Notes on Animal Health, August 2024: When You’re Allergic to the One You Love

Pets have never been more popular. It is estimated that 66% of U.S. households (86.9 million homes) own at least one pet, while globally approximately 33% of households keep one or more. Unfortunately, for a significant portion of the human population, pets come with a significant downside: allergies. The Allergy and Asthma Foundation of America estimates that 10–20% of the world’s population is affected by dog and/or cat allergies.

What exactly is an allergy? A simple definition would be when the body’s immune system responds in an excessive manner after exposure to a foreign protein, often referred to as antigen. Many of us know the clinical signs of an allergy first-hand. For dog and cat allergens, which typically are components of their saliva and skin, the antigens become aerosolized resulting in a stuffy nose, itchy, watery eyes, and scratchy throat.  These clinical signs are primarily, though not solely, mediated by the protein Immunoglobulin E (IgE). While the immune system makes other immunoglobulins, including IgM, IgG, and IgA, they are primarily produced in response to harmful or pathogenic antigens, such as those found in bacteria and viruses.

We currently associate IgE with allergic responses, but its original role may have been in the body’s defense against parasites, such as Trichinella, Strongloides, and Schistosoma. According to this hypothesis, in the developed world where these parasitic infections are uncommon, the IgE system has become dysregulated, triggering responses to antigens that are not associated with parasites or other disease-causing organisms.

For reasons that are not entirely understood, there are a number of antigens, including pollen, dust mites, pet dander, peanuts, and bee venom, that frequently cause allergic reactions in humans. Most allergies cause mild to moderate clinical signs, but if the allergy becomes severe, exposure can result in widespread IgE-mediated release of inflammatory mediators, including histamine, serotonin, prostaglandins and leukotrienes, causing cardiovascular collapse and death, referred to as anaphylaxis. While it is true that in most individuals pet allergies cause only mild to moderate clinical signs, repeated exposures can cause worsening of the clinical signs and anaphylactic reactions can occur. Therefore, it is important to understand pet allergies and what dog and cat lovers can do to reduce their risk of developing them or decrease severity of their allergy symptoms.

Diagnosis
The most common diagnostic test for animal allergies is the skin prick test, where tiny amounts of allergen extracts are pricked into the skin's surface on the back or forearm. Alternatively, the patient’s blood can be screened for the presence of IgE molecules that bind to specific cat or dog allergens. It is important to remember that individuals can be allergic to multiple species, as well as non-animal proteins, such as pollen or dust mites, which can complicate the diagnostic process.

You don’t have to actually own a pet
Although some families may intentionally avoid having certain pets at home because of a family member’s allergies, it is important to realize that pet allergens are often carried into schools and work environments on the clothing, shoes, or other belongings of pet owners. In fact, when homes with and without cats were studied, cat antigens were detectable in 95% of homes without cats. And another study found that dog antigens at concentrations above 10 mg/g of dust were present in 98% of homes with a dog and 16% of homes without a dog.

Hypoallergenic cats and dogs are a myth
Despite claims to the contrary, to date, there is no evidence that any of the naturally occurring cat breeds are actually hypoallergenic. For example, even the hairless Sphynx cats produce Fel d 1 proteins. Data for claims of hypoallergenic dogs are unsubstantiated as well, because antigen levels are similar between breeds considered “hypoallergenic” and those that are not. However, floor dust samples collected from homes with Labradoodles dogs were lower in total canine antigen amounts than homes with other breeds of dogs, which is likely due to their tendency to shed less than many other breeds, rather than any actual decrease in the levels of allergens they produce.

Prevention
One approach to preventing the development of allergies to furry pets, particularly in children, has been to avoid having pets in the household. However, results of a recent meta-analysis of 17 peer-reviewed studies found a protective effect of early-life pet ownership, in particular dog ownership, on the onset of allergies later in life, particularly food allergies. Sometimes referred to as the “hygiene effect,” it appears that growing up in less hygienic environments leads to the modulation of the gut microbiome and a higher level of endotoxins which potentially offer protection against allergen sensitization. However, the results of a Polish study that included over 18,000 people showed that while keeping furry animals in rural regions reduced allergic disorders, in cities these animals increased the symptoms of bronchial asthma, including the risk of cough and wheezing. Therefore, exposure in childhood to pets alone is not necessarily protective. More research is necessary to understand how and when exposure to certain antigens can induce tolerance rather than sensitization and allergies.


