About a quarter of the population is bracing for an attack from a seemingly innocuous source — pollen.

The perennial release of cedar pollen, which hits much of the archipelago between February and May each year, triggers an allergic reaction in about 1 in 4 of Japan’s population of 123 million people. Fits of sneezing abound as noses either clog or run freely, and eyes become so itchy there’s a temptation to scratch them from their sockets.

Cedar pollen allergies weren’t common in Japan until the mid-1960s, when Yozo Saito of Tokyo Medical and Dental University reported the first cases of people complaining of an irritation in their noses, throats and eyes near a cedar forest in Nikko, Tochigi Prefecture. Saito, dubbed the “father of hay fever” in Japan, named the affliction “Japanese cedar pollinosis” in 1964.

Hay fever — which is also caused by cypress and ragweed, among others — hurts not only our health but also the economy. Although it is obviously a boon for the producers of masks, goggles and air purifiers during pollen season, whatever benefits hay fever may have are subsequently offset by the negative impact of a quarter of the population staying inside.

A 2005 Dai-Ichi Life Research Institute report said hay fever was expected to dampen consumption by as much as ¥754.9 billion in the first three months of that year, pushing down the country’s quarterly gross domestic product by 0.6 percent. It is likely the economic damage from hay fever could have worsened ever since, as the number of people suffering from the symptoms has all but certainly increased.

Can we fight back or are we facing a constant battle against irritation? The Japan Times spoke with four prominent researchers in various fields to ascertain what they are doing to solve the nation’s annual fight against suffering.

Drug warfare

Kimihiro Okubo, a professor at Nippon Medical School Hospital’s Otorhinolaryngology Department, has been at the forefront of the country’s research and treatment of pollen allergies for many years.

Historically, antihistamines have been used to treat hay fever, with sufferers turning to them in droves in an attempt to alleviate symptoms such as watery or congested nasal passages and irritated eyes.

Recently, however, significant progress has been made in the field of immunotherapy, which aims to change the way in which the immune system responds to allergens, or allergy-causing foreign substances, Okubo says.

“The goal of immunotherapy is to change the body’s sensitivity to pollen,” Okubo says, adding that the treatment appears to work indefinitely if successful.

“For example, if a patient reacts after 30 particles of pollen are ingested into the body, immunotherapy is used in an attempt to raise that threshold to 100 particles,” Okubo says. “Symptoms such as sneezing and nose irritations are the direct result of the body defending itself against allergens. The idea is to inject more allergens into our body so that we become more accustomed to them and their presence does not trigger any inherent defense mechanism.”

The therapy has been available for a number of years in the form of an injection, or allergy shot, in which an extract of pollen allergen is injected into the skin of a hay fever sufferer’s arm. However, the shots are painful and the therapy involves numerous visits to a doctor over two years or more.

The more recent success of sublingual immunotherapy has given pollen sufferers greater hope.

A patient receiving sublingual immunotherapy, which is also designed to boost the body’s tolerance to allergens, is injected with small doses of cedar pollen under their tongue. The pollen is then absorbed through the lymph nodes in the neck that come into direct contact with pollen.

Okubo’s team started clinical trials for sublingual immunotherapy in 2000, reporting positive results in 2008. The drug was subsequently approved for general use in 2014 and has been covered by the public health insurance program ever since.

Sublingual immunotherapy has been found to eradicate symptoms related to cedar allergies for 30 percent of people who try it, Okubo says, adding that it also reduces symptoms for another 50 percent. The therapy has little effect on the remaining 20 percent, he says.

Advances in such treatment have made the application of immunotherapy much easier. Unlike the aforementioned injections, patients can administer the drug themselves after their first visit to a doctor, putting drops of the extract under their tongue and holding them there for two minutes. However, they must repeat the routine every day for three to five years.

In 2018, sublingual immunotherapy is expected to be produced in a tablet form, which will be easier for allergy sufferers to take. However, Okubo says that patients will be required to get a new prescription every two weeks from a doctor because it’s a new drug.

Another new treatment on the horizon is called lysosomal associated membrane protein immunotherapy. It’s been dubbed the “next-generation DNA vaccine.”

Developed by Johns Hopkins University in Baltimore, Maryland, and U.S. biotech firm Immunomic Therapeutics, the therapy is currently undergoing clinical trials.

