Systemic galectin-3 in smokers with chronic obstructive pulmonary disease and chronic bronchitis: The impact of exacerbations

Purpose: The carbohydrate-binding protein Galectin-3 is increased in several inflammatory diseases and has recently been forwarded as a systemic biomarker in chronic obstructive pulmonary disease (COPD). In this longitudinal study, we characterized the level of systemic Galectin-3 using blood from smokers with a history of COPD and chronic bronchitis (COPD-CB), during stable clinical conditions and exacerbations. Patients and Methods: The study population comprised 56 long-term smokers with COPD-CB, 10 long-term smokers without lung disease (LTS) and 10 clinically healthy never-smokers (HNS). Blood samples were analyzed for levels of Galectin-3, leukocyte populations and C-reactive protein (CRP). In addition, sputum samples from the COPD-CB group were analyzed for bacterial growth. Results: When comparing stable clinical conditions and exacerbations in the COPD-CB group, we found that the level of Galectin-3, just like that of CRP, leukocytes and neutrophils, respectively, was increased during exacerbations. However, this exacerbation-associated increase of Galectin-3 was modest. During stable clinical conditions of COPD-CB, the level of Galectin-3 was not elevated in comparison with HNS or LTS. Nor did this level of Galectin-3 distinguish patients that remained in a clinically stable condition throughout the study to those that developed an exacerbation. In addition, neither during stable clinical conditions nor during exacerbations, did the presence of bacterial growth in sputum alter Galectin-3 levels. In contrast to Galectin-3, the level of CRP, leukocytes and neutrophils, respectively, were increased during clinical stable conditions in the COPD-CB group compared with the other groups and were further enhanced during exacerbations. Conclusion: Systemic Galectin-3 is increased in a reproducible but modest manner during exacerbations in smokers with COPD-CB. During stable clinical conditions, the level of systemic Galectin-3 does not distinguish patients that remain clinically stable from those that develop exacerbations. This makes it less likely that systemic Galectin-3 may become a clinically useful biomarker in the current setting

Single breath N2-test and exhaled nitric oxide in men

SummaryThe N2 slope is an index of inhomogeneous distribution of ventilation and has been suggested to be suited for early testing of chronic obstructive pulmonary disease (COPD) in smokers. The aim of the present study was to examine the association between the fraction of exhaled nitric oxide (FENO) and the N2 slope in a random population of smoking and non-smoking men. Altogether 57 subjects were included in the study, 24 never-smokers, seven ex-smokers and 26 current smokers. Subjects were examined twice, in 1995 when they regarded themselves as healthy, and in a follow-up in 2001. Spirometry, N2 slope and high-resolution computed tomography (HRCT) were performed in 1995 while the follow-up examination included also measurement of FENO.The FENO value was significantly lower and the N2 slope higher in current smokers. In smokers but not in never- or ex-smokers FENO was correlated to the difference in N2 slope between 1995 and 2001 (rs=0.49, P=0.01). We analysed the data by multiple linear regression adjusted for smoking, mild respiratory symptoms and inhaled steroids. There were significant associations between FENO and the N2 slope both in 1995 and in 2001. The strongest association was found to exist with the change in N2 slope during these years.Sixteen of the subjects could be classified as having COPD, six with mild and ten with moderate COPD. There was a trend for an increase in N2 slope with increased severity of COPD; among subjects with no COPD the N2 slope in 2001 was 2.3% N2/L, and those with mild and moderate COPD had 2.5% N2/L and 3.9% N2/L, respectively (P=0.0004). No such trend was seen for FENO (17.8, 15.5 and 20.3 parts per billion (ppb), respectively, P=0.8).The results show that FENO is associated with the N2 slope, indicating that FENO reflects inflammatory changes in the peripheral airways of both non-smoking and smoking subjects

Airway inflammation in "healthy" smokers. Relation to lung function and high resolution CT findings

