New Thinking On Longstanding Asthma Treatments

Every day millions of asthma patients follow the standard doctor-recommended treatment: They take puffs from their steroid inhalers. Amber Keating is one of them. For 19 years, a daily steroid inhaler has been a cornerstone of the 42-year-old Los Angeles resident’s treatment. But in recent years she began to question its effectiveness as she had more flare-ups. So she was interested to see a new study in the New England Journal of Medicine showing that the majority of a group of patients with mild, persistent asthma did no better when taking a steroid inhaler than with a placebo. “This is something that doctors are prescribing and it doesn’t seem to be effective for some of us, so what’s that about?” says Ms Keating. More than 25 million people in the U.S. have asthma, including six million children. Mild, persistent asthma is a common form of the disease. Medical guidelines recommend taking a daily steroid inhaler to reduce inflammation in addition to an as-needed rescue inhaler when patients have difficulty breathing.

Stephen Lazarus, Professor of Medicine at the University of California, San Francisco and lead author of the study, says it may be time to re-evaluate these longstanding recommendations. A growing body of evidence suggests that there are different kinds of asthma that may need to be treated differently, doctors say. “As specialists, we don’t just settle for one size fits all. Other treatments may be more effective for a minority of asthmatics,” says Michael Wein, Chief of Allergy at Cleveland Clinic Indian River Hospital in Vero Beach, Fla. He and other doctors cautioned that asthma patients should continue to take their steroid inhalers every day while more research is being done. “Most patients taking steroid inhalers probably do need the steroid inhaler,” says Dr Wein.

Inhaled steroids are generally considered safe, but they are linked to some increased risks, including a reduction in bone density, glaucoma, cataracts and increased bruising. Children who take inhaled steroids long term may also have slightly stunted growth. The new research focuses on daily inhaler treatments; it’s not questioning the effectiveness of rescue inhalers. Dr Lazarus’s study found that for a set of asthma patients—those with low levels of a particular type of white blood cells—only about one-third did better when taking the standard daily inhaled steroid versus a placebo. At the start of the study, researchers analysed the mucus of the 366 patients to determine their levels of eosinophil, a type of white blood cell, says Dr Lazarus. About 73% had low eosinophil levels and 27% had high levels. High and low levels aren’t an indication of asthma’s severity but rather reflect different types of inflammation in the lungs’ airways.

The trial compared three treatments: an inhaled steroid called mometasone; a nonsteroidal treatment called tiotropium, which is a long-acting muscarinic antagonist or LAMA; and a placebo. Most people with high levels of eosinophils did better when taking a steroid inhaler versus a placebo. But patients with low eosinophil levels didn’t see similar success rates. “An astonishingly high proportion of people with mild asthma” have a type of inflammation which may not get better with steroid inhalers, says Dr Lazarus. “If you have patients who have been prescribed steroids and they don’t seem to be responding, the solution is not to escalate the dose and give them more and more, the solution is to think of alternative ways of managing asthma.” The majority of patients with low eosinophil levels who took a LAMA, which relaxes muscles and increases air flow to the lungs, did better than when on placebo but the difference was not statistically significant. Still, Dr Lazarus says this suggests a potentially better alternative treatment for certain asthma patients and he plans to do more research.

Another study in the same issue of NEJM found that mild or intermittent asthma patients could be treated just as effectively with a combination inhaler—an inhaled steroid and a long-acting beta agonist—on an as-needed basis rather than taking a steroid inhaler every day. “Should we be thinking about using these more as needed rather than having patients taking them on a daily basis?” says James Sublett, Chief Medical Officer of Family Allergy & Asthma in Louisville, Ky. In his experience, many patients may already be doing this because milder asthmatics often don’t use their inhalers regularly. But he cautions that patients with mild asthma often can’t perceive when they are about to have a flare-up. Currently, allergists check eosinophil levels through a blood test. In the study, researchers checked levels using coughed-up mucus. That test is harder and more expensive than a blood test, but may be more accurate. Experts say more work needs to be done to come up with an easy and accurate way to test eosinophil levels. Ms Keating says she doesn’t know if she has high or low levels of eosinophils. She recalls having had to pay $200 for her steroid inhaler one month when she was in between jobs and insurance providers. She also always has been concerned about the impact of steroid inhalers on her vision and bone density and regularly takes a calcium supplement. “I’m sort of astounded because there are these side effects from corticosteroids and they are also extremely expensive,” she says. “I plan to ask my asthma specialist next time I see him.”

Credit: Sumathi Reddy for The Wall Street Journal, 10 June 2019.