Pathophysiology

Normal cilia are made up of nine pairs of microtubules surrounding a central pair. Inner and outer dynein arms connect the microtubules, and the protein dynein uses adenosine triphosphate (ATP) to provide energy for ciliary motility. Primary ciliary dyskinesia (PCD) is a heritable disorder that is most often associated with a defect in the dynein arms (total or partial absence) resulting in defective ciliary motion; misalignment of the central pair of microtubules is also reported (Figure 6.1). Multiple genes are involved in the morphogenesis of cilia, and various genetic mutations have been described in humans that can result in dysgenesis and immotile cilia. Several dog breeds have been reported to develop PCD, and the genetic mutation has been described in Old English Sheepdogs (OES) affecting the CCDC39 gene, similar to the mutation in humans (Merveille et al. 2014). This is inherited as an autosomal recessive disorder, with prevalence of carriers of the defect ranging from 7 to 19% in the OES population (Merveille et al. 2014). A genetic defect has also been reported in Australian Shepherds (Christen et al. 2023) and the Alaskan Malamute (Anderegg et al. 2019). All organs that contain cilia are affected, including the respiratory tract, middle ear, and reproductive tract, leading to recurrent sinusitis and pneumonia, serous otitis, infertility, and hydrocephalus. PCD is accompanied by situs inversus in 50% or more of cases, and bronchiectasis can be present early in disease or develop later in life after multiple episodes of pneumonia occur. The combination of situs inversus, chronic sinusitis, and bronchiectasis has been referred to as Kartagener’s syndrome.

History and Signalment

PCD has been reported in the Dachshund, Bichon Frise, English Pointer, Springer Spaniel, Newfoundland, OES, and other breeds. It is rarely found in the cat. Clinical signs can be seen in puppies as early as 5 weeks of age, but animals can be older when the severity or recurrence of signs triggers evaluation. Historical complaints include chronic or recurrent sneezing, serous to mucoid nasal discharge, chronic cough, and episodes of antibiotic‐responsive pneumonia. Signs of otitis media (head tilt, aural discharge, or nystagmus) or infertility in breeding‐age animals have also been reported.

Physical Examination

Bilateral serous to mucopurulent nasal discharge is common and dogs can display evidence of pneumonia with a moist cough on tracheal palpation, increased tracheal sensitivity, and increased or harsh bronchovesicular sounds on auscultation. Generally animals remain bright and active despite respiratory infection, although severely affected animals can be febrile and cyanotic. Non‐respiratory abnormalities that can be found include hydrocephalus and bullous effusion.

Diagnosis

A complete blood count is often suggestive of infection, with increased neutrophil numbers and a left shift is possible. Thoracic radiographs reveal alveolar infiltrates during bouts of pneumonia. Repeated bouts of infection lead to bronchiectasis, although this can be a congenital defect in some animals. Airway sampling typically reveals a septic suppurative response and isolation of Mycoplasma and aerobic bacteria (Pasteurella, Streptococcus, and Staphylococcus) is common. Diagnosis of PCD requires documentation of functional and structural defects of cilia. In an intact male dog with the appropriate clinical history, lack of purposeful sperm motility is consistent with a diagnosis of PCD, although semen samples can be difficult to obtain in young animals. Respiratory ciliary function is assessed through tracheal scintigraphy using 99‐technetium‐labeled macroaggregated albumin deposited at the carina. Ciliary movement of the radiolabel is followed with a gamma camera, and animals with ciliary dyskinesia have no motion detected. Mycoplasma and Bordetella infections should be appropriately treated prior to performing tracheal scintigraphy, because infection with these organisms causes ciliostasis and can result in a false‐positive scintigraphic study.

Nasal or tracheal biopsies or a semen sample fixed in glutaraldehyde can be submitted for transmission electron microscopy to identify the characteristic ultrastructural abnormalities seen in PCD; however, electron microscopy is not widely available and a properly sectioned sample is critical to assess ciliary structures. A pathologist should be consulted prior to obtaining a biopsy to ensure that an adequate sample is obtained and that a proper interpretation can be provided. Dogs with PCD will have multiple defects in cilia (loss or shortening of dynein arms, loss of the central pair of microtubules, triplets in place of doublets, etc.) and will have >5–20% of cilia affected. Findings must be distinguished from those of acquired or secondary ciliary abnormalities, which can be found with a variety of chronic respiratory tract diseases. These secondary defects typically affect <5% of the affected cilia; however, compound cilia (multiple cilia contained within a single membranous layer) are often prominent. In human patients, PCD can occur in the absence of specific electron microscopy abnormalities and it is likely that this occurs in veterinary patients also, although it has not been specifically documented. Genetic screening is available for the mutations reported in certain breeds.

Treatment

Aggressive therapy for pneumonia with appropriate antibiotics is required and owners should be taught to recognize recurrence of disease so that treatment can be instituted immediately. Respiratory therapy with nebulization and coupage can be used to encourage clearance of respiratory secretions. Cough suppressants should never be used because of the risk for trapping infected secretions in the lower airways and promoting the development of secondary bronchiectasis.

Pathophysiology

Lung lobe torsion results when a lobar bronchus twists on its axis at the hilum of the lung, resulting in venous compression, congestion within the tissue, and swelling of the lung lobe. The lobes most commonly affected by torsion are the right middle lung lobe (particularly in large breed dogs) and the left cranial lung lobe (in Pugs and other small breed dogs). In cats, the left and right cranial lobes are affected most commonly, followed by the right middle lung lobe (Tinsdale et al. 2022), although torsion is much less common in cats than in dogs. Lung lobe torsion is often found in conjunction with pleural effusion that is exudative in character, although lobar torsion can be found in the absence of effusion.

The precise etiology of lung lobe torsion is unknown. In deep‐chested dogs and Pugs, it has been suggested that the conformation of the thorax plays a role in allowing the bronchus to rotate on its axis. Brachycephalic dogs also commonly have collapse of the bronchus to the left cranial lung lobe and this could play a role in the development of torsion. This has been referred to as primary lung lobe torsion (Rossanese et al. 2020) and is the most common cause of torsion in the dog. Torsion could possibly be associated with atelectasis of a lobe from bronchial obstruction caused by mucus impaction or a neoplasm with subsequent twisting of the lobar bronchus. Lobar consolidation due to infection might predispose to torsion, and a torsed lung lobe can develop a secondary infection due to loss of blood supply. Previous anesthesia and surgery have been implicated in some cases. Finally, it is possible that pleural effusion precedes lung lobe torsion, causing floatation or collapse of a lung lobe and an environment that allows the lobe to twist along the bronchial axis. These types of cases have been proposed to reflect secondary lung lobe torsion (Rossanese et al. 2020).

History and Signalment

There is an increased incidence of lung lobe torsion in deep‐chested dog breeds such as the Afghan hound and in Pugs. Dogs, particularly Pugs, as young as 3 months can be affected (Latimer et al. 2017), but it is most common in middle‐aged dogs (Park et al. 2018). Torsion is uncommon in the cat, but it has been found in cats with chronic, poorly treated lower airway inflammatory disease (likely preceded by lobar collapse associated with mucus obstruction), pulmonary carcinoma, or with pleural effusions, including chylothorax and pyothorax (Tinsdale et al. 2022). Clinical complaints can be acute (within 24 hours of torsion) or chronic (present for 2–3 months) in nature and include tachypnea or difficulty breathing, lethargy, anorexia, and coughing. Hemoptysis can be observed. In chronic cases, weight loss can be noted, likely in association with ill health due to the torsion.

Physical Examination

Tachypnea is a common finding, which could be a result of pleural effusion, lung consolidation, or a pain response. Heart and lung sounds can be muffled or absent focally in the region of the torsion or ventrally in the thorax due to the presence of pleural effusion. Elevated body temperature is detected in 25–50% of cases.

