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PubMed2006

The association between polymorphic genotypes of glutathione S-transferases and COPD in the Turkish population.

Although smoking is regarded as the most important causal factor in chronic obstructive pulmonary disease (COPD), only 10-20% of smokers develop symptomatic COPD, which indicates the presence of genetic predisposing factors in its pathogenesis. This study investigates the association between gene polymorphysims of glutathione S-transferases (GSTs) and COPD. Blood samples were taken from 149 patients and 150 healthy controls. Polymorphisms of GSTT1, GSTM1, and GSTP1 were genotyped using Real-Time PCR. Multivariate logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals between specific genotypes and COPD. There was no difference in the frequencies of the genotypes of GSTM1 and GSTT1 between the groups, but the GSTP1 Ile/Ile genotype was significantly higher in the patients than in the controls (61.1% vs. 38%). GSTP1 Ile/Val and Val/Val genotypes were associated with a decreased risk of COPD when compared to the Ile/Ile genotype (2.12-fold and 4-fold, respectively). Thus we suggest that the Val allele of GSTP1 may have a protective effect for development of COPD. Furthermore, when we evaluated the association between GSTP1 genes and smoking status, smokers with the GSTP1 Ile allele had an increased risk for the development of COPD. Among the combinations of the genotypes, the combination of GSTM1, GSTT1 null, and GSTP1 Val/Val was associated with the maximal increased risk (12-fold) of COPD. Thus to explain the ethiopathogenesis of COPD, investigation of a single gene family is inadequate. Based on our results and the previous data, further studies should be focused on the GSTP1 gene and the interactions with other genes such as polymorphisms of N-acetyltransferases, GSTM1 and GSTT1, microsomal epoxide hydrolase, and allelic variants of cytochrome P450.

Aged↗

PubMed2006

Retrospective incremental cost analysis of a hospital-based COPD Disease Management Programme in Sweden.

This paper reports on a retrospective analysis of hospital-based healthcare costs associated with the management of chronic obstructive pulmonary disease (COPD). During the second half of 2001, Simrishamn Hospital, Sweden, implemented a structured Disease Management Programme (DMP) for COPD and a total of 784 patients with COPD, enrolled in the DMP, were included in the analysis. The goal was to reduce the number of clinical events, such as severe exacerbations by early intervention, aggressive drug treatment, specialists easy available for advice, improved support for smoking cessation, increased number of scheduled follow-ups and closer tracking of high-risk COPD patients. The hospital administrative system provided data on resource consumption, such as outpatient care, inpatient care and drugs and unit cost, used in the economic analysis. The total cost of COPD drugs doubled (from euro 14,133 to euro 30,855 per year) as did the total number of outpatient visits (from 580 to 996 visits per year). The number of hospitalizations for acute COPD exacerbations and COPD with acute lower respiratory infection decreased from 67 to 25 per year. Total COPD-related healthcare costs decreased. The results presented here support the hypothesis that a COPD DMP can offer substantial overall direct cost savings.

Aged↗

PubMed2005

Characteristics of a population of COPD patients identified from a population-based study. Focus on previous diagnosis and never smokers.

OBJECTIVE: To identify factors associated with diagnosis and health-related quality of life (HRQL) impairment in chronic obstructive pulmonary disease (COPD) patients from a population-based epidemiological study. DESIGN AND PARTICIPANTS: This was an epidemiologic, multicenter, population-based study. Three hundred and sixty-three individuals diagnosed with COPD from a randomly general population sample of 4035 individuals aged 40-69 were included in the analyses. INTERVENTIONS: Forced spirometry was performed on eligible subjects, and the European Commission for Steel and Coal (ECSC) and the St. George's Respiratory Questionnaires (SGRQ) were completed. Logistic regression models were constructed to identify variables associated with the previous diagnosis of COPD and with COPD in never smokers. A multiple linear regression model attempted to identify variables influencing HRQL impairment. RESULTS: Only 79 (21.7%) COPD patients had been previously diagnosed. Disease severity based on FEV(1), worse SGRQ score, previous respiratory disease, as well as the presence of wheezing were significantly associated with previous diagnosis. Being a woman, older than 55, with previous respiratory disease and without expectoration or wheezing characterized COPD in never smokers. A worse HRQL was associated with chronic symptoms, especially dyspnea; and with older age, cardiac comorbidity and impairment in lung function. CONCLUSIONS: Diagnosis of COPD in the community is more likely in patients with worse lung function and HRQL, and wheezing is the symptom most strongly associated with a diagnosis of COPD. Women older than 55, with previous respiratory diseases, without respiratory symptoms and mild airflow obstruction constitute the majority of individuals with COPD who have never smoked. Chronic respiratory symptoms are strongly associated with impairment in HRQL.

