Inflammatory airway disease of horses

The purpose of this consensus statement is to provide a review of current knowledge and opinions concerning inflammatory airway disease (IAD) and to help practitioners differentiate IAD from heaves (or recurrent airway obstruction; RAO) and other inflammatory respiratory diseases of horses.     

Plasma and Pulmonary Fluid Endothelin in Horses with Seasonal Recurrent Airway Obstruction

Background: Summer pasture-associated recurrent airway obstruction (SPA-RAO), a seasonal airway obstructive disease of horses, is characterized by clinical exacerbation after exposure to pasture during warm months of the year. Endothelin (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory mediator, has been implicated in the pathogenesis of asthma and equine heaves.
Hypothesis: Immunoreactive ET-1 concentrations increase during clinical exacerbation and return to basal values during periods of disease remission.
Animals: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected.
Methods: Prospective, observational study. Bronchoalveolar lavage fluid (BALF), arterial and venous plasma samples, and clinical variables were obtained from affected horses during clinical exacerbation and remission. Samples and data of nonaffected horses were collected during the summer and winter on dates similar to affected horses. Immunoreactive ET-1 was determined using a commercial ELISA.
Results: The median and range ET-1 concentrations (pg/ml) in arterial (1.3, 0.7–1.8) and venous (1.3, 1.2–1.7) plasma and in BALF (0.3, 0.2–0.4), and pulmonary epithelial lining fluid (PELF) (25.5, 21–50) were greater in affected horses during clinical exacerbation compared with remission ( P < .01). The concentrations of immunoreactive ET-1 were greater in affected horses during clinical exacerbation compared with nonaffected horses ( P < .05).
Conclusions and Clinical Importance: During clinical exacerbation of SPA-RAO, ET-1 is increased in circulation and pulmonary secretions. Intervention with ET receptor antagonists should provide further information on the role of ET-1 in SPA-RAO.     

Evaluation of Right Ventricular Myocardial Function in Healthy Horses With Recurrent Airway Obstruction Using Tissue Doppler Imaging

It has been described in humans that chronic obstructive bronchitis leads to pathologic changes, especially in the right ventricular myocardium due to hypoxia, which can be assessed by tissue Doppler imaging (TDI). In our study, different TDI techniques, that is, pulsed-wave TDI and color TDI, were evaluated for applicability in different scan planes (apical long-axis view and short-axis view) for the analysis of right ventricular myocardial function in six healthy horses (control) and six horses affected with recurrent airway obstruction (RAO) (RAO group). Tissue Doppler imaging was applicable to all scan planes described. Myocardial movement directions in general and the absolute values of TDI parameters were assessable. Significantly reduced early diastolic filling velocities (E), elevated late diastolic filling velocities (A), thereby decreased E/A quotient, prolonged electromechanical coupling periods between electrocardiograph Q-wave and maximal velocities, and compensatory elevated systolic strain as well as diminished displacement could be observed in horses with RAO compared with the control group. To conclude, equine right ventricular myocardial function is assessable by TDI. Significant changes of right ventricular myocardial function could be demonstrated by TDI in horses with RAO compared with matched healthy controls. The hypothesis that RAO potentially leads to right ventricular dysfunction detectable by TDI before conventional echocardiography changes are evident is supported by this explorative study.     

Secretoglobin and Transferrin Expression in Bronchoalveolar Lavage Fluid of Horses with Chronic Respiratory Disease

Background

Lower expression of secretoglobin and transferrin has been found in the bronchoalveolar lavage fluid (BALF) of a small number of horses with experimentally induced signs of recurrent airway obstruction (RAO) compared to healthy controls.

Hypothesis/Objectives

Secretoglobin and transferrin BALF expression will be similarly decreased in horses with naturally occurring clinical signs of RAO and in horses with experimentally induced clinical signs of RAO as compared to healthy controls and intermediate in horses with inflammatory airway disease (IAD).

Animals

Recurrent airway obstruction‐affected and control horses were subjected to an experimental hay exposure trial to induce signs of RAO. Client‐owned horses with a presumptive diagnosis of RAO and controls from the same stable environments were recruited.

Methods

Pulmonary function and BALF were evaluated from control and RAO‐affected research horses during an experimental hay exposure trial (n = 5 in each group) and from client‐owned horses (RAO‐affected horses, n = 17; IAD‐affected horses, n = 19; healthy controls, n = 5). The concentrations of secretoglobin and transferrin in BALF were assessed using Western blots.

