TLR2‐dependent amelioration of allergic airway inflammation by parasitic nematode type II MIF in mice

In our previous studies, the recombinant type II macrophage migration inhibitory factor homologue (rAs‐MIF) secreted from Anisakis simplex suppressed experimental inflammation mouse model through IL‐10 production and CD4⁺CD25⁺Foxp3⁺ T‐cell recruitment. Also, TLR2 gene expression was significantly increased following rAs‐MIF treatment. To know the relation between TLR2 and amelioration mechanisms of rAs‐MIF, we induced allergic airway inflammation by ovalbumin and alum with or without rAs‐MIF under TLR2 blocking systems [anti‐TLR2‐specific antibody (α‐mTLR2 Ab) treatment and using TLR2 knockout mice]. As a result, the amelioration effects of rAs‐MIF in allergic airway inflammation model (diminished inflammation and Th2 response in the lung, increased IL‐10 secretion, CD4⁺CD25⁺Foxp3⁺ T‐cell recruitment) were diminished under two of the TLR2 blocking model. The expression of TLR2 on the surface of lung epithelial cell was significantly elevated by rAs‐MIF treatment or Pam3CSK (TLR2‐specific agonist) treatment, but they might have some competition effect on the elevation of TLR2 expression. In addition, the elevation of IL‐10 gene expression by rAs‐MIF treatment was significantly inhibited by α‐mTLR2 Ab or Pam3CSK pretreatment. In conclusion, anti‐inflammatory effects of the rAs‐MIF on OVA‐induced allergic airway inflammation might be closely related to TLR2.     

Low awareness of COPD among physicians

Introduction: Early identification of patients with chronic obstructive pulmonary disease (COPD) in the health care system followed by successful smoking cessation may prevent rapid lung function deterioration, development of severe COPD and respiratory failure. Objectives: The aim of this study was to determine the frequency of under‐diagnosed chronic obstructive lung diseases among current smokers. Materials and methods: The under‐diagnosis of COPD among smokers was determined in subjects who participated in a screening procedure aimed at recruiting COPD patients for a smoking cessation programme. In order to identify current smokers, a questionnaire was sent out to persons who had been on sick leave for various reasons certified by a physician for more than 2 weeks. Subjects who stated that they currently smoked more than eight cigarettes per day were invited to perform a lung function test. Results: A total of 3887 subjects performed spirometry, i.e. forced expiratory volume in 1 s and forced expirations, and among these, 674 (17.3%) had COPD according to the European Respiratory Society (ERS) consensus guidelines. Of those, 103 (17.3%) had physician‐diagnosed COPD. Productive cough was reported by 16.6% of the COPD subjects. Despite the fact that smokers were on sick leave certified by a physician, more than 80% of those with COPD had no previous diagnosis. As the COPD diagnosis cannot be based on reported symptoms, a spirometry on persons at risk must be performed. Conclusion: The awareness of COPD among primary care physicians has to increase and smokers above the age of 40, with and without respiratory symptoms, have to undergo spirometry if it is regarded important to establish the COPD diagnosis at an early stage. Please cite this paper as: Sundblad B‐M, Larsson K and Nathell L. Low awareness of COPD among physicians. The Clinical Respiratory Journal 2008; 2: 11–16.     

Expression of Interleukin (IL)-10, IL-17A and IL-22 in Serum and Sputum of Stable Chronic Obstructive Pulmonary Disease Patients

Abstract

Interleukin (IL)-17A, IL-22 and IL-10 have been implicated in the development of chronic obstructive pulmonary disease (COPD), but their expression in COPD is uncertain. Here we investigate the expression of IL-17A, IL-22 and IL-10 in the serum and sputum of COPD patients. Blood samples and induced sputum samples were collected from 94 patients with COPD, 23 healthy smokers, and 22 healthy control non-smokers. IL-17A, IL-22 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). We found that: 1) serum and sputum IL-17A were higher in COPD compared to healthy smokers and non-smokers; 2) serum IL-17A increased with COPD stages, it was inversely correlated with percentage of forced expiratory volume in the first second (FEV₁%) reference and positively correlated with C-reactive protein (CRP), Sputum IL-17A levels in the severe COPD patients were positively correlated with sputum neutrophils, and reversely correlated with sputum macraphages (p < 0.01); 3) serum and sputum IL-22 were significantly higher in COPD and healthy smokers than those in the non-smoker group, sputum IL-22 was similar in severe COPD (stage III and IV), which were higher than those in the other groups (p < 0.05); and, 4) serum and sputum IL-10 were similiar in COPD and healthy smokers, which were decreased compared to non-smokers. These data suggest that the increased level of IL-17A in serum and sputum plays important roles in the pathogenesis of COPD. The increased sputum IL-22 might also play important roles in the pathogenesis of COPD, while IL-10 secretion might be not only affected by COPD but also by cigarette smoke.     

