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Exercise-induced pulmonary hemorrhage (EIPH), also known as "bleeding" or a "bleeding attack", is the presence of blood in the airways of the lung in association with exercise. EIPH is common in
horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 mi ...
s undertaking intense exercise, but it has also been reported in human athletes, racing camels and racing greyhounds. Horses that experience EIPH may also be referred to as "bleeders" or as having "broken a blood vessel". In the majority of cases, EIPH is not apparent unless an endoscopic examination of the airways is performed following exercise. This is distinguished from other forms of bleeding from the nostrils, called epistaxis.


Epidemiology

EIPH often occurs in horses that race at high speeds, with the number of affected race horses increasing in proportion to the speed and intensity of the exercise. It may occur in racing Thoroughbreds (
flat racing Horse racing is an equestrianism, equestrian performance activity, typically involving two or more horses ridden by jockeys (or sometimes driven without riders) over a set distance for competition. It is one of the most ancient of all spor ...
, steeplechasing or jump racing), American Quarter Horses (incidence of 50–75%), Standardbreds (incidence of 40–60%), Arabians, and Appaloosas. EIPH also occurs in eventers,
jumpers Jumper or Jumpers may refer to: Clothing *Jumper (sweater), is a long-sleeve article of clothing; also called a top, pullover, or sweater **A waist-length top garment of dense wool, part of the Royal Navy uniform and the Uniforms of the United St ...
, polo ponies, endurance horses,
draft horse A draft horse (US) or draught horse (UK), also known as dray horse, carthorse, work horse or heavy horse, is a large horse bred to be a working animal hauling freight and doing heavy agricultural tasks such as plowing. There are a number o ...
s that pull competitively, and horses taking part in Western speed events such as barrel racing,
reining Reining is a western riding competition for horses in which the riders guide the horses through a precise pattern of circles, spins, and stops. All work is done at the lope (a version of the horse gait more commonly known worldwide as the cant ...
and
cutting Cutting is the separation or opening of a physical object, into two or more portions, through the application of an acutely directed force. Implements commonly used for wikt:cut, cutting are the knife and saw, or in medicine and science the sca ...
. It is rare in endurance horses or draft breeds. The lowest intensities of exercise which may cause EIPH are intense trotting (40–60% maximal oxygen uptake) and cantering at speeds of . EIPH occurs less frequently in stallions than mares or geldings.


Prevalence

Approximately 43 to 75% of horses have blood in the
trachea The trachea (: tracheae or tracheas), also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all animals' lungs. The trachea extends from ...
and bronchi following a single post-race endoscopic examination. In one study, all horses endoscoped on at least three separate occasions following racing had EIPH at least once. Epistaxis (blood coming from one or both nostrils) is much less common, occurring in 0.25–13% of cases. In a survey of over 220,000 horse starts in UK Flat and National Hunt (jump) racing, 185 cases of epistaxis were identified (0.83 per 1000 starts). Similar frequencies have been reported in Japan (1.5 per 1000 starts) and South Africa (1.65 per 1000 starts), whereas a higher frequency has been reported in Korean (8.4 per 1000 starts).


Clinical signs

Unless a horse has severe EIPH, with blood present at the nostrils (known as epistaxis), the main sign is usually poor athletic performance; other signs are generally subtle and not easy to detect. Frequent swallowing and coughing in the immediate post-exercise recovery period, and poor appetite post-performance may be suggestive of EIPH. A definitive diagnosis can only be made by endoscopic examination of the trachea. In the case where no blood is visible in the trachea, EIPH in the small airways may still be present and can be confirmed by a bronchoalveolar lavage. Impaired arterial blood gas (oxygen) tensions during intense exercise, increased blood lactate, and rarely death have been noted (likely due to ruptured chordae tendinae or a different mechanism of lung hemorrhage). Epistaxis is diagnosed when blood is visible at either or both nostrils during or following exercise. To confirm whether the blood is coming from the upper or lower airway requires further examination by endoscopy, although in some cases it is not possible to determine the location. In the majority of epistaxis cases, the blood originates from the lung. Epistaxis during or following exercise can less commonly occur as a result of upper airway hemorrhage, for example following head trauma, subepiglottic cysts,
atrial fibrillation Atrial fibrillation (AF, AFib or A-fib) is an Heart arrhythmia, abnormal heart rhythm (arrhythmia) characterized by fibrillation, rapid and irregular beating of the Atrium (heart), atrial chambers of the heart. It often begins as short periods ...
, or guttural pouch mycoses.