Adult↗

PubMed2006

Mexican American elders have similar severities of COPD despite less tobacco exposure than European American elders.

INTRODUCTION: Hispanics are the fastest growing ethnicity of the US population and the largest subset includes those of Mexican origin. Hispanics, including Mexican Americans (MAs), consistently report less tobacco exposure than European Americans (EAs), but limited data are available regarding differences in the clinical characteristics, severity of airflow obstruction, and functional status between MAs and EAs with chronic obstructive pulmonary disease (COPD). METHODS: Participants in a community-based study of aging and frailty among MAs and EAs, San Antonio Longitudinal Study of Aging, underwent spirometry. Participants with spirometry values consistent with COPD by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria are described here. RESULTS: Thirty-four percent (248/721) of the participants who underwent spirometry had evidence of GOLD Stages 1-4 COPD. Significantly more MAs with COPD reported being never smokers compared to EAs with COPD. Among those with COPD who also smoked, MAs reported significantly less tobacco exposure than EAs (15.7 vs. 32.4 pack-years, respectively), but both groups had surprisingly similar severities of airflow obstruction. Additionally, MAs had worse functional status and perceived health than did EAs. CONCLUSIONS: Despite significantly less exposure to tobacco smoke, MAs with COPD had a similar degree of obstruction to airflow compared with EAs with COPD. Healthcare providers should have a high index of suspicion for COPD in MAs who are exposed to even small amounts of cigarette smoke.

Aged↗

PubMed2006

External validity of randomized controlled trials in COPD.

BACKGROUND: COPD is a heterogeneous disease comprising a wide range of clinical phenotypes, depending on the degree to which emphysema, chronic bronchitis, reversible bronchospasm and small airways inflammation are present. Not all of these phenotypes may be represented among the subjects included in randomized controlled drug trials (RCTs) in COPD, making it difficult for doctors to know to what extent RCT evidence applies to individual patients. From a respiratory health survey of adults randomly selected from the community, we have estimated the proportion of subjects with COPD who would have been eligible for inclusion in major COPD RCTs. METHODS: A postal survey was sent to 3500 randomly selected individuals aged 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function tests. Subjects with COPD defined by post-bronchodilator spirometry were assessed against the eligibility criteria of 18 major RCTs cited in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. FINDINGS: Of 749 subjects completing the full survey, 117 had COPD. Of these, a median of 5% (range 0-20%) of subjects met inclusion criteria for the major RCTs. Of 55 subjects with COPD receiving treatment, 0-9% (median 5%) met inclusion criteria for the major RCTs. INTERPRETATION: The major COPD RCTs on which the GOLD treatment guidelines are based may have limited external validity. Over 90% of the COPD subjects in the community who were taking medication, did so on the basis of RCTs for which they would not have been eligible.

Adult↗

PubMed2002

[The epidemiology of COPD and asthma exacerbations in a general hospital].