Results

Naturally occurring and experimentally induced RAO horses had similar decreases in BALF transferrin expression, but secretoglobin expression was most decreased in naturally occurring RAO. Secretoglobin and transferrin expression were both lower in BALF of RAO‐affected horses than in IAD‐affected and control horses.

Conclusions and Clinical Importance

Secretoglobin and transferrin expression is decreased in BALF of RAO‐affected horses after both experimental and natural exposure. Secretoglobin and transferrin likely play clinically relevant roles in the pathophysiology of RAO, and may thus be used as biomarkers of the disease.     

Investigating the Link between Particulate Exposure and Airway Inflammation in the Horse

Inhalant exposure to airborne irritants commonly encountered in horse stables is implicated in the pathogenesis of inflammatory airway disease (IAD) and recurrent airway obstruction (RAO), non‐infectious, inflammatory pulmonary disorders that impact the health and performance of horses across all equine disciplines. IAD and RAO have overlapping clinical, cytological, and functional manifestations of the pulmonary response to organic dust and noxious gases encountered in the barn environment. Study of these diseases has provided important but incomplete understanding of the effect of air quality upon the respiratory health of horses. In this review, the principles of particulate exposure assessment, including health‐related aerosol size fractions and size‐selective sampling, the factors influencing air quality in equine environments, and the effect of air quality on the equine respiratory tract are discussed. The objective of this review is to provide the reader with a summary of the most common chronic inflammatory airway diseases in the horse and the principles of air sampling that are essential to the planning, interpretation, and assessment of equine respiratory health‐related exposure studies.     

Clinical Feasibility and Airway Deposition of Nebulized Voriconazole in Healthy Horses

Voriconazole (VRC) is a potential treatment for pneumomycosis in horses. The objectives of this study were to determine if the delivery of Vfend using a Flexineb nebulizer produced clinically significant [VRC] in lower airways. The hypothesis was that [VRC] after delivery by nebulization would be greater in the pulmonary epithelial lining fluid than plasma. A secondary objective was to determine [VRC] in upper airways through the collection of nasopharyngeal wash (NPW) samples. Voriconazole solution [Vfend-6.25 mg/mL, 100 (n = 2), 200 (n = 3), 500 (n = 1) mg] was nebulized once in 6 healthy geldings. Clinical responses, duration of nebulization, and [VRC] at various time points (up to 8 hours) in plasma, bronchoalveolar lavage fluid (BALF) supernatant and cell pellet, and NPW samples were recorded. Voriconazole (Vfend-6.25 mg/mL, 200 mg) was nebulized in 5 additional, healthy geldings, and [VRC] was measured in NPW samples pre- and postnebulization at time points up to 8 hours. The antifungal activity of BALF and NPW samples was determined using agar disk diffusion. Concentrations of voriconazole were below detection in plasma, BALF supernatant, and cell pellets for all time points and doses except the BALF cell pellet (0.4 μg/g) immediately after nebulization of 500 mg. For 5 horses, administered 200 mg of Vfend, mean [VCR] in NPW at the end of nebulization and 1, 6, and 8 hours postnebulization were: 30.8 ± 29, 1.0 ± 0.84, 0.2 ± 0.19, and 0.34 ± 0.67 μg/mL, respectively. Only NPW samples obtained immediately postnebulization showed antifungal activity. A nebulized Vfend solution is not recommended for the treatment of pneumomycosis in horses.     

Comparison of Serum Amyloid A in Horses With Infectious and Noninfectious Respiratory Diseases

The acute phase protein serum amyloid A (SAA) has been shown to be a useful inflammatory parameter in the horse, but studies showing SAA responses to specific respiratory disease etiologies are limited. The goal of this study was to evaluate SAA responses in horses with infectious and noninfectious respiratory diseases as well as healthy, control horses. Two hundred seven horses were grouped into the following categories: equine influenza virus (EIV), equine herpesvirus-4 (EHV-4), Streptococcus equi subspecies equi (S. equi ss equi), inflammatory airway disease (IAD), and healthy controls. Serum amyloid A concentrations were determined for all horses on serum using a stall-side lateral flow immunoassay test. Serum amyloid A levels were found to be significantly greater for infectious respiratory diseases (EIV, EHV-4, S. equi ss equi) and horses with IAD when compared to control horses. There was a significant difference between viral and bacterial infections and IAD. Although SAA values from horses with S. equi ss equi were significantly greater when compared to horses with viral infections (EIV/EHV-4), the wide range of SAA values precluded accurate classification of the infectious cases. In conclusion, SAA is more reliably elevated with infections of the respiratory tract rather than noninfectious airway conditions. This can facilitate early detection of respiratory infections, help track disease progression, and aid practitioners in making recommendations about proper biosecurity and isolation of potentially contagious horses.     

