Inhaled sodium pyruvate improved FEV1 and decreased expired breath levels of nitric oxide in patients with chronic obstructive pulmonary disease.
Exogenously administered sodium pyruvate has a variety of biological effects including antioxidant/anti-inflammatory effects. Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the airways mediated in part by reactive oxygen species (ROS) and reactive nitrogen species (RNS). The current therapies for COPD have limited efficacy. This study was designed to test the safety and therapeutic efficacy of inhaled pyruvate in COPD patients. Subjects were randomized to receive either sodium pyruvate or placebo three times per day over a 6-week period. Long-term efficacy was evaluated by spirometry and expired breath nitric oxide (NO) levels taken at baseline, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks. In addition, acute assessments (1 h pre- and 1 h postinhalation of compound) were made at day 0 and at 4 weeks. Subjects receiving inhaled pyruvate showed significant (p < 0.02) improvement of approximately 11% in forced expiratory volume in 1 sec (FEV(1)) at 6 weeks, whereas subjects receiving placebo did not. The inhalation of pyruvate or placebo had no significant effect on expired breath NO levels at any of the long-term outcome time points; measurements were made 12 h after the last inhalation of the compound. In contrast, acute assessments (1 h pre-and 1 h postinhalation of compound) of expired breath NO made at 4 weeks demonstrated that inhalation of pyruvate resulted in a significant (p </= 0.01) decrease (-22.7 +/- 6%) in expired breath NO compared to placebo (5.0 +/- 7%). Inhalation of pyruvate was well tolerated and was associated with improvement in FEV(1) and expired breath NO, and was considered clinically important in COPD. These beneficial effects of inhaled pyruvate in COPD may be optimized with adjustments in both dose and length of treatment.
Votto
John J
JJ
Department of Research, Hospital for Special Care, New Britain, Connecticut, USA.
Bowen
Janet B
JB
Barton
Randall W
RW
Thrall
Roger S
RS
D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001944:Breath Tests; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D019289:Pyruvic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013147:Spirometry / Q000379:methods; D013997:Time Factors
D000975:Antioxidants; D009569:Nitric Oxide; D019289:Pyruvic Acid