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.

The Swedish CArdioPulmonary BioImage Study: objectives and design.

Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

Invasive pneumococcal disease in patients with an underlying pulmonary disorder.

Chronic pulmonary disease is a recognized risk factor for invasive pneumococcal disease (IPD). However, previous studies have often not been large enough to allow detailed analyses of less prevalent pulmonary diseases, and findings regarding case fatality have been inconsistent. We examined the associations between an underlying pulmonary disease and IPD, and the impact of these diseases on the case fatality rate. Patients with IPD ≥18 years of age, between 1990 and 2008, were identified in microbiological databases. The associations between IPD and the pulmonary diseases were assessed using conditional logistic regression, comparing IPD cases to ten control subjects per case, randomly selected from the general population (matched for gender, year of birth and county of residence). Adjustments were made for other co-morbidities, level of education and socio-economic status, 4085 cases of IPD and 40 353 controls were identified. A more than four-fold increased risk of IPD was seen in chronic obstructive pulmonary disease, a doubled risk in asthma and a five-fold increased risk in subjects with pulmonary fibrosis. In univariate analysis, sarcoidosis and bronchiectasis were associated with a two-fold to seven-fold increase in the risk of IPD, but there was no statistical support for the associations when adjustments for confounders were made. No increased risk was seen in subjects with a history of pneumoconiosis or allergic alveolitis. The mortality following IPD was not increased in patients with chronic obstructive pulmonary disease, asthma, pulmonary fibrosis or bronchiectasis. Several chronic pulmonary diseases increase the risk of IPD but mortality following IPD seems not to be affected.

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.

Novel site-specific mast cell subpopulations in the human lung.

BACKGROUND: Lung mast cells are stereotypically divided into connective tissue (MC(TC)) and mucosal (MC(T)) mast cells. This study tests the hypothesis that each of these subtypes can be divided further into site-specific populations created by the microenvironment within each anatomical lung compartment. METHODS: Surgical resections and bronchial and transbronchial biopsies from non-smoking individuals were obtained to study mast cells under non-inflamed conditions. Morphometric and molecular characteristics of mast cell populations were investigated in multiple lung structures by immunohistochemistry and electron microscopy. RESULTS: MC(T) and MC(TC) coexisted in all compartments, with MC(T) being the prevailing type in bronchi, bronchioles and the alveolar parenchyma and MC(TC) being more abundant in pulmonary vessels and the pleura. Each of the MC(TC) and MC(T) phenotypes could be further differentiated into site-specific populations. MC(TC) were significantly larger in pulmonary vessels than in small airway walls, while the reverse was observed for MC(T). Within each MC(TC) and MC(T) population there were also distinct site-specific expression patterns of the IgE receptor, interleukin-9 receptor, renin, histidine decarboxylase, vascular endothelial growth factor, fibroblast growth factor, 5-lipoxygenase and leukotriene C4 synthase (eg, bronchial MC(T) consistently expressed more histidine decarboxylase than alveolar MC(T)). Renin content was high in vascular MC(TC) but markedly lower in MC(TC) in other compartments. For both MC(TC) and MC(T), the IgE receptor was highly expressed in conducting airways but virtually absent in alveolar parenchyma. CONCLUSIONS: These findings demonstrate novel site-specific subpopulations of lung MC(TC) and MC(T) at baseline conditions. This observation may have important implications in the future exploration of mast cells in a number of pulmonary diseases.

Plasma markers of inflammation and incidence of hospitalisations for COPD: results from a population-based cohort study.

BACKGROUND: The relationship between plasma markers of inflammation and the incidence of chronic obstructive pulmonary disease (COPD) is still unclear. This population-based study explored whether raised levels of five inflammation-sensitive plasma proteins (ISPs) predicted hospital admissions for COPD during 25 years of follow-up. METHODS: Spirometric tests and measurements of five ISPs (fibrinogen, ceruloplasmin, alpha(1)-antitrypsin, haptoglobin, orosomucoid) were performed in 5247 apparently healthy men from the city of Malmö (mean age 46 years). The incidence of hospitalisations for COPD was studied in relation to the number of ISPs in the fourth quartile. RESULTS: During the follow-up period, 258 men were admitted to hospital with COPD, 211 of whom were smokers at baseline. The incidence of hospital admissions for COPD was significantly associated with the number of raised ISPs. Adjusted for risk factors, the hazards ratio (95% CI) was 1.00 (reference), 1.28 (0.9 to 1.9), 1.29 (0.8 to 2.0) and 2.30 (1.6 to 3.2), respectively, for men with 0, 1, 2 and >or=3 ISPs in the top quartile (p for trend <0.001). This relationship was consistent in men with high and low lung function at baseline. The relationship with the incidence of hospital admissions for COPD was largely the same for all individual ISPs. CONCLUSION: Raised plasma ISP levels are associated with an increased incidence of COPD requiring hospitalisation.

