February 2008 Small Animal Respiratory Medicine Brendan C. McKiernan, DVM, Diplomate ACVIM (SA Internal Medicine) Southern Oregon Veterinary Specialty Center Pulmonary Physiology The main function of the respiratory system is obviously gas exchange, yet this system also participates in thermoregulation, the metabolism of endogenous and exogenous chemicals and mediators, and protection of the animal against inhaled substances. Oxygen is brought from the ambient air to the alveoli where it diffuses across the capillary membrane, into the blood and then is distributed to the tissues throughout the body as carbon dioxide moves in the opposite direction. The delivery of O2 into, and the transport of CO2 out of, the body varies with the animal's metabolism but it must be performed with minimal energy cost to the animal. The energy expended to breathe is referred to as the work of breathing (WB). Protection against inhaled particulates and gases is provided by a variety of pulmonary defense mechanisms. Changes in the function of these mechanisms can be caused by environmental as well as microbiologic agents and may lead to respiratory disease, which reduces the efficiency of gas exchanges and eventually the animal's performance. Our treatments can also impact these defense mechanisms and we must be aware of these interactions when initiating any treatment. Owners usually seek veterinary assistance because of changes in their animal's performance or behavior (typically the ability to exercise has decreased, the animal is showing signs of respiratory distress at rest, is making an unusual sound breathing or it is coughing/sneezing excessively). The clinical signs of respiratory disease (what an owner complains about, what you detect on examination) represent the animal's expression of the functional changes that have resulted secondary to the particular disease. Dys-function of one portion of the respiratory system leads directly to many of the presenting signs we commonly recognize in our patients…a simple example would be a coughing after eating/drinking or a change in an animal's voice pointing us to laryngeal disease and the need for a more thorough laryngeal evaluation. Most organs have considerable reserve before signs become apparent, and this is also true in the lung, where there must be considerable obstruction of small airways or flooding of alveoli before clinical signs are apparent. As there are few quantitative pulmonary function tests in veterinary medicine, the objective evaluation of respiratory disease may be difficult (more on this later when diagnostics are discussed). Understanding the four classical components of respiratory physiology will help recognize these functional changes and the pathology that might have caused them. 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. Increases in PaCO2 (hypercapnea) are uncommon in awake dogs due to their extensive collateral ventilation, if encountered this is an ominous clinical finding in my experience. Hypercapnea is also one of the main clinical indicators in the decision process of whether to place an animal on a ventilator. 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, another would be thoracic inlet "retraction" in an animal with upper airway obstruction. Another example in the horse is "heaves" where there is small airway obstruction and marked expiratory effort - we see this as well in dogs and cats with extensive small airway disease. 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. During inhalation, the respiratory muscles must work to overcome lung elasticity and frictional resistance to air flow in the airways. (Tissue and gas inertia is minimal - it 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; ? indicates the difference or change in the particular parameter, for instance ?in VT or tidal volume for a given ?in P or pressure). 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, fibrosis and pulmonary edema, stiffen the lung and cause a decrease in lung compliance. An animal with low lung compliance has difficulty breathing because the lung is more difficult to stretch/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 resistance of the air passages may be increased: by the presence of obstructions, such as mucus or masses, by the contraction of airway smooth muscle as a result of allergic responses or alterations in autonomic regulation, or as a result of edema in the walls of the airways, or by a combination of one or more of these. Airway resistance can be measured clinically in the anesthetized animal (RL = ?P/?V; its units are pressure (P)/flow (V), 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 developing and hopefully will 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 (V) to perfusion (Q) (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 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 exudate 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; when I do encounter an increase in CO2 in dogs it is a grave prediction for survival. 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 probably 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 clinical 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. Equal pressure point. As mentioned earlier, exhalation is normally a passive process, occurring as a result of the elastic recoil of the lungs and rib cage that were "stretched" (by the work of breathing) during inspiration. This recoil pressure results in increase in the transmural pressure (relative to atmospheric) and airflows out. In this (normal) situation the pressure within the airways exceeds intrapleural pressure and there is no dynamic collapse of the airways. If there is airway obstruction (bronchospasm, edema, secretions etc.) then airway resistance will increase. The animal may attempt to facilitate exhalation by increasing intrapleural pressure via active abdominal contraction of (mostly) the external abdominal oblique muscles. As intrapleural pressure increases, and as the pressure within the airways begins to decrease (due to frictional loss) the point at which these pressures are equal (the equal pressure point) begins to move towards the alveolus. The normal EEP is near the thoracic inlet. The increasing the airway further and if there is any structural weakening airway collapse may occur. Additional intrapleural pressure (active abdominal contraction/effort) begins to dynamically narrow the airways and does not result in greater expiratory flow - exhalation is said to be "flow limited". Careful observation and examination of an animal (performed while breathing at rest) may detect this increased expiratory effort (by visual inspection or by manual palpation), and a diagnosis or airway obstruction made. This is a very important and powerful clinical technique and diagnostic tool. Recognizing Your Patient's Respiratory Disease: Comments on Hx, Px, and Pulmonary Function Testing and Airway Endoscopy I specifically avoided the use of the term dyspnea in these talks - because