This retrospective study identified the clinical and epidemiological characteristics of patients coming to the emergency room of our hospital with exacerbated asthma or chronic obstructive pulmonary disease (COPD) in 1993 and 1994. We followed a previously established protocol to review the case histories of patients from both years. The 1,592 exacerbations we identified in 1,209 asthmatics accounted for 0.9% of all emergency visits, with a mean of 2.2 1.6 (0-9) visits daily. The 2,106 exacerbations of COPD in 1,208 patients accounted for 1.2% of all emergencies, with a mean 2.9 (1-12) visits per day. The mean age was 51.2 (14-93) years for asthmatics and 70.3 (29-96) years for COPD patients. Of asthmatics, 69.8% were women and 30.1% were men, whereas 91.4% of COPD patients were men. The readmission rate was 3.4% for asthmatics and 4.8% for COPD patients. The hospitalization rate was 26.7% for asthmatics and 49.4% for COPD exacerbation patients. The hospital saw 22.6% of asthma exacerbations between midnight and 8 a.m. and 41.6% of COPD exacerbations during the same time frame. For both diseases, more emergencies occurred in winter. Correlation between asthma and COPD and declared influenza cases in the community were r = 0.63 (p < 0.001) for asthma and r = 0.83 (p < 0.0001) for COPD. Our findings underline the considerable emergency care burden generated by exacerbations of obstructive airway diseases and suggest that community acquired respiratory infections are usually the underlying cause.

Adolescent↗

PubMed2003

Chronic obstructive pulmonary disease (COPD) in elderly subjects: impact on functional status and quality of life.

Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and disability. Many studies have investigated factors influencing quality of life (QoL) in middle-aged COPD sufferers, but little attention has been given to elderly COPD. The aim of the present study was to investigate the impact of COPD on QoL and functional status in the elderly. Sixty COPD patients and 58 healthy controls over 65 years old were administered Pulmonary Function Tests, 6 min Walking Test (6MWD) for exercise tolerance, the Barthel Index and Mini Mental State Examination (MMSE) for functional status, the Geriatric Depression Scale (GDS) for mood, and the Saint George Respiratory Questionnaire (SGRQ) for QoL. FEV1 and PaO2 were reduced in COPD patients. Also the distance walked during 6MWD was significantly shorter for patients than controls (282.5 +/- 89.5 vs. 332.9 +/- 95.2 m; P < 0.01). Moreover, COPD patients had significantly worse outcomes for the Barthel Index, GDS and SGRQ. The logistic regression model demonstrated that a decrease in FEV1 is the factor most strictly related to the deterioration of QoL in COPD patients. Mood was also an independent factor influencing QoL. In conclusion, elderly COPD patients show a substantial impairment in QoL depending on the severity of airway obstruction; symptoms related to the disease may be exaggerated by mood deflection.

Activities of Daily Living↗

PubMed2006

Are patient characteristics helpful in recognizing mild COPD (GOLD I) in daily practice?

OBJECTIVE: To determine whether in a high-risk group of middle-aged male current smokers, patient characteristics are useful to recognize mild COPD (GOLD stage I). DESIGN: In a cross-sectional study spirometry was performed according to the American Thoracic Society criteria. COPD was defined according to the GOLD criteria for COPD. SETTING: Primary care. SUBJECTS: Male smokers, aged 40-65 years, without documented lung disease in the population at large. MAIN OUTCOME MEASURES: Medical records were scrutinized to collect patient characteristics. Multiple logistic regression analysis was used to identify independent determinants of mild COPD. RESULTS: A total of 567 subjects participated. COPD, defined by a FEV1/FVC ratio < 0.7, was detected in 170 subjects (30.0%, 95% CI 26.2-33.9%). In 149 subjects (26.3%; 22.7-30.1%) COPD was mild (GOLD stage I) and in 21 subjects (3.7%; 2.3-5.6%) moderate (GOLD stage II). Only age and cough were independently associated with the presence of mild COPD. The ability of these determinants to discriminate between subjects with or without mild COPD was relatively poor (ROC area 0.65). Therefore no prediction rule was developed. CONCLUSION: Our results indicate that patient characteristics are not helpful to recognize mild COPD (GOLD stage I) in middle-aged male smokers.

