ORIGINAL PAPER
Chronic bronchitis in COPD patients is associated with increased risk of exacerbations: a cross-sectional multicentre study J. L. Corhay,1 W. Vincken,2 M. Schlesser,3 P. Bossuyt,4 J. Imschoot4 Linked Comment: Burgel. Int J Clin Pract 2013; 67: 1218–9.
1
Respiratory Department, Centre HospitalierUniversitaire du Sart-Tilman, Liege, Belgium 2 Respiratory Department, Universitair Ziekenhuis Brussel, Brussels, Belgium 3 Respiratory Department, Centre Hospitalier du Luxembourg, Luxembourg, Luxembourg 4 Medical Department, Takeda Belgium, Brussels, Belgium Correspondence to: Jean L. Corhay, Department of Pneumology, CHU Sart-Tilman B-35, Liege 4000, Belgium Tel.: 0032 43668888 Fax: 0032 43668846 Email: [email protected] Disclosures Jean L. Corhay has received consultancy honoraria from AstraZeneca, Boehringer Ingelheim/Pfizer, GlaxoSmithKline, Novartis and Takeda. Walter Vincken received consultancy honoraria from AstraZeneca, Boehringer Ingelheim/Pfizer, GlaxoSmithKline, Novartis, Mundipharma, MEDA and Takeda. Pascale Bossuyt and Johan Imschoot are employees of Takeda Belgium.
1294
SUMMARY
What’s known
Background and aims: Chronic bronchitis (CB) in chronic obstructive pulmonary disease (COPD) patients is associated with increased mortality, frequent exacerbations and faster disease progression. This study investigates the prevalence of CB in a large population of COPD patients to identify features associated with CB. Methods: Cross-sectional multicentre study in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 2–4 from Belgium and Luxembourg. Results: The 974 patients included were on average 67.8 9.6 years old; 72% were male, FEV1 was 52.5 15.8% of predicted. The prevalence of CB was 64% (622/974). In patients with CB, the number of pack-years smoked and the prevalence of chronic respiratory failure, cachexia and skeletal muscle wasting were significantly higher, whereas FEV1 and FEV1/VC were lower. The prevalence of CB increased with GOLD stage and was higher in patients with emphysema and those exposed to occupational risk factors. The CB group had more exacerbations, a higher percentage of patients with frequent exacerbations (37.3% vs. 14.2% of patients; p < 0.0001), increased COPD-related, non-intensive care unit hospitalisations and all-cause hospitalisation rates. In multiple logistic regression analysis, frequent exacerbation was the most important independent variable associated with CB, followed by current smoking, chronic respiratory failure, COPD duration and age. Conclusions: CB prevalence in GOLD stage 2–4 COPD patients is high. CB is related to current tobacco smoking, and prevalence increases with COPD severity and duration, emphysema and age. CB could be the hallmark of a subtype of COPD easy to identify in clinical practice, associated with increased disease severity and increased risk of exacerbation.
Introduction Chronic obstructive pulmonary disease (COPD) is a major health problem and a leading cause of morbidity and mortality in the adult population worldwide. Increasing evidence indicates that COPD is a heterogeneous disease (1) and that different subtypes or phenotypes may contribute to a variable extent to the severity of the disease. Chronic bronchitis (CB) is a clinically and epidemiologically useful entity, defined as the presence of cough and sputum production for at least 3 months in each of 2 consecutive years. Chronic cough and sputum production are symptoms of mucus hypersecretion in proximal airways. CB is a well-known feature present in a considerable percentage of COPD patients, although it was not included in the defini-
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable clinical presentation. Chronic bronchitis is present in a considerable percentage of COPD patients, but prevalence figures reported vary widely.