veterinarians can (and should) provide more specific terms when describing an animal's respiratory condition. Dyspnea simply means difficulty breathing and in human medicine is noted when the patient tells the physician that s/he is having trouble/difficulty breathing. It does not give the physician specific information about the cause of the respiratory distress and for this reason I prefer to use specific terms which might provide insight into the underlying etiology. In veterinary medicine we (the veterinary physician) observe specific characteristics that we equate to difficulty breathing and these characteristics should be explicitly stated as they are the terms that relay the detailed information about the patient's condition/problem. Terms and characteristics which I believe are more informative include those associated with: 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 An animal that is being referred to you for "dyspnea" is much better understood with a description of "respiratory distress associated with a marked inspiratory effort and loud wheezing". I encourage you to use these descriptors rather than the more ambiguous global term for respiratory distress. The basic understanding of respiratory physiology is very helpful (critical?) in the recognition of an animal suffering from respiratory disease. It is the deviation from normal function or dysfunction (e.g. coughing after drinking, increased expiratory/abdominal effort, exercise intolerance etc.) that alerts an owner that there is a problem. It is the veterinarian's ability to collate and interpret this information (the history) with a careful physical examination and a problem solving approach, which will enable accurate and timely diagnostics and treatment - especially when respiratory distress exists and everyone has been placed in an emotionally charged and stressful situation. 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). Taking time to talk with the owner and to determine the presence of new breathing sounds, reflexes associated with specific activities, the order or sequence of respiratory events and other characteristics is very worth-while and may be helpful in determining and/or localizing the primary problem. Examples include: New sounds made while sleeping - often associated with nasopharyngeal obstruction Gagging or retching after eating or drinking - possibly associated with aspiration due to laryngeal or pharyngeal dysfunction Gagging or retching while sleeping - as above or possible "GER" or meaesophagus Coughing then gagging/retching - think lower airway disease Gagging/retching then coughing - think aspiration due to laryngeal/pharyngeal dysfunction. 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. The table below 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. The table on the next page provides a summary of respiratory sounds and reflexes, which might help in assessing these patients. 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 decr: sounds dorsally ("distant") N lung sounds ventrally incr: resonance dorsally ("hollow") N resonance ventrally Hydrothorax N to incr: lung sounds dorsally decr: or absent lung sounds ventrally N resonance dorsally decr: resonance ventrally ("solid") Pneumonia Crackles, occ. wheeze decr: or absent lung sounds ventrally decr: resonance if lobe consolidated incr: tracheal sensitivity, moist cough Bronchitis, "Asthma" Crackles, occ. wheeze Cats - crackles may only be noted post tussively N to incr: resonance dorsally Palpable expiratory push/incr: effort incr: tracheal sensitivity Pulmonary edema Fine crackles, esp. ventrally Often note cardiac abnormalities Unknown/no change Fibrosis Fine crackles, prominent dorsally incr: tracheal sensitivity Hernia incr: BV lung sounds N to incr: heart sounds on N side decr: or absent lung/heart sounds on the side of the hernia decr: resonance on hernia side incr: resonance if stomach is herniated and gas filled Mass Small - no change Large - shift in heart sound location & absence of lung sounds Small - no change Large - decr: resonance ("solid") over the lesion Lung consolidation incr: BV to bronchial lung sounds plus/minus: crackles, sounds absent if bronchus filled decr: resonance over the affected lung lobe We use organ specific function testing on a routine basis - echocardiography for cardiac function and bile acids for liver function are 2 such examples. Although pulmonary function tests (PFTs) in human medicine have reached into the physician's office and are routinely done, similar tests are not commonly done on animals and are only available at a few veterinary teaching hospitals at the time being. Examples of such tests include: Tidal breathing flow volume loops (TBFVL) - these have proven capable of detecting significant upper and lower airway obstructive disease in dogs and cats. The newer ventilators with their graphical capabilities may be able to use this technique. The advantage is that these TBFVLs can be performed on the awake patient with a face mask. Measurements of airway resistance and lung compliance are not difficult to do but require significant equipment investment and a short but general anesthesia. Plethysmography is an old and proven PFT technique in human medicine but with the application of techniques that have been used in rodents previously (whole body and double chamber boxes) researchers at Tufts University have begun to adapt these to cats and dogs. Although years away from clinical availability, I hope this will eventually make PFTs standard in small animal specialty practice. One PFT that is available to all of us is the measurement of arterial blood gases (ABGs) the calculation of A-a gradients. Samples are easily obtained and can be run on small portable "point-of-care" units that have become available (e.g. I-Stat, IRMA) or placed in an ice bath and transported to a human hospital for analysis. Iced samples are stable for 4 or more hours - making hospital access feasible for nearly everyone. ABGs also provide important information on the animal's acid-base status and can be used in diabetic ketoacidosis, renal failure, ethylene glycol toxicosis and other metabolic diseases. Heparinized samples (1-3ml) may be collected from the dorsal pedal or femoral artery. Blood samples should be corked, stored on ice and transported to a laboratory/hospital. Classically the values obtained in clinically healthy dogs and cats (depending on elevation - they can be different at altitude) for O2, CO2 and pH are approximately 90-95mmHg, 32-36mmHg and 7.35-7.45 respectively. The overall efficiency of gas exchange in the lungs may be estimated by calculating the difference in partial pressure between alveolar and arterial O2 values (DA-aO2); in theory a perfect lung would have no difference since all O2 reaching the alveolus would be transferred to the arterial system. In reality there is a small difference (normally <15mmHg). The DA-aO2 may be calculated by using a value of 150mmHg (an approximation of the partial pressure of