慢性阻塞性肺疾病患者肺组织中血管内皮生长因子和诱生型一氧化氮合酶的表达及吸烟的影响

目的探讨慢性阻塞性肺疾病（COPD）患者肺组织中血管内皮生长因子（VEGF）、诱生型一氧化氮合酶（iNOS）的表达情况及吸烟对二者表达的影响。方法取46例因肺癌行肺叶切除患者的癌旁组织，依据吸烟及肺功能情况分成：（1）吸烟伴COPD组19例；（2）吸烟不伴COPD组12例；（3）不吸烟不伴COPD组15例。用免疫组化法检测肺组织VEGF及iNOS的表达。结果吸烟不伴COPD组（1．50±0．39，1．45±0．41）与不吸烟不伴COPD组（1．18±0．33，1．09±0．41）比较，肺组织VEGF、iNOS表达增强；吸烟伴COPD组（2．19±0．51，2．39±0．45）与不吸烟不伴COPD组比较表达明显增强。肺组织VEGF表达与iNOS表达呈明显正相关（r=0．78，P〈0．01）。肺组织VEGF表达与FEV。呈明显负相关（r=-0．67，P〈0．01）。结论吸烟以及轻度COPD患者肺组织VEGF、iNOS表达上调，iNOS、VEGF的过度表达可能参与COPD患者气道与血管重建和气流受限的过程。     

Increased neutrophil migration in smokers with or without chronic obstructive pulmonary disease

Background and objective: The number of airway neutrophils is increased in chronic obstructive pulmonary disease (COPD), and this may have a central pathophysiological role in the disease. In addition, activation of neutrophils increases their migration into sites of injury. We hypothesize that circulating neutrophils are activated in smokers. Methods: Peripheral blood neutrophils were isolated from healthy non‐smokers (n = 15), and smokers with (n = 15) or without COPD (n = 15), who were matched with regard to cumulative tobacco exposure, and chemotactic responses to N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP), interleukin‐8 (IL‐8, CXCL8) and leukotriene B₄ (LTB₄) were assessed using the ChemoTx System (Neuro Probe Inc., Gaithersburg, MD, USA). Serum tumour necrosis factor‐α (TNF‐α) concentrations were measured by ELISA. Surface expression of the neutrophil activation marker, CD11b, was measured by flow cytometry. Results: The chemotactic response to CXCL8 was increased in smokers with or without COPD (P < 0.05). Migration towards LTB₄ was increased in smokers without COPD compared with non‐smokers (P < 0.05), whereas there was no difference in fMLP‐induced chemotaxis between the groups. There was a correlation between serum TNF‐α levels and migration induced by IL‐8 (Rho = 0.442; P = 0.038) and LTB₄ (Rho = 0.428; P = 0.044) in the smokers. Furthermore, there was a tendency towards higher CD11b expression in the COPD group (P = 0.057). Conclusions: Chemotaxis of circulating neutrophils towards CXCL8, and partly towards LTB₄, is increased in smokers, indicating a systemic influence of smoking on cell activation, irrespective of the presence of airflow limitation. The relationship between TNF‐α and chemotactic response suggests that TNF‐α is involved in neutrophil activation, resulting in enhanced migration.     

Respiratory Viral Detection and Small Airway Inflammation in Lung Tissue of Patients with Stable,Mild COPD

Background: Viral respiratory tract infections are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In lung tissue specimens from patients with stable, mild COPD and from control smokers without airflow obstruction, we determined the prevalence and load of nucleic acid from common respiratory viruses and concomitant inflammation of small airways measuring less than 2-mm in diameter. Methods: Frozen lung tissue obtained from patients with stable, mild COPD (n = 20) and control subjects (n = 20) underwent real-time quantitative PCR (qPCR) for 13 respiratory viruses, and quantitative histology for inflammation of small airways. The two groups were compared for viral prevalence and load, and airway inflammation. The relationship between viral load and airway inflammatory cells was also analyzed. Results: Viral nucleic acid were detected in lung tissue of 18/40 (45.0%) of the individuals studied and included seven co-infections that were characterized by a “dominant virus” contributing to most of the total measured viral load. Lung tissue of COPD patients had a significantly higher prevalence of viral nucleic acid (particularly influenza A virus), and increased inflammation of small airways by macrophages and neutrophils versus controls. In qPCR-positive individuals, linear regression analysis showed a direct correlation between viral load and airway neutrophils, and between influenza A virus load and airway macrophages. Conclusion: The lung tissue of patients with stable, mild COPD has a higher prevalence and load of respiratory viruses versus non-obstructed control subjects, and increased inflammation of small airways. Respiratory viruses may represent potential targets in COPD patient management.     

