1. Upper airways (Figure 1) - the nasal turbinates/air passage-ways.
   In the nasal cavity, the epithelial surface over the turbinates is extensive, serving to warm and humidify air, as well as filter large particles from the incoming air stream. With nasal breathing, warming and humidification of inspired air is essentially complete before air reaches the lower airways.
   
   
2. Protective reflexes - The particular response (the reflex) that is elicited depends less upon the type, strength, intensity and duration of the stimulus applied to the irritant receptors, but rather to their location within the respiratory tract. Receptors may be stimulated by chemical, inflammatory and/or mechanical stimuli. Mechanical deformation may result either from material on the epithelial surface or be secondary to airway narrowing due to bronchoconstriction or external compression. Coughing, which is part of the clearance mechanism of the respiratory tract, is initiated by stimulation of subepithelial irritant receptors that are most numerous near the carina and in the larger bronchi.
   
   
   
   • Sneeze - irritation to the anterior portions of the nasal cavity
     
   • Reverse sneeze - described decades ago by physiologists, their "aspiration reflex", this is elicited by irritation to the dorsal nasopharyngeal mucosa
     
   • Cough - coordination of a deep inspiration, followed by a forceful expiration against a closed glottis and finally opening of that glottis to explosively expel air and luminal debris.
     
   • Airway narrowing - functions to attempt to limit the penetration of irritants deeper into the respiratory tract; includes laryngospasm & bronchospasm.
     
3. Mucociliary tree - Cilia beat in a coordinated motion to propel secretions out of the respiratory tract. Primary ciliary dyskenesia (PCD) is a congenital defect in cilial ultrastructure that usually results in secretion retention and chronic rhinitis and bronchitis.
   
   • Mucous layers - The epithelial cells of the respiratory tract are covered by a periciliary fluid of low viscosity (the sol layer) in which the cilia beat in a coordinated fashion. The gel layer, which may be continuous or in plaques, consists of viscous mucus that protects the sol layer from desiccation and also entraps inhaled particles. The presence of immunoglobulins (e.g. sIgA), complement, opsonins, and lysozyme in respiratory tract secretions assists in the killing/removal of viable particulates such as bacteria.
     
   • Cilia - beat in nose & trachea is towards the mouth
     
   • Tracheal mucus transport rates (TMTR) - in the normal individuals are approximately 20 mm/min in the trachea; TMTR decreases to between 2-5 mm/min in chronic bronchitis.
     
   Mucus secretion and ciliary activity are controlled under autonomic regulation. Stimulation of sympathetic nerves also causes secretion, alpha-receptors apparently being responsible for serous secretion and beta-receptors for mucin secretion. Vagal stimulation, e.g., following inhalation of an irritant substance increases mucus secretion by submucosal glands. Beta-adrenergic stimulation may increase mucociliary clearance. Some inflammatory mediators, particularly the lipoxygenase products of arachidonic acid metabolism (leukotrienes), are potent mucus secretagogues (caution, there are species differences). In the presence of chronic airway irritation (e.g. by dusts or chronic inflammation), submucosal glands hypertrophy and produce increased quantities of mucus, which may be difficult to move via the mucociliary system. I believe secretions like this are a common finding in some of the chronic nasal and lower airway cases that I encounter. Chronic irritation may also lead to goblet cell hyperplasia in peripheral airways so that mucus is secreted into bronchioles poorly equipped for mucus removal. The overall effect is one that can lead to mucus obstruction of peripheral airways and ventilation to perfusion (V/Q) inequalities, as well as the obvious presenting complaints of coughing and nasal discharge.
   
   
4. Bronchus associated lymphatic tissue (BALT) - located in the epithelium of the respiratory tract, analogous to the Pyer's patches of the intestinal tract; very important in Agn processing. The best grossly visible example of BALT is in the clinical condition of follicular pharyngitis.
   
   
5. Pulmonary macrophage (MO) - Particles deposited on the alveolar surface are cleared by phagocytic alveolar macrophages. These cells normally constitute approximately 70-85 per cent of the cells in fluids washed from the lung periphery, i.e. in a bronchoalveolar lavage.

1. Ventilation - Ventilation is simply the movement of air into and out of the lungs. Ventilation is usually "set" at a sufficient level to supply O2 and remove the CO2 produced by the tissues (and sensed by central and peripheral chemoreceptors). In order to do this, ventilation must increase whenever metabolic activity increases, as for example, during exercise. Approximately 33% of ventilation goes to dead space ventilation. Measuring arterial PaCO2 levels can objectively assess the actual adequacy of ventilation.
   
   Observing an animal breathe at rest is a very important diagnostic skill (observe from a distance, not after he is excited and on an exam table). Inhalation is normally an active process, occurring as the result of contraction of the diaphragm and to a lesser degree the external intercostal muscles. During exercise, or when there is increased respiratory drive, the "accessory muscles" of respiration may be used. These accessory muscles of respiration are located in the upper airway, where they dilate the nares, pharynx and larynx as well as in the neck and thorax, where they assist in enlarging the rib cage size. A classic example is seen in the nostril flaring of a racing horse. Observation that an animal has accessory muscle activation at rest is a clear sign of severe respiratory disease.
   
   Exhalation is normally a passive process, and occurs as a result of the elastic recoil of the lungs and rib cage that were "stretched" (by the work of breathing) during inspiration. Active abdominal exhalation in a resting dog or cat is a sign of extensive intrathoracic airway disease and is caused by contraction of (mostly) the external abdominal oblique muscles. Increased expiratory effort is often detected in dogs and cats with small airway disease although the horse provides the best example of this - heaves.
   
