Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive pulmonary disease.
BACKGROUND
In smoking COPD patients the bronchoalveolar lavage (BAL) fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA) metabolites, which contribute to inflammation and an increased bronchomotor tone.


OBJECTIVE
To investigate levels of AA metabolites in BAL fluid, before and after inhaled glucocorticoid therapy: fluticasone propionate (FP) 1 mg per day, or placebo.


METHODS
A double-blind placebo controlled trial lasting six months. COPD patients were selected by clinical criteria and the presence of bronchial hyper-responsiveness (BHR). Lung function was recorded and in BAL fluid we counted cell numbers and measured LTB4, LTC4/D4/E4, PGE2, 6kPGF1alpha, PGF2alpha and TxB2. A control group consisted of asymptomatic smokers (n=6).


RESULTS
Paired data were obtained from 9 FP treated and 11 placebo patients. BAL cells were almost exclusively alveolar macrophages. In patients and controls both cellularity and levels of AA metabolites were equal Cell numbers did not change after treatment. Statistically significant decreases after FP therapy were noticed for PGE2 (30%), 6kPGF1alpha (41%) and PGF2alpha (54%).


CONCLUSIONS
In COPD, the capability of inflammatory cells to produce certain AA metabolites was decreased after inhaled FP treatment. This result is discussed in its relation to clinical effects, the influence of smoking, and the results of an earlier, similar study in asthma patients.
Verhoeven
G T
GT
Department of Pulmonary and Intensive Care Medicine, University Hospital Dijkzigt and Erasmus University, EMCR, Rotterdam, The Netherlands. Verhoeven@lond.azr.nl
Garrelds
I M
IM
Hoogsteden
H C
HC
Zijlstra
F J
FJ
D000328:Adult; D000730:Androstadienes / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016718:Arachidonic Acid / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004311:Double-Blind Method; D000068298:Fluticasone; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy*; D008875:Middle Aged; D012129:Respiratory Function Tests; D012907:Smoking / Q000009:adverse effects*
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016718:Arachidonic Acid; D000068298:Fluticasone