Marked up-regulation of T lymphocytes and expression of interleukin-9 in bronchial biopsies from patients With chronic bronchitis with obstruction

STUDY OBJECTIVE: To examine the differences in the inflammatory cell and cytokine profile between patients with chronic bronchitis (CB) with and without airway obstruction compared to control subjects. DESIGN: We used bronchial biopsy samples from the patients and control subjects and analyzed them for the presence of CD3 T cells, CD68, major basic protein (MBP), elastase, and tryptase, as well as expression of messenger RNA (mRNA) coding for interleukin (IL)-4, IL-5, interferon (IFN)-gamma, IL-9, eotaxin, and IFN-gamma-inducible protein (IP)-10. The techniques of immunocytochemistry and in situ hybridization were used. Results were expressed as the number of immunoreactive and mRNA-positive cells per field. RESULTS: Increased number of elastase, CD68, and MBP-positive cells (n = 9, p < 0.01) was demonstrated in both groups of patients with CB compared to control subjects. In patients with CB and obstruction, the number of elastase, CD68, and the number of CD3-positive cells was significantly increased compared to patients with CB without obstruction (n = 9, p < 0.01). IFN-gamma mRNA expression was increased in both groups of patients with CB compared to control subjects (n = 9, p < 0.01). IL-9 mRNA was significantly increased only in patients with CB and obstruction (n = 9, p < 0.01). Co-localization studies demonstrated > 80% of all IL-9-positive cells to be CD3-positive T cells. IP-10 mRNA was significantly increased in both groups of patients with CB compared to control subjects (n = 9, p < 0.01). CONCLUSIONS: These results indicate a differential expression of inflammatory markers and cytokine mRNA in patients with obstructive CB. Increased presence of T lymphocytes and up-regulation of IL-9 and IP-10 mRNA expression in the bronchial biopsy samples may contribute to the airway obstruction in these patients.     

Urokinase‐type plasminogen activator system and human cationic antimicrobial protein 18 in serum and induced sputum of patients with chronic obstructive pulmonary disease

Background and objective: There is increasing evidence that the innate immune system plays an important role in the pathogenesis of COPD. The objective of this study was to quantify several innate immune biomarkers in serum and induced sputum of COPD patients, and healthy non‐smokers and smokers. Methods: Serum and induced sputum levels of urokinase‐type plasminogen activator (uPA), urokinase‐type plasminogen activator receptor (uPAR), urokinase‐type plasminogen activator inhibitor (PAI‐1) and human cationic antimicrobial protein 18 (CAP18) were measured by ELISA, in 13 patients with stage I or stage II COPD (COPD I + II), 15 patients with stage III or stage IV COPD (COPD III + IV), 18 healthy non‐smokers and 14 healthy smokers. In addition, membrane‐bound uPAR in peripheral blood and induced sputum was assessed by flow cytometry. Results: Levels of uPAR, PAI‐1 and CAP18 were elevated in induced sputum of COPD I + II and COPD III + IV patients, compared with healthy non‐smokers (P < 0.05) and healthy smokers (P < 0.05). uPAR, PAI‐1 and CAP18 levels were significantly higher in COPD III + IV patients compared with COPD I + II patients (P < 0.05). The expression of uPAR on induced sputum neutrophils and macrophages was significantly higher in COPD patients compared with healthy non‐smokers (P < 0.05) and healthy smokers (P < 0.05). Sputum uPAR and CAP18 levels showed significant inverse correlations with FEV₁% and 6MWD, and significant positive correlations with St. George's Respiratory Questionnaire scores. Conclusions: In COPD patients, increased induced sputum levels of uPAR, PAI‐1 and CAP18 were associated with airflow limitation, health status and exercise tolerance, suggesting that these biomarkers may be implicated in the pathogenesis of COPD.     

