An A*STAR study has suggested that wheezing and eczema in infancy are correlated with an increased risk of sensitization to airborne allergens, including allergic rhinitis (hay fever).
© Getty Images/Clover No.7 Photography
First, the bad news: There’s no simple cure for allergies…at least for now. One of the most widespread, allergic rhinitis (or hay fever) affects as much as five per cent of the world’s population. The hallmarks of this foe are sniffling, itching and sneezing, and it strikes indiscriminately, regardless of age or ethnic background.
No-one knows why some people develop this allergy and not others, but scientists in Singapore have recently found some important clues in studies on the impact of climate, cell responses and childhood experiences.
Allergies are essentially glitches of the immune system. Your body responds to some usually harmless material by activating an immune response that releases a number of substances. The main culprit, histamine, sparks inflammation and is responsible for the most irritating symptoms, such as itching and swelling.
In spring, people often suffer from what is known as seasonal or intermittent allergic rhinitis — triggered by pollen from trees and grasses, as well as fungal spores. Less seasonal, is the allergic rhinitis triggered by dust mites, animal dander (such as pet fur), mold and cockroaches. The latter can be a huge burden on large cities in tropical climes — environments in which dust mites thrive.
In fact, allergic rhinitis could be having a hefty effect on productivity worldwide. Roughly eight per cent of adults experience allergic rhinitis in the United States, while other national surveys have estimated prevalence rates of around six per cent in France and 29 per cent in the United Kingdom. More than just an irritation, common symptoms of allergic rhinitis are also loss of sleep, irritability and fatigue — all of which have an effect on performance at work and school.
The eight-legged culprit
A survey of 8,000 adults in Singapore published in Allergy in 2014 found an astounding 40 per cent of those surveyed reported symptoms of allergic rhinitis1.
People living in countries with similar climates in the tropical belt (Singapore, Malaysia, Indonesia and others) showed similar evidence of exposure to two species of dust mites, Dermatophagoides pteronyssinus (above) and Blomia tropicalis.
© K.H. Kjeldsen/Science Photo Library
In fact, by testing the blood of nearly 600 people, the team found a staggering 80 per cent of Singaporeans had antibodies called Immunoglobulin E (IgE) specific to house dust mites.
Two species of dust mite often found in mattresses, bed linen, carpets and upholstered furniture were implicated: Dermatophagoides pteronyssinus and Blomia tropicalis. And the unpleasant truth is that people are not allergic to the mites themselves, but their fecal matter.
“To verify our findings, we looked at a much larger sample size of more than 7,000 volunteers,” says Anand Andiappan, a senior research scientist at A*STAR’s Singapore Immunology Network (SIgN), who worked on the study with other colleagues at SIgN and collaborators at the National University of Singapore (NUS).
“Astonishingly, we found the figure was similarly high: 75 per cent of this larger group had antibodies against house dust mites.” That means that three-quarters of Singaporeans potentially have a dust mite allergy.
It’s not about your ethnicity
As part of the 2014 study, the researchers looked closely at the ethnic Chinese portion of respondents and found that climate, rather than genetics, appears to have the most impact on sensitization. Andiappan notes: “People who had just arrived in Singapore from mainland China seemed to have a much lower prevalence of the house dust mite allergy and allergic rhinitis symptoms compared to those who had stayed more than eight years.” In some cases, he says, the difference was evident after just three years of living in Singapore.
People from temperate climates, such as mainland China and Hong Kong, generally become more sensitive to house dust mites the longer they stay in Singapore, showing that this type of reaction is exacerbated by exposure and not genetics.
© Reproduced from Ref. 1 with permission from the European Academy of Allergy and Clinical Immunology (EAACI)
By contrast, there was no significant difference in reactivity to dust mites between Chinese people from Malaysia and those born in Singapore. This suggested that climate is a significant factor in determining exposure levels and allergic response: People from countries with similar climates in the tropical belt — Singapore, Malaysia, Indonesia and others — show similar reactivity to dust mites, suggesting they had been exposed before. People from temperate climates, such as mainland China and Hong Kong, generally become more sensitive to house dust mites the longer they stay in Singapore.
Dust mites thrive in the hot and humid conditions that are the norm in tropical zones. In temperate climates, although they can be a problem in the summer, they usually die off during the drier winter months.