Diagnostic Findings

Affected animals usually display a neutrophilic leukocytosis due to stress, inflammation, necrosis, or infection. Radiographs reveal consolidation or atelectasis of the affected lung lobe. Lobar opacity is a common radiographic finding and a vesicular lung pattern is considered pathognomonic for torsion (Figure 6.2). Abnormal bronchial position is visualized in some cases and detection is likely enhanced by the use of digital radiography and image adjustments. Pleural effusion can be found in over 80% of cases, either diffusely or in the region of the torsed lobe. Thoracocentesis is often indicated to alleviate respiratory distress and improve visualization of thoracic contents. Thoracic ultrasound with evaluation of pulmonary blood flow might be helpful in some cases, although the most common finding appears to be hepatization of the lung lobe. Bronchoscopy can document lung lobe torsion as the cause for lobar consolidation through visualization of a twisted appearance to the bronchial opening (Figure 6.3), although this can sometimes appear similar to bronchial collapse or stenosis. Finally, computed tomography (CT) can be performed where available to evaluate lung lobe changes and to identify underlying or concurrent conditions. Features consistent with lung lobe torsion include abrupt termination of the bronchus to the affected lung lobe, increased size of the lobe with augmented attenuation due to consolidation and emphysema, and lack of contrast enhancement due to compression on the vasculature (Seiler et al. 2008; Rossanese et al. 2020).

Thoracic fluid analysis reveals chyle or an inflammatory exudate (see Chapter 7) in up to one‐third of dogs, with a modified transudate or hemorrhage reported in the remaining cases (Park et al. 2018). Cytology of the fluid is indicated to rule out infectious or neoplastic disease, and samples should be evaluated by aerobic and anaerobic bacterial culture to rule out empyema. Histopathology of lung tissue usually shows pulmonary hemorrhage, inflammation, and infarction, but can sometimes reveal a primary disease process responsible for the torsion, such as neoplasia or bronchial obstruction.

Treatment

Lung lobectomy is required for appropriate treatment. The lobe should not be de‐rotated prior to removal because of the risk for ischemic injury associated with reperfusion. CT guidance is used to determine the appropriate approach, with an intercostal thoracotomy used most commonly. Video‐assisted thoracostomy can also be employed, and chest drain placement is used to maintain a negative intrapleural pressure in the first day after surgery. Chylothorax can resolve after lung lobectomy, but sometimes requires additional management (see Chapter 7).

Prognosis

The majority of dogs have an uncomplicated recovery from lung lobectomy with survival to discharge of up to 99% and an excellent long‐term prognosis (Rossanese et al. 2020). Cats appear to have concurrent diseases and require additional surgical procedures (Tinsdale et al. 2022); prognosis ranges from good to less favorable. Dogs that have torsion of the right cranial and right middle lung lobes concurrently, dogs with underlying neoplasia, and those with persistent effusion might have a worse prognosis (Park et al. 2018). Some dogs can develop torsion of a second lung lobe postoperatively.

Pathophysiology

Etiologic agents of viral pneumonia in the dog include canine distemper virus (CDV) and canine influenza virus (CIV). Less commonly, canine parainfluenza virus‐3 (CPIV), canine adenovirus‐2 (CAV‐2), canine herpesvirus (CHV‐1), and canine respiratory coronavirus (CRCoV) can cause parenchymal infection, but these organisms more typically result in airway disease, predispose to bacterial pneumonia, or are present as a co‐infecting organism in bacterial pneumonia (Viitanen et al. 2015). In the cat, feline calicivirus (FCV) is the most common viral cause of pneumonia, although feline herpesvirus‐1 (FHV‐1) can cause a severe tracheitis and pneumonia.

Viruses are spread by inhalation of aerosolized viral particles that gain access to the lower respiratory tract. These viruses cause diffuse epithelial cell death and provoke an inflammatory response, primarily within the interstitium. Most viral infections are self‐limiting, but they can predispose animals to bacterial bronchopneumonia and thus can lead to more severe systemic signs.

Non‐effusive feline infectious peritonitis (FIP) virus (the mutated coronavirus) can be associated with a granulomatous pneumonia positive for FIP virus antigen in 76% of cases (Slaviero et al. 2024). This is due to immune‐mediated vasculitis with secondary pyogranulomatous inflammation rather than to an infectious process and many cats have concurrent pleuritis and pleural effusion (see Chapter 7).

History and Signalment

Puppies and kittens are more susceptible to most viral agents than adult animals, with the exception of CIV, which tends to affect mature dogs. CHV‐1 can also affect mature dogs, resulting in viremia and pneumonia, although upper respiratory signs typically predominate. Generally, clinical signs are acute in onset and associated primarily with cough, but naso‐ocular discharge can also be present. Animals held in close confinement are more prone to viral infection and outbreaks are common. CDV results in more severe clinical and systemic signs of illness and is characterized by concurrent or sequential development of gastrointestinal and then neurologic signs, typically manifest as myoclonus, which warrants a guarded prognosis.

Physical Examination

Dogs or cats with viral pneumonia can have fever and/or tachypnea that ranges from mild to severe. Lung sounds may be slightly loud or harsh and tracheal sensitivity is usually present. Dogs with CDV can have chorioretinitis or neurologic deficits that involve the cerebrum, cerebellum, or spinal cord.

Diagnostic Findings

Diagnosis of a viral pneumonia is often based on clinical suspicion, history and signalment, environmental exposure, and vaccination status. A complete blood count will sometimes reveal lymphopenia early in viral infection. Viral pneumonia is expected to result in a diffuse interstitial pattern on thoracic radiographs, although bacterial complications can lead to alveolar infiltrates.

Various methods can be used to confirm the presence of virus or exposure to a virus, including culture, polymerase chain reaction (PCR) or reverse‐transcriptase PCR (RT‐PCR) for RNA viruses, and serology; however, it is more difficult to determine if the virus is actually the cause of disease (see canine infectious respiratory disease, Chapter 5). Airway wash fluid or pulmonary tissue can be analyzed by fluorescent antibody staining or application of immunohistochemistry to fixed tissue to identify virus‐specific antigen; however, tests are not widely available for all viruses and can be difficult to perform. Finally, electron microscopy can be used to detect viral inclusions in tissue samples.

Treatment

General supportive care measures are instituted, including subcutaneous or intravenous fluid therapy, airway humidification, and oxygen therapy as needed. Affected animals are kept segregated from other animals to avoid spread of disease. No specific antiviral therapy is generally recommended, but broad‐spectrum antibiotics are often administered to treat or to prevent secondary bacterial infection. Mycoplasma spp. are commonly found in conjunction with suspected viral infection, thus doxycycline or azithromycin would be appropriate for use.

Prognosis

Regular vaccination protects against most of the viral infections that can cause pneumonia and results in less severe clinical manifestations of disease. In general, viral pneumonia has a good prognosis, as most animals will respond to supportive care and treatment of secondary bacterial pneumonia. Dogs with distemper virus that develop neurologic disease have a poor prognosis in general, although some will survive.

Pathophysiology

Bacterial pneumonia occurs when large numbers of opportunistic pathogens overwhelm host defense mechanisms or when highly pathogenic organisms gain access to the airways. It can also result from failure of respiratory defense mechanisms, systemic immune compromise, or inhalation of a foreign body, oropharyngeal material, gastric contents, or a caustic substance (see later for aspiration pneumonia). Therefore, in the animal with bacterial pneumonia, a search should begin for an underlying disease or predisposing disorder that allows parenchymal infection. Enteric organisms, Pasteurella species, Bordetella, Mycoplasma, and anaerobes are the most common bacteria found in lower respiratory tract infections in adult dogs and in puppies (Johnson et al. 2013). In cats, Mycoplasma, Pasteurella, Streptococcus, and anaerobic species are found most commonly (Dear et al. 2021).

