Overactive T2 inflammation, a type of immune response linked to asthma, may be associated with worse symptoms of cystic fibrosis (CF), a finding that could pave the way for using anti-asthmatics for CF, a study suggests.

The study, “Association between Cystic Fibrosis exacerbations, lung function, T2 inflammation and microbiological colonization,” was published in Allergy, Asthma & Clinical Immunology.

T2 inflammation refers to a type of immune response involving white blood cells called eosinophils. When the body encounters a trigger such as pollen or dust, eosinophils are activated and release certain chemicals that cause inflammation.

While this is part of a normal immune response, T2 inflammation can sometimes go into overdrive. When this happens, it can cause asthma or other breathing problems.

More than a third of people with CF in the CF Foundation Patient Registry report having asthma. While CF and asthma have different causes and mechanisms, they can both lead to similar symptoms such as wheezing (noisy breathing with a whistling sound), coughing, and difficulty breathing.

There’s some evidence that T2 inflammation can contribute to a worsening of symptoms in people with CF. For example, when the lungs get inflamed, breathing can become harder and a flare-up of symptoms, called a pulmonary exacerbation, can occur.

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An illustration of a child coughing.

T2 inflammation markers and CF

Researchers in the U.S. hypothesized that if someone with CF has more T2 inflammation markers, their lungs might not work as well and they may have more exacerbations and be more likely to get an infection.

To test this, they looked at the clinical data of 74 adults who received care at the University of Virginia Medical Center from 2013 through 2018.

The patients’ mean age was 35.1 and 40 were women. More than two-thirds were receiving inhaled corticosteroids or CFTR modulators, a type of medication designed to tackle the underlying defect in CF.

The most common diseases coexisting with CF were asthma (82.3%), followed by CF-related diabetes (43.2%), and allergic bronchopulmonary aspergillosis (8.3%), which results from an infection with the fungus Aspergillus fumigatus in the lungs.

Average absolute eosinophil count (the total number of eosinophils) a year over the study period exceeded 300 cells per microliter of blood in 34 (45.9%) patients. Its median was significantly higher in patients with more than two exacerbations a year than in those with two or fewer.

The odds of more exacerbations happening with a high eosinophil count were 1.88 times the odds of them happening in those with a low eosinophil count. During an exacerbation, a patient may have to be hospitalized or placed on intravenous (into-the-vein) antibiotics.

As the eosinophil count increased, the probability the measurement was taken during an exacerbation also increased. It’s possible that the eosinophil count is “a marker of T2 inflammation regardless of trigger,” the researchers wrote.

While the researchers confirmed their hypothesis that a higher eosinophil count is linked to more frequent exacerbations, “it is unclear if exacerbations cause increased T2 inflammation or T2 inflammation predisposes to increased exacerbations,” they wrote.

The researchers also checked the levels of immunoglobulin E (IgE), an antibody produced by the immune system in response to a trigger. Fourteen (18.9%) patients had a maximum IgE that exceeded 180 international units per milliliter of blood.

Higher IgE levels were linked to a greater number of exacerbations a year, even after adjusting for the presence of atopy, which is a tendency to mount a heightened immune response to common allergens that would otherwise be harmless.

“This is a new finding and suggests that T2 inflammation may be partially responsible for increased exacerbations,” the researchers wrote.

A decline in lung function, measured using the percent predicted forced expiratory volume in one second, was linked to both higher absolute eosinophil count and IgE levels. The relationship held true after adjusting for age, sex, and the presence of a number of species of bacteria or fungi.

These findings support the use of anti-asthmatics in people with CF, which could have “the potential to lower the health care costs of hospitalization and decrease exposure to intravenous antibiotics,” the researchers wrote.

For example, mepolizumab, a GSK medication sold as Nucala and approved for severe asthma associated with eosinophils, has improved the clinical course of three adults with CF who had indicators of T2 inflammation.

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