Effects on performance

EIPH reduces a horse's racing performance. Severe EIPH (epistaxis) shortens a horse's racing career. Moderate to severe EIPH is associated with a worsened finishing position in a race, and finishing farther behind the winner. Horses with mild EIPH earn more prize money than those with more severe EIPH. While single bouts of EIPH may not even be apparent to the rider, owner or trainer of a horse unless an endoscopic examination is undertaken, the effect on performance within a single race appears to be significant but relatively subtle. In a 2005 study, horses finishing races with grade 4 EIPH were on average 6 metres behind those finishing with grade 0. However, the effect of repeated bouts of EIPH that occur with daily training may lead to more significant changes and a greater degree of tissue damage over time with consequent loss of lung function.


Diagnosis

As only one in ten cases of EIPH have epistaxis (bleeding from the nostrils), and as epistaxis can have causes other than EIPH, various diagnostic tools are used to diagnose EIPH.


Endoscopy

EIPH is most commonly diagnosed by endoscopic examination of the
trachea The trachea (: tracheae or tracheas), also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all animals' lungs. The trachea extends from ...
and larger bronchi, with the optimal timing for endoscopy being 60–90 minutes after hard exercise. This post-exercise delay allows time for blood within the lungs to travel to the trachea. Blood can usually be detected in the trachea or bronchi for 1–3 days after an episode of EIPH, but may be present for up to a week. The amount of blood visible in the trachea at the time of examination is most commonly graded on a scale of 0 (no blood) to 4 (airways awash with blood). In some mildly-affected horses, endoscopy must be performed on multiple occasions to confirm a diagnosis of EIPH. The level of restraint required to allow endoscopy to be performed depends on the horse; a nose twitch or sedation may be required.


Cytopathology

Cytopathology (examination under a
microscope A microscope () is a laboratory equipment, laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic ...
) of either a tracheal wash or a bronchoalveolar lavage sample can determine whether EIPH has occurred. # For acute hemorrhage the number of red blood cells present can be quantified using a hemocytometer. A normal lung wash sample contains fewer than 10 red blood cells/μl of fluid. In the case of EIPH, the numbers will be several magnitudes or more higher. #For chronic hemorrhage the presence of high numbers of hemosiderophages, with a lot of iron inside their vesicles, indicate that hemorrhage has occurred in the lung at some time in the past. Hemosiderophages are
alveolar macrophage An alveolar macrophage, pulmonary macrophage, (or dust cell, or dust eater) is a type of macrophage, a phagocytosis#Professional phagocytic cells, professional phagocyte, found in the airways and at the level of the pulmonary alveolus, alveoli in ...
s that have ingested and digested red blood cells from previous episodes of EIPH. The end product of the digestion of the red blood cells is an iron-storage complex known as hemosiderin.


Bronchoalveolar lavage

Bronchoalveolar lavage (BAL) is a procedure whereby a small volume of fluid is put into the airways in order sample the cells and fluids of the alveoli and epithelium of the bronchi. BAL may be performed using a BAL tube, which allows fluid to be added to and removed from the bronchi, or may be performed during endoscopy, if the endoscope has an irrigation channel. To perform BAL, the horse is usually sedated, and local anaesthetic is usually instilled into the airways to reduce coughing. BAL is less useful when severe hemorrhage has occurred. BAL results only reflect the situation in the localized region of the lung which has been lavaged, and may not be representative of the whole lung. The fluid obtained by BAL is submitted for cytological examination.