alveolar oxygen at sea level) in this formula: DA-aO2 = [150mmHg - (PaCO2 * 1.1)] - PaO2 Serial blood gas analyses are a sensitive method of evaluating whether there has been any progression or resolution of a given pulmonary disease, I commonly used them to monitor the progression of lung contusion cases as well as chronic bronchitic and pneumonic animals. Radiographic and clinical changes will typically lag behind ABG changes, I use them on a Q 24 hr basis to monitor changes in pulmonary function in many of my patients. Interpretation of Respiratory Sounds and Reflexes NB: Good auscultation depends on using a comfortable stethoscope, a quiet room listening area and maximizing tidal volume to generate airflow (which generates sound). Techniques useful for maximizing airflow include forced breath holding, airflow restriction (closure of 1 nostril), inducing a cough (listen on large INSP effort) and possibly rebreathing (CO2 effect) Sound/Reflex Bronchial sounds (N) Location heard / Timing Heard over the trachea and large airways in health; abnormal when heard elsewhere Characteristics Harsh, "wind blowing" sound; EXP is louder and longer than INSP Interpretation / Example Turbulent airflow; responsible for all sound generation in health. Indicates consolidation if heard in peripheral lung regions; abnormal when heard over periphery Sound/Reflex Vesicular sounds (N) Location heard / Timing Heard over peripheral airways Characteristics "Rustling of leaves" sound; INSP is slightly louder and longer than EXP Interpretation / Example Indicates normal air filled lung between stethoscope and sound generation (turbulent airflow) site Sound/Reflex Bronchovesicular sounds (N) Location heard / Timing Heard in intermediate lung regions in health Characteristics EXP changing, prolongs and becomes louder Interpretation / Example Fluid/tissue in lungs transmits EXP sound perception better. Indicates early lung disease Sound/Reflex Sneeze Location heard / Timing Forceful EXP nasal effort Characteristics Head thrown forward/down Interpretation / Example Irritation to nasal mucosa Sound/Reflex Reverse sneeze Location heard / Timing Forceful INSP nasal effort Characteristics Head often pulled back, mouth closed Interpretation / Example Irritation to dorsal nasopharyngeal mucosa Sound/Reflex Stertor / Snoring Location heard / Timing Upper airway noise; mainly on INSP or sometimes also on EXP Characteristics Congested or fluttering noise Interpretation / Example Sound produced as tissue or secretions transiently obstruct airflow; Elongated soft palate is example Sound/Reflex Stridor Location heard / Timing Heard over the upper airway (larynx and cervical trachea); an INSP sound Characteristics A whine or high pitch INSP wheeze; localizes (is loudest) over larynx Interpretation / Example Indicates airway narrowing/stricture; often associated with LP or mass Sound/Reflex Laryngeal brake Location heard / Timing Heard over the upper airway (larynx and cervical trachea); an EXP sound Characteristics A whine or high pitch EXP wheeze which localizes (is loudest) over larynx; a voluntary (?) glottic closure Interpretation / Example Animal's attempt to "self-PEEP" by retarding EXP flow and maintaining airway pressure/patency. Indicates diffuse and severe interstitial or alveolar DZ Sound/Reflex Crackles Location heard / Timing Heard mainly on INSP and over chest, may be early, late or pan-inspiratory (previous term = rales) Characteristics Discontinuous (shorter, ? 250msec) sounds; snap-crackle-pop like; describe as fine, medium or coarse Interpretation / Example Caused by airways snapping open; indicates airway closure, often due to fluid in/around them; pulmonary edema, pneumonia, fibrosis Sound/Reflex Wheeze Location heard / Timing Mainly on EXP and over chest, (previous term = rhonchi) Characteristics Continuous (longer, ? 250msec) sounds; like a musical note; describe as either high or low pitched Interpretation / Example Caused by airflow through a narrowed opening; examples include narrowing due to structure, compression, FB, tumor, hilar lymphadenopathy Sound/Reflex Cough Location heard / Timing Loudest over anterior chest & neck, audible in room, EXP sound Characteristics Forceful EXP effort, described as dry (non-productive) or moist (productive) Interpretation / Example Indicates tracheobronchial mucosal irritation; "productive" refers to amount of secretions produced Sound/Reflex Gagging / retching Location heard / Timing Audible in room; EXP sound Characteristics EXP event; head and neck extended, mouth open; like throat clearing Interpretation / Example Indicates clearance of mucus/secretions through larynx; often misinterpreted as vomiting or something being caught in the animal's throat by owners Sound/Reflex End expiratory snap or click Location heard / Timing Heard over chest, can also be felt with a hand on the chest wall as the animal coughs; indicator of airway collapse Characteristics An end-EXP snapping together of the walls of the large intrathoracic airways (trachea and mainstem bronchi) Interpretation / Example Pressure generated during cough exceeds ability of rigid cartilage support to keep airway patency and collapse occurs; Indicates intrathoracic (trachea, mainstem bronchi) collapse or malacia (softening) Sound/Reflex Goose honk Location heard / Timing Audible in room, usually loudest at thoracic inlet Characteristics A kazoo like, honking more continuous sound involving large caliber airways Interpretation / Example Associated with lengthy flattened airways (e.g. both intrathoracic & extrathoracic tracheal collapse) Sound/Reflex Pleural friction rub Location heard / Timing Heard over region of pleural inflammation, both on INSP & EXP at same point of respiratory cycle Characteristics Creaking or grating sound, high or low pitched and may be very localized Interpretation / Example Roughened pleural surfaces moving in contact against each other (must be in contact and not yet adhered) Key: INSP = inspiration or inspiratory; EXP = expiration or expiratory; LP = laryngeal paralysis; DZ = disease; (N) = normal lung sound Airway Endoscopy Performed by an experienced veterinarian, respiratory endoscopy 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, 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. Failure to perform a posterior or caudal rhinoscopy (due to a lack of flexible equipment or experience) is inexcusable. Examining only the anterior portion of the nasal cavities is performing only "half" of a full rhinoscopic procedure. By placing an animal under general anesthesia and the client under a financial burden when referral services are usually readily available is doing a disservice to both. Another concern that I have is when a detailed written description and photographic documentation is not made available to the client and especially the referring veterinarian. Always ask for - and expect - these from your specialist. 