Treatment Approaches

Environmental Interventions
First-line therapy for pet allergies is to decrease the amount of pet dander in the environment. As many people are allergic to more than just one allergen, it is important to address as many environmental allergens as possible.  Exposure to pet allergens can be reduced by keeping pets out of the bedroom and using high-efficiency particulate (HEPA) air filters to remove airborne allergens. Indoor air pollutants can aggravate symptoms of allergic airway disease. They include nitrogen dioxide from gas stoves and kerosene heaters, ozone from electrical appliances, and volatile organic compounds, such as cleaning agents, paints, and solvents. Exposure to these compounds should be minimized as well.

Pharmacotherapy
First-line treatments for pet allergies include oral antihistamines, many of which are available over the counter. They work by blocking the effects of histamine, one of the most common mediators of allergic signs. Additional options include second generation prescription antihistamines, nasal antihistamines and/or nasal corticosteroids. Finally, leukotriene modifiers, such as montelukast, may be useful, if corticosteroid nasal sprays or antihistamines are contraindicated or not effective.

If an individual suffers from asthma, it is important for them to know if they are allergic to pets, as exposure to pet dander can trigger acute asthmatic attacks. Appropriate long-term therapy, which may include corticosteroids, bronchodilators, and other immune modulatory drugs, as well as access to rapid acting bronchodilating agents, often called rescue inhalers, are important if the individual expects to be around pets. However, as pet allergens can be present on clothing and other belongings of pet owners in the absence of a pet itself, the pet allergic asthmatic needs to practice diligence at all times.

Reducing the amount of antigen shed by the pet
A relatively new approach for the treatment of cat allergies has been the introduction of a commercially available feline diet that contains antibodies harvested from eggs laid by chickens immunized to cat allergens. The diet has been shown to reduce the amount of active antigen on the cat and ultimately in the environment, and at least one study has shown that use of the diet improves allergic symptoms in cat allergic owners. In a similar manner, one of the Companion Fund’s portfolio companies, Pacagen, is developing products that contain nanobodies, which are small antibody-like proteins produced by Alpacas immunized against cat allergens. Their planned multi-modal approach will use these highly effective nanobodies, both topically and as part of the diet, to further reduce the amount of antigen shed by cats.

A different approach with the same goal is to immunize cats against their own antigens. To accomplish this, researchers created a vaccine containing a recombinant version of the most common cat antigen, the Fel d 1 gene. The vaccine was well tolerated and had no overt adverse effects. All vaccinated cats had a strong and sustained specific IgG antibody response, and the induced anti–Fel d 1 antibodies were of high affinity and exhibited strong neutralizing capability. The vaccinated cats shed less antigen into the environment and samples of their tears were less allergenic. Saiba Animal Health is currently working to commercialize the vaccine called HypoPet™.

In a far more expensive and controversial approach, researchers recently created hypoallergenic cats using the CRISPR-Cas9 system. In this study, the genomes of two founder cats were edited to inactivate the Fel d 1 gene. Although the treated cats were not homozygous for the mutated gene, when mated, they produced homozygous offspring. Only residual amounts of the Fel d 1 protein were detected in the offspring and it was hypothesized that this was the result of environmental contamination from other cats, because the wild type cats and genetically-modified cats were housed in the same room, though they were individually caged. Of note, no obvious adverse events were noted in the founder cats or their offspring, but the long-term effects of this genetic-modification on cat health and welfare has not been determined.

Immunotherapy
Exposure of an allergic individual to small amounts of the allergen(s), a process referred to as immunotherapy, has been used for over 100 years to decrease or eliminate allergic symptoms. Repeated exposures to small amounts of the protein induces tolerance in the immune system. The likelihood of success of immunotherapy varies with the species. For example, the medical literature on the use of dog extract immunotherapy in patients with dog allergies shows poor and conflicting results. This has been attributed to poor-quality extracts and the inherent complex allergenic profile of dogs, which remains without a clearly dominant allergen. Immunotherapy to address cat allergies is generally more reliable than the dog, likely because of the high prevalence of Fel d 1 sensitivity in the cat allergic population.

