Inhalation of budesonide/formoterol increases diaphragm muscle contractility

Chiyohiko Shindoh, Rie Shishido, Natsu Narumi, Naomi Murai, Masahito Miura

Research output: Contribution to journalArticlepeer-review


Background: Although budesonide/formoterol (BUD/FORM) is used clinically as a steroid/β2-agonist single inhaler, it has not yet been clarified whether BUD/FORM has inotropic effects on diaphragm muscles after inhalation. Methods: We examined the effects of BUD/FORM inhalation, endotoxin injection, and BUD/FORM inhalation plus endotoxin injection on diaphragm contractile properties and nitric oxide (NO) production. After these three treatments, the diaphragm muscle was dissected, and its contractile properties were measured. Histochemistry for the reduced form of nicotinamide adenine dinucleotide phosphate diaphorase was performed for each muscle to assess NO production. Results: The force-frequency curves showed an upward shift 1 h after inhalation (p < 0.05) in the BUD/FORM inhalation only group. The force-frequency curves showed a downward shift 4 h after injection (p < 0.001) in the endotoxin injection groups. In the BUD/FORM inhalation plus endotoxin injection groups, a downward shift in the force-frequency curves at 4 h after endotoxin injection was prevented. NO production was inhibited in the BUD/FORM inhalation plus endotoxin injection group compared with that of the endotoxin injection only groups. Conclusions: BUD/FORM inhalation has an inotropic effect on diaphragm muscle, protects diaphragm muscle deterioration after endotoxin injection, and inhibits NO production. Increments in muscle contractility with BUD/FORM inhalation are induced through a synergistic effect of an anti-inflammatory agent and β2-agonist.

Original languageEnglish
Pages (from-to)439-449
Number of pages11
JournalAllergology International
Issue number3
Publication statusPublished - 2012


  • Asthma
  • Diaphragm muscle
  • Endotoxin
  • Inhaled corticosteroid
  • Long-acting beta2-agonist

ASJC Scopus subject areas

  • Immunology and Allergy


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