What’s new The present study analyses the prevalence of chronic bronchitis and its association with disease and patient characteristics in a cross-sectional multicentre study in a large population of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2–4 COPD patients. Chronic bronchitis could be the hallmark of a subtype of COPD associated with increased disease severity and increased risk of exacerbation.
tion of COPD in any version of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report (2). Chronic bronchitis is considered a major manifestation of COPD, but the prevalence of CB in COPD varies widely. Lower prevalence was found in populationbased studies (14–30%) (3,4) and higher prevalence in clinical-based studies (27.3–74.1%) (1,5–10). It is suggested that CB is not an innocent manifestation in patients with COPD, as epidemiologic studies observed that CB in COPD patients is associated with increased mortality (11–13), frequent exacerbations including those requiring hospitalisation (4,7,9,10), worse respiratory symptoms (4,7), disease progression (14), physical activity limitation (4), and worse general health status (1,4,7). However, in the large observational evaluation of COPD longitudin-
ª 2013 John Wiley & Sons Ltd Int J Clin Pract, December 2013, 67, 12, 1294–1301. doi: 10.1111/ijcp.12248
Chronic bronchitis in COPD patients
ally to identify predictive surrogate endpoints (ECLIPSE) study, CB was not associated with an accelerated rate of decline in forced expiratory volume in 1 second (FEV1) (8), leaving the impact of CB on the disease course of COPD still controversial, despite some biological evidence of a distinct inflammatory cell profile in the airways of COPD patients with CB (15). CB associated with COPD could be a therapeutic target (16), reminding that early studies that validated inhaled corticoids in COPD selected patients on the presence of symptoms of CB (17,18) and that recent studies validated phosphodiesterase-4 inhibitor in preventing the development of exacerbation in COPD patients with CB (2). To address the uncertainty regarding the prevalence of CB in COPD patients, we analysed the prevalence of CB and its association with different disease and patient characteristics in a large population of GOLD stage 2–4 COPD patients from Belgium and Luxembourg.
Methods Population and study design In this cross-sectional multicentre study, we investigated the prevalence of CB and its association with disease and patient characteristics, exacerbations and COPD treatment in ambulant patients with moderate-to-severe COPD. Between October 2010 and April 2011, pneumologists from 16 pneumology departments in Belgium and Luxembourg (8 from the Flemish and 7 from the French speaking part of Belgium, 1 from Luxembourg) enrolled consecutive COPD outpatients fulfilling the study’s eligibility criteria. To be eligible, patients had to present with COPD of stages 2–4 according to the GOLD diagnostic criteria (2). The study protocol was approved by the ethics committee of Liege (B 70720109208) which acted as the central ethics committee for Belgium, and by the local ethics committees of all participating centres. Written informed consent was obtained from all patients prior to or at inclusion.
Data collection Data were collected using a structured questionnaire available in Dutch, French and German (Online supplemental Material/Appendix) in a single outpatient visit. The standardised questionnaire covered demographic data, COPD characteristics (duration, severity, presence of CB and emphysema), spirometric data, presence of pulmonary risk factors and comorbidities, exacerbations and hospitalisations over the last 12 months, and current COPD maintenance treatment. ª 2013 John Wiley & Sons Ltd Int J Clin Pract, December 2013, 67, 12, 1294–1301
Demographic data included age, gender, height and weight. Severity of pulmonary obstruction was assessed using the GOLD staging criteria (2). Spirometric data comprised postbronchodilator FEV1 (% predicted and absolute values) and postbronchodilator FEV1/VC (vital capacity, %). If available, data of three spirometric evaluations were collected; the most recent spirometry and spirometric evaluations performed about 6 months (interval of 4–8 months) and 12 months (interval of 10–14 months) before inclusion. The presence of emphysema was appreciated by the chest physician and radiologist, and based on their interpretation of CT scan of the thorax and/or on transfer factor of lung for carbon monoxide (TLCO) measurement. Chronic bronchitis was defined as cough and sputum production for at least 3 months in each of two consecutive years, in the absence of other causes of chronic cough (19). Smoking history included smoking status and number of pack-years. To investigate occupational risk factors, the exposure to mineral, organic or metallic dusts, fumes and vapours was assessed. The number and severity of exacerbations over the last 12 months was recorded. Exacerbations were graded as mild when the increased severity of respiratory symptoms could be controlled by the patient with an increase in the usual medication, as moderate when requiring treatment with systemic corticosteroids and/or antibiotics and as severe if hospitalisation or a visit to the emergency department was required. The number of exacerbations was determined according to the patient’s self-reported events (for mild and moderate exacerbations), and as noted in the medical file (for moderate and severe exacerbations). Additionally, the number of COPDrelated visits to the emergency department, visits to the emergency department without hospitalisation, COPD-related hospitalisation with or without stay in the intensive care unit and the overall number of hospitalisations (including those because of COPD) over the last year were recorded. Comorbidities were diagnosed by the chest physician according to personal clinical judgement and/or recorded from the data file of the patient. Comorbidities recorded included respiratory diseases (allergy, asthma and chronic respiratory failure), cardiovascular diseases (ischaemic heart disease, heart failure and hypertension), osteoporosis, skeletal muscle wasting, cachexia, diabetes mellitus, depression, anaemia, gastroesophageal reflux disease and lung cancer. The COPD treatment parameters comprised current COPD treatment as well as long-term oxygen therapy, influenza vaccination and smoking cessation therapy over the last 12 months.