Bacterial colonization of the respiratory epithelium incites chemotaxis of neutrophils. These inflammatory cells release proteolytic enzymes and reactive oxygen species to kill the bacteria; however, this process sets up an inflammatory environment within the lung. A delicate balance develops between control of bacterial growth and restriction of worsening lung inflammation. In some cases, overwhelming inflammation perpetuates lung damage, resulting in gas exchange abnormalities that can lead to respiratory failure.

Special consideration must be given to the possibility of pneumonic plague in animals from certain regions of the western United States (Colorado, New Mexico), Asia, and Africa, and in circumstances where exposure to the organism is possible (Pennisi et al. 2013; Nichols et al. 2014). Infection is caused by Yersinia pestis, and the disease is of marked zoonotic concern, particularly when an infected cat is encountered, because this species is more commonly affected by the pneumonic form of disease. Animals become infected through a bite from an infected flea or by ingestion of an infected mammalian host such as a prairie dog, squirrel, rabbit, or rodent, therefore exposure history is an important contributor to the diagnosis. While the bubonic form is more common (mandibular lymphadenopathy), the pneumonic form is more readily spread to humans through aerosolization of organisms.

History and Signalment

Pneumonia is encountered in any age of animal. Puppies are most commonly affected by primary infectious pneumonia, young hunting or sporting dogs are most commonly affected by foreign body pneumonia, and older animals develop bacterial pneumonia in association with aspiration injury or immune compromise. Certain dog breeds are predisposed to infectious pneumonia. For example, Irish Wolfhounds develop an unusual rhinitis/bronchopneumonia syndrome in young dogs (Clercx et al. 2003) as well as recurrent bacterial pneumonia in older dogs (Viitanen et al. 2019). Ciliary structural abnormalities, various forms of immunodeficiency (immunoglobulin insufficiencies or abnormal lymphocyte subpopulations), swallowing or esophageal dysfunction, and laryngeal paresis or paralysis have been ruled out in many affected dogs (Viitanen et al. 2019). Bronchiectasis was a common finding on CT along with mucosal irregularities on bronchoscopy in one study (Viitanen et al. 2019), although whether these are a cause or result of recurrent pneumonia is unclear. The reasons that Irish Wolfhounds develop recurrent bacterial pneumonia remain unclear.

Dogs or cats with bacterial pneumonia can have an acute history of a productive cough, labored breathing, and respiratory difficulty or distress However, some animals present with more chronic and vague signs of illness such as malaise, depression, anorexia, and weight loss. Importantly, even foreign body pneumonia can result in chronic clinical signs. Animals that display chronic antibiotic‐responsive pneumonia are suspicious for the presence of a foreign body, bronchiectasis, broncho‐esophageal fistula, or chronic recurrent aspiration injury. Nasal discharge can be found concurrently in dogs with pneumonia due to coincident nasal infection or when animals cough respiratory secretions into the nasopharynx (Figure 6.4).

Physical Examination

Abnormalities indicative of bacterial pneumonia are sometimes but not always found in the examination of the respiratory tract. Parenchymal infection with alveolar flooding by inflammatory debris should result in restrictive lung disease, and a rapid, shallow breathing pattern is expected, but this will depend on the extent of disease. Depending on the stage and severity of disease, thoracic auscultation can reveal loud, harsh bronchovesicular sounds or adventitious lung sounds (crackles or wheezes). Absence of lung sounds in a specific region of the thorax might be suggestive of lung consolidation or rarely, pleuropneumonia. Tracheal sensitivity is usually present, and with foreign body pneumonia or pneumonia in association with bronchiectasis, it is often dramatic. Cough followed by swallowing is suggestive of a process that is causing increased secretions in the lower airway.

A mucopurulent nasal discharge can be present in some animals. Although pneumonia is an inflammatory condition, fever is detected in <50% of affected adult dogs or puppies (Radhakrishnan et al. 2007) and the percentage of cats with pneumonia that have fever is likely <25%.

Diagnostic Findings

Peripheral leukocytosis with a left shift supports the diagnosis of bacterial pneumonia in an animal with appropriate clinical findings, although this was found in only 1/3 of cats (Dear et al. 2021) and is present in an unknown percentage of dogs. Neutropenia with a degenerative left shift can occur if acute fulminant pneumonia results in pulmonary sequestration of neutrophils. Leukogram findings likely reflect both the severity and the stage of disease, with leukopenia in the peracute stage and neutrophilia in the latter stages. Bands are present in variable percentages and likely reflect the severity of the inflammatory response. A biochemical profile and urinalysis assist in the diagnosis of underlying conditions such as diabetes mellitus and hyperadrenocorticism, which are associated with defective neutrophil function and might predispose an animal to pneumonia. Feline leukemia virus (FeLV)/feline immunodeficiency virus (FIV) serology should be performed in cats with pneumonia, although a direct association has not been made between viral status and the development of bacterial pneumonia. C‐reactive protein and other acute phase proteins have been investigated for use in the diagnosis and monitoring of pneumonia in dogs but these are often elevated in a variety of inflammatory processes. Nonetheless, future studies could show a role for these biomarkers in determining the severity of disease or response to therapy.

Pulse oximetry can be employed to approximate the severity of lung dysfunction as well as the need for oxygen supplementation, although it provides only a crude estimation of lung function. Hypoxemia is common in animals with moderate to severe parenchymal disease, and an arterial blood gas provides a more accurate assessment of oxygenation (see Chapter 2).

Thoracic radiographs obtained in the early stages of bacterial pneumonia demonstrate mild or diffuse interstitial infiltrates. Alveolar infiltrates with air bronchograms are considered the classic radiographic finding (Figure 6.5) and develop over time. In severe cases, these infiltrates can coalesce to cause lobar consolidation. A lobar or patchy segmental infiltrate can also be suggestive of underlying foreign body pneumonia, although pure interstitial infiltrates were seen in one‐third of such cases (Schultz and Zwingenberger 2008). Pleuropneumonia is uncommon in small animals unless a pleural foreign body or bite wound is the cause of pneumonia. In these cases, infection with Actinomyces can sometimes be found.

Direct airway sampling through tracheal wash, bronchoscopy with bronchoalveolar lavage (BAL), or fine‐needle aspiration of the lung is indicated to confirm the etiology of pneumonia and to obtain samples for Gram stain, aerobic and anaerobic bacterial culture with antibiotic sensitivity testing, Mycoplasma culture, and cytology. Of these techniques, tracheal wash is most suited for radiographically diffuse disease, while bronchoscopy (Figure 6.6) or fine‐needle lung aspiration would be preferred for focal disease (see Chapter 2). Bronchoscopy is particularly indicated for animals suspected of foreign body pneumonia because of the high success rate in providing resolution of disease. When either tracheal wash or bronchoscopy is performed, completion of a thorough laryngeal exam is warranted at the onset of anesthesia to rule out laryngeal dysfunction as a contributor to pneumonia. Gram staining characteristics and cytology can be useful for identifying the most likely infecting organism and initiating early antibiotic therapy.

Various bacteria can be recovered from the airways of healthy cats and dogs; therefore documentation of pneumonia requires isolation of bacteria in conjunction with detection of septic suppurative inflammation on airway cytology in an animal with clinical suspicion of pneumonia (Figure 6.7). Importantly, some animals will have observable intracellular bacteria on cytology but lack growth on culture while others (up to 25%) will lack intracellular bacteria yet still have a clinical diagnosis of pneumonia with growth of pathogens in culture. Interpretation of diagnostic results in light of the clinical picture is necessary, particularly when considering appropriate use of antibiotics.

