Comparative Respiratory Medicine; What We Can Learn From Understanding Human Respiratory Diseases
Brendan M. Corcoran, MVB, PhD, MRCVS
Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, The University of Edinburgh
Veterinary medicine can learn a lot from human medicine and over the years we have adopted ideas covering disease definition, diagnostic techniques and therapy that have greatly improved our understanding of companion animal respiratory diseases. The advantages of using human respiratory disease data in a veterinary context are obvious. Respiratory diseases, along with cardiovascular disease and cancer, are the main causes of morbidity and mortality in human patients in the developed world, and consequently vast resources are used worldwide to better understand these diseases. The vast numbers of human patients that can be studied, and recruited into controlled drug trials, is astounding and veterinary studies can never match that extent of data accumulation. Furthermore, human respiratory medicine (pulmonology) is a specialist discipline in itself, and has access to specialist centres, trained clinicians, technicians and pathologists, while companion animal respiratory medicine is still a minor sub-set of internal medicine or often included with cardiology in the discipline of cardiopulmonary medicine.
While the advantages of mining human respiratory medicine for ideas can be appreciated, the potential pit-falls of doing so also need to be considered. Anthropomorphising veterinary medicine is not advised; dogs are not small people, and similarly cats are not small dogs. The biological differences between humans, dogs and cats are numerous and this applies particularly to the respiratory system where there are major fundamental differences in anatomy and physiology. There is a tendency amongst some in the veterinary specialist community to place too much emphasis on the similarities between veterinary and human diseases, which often then prove to be unfounded. Just because a disease exists in humans does not mean it has to exist in dogs and cats. An additional problem is the tendency to try promoting veterinary disease as potential natural models of human disease. This can be of benefit to veterinary medicine as it will allow access to greater research funding sources that would not normally be available to veterinary research. However, we should not lose sight of the fact that the diseases we deal with are of veterinary importance in their own right, and their importance is not dependent on having close similarities to human diseases.
In this presentation, some examples of cross-over between human and veterinary respiratory medicine will be discussed, with the aim of illustrating where such comparison between the species can be of benefit and where it should be interpreted with caution.
The adoption of technology to aid diagnosis in veterinary respiratory medicine has been a major step forward in the last 30 years. The widespread use of thoracic radiography is testament to that and this is still the most useful diagnostic tool in respiratory medicine. The use of high resolution computed tomography (HRCT) for assessing lung disease is in the developmental stage and still limited to specialist referral practice. More detailed investigation of its utility in diagnosis still has to be determined before widespread adoption, but as in human respiratory medicine it may become a more preferred technique in due course if the problem of availability and cost can be resolved. Bronchoscopy has also crossed over from the human to veterinary world and is an invaluable tool in diagnosis. Its greater use, however, has not been matched with enough provision of training for veterinary surgeons, and the danger with any new technology is that it can be of little value in the hands of enthusiastic amateurs, and in many instances detrimental to patient welfare. The development of dedicated veterinary bronchoscopes shows there is a market for these products and this technique will be more widely used in the future by general practitioners. Pulmonary function testing (PFT) is one of the cornerstones of respiratory diagnostics in human medicine, and attempts have been made to incorporate such techniques into veterinary medicine. This has achieved limited success, simply because most of these techniques require patient co-operation in performing breathing maneuvers, something that is obviously not possible in veterinary patients. PFTs allow a much greater understanding of human respiratory disease and greatly assist diagnosis, but in veterinary medicine only barometric whole body plethysmography in cats appears to show any real promise.
The use of lung pathology in diagnosis is very advanced in human respiratory medicine, but rarely used effectively in veterinary medicine. This is in part due to concerns regarding the cost, morbidity, utility in diagnosis and the availability of experienced veterinary lung pathologists. In human respiratory medicine it is the combination of HRCT guidance, video-thoracoscopic biopsy techniques, and trained lung pathologists that has greatly improved the usefulness of lung biopsy in diagnosis, disease staging and determining prognosis. Pathology is also used in human medicine for the confirmation of disease type, but it is remarkable that only recently, consensus on lung pathology and disease definition has been reached for many important diseases. This is partly due to the marked heterogeneity that can exist for pathological changes in the same disease. In contrast, veterinary lung pathology, and knowledge as to how pathological findings correlate with specific clinical disease entities, is about 20 years behind human medicine. The aim for the future has to be to improve the quality and quantity of lung pathology data from the dog and cat; an idea that can be directly borrowed from the experience of human respiratory medicine.
