Fibroblast growth factor 23 is an independent marker of COPD and is associated with impairment of pulmonary function and diffusing capacity.

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that in recent years has been reported to have significant effects on numerous tissues. Chronic obstructive pulmonary disease (COPD) is associated with hypophosphatemia but the evidence for elevated plasma levels of FGF23 in COPD subjects is ambiguous. Recently, FGF23 has even been shown to be involved in the inflammatory pathways activated in COPD, so FGF23 could be a novel biomarker for COPD and impairment of pulmonary function. The purpose was thus to explore the association of FGF23 with COPD and measures of pulmonary function. This was a cross sectional study of 450 subjects who underwent spirometry, body plethysmography, determination of diffusing capacity (DL,CO) and biomarker analysis of FGF23, interleukin (IL)-1 receptor antagonist, IL-6 and IL-8. Forty-four participants were excluded due to missing data or renal impairment (eGFR <45 mL/min/m2). Spirometry identified 123 subjects with COPD. FGF23 levels were elevated in COPD subjects compared to non COPD subjects, and this remained significant after adjustment for age, sex and smoking habits (OR = 1.6, p = 0.02). Linear regression showed significant relationships between FGF23 and FEV1 (ß = -0.15, p = 0.003), RV/TLC (ß = 0.09, p = 0.05) and DL, CO (ß = -0.24, p < 0.001). In conclusion we found that plasma levels of FGF23 are elevated in COPD subjects even when adjusting for traditional risk factors. Furthermore, FGF23 is associated with impairment in lung function as measured by FEV1 and DL,CO. Further studies are needed to establish whether FGF23 could serve as a novel biomarker of COPD and emphysema development.

Matrix Metalloproteinases in COPD and atherosclerosis with emphasis on the effects of smoking.

BACKGROUND: Matrix metalloproteinases (MMP´s) are known biomarkers of atherosclerosis. MMP´s are also involved in the pathophysiological processes underlying chronic obstructive pulmonary disease (COPD). Cigarette smoking plays an important role in both disease states and is also known to affect the concentration and activity of MMP´s systemically. Unfortunately, the epidemiological data concerning the value of MMP´s as biomarkers of COPD and atherosclerosis with special regards to smoking habits are limited. METHODS: 450 middle-aged subjects with records of smoking habits and tobacco consumption were examined with comprehensive spirometry, carotid ultrasound examination and biomarker analysis of MMP-1, -3, -7, -10 and -12. Due to missing data 33 subjects were excluded. RESULTS: The remaining 417 participants were divided into 4 different groups. Group I (n = 157, no plaque and no COPD), group II (n = 136, plaque but no COPD), group III (n = 43, COPD but no plaque) and group IV (n = 81, plaque and COPD). Serum levels of MMP-1,-7,-10-12 were significantly influenced by smoking, and MMP-1, -3, -7 and-12 were elevated in subjects with COPD and carotid plaque. This remained statistically significant for MMP-1 and-12 after adjusting for traditional risk factors. CONCLUSION: COPD and concomitant plaque in the carotid artery were associated with elevated levels of MMP-1 and -MMP-12 even when adjusting for risk factors. Further studies are needed to elucidate if these two MMP´s could be useful as biomarkers in a clinical setting. Smoking was associated with increased serum levels of MMP´s (except for MMP-3) and should be taken into account when interpreting serum MMP results.

Associations between lung function and alcohol consumption--assessed by both a questionnaire and a blood marker.

BACKGROUND: Studies on the influence of alcohol consumption on lung function have shown conflicting results. Self-reported alcohol consumption may be inaccurate. This study used both a validated alcohol questionnaire and a blood marker of heavy alcohol consumption, and examined potential associations with different lung physiological variables. METHODS: The study population (450 subjects) answered an alcohol questionnaire (AUDIT-C) and performed spirometry, body plethysmography and a test for diffusing capacity for CO (DL,CO). Carbohydrate deficient transferrin (CDT), a clinically used blood marker for identifying heavy alcohol consumption, and C-reactive protein (CRP), a marker of systemic inflammation were analysed. RESULTS: Using AUDIT-C, 407 subjects were alcohol drinkers and 29 non-drinkers. Of the alcohol drinkers, 224 subjects were "hazardous drinkers" and 183 "moderate drinkers". Thirty-four subjects had a CDT ≥2.0% (=heavy drinkers). There was no difference in lung function between hazardous and moderate drinkers. Heavy drinkers had lower DL,CO (74% vs 83% PN, p = 0.003), more symptoms of chronic bronchitis (p = 0.001) and higher AUDIT-C scores (p < 0.001) than non-heavy drinkers. After adjustments (pack years and CRP) the difference in DL,CO (p = 0.037) remained. Multiple regression showed an association between CDT and both FEV1 (p = 0.004) and DL,CO (p = 0.012) in all alcohol drinkers, but not in never-smokers. The AUDIT-C score was associated with CDT (also after adjustments, p < 0.001) but not with any lung function variable. CONCLUSION: The results from this study suggest that alcohol and particularly heavy drinking has an independent additive negative effect on lung function in smokers.