In the past, pneumonia in the dog was typically caused by Gram‐negative enteric bacteria; however, with widespread use of fluoroquinolone antimicrobials, alternate bacteria are encountered. In a study from a university teaching hospital of dogs diagnosed with pneumonia (likely complicated pneumonia cases), Mycoplasma, Bordetella, and Pasteurella were isolated most commonly (Table 6.1). Multiple species were isolated in almost 50% of all cases, and almost 20% of infections were complicated by the presence of anaerobic bacteria (Johnson et al. 2013). Bacterial pneumonia is clinically recognized much less commonly in the cat than in the dog, and less information is available about potential causes. When specific cultures are performed, Mycoplasma, Pasteurella, and anaerobic species were found most commonly (Dear et al. 2021), although Streptococcus species were also found in many cases. An earlier study implicated Mycoplasma spp. as the most common isolate in feline pneumonia (Foster et al. 2004), although the role of Mycoplasma in lower respiratory tract infection in adult dogs or in cats remains controversial.

Treatment

While waiting to obtain results of cultures, antimicrobial treatment should be initiated using antibiotics likely to be effective against the organisms involved. The combination of a fluoroquinolone and penicillin derivative is used most commonly for initial therapy. Antibiotics are usually required for 1–2 weeks in cases with uncomplicated pneumonia, although the appropriate length of antibiotic therapy remains unknown. Obviously, any agents used for long‐term treatment should be based on results obtained from culture and susceptibility testing. Biomarkers such as C‐reactive peptide (CRP) continue to be investigated for use in determining the length of treatment necessary, and one study suggested shorter duration of antimicrobial use when CRP was used as a biomarker of infection (Viitanen et al. 2017). However, clinically the respiratory rate and effort, presence of cough or abnormal lung sounds, and pulse oximetry or blood gas data are used to determine when therapy can be discontinued. When bronchiectasis is the underlying condition, >6 weeks of therapy can be required (Table 6.2).

Bronchodilators are sometimes considered for animals with pneumonia. Theoretically there is a concern that use of a bronchodilator could increase ventilation to a consolidated lung region and worsen gas exchange; however, this is unlikely to play a substantial clinical role, particularly if using extended‐release theophylline, which is a very weak bronchodilator. Beta‐agonists could be considered as adjunct therapy in a cat with pneumonia given the high incidence of reactive airway disease in this species. This class of drug might also be considered in a puppy in which Bordetella bronchopneumonia is suspected or documented, because this organism has been demonstrated to increase lung resistance during experimental infection. Finally, dogs with aspiration pneumonia might benefit from a short course of a beta‐2‐agonist to combat acid‐induced bronchoconstriction. In general, bronchodilators can reduce the work of breathing and improve diaphragmatic strength; however, the potential for gastrointestinal toxicity associated with a methylxanthine drug must be considered. Also, use of enrofloxacin in combination with theophylline is not advised because of inhibition of theophylline metabolism, leading to higher plasma theophylline levels and potential toxicity.

Generalized supportive care and ancillary respiratory therapy will aid in resolution of pneumonia. Oxygen supplementation is beneficial in decreasing respiratory effort and improving clinical status. Promoting systemic hydration through use of intravenous fluids is very important for maintaining hydration of respiratory secretions and facilitating their removal from the respiratory tree. Saline nebulization followed by coupage is also beneficial in treatment of pneumonia by providing direct hydration of the lower airways, although clinical studies are lacking. See Chapter 3 for more information.

Prognosis

Most dogs and cats can be treated successfully for pneumonia, but therapy must be closely monitored and employed for an adequate amount of time depending on clinical response. In an animal with non‐resolving pneumonia, the possibility of a foreign body, pulmonary abscess, or underlying neoplastic process should be considered. In these cases, lung lobectomy is a viable option for the management of disease, although some dogs can have persistence of disease despite surgery. In one study, over half of the animals treated with lung lobectomy had resolution of disease (Murphy et al. 1997).

Pathophysiology

Organisms most commonly involved in systemic mycotic infections are thermally dimorphic fungi, existing as molds in the environment with transformation into yeasts following inhalation into the respiratory tract. In some cases, infection is resolved by the immune response. In an unknown percentage of dogs and cats, infection persists or progresses throughout the lung and regional lymph nodes or disseminates to other parts of the body. While ethnicity and immune status are recognized factors in the dissemination of disease in humans, less is known in veterinary species. The fungal organisms involved are characterized by specific geographic distribution. Histoplasma capsulatum and Blastomyces dermatitidis are found primarily in the Ohio/Mississippi river valley. Coccidioides immitis is found in the southwestern United States and in Central and South America. Other fungal organisms that occasionally cause pneumonia include Cryptococcus, Aspergillus, and Conidiobolus and these have world‐wide distribution. Pneumocystis is a rare cause of fungal pneumonia and is discussed under protozoal and other pneumonias, because the clinical syndrome is different from that of the mycotic infections described here.

Fungal organisms differ not only in geographic distribution but also in tissue trophism. In addition to pulmonary infection, all organisms tend to affect peripheral and internal lymph nodes; ocular and central nervous system tissue can also be involved. Histoplasma organisms infect the gastrointestinal tract, liver, spleen, and bone marrow, while causing skin lesions in cats. Blastomyces has a predilection for bone, skin, and the reproductive tract. C. immitis infects bone and cardiac structures in dogs, but often results in skin lesions in cats, as well as respiratory, bone, and ocular or neurologic signs in both species. Multi‐systemic involvement is one of the reasons these diseases are sometimes difficult to distinguish from neoplastic or septic processes. The widespread nature of disease also enhances the challenge of resolving infection, because therapeutic choices must be targeted to achieve specific tissue penetration depending on organ involvement.

History and Signalment

Dogs are infected with fungal pneumonia more frequently than cats and most animals are young, outdoor‐hunting breeds. Interestingly, cats with fungal pneumonia are often described as indoor pets, suggesting exposure to infecting organisms through fomites or via air flow through homes. A variety of historical complaints can be reported depending on the organ(s) affected. With respiratory system involvement, the most common complaints include tachypnea, cough, and respiratory difficulty. The pre‐patent period appears to be 2–4 weeks, and signs are often chronic (4 weeks or more), resulting in inappetence and weight loss. Depending on the organism involved, owners might report blindness with exophthalmos due to glaucoma or limited vision resulting from retinal lesions, lameness due to bone lesions, non‐healing skin lesions, or neurologic signs. Histoplasmosis can result in a severe protein‐losing enteropathy with diarrhea and weight loss, or spontaneous bleeding associated with thrombocytopenia and bone marrow involvement.

Physical Examination

Dogs and cats with fungal infections often present with fever, peripheral lymphadenopathy, and obvious signs of systemic illness. Abnormalities detected in the respiratory tract include labored respirations, tachypnea, and harsh bronchovesicular sounds or crackles. Wheezing or loud bronchial noises can be present when hilar lymphadenopathy results in bronchial compression, most often on the right side of the thorax. Tracheal sensitivity is often present. Ocular lesions include glaucoma, anterior uveitis, and chorioretinitis. Both central and peripheral neurologic deficits can be noted depending on the site of fungal granuloma formation. Ulcerated, draining skin lesions, testicular or prostatic enlargement, and bone pain can also be found depending on the infecting organism. Histoplasmosis affecting the bone marrow can result in severe thrombocytopenia and petechiation. Hepatosplenomegaly or a thickened gastrointestinal tract can also be found in animals with histoplasmosis.

Diagnostic Findings

Fungal infection should be suspected in an animal with multi‐systemic disease that has a history of travel to an area endemic for a fungal organism. However strict boundaries do not exist for the environmental niches, and given climate changes that are occurring world‐wide, the geographic localization of some fungal organisms seems to be expanding or changing. Laboratory testing commonly reveals a mild non‐regenerative anemia, neutrophilic and monocytic leukocytosis, hypoalbuminemia associated with chronic disease or gastrointestinal fungal infection, thrombocytopenia due to bone marrow involvement, and potentially hypercalcemia (primarily with blastomycosis).

