Cough

W. David Wilson • Jeffrey Lakritz

■ Definition Coughing, an important and normal respiratory defense mechanism, is the sudden, forceful, noisy expulsion of air through the glottis to clear mucus, particles, and other material from the tracheobronchial tree and glottis.

■ Pathophysiology The mucociliary escalator and the cough reflex are the major protective mechanisms that function together to remove material from the respiratory tract.^1,2 Particles trapped in mucus are transported to the trachea by continuous waves of ciliary motion, starting at the level of the terminal bronchioles. Coughing is associated with development of increased intrathoracic pressure and generation of high- velocity airflow out of the respiratory system. This rapid expulsion of air removes secretions accumulating within the tracheobronchial tree proximal to the level of the segmental bronchi.³ Coughing is thus a normal physiologic and protective response and a common clinical sign associated with a variety of cardiorespiratory disorders.

NEURAL PATHWAYS INVOLVED IN THE COUGH REFLEX. Coughing is an involuntary reflex; however, this reflex may be voluntarily initiated or suppressed.^2,3 The reflex pathways involve sensory receptors present within the airway epithelia, from the larynx to the respiratory bronchioles, with nerve fibers conducting afferent impulses within vagal, glossopha­ryngeal, trigeminal, and phrenic nerves.^1,3,4,5 The receptors, mainly irritant receptors, are particularly numerous within the proximal airways (trachea and bronchi), especially around the hilus of the lung and bifurcation of the bronchi.^1,4 Other receptors capable of activating the cough reflex are found within lung parenchyma, the pleura, and elsewhere. Brainstem neuronal pathways for the cough reflex in the horse are not well character­ized; however, in other species, afferent signals to the medulla oblongata are received and efferent fibers pass back down to the respiratory system within the vagal, phrenic, intercostal, and lumbar nerves and motor portions of the trigeminal, facial, hypoglossal, and accessory nerves to supply striated and smooth muscles of the larynx, tracheobronchial tree, diaphragm, intercostal muscles, abdominal muscles, and secretory glands of the respiratory tract.^1,5-7

Irritant receptors are stimulated by mechanical deformation induced by compressing the trachea; by bronchoconstriction, inert dusts such as carbon, irritant gases such as ammonia, and biological mediators such as histamine, prostaglandins, or bradykinins (Boxes 5.1 and 5.2).^2,4 Sensitivity to mechanical stimulation varies along the airway, and in horses the upper airway cough receptors appear to be less active than observed in many other species.⁸ For example, a stomach tube inadver­tently passed into the trachea frequently does not induce coughing until it reaches the carina.

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Bronchoconstriction is a consistent component of cough,^3,'^,8 and stimuli resulting in a cough may also induce reflex bron­choconstriction through parasympathetic innervation.⁴ However, cough and bronchoconstriction are separate airway reflexes.⁷ Whereas stimulation of irritant receptors in large airways induces both cough and reflex bronchoconstriction indepen­dently, stimulation of nerve endings in smaller airways does not directly initiate coughing but does cause bronchoconstric­tion. Bronchoconstriction may then initiate coughing indirectly.⁴ The role of bronchoconstriction in the induction of coughing is supported by studies in people demonstrating that administra­tion of bronchodilators is associated with reduction in the frequency or severity of coughing in asthma.^9,10 These studies

■ BOX 5.1

Causes of Coughing in Horses

Common Causes

Equine influenza A2 virus (H3N8)

Equine herpesvirus types 1 and 4 (EHV-1, EHV-4) Bacterial pneumonia

Bacterial pleuropneumonia, pleuritis

Recurrent airway obstruction (RAO or chronic obstructive pul­monary disease)

Mechanical causes (e.g., nonspecific dust irritation)

Pharyngitis (acute or chronic pharyngeal lymphoid hyperplasia) Postviral hyperreactive airways

Less Common Causes

Strangles (Streptococcus equi infection)

Equine viral arteritis

Other viruses (equine rhinitis A and equine rhinitis B) Parascaris equorum migration

Pharyngeal paresis

Guttural pouch empyema

Guttural pouch mycosis

Pharyngeal, laryngeal trauma or surgery

Postsurgical aspiration (e.g., after laryngeal prosthesis surgery) Epiglottal entrapment

Subepiglottal cyst or abscess

Chondritis, chondromas of the arytenoid cartilages Retropharyngeal abscess

Tracheal collapse (including scabbard trachea in ponies) Tracheal stenosis, stricture

Choke, esophageal obstruction

Aspiration pneumonia (foreign bodies, feed material) Inhalation pneumonia (smoke, thermal injury, noxious gases) Lungworm infection (Dictyocaulus arnfieldi)

Pulmonary abscessation Exercise-induced pulmonary hemorrhage (EIPH)

Pulmonary edema (smoke inhalation, acute renal failure, overhydra­tion, septicemia, anaphylaxis)

Summer pasture-associated obstructive airway disease (SPOAD) Left-sided heart failure

Congestive cardiac failure Neonatal septicemia

Uncommon Causes

Tuberculosis

Pneumoconiosis or silicosis; other interstitial pneumonias Eosinophilic interstitial pneumonia

Nocardiosis Coccidioidomycosis

Chlamydia psittaci pneumonia

Mycoplasma species pleuritis

Tularemia

Pulmonary hydatidosis Tracheal perforation or rupture

Cryptococcosis

Dorsal displacement of the soft palate (laryngopalatal dislocation) Rostral displacement of the palatopharyngeal arch Idiopathic laryngeal hemiplegia

Guttural pouch neoplasia

Rectus capitis ventralis muscle rupture

Adenovirus infection

Pneumocystis carinii (renamed PneumocystisJiroveci in humans) pneumonia

Esophageal ectasia, dysfunction, stricture, perforation; esophagitis Megaesophagus