Increased neutrophil expression of pattern recognition receptors during COPD exacerbations

Previously, we observed increased serum levels of damage‐associated molecular patterns (DAMPs) during COPD exacerbations. Here, gene expression of DAMP receptors was measured in peripheral blood neutrophils of COPD patients during stable disease and severe acute exacerbation. The expression of toll‐like receptor (TLR)2, TLR4 and NLR family, pyrin domain‐containing 3 (NLRP3) was significantly increased, while serum levels of the soluble form of the decoy receptor for advanced glycation end‐product (sRAGE) were decreased during exacerbation. Together, these data indicate that increased DAMP signalling contributes to activation of neutrophils during COPD exacerbations.     

Investigating the adverse respiratory effects of beta-blocker treatment: six years of prospective longitudinal data in a cohort with cardiac disease

Background: Globally, cardiovascular disease (CVD) is the leading cause of death. Beta‐blocker medications have well‐established survival benefit for myocardial infarction and heart failure. However, CVD frequently coexists with chronic obstructive airways disease (COPD), a disease in which beta‐blockers are traditionally avoided. Aim: We sought to investigate the adverse respiratory effects associated with long‐term beta‐blocker treatment in patients with cardiac disease, and presumed high risk of COPD. Methods: In this prospective cohort study, patients admitted with acute cardiac disease were recruited from the cardiology unit of a tertiary referral hospital. The treating cardiologist determined beta‐blocker treatment, independent of the study. Repeated measures of spirometry and respiratory symptom scores were assessed over 12 months. Respiratory exacerbations, cardiac events and survival were recorded over 6 years. Outcomes were compared according to beta‐blocker exposure. Results: Sixty‐four subjects participated, 30 of whom received beta‐blockers. Beta‐blockers did not adversely affect spirometry, respiratory symptoms or survival. However, considering two categories of respiratory exacerbations (symptom‐based vs treated), subjects taking beta‐blockers accumulated increased annual risk (relative risk (RR) 1.30, 95% confidence interval (CI) 1.11–1.53, P= 0.001 and RR 1.37, 95% CI 1.09–1.72, P= 0.008) and concluded with overall increased risk (RR 3.67, 95% CI 1.65–8.18, P= 0.001 and RR 4.03, 95% CI 1.26–12.9, P= 0.019), when compared with the group not taking beta‐blockers. Conclusion: Long‐term beta‐blocker treatment did not adversely affect lung function, respiratory symptom scores or survival, but was associated with increased risk of respiratory exacerbations.     

Automatic CPAP Performance in Patients with Sleep Apnea Plus COPD

Abstract

Background: Automatic CPAP devices have demonstrated good results in obtaining optimal fixed CPAP pressure to eliminate respiratory events in patients with sleep apnea-hypopnea syndrome (SAHS). However, automatic CPAP has not been fully studied in patients with COPD plus SAHS. Objectives: To analyse the performance of an automatic CPAP in severe COPD patients compared with SAHS patients with no associated co-morbidity. Methods: We compared 10 consecutive patients with SAHS and no associated co-morbidity and 10 patients with SAHS plus severe COPD who required CPAP titration. Automatic CPAP performance was studied during full-night PSG. Inadequate pressure increase periods, absence of pressure increases in reaction to respiratory events, air leak periods, and pressure behaviour in the face of erratic breathing periods were analysed. Results: The SAHS patients without co-morbidities vs. SAHS plus COPD patients presented: mean sleep efficiency, 80.2 (11.5)% vs. 76.5 (12.1)%; residual AHI, 6.3 (5.2) vs. 5.1 (7.7); residual CT90, 1 (3)% vs. 14 (1)%. The device´s performance demonstrates a mean of 1.2 (1.5) vs. 1.3 (1.2) periods of inadequate pressure increases; absence of pressure increases in reaction to respiratory events, 4.1 (5.4) vs. 0.6 (0.7) times; periods of air leaks, 1.3 (3.8) vs. 13.9 (11.7); mean optimal pressure, 9.1 (1.4) vs. 9.0 (1.9) cm H₂O. Conclusion: Titration with automatic CPAP could be as effective in patients with SAHS plus severe COPD as in patients with SAHS without COPD. However, the presence of more leakages must be taken into account.     

