Tomas Eagan

Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study

Chronic obstructive pulmonary disease (COPD) is considered an inflammatory pulmonary disorder with systemic inflammatory manifestations. The aim of this study was to assess the systemic levels of six inflammatory mediators in a large cohort of COPD patients and controls. 409 COPD patients and 231 healthy subjects, aged 40–75 yrs, were included from the first phase of the Bergen COPD Cohort Study. All COPD patients were clinically diagnosed by a physician, and had a forced expiratory volume in 1 s/forced vital capacity ratio less than 0.7 and a smoking history of >10 pack-yrs. The plasma levels of C-reactive protein (CRP), soluble tumour necrosis factor receptor (sTNFR)-1, osteoprotegrin, neutrophil activating peptide-2, CXCL16 and monocyte chemoattractant protein-4 were determined by ELISA. After adjustment for all known confounders, COPD patients had significantly lower levels of osteoprotegrin than subjects without COPD (p<0.05), and higher levels of CRP (p<0.01). Among COPD patients, CRP was elevated in patients with frequent exacerbations (p<0.05). sTNFR-1 and osteoprotegrin were both related to Global Initiative for Chronic Obstructive Lung Disease stage and frequency of exacerbations in the last 12 months (p<0.05). In addition, sTNFR-1 was significantly associated with important comorbidities such as hypertension and depression (p<0.05). The present study confirms that certain circulating inflammatory mediators are an important phenotypic feature of COPD.

Quantitative Computed Tomography Measures of Emphysema and Airway Wall Thickness Are Related to Respiratory Symptoms

RATIONALE There is limited knowledge about the relationship between respiratory symptoms and quantitative high-resolution computed tomography measures of emphysema and airway wall thickness. OBJECTIVES To describe the ability of these measures of emphysema and airway wall thickness to predict respiratory symptoms in subjects with and without chronic obstructive pulmonary disease (COPD). METHODS We included 463 subjects with chronic obstructive pulmonary disease (COPD) (65% men) and 488 subjects without COPD (53% men). All subjects were current or ex-smokers older than 40 years. They underwent spirometry and high-resolution computed tomography examination, and completed an American Thoracic Society questionnaire on respiratory symptoms. MEASUREMENTS AND MAIN RESULTS Median (25th percentile, 75th percentile) percent low-attenuation areas less than -950 Hounsfield units (%LAA) was 7.0 (2.2, 17.8) in subjects with COPD and 0.5 (0.2, 1.3) in subjects without COPD. Mean (SD) standardized airway wall thickness (AWT) at an internal perimeter of 10 mm (AWT-Pi10) was 4.94 (0.33) mm in subjects with COPD and 4.77 (0.29) in subjects without COPD. Both %LAA and AWT-Pi10 were independently and significantly related to the level of dyspnea among subjects with COPD, even after adjustments for percent predicted FEV(1). AWT-Pi10 was significantly related to cough and wheezing in subjects with COPD, and to wheezing in subjects without COPD. Odds ratios (95% confidence intervals) for increased dyspnea in subjects with COPD and in subjects without COPD were 1.9 (1.5-2.3) and 1.9 (0.6-6.6) per 10% increase in %LAA, and 1.07 (1.01-1.14) and 1.11 (0.99-1.24) per 0.1-mm increase in AWT-Pi10, respectively. CONCLUSIONS Quantitative computed tomography assessment of the lung parenchyma and airways may be used to explain the presence of respiratory symptoms beyond the information offered by spirometry.

Nonresponse in a community cohort study: predictors and consequences for exposure-disease associations.

We have assessed predictors for response in a Norwegian community cohort study, with an 11-year follow-up. We also examined to what extent the association of gender, age, and smoking to the incidence of respiratory symptoms and asthma differed if the analyses were based on the 65% (n = 2,079) initial responders, or were based on the 89% (n = 2,819) who responded after three reminders. The associations between the six symptoms/asthma and the gender, age, and smoking groups amounted to 42 odds ratios. The adjusted odds ratio for responding at follow-up was 1.39 (95% CI: 1.01, 1.90) for those being middle aged at baseline compared to younger subjects. The adjusted odds ratios for responding at follow-up for those being students, unemployed, or retired at baseline were 0.50 (95% CI: 0.35, 0.73), 0.29 (95% CI: 0.16, 0.55), 0.21 (95% CI: 0.13, 0.36), respectively, compared to being employed. Of the 42 odds ratios mentioned above, 25 differed less than 10% when comparing the initial and all respondents. Twelve differed 10-20% and five differed 20-45%. The study indicates that to ensure a high participation rate in a follow-up study one should pay special attention to those being late responders, unemployed, retired, or students at baseline. No overt differences were observed in the gender, age, and, smoking associations to the respiratory disorders when the analyses were based on the initial compared to all respondents.