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 may be 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 (often seen in brachycephalics). Miscellaneous changes: parasites (mites), drainage from eustachian tubes, NP wall abscess. Once the NP has been examined, the mouth gags can be removed and anterior rhinoscopy performed. The endoscope should initially be directed dorsally and medially (to bypass the bulbous alar cartilage) and then straightened out and advanced into the nasal cavity (parallel to the nasal septum). This will ensure that the scope enters the common meatus and minimizes the potential of trauma to the tissues at the entrance of the nasal cavity. With a small scope and a larger sized animal, it is possible to traverse the length of the nasal cavity and enter into the NP. Anterior rhinoscopy can be made very simple if the size of the air channels (the meatii) or simply the amount of visible space is carefully evaluated. The amount of visible space can only be: 1) normal; 2) increased; or 3) decreased. As in the NP, the anterior respiratory mucosa should be pink, not friable with minimal secretions present. The following structures may be visible during anterior rhinoscopy: 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. Typical lesions or abnormalities that may be encountered during anterior rhinoscopy include: 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. Cultures from the nasal cavity, although frequently positive, are not recommended as they are thought to be secondary to another (primary) problem and usually clear up with minimal antibacterial treatment if this underlying primary problem is resolved (e.g., tooth root abscess, foreign body). Pinch biopsy forceps may be passed through the endoscope (rigid and flexible) or along side the scope to biopsy a lesion in question using direct visual guidance. Care should be taken to obtain multiple biopsies and to get samples deep within the tissue (to avoid sampling the necrotic edge of a lesion). In the JAVMA study by Lent and Hawkins 83 of 94 cases (88.3%) had a definitive diagnosis made using gross rhinoscopy and rhinoscopic assisted biopsy. Touch imprints for cytology can be reviewed while awaiting histopathology results. Hydropulsion using sterile saline can not only obtain large amounts of tissue for biopsy but also relieve nasal obstruction in the majority of cases. Laryngoscopy is the gold standard for assessing laryngeal disease as it allows for the evaluation of both anatomic lesions as well as disorders of intrinsic laryngeal function/motion. Although routine equipment may be used (tongue depressor, light source), I firmly believe that using an endoscope allows for a more detailed evaluation of the larynx as well as allowing you to look into the NP and down into the trachea for any co-existing problems. Prior to anesthetizing the animal, be sure to evaluate for any loss of sensory function (gag reflex) in the oropharynx as this may be associated with an increased risk of future aspiration (especially important if laryngeal surgery is anticipated). Classically, a light plane of anesthesia (ideally so the animal is still gagging) has been recommended when evaluating the larynx. Following assessment of the laryngeal anatomy you should routinely use a respiratory stimulant (doxapram HC1, Dopram-V, 2.2 mg/kg BW IV) to overcome concerns about anesthetic depth and to maximize intrinsic laryngeal motion; the onset is fast, usually within 15-30 sec, with a duration of 2-3 minutes. The use of Dopram has allowed for a deeper plane of anesthesia initially and a better assessment of subtle anatomical abnormalities while still being able to assess intrinsic laryngeal function. Typical lesions that may be observed in the pharynx/larynx during laryngoscopy include: Elonagted 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! Resection of these is recommended only in the more severe cases - and after correction of the primary cause for the eversion. Laryngeal paralysis: motor loss may be unilateral or bilateral; may be subtle! Laryngeal sensory loss: a gagging/retching history may alert you to this diagnosis. The presence of secretions in the glottic lumen and proximal trachea, a poor gag reflex with normal Dopram stimulated intrinsic motion is highly suggestive of this disorder. Laryngeal collapse: a life threatening complication of chronic upper airway obstruction and a reason to correct these dogs' airways at an early age. Laryngeal neoplasia: lymphoma, squamous cell carcinoma are the most common types. Epiglottic entrapment: secondary to other inspiratory problems; may be intermittent. Biopsies should be taken under direct visualization. Edema may result from vigorous laryngeal manipulation and should be anticipated as well as treated with corticosteroids following completion of the procedure. Severely obstructive lesions may require the placement of a temporary tracheostomy to maintain a patent airway while ancillary measures are taken to treat the obstruction (corticosteroids for edema, laser resection of mass lesions, or perhaps definitive surgery for laryngeal paralysis). Problems that I have with some laryngoscopy procedures are as follows: Not using Dopram to stimulate intrinsic laryngeal motion Not being prepared to deal with severe respiratory crises once an animal is anesthetized: Cats - be prepared for a very small airway in suspected laryngeal disease cats - I like to have an 8 or 10Fr sterile male urinary catheter in addition to the smallest ET tube and stylet to intubate if needed Brachycephalic animals - your surgeon should be ready and available to correct the abnormalities identified while under this same anesthesia following your endoscopic evaluation. Placing these animals under general anesthesia as we all know involves some risk, having to do it twice (waking them up only to have someone else repeat the procedure) is a disservice again to both the animal and to the client. Not being prepared to look upstream (into the NP) as well as downstream (into the trachea) when suspected laryngeal lesions are suspected but not found on examination. Bronchoscopy has been an integral part of respiratory practice in veterinary medicine since at least the early 1970s. There is no question that bronchoscopy (including bronchoalveolar lavage for cytology and culture) is the gold standard for the diagnosis of lower respiratory tract diseases in small animals. Bronchoscopy may be used for diagnostic, therapeutic and prognostic purposes. Diagnostic bronchoscopy obtains visual information concerning the airways (e.g., compression, dynamic collapse, dilation) as well as samples (cytology, culture, and occasionally biopsy) to help establish a specific etiologic diagnosis. General anesthesia is necessary to control airway reflexes during bronchoscopy, thereby preventing trauma to the airways, and at the same time protecting the endoscope throughout the procedure. The ideal anesthetic should provide good patient restraint, have minimal cardiorespiratory effects, be either reversible or of short duration and allow for a smooth recovery period. The availability