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Chronic bronchitis in COPD patients
Determination of sample size As the reported prevalence of CB in COPD patients varies between 50% and 80%, a study population of approximately 1000 COPD patients is needed in order to have at least 251 patients in the group without CB. A sample size of 251 patients per group is necessary for a two-sided statistical test to detect a difference of 0.25 exacerbations/patient/year between patients with and without CB with at least 95% power, at a significance level of alpha = 0.05 and with an assumed common standard deviation of 1.0. An earlier study performed in France by Burgel et al. (10) with a similar design and end-points compared patients with and without CB in a cohort of 433 subjects. With a sample size of about 1000 patients it would be possible to identify additional features associated with CB in COPD patients.
Statistical analysis Patients were only included in the statistical analysis if the following minimal data were available: gender and age; GOLD stage; presence or absence of CB; number and severity of exacerbations over the last 12 months. Quantitative variables are reported as the mean standard deviation or median (5th and 95th percentiles); categorical variables are presented as percentages. Percentages are based on the total number of patients in the analysis set, i.e. missing values are also tabulated including percentages unless otherwise specified. Number and percentage of missing observations are provided for all parameters. Differences between patients with and without CB were analysed using Fisher’s exact test or the v2 test for binary variables, Mann–Whitney U-test for ordinal variables, and unpaired t-tests for normally distributed variables. CB prevalence was calculated using the normal approximation and presented as point estimate with the corresponding two-sided 95% confidence interval. All variables associated with the CB subtype with a p < 0.10 in univariate analysis were included in a multivariate logistic regression model to identify variables independently associated with CB. Statistical analysis was performed with Microsoft Excel version 2007 and Medcalc version 8.2.1.0 software (MedCalc Software, Mariakerke, Belgium). A p-value of 0.05 was considered statistically significant.
Results Population characteristics and prevalence of chronic bronchitis Data from 976 subjects were collected, 625 from the Flemish part and 311 patients from the French part of Belgium, and 38 patients from Luxembourg. Two
patients were excluded from the analysis because the minimal criteria for analysis were not met. Thus, data analysis was performed for 974 subjects. The characteristics of the study population are summarised in Table 1. Patients in this study were on average 67.8 9.6 years old, 72% were male and mean FEV1 was 52.5 15.8% of predicted. The prevalence of CB was 64% (CB present in 622/974 patients).
Comparison of COPD patients with and without chronic bronchitis No significant difference was observed between patients with and without CB for age, gender, smoking status, body mass index (BMI) (Table 1) and prevalence of most comorbidities (asthma, allergy, cardiovascular disease, osteoporosis, anaemia, lung cancer, depression and diabetes) (Table 2). Chronic respiratory failure, cachexia and skeletal muscle wasting, however, were more frequently present in the group with CB. The number of pack-years and COPD duration were higher, and both FEV1% predicted and FEV1/VC% were lower in patients with CB. The proportion of patients with CB increased with GOLD stage (Figure 1) and the prevalence of CB was higher in patients with emphysema and in patients exposed to occupational risk factors.