Adult↗

PubMed2005

Challenges associated with estimating minimal clinically important differences in COPD-the NHLBI perspective.

Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease that exemplifies the value, as well as the difficulties and challenges, of using minimal clinically important differences (MCID) in clinical research. Development and validation of better endpoints for clinical studies is critical to research progress in COPD. However, the clinical, genetic, and pharmacological heterogeneity of the COPD patient population complicates attempts to define and validate MCIDs for COPD. It is difficult to identify a single measurable outcome that reflects the many components of the COPD patient's health state. Acute exacerbations of symptoms, which COPD patients often experience, present another challenge in the development of MCIDs for this disease. Consequently, the NHLBI does not require the use of MCIDs in clinical research. This allows research on the causes, prevention and diagnosis of COPD and use of endpoints for which an MCID is not yet known. It is important for the scientific community to reach agreement on what is a meaningful MCID in therapeutic trials for COPD. Further research into the concept of the MCID and its application should enable therapeutic trials in COPD to yield knowledge that is more effectively translated into improved public health.

Data Interpretation, Statistical↗

PubMed2004

Trace elements as a component of oxidative stress in COPD.

OBJECTIVE: The purpose of this study was to assess the serum concentrations of those trace elements that act as a component of oxidative stress in COPD patients. Clinically stable COPD outpatients (n = 26) and healthy controls (n = 24) were studied. METHODOLOGY: Serum concentrations of copper (Cu) and zinc (Zn) were determined using a Varian Spectra AA220 flame atomic absorption spectrophotometer. Serum concentration of iron (Fe) was measured by the ferene assay, using a commercially available kit (IL Test Iron) with the ILAb 900 autoanalyser. The lipid peroxidation product malondialdehyde (MDA) in serum samples was measured spectrophotometrically in terms of TBARS (thiobarbituric acid reactive substances). RESULTS: The serum MDA concentration in COPD patients was found to be similar to the control group (0.68 +/- 0.15 nmol/mL vs 0.62 +/- 0.13 nmol/mL, respectively; P= 0.163). The serum concentrations of the trace elements in both study groups were in the normal reference range. There was no difference in Fe concentration between COPD patients and the control group (0.81 +/- 0.38 micro g/mL vs 0.92 +/- 0.41 micro g/mL; P= 0.360). Copper concentrations were higher (1.06 +/- 0.26 microg/mL vs 0.92 +/- 0.19 microg/mL; P <0.040); while zinc was lower in the COPD group compared to the controls (0.83 +/- 0.25 microg/mL vs 1.03 +/- 0.23 microg/mL; P= 0.006). Serum Zn concentrations were lower in the severe COPD patients compared to mild-moderate COPD patients (P = 0.038). CONCLUSION: The results of this study indicate that there are alterations in serum concentrations of trace elements in COPD patients, suggesting that they may play a role in the pathophysiology of this disease by virtue of their role in oxidative stress. We recommend further studies on the role of trace elements in the pathophysiology of COPD, their association with markers of oxidant/antioxidant status and on the clinical significance of their deficiency.

Aged↗

PubMed2004

Cost impact of COPD in Japan: opportunities and challenges?

OBJECTIVE: The Global Initiative for Obstructive Lung Disease highlights the importance of COPD from public health, health policy and clinical perspectives. In countries such as the USA, the economic impact of COPD exceeds that of many chronic conditions. There is a paucity of data on the economic burden of COPD in Japan. METHODOLOGY: Based upon publicly available information, a prevalence-based approach was used to construct a deterministic model to estimate the total direct and indirect costs of care for COPD in Japan. Data sources included a spirometry-based epidemiological study, the peer-reviewed literature, and governmental and industrial surveys. The most current data that addressed direct and indirect costs of care were utilized. RESULTS: In Japan, the estimated total cost of COPD is 805.5 billion yen (US 6.8 billion dollars) per year; 645.1 billion yen (US 5.5 billion dollars) in direct costs and 160.4 billion yen (US 1.4 billion dollars) in indirect costs. In direct costs, inpatient care accounted for 244.1 billion yen (US 2.1 billion dollars), outpatient care 299.3 billion yen (US 2.5 billion dollars), and home oxygen therapy 101.7 billion yen (US 0.9 billion dollars). The average annual total cost per patient for moderate/severe COPD is estimated to be 435,876 yen (US 3694 dollars); 349,080 yen (US 2958 dollars) per COPD patient in direct costs and 86,797 yen (US 795 dollars) in indirect costs. CONCLUSION: COPD imposes a high economic burden on the Japanese healthcare system. Health policy makers should direct urgent attention to increasing prevention, early diagnosis, and appropriate treatment of COPD.

