ANIMAL MODEL OF
Chronic Bronchitis
HUMAN DISEASE Animal Model: Chronic Bronchitis in Dogs Contributed by: E. B. Wheeldon, BVMS, PhD, MRCVS, Department of Pathology, School of Veterinary Medicine, University of California, Davis, CA 95616; R. G. Breeze, BVMS, PhD, MRCVS, Department of Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99163; H. M. Pirie, BVMS, PhD, MRCVS, MRC Path, Department of Veterinary Pathology, University of Glasgow Veterinary School, Bearsden, Glasgow, Scotland. Biologic Features
The dog is subject to a respiratory disease characterized dinically by a persistent cough and pathologically by chronic inflammation of the pulmonary airways, including mucus hypersecretion.1 Affected dogs are usually of the small or toy breeds, though occasional cases involving large breeds are seen. Typically, the disease affects obese, middle-aged, or older animals though with no apparent breed or sex incidence. There is a history of persistent intractable cough, usually of insidious onset. In a proportion of cases this cough is productive, though this is difficult to assess since the coughed up mucus is often swallowed. Pathologic examination of the lungs of affected animals reveals variable amounts of excess mucus in the large airways. This mucus is viscid in character and is admixed with varying amounts of cell debris and edema fluid. Pneumonia is often a complicating factor in these cases, since the chronic inflammation presumably predisposes the lung to infection. The bronchi have evidence of chronic inflammation with epithelial erosions and dedifferentiation, edema, and cellular infiltration of the lamina propria, resulting in folding of the bronchial wall into the lumen. Most importantly, there is evidence of mucus hypersecretion with an increase in the number of epithelial goblet cells with extension into small airways and an increase in the number and size of the mucous glands (Figure 1). Publication sponsored by the Registry of Comparative Pathology of the Armed Forces Institute of Pathology and supported by Public Health Service Grant RR 00301 from the Division of Research Resources, US Department of Health, Education and Welfare, under the auspices of Universities Assocaited for Research and Education in Pathology, Inc. Dr. Wheeldon was a recipient of a Wellcome Trust Research Fellowship at the time this work was carried out. Address reprint requests to Dr. E. B. Wheeldon, Department of Pathology, School of Veterinary Medicine, University of California, Davis, CA 95616. 0002-9440/79/0709-0355$01.00 355 o 1979 American Association of Pathologists
,
.
Figure 1-Comparison of cross-sections of bronchi from a normal dog (A) and a dog with chronic bronchitis (B). Note that the sparse mucous glands in the normal bronchus have proliferated in the dog with chronic bronchitis; in addition, there is thickening of the bronchial wall due to edema and
cellular infiltration.
Vol. 96, No. 1 July 1979
BRONCHITIS IN DOGS
357
Recognition of this condition by clinical criteria is often difficult since the main clinical sign of cough is nonspecific. Radiographic changes, though present in a proportion of cases, is of limited value as a diagnostic tool. An attempt has been made to define canine chronic bronchitis along the clinical descriptive lines adopted in humans, viz, a chronic or recurrent cough on most days of 2 consecutive months in the preceding year, excluding specific bronchopulmonary disease such as tuberculosis or Filaroides osleri infection. As in humans, the etiology of this condition remains obscure although, by analogy, the contributions made by air pollution and infection would seem to be important. Chronic bronchitis can be produced experimentally in dogs by exposing them to high levels of sulfur dioxide for periods of several months.2 Comparison With Human Disease
Chronic bronchitis in humans is characterized by a persistent cough due to mucus hypersecretion; again, there are increased numbers of epithelial goblet cells with extension into small airways and perhaps, most importantly, hypertrophy of the bronchial mucous glands.3 These features are all seen in the naturally occurring disease in the dog. The quantitative changes in mucous glands which have been studied extensively in humans using a variety of quantitation techniques 4-6 have their counterpart in the dog.7 Similarly, the qualitative changes in the secreted mucus detected in humans by histochemical techniques,8 have also been shown to occur in the dog, both in the naturally occurring disease I and in experimentally produced disease.10 These studies reveal a shift in the types of mucosubstances secreted. The major differences in canine chronic bronchitis compared to the human disease are epidemiologic; in the limited number of cases studied so far, there appears to be no urban incidence or sex predisposition. This is in marked contrast to humans where the disease typically occurs in urban areas, presumably due in part to atmospheric pollution and with a male preponderance, possibly due to cigarette smoking habits. Usefulness of the Model