Chronic bronchitis and COPD exacerbations The overall number of exacerbations per patient per year was significantly higher in patients with CB (2.08 2.78 vs. 1.05 1.71; p < 0.001), as were the numbers of mild (0.7 1.9 vs. 0.3 0.9; p = 0.002), moderate (1.1 1.4 vs. 0.5 0.9; p < 0.0001) and severe (0.3 0.8 vs. 0.2 0.6; p = 0.0185) exacerbations per patient per year (Table 3). The percentage of patients with frequent (moderate or severe) exacerbations (defined as two or more per patient per year) was higher in the CB group than in the group without CB (37.3% vs. 14.2% of patients; p < 0.0001). The percentage of patients who experienced mild, moderate or severe exacerbations over the last year was higher in the CB group (Figure 2). More hospitalisations and more COPD-related hospitalisations without stay at the intensive care unit were observed for COPD patients with CB (Table 4).
COPD treatment in patients with and without chronic bronchitis Chronic obstructive pulmonary disease patients with CB are treated more often with theophyllines, antibiotics and smoking cessation therapy, but less frequently used long-acting muscarinic antagonist (LAMA) monotherapy than COPD patients without ª 2013 John Wiley & Sons Ltd Int J Clin Pract, December 2013, 67, 12, 1294–1301
Chronic bronchitis in COPD patients
Table 1 Population characteristics and comparison of chronic obstructive pulmonary disease patients with (CB+) and without (CB ) chronic bronchitis
Total N = 974
Age (years) Gender (% female) Disease duration (years) FEV1 (% predicted)† FEV1/VC (%)† Smoking status, % (n) Never smoked Former smoker Current smoker Unknown Number of pack years, % (n)‡ 20 years Unknown Body mass index (kg/m²) Emphysema, % (n) Present Absent Unknown Occupational risk factors, % (n) Present Absent Unknown
9.63
CB+ N = 622
CB N = 352
p-value
67.02 9.93 29.0 6.37 5.87 55.3 15.2 53.7 10.8
0.0768* 0.6733 0.0003*
Chronic bronchitis in COPD patients is associated with increased risk of exacerbations: a cross-sectional multicentre study J. L. Corhay,1 W. Vincken,2 M. Schlesser,3 P. Bossuyt,4 J. Imschoot4 Linked Comment: Burgel. Int J Clin Pract 2013; 67: 1218–9.
1
Respiratory Department, Centre HospitalierUniversitaire du Sart-Tilman, Liege, Belgium 2 Respiratory Department, Universitair Ziekenhuis Brussel, Brussels, Belgium 3 Respiratory Department, Centre Hospitalier du Luxembourg, Luxembourg, Luxembourg 4 Medical Department, Takeda Belgium, Brussels, Belgium Correspondence to: Jean L. Corhay, Department of Pneumology, CHU Sart-Tilman B-35, Liege 4000, Belgium Tel.: 0032 43668888 Fax: 0032 43668846 Email: [email protected] Disclosures Jean L. Corhay has received consultancy honoraria from AstraZeneca, Boehringer Ingelheim/Pfizer, GlaxoSmithKline, Novartis and Takeda. Walter Vincken received consultancy honoraria from AstraZeneca, Boehringer Ingelheim/Pfizer, GlaxoSmithKline, Novartis, Mundipharma, MEDA and Takeda. Pascale Bossuyt and Johan Imschoot are employees of Takeda Belgium.
1294
SUMMARY
What’s known
Background and aims: Chronic bronchitis (CB) in chronic obstructive pulmonary disease (COPD) patients is associated with increased mortality, frequent exacerbations and faster disease progression. This study investigates the prevalence of CB in a large population of COPD patients to identify features associated with CB. Methods: Cross-sectional multicentre study in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 2–4 from Belgium and Luxembourg. Results: The 974 patients included were on average 67.8 9.6 years old; 72% were male, FEV1 was 52.5 15.8% of predicted. The prevalence of CB was 64% (622/974). In patients with CB, the number of pack-years smoked and the prevalence of chronic respiratory failure, cachexia and skeletal muscle wasting were significantly higher, whereas FEV1 and FEV1/VC were lower. The prevalence of CB increased with GOLD stage and was higher in patients with emphysema and those exposed to occupational risk factors. The CB group had more exacerbations, a higher percentage of patients with frequent exacerbations (37.3% vs. 14.2% of patients; p < 0.0001), increased COPD-related, non-intensive care unit hospitalisations and all-cause hospitalisation rates. In multiple logistic regression analysis, frequent exacerbation was the most important independent variable associated with CB, followed by current smoking, chronic respiratory failure, COPD duration and age. Conclusions: CB prevalence in GOLD stage 2–4 COPD patients is high. CB is related to current tobacco smoking, and prevalence increases with COPD severity and duration, emphysema and age. CB could be the hallmark of a subtype of COPD easy to identify in clinical practice, associated with increased disease severity and increased risk of exacerbation.
