Baseline information on individual studies included in the meta-analysis
| Source | Study design and original purposes | COPD patients | Controls | Inflammatory 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. | ||||
| Alessandri24 | Conducted 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 diseases | Healthy volunteers without any disease | Fibrinogen: Clauss method using KoaguLab 32-S coagulometer. |
| Dahl25 | Population based study conducted in Denmark. To test whether increased fibrinogen concentrations correlate with lung function and COPD hospitalisation rates in adults | Lowest quartile group of FEV1 % pred | Highest quartile group of FEV1 % pred | Fibrinogen: standard colorimetric assay |
| de Godoy31 | Conducted 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 diseases | Age matched healthy volunteers | TNF-α: enzyme linked assay (R&D System) |
| Dentener18 | Conducted 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 diseases | Healthy subjects with no evidence of COPD | CRP: polyclonal ELISA |
| Leucocyte: COBAS Micro | ||||
| Di Francia32 | Conducted 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 diseases | Healthy laboratory staff members | TNF-α: immunoradiometric method |
| Eid19 | Conducted 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 diseases | Healthy age and sex related subjects free of lung disease | CRP: enzyme linked immunosorbent assays |
| Engstrom26 | Population 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 FVC | Participants in the lowest quartile group of FVC% pred (<85%) without comorbid diseases. Men with reported long term cough associated with increased mucus production were excluded | Participants in the highest quartile group of FVC% pred (>105%). | Fibrinogen: electroimmunoassay method |
| James29 | Cross sectional survey of adults aged 25–79 years in Busselton, Western Australia. To investigate whether lung function and respiratory illness were related to leucocytes | Participants in the lowest quartile group of FEV1 % pred and with FEV1/FVC ratio <0.7 | Participants in the highest quartile group of FEV1% pred and with FEV1/FVC ratio >0.7 | Leucocyte: NR |
| Mannino20 | Cross 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 adults | FEV1/FVC <0.7 | FEV1/FVC ⩾0.7, FVC% ⩾80, free of lung disease | Fibrinogen: immunochemical method |
| CRP: latex enhanced nephelometry | ||||
| Leucocyte: standard method | ||||
| Mendall21 | Caerphilly 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 FEV1 | Participants in highest 25th percentile of FEV1 | CRP: in-house ELISA method |
| Schols23 | Conducted 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% predicted | Randomly selected from a population sample in the same area as the patients; aged over 50 years | IL-6: ELISA assay with detectable limit of 10 pg/ml |
| IL-8: ELISA assay with detectable limit of 20 pg/ml | ||||
| Takabatake33 | Conducted in Japan. To test whether systemic hypoxaemia observed in men with COPD might contribute to activation of TNF-α system and therefore cause weight loss | Diagnosed 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 levels | Age matched healthy male volunteers | TNF-α: enzyme linked immunosorbent assay (ELISA) kits |
| Vernooy35 | Conducted in Netherlands. To elucidate the relationship between local and systemic inflammation in smoking induced COPD | Diagnosed 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 diseases | 17 subjects with normal FEV1 and no medical history of lung disease. Smoking history of at least 15 pack years used as criterion for inclusion | IL-8: specific sandwich ELISA with detectable limit of 8 pg/ml |
| Yasuda22 | Conducted in Japan. To test whether the concentrations of sFas-L and sFas are related to CRP, TNF-α, or IL-6 | Diagnosed 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 conditions | Healthy age and sex matched volunteers without any disease | CRP: latex nephelometric immunoassy with detection limit of 0.3 mg/l. TNF-α: sandwich ELISA kit |