CHRNA5/CHRNA3 Locus Associates with Increased Mortality among Smokers

Polymorphisms in the nicotinic acetylcholine receptor gene (CHRNA5/CHRNA3 locus) have been associated with several smoking related traits such as nicotine dependence, cigarette consumption, smoking cessation, lung cancer, and COPD. The aim of this candidate gene study was to study the locus among the Finnish COPD patients and long-term smokers with regard to COPD risk, smoking behavior, cancer, and all-cause mortality. Genotyping of rs1051730, the locus tagging SNP was done in two longitudinal cohorts: Finnish COPD patients (N = 575, 74% men) and long-term smokers, all men (N = 1911). Finnish population sample (N = 1730) was used as controls. The analyses were done using logistic and Cox regression. The main findings were that the minor allele increased the risk of COPD when compared to the Finnish population at large (OR = 1.4, 95% CI 1.2-1.7, p = 3.2 × 10-5). Homozygosity for the risk allele was associated in both cohorts with all-cause mortality (crude HR 2.2, 95% CI 1.2–3.8 and 1.3, 95% CI 1.1–1.5, respectively), with any type of cancer (crude OR 2.3, 95% CI 1.0–5.1) among the COPD patients and with the number of pack-years (crude OR 1.4, 95% CI 1.1–1.9) among the male smokers. CHRNA5/CHRNA3 locus tagged by rs1051730, which has been previously associated with several smoking related diseases was now shown to be associated also with increased all-cause mortality among long-term smokers with or without clinical COPD further emphasizing the clinical importance of the finding.     

Associations between BODE Index and Systemic Inflammatory Biomarkers in COPD

Background: COPD is a multicomponent disease and systemic inflammation represents one of the possible mechanisms responsible for its systemic manifestations, including skeletal muscle weakness and cachexia. Fat-free mass index (FFMI) that reflects the skeletal muscle mass, has been shown to be associated with both dyspnoea and exercise capacity. We hypothesized that the multidimensional BODE index, that reflects the multicomponent nature of COPD, might be related to biomarkers of systemic inflammation. We further evaluated associations between FFMI and systemic inflammation. Methods: BODE index and FFMI were calculated in 222 stable COPD patients and 132 smokers or ex-smokers with normal lung function. Systemic inflammation was evaluated with the measurement of leptin, adiponectin, CRP, IL-6, and TNF-α in serum samples of COPD patients. Results: In patients with COPD, both BODE index and FFMI presented significant positive and negative associations respectively with leptin levels (R² 0.61 and 0.65, respectively), whereas FFMI presented an additional negative association with the levels of TNF-α (R² 0.38). No significant associations were observed in smokers or ex-smokers with normal lung function. Conclusions: Both BODE index and FFMI, are related to the circulating levels of leptin in patients with COPD, suggesting a possible role for leptin in the systemic component of COPD. The additional association of FFMI with TNF-α may further support a role of systemic inflammation in muscle wasting in COPD.     

Pathophysiology of Evolution of Small Airways Disease to Overt COPD

ABSTRACT

Background: The slope of phase III (single breath nitrogen test), an index of ventilation inhomogeneity, has been used for early detection of COPD. Tidal airway closure (cyclic opening and closure of the peripheral airways during tidal breathing; AC_T) and expiratory flow limitation (attainment of maximal expiratory flow during tidal expiration; EFL_T) cause small airways disease (SAD). The relationships of these indices with COPD severity may reflect the progress from SAD to overt COPD. Methods: In this cross-sectional study we have assessed for the first time the phase III slope, AC_T and EFL_T in 10 smokers with normal spirometry (group O) and 40 COPD patients with GOLD scores from I to IV. Results: In most group O smokers the phase III slope was increased, and further increased with GOLD severity (up to 800%pred in GOLD IV). A close correlation was found of slope with GOLD (r = 0.77). AC_T was absent in smokers with normal spirometry and in most patients with mild COPD. EFL_T first appeared in GOLD II patients and its prevalence progressively increased in GOLD III and IV patients. Conclusions: Most group O smokers exhibit increased phase III. With overt COPD there is a progressive increase in phase III and reduction of FEV₁/FVC ratio from GOLD I to IV. A reduction of FEV₁ occurs from GOLD stage II. As the disease progresses from moderate to severe, there is an increasing presence of AC_T. Tidal EFL, with dynamic hyperinflation and severe dyspnea is present only in GOLD III and IV.     