Absenteeism↗

PubMed2005

High resolution CT and bronchial reversibility test for diagnosing COPD.

BACKGROUND: COPD is defined by airflow limitation that is not fully reversible and is associated with relevant risk factors. The diagnosis requires that other causes of chronic airflow limitation (CAL) be excluded. We assessed the diagnostic utility of high resolution thoracic CT (HRCT) and bronchodilator reversibility to assist in making a diagnosis of COPD. METHODOLOGY: We investigated 516 consecutive patients whose FEV1/FVC was less than 70% after inhalation of bronchodilator. HRCT was performed on all subjects and a final diagnosis was made only after 3 months of treatment and repeated spirometry. RESULTS: Of 516 cases, 54.3% had COPD, 19.8% had asthma plus emphysema, and 13.2% had chronic asthma. The remaining 12.7% of patients with CAL had diffuse panbronchiolitis, bronchiectasis, bronchiolitis obliterans, or other miscellaneous diseases. In these minor diseases HRCT was essential in making a definitive diagnosis. The sensitivities of emphysema on HRCT and of absence of bronchodilator response for the diagnosis of COPD were 81% and 90%, respectively, and the specificities of the tests were 57% and 37%, respectively. In addition, HRCT revealed considerable heterogeneity of COPD. Emphysema was not recognized on HRCT in 18.6% of COPD patients. HRCT also revealed that 17.5% of COPD patients had other pulmonary complications including lung fibrosis compatible with usual interstitial pneumonia in the lung bases. CONCLUSIONS: HRCT and the bronchial reversibility test had reasonable sensitivities but low specificities for diagnosing COPD. HRCT has some additional advantages in detecting heterogeneity and concomitant lung diseases in COPD.

Administration, Inhalation↗

PubMed2005

Outcomes and health-related quality of life following hospitalization for an acute exacerbation of COPD.

OBJECTIVE: The purpose of this study was to understand the outcomes for patients admitted to hospital for an acute exacerbation of COPD, and to determine the factors influencing quality of life and health service utilization of patients with COPD. METHODOLOGY: Hospital outcomes of 282 patients with moderate and severe COPD, for an acute exacerbation, were retrospectively evaluated. After 24 months of follow up, health-related quality of life (QoL) and health service utilization (emergency room (ER) visit and readmission) in 54 patients admitted previously, were surveyed by questionnaires. RESULTS: Of 282 COPD patients admitted for an acute exacerbation, 28 patients (9.9%) died during hospitalization, 241 patients (85.5%) were discharged home, and only 13 patients (4.6%) needed long-term care facilities. Although over 50% of the patients had survived over 2 years after discharge, their QoL was poor. Patients who frequently went to the ER or were admitted, were those with poor QoL, severe dyspnoea and frequent exacerbation. COPD exacerbation and dyspnoea were the main factors influencing QoL of the patients. Age, comorbidity, QoL, FEV1, frequency of COPD exacerbation, long-term oxygen therapy, and family doctor were the factors determining the likelihood of patients visiting the ER. Frequency of COPD exacerbation, family doctor and living alone were the factors determining which patients were likely to be admitted to hospital. CONCLUSION: The outcomes and QoL of patients admitted for an acute exacerbation of COPD were poor. The major factors influencing QoL were frequency of COPD exacerbation and severity of dyspnoea. Improvement of social and medical networks (e.g. reducing the number of patients living alone and providing family doctors for patients) may reduce health care service utilization.