Progressive ethmoidal hematoma

Nasal or paranasal sinus neoplasia

Fistula (pharyngeal, esophageal, esophagobronchial, esophago- tracheal, bronchobiliary)

Foreign body (nasal, pharyngeal, laryngeal, tracheal, bronchial) Infarctive lobar pneumonia

Bronchopleural fistula Pleural mesothelioma

Pneumothorax

Pulmonary tumor, primary or metastatic Lymphosarcoma, lymphoma, leukemia Pulmonary aspergillosis Phycomycosis, pythiosis

Plant awn stomatitis

Anaphylaxis or acute drug reaction

Atrial fibrillation

Tetralogy of Fallot

Cor pulmonale

Endocarditis

Ruptured mitral chordae tendineae

Melioidosis, Pseudomonas pseudomallei (exotic) Glanders (exotic)

African horse sickness (exotic)

Toxic Causes

Crofton weed (Eupatorium adenophorum) α-Naphthyl thiourea (ANTU)

Pentachlorophenol Organophosphate

Carbamate

indicate that mediator release (blocked by cromolyn) causes bronchoconstriction (blocked by bronchodilators), which stimulates irritant receptors (blocked by local anesthetics) and causes coughing.⁴ Much of the airflow obstruction in horses with recurrent airway obstruction (RAO) appears to be mediated through these pathways and is eliminated with atropine, a parasympatholytic bronchodilator.⁴

Mechanics of Coughing

The mechanical events that produce coughing occur during four phases: inspiration, compression, expression, and relaxation.^2-4 The first three phases are necessary to create the decreased airway cross-sectional area and high airflow rates needed for an effective cough.

During forced expiration such as occurs with coughing, the increased pleural pressure is transmitted to the intrathoracic airways and alveoli. Intraalveolar pressure exceeds pleural pressure by an amount equal to the elastic recoil pressure of the lung.^4,11 A pressure gradient thus exists between the alveoli and atmospheric pressure at the nostrils and mouth. At a point in the airways known as the equal pressure point (EPP), the pressure in the airway lumen equals the pleural pressure because

■ BOX 5.2

Causes of Coughing in Ruminants

Common Causes

Mannheimia haemolytica or Pasteurella multocida pneumonia (includes shipping fever and enzootic calf pneumonia)

Histophilus somni pneumonia (B)

Lungworm infection, verminous pneumonia

Chronic bacterial pneumonia with abscessation or consolidation (Arcanobacterium pyogenes and other bacteria)

Infectious bovine rhinotracheitis (IBR; bovine herpesvirus type 1 [BHV-1]) (B, C)

Bovine respiratory syncytial virus (B)

Parainfluenza virus type 3

Mycoplasma species pneumonia

Caprine Mycoplasma mycoides subsp.

Abscess (oral, lingual, retropharyngeal, pharyngeal, laryngeal) Trauma (pharyngeal, laryngeal, tracheal, bronchial, chest wall) Esophageal obstruction, foreign body choke

Septicemia (neonates)

Less Common Causes

Bovine rhinovirus (B)

Bovine adenovirus (B)

Bovine malignant catarrhal fever (B)

Bovine virus diarrhea (BVD-MD) (B)

Herpesvirus DN-599 (B)

Bovine herpesvirus type 4 (BHV-4) (B)

Bovine coronavirus (B)

Pulmonary adenomatosis (Jaagsiekte) (O)

Ovine adenovirus (O)

Ovine progressive pneumonia and arthritis, maedi (O)

Caprine respiratory syncytial virus (C)

Caprine arthritis-encephalomyelitis (CAE) pneumonia (C) Aspiration, foreign body pneumonia

Foreign body (pharyngeal, laryngeal, tracheal, bronchial, pulmonary) Inhalation pneumonia (smoke, noxious gases, thermal injury) Pulmonary embolus from posterior vena cava thrombosis (B) Anaphylaxis or adverse drug reaction

Reaction to death of parasites after anthelmintic treatment (B) Milk allergy in cows (B)

Farmer's lung disease (hypersensitivity to Faenia rectivirgula and other mold spores) (B)

Atypical interstitial pneumonia (B)

Pleuritis, pleural effusion

Pneumothorax

Diffuse fibrosing alveolitis (B)

Left-sided heart failure (left atrioventricular [mitral] insufficiency, pericarditis, congenital cardiac defects, other causes)

High altitude disease (B)

Enzootic bovine leukosis (B) Chlamydia psittaci pneumonia

Uncommon Causes Diaphragmatic hernia Pleural mesothelioma (B, C)

Sarcocystosis (B) Sporadic bovine leukosis, thymic lymphosarcoma (B) Tuberculosis

Tularemia (O) Tracheal actinomycosis Tracheal collapse, stricture, stenosis Phycomycosis, pythiosis (B) Pulmonary aspergillosis Rhinosporidiosis

Zygomycosis, mucormycosis (B) Pulmonary listeriosis (B)

Pneumocystis carinii (renamed PneumocystisJiroveci in humans) pneumonia

Cor pulmonale (C) Neoplasia (nasopharyngeal, oropharyngeal, pulmonary) Postpartum hemolytic-uremic syndrome (B) Esophageal rupture, laceration, ulceration, megaesophagus, hiatal hernia

Neoplasia, skeletal (B, O)

Buss disease, chlamydial sporadic bovine encephalomyelitis (B) Winter dysentery (B)

Ascaris suum migration in calves (B) Rinderpest (exotic)

Theileriosis, East Coast fever (exotic) Melioidosis, Pseudomonas pseudomallei (exotic) Contagious bovine pleuropneumonia (exotic) (B) African bovine malignant catarrhal fever (exotic) (B) Virulent sheep and goat pox (exotic) (O, C) Peste des petits ruminants (exotic) (O, C) Contagious caprine pleuropneumonia (exotic) (C) Viral dermatitis of goats (exotic) (C) Ibaraki disease (exotic) (B)