The aim of the present study was to characterize the inflammatory pattern in "healthy"smokers and relate it to lung function, high resolution computed tomography (HRCT) findings and respiratory symptoms in order to identify smokers at risk to develop COPD. Subjects were recruited from a population study "Men born 1933 in Göteborg". Only smokers who considered themselves as healthy (n=58) were investigated. From the same population a random sample of healthy never-smokers (n=34) were recruited. All subjects underwent lung function tests, HRCT, and answered a questionnaire. Thirty smokers (30/58) and 18 never-smokers (18/34) accepted to undergo a bronchoscopy with bronchial lavage, bronchoalveolar lavage (BAL) and bronchial biopsies. The levels of neutrophil-associated soluble inflammatory markers e.g. human neutrophil lipocalin (HNL), were higher in smokers in both blood, bronchial lavage and BAL, as compared with never-smokers. Inflammatory markers in bronchial lavage and BAL were related to carbon monoxide transfer (DLCO) but not to forced expiratory volume in one second (FEV1). HRCT showed emphysematous changes in 25/57 smokers while only 1/32 never-smokers showed this. Such emphysematous changes in smokers were related to a decrease in transfer factor (DLCO/ VA) as well as to an increase in HNL in BAL. Smokers with emphysematous changes also had more alveolar macrophages in BAL as compared with smokers without changes. Bronchial biopsies were analysed according to some T cell subpopulations, in different compartments in never-smokers. In healthy never-smokers, an increased number of cytotoxic T cells (CD 8+) were found in the bronchial epithelium as compared with lamina propria. Also in smokers, the same gradient in bronchial biopsies was seen. Even if the number of CD8+ cells in lamina propria were not increased in smokers as compared with never-smokers, a relation between CD8+ cells and an impairment in FEV1 was demonstrated in smokers. In BAL in never-smokers, the proportion of different T cell activation markers were higher in BAL than in blood (e.g. HLA-DR, CD54+, CD69+). In BAL in smokers as compared with never-smokers, an increased proportion of CD8+ and decreased proportion of CD4+ T cells was seen. The CD4+/CD8+ ratio was also low. The occurrence of different respiratory symptoms in smokers who considered themselves as "healthy" were high. Smokers with symptoms had lower FEV1, FEV% and specific airway conductance (sGaw) as well as increased number of CD8+ cells in the bronchial biopsies as compared with smokers without symptoms. However, no relation between reported symptoms and soluble inflammatory markers in blood/BAL, emphysematous changes or lung function tests mainly reflecting the small airways, could be seen. In summary, smokers without any diagnosed pulmonary or bronchial disease, frequently report respiratory symptoms, have decreased lung function, emphysematous changes on HRCT and these findings are related to inflammatory markers in bronchial tissue and bronchial lavage, BAL and blood. Thus, "healthy" smokers have an inflammation in the bronchial mucosa suggesting early chronic obstructive pulmonary disease (COPD) or preclinical COPD

Influences of patient education on exacerbations and hospital admissions in patients with COPD – a longitudinal national register study

Introduction: Chronic obstructive pulmonary disease (COPD) contributes to impaired health-related quality of life (HRQoL). Patient education and smoking cessation programs are recommended to reduce the number of exacerbations and hospitalizations, but the effects of such programs have yet to be explored in larger samples. Objective: The aim was to explore the longitudinal effects of patient education and smoking cessation programs on exacerbations and hospital admissions in patients with COPD. Design: This is a register study where data from the Swedish National Airway Register, including 20,666 patients with COPD, were used. Baseline measures of demographic, disease-related, and patient-reported variables were compared with a follow-up, 10–30 months after baseline. Descriptive statistics and changes between baseline and follow-up were calculated. Results: Comparing those not participating in education programs to those who did, HRQoL deteriorated significantly between baseline and follow-up in non-participants; there was no change in either exacerbations or hospitalizations in either group; there was a significant difference in baseline HRQoL between the two, and, when controlling for this, there was no significant change (p = 0.73). Patients who participated in smoking cessation programs were younger than the non-participants; mean 66.0 (standard deviations (SD) 7.8) vs. mean 68.1 (SD 8.8), p = 0.006. Among participants in smoking cessation programs, the proportion with continued smoking decreased significantly, from 76% to 66%, p < 0.001. Exacerbations at follow-up were predicted by FEV1% of predicted value and exacerbations at baseline. Hospital admissions at follow-up were predicted by baseline FEV1% of predicted value and exacerbations at baseline. Conclusions: To prevent exacerbations and hospital admissions, treatment and prevention must be prioritized in COPD care. Patient education and smoking cessation programs are beneficial, but there is a need to combine them with other interventions

Early Predictors of Mortality in Patients with COPD, in Relation to Respiratory and Non-Respiratory Causes of Death - A National Register Study

Background: Both single factors and composite measures have been suggested to predict mortality in patients with chronic obstructive pulmonary disease (COPD) and there is a need to analyze the relative importance of each variable. Objective: To explore the predictors of mortality for patients with COPD in relation to respiratory, cardiac, and malignant causes, as well as all causes of death. Methods: After merging the Swedish Respiratory Tract Register (SRTR) and the Swedish Cause of Death Register, patients with respiratory, cardiac, and other causes of death were identified. Demographic and clinical variables from the deceased patients' first registration with the SRTR were compared. Three univariable and multivariable Cox proportional hazards regression analyses were conducted for different causes of death, with time from first registration to either death or a fixed end date as dependent variable, and variables regarding demographics, respiration, and comorbidities as independent variables. Results: In the multivariable Cox models, mortality for patients with all causes of death was predicted by older age 1.79 (CI 1.41, 2.27), lower percentage of predicted forced expiratory volume in 1 second (FEV1 %) 0.99 (CI 0.98, 0.99), lower saturation 0.92 (CI 0.86, 0.97), worse dyspnea 1.48 (CI 1.26, 1.74) (p<0.002 to p<0.001), less exercise 0.91 (CI 0.85, 0.98), and heart disease 1.53 (CI 1.06, 2.19) (both p<0.05). Mortality for patients with respiratory causes was predicted by higher age 1.67 (CI 1.05, 2.65) (p<0.05), lower FEV1% 0.98 (CI 0.97, 0.99), worse dyspnea 2.05 (CI 1.45, 2.90), and a higher number of exacerbations 1.27 (CI 1.11, 1.45) (p<0.001 in all comparisons). For patients with cardiac causes of death, mortality was predicted by lower FEV1% 0.99 (CI 0.98, 0.99) (p=0.001) and lower saturation 0.82 (CI 0.76, 0.89) (p<0.001), older age 1.46 (CI 1.02, 2.09) (p<0.05), and presence of heart disease at first registration 2.06 (CI 1.13, 3.73) (p<0.05). Conclusion: Obstruction predicted mortality in all models and dyspnea in two models and needs to be addressed. Comorbidity with heart disease could further worsen the COPD patient's prognosis and should be treated by a multidisciplinary team of professional specialists