Imaging


Radiography

Imaging the lungs by taking a radiograph (x-ray) of the chest cannot be used to diagnose EIPH, as the lungs of affected and unaffected horses share the same characteristics.


Pulmonary scintigraphy

Scintigraphy Scintigraphy (from Latin ''scintilla'', "spark"), also known as a gamma scan, is a diagnostic test in nuclear medicine, where radioisotopes attached to drugs that travel to a specific organ or tissue (radiopharmaceuticals) are taken internally a ...
of the lungs may detect moderate to severe alterations in the perfusion and possibly ventilation of the dorso-caudal lung. The use of radio-labelled red blood cells and scintigraphy to localise and or quantify hemorrhage is not useful due to general sequestration of labeled RBC by the lung, even in the absence of hemorrhage.


Post-mortem examination

EIPH seldom causes the death of a horse, but if an affected horse dies and undergoes a post-mortem examination, repeated episodes of EIPH will have caused a characteristic blue-gray-brown staining in the lungs. The staining is due to the presence of hemosiderin. The staining is usually most intense in the dorso-caudal region of the left and right diaphragmatic lobes which often progresses cranioventral with repetitive damage. There are often distinct borders between healthy lung tissue and those parts of the lungs that have been affected by EIPH. Other histopathologic findings include fibrosis,
bronchial artery In human anatomy, the bronchial arteries supply the lungs with oxygenated blood, and nutrition. Although there is much variation, there are usually two bronchial arteries that run to the left lung, and one to the right lung, and are a vital part o ...
neovascularization, venous remodeling, bronchiolitis, hemosiderin accumulation, increased tissue cellularity (i.e. hemosiderophages), multifocal areas of inflammation, and increased thickness of vascular and airway walls.


Causes

EIPH occurs when blood enters the air passages of a horse's
lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
, due to fractured capillaries. A variety of causes have been proposed, but EIPH is most likely a multi-factorial condition, involving airway, vascular, inflammatory, blood, cardiac, locomotory, and remodelling components. The primary mechanism is likely to be high pulmonary vascular pressures with concurrent negative airway pressures, causing extreme stress across the pulmonary capillary membrane (the fragile membrane separating blood in the pulmonary capillaries from the air-filled alveoli) and consequent hemorrhage into the air spaces of the lung. Other contributing factors may include upper airway obstruction, increased blood viscosity, abnormalities of cardiac origin (small cross-sectional area of atrioventricular valves, stiff valves, slow left ventricular relaxation time, right tricuspid valve regurgitation), preferential distribution of blood flow to the dorsocaudal lung regions, mechanical trauma, lower airway obstruction, inflammation, abnormalities of blood coagulation, inhomogeneity of ventilation and locomotory trauma. EIPH begins in the dorso-caudal region of the lung and progresses in a cranioventral direction over time.


High pulmonary blood pressures

The most widely accepted theory is that high transmural pressures lead to pulmonary capillary stress failure. There may be contributions from the bronchial circulation. Pulmonary capillary transmural pressure is determined by pulmonary capillary pressure and airway pressure. The horse has very high pulmonary vascular pressures during intense exercise, exceeding 100 mmHg in the pulmonary artery during intense exercise. During expiration the high positive pressures in the pulmonary blood vessels pushing out are opposed by high positive airway pressures pushing back and this does not place undue stress on the thin blood vessel walls. During inspiration, the high positive pressures in the pulmonary blood vessels pushing out are met by negative pressures distending the blood vessel and placing increased stress on the walls. Studies ''in vitro'' show that significant disruption of the pulmonary capillaries occurs at pressures of approximately 80 mmHg. ''In vivo'', significant EIPH occurs above a mean pulmonary artery pressure of around 80–95 mmHg. On the basis of this theory, any factor or disease that would increase pulmonary vascular pressures (e.g. hypervolaemia) or increase the magnitude of the negative pressures in the lung during inspiration (e.g. dynamic upper airway obstruction) would increase the severity of EIPH; however neither experimentally induced laryngeal hemiplegia nor dorsal displacement of the soft palate increase pulmonary capillary transmural pressure. Furthermore, the magnitude of exercise-induced pulmonary arterial, capillary and venous hypertension is reportedly similar in horses either with or without EIPH.