Toxic Causes

Organophosphate, carbamate Mercury (B) Iodine (B, O)

Insect fogger (B) Levamisole (O, C) Nitrogen dioxide (B) Hairy vetch (Vicia villosa) (B) Sneezeweed (Helenium species) Aflatoxicosis (C)

B, Bovine; C, caprine; O, ovine.

the elastic recoil pressure has dissipated.^2-4,11 In the intrathoracic airways rostral to this point, the intraluminal pressure is lower than the pleural pressure; therefore a transmural pressure gradient exists, which causes dynamic compression or collapse of the more proximal airways.^2,4,11 The location of the EPP is determined by elastic recoil pressures, and thus indirectly by lung volumes and the frictional resistance to flow in the airways between the alveoli and the EPP.⁴ At high lung volumes, elastic recoil pressure is high, resistance in peripheral airways is low, and the EPP is typically located in larger intrathoracic airways that resist collapse because they have cartilaginous support for their walls.⁴ As lung volume decreases, elastic recoil forces decrease, airway resistance increases, and the EPP moves more peripherally, subjecting lower and less well-supported parts of the tracheobronchial tree to dynamic compression.^3,4,11 Dynamic compression reduces the cross-sectional area of intrathoracic airways and thus increases the velocity of airflow through the narrowed segment.⁴ These spikes of accelerated airflow promote more effective shearing of mucus and debris from the airway wall and lumen during coughing.¹¹

Dynamic compression also increases the resistance to airflow.⁴ Once dynamic compression of peripheral (smaller) airways occurs, further increases in expiratory effort cause greater narrowing of the airway; thus the flow rate that can be generated at a given lung volume does not increase beyond a certain maximum point (maximum expiratory flow).⁴ Maximum expiratory flow decreases progressively as the animal exhales because lung volume declines.

Because maximum airflows are lower in smaller airways, coughing is probably less effective in clearing material from the smaller airways than from the larger ones.⁴ In the alveolar regions of the lung, gas flow is too slow for coughing to be an effective means of clearance.¹¹ Because only intrathoracic airways are dynamically compressed and subjected to these spikes of higher flow velocity during forced expiration, the extrathoracic trachea should be less effectively cleared by coughing.⁴ However, horses and other animals with long necks do not seem to have great difficulty in clearing their airways, although they do lower their heads and straighten their airways during coughing to assist the clearance process.

In diseases such as RAO that cause narrowing of the airway lumen, the increased resistance to airflow, especially in periph­eral airways, causes the EPP to move more peripherally toward the alveoli, resulting in a reduction in the maximum expiratory flow rate.^2,4 In this situation the effectiveness of coughing in clearing the airways is reduced. Thus administration of a bronchodilator may greatly improve the effectiveness of cough­ing in patients with RAO.⁴

COUGH STIMULI. Cough may be stimulated by bronchocon­striction; excessive mucous production; deposition of inhaled particles in the airways; release of inflammatory mediators; infectious diseases; exposure to hot or cold air; intramural or extramural pressure or tension on the airways (tumor, granu­loma, abscess, or decreased pulmonary compliance caused by restrictive disease such as interstitial fibrosis or pleural effusion); sloughing of airway epithelial cells; and enhanced epithelial permeability (pulmonary edema).¹² Epithelial sloughing and enhanced epithelial permeability increase the accessibility of cough receptors to the mechanical or chemical agents that stimulate them.

Although the role of mucus in coughing is not clear, normal amounts of mucus may have a protective effect by coating the epithelium with a layer that separates the receptors from irritants.⁴ Conversely, excessive accumulation of mucus in the airways, such as occurs in horses with RAO, may mechanically stimulate irritant receptors and cause coughing.⁴ Fluid flushed over the tracheobronchial epithelium stimulates irritant recep­tors, particularly if the fluid is hypertonic or hypotonic.^9,10,14 Coughing is also stimulated by fluid that lacks permeant anions (i.e., anions that have a hydrated size and membrane-penetrating characteristics similar to the chloride anion).¹⁵

Coughing is a prominent feature of cardiac disease in many species, although cardiac diseases are not often encountered in large domestic animals. Failure of the left side of the heart result­ing from congenital defects, valvular stenosis or incompetence, conduction disturbances, myocardial disorders, or restrictive pericardial disease causes an increase in pressure in the pulmonary venous return from the lung. This results in transudation of fluid from the pulmonary capillaries into the pulmonary parenchyma and airspaces (cardiogenic pulmonary edema) and causes swelling of the mucosal lining of small airways.² These changes stimulate cough receptors and initiate the cough reflex. Coughing that occurs secondary to cardiac disease is usually chronic, although acute-onset coughing may be observed with ruptured mitral chordae tendineae and bacterial endocarditis.¹⁶

Approach to Diagnosis of Coughing

HISTORY. The history should include questioning relative to the patient, the cough, the environment, and management. The age of the affected animal is important because many conditions have a marked age incidence. For example, R. equi pneumonia occurs primarily in foals younger than 6 months of age, equine herpesvirus type 4 predominantly affects weanling and yearling horses, and RAO affects primarily mature stabled horses. The use of the horse; its state of fitness; the presence of vices such as crib biting; and any history of contact with other horses at shows, events, sales, racetracks, or breeding farms should be determined.

Recent stressors such as transportation, surgery, strenuous activity, or weaning should be determined because these are known risk factors for conditions such as pneumonia and pleuropneumonia. The duration of ownership of the animal, its previous health, and the geographic location of origin, if it was recently purchased, may help identify regional diseases not normally seen in the area (e.g., systemic mycosis, lungworms, or silicosis in horses) or indicate the degree of stress likely to have been experienced recently. For recently purchased feedlot cattle and sheep, it should be determined if the animals were preconditioned before sale, their place of origin, the number of sale yards through which they have passed, and the duration of transportation.