Increased Parasite Resistance and Recurrent Airway Obstruction in Horses of a High‐Prevalence Family

Background: Equine recurrent airway obstruction (RAO) shares many characteristics with human asthma. In humans, an inverse relationship between susceptibility to asthma and resistance to parasites is suspected. Hypothesis/Objectives: Members of a high‐incidence RAO half‐sibling family (F) shed fewer strongylid eggs compared with RAO‐unaffected pasture mates (PM) and that RAO‐affected horses shed fewer eggs than RAO‐unaffected half‐siblings. Animals: Seventy‐three F and 73 unrelated, age matched PM. Methods: Cases and controls kept under the same management and deworming regime were examined. Each individual was classified as RAO affected or RAO unaffected and fecal samples were collected before and 1–3 weeks and 3 months after deworming. Samples were analyzed by combined sedimentation‐flotation and modified McMaster methods and classified into 3 categories of 0 eggs per gram of feces (EpG), 1–100 EpG, and >100 EpG, respectively. Results: PM compared with RAO‐affected F had a 16.7 (95% confidence interval [CI]: 2.0–136.3) times higher risk for shedding > 100 EpG compared with 0 EpG and a 5.3 (95% CI: 1.0–27.4) times higher risk for shedding >100 EpG compared with 0 EpG. There was no significant effect when RAO‐unaffected F were compared with their PM. RAO‐unaffected compared with RAO‐affected offspring had a 5.8 (95% CI: 0.0–1.0) times higher risk for shedding 1–100 EpG. Age, sex, breed, and sharing pastures with other species had no significant confounding effects. Conclusion and Clinical Importance: RAO is associated with resistance against strongylid parasites in a high‐prevalence family.     

Acute Phase Proteins in Racehorses with Inflammatory Airway Disease

Background

Systemic inflammation is observed in horses with heaves and could also be present in horses with a lesser degree of pulmonary inflammation.

Hypothesis/Objectives

It was hypothesized that racehorses with inflammatory airway disease (IAD) have increased concentration of circulating acute phase proteins. The objective of this study was to compare serum acute phase proteins of racehorses with and without lower airway inflammation.

Animals

Serum from 21 client‐owned Standardbred racehorses with exercise intolerance and lower airway inflammation and serum from 10 client‐owned Standardbred racehorses with exercise intolerance without lower airway inflammation.

Methods

In a case–control study, serum samples from previously characterized horses presented for exercise intolerance with or without lower airway inflammation based on bronchoalveolar lavage fluid cytology were analyzed for serum amyloid A protein (SAA), C‐reactive protein (CRP), and haptoglobin using commercial ELISAs.

Results

There was no significant differences between groups for SAA (non‐IAD versus IAD, median (range): 3.47 (0.06–34.94) versus 6.33 (0.06–80) μg/mL, P = .49), CRP (10.87 (2.05–29.03) versus 4.63 (0.02–31.81) μg/mL, P = .23) or haptoglobin (900.36 (607.99–2018.84) versus 749.54 (530.81–1076.95) μg/mL, P = .09).

Conclusions and Clinical Importance

In this population of poorly performing racehorses in training, serum SAA, CRP, and haptoglobin were not helpful in distinguishing between horses with IAD from horses with exercise intolerance from other causes.     

Effects of genetic and environmental factors on chronic lower airway disease in horses

Background : Environment and genetics influence the manifestation of recurrent airway obstruction (RAO), but the associations of specific factors with mild, moderate, and severe clinical signs are unknown.
Hypothesis : We hypothesized that sire, feed, bedding, time outdoors, sex, and age are associated with clinical manifestations of mild, moderate, and severe lower airway disease.
Animals : Direct offspring of 2 RAO-affected Warmblood stallions (F1S1, n = 172; F1S2, n = 135); maternal half-siblings of F1S1 (mHSS1, n = 66); and an age-matched, randomly chosen control group (CG, n = 33).
Methods : A standardized questionnaire was used to assess potential risk factors and to establish a horse owner assessed respiratory signs index (HOARSI 1–4, from healthy to severe) according to clinical signs of lower airway disease.
Results : More F1S1 and F1S2 horses showed moderate to severe clinical signs (HOARSI 3 and HOARSI 4 combined, 29.6 and 27.3%, respectively) compared with CG and mHSS1 horses (9.1 and 6.2%, respectively; contingency table overall test, P < .001). Sire, hay feeding, and age (in decreasing order of strength) were associated with more severe clinical signs (higher HOARSI), more frequent coughing, and nasal discharge.
Conclusions and Clinical Relevance : There is a genetic predisposition and lesser but also marked effects of hay feeding and age on the manifestation of moderate to severe clinical signs, most markedly on coughing frequency. In contrast, mild clinical signs were not associated with sire or hay feeding in our populations.     