Benefits, for patients with late stage chronic obstructive pulmonary disease, of being cared for in specialized palliative care compared to hospital. A nationwide register study

Background: In early stage chronic obstructive pulmonary disease (COPD), dyspnea has been reported as the main symptom; but at the end of life, patients dying from COPD have a heavy symptom burden. Still, specialist palliative care is seldom offered to patients with COPD; they more often receive end of life care in hospitals. Furthermore, symptoms, symptom relief and care activities in the last week of life for COPD patients are rarely studied. The aim of this study was to compare patient and care characteristics in late stage COPD patients treated in specialized palliative care (SPC) versus hospital. Methods: Two nationwide registers were merged, the Swedish National Airway Register (SNAR) and the Swedish Register of Palliative Care (SRPC). Patients with COPD and < 50% of predicted forced expiratory volume in 1 s (FEV1), who had died in inpatient or outpatient SPC (n = 159) or in hospital (n = 439), were identified. Clinical COPD characteristics were extracted from the SNAR, and end of life (EOL) care characteristics from the SRPC. Descriptive statistics were used to describe the sample and the registered care and treatments. Independent samples t-test, Mantel–Haenszel chi-square test and Fisher’s exact test was used to compare variables. To examine predictors of place of death, bivariate and multivariate logistic regression analyses were performed with a dependent variable with demographic and clinical variables used as independent variables. Results: The patients in hospitals were older and more likely to have heart failure or hypertension. Pain was more frequently reported and relieved in SPC than in hospitals (p = 0.001). Rattle, anxiety, delirium and nausea were reported at similar frequencies between the settings; but rattle, anxiety, delirium, and dyspnea were more frequently relieved in SPC (all p < 0.001). Compared to hospital, SPC was more often the preferred place of care (p < 0.001). In SPC, EOL discussions with patients and families were more frequently held than in hospital (p < 0.001). Heart failure increased the probability of dying in hospital while lung cancer increased the probability of dying in SPC. Conclusion: This study provides evidence for referring more COPD patients to SPC, which is more focused on symptom management and psychosocial and existential support

Adherence to treatment recommendations for chronic obstructive pulmonary disease-results from the Swedish national airway register

Introduction: Swedish guidelines adhere to the international GOLD document regarding management of chronic obstructive pulmonary disease (COPD). Based on data from the Swedish National Airway Register (SNAR) the aim was to evaluate adherence to guidelines of pharmacological treatment of COPD in Swedish primary and secondary care. Methods: During a period of 18 months, data on symptoms (CAT, mMRC), lung function, exacerbation history and pharmacological treatment from 15,595 COPD patients from 853 primary care and 125 secondary care clinics were collected from SNAR. Patients with a co-diagnosis of asthma were excluded. Patients were divided into four treatment groups: no pharmacological treatment, short-acting bronchodilators alone, long-acting bronchodilators alone and ICS alone or in combination with bronchodilators. Results: Of the patients, 29% were in GOLD group A, 58% in group B, 2% in group C and 11% in group D. CAT score was ≥10 and mMRC score was below 2 in 30.9% of the patients and mMRC score was ≥2 and CAT score &lt;10 in 4.2% of the patients. In 61.4% of the patients, no exacerbation was registered during the last year. Long-acting bronchodilators were prescribed for 78% and ICS for 46% of all patients. In groups A, B, C and D, respectively, 21%, 11%, 11% and 5% did not receive any inhaler therapy; 67%, 81%, 81% and 90% received long-acting bronchodilators; 33%, 46%, 55% and 71% received any ICS containing therapy and 19%, 34%, 39% and 61% received triple therapy. Discussion: Data from the SNAR indicate that only a minority of COPD patients were untreated. There was a liberal use of ICS containing drug combinations in subjects who do not have an indication for ICS. A considerable proportion of subjects at high risk of exacerbations did not receive ICS treatment