Inflammation

The negative impact of persistent bronchial inflammation on long-term pulmonary function can not be overstated. Airway inflammation leads to structural changes that are collectively referred to as "airway remodeling". Thickening of the basement membrane, bronchial smooth muscle hypertrophy, goblet cell hyperplasia, submucosal gland hypertrophy, airway wall thickening, loss of alveolar-bronchiolar attachments, angiogenesis, and fibrosis are hallmarks of airway remodeling secondary to ongoing airway inflammation.4-6 Ultimately, airway narrowing, mucous plug formation, airway hyperreactivity, decreased immune defenses, altered gas exchange, and an overall loss of lung function results in the development or exacerbation of clinical signs such as cough, wheeze, exercise intolerance, respiratory distress or cyanosis. Since these structural changes are permanent, prevention is imperative. Structural and functional deterioration of the lung can be averted by alleviating inflammation, even in asymptomatic patients.

A lack of clinical signs or resolution of clinical signs ("clinical remission") is a poor predictor of airway inflammation in humans with airway disease.7,8 Treatment decisions based on clinical signs alone may fail to adequately prevent both acute and long-term complications associated with inflammatory bronchial diseases. Because clinical signs fail to indicate the presence of inflammation and because the treatment of subclinical inflammation decreases long-term complications in humans, one should question the utility of basing treatment decisions on clinical signs alone in small animals.

While thoracic radiography has been proposed as a tool to monitor the success of therapy in dogs and cats with inflammatory bronchial diseases, up to 50% of dogs with chronic bronchitis and up to 23% of cats with feline lower airway disease have normal thoracic radiographs.1,3,9,10 In humans, thoracic radiography is not recommended in the routine assessment of patients with inflammatory bronchial diseases as it does not provide useful information for treatment planning and results in altered patient management in only a small percentage of cases.11 Although thoracic radiographs may be indicated in patients at initial presentation or after development of new or differing clinical signs to rule out confounding cardiac or respiratory disease, their value as a routine monitoring tool for inflammatory bronchial disease warrants investigation. Explicitly, it is important to determine if there is a correlation between improvement of thoracic radiographic lesions and inflammatory airway cytology in dogs and cats being treated for inflammatory bronchial disease.

Clinical Case Examples

Examples of dogs and cats diagnosed with inflammatory bronchial disease and being treated with glucocorticoids will be presented. In particular, a focus on how clinical and radiographic improvement correlates with airway inflammation (as documented by bronchoalveolar lavage fluid collection) will be shown.

Conclusions

Despite apparent resolution of clinical signs and improvement of radiographic changes, dogs and cats with inflammatory airway disease being treated with glucocorticoids may still have with subclinical inflammation. Given that even subclinical inflammation can lead to airway remodeling, more invasive diagnostic testing (i.e., bronchoalveolar lavage fluid collection) may prove critical in monitoring these patients until less invasive diagnostic can be developed.

References

1.  Padrid P, et al. J Vet Intern Med 1990;4:172.

2.  Moise N, et al. J Am Vet Med Assoc 1989;194:1467.

3.  Corcoran B, et al. J Small Anim Pract 1995;36:481.

4.  Hoshino M. Clin Rev Allergy Immunol 2004;27:59.

5.  Bergeron C, et al. Chest 2006;129:1068.

6.  McKiernan B. Vet Clin North Amer Small Anim Pract2000;30:1267.

7.  Laprise C, et al. Eur Respir J 1999;14:63.

8.  Van Den Toorn LM, et al. Am J Respir Crit Care Med 2001;164:2107.

9.  Mantis P, et al. J Small Anim Pract 1998;39:518.

10. Adamam-Moraitou K, et al. J Feline Med Surg 2004;6:227.

11. Blair D, et al J Thorac Imaging 1986;1:23.

Speaker Information
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Carol Reinero, DVM, DACVIM, PhD
University of Missouri
Columbia, MO


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