A real-life cost-effectiveness evaluation of budesonide/formoterol maintenance and reliever therapy in asthma.

OBJECTIVE: To evaluate direct asthma-related costs in Swedish primary care in a real-life setting. DESIGN: 12-month open-label study. SETTING: Swedish primary care in a real-life setting. PARTICIPANTS: 1776 patients with persistent asthma. INTERVENTIONS: Patients with persistent asthma were randomised to one of three treatments: a free adjustable combination of budesonide (100-400 microg/inhalation) and formoterol (4.5 or 9 microg/inhalation) via separate inhalers plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, two inhalations twice daily) plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, one inhalation twice daily or two inhalations once daily), for maintenance plus additional inhalations as needed. Doses depended on previous inhaled corticosteroid dose. Patients attended the clinic at 0, 1.5, and 12 months. Telephone interviews were conducted at 4, 6, 8, and 10 months. MAIN OUTCOME MEASURES: The primary endpoint was direct asthma-related healthcare costs. RESULTS: Statistically significant reductions in annual direct costs per patient were observed with budesonide/formoterol maintenance and reliever therapy compared with the free adjustable combination of budesonide and formoterol (-13%, P<0.001) and fixed-dose budesonide/formoterol plus terbutaline (-20%, P<0.001). Time to first severe exacerbation did not differ significantly across treatment groups, with a mean reduction of 28% versus the free adjustable combination of budesonide and formoterol (P=0.076). Patients receiving budesonide/formoterol maintenance and reliever therapy used a significantly lower daily dose of budesonide compared with the conventional (P<0.001). CONCLUSIONS: This study reports direct cost savings with budesonide/formoterol maintenance and reliever therapy compared with conventional treatment regimens with at least equivalent efficacy.

Mortality risks among heavy-smokers with special reference to women: a long-term follow-up of an urban population.

Increased mortality risks associated with smoking are well established among men. There are very few population-based studies comprising a sufficient number of heavily smoking women, measuring the direct effect of smoking on mortality risks. Between 1974 and 1992, 8,499 women and 13,888 men attended a health screening programme including reporting of smoking habits. Individuals were followed for total mortality until 2005. All-cause, cancer, cardiovascular, lung cancer and respiratory mortality were calculated in smoking categories <10 g per day, 10-19 g per day, and > or =20 g per day with never-smokers as a reference group and with adjustments for co-morbidities, socio-economic and marital status. For respiratory mortality and lung cancer adjustments for FEV(1), socio-economic and marital status were performed. Smoking was associated with a two to almost threefold increased mortality risk among women and men. The relative risk (RR) with 95% confidence interval, (CI) for women who smoked 10-19 g per day was 2.44 (2.07-2.87), and for those who smoked 20 g per day or more the RR (95% CI) was 2.42 (2.00-2.92). Smoking was a strong risk factor for cardiovascular mortality among women, the RR (95% CI) for women who smoked 10-19 g per day was 4.52 (3.07-6.64). Ex-smoking women showed increased risks of all-cause mortality; RR (95% CI) 1.26 (1.04-1.52) cancer (excluding lung cancer); RR (95% CI) 1.42 (1.07-1.88) and lung cancer RR (95% CI) 2.71 (1.02-7.23) mortality. However, the cardiovascular; RR (95% CI) 1.18 (0.69-2.00) and respiratory; RR (95% CI) 0.79 (0.16-3.84) mortality risks were not statistically significant. This study confirms that as for men, middle-aged heavily smoking women have a two to threefold increased mortality risk. Adjustments for co-morbidity, socio-economic and marital status did not change these results.

Possible protection by inhaled budesonide against ischaemic cardiac events in mild COPD.