Incidence of asthma and respiratory symptoms by sex, age and smoking in a community study

The purpose of this study was to establish incidence rates for a wide range of respiratory symptoms and asthma, and relate them to sex, age, and smoking habits. A cohort established in 1985 as a random sample from the population of Western Norway, aged 15–70 yrs, was followed-up in 1996–1997. Of the initial cohort of 3,786 subjects, a total of 2,819 replied to mailed questionnaires at both baseline and follow-up. The 11‐yrs cumulative incidence of asthma was 4.0% in males and 3.5% in females. For respiratory symptoms, the cumulative incidences for both sexes varied between 2.0% (dyspnoea grade 4) and 25.8% (wheezing), being higher in females than males for most symptoms. For calculation of odds ratios (ORs) multivariate logistic regression analyses were used. The sex and smoking-adjusted incidences increased by age for all symptoms except wheezing and attacks of dyspnoea. Those starting to smoke within the follow-up had ORs of 1.9–2.2 for the cough symotoms compared to never-smokers, after adjusting for sex, age, and pack-yrs. To conclude, the 11‐yrs incidence of dyspnoea increased with increasing pack-yrs, after adjusting for sex, age, and changes in smoking habits. This indicated that when analysing other risk factors, adjustment has to be made for the risks posed by smoking, sex and age.

Original articlesNonresponse in a community cohort study: Predictors and consequences for exposure–disease associations

We have assessed predictors for response in a Norwegian community cohort study, with an 11-year follow-up. We also examined to what extent the association of gender, age, and smoking to the incidence of respiratory symptoms and asthma differed if the analyses were based on the 65% (n = 2,079) initial responders, or were based on the 89% (n = 2,819) who responded after three reminders. The associations between the six symptoms/asthma and the gender, age, and smoking groups amounted to 42 odds ratios. The adjusted odds ratio for responding at follow-up was 1.39 (95% CI: 1.01, 1.90) for those being middle aged at baseline compared to younger subjects. The adjusted odds ratios for responding at follow-up for those being students, unemployed, or retired at baseline were 0.50 (95% CI: 0.35, 0.73), 0.29 (95% CI: 0.16, 0.55), 0.21 (95% CI: 0.13, 0.36), respectively, compared to being employed. Of the 42 odds ratios mentioned above, 25 differed less than 10% when comparing the initial and all respondents. Twelve differed 10-20% and five differed 20-45%. The study indicates that to ensure a high participation rate in a follow-up study one should pay special attention to those being late responders, unemployed, retired, or students at baseline. No overt differences were observed in the gender, age, and, smoking associations to the respiratory disorders when the analyses were based on the initial compared to all respondents.

Chronic Obstructive Pulmonary Disease Is Associated with Low Levels of Vitamin D

Introduction COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported. Methods Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40–76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls. Levels <20 ng/mL defined deficiency. Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models. Results COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI. Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29). Summertime decreased the risk of vitamin D deficiency (OR = 0.22). Conclusion COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels.

Neutrophil gelatinase-associated lipocalin: a biomarker in COPD.

BACKGROUND Neutrophil gelatinase-associated lipocalin (NGAL) is an antimicrobial peptide that could be involved in the pathogenesis of COPD. This study aimed to measure the plasma levels of NGAL in a large cohort of patients with COPD and control subjects and examine the levels of NGAL by COPD characteristics. METHODS The study included 402 patients with COPD and 229 control subjects aged 40 to 76 years from the Bergen COPD Cohort Study. All patients with COPD had an FEV(1)/FVC ratio of < 0.7, an FEV(1) < 80% predicted, and a smoking history of ≥ 10 pack-years. Plasma levels of NGAL were determined by enzyme immunoassay. Linear regression models were fitted with NGAL as the outcome variable. Confounders examined were sex, age, smoking, Charlson comorbidity score, use of inhaled steroids, neutrophil cell count, plasma creatinine and ferritin, and C-reactive protein. RESULTS Mean ± SD plasma concentrations of NGAL were 75.1 ± 31.8 ng/mL in patients with COPD and 56.5 ± 22.0 ng/mL in control subjects (P < .01). NGAL levels were bivariately associated with age, smoking, body composition, Charlson comorbidity score, neutrophil blood count, creatinine, and C-reactive protein but were significantly elevated in patients with COPD, even after adjustment for confounders. Frequent exacerbations and hypoxemia was associated with higher levels of NGAL, whereas increasing Global Initiative for Chronic Obstructive Lung Disease stage was associated with lower levels of NGAL among patients with COPD. CONCLUSIONS Plasma levels of NGAL were significantly higher in patients with COPD compared with control subjects. NGAL was related to important COPD characteristics.