When evaluating the potential for contagious diseases or those related to common environmental conditions, the vac­cination status of the affected animal and herdmates and the presence of similar clinical signs in other in-contact animals sharing common facilities or common airspaces should be determined. In nursing animals, the vaccination status of the dam is important. A history of other signs such as anorexia, nasal discharge, weight loss, exercise intolerance, stridor, lymphadenopathy, facial swelling, diarrhea, colic, and edema may provide important clues to the cause of the current problem. Weight loss occurs in many acute and chronic diseases, both infectious and noninfectious. Anorexia may indicate that eating is too painful for an animal, for example, because of a painful nasopharyngeal lesion or because the animal is devoting so much effort to breathing that it will not eat.

Environmental considerations such as the introduction of new animals into the environment or the return of animals from shows, sales, training centers, or breeding farms should increase the suspicion of infectious viral or bacterial diseases such as IBR in cattle or influenza in horses. For diseases such as R. equi pneumonia in foals, it is useful to know if similar cases have been seen on the premises in the past. The type of housing or pasturing facilities should be evaluated, particularly with regard to airspace, ventilation, sanitation, stocking density, dust, shade, and shelter. Equine stabling facilities that have enclosed barns, particularly when the stalls face a central arena or are located under a hay storage loft, promote the spread of contagious agents and almost invariably increase the concentration of dust, mold spores, and noxious gases such as ammonia and tractor exhaust fumes in the environment. The type of feed and bedding, storage facilities, and feeding arrangements should be evaluated, especially in chronically coughing horses suspected of having allergic lung disease. Quantitative measures of ventilation and environmental quality can be made and can prove helpful in case management and in monitoring the effectiveness of measures to reduce environmental dust and other pollutants.¹⁷ Similarly, the sampling of air in barns or paddocks using special devices allowing quantitation of bacterial pathogens such as R. equi may prove useful for assessing risk of infection.

The quality of the feed should be evaluated visually and by smell, particularly with regard to the presence of mold spores. General management, pasture management, and parasite control measures should also be evaluated, especially if lungworm infection is suspected. Horses with lungworm infection almost invariably have a history of current or previous co-grazing with donkeys. The season and seasonal incidence of recurrence of the coughing can provide useful clues (e.g., marked seasonal worsening of signs in the late autumn when horses are stabled suggests chronic allergic respiratory disease). Similar to the conditions mentioned for horses, cattle pastured during the warmer months of the year and housed during the colder months may demonstrate recurrent episodes of respiratory dysfunction and cough associated with allergies to dusts present in stored hay or bedding. The history should also include the nature of previous treatments and the response.

Important historical features of the cough include the time and speed of onset; frequency; duration (chronic if longer than 1 month); relation to feeding, housing, or weather; relation to exercise and timing during exercise; improvement, deterioration, or other change since onset; and the presence of and similarity to previous episodes of coughing or respiratory disease. Many coughs are exacerbated by exercise because exercise places greater stress on the respiratory tract. The resulting rapid airflow improves mobilization of secretions and irritates the airway directly. Coughs that occur during eating suggest specific or nonspecific sensitivity to molds, pollen, or other dusts in feed; inflammatory conditions of the larynx or pharyngeal region; laryngeal or pharyngeal problems, including complications of surgery, that interfere with swallowing or guarding of the lower airway; or esophageal obstruction (choke). The effort involved in coughing and associated pain may also give clues to the cause of the cough.

The character of the cough should be evaluated because certain features of a cough tend to point toward its origin and possible causes but are by no means pathognomonic for either. Coughs originating in the upper airway are usually of acute onset, loud, harsh, coarse, dry, hacking, and nonproductive in character. Painful upper airway conditions such as acute pharyngitis, strangles, or necrotizing laryngitis can make the cough more muted. Lower airway coughs are usually soft, deep, and productive (mucus, pus) and tend to be more persistent than coughs originating in the upper airway. However, chest pain frequently attenuates coughing in horses with pleuropneumonia. In horses the fixed position of the larynx within the nasopharynx usually precludes expectoration of sputum into the mouth; thus the productive nature of the cough is difficult to assess. Excess mucus or exudate that is coughed up into the pharynx is usually swallowed; thus a cough can be productive without evidence of a nasal discharge. Swallowing efforts that follow a cough generally indicate that the cough is productive.

PHYSICAL EXAMINATION. The physical examination should include both distant and close evaluation of the patient and the environment. In addition to a detailed examination of the respira­tory and cardiovascular systems, a general physical examination should also be completed so that diseases in other systems can be detected and systemic manifestations of cardiopulmonary disease can be evaluated. The attitude of the animal, the respiratory rate and character, the presence of excessive intercostal or abdominal respiratory effort or of a “heave line” or “barrel chest,” the pres­ence and nature of respiratory distress or stridor at rest, and the presence and character of any nasal and ocular discharge should be noted before the animal is restrained. The following should then be determined: (1) rectal temperature, pulse rate, pulse rhythm and character, mucous membrane color, and capillary refill time; (2) symmetry of airflow from each nostril; (3) odor from the nostrils and mouth; (4) facial symmetry and swelling; (5) resonance or painful response on percussion of the maxillary and frontal sinuses; (6) enlargement of submandibular, parotid, retropharyngeal, prescapular, and other regional lymph nodes; (7) enlargement of the parotid salivary glands or thyroid gland; (8) swelling, pain, or palpable abnormalities in the retropharyngeal region; (9) palpable swelling or flattening of the cervical trachea; and (10) masses at the thoracic inlet and palpable turbulence such as a tracheal rattle in the extrathoracic airway. The oral cavity should also be examined. If spontaneous coughing is not heard during the physical examination, a cough should be induced after auscultation of the airways by pinching the larynx or trachea, and it should be ascertained whether the induced cough sounds like the animal's spontaneous cough. Pinching of the trachea generally causes normal animals to cough once or twice, whereas it often induces paroxysmal coughing in animals with lower airway disease. The laryngeal or tracheal cough reflexes show increased sensitivity in most infective and inflammatory airway diseases.¹⁶