of newer, short acting and/or reversible injectable anesthetics has allowed bronchoscopy to be performed on patients with minimal concern. My current anesthetic protocol utilizes either atropine or glycopyrolate, with either acepromazine or butorphanol for premedication; valium and propofol are used for the anesthetic procedure. I prefer not to intubate my patients until the recovery phase of the procedure. I do provide supplemental oxygen via a catheter placed into the lower trachea or through the biopsy channel of the endoscope. This form of anesthesia is very beneficial because it not only provides adequate anesthesia for the procedure, but also allows for rapid patient recovery, an important factor in geriatric patients. The bronchoscopist must have a good understanding of normal endoscopic lung anatomy (Figure to the right) if she/he is to recognize subtle abnormalities and diseases. The differentiation (recognition) of normal from what is abnormal is a subjective one. Experience and practice greatly improve the clinician's ability to detect lesions at an early stage. I routinely examine the larynx (anatomy and intrinsic function/motion if possible), the cervical and intrathoracic trachea and then the carina before sequentially evaluating all the lobar and finally as many segmental and/or sub-segmental bronchi as possible (the latter varies with patient and endoscope size). Changes in gross anatomy, fixed and dynamic lumen size, abnormalities in airway shape, mucosal/submucosal characteristics, and the presence of secretions should be noted. Experience and practice will improve an endoscopist's ability to detect early lesions. Samples obtained (cytology, culture, and biopsy) are then relied upon to establish a specific diagnosis. Again, as with all endoscopy procedures, a detailed written description and photographic documentation should be made available to the client and especially to the referring veterinarian. Always ask for - and expect - a complete bronchoscopic report from your specialist. With a bronchoscopy the description should include an assessment of the upper airway (larynx, trachea) as well as the intrathoracic airways. The location of mucosal and airway obstructive lesions (fixed or dynamic) as well as the sites of sample collection should be described. Bronchoalveolar lavage (BAL) is essentially a washing of the distal airways and alveoli. Material obtained from this area is thought to be representative of the distal airways, alveoli, and the intersitium of the lungs. The bronchoscope (or catheter) is advanced distally and gently wedged in a selected bronchus and then 10-20ml of sterile saline is flushed into the airways and immediately aspirated using gentle syringe suction. Ideally I try to use two aliquots per site and two sites per animal (smaller amounts in cats). The sites are evaluated individually with total cell counts and a cytospin for differential cell counts but I combine the fluid for a quantitated BAL culture. Difficulties with the procedure (poor returns) may be expected when a proportionately large endoscope prevents wedging in a smaller bronchus, or when the airways are malacic. In the former situation, the fluid is dispersed into too large an area to be easily retrieved, and in the latter, the airways collapse (even with gentle suction), preventing the return of any significant volume of the infusate. The predominant cell in all species should be the alveolar macrophage (70+%), with approximately 3-8% of all other cell types (except the cat which may have up to 20%+ eosinophils and still be considered healthy). Many pathologists interpret this BAL cell differential as "granulomatous" in nature but that is incorrect! Macrophages are the normal cell to be seen on a good BAL. Cultures from the lower airways are helpful in establishing a specific diagnosis and selecting an appropriate antibiotic based on sensitivity results. Gram stains help in interpreting culture results and provide early insight into correct antibiotic selection. Contamination resulting from the mixing of upper respiratory tract secretions with lower airway samples must obviously be avoided. (finding squamous epithelium and/or the large bacterium Simonsiella spp. both are indicative of oral cavity contamination). Peeters recently showed that quantitated BAL cultures are important in the differentiation of airway colonization from actual infection. Mycoplasma cultures are possible using specialized transport media (e.g., Amies media) and overnight shipment to selected laboratories. Microbiological results must always be interpreted in light of the cytology obtained from the same site. The Brachycephalic Airway Syndrome Veterinarians must appreciate and anticipate the breadth and potential severity of problems that may present in brachycephalic dogs and even cats. All brachycephalic breeds (e.g. Bulldogs, Pugs, Bostons etc.) can be assumed to have some degree of airway obstruction due to their head (and possible tracheal) confirmation. 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 (preferably at the time they are neutered) to prevent the onset of irreversible airway changes. Significant abnormalities may exist even in the very young and relatively asymptomatic animal. The brachycephalic airway syndrome (BAS) is a well known problem in small animal medicine. There are multiple possible abnormalities these animals may suffer with but early diagnosis and surgical intervention may allow for a nearly normal life. Endoscopy and not simple oral examination is required for complete assessment of a brachycephalic animal's airways and is strongly recommended in order to fully appreciate all of the BAS components. Chest radiographs are needed to document tracheal hypoplasia; OFA is now helping to collate this data, their directions and submission forms are available at http://www.offa.org/trachhypoappbw.pdf. Early intervention is absolutely critical to prevent progression of these obstructive conditions; endoscopic evaluation and surgery should be done at an early age (when neutered for instance). Airway endoscopy is required to evaluate for all seven (7!) potential brachycephalic airway syndrome components. A thorough physical examination should be done prior to general anesthesia and endoscopy. Some of these are well known and others less well appreciated, starting at the nose and going caudally the brachycephalic airway syndrome list includes: Stenotic nares Nasopharyngeal turbinates Elongated soft palate Laryngeal / pharyngeal edema Everted laryngeal saccules Laryngeal collapse - doxapram HCl (2.2mg/kg IV) is used to increase ventilatory effort and document subtle dynamic laryngeal collapse lesions. Hypoplastic trachea. Obese animals will benefit from weight loss prior to anesthesia and any airway surgery - some may even avoid the need for surgery if weight loss is sufficient! Over 50% of total airway resistance is normally partitioned to be in the upper airways…at least in normal dogs and cats! Although unmeasured, a