Breeds of domestic cattle are organized in two subspecies categories: Bos taurus indicus, commonly referred to as ‘zebu’, and Bos taurus, or ‘taurine’. Zebu, the popular humped-back cattle is well adapted to hot tropical climate, while the domesticated taurine conforms to cooler or temperate one.

Cow hair and dander are the main sources of bovine respiratory allergens. Sensitization and development of allergic diseases such as asthma, allergic rhinitis/conjunctivitis, and atopic dermatitis are attributed to allergen exposure. Sensitization to cattle allergens turns out to be more frequent with age, however most of the times it stays asymptomatic. Cow allergens pose high risk of occupational allergy for not only ranchers and veterinary surgeons, but also for butchers, workers in cheese-producing facility, bakers, chefs, laboratory technicians, and even beauticians.

Immunoelectrophoretic studies have identified almost seventeen different antigenic components, four major allergens, and six minor allergens in bovine materials. The allergens detected through various studies are proteins of molecular weights 11, 15, 20, 22, 36, 50, 62.3 and >200 kDa. The two main allergenic molecules of bovine dander are Bos d 1 (molecular mass 24-25 kDa, PI 3.6) and Bos d 2 (20-22 kDa, PI 4.2). Exposure to the lipocalin Bos d 2, found in cow dander and urine, can induce respiratory inflammation, rhinitis, and dermatitis among sensitized people working in dairy farms.

A few Deer allergens have shown cross-reactivity with cow allergens. Also, the allergen molecules of cow dander show extensive cross-reactivity with dog allergen Can f 4 and guinea pig allergen Cav p 2.

Allergen immunotherapy has proven to be safe and effective for allergic rhinitis and asthma from cow dander.

Nature

The coat color of cows diversely varies from black, brown, grey to white. All existing variants of cow have a black muzzle, black eyelid, black to grayish hoof, and black, brown to white color tail. Known to have a docile to moderate temperament, they possess medium to small size hump, prominent dewlap and naval flaps. The average chest girth of a cow can measure to about 51 inches, while the body reaches almost 66 inches in length and 43 inches in height. In a study conducted on a total of 186 dairy cattle from three different agro-climatic zones of India, observations revealed that the average daily milk yield and peak milk yield of the cows were in the range of 3.59 kg and 4.44 kg, respectively with an average lactation length of 238 days; the records from different zones were shown to be similar (1).

Habitat

Cattle are generally seen around gentle slopes, forest edges, wet meadows, and areas near water as well as areas far from water on plateaus.(2)

Domestic cattle breeds are organized in two subspecies categories: Bos taurus indicus, commonly referred to as ‘zebu’, and Bos taurus, commonly referred to as ‘taurine’. Zebu has a hump on its back and is adapted to hot tropical climates, while taurine is abundant to cooler and temperate climates. The taurine cattle is believed to have a Neolithic origin and domestication in the Fertile Crescent (3).

Taxonomy

Worldwide distribution

Sensitization to cattle allergens ends up being more frequent with age, however much of the time it stays asymptomatic. As opposed to Poland and most other European nations, in Finland, cattle allergens are one of the prominent causes of work-related contact urticaria. Finnish researchers have affirmed the connection between allergen concentration in cow sheds and immune reactivity of the ranchers (6).

In a retrospective observational study conducted in Germany, a total of 513 cattle-allergic farmers (age 14-74 years, mean age:40.7 years; 45.6% women, 54.4% men) with suspected occupational cattle-allergic airways disease were enrolled. Among all the patients enrolled, while 24.8% reported with cattle-related symptoms of asthma, 11.7% with rhinitis, and 60% with both asthma and rhinitis, only 34.5% reported an airways obstruction in the lung function test. Of the total, 62.5%  with an officially recognized occupational disease (42.1%, n=216) had an initial employment disability with a rating of 20% or above (7).