Patients undergoing such treatment do not directly receive an extract of cedar pollen. Instead, DNA instructions for producing allergenic proteins are injected into a cell of hay fever sufferers, which allows their immune system to respond more quickly to pollen exposure and either prevent an allergic reaction or alleviate the symptoms, according to the biotech firm.

If approved for commercial use, lysosomal associated membrane protein immunotherapy treatments would be complete in five to eight injections, Okubo says, adding that the exact details are still being worked out, including the number of shots a patient requires and the interval between them.

As for this coming pollen season, Okubo says cedar pollen will generally be in greater concentration in western Japan, with levels expected to be about two times higher in the western part of the country.

In addition to medication, Okubo says that masks and goggles are recommended, as well as staying indoors as much as possible.

Pollen and air pollution

Seiyo O, an associate professor of environmental engineering at Saitama University, has studied the link between pollen and air pollution. His research provides valuable insight into why hay fever appears to be more prevalent in urban areas, instead of in the countryside where pollen is abundant.

O, a naturalized Japanese citizen who came from China as a researcher 28 years ago, has long believed that hay fever is exacerbated when pollen mixes with other pollutants in the air and fragments into smaller particles. For years, however, his hypothesis was dismissed by mainstream academics, he says.

In May 2003, a committee of scientists commissioned by the Tokyo Metropolitan Government said they had discovered for the first time in Japan that exhaust gas emissions from diesel engines could trigger the onset of hay fever or worsen symptoms. In a world first, they also found that rats born from pregnant mothers exposed to diesel emissions were more likely to suffer from a pollen allergy.

But O, who served on the committee, disagreed with the scientists’ ultimate conclusion that there’s no clear epidemiological link between people’s exposure to diesel emissions and their likelihood of suffering from hay fever.

“I thought, ‘It simply can’t be true,'” O says. “At that time, Saitama University had a dormitory in the (rural) Chichibu region, where students would gather for study seminars and such. The area is surrounded by cedar trees and pollen is everywhere, but I saw no one suffering from hay fever. Back in the (more urban) city of Saitama, where the university campus is, 1 in 3 people have hay fever. I believed that there must be a reason for this and so I decided to dig deeper.”

O has subsequently found that the surface membranes of cedar pollen particles — each with a diameter of around 30 micrometers — are typically damaged as the pollen travels from the mountains to the cities and comes into contact with pollutant chemicals in the air. Common pollutants include such things as car emissions or the yellow sand that travels across Japan from China and Mongolia, where air pollution is also serious, O says.

Mainstream pollen experts initially questioned O’s hypothesis, arguing that “pollen is simply pollen,” he recalls.

However, O succeeded in convincing them to change their tune after he used a special electronic telescope to capture video footage of airborne pollen particles growing in size as they absorbed humidity and then ruptured.

Once pollen particles break down, they can measure as little as PM1.1 (fine particle matter with a size of 1.1 micrometers) and can therefore be more easily ingested by people. Such tiny particle matters accumulate in the respiratory tract or lungs and trigger symptoms such as coughing or even asthma, O says. In addition, O says that fragmented pollen particles tend to accumulate by the side of roads, so children and pets in particular are affected.

To reduce exposure, O says people should wear masks and pollen goggles when going out, but preferably ones that block PM2.5 particles. He also recommends people to check not only pollen forecasts but also the concentration of PM2.5, and refrain from going out on days when both pollen and PM2.5 levels are high.

More fundamentally, O says, there is a need to think harder about ways to reduce air pollution.

“Pollen wouldn’t break down without air pollution,” he says. “If pollen particles stay as large as 30 micrometers they would eventually be washed away (by rain). The bigger problem is polluted air, which causes the pollen to fragment.”

Tracking hay fever on social media

Computer scientist Eiji Aramaki has tried to harness the power of social media to monitor and predict hay fever trends since 2011.

It’s an emerging field but Aramaki is serious about his artificial intelligence-powered research, which has potential to capture disease trends more quickly and accurately than conventional approaches.

“Every minute, 4 million Facebook ‘likes’ and 340,000 tweets are created,” says Aramaki, an associate professor at the Nara Institute of Science and Technology. “Some of these actions on social media provide medically useful information. If we can farm just a little bit of these actions, it might lead to huge discoveries that could overturn conventional surveillance systems.”

In 2012, Aramaki started using Twitter to map flu trends (mednlp.jp/influ_map) He recorded all tweets that people across Japan posted about the seasonal infectious disease and its symptoms, whether that be complaints about catching a bout or talk of vaccinations they or their friends got.