significantly greater percentage can be expected in brachycephalic animals. Structural narrowing (stenotic nares, tracheal hypoplasia), mucosal edema/swelling, dynamic airway collapse (laryngeal collapse) all greatly increase to the work of breathing in these animals, and eventually may progress to respiratory failure. Although not all of the list above can be surgically corrected, small increases or improvement in airway caliber can have significant positive effects on airway resistance as shown by Poiseuille's law of resistance, where resistance (R) = 8 n l / ? r4. Looking at this formula it becomes apparent that small changes in the radius of an airway will have major changes on the resistance. Decreasing the radius of an airway by half will result in a 16 fold increase in the resistance. As a result any improvement (even if all can not be corrected) will reduce the work of breathing and be of benefit to the animal. Treatment: I normally talk about a combination of choices in the treatment of the brachycephalic airway problems. Medical, dietary and surgical options can be made. Medical therapy is aimed at reducing airway inflammation, mucosal edema and airway obstruction. Management is included in and is a big part of this approach as well. Corticosteroids are advisable prior and following airway surgery to minimize mucosal edema. Likewise, avoiding excessive excitement and activity immediately post-surgery is advisable to minimize the chance for inducing additional mucosal edema. Sedation of brachycephalic animals should be done cautiously as it will often make these animals worse as oropharyngeal tissues relax and further narrow the airways. My preference is to avoid acepromazine (which works very well in laryngeal paralysis cases) in favor of a light dose of a narcotic. Obese animals are often more severely affected; weight loss should be a major goal of medical therapy on these cases. I feel very strongly that surgical intervention should be performed at the time of endoscopy to avoid the risks as well as the costs of multiple anesthesia episodes in these patients. Not all conditions are surgically treatable, none-the-less significant airway improvement may be achieved with one or more of these procedures. The CO2 laser is my preferred method of correcting these problems. Specific surgical procedures include: Stenotic nares - removal of a portion of the alar fold deep into the nostril (no sutures), depigmentation is common initially but the tissue will re-pigment over a 6-8 week period. Nasopharyngeal turbinates - laser removal of these turbinates is being done but it not routinely possible at this time (you can send your cases to Leipzig Germany). NP turbinates should however be documented and the owner made aware that this portion of the overall airway obstructive disease will not be corrected. The photo to the right is of the nasopharynx showing turbinates growing form the choanae and obstructing a significant portion of the airway. Elongated soft palate - the tip of the palate should just overlap the epiglottis. Care must be taken to not remove too much tissue or the palate will not be able to cover and protect the nasopharynx properly and material will get into the nasal cavity. Remember to allow for some tissue retraction once tissue swelling subsides. Everted laryngeal saccules - these are secondary to another primary problem, and if these are mild, only edematous and not yet fibrotic they can often be left untouched after dealing with the primary problem (elongated soft palate for instance). Laryngeal collapse - dynamic collapse of the cuneiform processes of the arytenoids is an extremely severe, end stage condition. Partial arytenoidectomy, a modification of a laryngeal tie-back procedure or a permanent tracheostomy are the only treatment options. Tracheal hypoplasia should be identified and the owner informed that although no surgery is available to correct it at this time, treatment of other components will however help improve the animal's overall airway resistance and breathing. Enlarged tonsils are often encountered secondary to chronic irritation and should be removed if they are felt to contribute to airway obstruction when examined. Tracheostomy should be avoided if at all possible as the level of care required as well as the potential for complications may increase significantly. Aftercare is critical for these patients. Careful observation by experienced nursing and professional staff is required for optimal success. 24/7 care is mandatory. The major prognostic indicators in these cases are: Chronicity - older animals with years of "micro-trauma" and mucosal edema (which often progresses to proliferative and fibrotic changes) are much more difficult to manage and treat. Obesity is a significant negative finding in these animals. Weight management must be stressed and if possible achieved prior to scheduling anesthesia and endoscopy/surgery. Chronic Bronchitis / Tracheal Collapse When I was sitting in class last century (!), it was questioned whether there was such a thing as naturally occurring chronic bronchitis (CB) in dogs, but now it is recognized as a common disease of varying degrees of morbidity. CB is the term initially applied by Wheeldon in 1974 to describe the pathology in dogs associated when chronic coughing occurred for two or more consecutive months during the proceeding year and which is not attributable to another cause (e.g. neoplasia, CHF). It also implies a non-reversible (indeed it is normally a slowly progressive) condition. Both dogs and cats develop CB, and the 2 month time course has been generally extended to apply to cats as well as to dogs. History. Coughing is the hallmark of lower airway disease. Tracheobronchitis (acute and chronic) typically has the dry, hacking, non-productive cough; post-tussive gagging is common and owners often misinterpret this as "vomiting". Pneumonia is associated with the moist, productive cough. Another major difference is that tracheobronchial disease usually has few if any systemic signs (lethargy, anorexia, fever, depression). Coughing may occur at any time during the day but is common following exertion (exercise intolerance), at night (nocturnal coughing) as secretions accumulate, or when if the trachea is irritated - for instance with "leash pulling". Wheezing, breathing with an expiratory effort, exercise intolerance, cyanosis and even syncope may be noted. Physical examination. With pre-existing tracheal irritation/inflammation, any additional irritation (by palpation or manipulation) of the trachea normally results in coughing; this "increased tracheal sensitivity" is a non-specific indicator of existing inflammation or irritation. The large inspiration required to generate a cough can be used to listen for crackles as they tend to occur on inspiration. An expiratory abdominal push (increased effort during quiet/resting breathing) and/or end-expiratory wheezing are characteristics encountered in patients with severe small airway disease. Most CB