   During inhalation, the respiratory muscles must work to overcome the lung elasticity and frictional resistance to air flow in the air passages. (The inertia involved in moving tissue and gas is minimal, and is usually ignored.) The elastic recoil of the lung is a result of the collagen and elastic tissue in the alveolar septa as well as the surface tension of the fluid lining the alveoli. The elastic recoil of the lung is measured as lung compliance (C =?VT/?P; the units are volume/pressure e.g. ml/cmH2O). In disease, there can be an increase in the amount of collagen within the lung or there can be an increase in surface tension, both of which increase the elastic recoil of the lung (stiffens the lung), reducing compliance and making it more difficult to inhale. Many diseases, such as pneumonia and pulmonary edema, stiffen the lung and cause a reduction in lung compliance. An animal with low lung compliance has difficulty breathing because the lung is more difficult to stretch and expand; this animal will classically breathe more rapidly and more shallowly than normally.
   
   The second factor to be overcome during inhalation is the frictional resistance of the airways to airflow. In normal animals, approximately 50-70% of total resistance is in the upper airways (implications for our brachycephalic patients!). In the tracheobronchial tree, the majority of resistance is in the central airways (larynx, trachea and bronchi) with the small airways, the bronchioles, contributing very little. For this reason, obstructions of the upper airway or of the trachea and bronchi cause much more severe respiratory distress than obstruction of the bronchioles. Obstruction of the bronchioles must be extensive and severe to cause a major increase in the work of breathing. In respiratory disease, the frictional resistance of the air passages is increased by 1) the presence of obstructions, such as mucus or masses, 2) by the contraction of airway smooth muscle as a result of allergic responses or alterations in autonomic regulation, or 3) as a result of edema in the walls of the airways. Airway resistance can be measured clinically in the anesthetized animal (RL = ?P/?V; its units are pressure/flow, or cmH2O/ml/s). Recent advances in respiratory physiology have allowed for the measurement of airway reactivity in healthy awake cats using a barometric whole-body plethysmograph, a technique that clinicians at Tufts University are working on and which may become available for clinical use in the future.
   
   
2. Distribution - Inhaled air must be distributed throughout the air passages to all alveoli within the lung. The distribution of airflow is determined by a combination of the frictional resistance of the air passages and by local changes in lung compliance. Uneven distribution of ventilation is a major cause of abnormal gas exchange in lung disease. Maldistribution of inspired gas results in an inequality of ventilation to perfusion (referred to as a V/Q abnormality), and clinically to hypoxemia, exercise intolerance and tachypnea for instance.
   
   
3. Diffusion - The transfer of gas between the alveolus and the capillary blood occurs by a process of diffusion. Diffusion is a passive process, depending on a number of factors (Figure 3) including partial pressure differences of a gas on either side of the large surface area of the alveolar-capillary membrane. In disease, these factors can be altered because (for example) the alveoli are flooded with exudates or because of changes of the distribution of blood flow (e.g. pulmonary emboli). Carbon dioxide, because of its greater solubility, diffuses much more readily than O2. Lung disease, therefore, is more likely to cause hypoxemia than it is to cause an increase in CO2 tension.
   
   The efficiency of gas exchange in the lung is determined by the matching of ventilation to blood flow. In normal alveoli, the ratio of ventilation to blood flow is close to 1, but even in normal lungs there exist regions that have more ventilation than blood flow (more dorsal regions) and some that receive more blood flow than ventilation (the more ventral regions). In small animals these differences are of minor importance. In disease, a wide variety of ventilation to blood flow ratios can exist in the lung. Low V/Q ratio regions of the lung occur as a result of airway obstruction or flooding of the alveoli with exudates. These low V/Q ratio units are extremely common in lung disease and give rise to hypoxemia. Although V/Q is not readily measured, the overall efficiency of gas exchange in the lung can be calculated by measuring the difference between the Alveolar-arterial partial pressure of O2, the DA-aO2 or simply the "A-a gradient" (refer to discussion below).
   
   
4. Perfusion - The blood flow to the gas exchange region of the lung is delivered by the right ventricle, and must be matched to ventilation if a normal V/Q ratio is to exist. When pulmonary vascular disease exists, (e.g. pulmonary hypertension secondary to chronic bronchitis, canine heartworm disease), or when there is a low pulmonary artery pressure, (e.g. shock), the distribution of blood flow can be abnormal and can lead to signs of respiratory disease.
   

1. Obstructive diseases - those that obstruct the movement of air flow into or out of the lungs. Usually associated with increases in airway resistance. Typically results in a slower and deeper respiratory pattern than normal. Clinical examples include: chronic bronchitis, bronchiolitis, compressive tracheobronchial lesions (hilar lymphadenopathy), laryngeal diseases (paralysis, everted saccules, laryngeal collapse, tumor).
   
2. Restrictive diseases - those that restrict the expansion of the lungs or chest wall. Usually associated with a decrease in compliance, i.e. stiffer lungs/chest wall. Typically these diseases result in a faster and more shallow respiratory pattern than normal. Clinical examples include: pleural filling defects (accumulations of air or fluid), pulmonary fibrosis, pulmonary edema, pneumonia, and severe obesity.
   
3. Diffusion impairment - thickening of the alveolar - capillary membrane. This is difficult to define accurately but is not recognized as a major clinical problem in veterinary medicine.
   
4. Pulmonary vascular disease - A serious and increasingly common problem in small animals. Examples include pulmonary hypertension, pulmonary emboli and canine heartworm disease.
   

• Rate and volume - fast/slow, deep/shallow
  
• Effort - increased or decreased (based on visual, audible or palpable findings)
  
• Timing - inspiratory, expiratory; fast, slow
  
• Amplitude - quiet, loud
  

1. Signalment, or the animal's description - classically the age, breed and sex; it is a useful reminder of common differential diagnoses that might be encountered in a particular animal; a good example is the 11yr old, male Black Lab with inspiratory noise and exercise intolerance. *
   
   
2. History. Many cases of respiratory distress are associated with trauma and the history and observations that an owner can provide can be very helpful. Some cases are secondary to chronic infectious, metabolic/endocrine, toxic or commonly, preexisting cardiac disorders. Inquiring into the animal's previous medical and travel history as well as home/living environment (for instance chronic coughing, exposure to other animals, use as a hunting animal, presence of anticoagulants in the household) may alert you to specific differential diagnoses for consideration. Reading the animal's problem list (assuming this is your own patient that has been seen before) may point out potential concerns relating to a current problem of respiratory distress (such as Cushing's disease, hypoalbuminemia, recent trauma or bite wounds in a cat).
   
