Asthma rates have been surging around the globe over the past three decades, and for a long time researchers thought they had a good idea of what might be fueling the increase: the world we live in is just a little too clean. According to this notion—known as the hygiene hypothesis—exposure in early childhood to infectious agents programs the immune system to mount differing highly effective defenses against disease-causing viruses, bacteria and parasites. Better sanitary conditions deprive the immune system of this training, so that for reasons that are still unclear, the body pounces on harmless particles—such as dust and ragweed—as if they were deadly threats. The resulting allergic reaction leads to the classic signs of asthma: chronic inflammation or swelling of the airways and acute spasms of those passageways.
Or so the thinking went. Although a lot of data support the hygiene hypothesis for allergies, the same cannot be said for asthma. Contrary to expectations, asthma rates have skyrocketed in urban areas in the U.S. that are not particularly clean. Moreover, the big increase in asthma rates in developed countries did not kick off until the 1980s—well after general sanitary conditions in the richer parts of the world had improved. And some studies are beginning to show that far from protecting children from asthma, respiratory infections in early childhood may actually be a risk factor for it.
The collapse of the hygiene hypothesis as a general explanation for the startling jump in asthma rates has led physicians and scientists to a new realization: asthma is a much more complex condition than anyone had truly appreciated. Indeed, it may not be even be a single disease. Studies now suggest that only half of asthma cases have an allergic component.
The prevention and treatment implications are significant. If, for instance, it is true that allergy is not a fundamental cause of asthma in many people, then an alternative mix of treatments may be more effective for those individuals. To root out asthma’s cause (or causes) and properly treat the burgeoning number of people who are affected—300 million globally at last count—scientists will have to come to grips with the biology of its various forms.
The hygiene hypothesis was first described in 1989 by David P. Strachan, a British epidemiologist who was studying hay fever. The more children in a family, he noticed, the lower the rates of hay fever and eczema, an allergic skin condition. Children in large families tend to swap colds and other infections more often than children with fewer siblings. Could it be that increased exposure to pathogens from their many siblings was protecting children from large families against allergies?
That same year Erika von Mutius, an epidemiologist at Munich University, was looking into the effect of air pollution on asthma in what was then East and West Germany. Children from dirtier East Germany, she was shocked to find, had dramatically less asthma than their West German counterparts living in cleaner, more modern circumstances. The East German children, unlike their Western counterparts, had spent more time in day care and thus had likely been exposed to many more viruses and bacteria. “That was astonishing,” she recalls, and led to “a major shift” in thinking.
These findings sparked intense debate among scientists. What is it about unhygienic living that might protect against asthma? One of the more popular explanations in the following decades entailed a balance between the immune cells that are involved in the body’s reaction to most viruses and bacteria and those that are involved in the reaction to most parasites and allergens. These two groups of cells produce chemicals that inhibit each other. Early-childhood exposure to bacteria and viruses would cause the infection-related cells to become active, keeping the allergy- and parasite-related cells in check. Without that interplay, the allergy-related cells would later become overreactive, starting an allergic chain reaction that became chronic and ended in constricted airways, asthmatic spasms and labored breathing.