animals are bright, alert and afebrile. Bronchovesicular lung sounds and end-inspiratory crackles are commonly heard. Wheezing may be noted, especially when airflow initially moves through airways obstructed by secretions. An end-expiratory "snap" may be heard in dogs with decreased cartilage rigidity, as the increased intrathoracic pressure generated with an active expiratory effort often collapses central airways (normal airways will narrow but do not collapse) and the airway walls literally "snap" together. Active abdominal (external abdominal oblique muscle contraction) during quiet breathing is an excellent indicator of small airway disease. See Table 3 for a complete summary of respiratory sounds and reflexes. In cats with CB, lung sounds may be normal at rest but (post-tussive) crackles become prominent after coughing is induced as secretions are loosened. Tracheal sensitivity should be evaluated in all patients. Tachypnea is a more frequent primary complaint in cats than in dogs with CB. A careful cardiac examination is important in order to differentiate heart disease from CB; in many cases this can be difficult to do. Murmurs secondary to valvular insufficiency are common in older, small breed dogs (but not in cats); these cases must not be misinterpreted as being in CHF. A simple but fairly accurate method of determining whether CHF or CB is present in the dog (less so in the cat) is to examine the resting heart rate; CHF is associated with an elevated heart rate while CB usually results in a normal to slower heart rate due to vagal stimulation. Differential diagnoses for an animal presented in respiratory distress and with a history of coughing, crackles, exercise intolerance and a murmur include: bronchitis, pneumonia, bronchiectasis, aspiration secondary to laryngeal dysfunction, allergic lung disease, compression on a mainstem bronchus (LAE, hilar lymphadenopathy), foreign bodies, pulmonary hypertension, HW or other cardiopulmonary parasitic disease and primary cardiac problems. Diagnostic tests for patients with suspected lower airway disease/respiratory distress include: ABGs - These are easy to do and provide the only functional assessment of overall lung function available in practice. Parasite evaluation - fecal exam(s) including Baerman, 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 previous discussion). 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, pulmonary fibrosis for instance requires a tissue sample to confirm this diagnosis. Thoracoscopy is beginning to be used to obtain lung biopsies for histopathologic confirmation of the lung problem. Examples of lower airway problems that may lead to an animal's respiratory distress include: 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 many diseases including chronic bronchitis. 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, specifically those proven (based on scoping) to only involve the cervical trachea are candidates for this surgery. This procedure in the hands of an experienced surgeon is an excellent treatment option. Recently intraluminal 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). Stents can be placed under fluoroscopic, radiographic and bronchoscopic guidance. Case selection is critical, owner education is mandatory as they must understand the limitations and potential complications of this procedure. A new study showed that functional (bile acids) as well as biochemical (ALT and ALP) changes would improve following successful surgical treatment of tracheal collapse cases. Severe dental disease should be treated aggressively to minimize secondary bacterial showering of the lower airways in these and in CB patients. 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 a lobectomy may be required to fully resolve the pneumonia. Respiratory Therapy / Aerosol Therapy There are three general goals of respiratory therapeutics that I typically talk about: 1) the control of secretions - treating the underlying problem, 2) the maintenance of alveolar ventilation (ensuring adequate tissue oxygenation) and 3) the normalization of pulmonary (excessive) reflexes. 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. Culture and cytology are the main (only?) methods in determining when antibiotics or corticosteroids are definitely 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. 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). 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. For upper airway diseases antibiotics with a good Gm positive spectrum are best. The route of administration is a concern for lower airway diseases. If the infection is thought to be tracheobronchial (intra-luminal) then concern about antibiotic penetration into the lumen of the airways exists (i.e. does the antibiotic actually penetrate into bronchial secretions). Aerosolized antibiotics may be helpful in selected cases of infectious tracheobronchitis (specifically those due to Bordetella infections). Corticosteroids - These drugs constitute an important treatment option for allergic diseases as well as in chronic bronchial disease to decrease cellular infiltration. Oral short acting steroids (prednisolone/prednisone) are preferred for ease of dosage adjustments which is import in chronic conditions. Inhaled steroids are also being used more frequently. 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: The goal is to either deliver drugs into the lower airways or to loosen accumulated secretions. It is typically used in conjunction with physiotherapy. Efficacy is debatable. Antibiotics should NOT be aerosolized unless it is directly via a facemask and then are indicated only for airway (not primary parenchymal) infections. Ensure adequate systemic hydration first. Small volume (medicine) aerosol therapy utilizes jet or ultrasonic nebulizers; they produce particles of between 0.5-3 micra in size which are best for deposition in the lower respiratory tract, again only when delivered via a face mask (not into a cage. Metered dose inhalers (MDIs) are the current "rage" for delivering drugs via face mask into the lower airways - see the discussion at the end of this section. Large volume aerosol therapy has seemed beneficial in many cases of lobar pneumonia. This is done using bland aerosol therapy (sterile saline) in an enclosed cage with a larger ultrasonic unit; aerosol times are ~ 30-45 minutes 2-4 x/day and should always be followed by physiotherapy. 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 very practical for us). Expectorants: In principle an excellent idea; poor in reality. Recently interest has been shown (on TV!) in a mucolytic for people - Mucinex® - but there is no information (even testimonials) about using it in dogs and cats - anyone here used it?? 