Asthma is one of the most common human respiratory diseases and is a major cause of morbidity, particularly in the young. The existence of asthma in the cat has been suggested for many years and at times the desire to use human derived data to improve understanding of feline asthma has been misplaced. The capacity for veterinary medicine to study asthmatic cats is not comparable to human medicine, where studies can involve recruitment of 1000s of patients, and the lack of easily used and reproducible PFTs makes proving feline asthma is the same as human asthma very difficult. For example, the radiographic changes seen with feline asthma, if applied to human respiratory disease, would be more reminiscent of pulmonary aspergillosis. The one situation where feline asthma has been slightly ahead in its thinking is in the widespread use of glucocorticosteroids rather than bronchodilators for treatment. This (due more to serendipity than based on evidence) illustrates the importance of airway inflammation in asthmatic disease, a factor that is now readily understood in human asthma. The subsequent use of spacer inhalers in the treatment of cats has been a direct copying of the technique used in paediatric pulmonology and appears to have been reasonably effective. In contrast, an error was made in adopting the use of anti-leukotriene inhibitors in the treatment of asthmatic cats, which was based purely on their efficacy in human patients.
Idiopathic Pulmonary Fibrosis (IPF)
IPF is emerging as a chronic disease of major importance in human respiratory medicine. Up to 40,000 new cases are identified in the USA annually and about 6,000 in the UK. For several years an IPF-like condition has been suggested to exist in the dog, and in many ways the clinical features of the disease are so reminiscent of the human disease that such an assertion is not unreasonable. However, there is still no pathological proof that canine and human IPF are the same disease, and only recently in 2004 has the pathological characterisation of human IPF as 'usual interstitial pneumonitis' being agreed by international authorities. Interestingly, this pathological description has been reported in the cat and horse, but in both those species the clinical features of the disease have not been reported in detail. For the dog, the prevalence of the disease in specific breeds, namely the West Highland white terrier, makes it a tempting model for human IPF as it may allow identification of genetic markers. To make use of the canine disease as a model necessitates pathological proof they are one and the same disease. Nevertheless, ideas regarding the treatment and management of canine IPF can be adopted from experience with the human disease. IPF is a slowly progressive disease that results in respiratory failure and medical treatment is typically ineffective. The one treatment that seems to help is the use of sildenafil (Viagra) to control secondary pulmonary hypertension, and this in itself can improve quality of life and has been shown to do so in both humans and dogs.
Chronic bronchitis in humans and dogs has many similarities. The condition in both species can be classified as a mucus hyper-secretory disorder, which results in chronic coughing. Additional changes seen in both species include hypertrophy of mucous glands, neutrophilic inflammation of the airway epithelium, airway wall thickening and fibrosis, epithelial cell hyperplasia and smooth muscle hypertrophy. The concurrent loss of ciliated epithelium impedes removes of secretions from the airways and results in mucus plugging of smaller airways. There the similarities between the species tend to stop. Human chronic bronchitis is a very common condition, typically associated with environmental work-place pollutants, cigarette smoking, poor housing and social deprivation and can include familial and genetic factors, and in some patients alpha1-antitrypsin deficiency; these factors can be clearly recognised to predispose to chronic bronchitis. In dogs the disease is relatively uncommon and none of these factors appear to be important, except that the disease appears to be more prevalent in small terrier breeds of dogs, which might suggest a genetic predisposition. Terrier breeds also have a tendency to other respiratory diseases, particularly tracheal collapse, and these diseases might affect the predisposition. The disease in both dogs and humans have a similar prognosis in that they are irreversible and eventually result in respiratory failure, but differ in that human chronic bronchitis patients often have concurrent emphysema and develop chronic obstructive pulmonary disease and dogs often develop bronchiectasis and bacterial bronchopneumonia.
Chronic bronchitis is a good example of a disease with shared similarity between species, but also clearly illustrates the fundamental differences between the species in terms of respiratory anatomy and physiology and the response to pathological processes.
There is much we can learn about veterinary respiratory disease from what is understood in human respiratory medicine and there are many ideas, techniques and treatments we can borrow. However, it is equally important to be aware of the differences between the species as this in itself can be just as useful to the understanding of disease development, progression and outcome. Attaching importance to differences rather than similarities also protects us from making the fundamental mistake of presuming the same diseases are the same in every species.