The larynx, trachea, lungs, and heart should be carefully auscultated, as should both sides of the chest, in a quiet environ­ment with the animal at rest and after the rate and depth of respiration have been increased by application of a rebreathing bag, by temporary occlusion of the nostrils, or by light exercise (see the Cyanosis section later). Auscultation of the trachea and larynx should be performed at an early point in the examination, before a rebreathing bag is applied, in order to assess the potential for upper airway obstruction during the examination of the thorax. Auscultation permits detection of turbulent airflow, increased or decreased bronchovesicular sounds, wheezes, crackles, pleural friction rubs, or pleural fluid splashes, all of which indicate disease of the airways, pulmonary parenchyma, or pleura. Wheezes and crackles reflect airway narrowing and dynamic airway collapse, respectively, and are both evidence of small airway disease.¹⁶ A small (12 L) or medium-size (52 L) plastic trash bag makes an adequate rebreathing bag; a plastic rectal sleeve is satisfactory for foals or calves if the opening is stretched so that it does not occlude the nostrils. The response to application of a rebreathing bag should also be noted. Most horses tolerate this procedure well and breathe more deeply, whereas animals with chest pain often do not. Normal horses do not cough when the bag is applied unless they have been eating recently, whereas horses with airway irritation caused by pneumonia or other conditions often cough paroxysmally in response to application of a rebreathing bag. The time taken to regain the normal respiratory rate and character after removal of the bag provides a reasonable, qualitative indicator of ventilatory reserve. Normal animals recover quickly, within a few breaths, whereas respiration may be altered for several minutes in animals with significant lung disease. On removal of the rebreathing bag, the expired air in the bag can be smelled to determine if odors suggestive of necrotic tissue are present.

The chest wall should be palpated to detect pleural friction rubs or lesions such as rib fractures, and the symmetry of chest expansion should be determined. Young calves with chest deformation (unilateral or bilateral) and severe inspiratory and expiratory respiratory distress should be evaluated for fractured ribs that are causing tracheal compression/stenosis (see Chapter 31 for horses and more on ruminants). Temporary tracheostomy does not relieve this respiratory embarrassment. Unilateral chest pain (pleurodynia) often reduces chest excursion on the affected side. Both sides of the chest should be percussed systematically to detect changes in resonance and chest pain. The caudoventral percussion border in the normal horse traces from the level of the tuber coxae at the seventeenth intercostal space (the horse normally has 18 pairs of ribs) to the level of the tuber ischii at the fifteenth intercostal space to the midthorax at the thirteenth intercostal space to the level of the point of the shoulder at the eleventh intercostal space; it continues as a curving line to a point 1 to 3 inches above the olecranon. The normal caudoventral percussion boundary in cattle and small ruminants traces from the eleventh intercostal space at the level of the lateral edge of the epaxial musculature to the ninth rib at a level halfway between the costochondral junction and the lateral edge of the epaxial musculature to the fifth rib at the olecranon (cattle, goats, and sheep normally have 13 pairs of ribs). Percussion is an important diagnostic tool in all large animals, but it is most useful in foals, calves, and goats. The precise percussion boundaries, degree of resonance, and auscultation findings are influenced by age, size, body condition, fitness, and hair coat, as well as by disease processes; a gas-filled abdominal viscus can also confuse interpretation. Hyporesonance (dullness) may indicate pulmonary consolidation, large mass lesions, cardiomegaly, pleural effusion, or other pleural disease. Free pleural fluid usually causes an abrupt change from normal resonance above a horizontal fluid line to hyporesonance below this line. Hyperinflation or pneumothorax may cause hyperresonance with or without expan­sion of the normal percussion boundaries. A painful response to percussion may indicate pleuritis or some other inflammatory process involving the parietal pleura. Painful responses may be dramatic and potentially injurious to the examiner.

In cattle the presence of thoracic or cranial abdominal pain should be ascertained by application of upward pressure to the xiphoid area with the knee or by application of downward pressure with both hands just caudal to the withers. Animals with cranial abdominal or thoracic pain resist these maneuvers and may make an audible or auscultatable grunting noise. Signs such as jugular distention or pulsation (or both) and peripheral edema, which may indicate heart failure, should be noted. As well, the heart should be auscultated to detect murmurs, dysrhythmias, muffling of heart sounds, or other abnormalities that would indicate the need for further cardiovascular diagnostic procedures.

COMPLETE BLOOD COUNT. A complete blood count includ­ing fibrinogen concentration usually reveals nonspecific findings but may be useful in the evaluation of cases in which primary or secondary inflammatory conditions are suspected and in conditions such as pulmonary thromboembolism secondary to caudal vena cava thrombosis (CVCT) in cattle and guttural pouch mycosis in horses in which blood-loss anemia is likely to be a complicating problem. Acute viral infections often induce a transient anemia and leukopenia, predominantly lymphopenia, followed by a monocytosis during recovery. Neutrophilia and hyperfibrinogenemia are features of many inflammatory conditions but are usually most marked when bacterial infection is involved. Some parasitic diseases (e.g., lungworm infection in cattle) may induce eosinophilia, as may allergic conditions, but eosinophilia is not a common feature of either lungworm infection or allergic RAO in the horse.