Decline in respiratory symptoms in service workers five months after a public smoking ban

Objective: To evaluate the effect of a total ban on smoking indoors in restaurants and other hospitality business premises in Norway, on respiratory symptoms among workers in the industry. Methods: Phone interviews with 1525 employees in the hospitality business were conducted immediately before the enacting of the law. In a follow-up study five months later, 906 of the workers from the baseline sample participated. Questions were asked on demographic variables, passive smoking exposure, personal smoking, attitudes towards the law, and five respiratory symptoms. Change in symptom prevalence was analysed with McNemar’s test and with analysis of variance (ANOVA) for repeated measures. Results: The prevalence of all five symptoms declined after the ban; for morning cough from 20.6% to 16.2% (p < 0.01); for daytime cough from 23.2% to 20.9%; for phlegm cough from 15.3% to 11.8% (p < 0.05); for dyspnoea from 19.2% to 13.0% (p < 0.01); and for wheezing from 9.0% to 7.8%. ANOVA showed that the largest decline in symptom prevalence was seen among workers who themselves gave up smoking, and subjects with a positive attitude towards the law before it took effect. Conclusion: A significant decrease in respiratory symptoms among service industry workers was found five months after the enacting of a public smoking ban.

Comparison of 2011 and 2007 Global Initiative for Chronic Obstructive Lung Disease Guidelines for Predicting Mortality and Hospitalization

RATIONALE The GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2011 update on chronic obstructive pulmonary disease (COPD) bases disease classification on level of dyspnea, exacerbation history, and FEV1, whereas the previous GOLD categorized disease severity according to FEV1 only. Information on how the new classification predicts long-term hospitalizations and mortality is limited. OBJECTIVES To examine how GOLD 2011 predicts hospitalizations and mortality over an 8-year period and to assess differences in predictive ability between GOLD 2011 and GOLD 2007. METHODS In the GenKOLS study, 912 patients with COPD (FEV1/FVC < 0.7 and FEV1 < 80% predicted) aged 40 to 91 years were clinically examined. Patients answered questionnaires and performed lung function testing in 2003-2005. The population was followed for 8 years regarding hospitalizations (all-cause, respiratory) and mortality (all-cause, respiratory, cardiovascular). We performed logistic regression and receiver operating curve analyses for GOLD 2007 and GOLD 2011 with estimations of area under the curve (AUC) to compare the different classifications. MEASUREMENTS AND MAIN RESULTS Twenty percent of patients were classified as GOLD 2011 group A (mild), 30% as group B, 6% group as C, and 44% as group D (very severe). Patients in GOLD 2011 group D had odds ratios of 4.1 (95% confidence interval [CI], 2.5-6.7), 9.6 (95% CI, 3.4-27.0), and 3.0 (95% CI, 0.7-13.2) relative to group A for all-cause, respiratory, and cardiovascular mortality, respectively, and 3.8 (95% CI, 2.4-5.9) and 13.0 (95% CI, 6.6-25.6) for all-cause and respiratory hospitalizations, respectively. Associations were similar also for GOLD 2007. The adjusted AUC values for GOLD 2011 and GOLD 2007 were 0.82/0.82 for respiratory mortality (P = 0.87) and 0.77/0.76 for respiratory hospitalizations (P = 0.51). CONCLUSIONS The predictive ability of GOLD 2011 did not differ significantly from GOLD 2007 in terms of hospitalizations and mortality.

Predictors of diagnostic yield in bronchoscopy: a retrospective cohort study comparing different combinations of sampling techniques.

BackgroundThe reported diagnostic yield from bronchoscopies in patients with lung cancer varies greatly. The optimal combination of sampling techniques has not been finally established.The objectives of this study were to find the predictors of diagnostic yield in bronchoscopy and to evaluate different combinations of sampling techniques.MethodsAll bronchoscopies performed on suspicion of lung malignancy in 2003 and 2004 were reviewed, and 363 patients with proven malignant lung disease were included in the study. Sampling techniques performed were biopsy, transbronchial needle aspiration (TBNA), brushing, small volume lavage (SVL), and aspiration of fluid from the entire procedure. Logistic regression analyses were adjusted for sex, age, endobronchial visibility, localization (lobe), distance from carina, and tumor size.ResultsThe adjusted odds ratios (OR) with 95% confidence intervals (CI) for a positive diagnostic yield through all procedures were 17.0 (8.5–34.0) for endobronchial lesions, and 2.6 (1.3–5.2) for constriction/compression, compared to non-visible lesions; 3.8 (1.3–10.7) for lesions > 4 cm, 6.7 (2.1–21.8) for lesions 3–4 cm, and 2.5 (0.8–7.9) for lesions 2–3 cm compared with lesions <= 2 cm. The combined diagnostic yield of biopsy and TBNA was 83.7% for endobronchial lesions and 54.2% for the combined group without visible lesions. This was superior to either technique alone, whereas additional brushing, SVL, and aspiration did not significantly increase the diagnostic yield.ConclusionIn patients with malignant lung disease, visible lesions and larger tumor size were significant predictors of higher diagnostic yield, after adjustment for sex, age, distance from carina, side and lobe. The combined diagnostic yield of biopsy and TBNA was significant higher than with either technique alone.