3.2.

INHALATION OF SULFIDE DIOXIDE

SO2 is a major component of industrial smog that, when inhaled in dogs, produces
responses similar to those of chronic bronchitis. Experimentation involves exposure to SO2
for many months, and even dogs are allowed to breathe through tracheostomy to minimize
the removal of SO2 through the nose and pharynx and maximize deposition in the
intrathoracic airways.
The short-term effects of this exposure are:

3.2.1. Acute phase responses

In dogs, SO2 administered directly in the lungs produces transient bronchoconstriction
followed by a period of hypersensitivity to inhalation. There is also epithelial damage of the
respiratory tract and leukocyte infiltration.

3.2.2. Lung pathology

Very similar human chronic bronchitis:
- Hypertrophy and hyperplasia of the mucous glands of the respiratory tract
- Thickening of the airway epithelium
- mucus hypersecretion
- Thickening of the smooth muscle of the respiratory tract and inflammation with
inflammatory cell entry.

3.2.3. Pulmonary pathophysiology

In the long term, SO2 in dogs produces many of the clinical symptoms of chronic bronchitis
in humans:
- Cough
- Increased mucus production
- Obstruction of the respiratory tract. The reactivity of the airway to inhaled
bronchoconstrictors is reduced after chronic inhalation of SO2 in dogs. It is thought to be
due to an increased mucoepithelial barrier after chronic exposure to SO2.

3.3. INHALED PROTEOLYTIC ENZYMES

It is believed that the pathogenesis of human emphysema is due to the non-inhibited
proteolysis of pulmonary elastic tissue. In dogs, the pathology that resembles human
panacinar emphysema is produced by instillation or aerosolization of proteolytic enzymes in
the lungs. Papain is the proteolytic enzyme that is commonly used.

3.3.1. Acute phase response

The main acute response is pulmonary congestion with the presence of petechia
accompanied by edema, inflammation and cellular infiltration, characterized mainly by an
acute increase in neutrophils and macrophages, and a slight degree of destruction of the
alveolar wall.
Precautions are taken to ensure the recovery of dogs after exposure, such as the use of
short-acting anesthetics, pretreatment with bronchodilators ...
3.3.2. Lung pathology
Histologically, changes in pulmonary pathology resemble those of human panacinar
emphysema, and include:
- Damage to the alveolar walls.
- Increase of air spaces.
- Formation of spaces in the septal interstice of the alveoli. It has also been seen that
papain causes damage and remodeling of the smooth muscle pulmonary vasculature.
However, no histological changes are observed in the upper respiratory tract.

3.3.3. Pulmonary pathophysiology

The changes are also identical to those observed in human panacinar emphysema, whose
main consequence is an obstruction of peripheral air flow. Gas exchange is also negatively
affected by exposure to papain.

The model of emphysema induced by papain in dogs has been used to:
1. Validate new methodologies before they are tested in humans, such as helping to predict
the improvement or deterioration of lung function in patients with COPD
2. Validate a variety of new techniques for diagnosis and treatment, such as:
- Use of magnetic resonance
- Deposition of inhaled aerosols in the lungs
- Infrared thoracoscopy.
3. Evaluate different means of ventilatory support such as high frequency jet ventilation
or constant flow ventilation.
4. Evaluate new surgical devices such as the implantation of post-surgery breathing
valves in patients with advanced forms of COPD.

4. Summary
Dogs have been used to investigate in the areas of asthma and COPD, and studies have
shown remarkable stability. Airway hyperreactivity and bronchoscopy can be assessed by
mapping the divisions of the pathways. Their ease of handling and size have made them an
ideal species for long-term exposure to inhaled irritants such as SO2 and cigarette smoke.
Many of the drugs used to treat human asthma and COPD have been shown to be effective
in dogs. Lung inflammation has not been thoroughly investigated in COPD dogs. Future
research is expected to provide the immunological and inflammatory tools to more fully
characterize this aspect of canine research.