Thoracic radiographs reveal a variety of pulmonary infiltrative patterns including a miliary or nodular infiltrates, generalized interstitial or bronchial pattern, lobar consolidation, or a mass effect. Hilar or sternal lymphadenopathy is relatively common in dogs (Figure 6.8). Many of the radiographic findings in dogs affected with fungal disease can mimic those found in primary or metastatic neoplasia. In cats, a miliary or nodular interstitial pattern is relatively common (Figure 6.9), although sometimes radiographs can mimic those found in feline bronchial disease or pulmonary fibrosis.

Serologic assays for most fungal infections (histoplasmosis, blastomycosis, and coccidioidomycosis) are variably useful, because animals in endemic regions will usually develop a positive antibody titer due to exposure to the organism. Also, a serologic response takes time to mount and dogs with fulminant infection due to blastomycosis are often negative in the early stages of disease. In contrast, serology for antibodies to coccidioidomycosis remains a useful screening tool. In a dog or cat with appropriate clinical findings and travel to an area endemic for C. immitis, a positive coccidioidomycosis titer can be considered relatively diagnostic, particularly if a quantitative agar gel immunodiffusion test for immunoglobulin (Ig) M and IgG is performed (University of California, Davis School of Medicine, www.ucdmc.ucdavis.edu/medmicro/cocci). Coccidioides antibody lateral flow assays are rapid tests that can provide early suspicion of the diagnosis of coccidioidomycosis, (Grill et al. 2024) although cross‐reactivity is noted in cases of histoplasmosis with some tests. Follow‐up quantitative immunodiffusion titers are recommended to provide more information on the likelihood of infection and to follow the course of disease.

Serum or urine antigen tests have better accuracy in the diagnosis of blastomycosis and histoplasmosis despite cross‐reactivity for these fungal organisms. An enzyme immunoassay (MiraVista Diagnostics, Indianapolis, IN) directed against the galactomannan antigen on the cell wall of fungal organisms demonstrated slightly better sensitivity when performed on urine samples than when applied to serum (Spector et al. 2008). In addition, this test can be useful in monitoring response to therapy, because antigen levels decline with azole treatment and rebound with relapse (Foy et al. 2014).

Diagnosis of a fungal infection can be confirmed by cytologic or histologic assessment of lymph node or organ aspirates, airway samples obtained by tracheal wash or BAL, skin impression smears, rectal scrapes, aqueocentesis samples, or bone marrow evaluation. Fungi are of distinctive sizes and shapes and are usually surrounded by pyogranulomatous inflammation (Table 6.3). Culture is rarely needed to confirm the diagnosis and is not advised in cases suspected of coccidioidomycosis because of zoonotic concerns for laboratory personnel.

Treatment

Depending on the severity and extent of illness, fungistatic or fungicidal therapy might be preferred in an animal with fungal pneumonia (see Chapter 3). In animals with a severe fungal burden in the respiratory tract, die‐off of organism can result in respiratory distress syndrome. In select cases, a non‐steroidal anti‐inflammatory agent or a glucocorticoid is employed to reduce the risk of severe pulmonary inflammation. Glucocorticoids are also sometimes used to reduce hilar lymphadenopathy when it is creating a substantial contribution to respiratory distress and cough because of bronchial obstruction. Despite concerns about immunosuppression impacting control of fungal disease, short‐term use of glucocorticoids has not resulted in worsened outcome.

Long‐term therapy with azoles (5–9 months) should be anticipated in all cases, and frequent monitoring is required to ensure effective treatment of fungal infection. Remission rates in dogs or cats with blastomycosis and histoplasmosis range from 60 to 90% and no difference has been found when using fluconazole versus itraconazole (Mazepa et al. 2011; Wilson et al. 2018). Higher urine or serum antigen titers at the time of diagnosis in dogs might mean that azole therapy will be required for a longer period of time.

Prognosis

Survival rates for animals with fungal pneumonia are not specifically known, although dogs that survive the first week of treatment are often cured of disease with long‐term treatment. Dogs with lower urine antigen concentration and less severe radiographic scores for lung lesions tended to have better survival than those with higher scores (Motschenbacher et al. 2021). The need for oxygen supplementation is often reported as a negative prognostic indicator for animals with fungal pneumonia and this likely reflects the severity of pulmonary dysfunction. The final outcome depends not only on the severity of lung disease, but also on the presence of other organ involvement. Surgery is often required for a dog with a painful glaucomatous eye, in an intact male dog that might sequester organisms in the prostate, or in a dog with a consolidated lung lobe. Despite appropriate therapy, relapses still occur in 20–30% of dogs with histoplasmosis or blastomycosis (Mazepa et al. 2011; Wilson et al. 2018). This rate of relapse is likely similar for infection with C. immitis as well as fungal infections in cats.

Pathophysiology

Although rare, pneumonia can result from infection with protozoan organisms such as Neospora caninum and Toxoplasma gondii. In addition, Pneumocystis canis, an organism that shares some characteristics of protozoans but has been classified as a fungal organism, can result in presentation for pneumonia. Pneumocystis organisms can be found in the lungs of normal, healthy individuals at a low level (considered colonization) and development of infection is typically associated with immunosuppression allowing expansion of the number of organisms present (Danesi et al. 2017). In dogs, a combined congenital immuno‐deficiency is suspected in the Miniature Dachshund (Lobetti 2000) and an IgG deficiency has been proposed in Cavalier King Charles Spaniels (Watson et al. 2006) that results in Pneumocystis pneumonia in these breeds. Iatrogenic immunosuppression has the potential to reactivate or worsen infection by any of these organisms. All of these protozoal and similar organisms can cause neutrophilic inflammation and interstitial pneumonia.

History and Signalment

Pneumonia due to Neospora can be seen in congenitally infected puppies in conjunction with ascending paralysis of the limbs. Disease is associated with a high fatality rate. Toxoplasma pneumonia of cats or kittens is usually associated with severe systemic disease and rapidly progresses to death. In the dog, toxoplasmosis is less common, but infection can also result in pneumonia. Pneumocystosis has been reported most commonly in Miniature Dachshunds less than 1 year of age and in adult Cavalier King Charles Spaniels, as well as sporadically in other breeds. Typical presenting complaints with Pneumocystis pneumonia include progressively worsening exercise intolerance and tachypnea, chronic cough, and gradual weight loss.

Physical Examination

Tachypnea with labored respiration or increased respiratory effort is common. Fever is generally absent or body temperature only mildly elevated, and animals display a poor body condition score. Respiratory auscultation is generally unremarkable or harsh bronchovesicular sounds are noted, and a dry cough can be triggered by tracheal palpation. Systemic or neurologic signs can be seen in animals with toxoplasmosis or neosporosis. Chorioretinitis has been reported with Pneumocystis pneumonia (Johnson et al. 2023) and is also possible with infection by Toxoplasma organisms, where uveitis, iritis, iridocyclitis, or chorioretinitis can be seen.

Diagnostic Findings

Standard laboratory tests reveal non‐specific findings of neutrophilic leukocytosis. Positive serology for Neospora in conjunction with clinical signs provides a presumptive diagnosis. A diagnosis of Toxoplasma would be suspected in an animal with relevant clinical findings that has a positive IgM titer or a fourfold increase in IgG titer in conjunction with a positive response to treatment. It is rare to document Toxoplasma oocysts in the feces. In Cavalier King Charles Spaniels suspected of pneumocystosis, measurement of serum immunoglobulins should be considered.