Aramaki has come up with an algorithm through which AI-powered computers instantly rate each tweet and judge the likelihood of the tweet coming from an actual flu patient. Not only that, the computers are able to work out a Twitter user’s gender, age group and the prefecture that they live in.

The computers are programmed to refine their skills through “machine learning” in order to separate tweets related to the flu from other tweets.

Aramaki then cross-checked the results of his analysis with weekly patient numbers that are reported by hospitals and clinics nationwide and tallied by the National Institute of Infectious Diseases.

The results were incredible, he says.

The trend curve showing the number of posts that his computers judged to be coming from influenza patients matched the medical reports announced by the National Institute of Infectious Diseases almost perfectly. When the two charts were overlaid, it showed the ebb and flow of influenza reports arrived a little earlier in the Twitter chart, suggesting that the tweets were probably closer to real-time trends.

“Hospital reports have a time lag of about a week,” Aramaki says. “Tweets can be collected on a real-time basis.”

His experiences in tracking hay fever have been a little more complicated and, as a result, more speculative in nature. Unlike influenza, there’s no nationwide reporting system for hay fever, which means that it’s hard to verify the accuracy of his Twitter surveillance program (mednlp.jp/kafun/index2.html)

During pollen season, the environment ministry, local governments and private-sector weather forecasters release daily predictions based on the amount of pollen detected by air sensors nationwide.

However, it takes time for pollen particles in the air to be ingested, triggering allergic symptoms, so providing a forecast by region is not very helpful in determining when or how a person might be affected by hay fever. Adding to the problem, pollen also becomes more toxic when mixed with air pollution.

“The time gap (between pollen’s dispersal and the onset of symptoms) is large,” he said, adding that the data charts — the tweets on hay fever and actual pollen levels — don’t quite match. He almost abandoned his research once, thinking it wasn’t useful before ultimately changing his mind.

“I think there’s a chance that tweets are a better gauge of hay fever trends than pollen data,” he says.

More generally, Aramaki does envision a future in which social media users will be able to predict and prevent the spread of disease.

“If more people realize that their tweets can be used to forecast the spread of common diseases, they might become more active in tweeting about their condition, thus raising the accuracy of such data,” he says. “It might spur a social movement where people try to prevent common diseases by tweeting their experiences here and there. It’s kind of like recycling, which can only succeed if everyone cooperates. If SNS starts to fulfill such a function, it could turn into a basic social tool.”

The root of the problem

Forestry management is just as important as high-tech air filters, face masks and medicine.

Takayuki Kawahara, a research director at the Forestry and Forest Products Research Institute, says there’s no quick fix to the pollen problem. He adds, however, that several projects are underway at the government-affiliated organization to keep the problem from worsening.

The rise of hay fever, especially allergies caused by cedar pollen, has a lot to do with Japan’s forestation policy after World War II, when demand for timber surged as the nation rebuilt itself.

Cedar was the tree of choice, especially in eastern Japan, because it grew quickly and could easily be turned into timber. In western Japan, on the other hand, cypress was popular, but that tree also came with its own allergen risk.

A majority of the nation’s cedar trees are now 50 years or older — their prime age. However, imports of cheap timber as well as a decline in the number of aging forestry workers have meant that a lot of the trees that were supposed to have been cut down have been left unattended, resulting in the perennial pollen pollution.

Kawahara acknowledges that the institute’s efforts to get to the bottom of the pollen problem started pretty late — about 15 years ago, nearly 40 years after the first cases of an allergy to cedar pollen were confirmed.

The researchers now select and cross-breed cedar trees that grow well and emit pollen totaling less than 1 percent of normal cedar trees. Such trees now make up 80 percent of all cedar trees that have been planted in the Kanto region in recent years, Kawahara says.

A novel approach being explored by the institute is the use of a natural fungus that infects only male cedar flowers. In a study published in 2013, researchers sprayed the fungus — Sydowia japonica — on male flowers on six cedar tree branches in Ibaraki and Kumamoto prefectures.

The study showed that 80 percent of the flowers sprayed with the fungus withered and died within two or three months, keeping the pollen from being dispersed.

However, it will take years for such a spray to be commercialized, Kawahara says, as researchers need to carefully check if the fungus is safe enough for humans and other vegetation.