   Table 2 - Findings of auscultation, palpation and percussion in selected pleural and parenchymal disorders. (NB - assumes the patient is sternal or standing)

   Disease	Auscultation	Palpation & Percussion
   Pneumothorax	o ? sounds dorsally ("distant") o N lung sounds ventrally	o ? resonance dorsally ("hollow") o N resonance ventrally
   Hydrothorax	o N to ? lung sounds dorsally o ? or absent lung sounds ventrally	o N resonance dorsally o ? resonance ventrally ("solid")
   Pneumonia	o Crackles, occ. wheeze o ? or absent lung sounds ventrally	o ? resonance if lobe consolidated o ? tracheal sensitivity, moist cough
   Bronchitis, "Asthma"	o Crackles, occ. wheeze o Cats - crackles may only be noted post tussively	o N to ? resonance dorsally o Palpable expiratory push/? effort o ? tracheal sensitivity
   Pulmonary edema	o Fine crackles, esp. ventrally o Often note cardiac abnormalities	o Unknown/no change
   Fibrosis	o Fine crackles, prominent dorsally	o ? tracheal sensitivity
   Hernia	o ? BV lung sounds o N to ? heart sounds on N side o ? or absent lung/heart sounds on the side of the hernia	o ? resonance on hernia side o ? resonance if stomach is herniated and gas filled
   Mass	o Small - no change o Large - shift in heart sound location & absence of lung sounds	o Small - no change o Large - ? resonance ("solid") over the lesion
   Lung consolidation	o ? BV to bronchial lung sounds o crackles, sounds absent if bronchus filled	o ? resonance over the affected lung lobe

   
   
   

3. Physical Examination. A quick assessment of an animal's condition upon presentation (triage) is essential. Many animals in respiratory distress have minimal reserves with which to handle the additional stress of transportation, physical examination and diagnostic testing used to determine the underlying cause of their distress. A calm, compassionate approach that deals with the animal's fear, anxiety and possible pain is important.
   
   If significant distress (open mouth breathing, cyanosis, orthopnea) is present the veterinarian must determine if the cause is airway (e.g. laryngeal paralysis), pleural (hernia, effusion) or primary lung (pneumonia, pulmonary edema) and act accordingly. I use a visual assessment of the respiratory rate, effort (I vs E) and auscultation (pleural air/fluid, crackles, wheezing) to make my initial evaluation. Table 2 summarizes some of the classical findings of auscultation and percussion associated with various airway, parenchymal and pleural filling defects in animals and is a good reminder for us to use both exam techniques in our patients. Be sure to listen to both right and left lung fields, the upper airways (nasal and laryngeal) as well as to the heart for possible cardiac involvement. Table 3 provides a summary of respiratory sounds and reflexes, which might help in assessing these patients.
   
   
4. Diagnostic Tests. There are few routine clinical pathology tests that are specifically diagnostic in respiratory distress situations. A complete laboratory evaluation (CBC, serum chemistries and a urinalysis) none-the-less is recommended as a baseline for future reference/comparison, to rule out co-existing disease and in anticipation of anesthesia if it may be required. A severe left shift, marked eosinophilia, profound anemia, coagulopathy or hypoalbuminemia are examples of abnormal laboratory tests that might relate to a specific cause for an animal's respiratory distress, and if found would warrant further investigation. Parasite evaluation may be indicated depending on your geographical location and the incidence of these parasites in your area - for instance canine heartworm (Dirofilaria immitis).
   

Area of Interest	View
Turbinates	Open mouth and/or intra-oral
Sinuses	"Frog-eye" or lateral
Maxillary teeth	Lateral oblique & intra-oral dental films (best)
Nasopharynx / larynx	Lateral - mouth closed, head/neck straight

Respiratory endoscopy (when performed by an experienced veterinarian) is one of the most valuable diagnostics available for the evaluation of airway diseases in dogs and cats. Its application in cases of respiratory distress may be limited by the necessity for general anesthesia and this "cost-benefit" ratio will always have to be carefully evaluated.

Rhinoscopy is the visual assessment of the nasal cavity, nasopharynx (NP) and in some instances the paranasal sinuses. (Bronchoscopy will be discussed later) A complete examination (which includes evaluating both the anterior and posterior portions of the nasal cavity and nasopharynx) requires general anesthesia and specific endoscopic equipment. There are a variety of reasons to consider performing rhinoscopy including complaints of sneezing and reverse sneezing, nasal discharge, epistaxis, abnormal sounds and/or often some degree of airflow obstruction. Animals with epistaxis should have a coagulation profile (e.g., platelet count, PT/PTT and/or a mucosal bleeding time - MBT) performed and their blood pressure checked prior to starting as these patients may have an increased risk of bleeding.

For a complete evaluation of the nasal cavity, sinuses and nasopharynx the assessment should include skull radiographs (see Table 4), rhinoscopy and periodontal probing. Due to strong airway protective reflexes (sneezing and gagging), rhinoscopy requires a deep plane anesthesia, especially for posterior rhinoscopy. Topical lidocaine, sprayed on the mucosal surfaces, may help blunt some of these reflexes. Some degree of patience and practice is required to maneuver a flexible endoscope around the soft palate and into a position to clearly visualize the NP.

When properly positioned the following structures will be visible: the free edge of the soft palate, soft palate, mucosa of the dorsal nasopharyngeal wall, opening to the Eustachian tubes (on the dorsal, lateral walls), choanae, and some of the ectoturbinates in either nasal cavity or vomer bone and the nasal septum. The mucosa should be pink and not friable; there should be minimal secretions and the choanae should be patent.