Thoracic radiographs in protozoal or Pneumocystis pneumonia most commonly reveal diffuse interstitial or nodular infiltrates (Figure 6.10), although alveolar densities are occasionally seen. Pneumocystis can be identified in tracheal wash, BAL fluid, or fine‐needle lung aspirate, although detection can be challenging. Pneumocystis organisms appear as trophic forms ranging in size from 2 to 8 μm, or as cysts which are 5–10 μm in size and contain two to eight small inclusions that are 1–3 μm in diameter (Figure 6.11). Fine‐needle aspirate samples might have greater diagnostic yield, and Giemsa staining of airway fluid can sometimes enhance recognition (Weissenbacher‐Lang et al. 2018). Quantitative PCR‐based testing has recently been reported and likely will become the diagnostic standard (Danesi et al. 2017). Toxoplasma tachyzoites that can be found in BAL fluid are 2 × 6 μm and are found extracellularly or intracellularly within macrophages. Necropsy findings in protozoal‐type pneumonias are typically diagnostic.

Treatment

Toxoplasma is most commonly treated with clindamycin (12.5 mg/kg orally [PO] twice a day [BID]) or trimethoprim‐sulfa (15 mg/kg PO daily to BID) for >4 weeks. Clindamycin might also be effective for Neospora. Treatment of Pneumocystis pneumonia relies on the use of trimethoprim‐sulfa at 15–30 mg/kg PO BID–TID for 4 weeks or longer as needed. Dogs treated with trimethoprim‐sulfa should be monitored for development of keratoconjunctivitis sicca, anemia due to folate deficiency, and liver toxicity throughout treatment. Standard supportive care for pneumonia with oxygen supplementation should also be employed as needed.

Prognosis

Pulmonary toxoplasmosis or neosporosis is often fatal in young animals. Young adult Cavaliers with pneumocystosis might have a relatively good prognosis (Watson et al. 2006), although other scattered reports suggest <50% survival in animals with Pneumocystis pneumonia. It is likely that the degree of lung involvement determines response to therapy (Figure 6.12).

Pathophysiology

Eosinophilic lung disease in the dog is a poorly understood disorder. Heartworm disease, lung parasitism, and larval migration of parasites are recognized causes of pulmonary eosinophilia; however, primary eosinophilic infiltration of the lung can occur in the absence of an identifiable inciting cause. The finding of increased CD⁴⁺ T‐cells in BAL fluid suggested that a type II hyper‐sensitivity response might be responsible for eosinophilic bronchopneumopathy (EBP) (Clercx et al. 2002), although cytokine profiles in airway tissues from affected dogs did not support a Th2 or allergic response (Peeters et al. 2006). Eosinophilic lung disease can result in a spectrum of clinical syndromes including a condition described as similar to chronic bronchitis (EB), a more severe pneumonic form (EBP), and eosinophilic granuloma (EG), characterized by nodules or masses within airways (Johnson et al. 2019). This might be an artificial categorization of eosinophilic lung diseases in dogs, and it is unclear whether these disorders share the same etiopathogenesis or have differing stimuli for induction of disease.

History and Signalment

Dogs with eosinophilic lung disease are usually young adults, ranging from ~1 year to 8 years of age, and can be of any breed or size. Owner complaints can be present for months to years prior to presentation and generally include a harsh, unrelenting cough and progressive respiratory difficulty with exercise intolerance. Some dogs have concurrent nasal discharge or are systemically ill with lethargy and anorexia. Lack of response to antibiotics is common in the history.

Physical Examination

Increased or harsh bronchovesicular lung sounds are frequently present and harsh crackles can be detected, particularly in animals with concurrent airway collapse. In some cases, expiratory wheezes might also be heard. Tracheal palpation often results in a moist, productive cough with expectoration of white foam, although some dogs have a more honking nature to the cough. Some dogs display yellow‐green nasal discharge but nasal airflow is preserved, regional lymph nodes are normal, and no other abnormalities in physical examination findings are anticipated. Body temperature is sometimes elevated in dogs with pneumonic signs.

Pathophysiology

Aspiration pneumonia is a serious and potentially life‐threatening inflammatory and/or infectious lung process that occurs secondary to inhalation of gastric or oropharyngeal contents. Pulmonary injury results from chemical pneumonitis and the effect of particulate matter in the lung, inflammatory pulmonary responses, and development of bacterial pneumonia. Initially, aspiration of gastric acid alters surfactant function, resulting in loss of surface tension and atelectasis. Injury to epithelial cells allows bacterial invasion and also exposes nerve endings between epithelial cells, resulting in bronchoconstriction. Resultant inflammation and infection increase mucus production, causing airway obstruction and difficulty breathing. Ventilation/perfusion mismatching results in hypoxemia. Severe aspiration injury is associated with increased alveolocapillary permeability and development of acute respiratory distress syndrome due to non‐cardiogenic pulmonary edema (see Chapter 8).

Aspiration pneumonia can often be ascribed to one underlying disease, but multiple predisposing factors can also be found. Esophageal dysfunction or megaesophagus, vomiting or chronic enteropathies, neurologic disorders associated with recumbency or loss of consciousness, laryngeal dysfunction or surgery, and anesthetic‐related aspiration events are identified most commonly (Kogan et al. 2008b; Ovbey et al. 2014; Levy et al. 2019). In the latter, regurgitation while under anesthesia and use of hydromorphone at induction were most relevant in the development of aspiration pneumonia (Ovbey et al. 2014). The type of procedure also played a role in the occurrence of aspiration, with animals requiring upper airway surgery at the highest risk, followed by endoscopic procedures, thoracotomy, laparotomy, and neurosurgery. Brachycephalic syndrome can also result in aspiration pneumonia or pneumonitis, because many dogs have concurrent respiratory and gastrointestinal dysfunction associated with conformational issues and require surgical correction of upper airway obstruction.

History and Signalment

Aspiration pneumonia appears to be much more common clinically in dogs than in cats, and any age or breed can be affected because of the multitude of predisposing diseases that result in aspiration pneumonia. Large breed dogs predominate in some studies because of the commonality of esophageal and laryngeal dysfunction, although brachycephalic breeds have been found to have approximately a fourfold increase in the incidence of aspiration pneumonia (Darcy et al. 2018). Interestingly, large breed dogs and Pugs tend to be older at the time of diagnosis, while Bulldogs and French Bulldogs are younger (Kogan et al. 2008a; Darcy et al. 2018). Cough and increased respiratory rate or effort are noted in more than half of the canine cases. Generally the history will provide clues to the underlying disease process leading to aspiration, such as a recent vomiting episode, seizure, or anesthetic event; however, it is uncommon for the aspiration episode to be witnessed. Also, occult and micro‐aspiration likely account for more lower respiratory disease than is currently recognized.

Cats with aspiration pneumonia tend to have a shorter duration of illness (<2 weeks) compared to cats with bacterial bronchopneumonia (up to 9 months), and cough is less common in cats with aspiration compared to bronchopneumonia (Dear et al. 2021). Increased respiratory effort can be obvious to owners (Levy et al. 2019).

Physical Examination

Abnormal lung sounds are found in over half of dogs and cats with aspiration pneumonia, although many will be described as harsh or loud lung sounds, while a lesser percentage will have detectable crackles or wheezes. Normal lung sounds have been reported in 30% of dogs and approximately 10% had dampened lung sounds (Kogan et al. 2008a). Fever (temperature >39.2°C [>102.5°F]) or tachypnea (respiratory rate >30 breaths/minute) is expected in dogs with pneumonia, but these are found in less than half of affected dogs. In contrast, cats with aspiration pneumonia tend to be hypothermic and tachypnea is relatively common with any lower respiratory disease (Dear et al. 2021).

The remainder of the physical examination is important for determining the underlying etiology of aspiration. Stridor over the larynx is suspicious for laryngeal disease, and some dogs with laryngeal paralysis display a reduced gag reflex associated with generalized neuromuscular disease, along with decreased proprioceptive placing, more prominent in the rear limbs and sometimes only unilateral. In such animals, complete neurologic assessment is warranted. Careful observation of the animal prehending and eating food or drinking water is beneficial in detecting subtle abnormalities in pharyngeal or esophageal function. Abdominal pain might support ongoing pancreatitis as a cause for vomiting, with secondary aspiration injury, or thickened bowel loops caused by an enteropathy can occasionally be found (although this would be much more commonly identified in a cat than in a dog).