Introduction Chronic obstructive pulmonary disease (COPD) is a major health problem and a leading cause of morbidity and mortality in the adult population worldwide. Increasing evidence indicates that COPD is a heterogeneous disease (1) and that different subtypes or phenotypes may contribute to a variable extent to the severity of the disease. Chronic bronchitis (CB) is a clinically and epidemiologically useful entity, defined as the presence of cough and sputum production for at least 3 months in each of 2 consecutive years. Chronic cough and sputum production are symptoms of mucus hypersecretion in proximal airways. CB is a well-known feature present in a considerable percentage of COPD patients, although it was not included in the defini-
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable clinical presentation. Chronic bronchitis is present in a considerable percentage of COPD patients, but prevalence figures reported vary widely.
What’s new The present study analyses the prevalence of chronic bronchitis and its association with disease and patient characteristics in a cross-sectional multicentre study in a large population of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2–4 COPD patients. Chronic bronchitis could be the hallmark of a subtype of COPD associated with increased disease severity and increased risk of exacerbation.
tion of COPD in any version of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report (2). Chronic bronchitis is considered a major manifestation of COPD, but the prevalence of CB in COPD varies widely. Lower prevalence was found in populationbased studies (14–30%) (3,4) and higher prevalence in clinical-based studies (27.3–74.1%) (1,5–10). It is suggested that CB is not an innocent manifestation in patients with COPD, as epidemiologic studies observed that CB in COPD patients is associated with increased mortality (11–13), frequent exacerbations including those requiring hospitalisation (4,7,9,10), worse respiratory symptoms (4,7), disease progression (14), physical activity limitation (4), and worse general health status (1,4,7). However, in the large observational evaluation of COPD longitudin-
ª 2013 John Wiley & Sons Ltd Int J Clin Pract, December 2013, 67, 12, 1294–1301. doi: 10.1111/ijcp.12248
Chronic bronchitis in COPD patients
ally to identify predictive surrogate endpoints (ECLIPSE) study, CB was not associated with an accelerated rate of decline in forced expiratory volume in 1 second (FEV1) (8), leaving the impact of CB on the disease course of COPD still controversial, despite some biological evidence of a distinct inflammatory cell profile in the airways of COPD patients with CB (15). CB associated with COPD could be a therapeutic target (16), reminding that early studies that validated inhaled corticoids in COPD selected patients on the presence of symptoms of CB (17,18) and that recent studies validated phosphodiesterase-4 inhibitor in preventing the development of exacerbation in COPD patients with CB (2). To address the uncertainty regarding the prevalence of CB in COPD patients, we analysed the prevalence of CB and its association with different disease and patient characteristics in a large population of GOLD stage 2–4 COPD patients from Belgium and Luxembourg.
Methods Population and study design In this cross-sectional multicentre study, we investigated the prevalence of CB and its association with disease and patient characteristics, exacerbations and COPD treatment in ambulant patients with moderate-to-severe COPD. Between October 2010 and April 2011, pneumologists from 16 pneumology departments in Belgium and Luxembourg (8 from the Flemish and 7 from the French speaking part of Belgium, 1 from Luxembourg) enrolled consecutive COPD outpatients fulfilling the study’s eligibility criteria. To be eligible, patients had to present with COPD of stages 2–4 according to the GOLD diagnostic criteria (2). The study protocol was approved by the ethics committee of Liege (B 70720109208) which acted as the central ethics committee for Belgium, and by the local ethics committees of all participating centres. Written informed consent was obtained from all patients prior to or at inclusion.