Typical lesions and abnormalities that I have encountered in the NP include:

• Mucosal abnormalities: inflammation, hyperemia, increased mucosal fragility or friability, and lymphoid follicle development (an indicator of chronic irritation) or mucosal proliferative lesions (caution - lymphoma in cats can look grossly the same).
  
• Decreased amount of space in the NP: due to tumor, polyp, foreign body, stricture, web, excess secretions or even "ectopic" (NP) turbinate development (seen in brachycephalics).
• Miscellaneous changes: parasites (mites), drainage from eustachian tubes, NP wall abscess.

• Opening to the nasolacrimal duct - ventral edge of the alar cartilage.
  
• Nasal septum (vertically aligned, opposite of turbinates).
  
• Turbinates (dorsal and ventral chonchae), all arise from lateral aspect of the nasal cavity.
  
• Four meatii (dorsal, middle, ventral and common) - it is important to note the meatus size!
  
• Ethmoidal labyrinth caudally.
  
• Maxillary and frontal sinuses - only reached if there has been turbinate destruction/loss.
  

• Mucosal abnormalities: inflammation, hyperemia, increased mucosal fragility or friability, lymphoid follicle development (less commonly found than in the NP).
  
• Increased amount of visible space: turbinate loss, chronic inflammation (usually associated with such conditions as canine nasal aspergillosis or secondary to bacterial infections, e.g., due to tooth abscess, foreign body or feline viral infection).
  
• Decreased amount of visible space: the normal air space (meatus) is filled by secretions, tissue (tumor, granuloma, polyp), or foreign body.
  
• Secretions: all types.
  
• Miscellaneous findings: parasites (nasal mites), fungal plaques.
  

• Elongated soft palate: should be anticipated and resected at the time of scoping if possible.
  
• Laryngeal mucosal edema: this can be severe in animals with a chronic history of upper airway noise (again, anticipate in those with known problems such as brachycephalics).
  
• Edematous/everted laryngeal saccules (lateral ventricles): eversion can be very dynamic so look closely at rest as well as following Dopram administration!
  
• Laryngeal paralysis: may be unilateral or bilateral.
  
• Laryngeal collapse: a life threatening complication of chronic upper airway obstruction.
  
• Laryngeal neoplasia: lymphoma, squamous cell carcinoma are the most common types.
  
• Epiglottic entrapment: secondary to other inspiratory problems; may be intermittent.
  

• Sneezing and reverse sneezing (also called the "aspiration reflex," a normal response to any irritation of the dorsal nasopharyngeal mucosa).
  
• Nasal discharge: determine type (serous, mucoid, purulent, bloody etc.), amount, frequency, whether (when it was first noticed) unilateral or bilateral, if the character has changed, and if it is worse at any specific time of the day. The discharge may sometimes be due to chronic pneumonia or vomiting (secretions are thrown or coughed into the nasopharynx, and then noticed as a nasal discharge).
  
• Respiratory sounds/noise: does the animal make any sound while breathing (with exertion or while sleeping)? Sounds which are new or only recently noted are likely important indicators of airway obstruction. Ask if there are any voice (bark, meow/purr) changes (laryngeal disorders?).
  
  • Stertor, a snoring sound, due to an intermittent physical obstruction usually heard on inspiration (e.g., soft palate, NP mass).
    
  • Snorting, found with obstructions secondary to accumulated secretion (e.g. nasal).
    
  • Stridor, an inspiratory wheeze or noise, typically associated with high cervical tracheal/laryngeal airway narrowing lesions.
    
• Exercise intolerance - usually accompanied by an increased inspiratory effort and often with pronounced stridor.
  
• Open mouth breathing - may indicate bilateral nasal and/or nasopharyngeal obstruction.
  
• Cheek puffing - often noted on expiration with NP obstruction (e.g. masses)
• Coughing after eating or drinking.

• For epistaxis: look at platelet numbers and function (mucosal bleeding time), PT/PTT as well as arterial blood pressure (for systemic hypertension); check medication history for aspirin and/or the use of alpha agonists.
  
• For feline calici virus (FCV): only available by virus isolation at this time.
  
• For feline herpes virus (FVF), Chlamydia and Mycoplasma: PCR tests are available to help diagnose these agents. The test may be performed on either a conjunctival scraping or tissue (conjunctiva or nasal) biopsy; transport media is required (sterile saline often works).
  
• For nasal fungal disease: canine aspergillosis - fungal serology is not a sensitive test; for feline cryptococcosis the Latex agglutination test has good sensitivity.
  
• Dental evaluation - under anesthesia do complete periodontal probing, dental radiographs.
  
• For any nasal, NP or laryngeal disorder - the best tests include:
  
  • radiography (skull and dental radiographs as well as CT and MRI which have particular application to nasal and sinus disease), and especially
    
  • complete periodontal / dental examination
    
  • endoscopy (see discussion above).
    

• Reverse sneeze: this is a normal reflex to the irritation of the dorsal wall of the nasopharynx, and characterized by the sudden onset of forceful and paroxysmal inspiratory efforts. Although not a serious problem for the animal, if is a common cause of concern to owners! There is no specific treatment (except for an underlying cause if found - nasal mites are a common cause in my experience). NP inflammation (including severe follicular pharyngitis) is associated with reverse sneezing. Any irritant can be the trigger for this reflex. If no specific trigger can be found I will often prescribe a trial therapy of an anti-inflammatory (steroids or piroxicam).
  