Diagnostic Findings

Neutrophilia with a left shift is present in the majority of affected dogs and cats, indicating a response to inflammation, and albumin is often mildly decreased, perhaps due to lung inflammation and vascular leakage. Pulse oximetry or arterial blood gas analysis can be helpful in assessing the degree of lung dysfunction because some dogs are markedly hypoxemic.

The classic radiographic description of aspiration pneumonia is an alveolar infiltrate in the cranioventral or middle lung lobe region; however, approximately 25% of dogs can have an interstitial infiltrate at the time of diagnosis. Aspiration into the right lung occurs in over 50% of canine cases, while both sides of the lung are involved in 12% (Kogan et al. 2008a). The most commonly involved lung lobe is the right middle lobe (Figure 6.17), followed by the right cranial and the caudal segment of the left cranial lobe, and the cranial segment of the left cranial lung lobe, although any lung lobe can be involved, depending on the position of the animal at the time of aspiration. Cats with aspiration tend to have alveolar infiltrates and a more multifocal distribution in comparison to cats with bacterial bronchopneumonia. Right middle lobar consolidation also occurs in cats with aspiration (Levy et al. 2019; Dear et al. 2021) and must be differentiated from right middle lobar collapse, which is common in cats with inflammatory airway disease. The left cranial lung lobe is also commonly involved in aspiration events in cats (Levy et al. 2019).

Airway samples are not always obtained in animals suspected of aspiration injury because of concerns about further aspiration following sedation or because anesthesia is required for collection of airway fluid. When infection is present, airway wash samples would be expected to reveal septic suppurative inflammation and various bacterial species, particularly Pasteurella, enteric organisms, and Mycoplasma (Darcy et al. 2018), although Mycoplasma and anaerobes appear to predominate in cats (Dear et al. 2021). If only chemical injury is present, neutrophilic inflammation in the absence of intracellular bacteria would likely predominate.

Treatment

Antibiotic administration in the patient with presumed aspiration pneumonia is controversial because not all aspiration events are associated with infection, and some dogs can recover without the use of antimicrobials (Cook et al. 2021). When infection is confirmed, clinical disease is severe, or systemic manifestations are suggestive of infection, broad‐spectrum agents are usually given for 1–2 weeks. Depending on the severity of disease, a potentiated penicillin derivative is typically chosen, or the combination of a penicillin and fluoroquinolone is used. A bronchodilator trial using terbutaline might be considered in the acute stage of disease, particularly if expiratory effort or wheezing suggests bronchoconstriction. Maintenance of airway hydration with intravenous fluids is important. Saline nebulization can be helpful but coupage is not usually recommended in animals with aspiration pneumonia because of the potential to increase intraabdominal pressure and augment vomiting. Also, coupage is challenging to perform in recumbent patients. Glucocorticoids are not recommended despite the fact that an inflammatory response contributes to pulmonary injury, and non‐steroidal agents are typically not administered due to concerns about gastrointestinal side effects.

Animals that are not markedly hypoxemic or exhibiting dramatic respiratory effort can be maintained without supplemental oxygen, because experimental evidence suggests that oxygen can enhance acid‐induced injury in models of aspiration injury. However, aspiration pneumonia can lead to acute respiratory distress syndrome (see Chapter 8), and in these patients, mechanical ventilation can be required to support oxygenation while pulmonary injury resolves.

Perhaps the most important consideration in the animal with aspiration pneumonia is to provide appropriate management of the primary disease responsible for aspiration. This will assist in avoidance of further aspiration and perpetuation of airway injury. Suppression of gastric acid can be helpful in some cases, although there is a theoretical concern that allowing gastric pH to rise will increase bacterial load in the aspirated material and possibly worsen the infectious component of aspiration injury. Some acid suppressants can promote vomiting, thus increasing the potential for aspiration events. Continual monitoring is advised. Providing food and water in an upright position is important for animals with esophageal or laryngeal disease. Modification of the consistency of the diet should be instituted in dogs, because some animals are better able to prehend and swallow kibble while others do well with meatball feeding.

Prognosis

Aspiration pneumonia carries a relatively good prognosis, with survival rates of 75–80% despite the presence of more than one predisposing disorder for aspiration (Kogan et al. 2008b; Levy et al. 2019). Radiographic severity of disease does not necessarily correlate with survival and further classification of disease severity is likely necessary to establish factors important in prognosis.

Pathophysiology

In human medicine, interstitial lung diseases (ILD) have been reported to develop secondary to infectious organisms (bacteria, viruses, or fungi), immune‐mediated disease, exposure to drugs (e.g. antimicrobial or anti‐arrhythmic agents) or inhaled toxins (e.g. paraquat, hydrocarbon‐containing sprays, industrial flavorings), and in association with neoplasia. It is suspected that similar disorders or exposures that damage the alveolar‐capillary membrane can lead to ILD in dogs and cats. Epithelial cell activation, induction of inflammation, and dysregulated mesenchymal repair lead to structural changes in the alveolar unit with enhanced interstitial collagen deposition. This results in reduced lung compliance and dysfunctional gas exchange.

Various pathologic forms of ILD have been described in dogs and cats, including idiopathic pulmonary fibrosis (IPF), cryptogenic fibrosing alveolitis, and bronchiolitis obliterans with organizing pneumonia. Some of these diseases are characterized by inflammation, while in others, the interstitium is infiltrated by fibroblasts and there is collagen deposition, smooth muscle and alveolar epithelial metaplasia, with very little inflammation. This is of obvious importance when considering the value of treatment with anti‐inflammatory agents.

An IPF‐like condition has been described in the cat (Cohn et al. 2004) and is the most common form of ILD in the West Highland White Terrier. In the Westie, transforming growth factor beta, endothelin‐1, and micro‐aspiration injury likely play key roles in the pathogenesis, although a genetic predisposition is also suspected (Heikkilä et al. 2011; Syrjä et al. 2013; Krafft et al. 2014; Määttä et al. 2018). Failure of collagenolysis has also been implicated as part of the pathology in the West Highland White Terrier. Some dogs can be affected by concurrent bronchitis, which results in chronic cough and can obscure dysfunction associated with the underlying lung disease. In the cat, coincident pulmonary neoplasia has been noted in 25% of pulmonary fibrosis cases (Cohn et al. 2004).

History and Signalment

IPF afflicts West Highland White Terriers more commonly than other Terrier breeds and can also be found in various types of cats. Animals are usually middle‐aged to older at the time of presentation, and there is generally a long history of chronic deterioration in respiratory function. Tachypnea develops over time and exercise intolerance becomes more pronounced. These changes are often ascribed to aging and pulmonary dysfunction goes unrecognized until late in the course of disease. A dry, non‐productive cough predominates in some animals, or owners may report loud respirations or rapid breathing. Systemic signs of lethargy, anorexia, and weight loss are relatively common, especially in cats. Severely affected animals can develop syncope due to hypoxemia or pulmonary hypertension.

Occasionally, younger (2–5‐year‐old) large breed dogs develop ILD of unknown etiology, and acute onset of severe tachypnea can be the only sign of disease in these dogs. Potential etiologies include an autoimmune or hypersensitivity disorder, inhalational exposure to a toxin or particulate matter, paraquat ingestion, or an unrecognized viral infection. Sporadic cases have been poorly characterized.