Pulmonary function measurements immediately after exercise are correlated with neutrophil percentage in tracheal aspirates in horses with poor racing performance

Inflammatory airway disease (IAD) is common in racehorses, and is a cause of wastage in the industry. IAD has been diagnosed by measurement of percent neutrophils (N%) in tracheal aspirates (TA). The aim of this study was to investigate whether spirometric indices of pulmonary function were correlated with N% in TAs. Limits to breathing were measured by analyses of relationships between relative times and relative respiratory gas flows during inspiration and expiration in individual breaths recorded after exercise. Horses with higher N% had significantly lower relative gas flows at the same relative times during inspiration and expiration, suggesting a limit to breathing. These findings confirm a physiological basis for the measurement of N% in TA after exercise for diagnosis of IAD. Spirometric pulmonary function testing using analyses of individual breaths after exercise has application for assessment of pulmonary function and poor exercise performance.     

Efficacy and safety of sound wave treatment of recurrent airway obstruction in horses

Background: One proposed nonmedical therapy for recurrent airway obstruction (RAO) in horses is a handheld acoustic device that propels sound waves from the nose down the tracheobronchial tree where it is intended to dislodge mucous and relax bronchospasm, permitting clearance of mucoid secretions. Objective: To evaluate the effectiveness and safety of this device when used as per the manufacturer's recommendations as a treatment for RAO. Animals: Nine adult horses previously diagnosed with RAO. Methods: Prospective, cross‐over clinical trial. Horses were exposed to a dusty environment until airway obstruction developed as defined by standard lung mechanics (SLM). Horses were randomly assigned to receive either acoustic therapy or a sham treatment for 4 weeks while being maintained in this environment. Horses were evaluated by clinical scores, SLM, and forced expiration regularly for 4 weeks. The opposite treatment was administered after a washout period. Results: Seven horses received the treatment; 9 received the sham. There were no changes (P > .05) in clinical score, maximal change in transpulmonary pressure (ΔP_Lmax), lung resistance (R_L), or the forced expiratory flow rate averaged over the last 75–95% of expiration (FEF_75?95%) over the study period. The device was determined to be safe, although several minor adverse effects were noted, including head tossing, coughing, and chewing during treatment. Conclusions and Clinical Importance: Treatment with this device did not improve clinical signs or lung function in horses with RAO kept in a dusty environment. Currently accepted treatments, including environmental management and medical therapy, should be recommended.     

Age Effects on Blood Gas,Spirometry, Airway Reactivity,and Bronchoalveolar Lavage Fluid Cytology in Clinically Healthy Horses

Background

Despite the increasing number of geriatric horses attended by veterinarians, there is a lack of understanding of aging‐related changes on the respiratory system of horses.

Objective

To identify aging‐related changes on the respiratory function and bronchoalveolar lavage fluid (BALF) cytology of horses.

Animals

Fifteen healthy young adult (2–11 years) and 16 healthy aged (≥20 years) horses.

Methods

The respiratory system was examined by measurement of arterial blood gases (ABG), use of respiratory inductive plethysmography (RIP) for assessment of breathing pattern and ventilatory parameters, histamine bronchoprovocation, and BALF cytology.

Results

No significant differences were detected with regard to values obtained by ABG or bronchoprovocation of young adult and aged healthy horses. In aged horses, there were significant differences in mean ± SD of the following parameters when compared to young horses: prolonged expiratory time (Te) measured by RIP (3.9 ± 1.5 s versus 3.0 ± 0.6 s), decreased percentage of alveolar macrophages (40.6 ± 11.3% versus 53.5 ± 9.6%), and increased percentage of lymphocytes (53.4 ± 9.5% versus 43.9 ± 11.0%). No correlations between airway reactivity and ventilatory parameters, ABG, or BALF cytology were found in this asymptomatic population.

Conclusions

These results suggest that aging does not cause changes in the results obtained by ABG, most RIP‐derived variables, and bronchoprovocation in the horse. A decreased percentage of macrophage and an increased percentage of lymphocytes in the BALF cytology may be expected in the asymptomatic geriatric horse and may be a result of aging.