• Nasopharyngeal stenosis or webbing: A problem in cats (primarily) of any age; this is a transverse sheet of scar tissue formed above the soft palate and obstructing the flow of air through the NP. Typically has a small pinhole size opening for airflow. Webbing is believed to result during the healing process after various injuries to the air passages (infectious, traumatic). Scar tissue has also been observed within the nasal cavities. Diagnosis is best made via direct visualization (rhinoscopy). Treatment is to surgically resect the lesion, usually via splitting the soft palate, removing the web and closing the palate. Complications include dehisence of the palate and reformation of the web. Recently success has been reported using a ballooning technique to break the web down. The difficulty with any of these procedures is to prevent the scar tissue (web) from reforming again.
  
• Nasal foreign bodies - in my experience, the majority of these cases involves material that the animal has mouthed and then when trying to get rid of it has thrown it up into the NP; caudal (flexible) rhinoscopy is needed to identify and deal with these cases. Vigorous nasal flushing with sterile saline is helpful in removing these.
  
• Brachycephalic airway syndrome. I am continually amazed at the severity of inflammation that is seen in these cases. The syndrome includes or is associated with a number of specific problems; these airway problems should be aggressively dealt with early in life to prevent the onset of irreversible airway changes:
  
  • Stenotic nares - resect if they are narrowed and there is paradoxical inspiratory motion.
    
  • Elongated soft palate - the most common problem, I recommend that all brachycephalic dogs have this corrected when they are neutered if not sooner if indicated (along with other abnormalities identified on examination).
    
  • Laryngeal edema - some degree (often severe) of edema will be present in almost every case; steroids are indicated following surgical correction of these problems and in many cases should be given prior to surgery in attempt to reduce airway inflammation. Chronic edema can lead to fibrosis over time (many dogs suffer from years of inflammation).
    
  • Everted laryngeal saccules - these are secondary to other problems but with time they can become fibrotic and not resolve following removal of the other (inciting) airway problems.
    
  • Laryngeal collapse - an end stage process caused by cartilage failure secondary to long standing inflammation and inspiratory effort; prognosis for these dogs is grave.
    
  • Tracheal hypoplasia - I recommend checking all brachycephalic dogs for this (a straight lateral chest radiograph) prior to any upper airway surgery.
    
  • Enlarged tonsils - these can be quite large secondary to chronic irritation and should be removed if they contribute to airway obstruction when examined.
    
  • NP turbinates - normal nasal turbinates which extend into the NP during development and appear to act as another site of airway obstruction in these dogs.
    
• Laryngeal paralysis - this is a common problem in large breed dogs (as an acquired, slowly progressive neuropathy), as well as in some breeds of dogs as a congenital problem (the Bouvier, Siberian Huskies, Dalmatians etc.). Cats can also be affected - I will see 6-10 of these each year. Dopram administration will assist in assessing intrinsic laryngeal function and should be a standard part of any complete laryngoscopy. At our hospital we have begun to evaluate these cases more critically at the time of diagnosis to include an evaluation of the site of obstruction (vocal cords or arytenoids?), the degree of arytenoid motion (fixed and rigid or easily abducted?) and the location of the upper esophageal sphincter in attempts to define criteria for selecting the best surgical technique for treating them. Laryngeal surgery is only recommended when respiratory distress is severe due to the high incidence of aspiration pneumonia that has been reported (approximately 25%). Surgical procedures include the standard arytenoid "tie-back" surgery as well as laser procedures (vocalcordectomy and partial laryngectomy in cats). The risks of intra-laryngeal surgery have always been subsequent scarring (granulation tissue); the topical use of Mitomycin-C (an older chemotherapeutic agent) has shown great promise in preventing this potential complication and we use it routinely in these cases.
  

• ABGs - These are easy to do and provide the only functional assessment of overall lung function available in practice.
  
• Parasite evaluation - fecal exam(s), HW testing (endemic areas, dogs with a travel history)
  
• CBC - Useful in those with systemic signs (pneumonia cases primarily). Less than 40% of confirmed allergic airway cases (those with eosinophils on airway cytology) have an absolute peripheral eosinophilia. Be careful - pneumonia can exist and be severe despite a normal CBC!
  
• Radiography - Thoracic radiography provides one of the most widely available methods for evaluating the tracheobronchial tree and lung parenchyma. Bronchial disease normally demonstrates the thickened bronchi ("donuts", "tram lines"). Parenchymal diseases usually cause an increase in interstitial density, which increases with severity to an alveolar pattern and eventually to lobar consolidation. Changes may be patchy, lobar or diffuse. Remember however that functional changes and visible structural changes do not always parallel each other.
  
  • Thoracic radiography should include views made in at least two planes; lateral and either the VD or DV position. I prefer to obtain 3 views of the chest, both right and left laterals and the VD view for the evaluation of lung diseases.
    
  • For optimal demonstration of parenchymal lesions, thoracic radiographs should be obtained at peak inspiration (for dynamic airway lesions both peak inspiratory and peak expiratory radiographs should be obtained).
    
• Airway cytology is necessary to determine an etiologic diagnosis and in order to recommend the most appropriate/specific therapy. Samples may be obtained via transtracheal wash, fine needle lung aspiration or bronchoalveolar lavage during bronchoscopy. Samples should be examined both cytologically as well as by culture and sensitivity determination. Extensive cytology experience is not required in order to differentiate between many of the common causes of coughing. Each technique has reasons pro and con as well as different risks associated with the procedure.
  
  • Transtracheal aspiration biopsy (TTA) is indicated in acute (when a culture is needed) or in chronic lower respiratory tract diseases when other routine tests have failed to establish a diagnosis. A large bore (e.g. 16ga), "thru-the-needle" type jugular catheter, 3 way valve, sterile saline, syringes and microscopic slides are all that is required. Lidocaine (2%) is sufficient for local anesthesia; general anesthesia should be avoided due to cough suppression. When properly placed the tip of the catheter should be just proximal to the carina. Care must be taken if a trans-oral technique is used in order to avoid oral cavity contamination. The amount of fluid injected will vary with both the disease and the size of the patient. I typically inject 3-5 ml aliquots of sterile saline and, after the animal has coughed, aspirate until a visible sample is obtained (repeat as needed to obtain a sample). A trans-oral approach (passing a catheter through a sterile trach tube) may be used as well (be careful to avoid contamination with oral secretions).
    
