Type 2 inflammation in CF linked to worse lung function
CFTR modulators reduce inflammation, study finds
Nearly two-thirds of cystic fibrosis (CF) patients in a study showed signs of type 2 inflammation, which was associated with worse lung function, more infections, and a higher risk of death.
This form of inflammation, most commonly linked to allergic conditions, was reduced somewhat after treatment with CFTR modulator therapy.
The study, “Type 2 inflammation in cystic fibrosis is a predictor of mortality and targeted with CFTR modulator therapy,” was published as a letter to the editor in Allergy.
The thick and sticky mucus that accumulates in CF lungs offers a breeding ground for infection-causing bacteria, leaving patients prone to severe infections that cause inflammation, damage, and lung function declines. CF airways are characterized by inflammation driven predominately by neutrophils, a class of immune cells that are often involved in the response to bacterial invaders.
It has recently become recognized that another type of inflammation — type 2 inflammation — is also present in CF and may contribute to worse outcomes for patients.
Excess eosinophils
This type of inflammation is characterized by an excess of immune cells called eosinophils, increased production of a class of antibodies called immunoglobulin E (IgE), and elevated levels of the IL-4 and IL-13 inflammatory signaling molecules.
Type 2 inflammation is perhaps best recognized for its role in allergic conditions, but is also involved in driving other types of immune responses. Increased type 2 inflammation has been observed in CF patients and animal models, according to the authors.
To learn more about the relationship, the researchers looked at electronic health records from CF patients in the U.S., specifically looking at blood tests that evaluated eosinophils and IgE levels. An elevation in either one was considered a sign of type 2 inflammation.
Among 483 adult CF patients, 316 (65.4%) showed signs of type 2 inflammation and 167 did not. The two groups were similar in terms of age, sex, and racial distribution.
Patients with this type of inflammation showed overall signs of greater disease burden compared to those without it, including significantly more prescriptions for inhaled and systemic corticosteroid treatments.
Co-existing allergic conditions were also significantly more common in that group of patients, as were respiratory complications. These included higher rates of infection with Pseudomonas aeruginosa and Staphylococcus aureus, two common infection-causing bacteria found in the CF lungs, as well as fungal infections.
Complications associated with such infections, like antibiotic resistance, pneumonia, and lung abscesses (localized collections of pus or dead tissue within the lung), were also more common.
Moreover, type 2 inflammation was associated with reduced lung function. Increases in blood IgE levels were associated with proportional decreases in lung function. These patients were also at a more than two times higher risk of death relative to patients without type 2 inflammation.
“Our study demonstrates a T2 endotype [subtype] exists within CF characterized by increased obstructive pulmonary disease, and distinct … signature of increased allergic disease, infections, and burden of CF complications,” the researchers wrote.
Treatment with highly effective CFTR modulator therapy — Trikafta (elexacaftor/tezacaftor/ivacaftor) or Kalydeco (ivacaftor) — led to a mean 30% reduction in blood IgE levels, whereas treatment with Orkambi (ivacaftor/lumacaftor) and Symdeko (tezacaftor/ivacaftor) led to a 13% reduction.
The researchers said it is critical to understand how pathogens that commonly cause infections in the CF airways contribute to type 2 inflammation, or vice versa. “Further studies identifying modifiers of [type 2] inflammation in CF may have prognostic and therapeutic importance in this vulnerable population,” they wrote.
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