NASAL OR NASOPHARYNGEAL SWABBING. Nasal or naso­pharyngeal swabbing with direct cytologic examination and culture or molecular diagnostic testing are indicated for confirmation of viral or bacterial infections that involve the upper airway. Because a large number of bacteria normally inhabit the nasopharynx, only the presence of Streptococcus equi or some other pathogen not considered part of the resident flora can be considered significant in horses. When clinical signs suggest a viral respiratory infection, especially when an outbreak of coughing occurs in several animals, molecular detection by polymerase chain reaction (PCR), antigen detection by antigen-capture enzyme-linked immunosorbent assay (ELISA), or virus isolation from nasal or nasopharyngeal swabs, tracheal wash, and/or buffy coat (ethylenediaminetetraacetic acid [EDTA] blood) samples collected during the acute phase of the disease is indicated, as may be viral serologic tests on acute and convalescent serum samples.¹⁸ Under these circum­stances, sampling as many of the most severely affected, often younger, animals as early as possible in the disease course maximizes the chances of establishing an etiologic diagnosis. Nasal swabs are slightly easier to collect than nasopharyngeal swabs and yield similar results when sensitive PCR tests are used¹⁹; however, nasopharyngeal swabs are preferred for virus isolation by many diagnostic laboratories. Nasal swabs are best collected using 6-inch Dacron or rayon (not cotton) swabs, whereas nasopharyngeal swabs are best collected using longer, larger swabs (e.g., Fox 16-inch Procto Swabs, Allegiance Health Care, Hayward, Calif.). Swabs should be placed in capped tubes for submission for PCR testing or into viral transport medium for immediate submission to the laboratory if virus isolation will be requested. It is best to use the transport medium supplied by the respective laboratory to ensure compatibility with viral culture systems. Antigen-capture ELISA (e.g., influenza Directigen Flu A test, Becton-Dickinson, Franklin Lakes, N.J.) and PCR tests are available for testing of nasal or nasopharyngeal swabs and other samples to confirm a diagnosis of viral infection.¹⁸ These rapid-screening tests are sensitive and less cumbersome to perform than virus isolation, do not require such stringent conditions for handling and transporting samples, and provide results sufficiently quickly that specific control measures can be implemented. However, they do not yield an isolate that can be used to monitor genetic and antigenic evolution of the viral agent. Serologic testing often provides only retrospective information, but it can prove helpful in the formulation of future control measures, including vaccination. The larger the number of animals tested, the more informative are the results of serologic testing in a herd or flock. Serologic testing is also indicated when pneumonia caused by Coccidioides immitis or other fungal agents is suspected.

ENDOSCOPIC EXAMINATION. Endoscopic examination of the nasal passages, conchae (turbinates), pharynx, larynx, and trachea allows the presence, nature, and source of exudates and the presence of anatomic or functional abnormalities or mass lesions to be noted. Endoscopic examination of the upper airway of the horse to evaluate for partial airway obstruction is best performed without the use of sedatives or tranquilizers if possible because these alter the tone and function of the muscles supporting laryngeal and pharyngeal anatomy and function and may confuse interpretation of endoscopic findings. In the horse the interior of the guttural pouches may be examined by advancing the endoscope through the pharyngeal openings of each guttural pouch using a guidewire such as a closed biopsy instrument passed through the biopsy channel of the endoscope and into the pouch. Most coughing horses have lower airway disease, which may be reflected in accumula­tion of endoscopically visible exudate in the horizontal trachea, particularly after exercise. Lungworm larvae may be grossly visible in the trachea of horses with lungworm infection. Deeper bronchoscopic examination is necessary to determine whether exudate reflects diffuse airway disease or it arises from a specific area of the lung, such as would occur with a pulmonary abscess or a foreign body lodged in a bronchus. Sedation may or may not be necessary to permit endoscopic examination of the extrathoracic airways in the standing horse; however, sedation with xylazine (1.1 mg/kg IV), detomidine (0.04 mg/kg IV), or romifidine (0.04 to 0.12 mg/kg IV) supplemented with butor­phanol (0.1 to 0.2 mg/kg IV) is recommended to facilitate bronchoscopy and to dampen the cough reflex, as is spraying of the carina and bronchial branches with 2% lidocaine via the biopsy channel of the endoscope to reduce coughing during the procedure. Tracheobronchial aspiration and bronchoalveolar lavage (BAL) can be performed by introducing appropriate catheters via the biopsy channel of the endoscope.

TRACHEAL ASPIRATION. Tracheal aspiration with cytologic studies and quantitative or semiquantitative aerobic and anaerobic culture, or PCR testing, of collected samples is indicated in the evaluation of patients suspected of having disease of the lungs or pleura, particularly if an infectious cause is likely. Tracheal wash samples collected using the percutaneous transtracheal technique are preferred for bacterial culture because they are not contaminated by oropharyngeal organisms.^20,21 Collection of samples by introducing a sterile catheter through the biopsy channel of a presterilized endoscope inserted within a sterile sheath, or by introducing a double-sheathed catheter via the biopsy channel, is acceptable and less subject to complications than is the transtracheal technique, but samples obtained trans- endoscopically may be contaminated with Pseudomonas species and anaerobic bacteria despite the use of a guarded technique.²¹ If tracheal aspiration will be performed percutaneously, the procedure should precede endoscopic examination of the lower airways to avoid contamination. Culture may fail to reveal the primary bacterial pathogen, especially in animals that have been treated with antibiotics. The diagnostic value of tracheal wash samples can be improved by discontinuing antibiotic therapy for at least 24 hours before collecting samples, rapidly processing samples, using antibiotic removal devices and selective culture media, and, if necessary, repeating sampling. Culture results should be evaluated in relation to the clinical signs, clinical experience (especially on the farm of origin of the patient), results of cytologic evaluation, and response to treatment. The trachea is not a sterile environment; therefore culture of small numbers of bacteria without cytologic evidence of infection is of questionable significance.