Five‐year outcome in COPD patients after their first episode of acute exacerbation treated with non‐invasive ventilation

Background and objective: Little is known about long‐term survival of patients surviving the first episode of type II respiratory failure requiring non‐invasive ventilation (NIV). We aimed to determine the 1‐, 2‐ and 5‐year survival, cause of death and potential prognostic indicators in this patient cohort. Methods: We retrospectively identified 100 sequential COPD patients (mean age 70, mean FEV₁ 37% predicted) treated with NIV for the first time. Mortality and data on hospital morbidity and potential prognostic factors were collected from patient records and a State Health Data Linkage Service. Results: Survival at 1, 2 and 5 years was 72%, 52% and 26%, respectively. Respiratory failure secondary to COPD was the commonest cause of death (56.8%), followed by cardiovascular events (25.7%). Readmission rate at 1 year was 60% for those who survived 2 years or more and 52% for those deceased within 2 years. Recurrent respiratory failure requiring NIV was observed in 31% of the cohort. Only advance age (P = 0.04), BMI (P = 0.014) and prior domiciliary oxygen use (P = 0.03) correlated with death within 5 years. Severity of respiratory failure did not correlate with mortality. Conclusions: The 2‐ and 5‐year mortality rates for patients with COPD surviving their first episode of respiratory failure requiring NIV are high. Physiological measures of the severity of respiratory failure at presentation do not predict subsequent survival and nor does the time interval between first and second admissions requiring NIV. Age, BMI and prior need for domiciliary oxygen are the main predictors of mortality at 5 years.     

Monocytes from children with clinically stable cystic fibrosis show enhanced expression of Toll‐like receptor 4

Lung disease in patients with cystic fibrosis (CF) is characterized by recurrent bacterial respiratory infections and intense airway inflammation. Pattern recognition receptors such as Toll‐like receptor 2 (TLR2) and TLR4 identify bacterial pathogens and activate the innate immune response. We therefore hypothesized that increased expression of these receptors would be found on circulating immune cells from children with CF. A cohort of 66 young children (median age 3 years) with CF was studied and compared to both healthy controls (n = 14) and children without CF who were being investigated for recurrent respiratory infections (non‐CF disease controls; n = 17) of a similar age. Surface expression of TLR2 and TLR4 on peripheral blood monocytes was analyzed using flow cytometry. TLR4 expression was significantly higher in patients with CF compared to healthy controls (P = 0.017) and non‐CF disease controls (P = 0.025) but did not vary according to the presence or absence of pulmonary infection with Gram‐negative or Gram‐positive bacteria (P = 0.387) in the CF group. In contrast, TLR2 expression was similar across all three study groups (P = 0.930). The increased surface expression of TLR4 seen in young children with CF appears to be related to having CF per se and not related to current pulmonary infection. Pediatr. Pulmonol. © 2010 Wiley‐Liss, Inc.     

Explained variance for blood gases in a population with COPD

Introduction: Variation of blood gas levels in chronic obstructive pulmonary disease (COPD) patients has not been extensively reported and there is limited knowledge about predictors of chronic respiratory failure in COPD patients. Objectives: The aim of this study was to identify predictors of hypoxemia, hypercapnia and increased alveolar‐arterial oxygen difference in COPD patients. We hypothesized that prediction of arterial blood gases will be improved in multivariate models including measurements of lung function, anthropometry and systemic inflammation. Methods: A cross‐sectional sample of 382 Norwegian COPD patients, age 40–76, Global Initiative for Chronic Obstructive Lung Disease stage II–IV, with a smoking history of at least 10 pack‐years, underwent extensive measurements, including medical examination, arterial blood gases, systemic inflammatory markers, spirometry, plethysmography, respiratory impedance and bioelectrical impedance. Possible predictors of arterial oxygen (PaO₂), arterial carbon dioxide (PaCO₂) and alveolar‐arterial oxygen difference (AaO₂) were analyzed with both bivariate and multiple regression methods. Results: We found that various lung function measurements were significantly associated with PaO2, PaCO₂ and AaO₂. In addition, heart rate and Fat Mass Index were predictors of PaO₂ and AaO₂, while heart failure and current smoking status were associated with PaCO₂. The explained variance (R²) in the final multivariate regression models was 0.14–0.20. Conclusions: With a wide assortment of possible clinical predictors, we could explain 14–20% of the variation in blood gas measurements in COPD patients. Please cite this paper as: Saure EW, Eagan TML, Jensen RL, Voll‐Aanerud M, Aukrust P, Bakke PS and Hardie JA. Explained variance for blood gases in a population with COPD. Clin Respir J 2012; 6: 72–80.