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 aerosol or nose spray. Non-specific airway inflammation (irritation) is one problem which I commonly encounter in the Denver area and seems to be very difficult for me 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 on a pathology report. Anti-inflammatory therapy (steroids or NSAIDs) and or long term doxycycline 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 that detects 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 (when the work of breathing is excessive or there is persisting hypoventilation). 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 as an additive therapy 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 materials on the mucosal surface. Cough is most effective at removing materials from the intrathoracic larger airways and 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. Inhaled steroids are the current in-vogue thing to be using and are discussed elsewhere. We are all familiar with the adverse effect of inducing diabetes mellitus in cats who have received these drugs. NSAIDs have also been useful in some of these cases (I prefer piroxicam 0.3mg/kg once daily - ensuring that no other steroids or NSAIDS are being used at the same time and monitoring for potential side effects). 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 bronchodilator use but these tests are only available in a veterinary research setting 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 classes of bronchodilators that have been used in human and veterinary medicine: 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 but have not been used in small animal medicine. 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") and is my drug of choice in these cats. Methylxanthines are a family of drugs that have been used in veterinary medicine for over 90 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. The beneficial effects of theophylline 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). Potential side effects of methylxanthines (e.g. aminophylline and theophylline) in dogs and cats include tachycardia, restlessness, excitability, vomiting, and diarrhea; side effects are unlikely using proven extended-release oral theophylline products (not generics!). EDTA plasma samples (drawn 4-5 hours in the dog and 10-12 hours in the cat post pilling) may be run to evaluate peak plasma theophylline concentrations. Combination therapy with drugs that inhibit hepatic P450 enzymes (erythromycin, cimetidine and fluoroquinolones) should be used with caution since plasma theophylline concentrations may be significantly altered (increased). Numerous theophylline (all human) products have been evaluated in dogs and cats, however few have shown suitable pharmacokinetics to be used on a routine clinical basis. Theo-Dur and Slo-bid were 2 such products that were available in the US for human use but unfortunately were discontinued a few years ago. Another company's product has recently been evaluated and is now the only theophylline product available in the US that is proven to have suitable kinetics for canine use (Inwood Labs brand extended-release theophylline tablets - the capsules were recently discontinued unfortunately). The dose for the dog is 10mg/kg PO BID and 15mg/kg PO once daily (in the evening) in the cat. Your local pharmacy or veterinary distributor can get this for you (or carries it). Based on some experimental "feline asthma" research in the 90's, alternative recommendations for the treatment have included serotonin receptor inhibition (found to be a mediator of feline airway constriction; e.g. cyproheptadine) and the use of cyclosporine in refractory cases (as another method for suppressing airway inflammation). These have shown to be beneficial in Dr. Padrid's published work but there is limited experience with it clinically. Many human asthmatics are now treated with new drug therapies such as leukotriene receptor blockers, or inhibitors of the enzyme 5-lipoxygenase which is responsible for the formation of leukotrienes themselves. These "human" drugs include Zileuton (Zyflo) an inhibitor of 5-lipoxygenase, montelukast (Singulair) and zafirlukast (Accolate), both leukotriene receptor blockers. Clinical efficacy in people has been demonstrated in a number of large clinical trials. There has been a lot of electronic (the internet) discussion for using these agents in feline airway disease but (based on 2 separate scientific studies) this class of drugs has not been shown to be efficacious in cats to date. Recently, there has been considerable discussion about the use of metered dose inhalers (MDIs). Although there are many testimonial cases (mine included!) that attest to the efficacy and success of inhaled steroids and bronchodilators, no detailed peer-reviewed articles have been published to my knowledge. The major point with MDIs (and aerosol therapy in general) is the delivery system. In human medicine considerable time and training is provided patients to ensure the correct delivery of these aerosols. In veterinary medicine we must rely on spacers (as is needed in infants and children) to hold the aerosolized medications while the animal breathes it in. A facemask must be used and we are just learning how to effectively do this. Aerocat®, Aerodawg® and the new Nebulair® line of products are some veterinary systems that are available - there are also numerous pediatric units that may work as well (e.g. the Panda® mask and chamber). DVM Pharmaceuticals has developed a product line (the Nebulair® system) specifically for aerosol therapy in small animals, including a feline face mask, an aerosol chamber, a portable ultrasonic nebulizer and a canine aerosol circuit. Research on these new aerosol components is currently underway. Attention to the animal's environment is an important part of good respiratory therapy. Looking for potential airway irritants can be time consuming but when found very rewarding. Some of the possible triggers of airway irritation that I ask owners about include: smokers in the house, dusty and/or scented cat litter, use of room fresheners or deodorizers, frequency of filter changes on air conditioners and forced air furnaces, recent house changes (moving, remodeling) etc. Home oxygen therapy: Many of these chronic respiratory diseases (or sequelae to disease) result in clinical hypoxemia. We have used home oxygen administration to help treat these cases, especially in those confirmed to have pulmonary hypertension. Small to medium sized dogs (or cats - although I have not treated any cats with home O2) can spend their night time hours (at minimum) in these semi closed containers (cages) so as to relieve any hypoxic pulmonary vasoconstriction during those hours (33% of the day isn't bad for "cardiac relief"!). Concerns for excessive CO2 build-up (manifested as hyperventilation) or excess humidity build-up have not been encountered. Using a rented electric oxygen concentrator I have measured the FIO2 in a home made cage at 52% after 2 dogs had been in it overnight - with no increase in respiratory rate, temperature or humidity. Flow rates of up to 5 lpm are possible with these units.

© 2008 - Brendan C. McKiernan, DVM, Diplomate ACVIM (SA Internal Medicine) - All rights reserved