Aged↗

PubMed2005

COPD: a prevalence estimation model.

OBJECTIVES: COPD is increasingly recognized as a leading cause of global morbidity and mortality. Prevalence estimates for COPD are generally unavailable or unreliable. Thus, a simple and valid model for estimating COPD prevalence would provide essential information for policymakers in addressing a major burden of worldwide illness. METHODOLOGY: We modelled the relationships among readily available demographic data (e.g. age, gender), smoking prevalence, and COPD prevalence based on a literature review. We also included risks of COPD from environmental pollution and associations with socioeconomic status. RESULTS: The model specifies a minimum of eight input variables to predict COPD prevalence in a given population: population by age, gender, smoking prevalence, prevalence of COPD among smokers, proportion living in rural areas, country by level of development, and exposures to environmental pollution. Actual COPD prevalence data from large population-based studies in Spain, Norway, Poland and Nepal compared favourably with the model projections (P > or = 0.10). CONCLUSION: The model is a simple tool for estimating the prevalence of COPD populations in a given region or country. Further studies are needed to prospectively validate the model and test the assumptions upon which it is based.

Adult↗

PubMed2006

Comparison of airway dimensions in different anatomic locations on chest CT in patients with COPD.

OBJECTIVE: It is not well known whether there is heterogeneity in the airway dimensions at different anatomic locations in individual patients with COPD. The first objective was to compare airway dimensions of the basal segment bronchus between COPD patients and healthy controls. The second and third objectives were to compare the airway dimensions in two anatomic locations, and to investigate the relationship between CT measurements and pulmonary function among COPD patients. METHODS: Thirty males with COPD (aged 68.7 +/- 8.1 years) and 18 healthy males (aged 64.9 +/- 14.0 years) were enrolled in the study. COPD was diagnosed according to the criteria of the Global Initiative for Obstructive Lung Disease Workshop Report. Pulmonary function tests and CT scans were performed on all subjects. Airway dimensions and lung attenuation were automatically determined using methods that were validated with a phantom. RESULTS: Age, smoking index and height did not significantly differ between the COPD patients and healthy controls. The COPD patients had a significantly thicker airway wall than healthy controls. Among the COPD patients, there were no significant differences in the airway dimensions of bronchi in different segments; however, the airway and lung attenuation measurements of the lower lung field were more strongly correlated with FEV(1) than those of the upper lung field. CONCLUSION: Patients with COPD had no significant heterogeneity in airway dimensions at different anatomic locations. The airway and lung attenuation measurements of the lower lung field were more strongly correlated with airflow limitation than those of the upper lung field.

Aged↗

PubMed2003

Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD.

BACKGROUND: The pathophysiology of chronic obstructive pulmonary disease (COPD) features pulmonary inflammation with a predominant alveolar macrophage involvement. Bronchoalveolar macrophages from patients with COPD release increased amounts of inflammatory cytokines in vitro, an effect that is not inhibited by the glucocorticosteroid dexamethasone. Resveratrol (3,5,4'-trihydroxystilbene) is a component of red wine extract that has anti-inflammatory and antioxidant properties. A study was undertaken to determine whether or not resveratrol would inhibit cytokine release in vitro by alveolar macrophages from patients with COPD. METHODS: Alveolar macrophages were isolated from bronchoalveolar lavage (BAL) fluid from cigarette smokers and from patients with COPD (n=15 per group). The macrophages were stimulated with either interleukin (IL)-1beta or cigarette smoke media (CSM) to release IL-8 and granulocyte macrophage-colony stimulating factor (GM-CSF). The effect of resveratrol was examined on both basal and stimulated cytokine release. RESULTS: Resveratrol inhibited basal release of IL-8 in smokers and patients with COPD by 94% and 88% respectively, and inhibited GM-CSF release by 79% and 76% respectively. Resveratrol also inhibited stimulated cytokine release. Resveratrol reduced IL-1beta stimulated IL-8 and GM-CSF release in both smokers and COPD patients to below basal levels. In addition, resveratrol inhibited CSM stimulated IL-8 release by 61% and 51% respectively in smokers and COPD patients, and inhibited GM-CSF release by 49% for both subject groups. CONCLUSIONS: Resveratrol inhibits inflammatory cytokine release from alveolar macrophages in COPD. Resveratrol or similar compounds may be effective pharmacotherapy for macrophage pathophysiology in COPD.