The future for pet allergy sufferers
As long as pets are part of our lives, some of us will develop allergies to them. While one day we may be able to genetically modify our pets to avoid these problems, there are a number of options currently available to minimize the amounts of allergens pets produce, as well as the severity of our allergic symptoms. With some effort, we can learn to co-exist with our beloved pets even if we are allergic.

– Cindy Cole, DVM, PhD, DACVCP



First Five
First Five is our curated list of articles, studies, and publications for the month.

1/ The consciousness of the beasts
Consciousness is difficult to define, but one simple definition might be the fact of awareness by the mind of itself and the world. Because one can never truly know what is going on in another organism’s brain, who does and does not have consciousness is difficult to prove.  The results of numerous studies over the last few decades, however, indicate that consciousness is not unique to humans. For example, crows have been shown to learn from previous experiences. Numerous species, including octopuses and bees appear to enjoy playing, suggesting they can experience pleasure. This has led to a consensus statement called the New York Declaration on Animal Consciousness which states in part: “The empirical evidence indicates at least a realistic possibility of conscious experience in all vertebrates (including all reptiles, amphibians and fishes) and many invertebrates (including, at minimum, cephalopod mollusks, decapod crustaceans and insects).” The ethical implications for this consensus and how widespread its acceptance becomes will certainly be interesting to watch and discuss in the coming months and years.

2/ Pets to outnumber children in China
According to an analysis by Goldman Sachs, refenced in The Financial Times, China’s urban pet population will surpass the number of children under the age of four this year, creating a $12bn market for pet food by the end of the decade. The US investment bank’s estimate of China’s toddler-to-pet balance forecasts the supremacy of pets continuing to rise in coming years as younger Chinese opt for cats and dogs over starting families. In this regard, China is following a trend long established in Japan where the pet population of 20 million is roughly four times larger than the 5 million under-four human population.

3/ Attack of the Whales
For some months there have been reports of pods of Orca whales, often referred to as killer whales, attacking and sinking boats in and around the Straits of Gibraltar, Spain, Portugal and France. Now humpbacks seem to want in on the action, with one breaching onto and ultimately capsizing a boat off the coast of New Hampshire in July. There have been a number of hypotheses for the unusual behavior. Some have proposed that one or more of the whales were injured by a boat, and are seeking revenge. Others postulate that the whales are just playing with the boats, arguing that prior to ramming or breaching onto the small boats, they typically do not demonstrate any aggressive behavior. Although we do not know the reasons behind these interactions, at least one study seems to indicate they are increasing.

4/ You can’t judge a study by the press release
Recently a press release claimed that the results of a clinical trial that evaluated a proprietary blend of non-disclosed ingredients showed the first clinical evidence that it is possible to reverse age-related decline in dogs. However, the actual study results provide reason for skepticism. For example, while some measures of canine cognition improved with the treatment, cognition also improved in the placebo-treated group. In addition, the authors reported that dogs treated with the recommended dose of the supplement improved in several owner-reported metrics, such as activity levels and happiness, and had lower frailty scores at the end of the study compared to dogs treated with placebo or a lower dose of the product. However, those differences were not statistically significant, which means they could have occurred just by chance. Finally, while the study found no difference in the occurrence of adverse events between treatment and control groups, it is not possible to determine the long-term safety of these unknown compounds from a 6-month clinical study. Pet owners need to be wary of claims made in press releases, and should ask their veterinarian for advice on the validity of supplement claims in order to protect their pets’ health and welfare.

5/ The quest for longevity targets continues
A number of pathways important in inflammation, including ERK, AMPK and mTORC1 have also been identified as playing key roles in longevity and health span. The results of a recent study suggest that IL-11, a pro-inflammatory cytokine of the IL-6 family, may also play an important role in aging. When the IL-11 pathway was eliminated in genetically engineered mice, the lives of both sexes were extended by 24.9% on average. In a similar manner, when mice were treated with antibodies directed at IL-11 from 75 weeks of age until death, their median lifespan was extended by 22.5% in males and 25% in females. Together, these findings suggest that the pro-inflammatory factor IL-11 may play a role in mammalian health span and lifespan, though more research is needed to understand how these findings can be applied to other mammals such as dogs, cats, and humans.