BRONCHOALVEOLAR LAVAGE. Samples collected by BAL are less useful than those collected by tracheal aspiration for evaluating infectious lower airway diseases and focal pulmonary conditions because the technique samples secretions from only a limited area of the caudodorsal lung on one side and is subject to contamination during introduction of the BAL tube through the nasopharynx. However, BAL yields better samples for cytologic assessment and is therefore preferred for evaluation of patients with generalized, noninfectious lower airway diseases such as RAO or silicosis.¹⁸ BAL samples can be collected under endoscopic guidance by means of catheters introduced through the biopsy channel of a suitable endoscope (investigation of chronic pleural diseases such as abscesses, pleural adhesions, and possible primary or metastatic pulmonary or pleural neoplasia such as lymphosarcoma, gastric squamous cell carcinoma, or meso­thelioma. The procedure can be performed in a standing, sedated patient by using a sterile rigid or fiberoptic endoscope. This procedure is indicated for patients in which large intra- thoracic masses and adhesions have been demonstrated by ultrasonography or thoracic radiology and when less invasive techniques have failed to provide the necessary diagnostic information. Pleuroscopy allows direct visualization of affected structures and provides an opportunity to biopsy masses or aspirate fluid. The pleuroscopy procedure is associated with complications (e.g., pneumothorax, lung laceration, infection) that should be anticipated in advance.

FECAL EXAMINATION. Fecal examination using the Baermann technique to detect lungworm larvae is indicated in ruminants suspected of having a lungworm infection. Because lungworm infection in the horse rarely becomes patent, larvae are not usually demonstrable by fecal examination. Pulmonary signs related to Parascaris equorum infection in foals occur during the prepatent (migratory) period; therefore the fecal flotation test for ascarid eggs often yields a negative result despite significant parasitic infection.

RADIOGRAPHIC EXAMINATION. Radiography of the chest is indicated in patients suspected of having lower airway disease to determine the presence, severity, and pattern of disease changes involving the lungs, pleura, and mediastinum. Four overlapping lateral projections are usually required to evaluate the whole lung field in an adult horse. Because ventrodorsal projections are possible only in young large animals, lateral projections from each side may be necessary to lateralize lesions within the chest. Radiographs of the lungs are particularly useful for determining the prognosis and for monitoring the response to therapy of pulmonary diseases such as bacterial pneumonia and lung abscesses. The cardiac silhouette and the pattern and caliber of the aorta, vena cava, pulmonary artery, pulmonary veins, and other vessels should be evaluated for evidence of cardiac failure and pulmonary vascular disease. Radiographs of the pharynx, retropharyngeal area (including guttural pouches in the horse), larynx, and proximal trachea are indicated in some cases to confirm problems not definitively diagnosed by clinical examination and endoscopy.

NUCLEAR SCINTIGRAPHY. Nuclear scintigraphy using aerosolized technetium-99m (^99mTc)-labeled diethylenetriamine­pentaacetic acid (DPTA) and intravenously injected ^99mTc-labeled microaggregated albumin particles has been used to determine patterns of pulmonary ventilation, perfusion, and ventilation/ perfusion ratios.^20,28 This technique requires special equipment and personnel but provides an objective assessment of pulmonary function and gas exchange capability.²⁸

BIOPSY. Biopsy, with histologic evaluation of samples, is indicated to diagnose certain mass lesions such as neoplasms, cysts, polyps, fungal granulomas, or foreign body granulomas in or surrounding the airway. Masses in the airway can be biopsied through the biopsy channel of an endoscope, but these samples inevitably are small. Biopsies can also be collected at the time of exploratory or corrective surgery from lesions in the upper airway. Lung biopsies can be collected blindly, using Tru-Cut, Biopty, or similar instruments, preferably from the peripheral areas of the lung to reduce the likelihood of serious hemorrhage (see Chapter 31). Focal lesions can be visualized ultrasonographically or radiographically during the percutaneous biopsy procedure to improve the likelihood of obtaining diagnostic specimens. Lung biopsy is most useful for diagnosing diffuse nonseptic conditions such as pneumoconiosis. The inherent risks associated with the procedure indicate that percutaneous lung biopsy should be reserved for circumstances in which the animal is not showing signs of marked respiratory distress, uncontrollable coughing, or bleeding disorders and a high likelihood exists that the procedure will yield significant diagnostic information. Open lung biopsy is possible, albeit rarely indicated.

IMMUNOGLOBULIN DETERMINATIONS. Quantitative immu­noglobulin determinations and possibly other immune function tests may be indicated in animals, especially the young, with chronic or recurrent respiratory tract infections or other indications of immune compromise.

ALLERGEN TESTING. Intradermal testing (IDT) for allergens, a radioallergosorbent test (RAST), ELISA tests for immunoglobulin E (IgE) on serum, and inhaled challenge have been advocated to evaluate horses suspected of having allergic respiratory disease based on exacerbation of signs in certain environments or with certain feeding practices. Although there are anecdotal reports that horses with RAO have been hyposensitized successfully using allergens selected on the basis of these allergen tests, the authors are unaware of documentation in well-controlled studies. In addition, a recent study showed that compared with normal non-atopic horses, RAO-affected horses did not have a significantly greater number of positive reactions in IDT against any allergen group (molds, grasses, weeds, trees, and insects), leading the authors to conclude that reactions to individual allergens in IDT should not be used to determine that horses have clinically relevant hypersensitivity.²⁹ Many normal horses show sensitivity to individual mold spores and other allergens, and there is poor correlation between the dermal and pulmonary reactivities to mold antigens.¹³ Furthermore, when compared with the results of IDT, RAST and ELISA serum allergy tests have been shown to have low sensitivity in detecting allergen sensitivity.³⁰ Although the use of recombinant allergens rather than crude mold extracts in ELISA tests substantially improves sensitivity in detecting levels of allergen-specific IgE,³¹ and significantly more RAO-affected horses than normal horses have high allergen-specific IgE levels, the degree of overlap of results precludes its use for diagnostic purposes.³² The crude trial-and-error approach of adding or removing potential allergens from the environment is sometimes helpful diagnostically and therapeutically in RAO cases in which an allergic cause is suspected. Feeding of pellets instead of hay and using shredded paper, peat moss, or wood shavings instead of straw bedding are common examples of this approach (see the RAO section in Chapter 31). Allergen testing or serologic evaluation of adult cattle with historical evidence of recurrent, seasonal, respiratory disease (extrinsic allergic alveolitis) have not proven diagnostic of specific allergen-induced disease; rather, results merely suggest prior exposure to molds (see Chapter 31).

