Anti-inflammatory effects of inhaled carbon monoxide in patients with COPD: a pilot study

被引:159
作者
Bathoorn, E.
Siebos, D-J.
Postma, D. S.
Koeter, G. H.
van Oosterhout, A. J. M.
van der Toorn, M.
Boezen, H. M.
Kerstjens, H. A. M.
机构
[1] Univ Med Ctr Groningen, Groningen Res Inst Asthma & COPD GRIAC, Dept Pulmonol, NL-9700 RB Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Lab Allergol & Pulm Dis, Groningen, Netherlands
[3] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands
关键词
carbon monoxide; chronic obstructive pulmonary disease; inflammation; sputum induction;
D O I
10.1183/09031936.00163206
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
In vitro and in vivo studies have shown that carbon monoxide (CO) has both anti-inflammatory and anti-oxidant capacities. Since chronic obstructive pulmonary disease (COPD) is characterised by inflammation and oxidative stress, low-dose CO could be of therapeutic use. The aim of the present study was to investigate the feasibility and anti-inflammatory effects of 100125 ppm CO inhalation in patients with stable COPD. In total, 20 ex-smoking COPD patients with post-bronchodilator forced expiratory volume in one second (FEV1) > 1.20 L and FEV1/forced vital capacity < 70% were enrolled in a randomised, placebo-controlled, crossover study. Effects on inflammation were measured in induced sputum and blood. CO inhalation was feasible and patients' vital signs were unaffected; 2 h center dot day(-1) inhalation of lowdose CO on 4 consecutive days led to a maximal individual carboxyhaemoglobin level of 4.5%. Two exacerbations occurred in the CO period. CO inhalation led to trends in reduced sputum eosinophils (median reduction 0.25% point) and improved responsiveness to methacholine (median provocative concentration causing a 20% fall in FEV1 0.85 versus 0.63 mg center dot mL(-1)). Inhalation of 100-125 ppm carbon monoxide by patients with chronic obstructive pulmonary disease in a stable phase was feasible and led to trends in reduction of sputum eosinophils and improvement of responsiveness to methacholine. Further studies need to confirm the safety and efficacy in inflammatory lung diseases.
引用
收藏
页码:1131 / 1137
页数:7
相关论文
共 30 条
[1]   EFFECTS OF SMOKING INTERVENTION AND THE USE OF AN INHALED ANTICHOLINERGIC BRONCHODILATOR ON THE RATE OF DECLINE OF FEV(1) - THE LUNG HEALTH STUDY [J].
ANTHONISEN, NR ;
CONNETT, JE ;
KILEY, JP ;
ALTOSE, MD ;
BAILEY, WC ;
BUIST, AS ;
CONWAY, WA ;
ENRIGHT, PL ;
KANNER, RE ;
OHARA, P ;
OWENS, GR ;
SCANLON, PD ;
TASHKIN, DP ;
WISE, RA .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1994, 272 (19) :1497-1505
[2]   Bronchodilatation in vivo by carbon monoxide, a cyclic GMP related messenger [J].
Cardell, LO ;
Ueki, IF ;
Stjärne, P ;
Agusti, C ;
Takeyama, K ;
Lindén, A ;
Nadel, JA .
BRITISH JOURNAL OF PHARMACOLOGY, 1998, 124 (06) :1065-1068
[3]   Carbon monoxide attenuates aero allergen-induced inflammation in mice [J].
Chapman, JT ;
Otterbein, LE ;
Elias, JA ;
Choi, AMK .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2001, 281 (01) :L209-L216
[4]   Standardised methodology of sputum induction and processing [J].
Djukanovic, R ;
Sterk, PJ ;
Fahy, JV ;
Hargreave, FE .
EUROPEAN RESPIRATORY JOURNAL, 2002, 20 :1S-2S
[5]   Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis [J].
Fujita, T ;
Toda, K ;
Karimova, A ;
Yan, SF ;
Naka, Y ;
Yet, SF ;
Pinsky, DJ .
NATURE MEDICINE, 2001, 7 (05) :598-604
[6]   Health status measurement in COPD:: the minimal clinically important difference of the clinical COPD questionnaire [J].
Kocks, J. W. H. ;
Tuinenga, M. G. ;
Uil, S. M. ;
van den Berg, J. W. K. ;
Stahl, E. ;
van der Molen, T. .
RESPIRATORY RESEARCH, 2006, 7 (1)
[7]   Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the lung of severe COPD patients [J].
Maestrelli, P ;
Páska, C ;
Saetta, M ;
Turato, G ;
Nowicki, Y ;
Monti, S ;
Formichi, B ;
Miniati, M ;
Fabbri, LM .
EUROPEAN RESPIRATORY JOURNAL, 2003, 21 (06) :971-976
[8]  
MAINES MD, 1986, J BIOL CHEM, V261, P411
[9]   Short-term smoke exposure attenuates ovalbumin-induced airway inflammation in allergic mice [J].
Melgert, BN ;
Postma, DS ;
Geerlings, M ;
Luinge, MA ;
Klok, PA ;
van der Strate, BWA ;
Kerstjens, HAM ;
Timens, W ;
Hylkema, MN .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2004, 30 (06) :880-885
[10]   Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1 [J].
Morse, D ;
Pischke, SE ;
Zhou, ZH ;
Davis, RJ ;
Flavell, RA ;
Loop, T ;
Otterbein, SL ;
Otterbein, LE ;
Choi, AMK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (39) :36993-36998