Locomotory associated trauma

This theory is based on the fact that, during galloping, the absence of any bone attachment of the forelegs to the spine in the horse causes the shoulder to compress the cranial rib cage. The compression of the chest initiates a pressure wave of compression and expansion which spreads outwards. However, due to the shape of the lung and reflections off the chest wall, the wave of expansion and compression becomes focussed and amplified in the dorso-caudal lung. The alternate expansion and compression at the microscopic level in adjacent areas of lung tissue creates
shear stress Shear stress (often denoted by , Greek alphabet, Greek: tau) is the component of stress (physics), stress coplanar with a material cross section. It arises from the shear force, the component of force vector parallel to the material cross secti ...
and capillary disruption. The theory predicts that hemorrhage would be more severe on hard track surfaces, but it does not explain why EIPH can occur in horses during swimming exercise.


Veno-occlusive remodelling

This theory proposes how high pulmonary venous pressures may lead to the capillary rupture and the tissue changes observed in EIPH. Regional veno-occlusive remodeling, especially within the caudodorsal lung fields, contributes to the pathogenesis of EIPH, with the venous remodeling leading to regional vascular congestion and hemorrhage, hemosiderin accumulation, fibrosis, and bronchial angiogenesis.


Risk factors

While all horses undertaking intense exercise experience some degree of EIPH, some horses consistently experience greater haemorrhage and other horses experience isolated episodes of increased EIPH. In the case of horses that consistently demonstrate greater severity of EIPH this is most likely due to congenital factors, such as very high pulmonary vascular pressures. In horses that experience isolated episodes of increased severity of EIPH, possible contributing factors may include, amongst others, pulmonary infection or atrial fibrillation, inflammation, longer distances, longer duration of exercise, hard surfaces, steeplechasing/hurdling, increased length of career, breed (i.e. Thoroughbred greater than Standardbred), time in training/racing, genetics, and cold temperatures.