Physical Examination

Tachypnea can be dramatic in affected animals, with respiratory rates of 100–150 breaths/minute in the absence of panting. The classic auscultatory finding in Westies with IPF is inspiratory crackles, which can be soft or loud and often present diffusely throughout all lung fields. In cats, lung sounds can be harsh or loud or adventitious sounds (crackles and wheezes) might be ausculted. Animals with secondary pulmonary hypertension can develop a right‐sided systolic murmur of tricuspid regurgitation or a split‐second heart sound. The remainder of the physical examination is usually unremarkable unless cor pulmonale results, which could be associated with ascites, pleural effusion, or distended jugular veins.

Diagnostic Findings

The minimum database is used to rule out concurrent systemic diseases. Laboratory findings of a neutrophilic leukocytosis and mild hyperproteinemia reflect chronic inflammation. Pulse oximetry (or arterial blood gas) is recommended to assess the degree of dysfunction, because dramatic hypoxemia – partial pressure of oxygen (P_aO₂) <50 mmHg – can be seen in some dogs. The search for serum and BAL biomarkers that would provide a less invasive means of confirming a diagnosis of IPF is ongoing.

Thoracic radiographs in dogs typically show a generalized or diffuse mild, moderate, or severe interstitial pattern that obscures visualization of the vasculature, and CT can highlight the severity of the infiltrate (Figure 6.18). Moderate cardiomegaly is relatively common in affected dogs and is primarily right‐sided. Variable diffuse or patchy interstitial, bronchial, and/or coalescing alveolar infiltrates are observed in cats, and radiographic changes are generally described as severe, with caudal lobes more prominently involved (Cohn et al. 2004). Additional findings include bronchiectasis (Figure 6.19) or cavitated lesions, which could indicate concurrent neoplasia. Right‐sided heart enlargement or pulmonary artery dilation could be a sign of pulmonary hypertension in cats also. Whether present or not, echocardiography should be considered in the diagnostic work‐up of suspected cases of ILD to document pulmonary hypertension (see Chapter 8).

CT identification of ground‐glass opacities and the pattern of honeycombing are considered the gold standard in the diagnosis of IPF in humans. Ground glass opacities are described as a hazy attenuation of the lung parenchyma that preserves visualization of bronchovascular structures. Honeycombing is the descriptive term used for the clusters of uniformly sized cystic airspaces that represent collapse of fibrotic alveoli and dilation of the alveolar duct. This finding is considered indicative of end‐stage lung disease. While thoracic CT is being used more commonly in veterinary medicine than previously, the need for anesthesia to obtain breath‐hold images in dogs along with the cost of the procedure can prohibit use of this imaging modality. Sedated high‐resolution CT was capable of identifying ground‐glass opacifications and mosaic patterns more commonly in affected West Highland White Terriers than in controls (Roels et al. 2017), although it is unclear whether these lesions should be considered pathognomic in the absence of histologic confirmation of disease.

Definitive diagnosis of ILD requires histopathologic evaluation of a lung sample obtained through thoracotomy, thoracoscopy, or key‐hole lung biopsy. Preoperative CT is recommended to identify the extent of parenchymal changes and, importantly, to identify a site for lung biopsy or lobectomy, because the disease is often patchy in distribution. Histopathologic findings of alveolar septal fibrosis, type II pneumocyte hyperplasia, smooth muscle cell hyperplasia, and epithelial metaplasia can be locally extensive or diffuse. Airway sampling by tracheal wash or bronchoscopy can be performed as a less invasive alternative to lung biopsy, although a non‐specific increase in non‐degenerate neutrophils and/or lymphocytes is typically seen.

Treatment

Unfortunately, treatment options for IPF are limited and fibrotic changes do not respond to anti‐inflammatory therapy, although signs of concurrent bronchitis can be alleviated by oral or inhaled glucocorticoids. Anti‐fibrotic drugs used in humans (pirfenidone, nintedanib) or anti‐mediator drugs have not been fully evaluated in dogs and can be toxic, as well as expensive. Exposure to toxins and inhalational injury should be avoided, microaspiration should be managed, weight control is important, and a trial on extended‐release theophylline could be considered to lessen respiratory effort. In some animals, oxygen therapy at night can improve daytime activities, and treatment of pulmonary hypertension with sildenafil or tadalafil can improve overall health and well‐being (see Chapter 8). Alternate therapy remains under investigation pending further information regarding the etiology of disease.

Pathophysiology

Primary pulmonary neoplasia is almost always malignant and is characterized by the histology of the cell origin. The most common lung tumor in dogs and cats is pulmonary carcinoma but pulmonary adenocarcinoma, bronchoalveolar carcinoma, histiocytic sarcoma (which can be primary or disseminated with pulmonary metastasis), and neuroendocrine tumors can be encountered, among other less common tumors (Fowler et al. 2020; McPhetridge et al. 2022). Pulmonary lymphosarcoma is relatively uncommon. Primary neoplasms are staged based on the TNM (Tumor–Node–Metastasis) classification, with T1 indicating a solitary mass, T2 multiple masses, and T3 a tumor invading local tissues or with distal metastasis. N0 and M0 indicate no nodal involvement or metastasis.

Pulmonary neoplasia in humans is caused predominantly by smoking, which results in the generation of endobronchial lesions. Studies to date have not confirmed a definitive association between smoke, pollutants, or environmental particulate matter such as anthrocosis, silicosis, and pneumoconiosis in the development of pulmonary neoplasia in dogs and cats, although exposure to household radon appears to increase the risk of pulmonary neoplasia by two‐fold (Fowler et al. 2020).

The lung is a very common site for metastasis from carcinomas or sarcomas because of its rich capillary bed, and metastatic disease is much more common than primary. Tumors that commonly metastasize to the lung include hemangiosarcoma, osteosarcoma, thyroid carcinoma, and mammary carcinoma. Also, primary pulmonary neoplasia in dogs and cats often results in intrapulmonary metastasis, which can make it hard to differentiate primary from metastatic disease, particularly in cats. Cats can also demonstrate metastasis to the digits (Gottfried et al. 2000) or to the tail.

Prognosis

The presence of respiratory signs at the time of diagnosis appears to be associated with a worsened prognosis in dogs and cats. Prognosis also depends on tumor histology, state of differentiation, and mitotic index. Abnormal appearance of local lymph nodes on thoracic CT or intrapulmonary metastasis are negative prognostic indicators, as is tumor size >7 cm (Lee et al. 2020). In some situations, the presence of pleural effusion worsens prognosis.

In dogs treated with lobectomy for a solitary pulmonary mass, median survival for various forms of primary pulmonary carcinoma ranges from 2 to 30 months. Localized pulmonary histiocytic sarcoma has a better prognosis than disseminated disease, with a survival time of approximately 13 months following surgery and chemotherapy (Marlowe et al. 2018). In cats with histologically well‐differentiated pulmonary tumors, median survival is 2 years, while those with poorly differentiated neoplasms have <3 months median survival (Hahn and McEntee 1998). Unfortunately, many animals with primary pulmonary neoplasia have metastasis to bronchial lymph nodes, other lung lobes, pleura, skeletal muscle, skin, liver, spleen, or brain at the time of diagnosis. In addition, recurrence of neoplasia or metastasis can be encountered later in life.

In dogs that were not surgical candidates, improved quality of life and acceptable survival (median ~6 months) was reported with use of metronomic chemotherapy that included piroxicam, cyclophosphamide, and thalidomide (Polton et al. 2018). Metronomic chemotherapy is long‐term, low‐dose treatment designed to control neoplastic growth through anti‐angiogenic and anti‐inflammatory mechanisms, rather than to kill neoplastic cells. Piroxicam alone can be palliative in some dogs with pulmonary neoplasia that are not surgical candidates and is associated with few side effects when administered at 0.3 mg/kg/day. In cats with metastatic pulmonary carcinoma, palliative treatment with chemotherapy may result in a mildly better response than those treated only with a glucocorticoid or non‐steroidal agent, although the median survival time in either group was <2 months in one study (Treggieri et al. 2021). Clinical signs appeared to improve in both groups of cats.