A disease such as chronic bronchitis, which is of complex nature, having a multiple etiology with attendant predisposing and exacerbating factors, together with an imperceptible onset and insidious progress through unremarkable stages over a period of years, would be more readily understood by the use of a natural animal model. Such a model would enable workers to pinpoint the precise contributions made by the various factors
358
WHEELDON ET AL
American Journal of Pathology
implicated in the etiology and pathogenesis of this disease. The dog lives in close association with humans, is exposed to the same atmospheric pollutants, and is affected by a group of respiratory diseases. The role of infectious agents, particularly in the young dog, on the production of bronchopulmonary disease in later life would provide a valuable mechanism to study the possible role of childhood respiratory illness in the pathogenesis of human chronic bronchitis, an aspect which has been studied epidemiologically in humans.11 References
1. Wheeldon EB, Pirie HM, Fisher EW, Lee R: Chronic bronchitis in the dog. Vet Rec 94:466-471, 1974 2. Chakrin LW, Saunders LZ: Experimental chronic bronchitis. Pathology in the dog. Lab Invest 30:145-154, 1974 3. Reid L: Pathology of chronic bronchitis. Lancet 1:275-278, 1954 4. Reid L: Measurement of the bronchial mucous gland layer: A diagnostic yardstick in chronic bronchitis. Thorax 15:132-141, 1960 5. Restrepo G, Heard BE: The size of bronchial glands in chronic bronchitis. J Pathol Bacteriol 85:305-310, 1963 6. Hale FC, Olsen CR, Mickey MR Jr: The measurement of bronchial wall components. Am Rev Resp Dis 98:978-987, 1968 7. Wheeldon EB, Pirie HM: Measurement of bronchial wall components in young dogs, adult normal dogs, and adult dogs with chronic bronchitis. Am Rev Resp Dis 110:609-615, 1974 8. Reid L: Histochemical and enzyme studies of bronchial mucus. Med Thorac 22:6168, 1965
9. Wheeldon EB, Pirie HM, Breeze RG: A histochemical study of the tracheobronchial mucosubstances in normal dogs and dogs with chronic bronchitis. Folia Vet Lat 6:45-58, 1976 10. Spicer SS, Chakrin LW, Wardell JR Jr: Effect of chronic sulfur dioxide inhalation on the carbohydrate histochemistry and histology of the canine respiratory tract. Am Rev Resp Dis 110:13-24, 1974 11. Colley JRT, Douglas JWB, Reid DD: Respiratory disease in young adults: Influence of early childhodd lower respiratory tract illness, social class, air pollution, and smoking. Br Med J 3:195-198, 1973
Chronic Bronchitis
HUMAN DISEASE Animal Model: Chronic Bronchitis in Dogs Contributed by: E. B. Wheeldon, BVMS, PhD, MRCVS, Department of Pathology, School of Veterinary Medicine, University of California, Davis, CA 95616; R. G. Breeze, BVMS, PhD, MRCVS, Department of Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99163; H. M. Pirie, BVMS, PhD, MRCVS, MRC Path, Department of Veterinary Pathology, University of Glasgow Veterinary School, Bearsden, Glasgow, Scotland. Biologic Features
The dog is subject to a respiratory disease characterized dinically by a persistent cough and pathologically by chronic inflammation of the pulmonary airways, including mucus hypersecretion.1 Affected dogs are usually of the small or toy breeds, though occasional cases involving large breeds are seen. Typically, the disease affects obese, middle-aged, or older animals though with no apparent breed or sex incidence. There is a history of persistent intractable cough, usually of insidious onset. In a proportion of cases this cough is productive, though this is difficult to assess since the coughed up mucus is often swallowed. Pathologic examination of the lungs of affected animals reveals variable amounts of excess mucus in the large airways. This mucus is viscid in character and is admixed with varying amounts of cell debris and edema fluid. Pneumonia is often a complicating factor in these cases, since the chronic inflammation presumably predisposes the lung to infection. The bronchi have evidence of chronic inflammation with epithelial erosions and dedifferentiation, edema, and cellular infiltration of the lamina propria, resulting in folding of the bronchial wall into the lumen. Most importantly, there is evidence of mucus hypersecretion with an increase in the number of epithelial goblet cells with extension into small airways and an increase in the number and size of the mucous glands (Figure 1). Publication sponsored by the Registry of Comparative Pathology of the Armed Forces Institute of Pathology and supported by Public Health Service Grant RR 00301 from the Division of Research Resources, US Department of Health, Education and Welfare, under the auspices of Universities Assocaited for Research and Education in Pathology, Inc. Dr. Wheeldon was a recipient of a Wellcome Trust Research Fellowship at the time this work was carried out. Address reprint requests to Dr. E. B. Wheeldon, Department of Pathology, School of Veterinary Medicine, University of California, Davis, CA 95616. 0002-9440/79/0709-0355$01.00 355 o 1979 American Association of Pathologists
,
.