  • A fine needle lung aspirate (FNA) is indicated when there is diffuse lung disease or when a large region of lung is diseased (e.g. lung mass or consolidated lobe). The aspirate should be obtained from a region identified by radiography, using a small gauge needle (typically a 1-1.5" x 22-25 ga. needle) and a 6 ml syringe. The needle should be inserted in front of the rib and (with respiration stopped) thrust into the lung, aspiration applied and then the needle quickly withdrawn. Only a small sample (perhaps enough for 1 or 2 cytology slides) will normally be obtained although repeated samples can be used to obtain material for culture. Be careful performing a fine needle lung aspirate in an animal with an active expiratory effort as the risk of inducing a pneumothorax is increased.
    
  • Bronchoscopy with full BAL is my preferred method of collecting samples from the lower airways (see discussion above).
    
• Electrocardiography (ECG) an Echocardiography (Echo): One of the major differential diagnoses for the coughing animal is primary heart disease. Chamber enlargement due to volume overload may be associated with pulmonary edema and coughing. LAE may induce coughing directly by direct compression of the left principal bronchus (visible on lateral chest radiographs and at bronchoscopy). Enlargement of other chambers, e.g. the RA and RV, have been associated with chronic lower respiratory tract diseases and the development of cor pulmonale.
  
• Thoracotomy - if other diagnostics have failed to establish a firm diagnosis exploratory surgery should be considered. Thoracoscopy is beginning to be used to obtain lung biopsies for histopathologic confirmation of the lung problem.
  

• Chronic bronchitis - A specific etiology for CB is rarely determined. Chronic airway inflammation leads to chronic coughing. The primary effects on the respiratory system are hypoxemia, exercise intolerance and respiratory distress.
  
  • Recurrent airway inflammation (e.g. infections, inhaled irritants) is suspected. Acute exacerbations are commonly superimposed on a chronic course. Persistent tracheobronchial irritation results in chronic coughing and changes in the epithelium and wall of the tracheobronchial tree. Mucus production is increased due to changes in glandular structures as well as goblet cells. Other commonly reported changes include airway inflammation, epithelial edema, thickening and metaplasia. Airway narrowing (with the associated increase in resistance and decreased expiratory air flow rates) is the net effect of these changes. In severe cases the work of breathing increases and is detected as respiratory distress (an increase in breathing rate/effort, disproportionate to the patient's level of exertion).
    
  • Changes in the histochemical structure of the cartilaginous rings in the trachea and/or the plates in the bronchial walls result in a weakening of the wall and collapse of the affected airways (tracheobronchial malacia or tracheal collapse when the trachea itself is affected). Secondary effects on the heart (cor pulmonale) may lead to pulmonary hypertension and may be severe. Syncopal episodes are frequently reported in dogs with chronic coughing due to decreased blood flow thorough the brain. Hepatomegaly secondary to passive congestion may occur.
    
  • CB is typically thought of as a small/toy breed dog problems, but it is also commonly observed in large dogs. Bronchiectasis has frequently been observed in young to middle aged Cocker Spaniels following a long history of CB. Siamese cats have been reported to be more frequently and more severely affected than other breeds of cats. CB most often affects middle aged and older animals. Ciliary dyskenesia is usually reported in young dogs and results in chronic bronchial disease (including bronchiectasis) due to poor secretion clearance and recurrent infections. A female sex predilection has been suggested by some authors in feline CB, but not our studies. No sex predilection has been noted for canine CB. The patient's body condition score (BCS) should be determined as obesity is a common and significant morbidity factor in canine CB.
    
• Tracheal collapse - I believe that this disorder is brought on by small airway disease leading to the previously described histochemical changes in the cartilage which allows collapse to occur as increased intrathoracic pressures are generated to facilitate exhalation. The medical treatment of these cases is very similar to the treatment for CB. Diet is critical and these animals must be prevented from becoming obese. Selected cases of tracheal collapse may benefit from surgery; careful examination of the airways (bronchoscopy) is needed to select these cases. The placement of external plastic ring supports has been used with good success in selected cases. Recently tracheal stents have been reported in tracheal collapse cases but should be only considered in very severe cases and are associated with potential complications (granulation tissue formation). Severe dental disease should be treated aggressively to minimize secondary bacterial showering of the lower airways in these and in CB patients.
  
• Pneumonia - various types (viral, bacterial (primary, secondary to foreign body, aspiration etc.), fungal, parasitic etc.) exist and are discussed below.
  
• Pulmonary fibrosis - West Highland White Terriers have been noted to develop a progressive disorder characterized by chronic coughing, tachypnea and crackles. The location of the pulmonary infiltrates as well as the location of audible crackles seems to be more caudodorsal than in other bronchitis cases. Fibrosis is thought to be present in these cases but detailed clinical and pathologic studies of the condition are lacking. Lung biopsy is needed to confirm this diagnosis. Treatment is typically the same as for CB cases.
  
  Neoplasia - We encounter primary and metastatic tumors on a regular basis. Three view chest radiographs are indicated in order to fully evaluate all lung fields for involvement. Diagnosis is based on cytology or histopathology from a tissue biopsy. Abdominal ultrasound is indicated to ensure that there are no distant primary sites before surgery is considered. Surgical intervention for suspected primary lung tumors is recommended as early in the disease process as possible. The median survival time for primary lung tumors varies significantly based on whether the hilar lymph node is involved or not - always have a hilar node biopsied as part of the surgery.
  