Management and treatment

Furosemide (trade name: Lasix) administered prior to racing or strenuous exercise in Thoroughbred and Standardbred racehorses reduces the severity EIPH in 68% of horses. Up to 85% of Thoroughbred racehorses in the United States have been administered furosemide at least once during their racing career. Furosemide decreases pulmonary arterial pressure via its diuretic effects, bronchodilates, and redistributes blood flow during exercise. It reduces EIPH ranging from 90% at sub-maximal exercise and about 50% at maximal exercise intensities. However, over time, it causes electrolyte imbalances and has reduced effectiveness. Furosemide is prohibited in competing horses in some countries, and by the
International Olympic Committee The International Olympic Committee (IOC; , CIO) is the international, non-governmental, sports governing body of the modern Olympic Games. Founded in 1894 by Pierre de Coubertin and Demetrios Vikelas, it is based i ...
. The United States and Canada are the only countries which permit furosemide use during racing. Other vascular agents such as nitric oxide (NO), n-nitro-l-arginine methyl ester (L-Name), nitroglycerin, NO + phosphodiesterase inhibitors (e.g.,
sildenafil Sildenafil, sold under the brand name Viagra among others, is a medication used to treat erectile dysfunction and pulmonary hypertension, pulmonary arterial hypertension. It is also sometimes used off-label for the treatment of certain sym ...
), and endothelin receptor antagonists have no effect, and in some cases worsen of the EIPH. Equine nasal strips are a non-pharmacological option with strong scientific support for the prophylactic reduction of exercise-induced pulmonary hemorrhage (EIPH). Numerous studies have hypothesized—and Holcombe et al. (2002) confirmed—that the strip’s spring-like action prevents collapse of the soft tissues within the nasal cavity. This mechanism maintains airway diameter during exercise, countering the exponential rise in airway resistance and work of breathing that, if unchecked, accounts for over 50% of total inspiratory resistance. By reducing inspiratory resistance, the strip decreases the negative pressure on the delicate blood-gas barrier, thus reducing capillary rupture and consequent hemorrhage into the airways. Moreover, the nasal strip elicits a proportionately greater reduction in inspiratory resistance and EIPH as exercise duration and intensity increases. At maximal exertion, the nasal strip’s effectiveness in reducing EIPH matches that of furosemide, 8 and combining Lasix with the nasal strip has a synergistic effect in further reducing EIPH. Both treadmill 5,37and racetrack 9studies have shown that horses with severe bleeding experience the greatest benefit from nasal strips. Additionally, the strip lessens the work and blood flow needed by the inspiratory muscles, allowing more oxygenated blood to be diverted to locomotory muscles, increasing exercise tolerance. 5,37,38,40 Nasal strips are widely approved for flat and harness racing in North America, multiple international jurisdictions, and by all major non-racing regulatory bodies. 0 Bronchodilatation is already maximized in the exercising horse, therefore bronchodilatory agents such as ipratropium, albuterol, or clenbuterol are not effective in reducing EIPH. Coagulation dysfunction is not a cause of EIPH, and anticoagulatory agents, including carbazochrome salicylate, aspirin, Premarin, Amicar, and
vitamin K Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-translational modification, post-synthesis modification of certain proteins ...
, are not effective in reducing EIPH, and in some cases may worsen it. Omega-3 fatty acids ( DHA and EPA) reduce EIPH, presumably via increasing the functionality of the
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s (WBCs) in removing the blood from the lungs. Concentrated equine serum reduced EIPH by 53% through a combined mechanism of a 30% reduction in inflammation and an increased functionality of the WBCs. Other anti-inflammatory agents, such as hesperidin-citrus bioflavinoids,
vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is also a generic prescription medication and in some countries is sold as a non-prescription di ...
, NSAIDs such as phenylbutazone,
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
s, heated water vapor therapy, cromoglicic acid or nedocromil, have no beneficial effects in reducing EIPH severity. Phenylbutazone can partially reverse the beneficial effects of furosemide. Other ineffective treatments include leukocyte elastase protease inhibitors, the EIPH Patch, hyperbaric oxygen therapy, pentoxyfylline, guanabenz, clonidine,
snake venom Snake venom is a highly toxic saliva containing zootoxins that facilitates in the immobilization and digestion of prey. This also provides defense against threats. Snake venom is usually injected by unique fangs during a Snakebite, bite, though ...
, and enalapril. Horses that undergo surgical correction for upper airway dysfunction are rested, and are under environmentally controlled environments with reduced dust may see some benefit. In conclusion, administering furosemide (Lasix) four hours before racing and wearing equine nasal strips (FLAIR®) are the only treatments scientifically proven to effectively reduce EIPH in horses. These interventions remain the standard in EIPH management, supported by their proven efficacy in multiple controlled studies. Bayly, Warwick and Van Erck Emmanuelle (5-6 February 2024). Exercise-Induced Pulmonary Hemorrhage (EIPH): Not Just a Racehorse Disorder. 27th Equine Health and Nutrition Conference. Ocala, FL. pp. 43-47.


References


Sources

* Hinchcliff, K. W. (2009). "Exercise-induced pulmonary hemorrhage". ''Advances of Equine Nutrition,'' 4: 367-374. * * Mason, D. K., E. A. Collins, et al. (1983). Exercise-induced pulmonary haemorrhage in horses. 1st International Conference on Equine Exercise Physiology, Oxford, UK. * * * * * * Roberts, C.A., Hillidge, C. and Marlin, D.J. (1993) Exercise induced pulmonary haemorrhage in racing thoroughbreds in Great Britain. 1st International EIPH Conference, Guelph, Canada, p11. *


Further reading

* * . * Hinchclif, K.W. (2007) Exercise-induced pulmonary haemorrhage in equine respiratory medicine and surgery, eds McGorum, Dixon, Robinson and Schumacher, Saunders Elsevier, page 620-621. {{DEFAULTSORT:Exercise Induced Pulmonary Hemorrhage Horse diseases