Epidemiological studies have indicated that chronic obstructive pulmonary disease (COPD) may be associated with an increased incidence of ischaemic cardiac events. The current authors performed a post hoc analysis of the European Respiratory Society's study on Chronic Obstructive Pulmonary Disease (EUROSCOP); a 3-yr, placebo-controlled study of an inhaled corticosteroid budesonide 800 microg.day(-1) in smokers (mean age 52 yrs) with mild COPD. The current study evaluates whether long-term budesonide treatment attenuates the incidence of ischaemic cardiac events, including angina pectoris, myocardial infarction, coronary artery disorder and myocardial ischaemia. Among the 1,175 patients evaluated for safety, 49 (4.2%) patients experienced 60 ischaemic cardiac events. Patients treated with budesonide had a significantly lower incidence of ischaemic cardiac events (18 out of 593; 3.0%) than those receiving placebo (31 out of 582; 5.3%). The results of the present study support the hypothesis that treatment with inhaled budesonide reduces ischaemic cardiac events in patients with mild chronic obstructive pulmonary disease.

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.

Predictors of COPD symptoms: does the sex of the patient matter?

Although chronic obstructive pulmonary disease (COPD) patients frequently report symptoms, it is not known which factors determine the course of symptoms over time and if these differ according to the sex of the patient. The current study investigated predictors for presence, development and remission of COPD symptoms in 816 males and 312 females completing 3-yr-follow-up in the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP). The following were included in generalised estimating equations logistic regression analyses: explanatory variables of treatment; pack-yrs smoking; age, forced expiratory volume in one second % predicted (FEV1 % pred); annual increase in FEV1 and number of cigarettes smoked; body mass index; and phadiatop. Interaction terms of sex multiplied by explanatory variables were tested. Over 3 yrs, similar proportions of males and females reported symptoms. In males only, higher FEV1 % pred was associated with reduction in new symptoms of wheeze and dyspnoea, and symptom prevalence was reduced with annual FEV1 improvement and phlegm prevalence reduced with budesonide treatment (odds ratio 0.66; 95% confidence interval 0.52-0.83). Additionally an increase in the number of cigarettes smoked between visits increased the risk of developing phlegm (1.40 (1.14-1.70)) and wheeze (1.24 (1.03-1.51)) in males but not females. The current study shows longitudinally that symptom reporting is similar by sex. The clinical course of chronic obstructive pulmonary disease can differ by sex, as males show greater response to cigarette exposure and treatment.

Predictors of lung function and its decline in mild to moderate COPD in association with gender: results from the Euroscop study.

BACKGROUND: There is increasing appreciation of gender differences in COPD but scant data whether risk factors for low lung function differ in men and women. We analysed data from 3 years follow-up in 178 women and 464 men with COPD, participants in the Euroscop Study who were smokers unexposed to inhaled corticosteroids. METHODS: Explanatory variables of gender, age, starting age and pack-years smoking, respiratory symptoms, FEV(1)%FVC and FEV(1)%IVC (clinically important measures of airway obstruction), body mass index (BMI), and change in smoking were included in multiple linear regression models with baseline and change in post-bronchodilator FEV(1) as dependent variables. RESULTS: Reduced baseline FEV(1) was associated with respiratory symptoms in men only. Annual decline in FEV(1) was not associated with respiratory symptoms in either men or women, and was 55 ml less in obese men (BMI 30 kg/m(2)) than men having normal BMI, an effect not seen in women. It was 32 ml faster in women with FEV(1)%FVC

Exacerbations of COPD: quantifying the patient's perspective using discrete choice modelling.

Patient-centred care is the current vogue in chronic obstructive pulmonary disease (COPD), but it is only recently that robust techniques have become available to determine patients' values and preferences. In this international cross-sectional study, patients' concerns and expectations regarding COPD exacerbations were explored using discrete choice modelling. A fractional factorial design was used to develop scenarios comprising a combination of levels for nine different attributes. In face-to-face interviews, patients were presented with paired scenarios and asked to choose the least preferable. Multinomial logit (with hierarchical Bayes) methods were used to estimate utilities. A total of 125 patients (82 males; mean age 66 yrs; 4.6 mean exacerbations.yr-1) were recruited. The attributes of exacerbations considered most important were impact on everyday life (20%), need for medical care (16%), number of future attacks (12%) and breathlessness (11%). The next most important attributes were speed of recovery, productive cough and social impact (all 9%), followed by sleep disturbance and impact on mood (both 7%). Importantly, analysis of utility shifts showed that patients most feared being hospitalised, housebound or bedridden. These issues were more important than symptom improvement. Strategies for the clinical management of chronic obstructive pulmonary disease should clearly address patients' concerns and focus on preventing and treating exacerbations to avoid these feared outcomes.