A Finnish study enrolling 815 individuals with occupational allergic contact dermatitis (29.5% suffering from contact urticaria and 70.5% with allergic contact dermatitis) revealed that cow dander (44.4%) was one of the major causative allergens towards occupational contact urticaria (8). Skin-prick tests (SPTs) with in-house and available commercial cow dander extracts was performed in a total of 102 patients with a presumed cow-related occupational rhinitis, asthma, and/or contact urticaria. In-house SPT extract resulted in more positive reactions (≥ 3mm wheal) compared to the two commercial agents (44% vs 34% and 11%, p=0.006 and 0.001 respectively).  Out of 21 patients who took up nasal provocation tests (NPTs) with both in-house and commercial extracts, 62% responded distinctly to the in-house allergen extract, while 24% responded to both extracts (p<0.001). Traces of odorant-binding proteins (Bos d OBP), bovine serum albumin (Bos d 6), and lipocalins (Bos d 2) and several minor allergens were found in the in-house extract (9).

Risk factors

Sensitization and development of allergic diseases such as asthma, allergic rhinitis/conjunctivitis, and atopic dermatitis attribute their risk primarily to allergen exposure. (10). Prolonged, consistent exposure to allergens lead to occupational allergies that can be a distressing and debilitating threat to individuals working in certain types of work-environments. To exemplify, cow hair and dander were found to be the important inducers of such occupational allergies in farmers exposed to cattle. (11). Cow stables are epicenters to bovine allergens. Data collected from several studies illustrated very high and strongly variable allergen concentrations as airborne as well as settled dust samples. Allergen levels differed up to 200-fold among stables and were about 1000-fold higher than homes. (10). Moreover,  the major allergen Bos d 2 has high stability that escalates the risk of exposure to ranchers. (6)

Living environment

The terrestrial biomes where Bos taurus can be traced are desert or dunes, savannas, grasslands, chaparral, forests, and scrub forests. A large majority of Bos taurus are domesticated and can be seen in agricultural areas (12). 

Worldwide distribution

As evident from archaeological and genomic studies, the ancestors of Taurine cattle (Bos taurus) were domesticated from Bos primigenius in the Fertile Crescent during the Neolithic age, more than10,000 years ago (13). Bos grunniens, Bos frontalis, and Bos javanicus hybridize with taurine and zebu cattle, and almost all of the Asian cattle populations are hence of mixed species origin, contributing uniquely and substantially to the cattle resources (14).

As human migrated, cattle too did, leading to domestic cattle of taurine, indicine, or mixed origin spreading around Asia, Africa, Europe, and the New World. This adaptation of cattle to different environmental conditions  resulted in huge variation in appearance and performance (15). Eventually cattle were introduced to most parts of Asia, Africa, and Europe, and even today, seasonal migrations can be seen generously in Alpine Europe, and, several parts of Africa and Asia. Hinting at livestock herding for cattle husbandry through nomadic pastoralism that is still common in central Africa, domestication, dispersal and adaptation of cattle resources furnish the basis of genetic diversity today (14).

Allergic rhinitis

Owing to the presence of airborne as well as settled dust allergens, respiratory conditions like occupation-related allergic rhinitis and asthma show a significantly high prevalence at- and in the vicinity of animal farms (16).

Recently, occupational rhinitis (OR) has been recognized as one of the strong consequences of occupational hazard due to exposure of individuals to workplace allergens. As per the recorded evidence OR is closely associated with, as well as, 2–4 times more frequent than occupational asthma (OA). It is an important clinical entity, as it is one of the major risk factors for the development of OA. Allergic rhinitis can be non-IgE mediated or IgE-mediated OR primarily due to high molecular weight agents triggering airway inflammation and intense T-helper-2 (Th2) response. (17).

Asthma

Nasal symptoms are present in up to 90 % of individuals with OA and OR and may be a marker of developing OA (17). In many countries, asthma due to cow allergens is a significant occupational hazard (18). Animal dander is one of the important causative factors and triggers of bronchial asthma (19) and for sensitized persons, cow allergen is a potent health risk for allergic sensitization and disease (20).

Korinth G et al. (2005) reported a case of a 37-year-old female with complain of daily asthmatic symptoms, which, increased within 12 years. Milking with a conventional device exposed and sensitized her to cow dust-derived allergen and was diagnosed with allergic bronchial asthma, as demonstrated by positive SPT and by detection of IgE antibodies. In a separate specific inhalation challenge test using a 10% extract of cow dust-derived allergens a 330% increase in airway resistance was also determined (21).