Impulse oscillometry may be of value in detecting early manifestations of COPD.

BACKGROUND: Spirometry is used to diagnose chronic obstructive pulmonary disease (COPD). The Impulse oscillometry system (IOS) allows determination of respiratory impedance indices, which might be of potential value in early COPD, although previous experience is limited. We examined pulmonary resistance and reactance measured by IOS in subjects with or without self-reported chronic bronchitis or emphysema or COPD (Q+ or Q-) and subjects with or without COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (G+ or G-). METHODS: From a previous population-based study 450 subjects were examined with spirometry and IOS and answered a questionnaire on respiratory symptoms and diseases. RESULTS: Seventy-seven subjects were Q+, of whom 34 also were G+. Q+/G- subjects (n = 43) reported respiratory symptoms more frequently (35-40% vs 8-14%) but had higher FEV(1) (100% vs 87%) than Q-/G+ subjects (n = 90), p < 0.05 for both comparisons. Q+ subjects had higher pulmonary resistance and lower pulmonary reactance than Q- subjects (p < 0.01 for all comparisons). The same pattern was seen both in G+ subjects ((Q+/Q-) R5 0.39/0.32, R5-R20 0.10/0.07, X5 0.13/0.09, AX 0.55/0.27, p < 0.05 for all) and G- subjects ((Q+/Q-) R5 0.35/0.29, R5-R20 0.08/0.06, X5 0.10/0.08, AX 0.31/0.19 p < 0.05 for all) except for R20 (adjusted for gender and age). CONCLUSIONS: Self-reported chronic bronchitis or emphysema or COPD was associated with higher pulmonary resistance and lower pulmonary reactance measured by IOS, both among subjects with and without COPD according to GOLD criteria. IOS may have the potential to detect pathology associated with COPD earlier than spirometry.

Total desmosines in plasma and urine correlate with lung function.

The aim of the present study was to evaluate the relationship between the matrix degradation biomarkers, desmosine and isodesmosine (desmosines), and lung function. Plasma and creatinine-corrected urinary total desmosines (P- and U-desmosines, respectively), lung function and diffusing capacity of the lung for carbon monoxide (D(L,CO)) were measured in a cohort of subjects from the Swedish Twin Registry. Concentrations of U- and P-desmosines were measured in 349 and 318 subjects, respectively; approximately one-third of subjects had chronic obstructive pulmonary disease (COPD). Age, female sex, body mass index (BMI) and smoking were significantly associated with U-desmosines in a multiple linear regression analysis. In the overall population, after adjustments for age, sex, height, BMI and smoking, concentrations of U-desmosines were significantly correlated with all lung function measures, and P-desmosines with forced expiratory volume in 1 s and D(L,CO) (p<0.05). With the exception of residual volume versus P-desmosines, relationships between concentrations of desmosines and lung function measures were markedly stronger in subjects with COPD compared with those without COPD. These cross-sectional data showing associations between desmosines and several lung function variables suggest that desmosines, particularly U-desmosines, could be a useful biomarker of COPD status.

Incidence and remission of self-reported allergic rhinitis symptoms in adults.

BACKGROUND: A few studies have examined the incidence and remission of allergic rhinitis (AR) in the same general population. METHODS: A questionnaire focused on respiratory symptoms and airway diseases was mailed out in 1992 and in 2000 to the same subjects. Of 4933 subjects, in 1992 aged 20-59 years, 4280 (86.8%) answered at both occasions. AR was defined on self-reported AR and a simultaneous report of nasal symptoms provoked by exposure either to tree-, grass-pollen, furred animals or house dust. Multiple logistic regression adjusted for age and gender was used to analyze potential predictors, reported in 1992, for incidence and remission of AR. RESULTS: The prevalence of AR increased from 12.4% in 1992 to 15.0% in 2000. The incidence of AR from 1992 to 2000 was 4.8%, while 23.1% of the cases with AR in 1992 stated no AR symptoms in 2000 indicating remission. The highest incidence was seen in the youngest age group (20-29 years), whereas remission was highest in the oldest age group (50-59 years). Asthma symptoms during the last year (as reported in 1992) predicted increased incidence of AR and less chance for remission, 1.89 (95%CI 1.08-3.31) and 0.52 (0.31-0.87), respectively. Family histories of AR or asthma predicted increased incidence of AR 1.99 (1.42-2.80) and 1.62 (1.10-2.37), respectively, but were not associated with chance for remission, OR = 1.23 (0.81-1.87) and 0.94 (0.60-1.48). CONCLUSION: This study showed that AR became more common between 1992 and 2000, but also indicated remission in about 20% of the cases within the 8-year period, particularly in older ages. Asthma seems to be associated with higher risk for AR as well as less chance for remission, while heredity of asthma (or AR) may only be associated with the risk for the development and not remission of AR.