Relationship between respiratory symptoms and medical treatment in exacerbations of COPD.

Exacerbations of chronic obstructive pulmonary disease (COPD) can be defined symptomatically or by healthcare contacts, yet the relationship between these events is unknown. Data were collected during a 1-yr study of the budesonide/formoterol combination in COPD patients, where exacerbations, defined by increases in treatment, were compared with daily records of respiratory symptoms, rescue medication use and peak expiratory flow (PEF). The relationship between changes in these variables and the medical event was examined using different modelling approaches. Data from the first exacerbation treated with oral corticosteroids and/or antibiotics and/or hospitalisation (event based) were available in 468 patients. Patients exacerbating were significantly more breathless and more likely to report cough than healthy patients, but did not differ in baseline spirometry. Exacerbations defined by changes in individual symptoms were only weakly related to event-based exacerbations; however, defined with 63% of such events being predicted from symptom changes. Changes in rescue medication use or PEF were poor predictors of event-based exacerbations. The mean peak change in symptoms was closely related to the onset of therapy. In conclusion, event-based exacerbations are a valid way of identifying acute symptom change in a chronic obstructive pulmonary disease population. However, daily symptom monitoring is too variable using the current diary cards to make individual management decisions.

Effect of treatments on the progression of COPD: report of a workshop held in Leuven, 11-12 March 2004.

During the last decade several long term studies of interventions in patients with COPD have been published. This review analyses the potential of these interventions to alter the progression of the condition. The only treatment that has unequivocally been shown to reduce the rate of decline in FEV(1) is smoking cessation. Active psychological intervention in combination with pharmacotherapy is required. Other treatments may have an effect on the rate of decline in FEV(1) but this appears to be very small, at most. Several treatments affect the exacerbation rate and therefore might affect the progression of the disease. Further studies are warranted to examine this effect.

Bronchial mucosal mast cells in asymptomatic smokers relation to structure, lung function and emphysema.

The pathologic mechanisms of chronic obstructive pulmonary disease (COPD) most certainly involves neutrophil granulocytes, cytotoxic T-cells, macophages and mast cells. The aim of this study was to investigate the relation between the number of mast cells in different compartments in bronchial biopsies of central proximal airways to structural changes, lung function tests and emphysema detected by high resolution computed tomography (HRCT). Twenty nine asymptomatic smoking and 16 never-smoking men from a population study were recruited. Central bronchial biopsies were stained to identify mast cells by immunohistochemistry. The number of mast cells in the epithelium, lamina propria and smooth muscle as well as epithelial integrity and thickness of the tenascin and laminin layer were determined. Smokers had increased numbers of mast cells in all compartments (P<0.001). Structural changes were correlated to mast cell numbers with the closest associations to mast cell numbers in the smooth muscle [epithelial integrity (R(S)=-0.48, P=0.008), laminin layer (R(S)=0.63, P=0.0002), tenascin layer (R(S)=0.40, P=0.03)]. Similar correlations between mast cells and lung function tests were seen [functional residual capacity (FRC) (R(S)=0.60, P=0.0006), total lung capacity (TLC) (R(S)=0.44, P=0.02) and residual volume (RV) (R(S)=0.41, P=0.03)]. No correlations could be detected between mast cells and FEV1 or to emphysema. Smoking is associated with an increase of mast cells in all compartments of the bronchial mucosa, including smooth muscle, and this is related to altered airway structure and function.

COPD exacerbations: the importance of a standard definition.

Efforts to assess the efficacy of new therapies in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) have been hampered by the lack of a widely agreed and consistently used definition. A variety of definitions have been used in clinical studies, based on changes in patient symptoms or the requirement for antibiotic therapy, oral steroids or hospitalisation. To date, none of these definitions have been assessed in detail for their reliability, responsiveness and validity determined. Considerable heterogeneity in the aetiology and manifestation of COPD exacerbations makes identification and quantification of defining symptoms extremely difficult. New approaches are therefore being sought with a view to identifying a serum or tissue marker that can be used as a valuable diagnostic tool. Improvements in data recording will also contribute to the accuracy of data retrieval and assessment. If we are to progress to a level of sophistication seen in the diagnosis and management of other diseases, it is evident that considerable research efforts will be required to improve our understanding of COPD exacerbations and develop a standard definition for these events, thereby facilitating the assessment of therapeutic approaches.