Table 1

 Baseline information on individual studies included in the meta-analysis

SourceStudy design and original purposesCOPD patientsControlsInflammatory marker and laboratory measurement
COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; CRP = C-reactive protein; TNF-α = tumour necrosis factor-α; IL = interleukin; pred = predicted; NR = not reported, MI = myocardial infarction; sFas-L = soluble Fas/Apo-1 receptor ligand; sFas = soluble Fas/Apo-1 receptor.
Alessandri24Conducted in Italy. To test whether a hypercoagulability state is present in patients with COPD(1) FEV1/FVC <0.7. (2) Haematocrit value <50%. (3) No comorbid diseasesHealthy volunteers without any diseaseFibrinogen: Clauss method using KoaguLab 32-S coagulometer.
Dahl25Population based study conducted in Denmark. To test whether increased fibrinogen concentrations correlate with lung function and COPD hospitalisation rates in adultsLowest quartile group of FEV1 % predHighest quartile group of FEV1 % predFibrinogen: standard colorimetric assay
de Godoy31Conducted in the US. Age matched healthy volunteers as controls. To examine whether TNF-α and IL-1β produced by peripheral blood monocytes are increased in weight losing COPD patients(1) FEV1/FVC <0.6. (2) At least 6 wk stability. (3) Exclusion of patients receiving oral corticosteroids or with comorbid diseasesAge matched healthy volunteersTNF-α: enzyme linked assay (R&D System)
Dentener18Conducted in the Netherlands. To test the hypothesis that the chronic inflammatory process present in COPD is due to a defective endogenous anti-inflammatory mechanism(1) FEV1 <80% predicted. (2) β2 agonist reversibility of <15% or 200 ml. (3) FEV1/FVC ratio <70%. (4) Stable clinical condition. (5) Exclusion of patients with comorbid diseasesHealthy subjects with no evidence of COPDCRP: polyclonal ELISA
Leucocyte: COBAS Micro
Di Francia32Conducted in France. 30 patients met the criteria were consecutively admitted. To test whether serum levels of TNF-α are related to weight loss in patients with COPD(1) FEV1/FVC <0.6. (2) Irreversibility of airflow obstruction. (3) Creatine clearance in the normal range. (4) Stable clinical condition. (5) Exclusion of patients with comorbid diseasesHealthy laboratory staff membersTNF-α: immunoradiometric method
Eid19Conducted in the UK. Community based patients recruited from a hospital respiratory clinic. To test whether skeletal muscle loss is associated with inflammatory and catabolic responses in COPD(1) History of cigarette smoking. (2) Respiratory symptoms. (3) β2 agonist bronchodilator reversibility <10%. (4) Further confirmation during 1 year follow up. (5) Stable clinical condition. (6) Exclusion of patients with comorbid diseasesHealthy age and sex related subjects free of lung diseaseCRP: enzyme linked immunosorbent assays
Engstrom26Population based study conducted in Sweden. To explore whether plasma levels of fibrinogen and other inflammation sensitive plasma proteins are related to FVC and whether these proteins contribute to the increased incidence of MI and death among men with reduced FVCParticipants in the lowest quartile group of FVC% pred (<85%) without comorbid diseases. Men with reported long term cough associated with increased mucus production were excludedParticipants in the highest quartile group of FVC% pred (>105%).Fibrinogen: electroimmunoassay method
James29Cross sectional survey of adults aged 25–79 years in Busselton, Western Australia. To investigate whether lung function and respiratory illness were related to leucocytesParticipants in the lowest quartile group of FEV1 % pred and with FEV1/FVC ratio <0.7Participants in the highest quartile group of FEV1% pred and with FEV1/FVC ratio >0.7Leucocyte: NR
Mannino20Cross sectional, multistage probability representative sample of civilian non-institutionalised US population. To assess the relation of impaired lung function to circulating levels of CRP and fibrinogen in adultsFEV1/FVC <0.7FEV1/FVC ⩾0.7, FVC% ⩾80, free of lung diseaseFibrinogen: immunochemical method
CRP: latex enhanced nephelometry
Leucocyte: standard method
Mendall21Caerphilly Prospective Heart Disease Study conducted in South Wales. To examine whether the low grade inflammation indicated by CRP may be the mechanism whereby non-circulating risk factors may influence pathogenesis of ischaemic heart disease.Participants in lowest 25th percentile of FEV1Participants in highest 25th percentile of FEV1CRP: in-house ELISA method
Schols23Conducted in Netherlands. To investigate whether the increased resting energy expenditure seen in some COPD patients is related to systemic inflammatory response.(1) Moderate to severe COPD (FEV1 % pred of 37%). (2) β2 agonist bronchodilator (400 µg salbutamol) reversibility of <10%. (3) Stable clinical condition. (4) Resting energy expenditure <105% or >120% predictedRandomly selected from a population sample in the same area as the patients; aged over 50 yearsIL-6: ELISA assay with detectable limit of 10 pg/ml
IL-8: ELISA assay with detectable limit of 20 pg/ml
Takabatake33Conducted in Japan. To test whether systemic hypoxaemia observed in men with COPD might contribute to activation of TNF-α system and therefore cause weight lossDiagnosed according to ATS criteria: (1) Irreversible chronic airflow obstruction. (2) Stable for at least 3 months. (3) Exclusion of patients with conditions known to affect serum TNF-α levelsAge matched healthy male volunteersTNF-α: enzyme linked immunosorbent assay (ELISA) kits
Vernooy35Conducted in Netherlands. To elucidate the relationship between local and systemic inflammation in smoking induced COPDDiagnosed according to ATS criteria: (1) Stable clinical condition. (2) Predicted FEV1 <70%. (3) β2 agonist bronchodilator reversibility of <11% or 200 ml. (4) Previous history of at least 20 pack-years smoking. (5) Exclusion of patients receiving inhaled steroids or with comorbid diseases17 subjects with normal FEV1 and no medical history of lung disease. Smoking history of at least 15 pack years used as criterion for inclusionIL-8: specific sandwich ELISA with detectable limit of 8 pg/ml
Yasuda22Conducted in Japan. To test whether the concentrations of sFas-L and sFas are related to CRP, TNF-α, or IL-6Diagnosed by history, physical examination, radiographic examination and lung function tests. Conditions: (1) Stable clinical condition. (2) No recent change of drugs. (3) Normal left ventricular ejection fraction. (4) Normal plasma creatinine concentration. (5) Absence of other pathological conditionsHealthy age and sex matched volunteers without any diseaseCRP: latex nephelometric immunoassy with detection limit of 0.3 mg/l. TNF-α: sandwich ELISA kit