To Olaf Rötzschke, a principal investigator at SIgN who is now leading the most comprehensive adult allergy cohort study conducted in Singapore, these findings were nothing short of “spectacular”. He began to look more closely at the problem.
Usually, Rötzschke says, allergy studies are complicated by the sheer number of factors that could be involved, such as pollen, fungi and animal dander. “The advantage here in Singapore is that we have a perfect environment for analysis because the problem-causing allergen [dust mites] is so specific.”
“We started out with a big exploratory study — we weren’t even focusing on allergies at the beginning,” says Rötzschke. “We effectively cast a net, and this fishing approach enabled us to build a huge database, so we could really dive into exploring immune responses and genomics.”
Rötzschke points out that urbanization and lifestyle changes — namely, spending more time indoors — may be the most significant factors behind an overall increase in the prevalence of airborne allergies in recent decades.
This increasing tendency to stay indoors is not limited to Singapore. “What we are seeing here will become more relevant to other countries,” Rötzschke points. “So, I consider this a unique chance for us to become a world-leading center for allergy research.”
Why some people will never know they’re allergic
One intriguing conclusion drawn from Andiappan’s 2014 study was that not everyone who tests positive for the house dust mite allergy (roughly 80 per cent) goes on to have symptoms (roughly 40 per cent).
During a bout of allergic rhinitis (hay fever), white blood cells respond to contact with allergens, such as dust mite fecal matter, by releasing histamine, which creates swelling and inflammation. For some people this obvious part of the process doesn’t occur, and so they will probably never know they are having an allergic response to an allergen.
© Kateryna Kon/Getty Images
In 2017, Rötzschke and his team made a breakthrough regarding protection from allergic rhinitis based on a phenomenon called basophil anergy2.
Basophils are cells in the blood that detect allergens and trigger allergy symptoms. In some cases, these basophils become inactive. This so-called ‘anergy state’ correlates with people who don’t develop allergic rhinitis, which could be one explanation for why some people whose Immunoglobin E antibodies levels would suggest that they are allergic, don’t develop symptoms.
Rötzschke says that it’s possible that this process of shutting down basophils could provide a mechanism for targeted treatment of AR that involves “switching off” nasal allergies.
Early risk factors and early diagnosis
No one knows yet if treatments targeting basophils will become a reality, but some people can already train their immune system to respond better through exposure to small doses of an allergen over long periods. This method, called allergen-specific immunotherapy, is widely considered to be the best treatment option for allergies.
To give sufferers the best chance of benefitting from such treatment, more studies are focusing on immune response in early childhood to find ways to predict the likelihood of developing respiratory allergies later in life.
For example, a study in Sweden has shown that onset of eczema in the first year of life was linked to increased risk of developing asthma and allergic rhinitis later on3.
In the first large-scale study of its kind in Singapore, Evelyn Loo, co-workers at the Singapore Institute for Clinical Sciences and collaborators at NUS, among others, found that wheezing and eczema before 18 months is associated with increased risk of senzitisation to allergens, including house dust mites, at three years of age4.
They conclude that the common long-term effect of impaired airway function caused by early-onset wheezing or eczema might make children more vulnerable when exposure to allergens in later life.
The earlier people pick up on dust mite allergy symptoms, the better, says Andiappan. Most adults unfortunately seem to be self-diagnosing, he says, and ignoring symptoms or taking over-the-counter antihistamines, which only offer short-term relief. “As the house dust mite trigger doesn’t immediately lead to severe reactions, people tend to be less cautious about it.”
It’s important Andiappan advises, to get yourself properly diagnosed via a skin prick or a blood test. “If you’re constantly exposed to the allergen over a long period of time, it could affect disease treatment adversely, so our recommendation is early diagnosis.”
Following up with the group of people who ‘carry’ the allergy without adverse effects will be another crucial next step for clinical research. This is where the study of epigenetics — changes in gene expression that do not involve changes to your DNA — will become increasingly important.
A curious side note is the fact that Rötzschke himself says he does not have allergic rhinitis, even though he has been based in Singapore for the last decade, after spending many years in temperate climes both in Europe and the in US.
“I fall exactly into that area where I’m supposed to have a response to house dust mites, but I don’t. Why am I not allergic?” he asks. “It may be that my genetics renders my basophils inactive.” This broad question is among the many things he and his team will investigate next.
A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network and the Singapore Institute of Clinical Sciences (SICS).