• Foreign body - On occasion an owner will witness and know that a foreign body (FB) was aspirated; usually it is the ensuing pneumonia that alerts us to this possibility. The animal's use (i.e. a hunting dog that runs in fields) is an important part of the history and can alert the veterinarian to this possibility. Diagnosis is based on finding the FB, on bronchoscopy or at the time of surgery (lung lobectomy). Treatment for the ensuing bacterial pneumonia (see below) is important following removal. Bronchiectasis may develop secondary to the FB being in the bronchus and even if it can be removed bronchoscopically a lobectomy may be required to fully resolve the pneumonia.
  

1. Control of secretions: Secretions may be controlled by either decreasing their production (the best choice) or increasing/facilitating the removal of excess, accumulated secretions.
   
   • Specific methods of controlling secretions
     
     • Methods of decreasing production of secretions: Antibiotics and corticosteroids - culture and cytology are the main methods in determining when each is indicated.
       • Cultures - Bacterial cultures from the upper airways (nasal cavity) are rarely helpful as infections there are secondary; cultures for lower airway disease must be obtained from the lower airways, tonsillar swabs are not indicative of flora in the lower airways. Chronic bronchitis is not normally associated with significant bacterial growth (see discussion on quantitated cultures).
       • Drugs -
         1. Antibiotics: Use bactericidal antibiotics that have a good spectrum of activity. A Gram (Gm) stain is helpful in determining an antibiotic, although each case should have it's own sensitivity if possible (especially if you observe Gm negative organisms). For upper airway diseases antibiotics with a good Gm positive spectrum are best. Most pathogens in the lower airways (~85+ %) are Gram negative (e.g. E. coli, Klebsiella, Pseudomonas spp. etc.). Cephalosporins, potentiated sulfas, amoxicillin or amoxicillin/clavulanate, and fluoroquinolones are usually good choices for lower airway infections.
            
            The route of administration is a concern for lower airway diseases. If the infection is thought to be tracheobronchial (intra-luminal) then there should be concern about antibiotic penetration into the lumen of the airways (i.e. does the antibiotic actually penetrate into bronchial secretions). Intratracheal injections or aerosolized antibiotics may be helpful in selected cases of infectious tracheobronchitis (specifically those due to Bordetella infections).
            
            
         2. Corticosteroids - These drugs constitute an important treatment option for allergic diseases as well as in chronic bronchial disease to decrease cellular infiltration (see Figure 6). Oral short acting steroids (prednisone) are preferred for ease of dosage adjustments which is import in chronic conditions. Inhaled steroids are also being used more frequently (see discussion below).
            
         3. Antifungals - With the availability of new oral antifungals (itraconazole, fluconazole), effective antifungal therapy can be accomplished at for most infections (e.g. cryptococcosis). Topical treatment (enilconazole, clotrimazole) is preferred for nasal aspergillosis in dogs.
            
   • Non-specific methods of controlling secretions. Non-specific means of removing secretions including methods designed to "loosen" secretions (e.g. aerosol therapy and expectorants) and those which are designed to improve the rate of their clearance from the tracheobronchial tree (e.g. cough facilitation and chest physiotherapy) should be used. Agents which "dry up" secretions may be tried when other means have failed (often chronic, bilateral mucoid nasal discharge cases).
     
     • Aerosol therapy: Goal is to loosen secretions. Always used in conjunction with physiotherapy. Efficacy is debatable. Antibiotics should NOT be aerolosized unless it is directly via a facemask and then are indicated only for airway (not parenchymal) infections. Ensure adequate systemic hydration before using aerosol therapy.
       
       • Equipment - Ultrasonic nebulizers are best; they produce particles of between 0.5-3 micra in size which are best for deposition in the lower respiratory tract. The new Nebulair unit (DVM Pharmaceuticals) is useful for short term, face-mask nebulization.
         
       • Fluid - bland aerosol therapy using sterile 0.9% NaCl.
         
       • Technique - aerosol therapy for 30-45 minutes (using a larger ultrasonic unit), 2-4 x/day in a closed cage followed by physiotherapy has seemed beneficial in many cases of lobar pneumonia.
         
     • Physiotherapy: designed to increase clearance by:
       
       • improving tidal ventilation (mild forced exercise, IPPB) - provides a milking action to the tracheobronchial tree which facilitates secretion clearance.
         
       • increasing the frequency of coughing (manually stimulating a cough reflex via chest wall coupage, vibration, or tracheal manipulation), or
         
       • assisting gravitational drainage of secretions (postural drainage is done in human medicine, not practical for us).
         
     • Expectorants: In principle an excellent idea; poor in reality.
       
     • Decongestants - Designed to dry up secretions, I use them rarely, only when a specific diagnosis was not obtained and the discharge persists and is a problem for the owner. Alpha agonists (pseudophed 0.1-0.4mg/kg BID-TID, PO) may help.
       
     • Some nasal conditions result in structural abnormalities (nasal polyps, nasopharyngeal webbing) leading to airflow obstruction and must be treated surgically. Destructive rhinitis in cats following chronic viral disease may be associated with significant retained secretions and benefit from simple saline administration (aerosol or nose spray).
       
     • Non-specific airway inflammation (irritation) is one problem which I commonly encounter in the Denver area and which seems to be very difficult to resolve. It is typically characterized by sneezing and a bilateral, slightly opaque to whitish nasal discharge. Diagnostics to document an underlying problem are unrewarding; biopsies show the non-specific lymphoplasmacytic rhinitis we have grown to hate. Anti-inflammatory therapy (steroids or NSAIDs) may be used, at least on a trial basis. A change in dog's environment may also help.
       
   
   
2. Maintenance of alveolar ventilation: Adequate alveolar ventilation is the principal requirement for normal blood gases, tissue oxygenation and acid-base balance. Arterial blood gas analysis is required to quantify these abnormalities. Hypoventilation (inadequate alveolar ventilation) leads to the accumulation of carbon dioxide, hypoxemia, and respiratory acidosis. Hypoventilation may be caused by 1) damage to the central nervous system (coma, drugs), 2) injury to the peripheral nerves (laryngeal/diaphragmatic paralysis), 3) damage to the respiratory pump (diaphragmatic hernia, fractured ribs, muscle fatigue), or 4) primary respiratory disease (parenchymal and airway disease).
   