Obstructive airways diseases, smoking and use of inhaled corticosteroids in southern Sweden in 1992 and 2000.

OBJECTIVE: To examine the prevalence of obstructive pulmonary diseases, respiratory symptoms, smoking habits and pulmonary medication in an adult population, and to compare the results with a study performed in the same geographical area in 1992. DESIGN: In 2000, a postal questionnaire was sent to a randomly selected population of 5179 subjects aged 20-59 years living in southern Sweden. RESULTS: The participation rate was 71.3%. Self-reported asthma was reported by 8.5% of all respondents (vs. 5.5% in 1992, P < 0.001) and 14.5% of females aged 20-29 years. Self-reported chronic bronchitis and/or emphysema and/or chronic obstructive pulmonary disease (CBE/COPD) was reported by 3.6% (vs. 4.6% in 1992, non-significant) with the highest prevalence (5.7%) in the 50-59 year cohort. Smoking decreased from 33.3% in 1992 to 28.4% in 2000 (P < 0.05). About 46% of asthmatics reported nocturnal respiratory symptoms, and 69% reported having had asthma symptoms in the last 12 months. Use of inhaled steroids increased in subjects with asthma and CBE/COPD from 19.4% to 36.5% (P < 0.05) and from 8.6% to 30.0% (P < 0.05), respectively. CONCLUSIONS: Self-reported asthma increased significantly between 1992 and 2000, but the prevalence of CBE/COPD was unchanged. The high proportion of reported symptoms in asthmatics despite an increased use of steroids suggests that further efforts are needed to improve asthma treatment.

Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma.

Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500 microg/day) were randomized to once-daily budesonide/formoterol (80/4.5 microg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5 microg, 1 inhalation), or a corresponding dose of budesonide once-daily (200 microg, 1 inhalation in the evening). All patients received budesonide (100 microg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterol (24.1 l/min), and both were greater than with budesonide (5.5 l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma.

Increased serum levels of carbohydrate-deficient transferrin in patients with chronic obstructive pulmonary disease.

OBJECTIVE: The reason that only a minority of smokers develop chronic obstructive pulmonary disease (COPD) is still largely unknown. Glycosylation defects are involved in the pathological mechanisms in cystic fibrosis (CF), where chronic progressive obstructive lung disease dominates the clinical picture. Whether defects of protein glycosylation occur in COPD has not previously been examined. Increase in carbohydrate-deficient transferrin (CDT) in serum seems to function as an indicator of general defects of N-glycosylation. Recently, one study observed high serum CDT concentrations in CF patients. We examined whether subjects with COPD also have increased serum CDT levels. METHOD AND RESULTS: A total of 131 randomly selected individuals, 45-64 years of age, underwent a medical examination, spirometry and blood tests. Serum CDT was determined using high performance liquid chromatography. In subjects diagnosed as having COPD (n = 15), multiple logistic regression analyses demonstrated a significant relationship between the diagnosis of COPD and CDT, even after all efforts were made to take the influence of age and smoking into account (odds ratio 3.16, 95% CI 1.11-8.95). Also, in subjects with COPD there was an inverse partial correlation between forced expiratory volume in 1 s (FEV1) and serum CDT (r = -0.81, p = 0.001). CONCLUSION: These results suggest that protein glycosylation defects occur in COPD and, in addition, might be involved in the pathogenetic mechanisms of the disease. It seems that further investigation of the protein glycosylation in COPD is warranted.

Detection of chronic obstructive pulmonary disease (COPD) in primary health care: role of spirometry and respiratory symptoms.

OBJECTIVE: To evaluate the role of spirometry and respiratory symptoms in the detection of chronic obstructive pulmonary disease (COPD) in primary health care. DESIGN: A cross-sectional study. SETTING: A primary health centre in Landskrona, southern Sweden. SUBJECTS: 164 subjects who in 1992 had answered a postal questionnaire concerning obstructive pulmonary diseases and respiratory symptoms. They were aged 45-64 years, with a mean of 55 years. MAIN OUTCOME MEASURES: In 1997, the subjects were invited to perform a spirometry and a medical examination and to answer the same questionnaire as in 1992. Subjects with a forced expiratory volume in 1 second (FEV1) < 85% of the predicted normal value performed reversibility tests. RESULTS: 131 subjects participated in the examinations. 15 subjects (11.5%) were diagnosed as having COPD. Only three of them had been previously diagnosed as having a respiratory disease. Many commonly occurring respiratory symptoms were associated with a reduction in FEV1. CONCLUSIONS: Spirometry examinations in primary health care improve the probability of detecting COPD. A spirometry examination should be considered for patients with respiratory symptoms. It should also be considered for middle-aged smokers, even if they are symptom-free.