PULMONARY FUNCTION TESTING. Except for measurement of pleural pressure using an esophageal balloon catheter attached to a pneumotachograph, pulmonary function testing and evaluation of airway dynamics during exercise have until recently been largely research techniques that were not readily applicable to clinical patients. Development of the minimally invasive techniques of oscillometry (forced oscillatory mechanics [FOM]), forced expiratory maneuvers, and flow metrics now permits physiologic assessment of lung function in clinical patients.^33,34 When coupled with histamine provocation tests to assess airway reactivity and bronchodilator response tests, pulmonary function tests can provide a considerable amount of information to guide therapy and prognosis. Indications for pulmonary function testing might include evaluating horses with a history of poor performance or exercise intolerance but no other detectable abnormalities; assessing the degree of functional impairment in horses with known evidence of respira­tory disease; assessing the efficacy of therapeutic regimens; determining if a horse has recovered from a diagnosed respira­tory disorder and can be returned to training; and ruling out functional pulmonary abnormalities in horses with upper airway conditions.

BRONCHODILATOR RESPONSE TESTING. Bronchodilator response testing involves determining the response of measured pulmonary functions and pleural pressures to rapidly acting bronchodilator drugs such as albuterol (450 to 900 μg) or ipratropium bromide, administered by aerosol, or atropine administered parenterally.³³ Results are often helpful in determining the pathogenesis of RAO and the likely response to bronchodilator therapy. In the field setting, useful information can be gained by assessing the response of respiratory rate, respiratory character, and lung sounds to intravenous (IV) administration of a low dose of atropine (5 to 7 mg/450-kg horse). This test can be made more objective by measuring pleural pressures using a Ventigraph recorder (Boehringer Ingelheim Vetmedica, Inc., St Joseph, Mo.) attached to an esophageal catheter or flowmetric techniques.^13,33,35,36

DIFFERENTIAL DIAGNOSIS OF COUGHING. The differential diagnosis of coughing can be enhanced by arbitrarily categoriz­ing it on the basis of duration of signs into acute or chronic (>1 month) and by the presence or absence of fever.³ It should be kept in mind that some acute coughs become chronic and that, conversely, conditions that cause chronic coughing may be seen early in the disease course. Conditions typically associated with acute coughing include viral, bacterial, and parasitic infec­tions of the upper and lower respiratory tract; acute allergic reactions or acute toxic injury to the lung; foreign bodies; choke; injuries to the larynx, trachea, or chest; pharyngeal or laryngeal dysfunction secondary to neurologic disorders or surgery; aspiration of food material or foreign bodies; smoke inhalation; and compressive upper airway lesions such as retropharyngeal abscesses or necrotic laryngitis. In most instances, outbreaks of sudden-onset coughing in groups of animals are the result of viral infection involving the upper and lower respiratory tract.^8,16

Conditions typically associated with chronic coughing include chronic bacterial pneumonia; pulmonary abscess; chronic pleuritis; chronic allergic pulmonary diseases such as RAO in horses and farmer's lung disease of cattle; postviral bronchial hyperreactivity; chronic viral respiratory disease such as ovine progressive pneumonia; irritant airway disease caused by environmental irritants such as dust; lungworm infections, particularly in horses and small ruminants; functional or anatomic problems in the pharynx or larynx that interfere with guarding of the airway, including postsurgical problems; heart failure resulting in pulmonary edema; tumors or polyps in the upper airway or lung; mycotic infections of the upper airway, lung, or pleura; chronic guttural pouch infections in horses; tracheal collapse, especially in ponies; chronic interstitial disease such as pneumoconiosis caused by inhalation of particulate material; and so-called nuisance coughs. Nuisance coughs are common in horses, especially at the beginning of exercise, which emphasizes the fact that coughing is a normal airway- protective mechanism and not always evidence of disease. Nuisance coughs tend to bother the owner more than the horse and can result from habit; vices such as crib biting, wind sucking, or greedy eating; and environmental factors such as dust, ammonia, and cold air. Some nuisance coughs resolve after modifying the stabling or work environment.

Cough with fever usually indicates a primary infectious cause or a secondary infection superimposed on a noninfectious cause.³⁷ Fever is a typical but not invariable feature of aspiration pneumonia, bacterial pneumonia, pulmonary abscess, viral respiratory tract infection, strangles, fungal pneumonia, pleuropneumonia (bacterial, viral, or mycoplasmal), acute bronchointerstitial pneumonia, and thoracic neoplasia.³⁷

Cough without fever is typically found in RAO, abnormalities of the larynx or pharynx, parasitic pneumonia, exercise-induced pulmonary hemorrhage (EIPH), tracheobronchial foreign body, tracheal collapse, and airway-oriented neoplasia (e.g., bronchial carcinoma).³⁷ Horses with chronic interstitial pneumonia such as silicosis or granulomatous pneumonia are usually afebrile but may have mild to moderate fever.¹