Aged↗

PubMed2005

Oxidative stress and airway inflammation in severe exacerbations of COPD.

BACKGROUND: A study was undertaken to assess both oxidative stress and inflammation in the lungs of patients with chronic obstructive pulmonary disease (COPD) during severe and very severe exacerbations compared with those with stable COPD, healthy smokers, and non-smokers. Two sites within the lungs were compared: the large airways (in sputum) and the peripheral airways (by bronchoalveolar lavage (BAL)). METHODS: BAL fluid cell numbers and levels of tumour necrosis factor (TNFalpha) and interleukin (IL)-8 were measured as markers of airway inflammation and glutathione (GSH) levels as a marker of antioxidant status. Nuclear translocation of the pro-inflammatory transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) were also measured by electromobility shift assay in BAL fluid leucocytes and lung biopsy samples. RESULTS: Influx of inflammatory cells into the peripheral airways during exacerbations of COPD was confirmed. Increased IL-8 levels were detected in BAL fluid from patients with stable COPD compared with non-smokers and healthy smokers, with no further increase during exacerbations. In contrast, IL-8 levels in the large airways increased during exacerbations. GSH levels were increased in the BAL fluid of smokers (444%) and patients with stable COPD (235%) compared with non-smokers and were reduced during exacerbations (severe 89.2%; very severe 52.3% compared with stable COPD). NF-kappaB DNA binding in BAL leucocytes was decreased in healthy smokers compared with non-smokers (41.3%, n = 9, p<0.001) but did not differ in COPD patients, whereas AP-1 DNA binding was significantly decreased during exacerbations of COPD. CONCLUSION: There is evidence of increased oxidative stress in the airways of patients with COPD that is increased further in severe and very severe exacerbations of the disease. This is associated with increased neutrophil influx and IL-8 levels during exacerbations.

Bronchitis↗

PubMed2005

C-reactive protein in patients with COPD, control smokers and non-smokers.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have raised serum levels of C reactive protein (CRP). This may be related directly to COPD and its associated systemic inflammation or secondary to other factors such as concomitant ischaemic heart disease (IHD) or smoking status. The aim of this study was to evaluate IHD and smoking as potential causes of raised CRP levels in COPD and to test the association between inhaled corticosteroid (ICS) use and serum CRP levels. METHODS: Cross sectional analyses comparing cohorts of 88 patients with COPD, 33 smokers (S), and 38 non-smoker (NS) controls were performed. Clinical assessments included a complete medical history, pulmonary function, 6 minute walk test (6MWT), cardiopulmonary exercise test, and high sensitivity serum CRP measurements. RESULTS: Serum CRP levels were significantly higher in patients with COPD (5.03 (1.51) mg/l) than in controls (adjusted odds ratio 9.51; 95% confidence interval 2.97 to 30.45) but were similar in the two control groups (S: 2.02 (1.04) mg/l; NS: 2.24 (1.04) mg/l). There was no clinical or exercise evidence of unstable IHD in any of the subjects. CRP levels were lower in COPD patients treated with ICS than in those not treated (3.7 (3.0) mg/l v 6.3 (3.6) mg/l); this association was confirmed in an adjusted regression model (p<0.05). CONCLUSION: CRP levels are raised in COPD patients without clinically relevant IHD and independent of cigarette smoking, and reduced in patients with COPD using ICS. CRP may be a systemic marker of the inflammatory process that occurs in patients with COPD.

Adrenal Cortex Hormones↗