   Animals with disease of the lung parenchyma often manage to maintain alveolar ventilation and eliminate carbon dioxide, but do so at an increased cost (work of breathing). Measurement of the DA-aO2 (difference in partial pressure of oxygen between the alveolus and the arterial blood) is a sensitive way to detect abnormalities in the overall efficiency of gas exchange in the lungs. Respiratory failure is often described in terms of the ABGs, specifically a PaO2 less than, or a PaCO2 greater than 60mmHg. The restoration of adequate blood gases in an animal with respiratory problems should be directed at eliminating the specific cause of the disease. Ventilator support can be used for short-term assistance in selected cases. The work of breathing is always of concern in respiratory cases - muscle fatigue is a problem in chronic cases. Theophylline has been shown to be a positive ionotrrope to the diaphragm (in dogs a 25% increase in diaphragmatic contractility has been reported with plasma theophylline in the "normal" rage) and could be reasonably considered in many cases of chronic respiratory distress.
   
   
3. Normalization of reflexes: Excessive reflexes, which are of concern, include sneezing and reverse sneezing, coughing and airway narrowing reflexes (laryngospasm and bronchospasm). These reflexes are a part of the normal pulmonary defenses and should not be suppressed unless they are excessive and/or debilitating.
   
   • Coughing is the sudden and often loud ejection of air from the lungs. It is a normal protective reflex, not commonly observed in healthy animals, but necessary in the diseased animal. During a cough, the intrapleural pressure rises dramatically and as a result the intrathoracic airways are compressed. Air is expelled through a narrowed airway and this serves to dislodge irritant materials. Cough is most effective at removing materials from the intrathoracic larger airways, but is not effective in clearing the bronchioles. Coughing is an essential clearance mechanism in lung disease and should not be suppressed unless the cough is dry (non-productive) or physically tiring to the animal, and an attempt has been made to treat a specific cause.
     
     • Antitussives - Classes of these drugs include:
       
       • Peripherally acting antitussives include mucosal anesthetics, mucolytics, demulcents, and perhaps bronchodilators.
         
       • Centrally acting antitussives include both the narcotic and the non-narcotic drugs such as morphine, codeine, hydrocodine, butorphanol and dextromethorphan.
         
     • Anti-inflammatories - airway inflammation is of concern in many respiratory distress diseases including chronic bronchitis and "feline asthma". Systemic corticosteroids are commonly recommended (e.g. prednisolone), typically starting out at 0.5-1.0mg/kg PO BID and tapering to an EOD schedule. I prefer to use oral prednisolone and educate the owners as to how and when to adjust their pet's requirements (based on the frequency of coughing). Long acting, repositol steroids (DepoMedrol) are effective but should be avoided if possible due to the inability to manage the fluctuating steroid requirements that many of these animals have. We are all familiar with the adverse effect of inducing diabetes mellitus in cats who have received these drugs.
       
   • Airway narrowing: Both laryngospasm and bronchospasm occur in response to irritation of the epithelial receptors.
     
     • Laryngospasm - Normally laryngospasm is not a clinical problem unless there is actual laryngeal manipulation or when chronic irritation leads to edema. Topical anesthetics, corticosteroids and "TLC" are the treatments/preventions.
       
     • Bronchospasm - Bronchodilators are commonly used in the treatment of canine and feline airway disease. Pulmonary function testing is used in human medicine to determine the indication for the use of these agents but these tests are not available in veterinary medicine at this time. The indications for using bronchodilators in dogs and cats are quite subjective, but include historical (chronic cough, wheezing), and physical findings (expiratory effort/abdominal push, crackles, increased tracheal sensitivity) as well as radiographic findings (bronchial pattern, diaphragmatic flattening).
       
       • Beneficial effects of bronchodilators include bronchodilation, increased mucociliary clearance, improvement in diaphragmatic contractility, decreased pulmonary artery pressure, increased CNS sensitivity to PaCO2 and stabilization of mast cells (depending on drug) to name a few. Although bronchodilation is a proven fact in man (via pulmonary function testing), evidence for drug-induced bronchodilation has been demonstrated in the horse but is sparse in the dog and cat.
         
   There are three types of bronchodilators that have been used in human and veterinary medicine: (1) the anticholinergics, (2) the beta-adrenergic agonists and (3) the methylxanthines.
   
   • Anticholinergics have unwarranted side effects that preclude long-term use. Newer anticholinergics, developed for use in human medicine, are available as self-actuated aerosol inhalers.
     
   • Beta adrenergics (agonists) - terbutaline
     (0.625 mg/cat Q12; 1.25-5 mg/dog Q8-12; and
     albuterol, 25-50 mcg/kg Q8 in dogs) have been
     recommended in treating chronic obstructive
     airway disease. Injectable terbutaline (0.01 mg/kg IV or SQ) may be used for severe bronchoconstriction (e.g. "status asthmaticus").
     
   • Methylxanthines are a family of drugs that have been used in veterinary medicine for over 80 years, and include theophylline, caffeine and theobromine. Theophylline is considered to have been one of the major drugs for the treatment of asthma and other chronic obstructive pulmonary diseases in man. Theophylline has been used extensively for the treatment of human asthma and other reversible airway diseases.
     
   Beneficial effects on the respiratory system include bronchodilation (via smooth muscle relaxation), enhanced mucociliary clearance, stimulation of the respiratory center and an increased sensitivity to PaCO2, increased diaphragmatic contractility and stabilization of mast cells. There are species differences in susceptibility to theophylline toxicities, and there may also be a difference within the same species depending on the route of administration (e.g. IV vs. oral) and the duration of therapy (acute vs. chronic).
   

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