Santiago and his colleagues (1997) presented a case of two male cow farmers with symptoms of rhino-conjunctivitis and asthma. Skin tests were found to be positive for cow dander. The serum IgE was 383 and 477 kU/L. The specific IgE test was positive for cow dander, 20.10 and 36.4 kU/L (class 4). The provocation test was positive with a concentration of 500 standardized biological units (SBU). These results supported prevalence of asthma in farmers due to cow dander exposure (22). 

Other diseases

In Finland, one of the most common causes of occupational contact urticaria is cow dander that can also cause allergic contact dermatitis, as investigated by patch test. (23). Cow allergens pose high risk of occupational allergy for not only ranchers and veterinary surgeons, but also for butchers, workers in cheese-producing facility, bakers, chefs, laboratory technicians, and even beauticians (6).

Allergen immunotherapy

Allergen immunotherapy (AIT) is suitable for those patients with AR who remain unresponsive to pharmacologic treatment. In allergic asthma, AIT has been proven to be safe and efficacious (24). In a study it was demonstrated that subcutaneous immunotherapy with cow dander reduced rhinitis symptoms in a cow breeder mono-sensitized to cow dander (17).

Prevention strategies

Avoidance

Traditional milking requires close animal contact and hence due to intense direct exposure it is difficult to prevent sensitization in stock farming. Exposure minimization to allergens at workplaces can be an effective alternative to complete elimination. For farmers who are allergic to cow dust, the use of a milking robot is an appropriate technical measure to reduce allergen-exposure (21).

Allergenic molecules

Cow hair and dander are the main sources of bovine respiratory allergens. Seventeen different antigenic components, four major allergens, and six minor allergens were detected in bovine materials using  crossed immunoelectrophoresis (25).

•  Bos d 1 (molecular mass 24-25 kDa, PI 3.6): a major allergen in cow dander (5).
  
•  Bos d 2 (20-22 kDa, PI 4.2): another major allergenic protein in cow dander and urine (26). It belongs to the family of lipocalins which are proteins capable of binding small hydrophobic molecules (5). Immunoblotting analysis suggested that 90% or more patients having cattle-associated asthma have IgE antibodies against natural Bos d 2 (25). 
•  Bos d 23 k( 23-kDa protein) – an important allergen present in cow dander associated to a family of odorant-binding proteins (25).
•  Bos d 3 (11 kDa): one of the minor allergens belonging to the S100 calcium-binding protein A7 family. The frequency of IgE reactivity to recombinant Bos d 3 is approximately 40% in individuals suffering from cattle-allergy (25).
• Additional minor allergens present in cow hair and dander extracts are serum albumin Bos d 6 (67 kDa) and IgG Bos d 7 (160 kDa). (25)
• Other identified bovine allergens include: Bos d 4, 5 and 9 -12 comprising of milk proteins that are related to food allergy (25)

Biomarkers of severity

Bovine dander is a source of potent allergens which result in various occupational allergic disorders. Bovine dander extracts comprise of numerous allergenic proteins, its two main allergens being, Bos d 1 (molecular mass 24-25 kDa, PI 3.6) and Bos d 2 (20-22 kDa, PI 4.2). Patients with cattle-associated asthma have demonstrated the highest prevalence of IgE antibodies against 20- and 22-kDa proteins, as assessed by immunoblotting after sodium dodecyl sulfate polyacrylamide gel electrophoresis (27).

Cross-reactivity

A 23 kDa protein from cow dander, related to a family of odorant-binding proteins, and having cross-reactivity with Can f 4 (dog allergen), was purified and identified using amino acid sequencing and mass spectrometry. They shared 37% sequence identity (28). Major deer allergens with molecular weights of 22 and 25 kDa have shown cross-reactivity with the corresponding cow allergens (29). Allergen in guinea pig Cavia porcellus 2 (Cav p 2), a non-glycosylated 17 kDa lipocalin, has 39% sequence similarity with Bos d 2, the major allergen protein of cow dander (30).

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Magnus Borres

Last reviewed: October  2020