From the Journals

FLU/SAL inhalers for COPD carry greater pneumonia risk



For well over a decade the elevated risk of pneumonia from inhaled corticosteroids for moderate to very severe COPD has been well documented, although the pneumonia risks from different types of ICSs have not been well understood.

Researchers from Taiwan have taken a step in to investigate this question with a nationwide cohort study that reported inhalers with budesonide and beclomethasone may have a lower pneumonia risk than that of fluticasone propionate/salmeterol inhalers (CHEST. 2020;157:117-29).

The study is the first to include beclomethasone-containing inhalers in a comparison of ICS/long-acting beta2-agonist (LABA) fixed combinations to evaluate pneumonia risk, along with dose and drug properties, wrote Ting-Yu Chang, MS, of the Graduate Institute of Clinical Pharmacology at the College of Medicine, National Taiwan University in Taipei, and colleagues.

The study evaluated 42,393 people with COPD in the National Health Insurance Research Database who got at least two continuous prescriptions for three different types of inhalers:

  • Budesonide/formoterol (BUD/FOR).
  • Beclomethasone/formoterol (BEC/FOR).
  • Fluticasone propionate/salmeterol (FLU/SAL).

The study included patients aged 40 years and older who used a metered-dose inhaler (MDI) or dry-powder inhaler (DPI) between January 2011 and June 2015.

Patient experience with adverse events (AEs) was a factor in risk stratification, Mr. Chang and colleagues noted. “For the comparison between the BEC/FOR MDI and FLU/SAL MDI, the lower risk associated with the BEC/FOR MDI was more prominent in patients without severe AE in the past year,” they wrote.

The study found that BUD/FOR DPI users had a 17% lower risk of severe pneumonia and a 12% lower risk of severe AEs than that of FLU/SAL DPI users. The risk difference in pneumonia remained significant after adjustment for the ICS-equivalent daily dose, but the spread for AEs didn’t.

BEC/FOR MDI users were 31% less likely to get severe pneumonia and 18% less likely to have severe AEs than were FLU/SAL MDI users, but that difference declined and became nonsignificant after adjustment for the ICS-equivalent daily dose.

The study also found that a high average daily dose (> 500 mcg/d) of FLU/SAL MDI carried a 66% greater risk of severe pneumonia, compared with that of low-dose users. Also, medium-dose BEC/FOR MDI users (FLU equivalent 299-499 mcg/d) had a 38% greater risk of severe pneumonia than low-dose (< 200 mcg/d) users.

The variable pneumonia risks may be linked to each ICS’s pharmacokinetics, specifically their distinct lipophilic properties, Mr. Chang and colleagues wrote. Fluticasone propionate is known to be more lipophilic than budesonide, and while beclomethasone is more lipophilic than both, as a prodrug it rapidly converts to lower lipophilicity upon contact with bronchial secretions. “In general, a lipophilic ICS has a longer retention time within the airway or lung tissue to exert local immunosuppression and reduce inflammation,” Mr. Chang and colleagues stated.

The Taiwan Ministry of Science and Technology provided partial support for the study. Mr. Chang and colleagues have no relationships to disclose.

SOURCE: Chang TY et al. CHEST. 2020;157:117-29.

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