There was only one problem. As more data came in, they failed to tell the same story as the hygiene hypothesis. Children in Latin America with high rates of supposedly protective infection have even higher rates of asthma than children in western Europe. Inner-city children in Chicago and New York have quite high rates of asthma, despite unhygienic living. And the rates of asthma varied among countries with very similar histories of cleanliness—indicating that there was more to it than tidiness. For example, by 2004 Sweden’s asthma cases had increased to 10 percent, according to one international study, while the number of cases in the U.K. had soared to 20 percent.
In addition, research showed that the relation between asthma and allergy is not at all straightforward. Some cases of asthma are indeed triggered by allergies, although the consensus among researchers over the past decade is that the connection is probably not as clear-cut as the hygiene hypothesis would suggest. Still other layers of immune regulation must be involved. Maria Yazdanbakhsh, a parasitologist at Leiden University in the Netherlands, has shown that people infected with parasitic worms have very high levels of the allergy-related immune cells but very low rates of asthma, disproving a direct connection between allergy and asthma in these cases at least.
What is more, a landmark review of asthma studies in 1999 by Neil Pearce, now at the London School of Hygiene and Tropical Medicine, demonstrated that at least half of asthma cases in the general population have no connection to allergic reactions at all. These could never be explained by the hygiene hypothesis.
In fact, the same factors that the hygiene hypothesis suggests protect people from developing allergic asthma may cause them to develop nonallergic asthma. “We think that dirt protects against allergic asthma, as foretold by the hygiene hypothesis, but increases the risk of having a nonallergic form,” says Laura Rodrigues of the London School of Hygiene and Tropical Medicine, who studies asthma in Latin America. Pollutants in the air can irritate the airways and cause inflammation that leads to constricted breathing. Childhood colds, which the hygiene hypothesis suggested might help prevent development of asthma, can actually be a risk factor for asthma, especially if severe, says James E. Gern, a pediatrician who studies colds and asthma at the University of Wisconsin–Madison. “Early-life infections are an indicator of asthma risk rather than protective in any way,” he says.
Besides the hygiene hypothesis, what can explain the increase in asthma rates? Other suggested causes include a rise in sedentary lifestyle, which could affect lung strength, and the rise in obesity, which increases inflammation throughout the body. A reworking of the hygiene hypothesis that focuses on changes in the normal nondisease-causing bacteria that live inside and on the body (in the intestines or the airways or on the skin) has promise. Studies by von Mutius and others have shown that children who live on farms where cows or pigs are raised and where they drink raw milk almost never have asthma, allergic or otherwise. Presumably because the children drank unpasteurized milk and handled livestock, they have different strains of normal bacteria in their airways that are somehow more protective than those found in city kids.
But the short answer to the question of why asthma has increased, according to Pearce, von Mutius, Rodrigues and many others, is, “We don’t know.” Pearce, in particular, wonders whether modernization in general or westernization in particular may play a role. “There is something about westernization that means people’s immune systems function in a different way,” he says. “But we don’t know what the mechanism is.”