Figure 1-Comparison of cross-sections of bronchi from a normal dog (A) and a dog with chronic bronchitis (B). Note that the sparse mucous glands in the normal bronchus have proliferated in the dog with chronic bronchitis; in addition, there is thickening of the bronchial wall due to edema and
cellular infiltration.
Vol. 96, No. 1 July 1979
BRONCHITIS IN DOGS
357
Recognition of this condition by clinical criteria is often difficult since the main clinical sign of cough is nonspecific. Radiographic changes, though present in a proportion of cases, is of limited value as a diagnostic tool. An attempt has been made to define canine chronic bronchitis along the clinical descriptive lines adopted in humans, viz, a chronic or recurrent cough on most days of 2 consecutive months in the preceding year, excluding specific bronchopulmonary disease such as tuberculosis or Filaroides osleri infection. As in humans, the etiology of this condition remains obscure although, by analogy, the contributions made by air pollution and infection would seem to be important. Chronic bronchitis can be produced experimentally in dogs by exposing them to high levels of sulfur dioxide for periods of several months.2 Comparison With Human Disease
Chronic bronchitis in humans is characterized by a persistent cough due to mucus hypersecretion; again, there are increased numbers of epithelial goblet cells with extension into small airways and perhaps, most importantly, hypertrophy of the bronchial mucous glands.3 These features are all seen in the naturally occurring disease in the dog. The quantitative changes in mucous glands which have been studied extensively in humans using a variety of quantitation techniques 4-6 have their counterpart in the dog.7 Similarly, the qualitative changes in the secreted mucus detected in humans by histochemical techniques,8 have also been shown to occur in the dog, both in the naturally occurring disease I and in experimentally produced disease.10 These studies reveal a shift in the types of mucosubstances secreted. The major differences in canine chronic bronchitis compared to the human disease are epidemiologic; in the limited number of cases studied so far, there appears to be no urban incidence or sex predisposition. This is in marked contrast to humans where the disease typically occurs in urban areas, presumably due in part to atmospheric pollution and with a male preponderance, possibly due to cigarette smoking habits. Usefulness of the Model
A disease such as chronic bronchitis, which is of complex nature, having a multiple etiology with attendant predisposing and exacerbating factors, together with an imperceptible onset and insidious progress through unremarkable stages over a period of years, would be more readily understood by the use of a natural animal model. Such a model would enable workers to pinpoint the precise contributions made by the various factors
358
WHEELDON ET AL
American Journal of Pathology
implicated in the etiology and pathogenesis of this disease. The dog lives in close association with humans, is exposed to the same atmospheric pollutants, and is affected by a group of respiratory diseases. The role of infectious agents, particularly in the young dog, on the production of bronchopulmonary disease in later life would provide a valuable mechanism to study the possible role of childhood respiratory illness in the pathogenesis of human chronic bronchitis, an aspect which has been studied epidemiologically in humans.11 References
1. Wheeldon EB, Pirie HM, Fisher EW, Lee R: Chronic bronchitis in the dog. Vet Rec 94:466-471, 1974 2. Chakrin LW, Saunders LZ: Experimental chronic bronchitis. Pathology in the dog. Lab Invest 30:145-154, 1974 3. Reid L: Pathology of chronic bronchitis. Lancet 1:275-278, 1954 4. Reid L: Measurement of the bronchial mucous gland layer: A diagnostic yardstick in chronic bronchitis. Thorax 15:132-141, 1960 5. Restrepo G, Heard BE: The size of bronchial glands in chronic bronchitis. J Pathol Bacteriol 85:305-310, 1963 6. Hale FC, Olsen CR, Mickey MR Jr: The measurement of bronchial wall components. Am Rev Resp Dis 98:978-987, 1968 7. Wheeldon EB, Pirie HM: Measurement of bronchial wall components in young dogs, adult normal dogs, and adult dogs with chronic bronchitis. Am Rev Resp Dis 110:609-615, 1974 8. Reid L: Histochemical and enzyme studies of bronchial mucus. Med Thorac 22:6168, 1965
9. Wheeldon EB, Pirie HM, Breeze RG: A histochemical study of the tracheobronchial mucosubstances in normal dogs and dogs with chronic bronchitis. Folia Vet Lat 6:45-58, 1976 10. Spicer SS, Chakrin LW, Wardell JR Jr: Effect of chronic sulfur dioxide inhalation on the carbohydrate histochemistry and histology of the canine respiratory tract. Am Rev Resp Dis 110:13-24, 1974 11. Colley JRT, Douglas JWB, Reid DD: Respiratory disease in young adults: Influence of early childhodd lower respiratory tract illness, social class, air pollution, and smoking. Br Med J 3:195-198, 1973