Data collection Data were collected using a structured questionnaire available in Dutch, French and German (Online supplemental Material/Appendix) in a single outpatient visit. The standardised questionnaire covered demographic data, COPD characteristics (duration, severity, presence of CB and emphysema), spirometric data, presence of pulmonary risk factors and comorbidities, exacerbations and hospitalisations over the last 12 months, and current COPD maintenance treatment. ª 2013 John Wiley & Sons Ltd Int J Clin Pract, December 2013, 67, 12, 1294–1301
Demographic data included age, gender, height and weight. Severity of pulmonary obstruction was assessed using the GOLD staging criteria (2). Spirometric data comprised postbronchodilator FEV1 (% predicted and absolute values) and postbronchodilator FEV1/VC (vital capacity, %). If available, data of three spirometric evaluations were collected; the most recent spirometry and spirometric evaluations performed about 6 months (interval of 4–8 months) and 12 months (interval of 10–14 months) before inclusion. The presence of emphysema was appreciated by the chest physician and radiologist, and based on their interpretation of CT scan of the thorax and/or on transfer factor of lung for carbon monoxide (TLCO) measurement. Chronic bronchitis was defined as cough and sputum production for at least 3 months in each of two consecutive years, in the absence of other causes of chronic cough (19). Smoking history included smoking status and number of pack-years. To investigate occupational risk factors, the exposure to mineral, organic or metallic dusts, fumes and vapours was assessed. The number and severity of exacerbations over the last 12 months was recorded. Exacerbations were graded as mild when the increased severity of respiratory symptoms could be controlled by the patient with an increase in the usual medication, as moderate when requiring treatment with systemic corticosteroids and/or antibiotics and as severe if hospitalisation or a visit to the emergency department was required. The number of exacerbations was determined according to the patient’s self-reported events (for mild and moderate exacerbations), and as noted in the medical file (for moderate and severe exacerbations). Additionally, the number of COPDrelated visits to the emergency department, visits to the emergency department without hospitalisation, COPD-related hospitalisation with or without stay in the intensive care unit and the overall number of hospitalisations (including those because of COPD) over the last year were recorded. Comorbidities were diagnosed by the chest physician according to personal clinical judgement and/or recorded from the data file of the patient. Comorbidities recorded included respiratory diseases (allergy, asthma and chronic respiratory failure), cardiovascular diseases (ischaemic heart disease, heart failure and hypertension), osteoporosis, skeletal muscle wasting, cachexia, diabetes mellitus, depression, anaemia, gastroesophageal reflux disease and lung cancer. The COPD treatment parameters comprised current COPD treatment as well as long-term oxygen therapy, influenza vaccination and smoking cessation therapy over the last 12 months.
1295
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Chronic bronchitis in COPD patients
Determination of sample size As the reported prevalence of CB in COPD patients varies between 50% and 80%, a study population of approximately 1000 COPD patients is needed in order to have at least 251 patients in the group without CB. A sample size of 251 patients per group is necessary for a two-sided statistical test to detect a difference of 0.25 exacerbations/patient/year between patients with and without CB with at least 95% power, at a significance level of alpha = 0.05 and with an assumed common standard deviation of 1.0. An earlier study performed in France by Burgel et al. (10) with a similar design and end-points compared patients with and without CB in a cohort of 433 subjects. With a sample size of about 1000 patients it would be possible to identify additional features associated with CB in COPD patients.
Statistical analysis Patients were only included in the statistical analysis if the following minimal data were available: gender and age; GOLD stage; presence or absence of CB; number and severity of exacerbations over the last 12 months. Quantitative variables are reported as the mean standard deviation or median (5th and 95th percentiles); categorical variables are presented as percentages. Percentages are based on the total number of patients in the analysis set, i.e. missing values are also tabulated including percentages unless otherwise specified. Number and percentage of missing observations are provided for all parameters. Differences between patients with and without CB were analysed using Fisher’s exact test or the v2 test for binary variables, Mann–Whitney U-test for ordinal variables, and unpaired t-tests for normally distributed variables. CB prevalence was calculated using the normal approximation and presented as point estimate with the corresponding two-sided 95% confidence interval. All variables associated with the CB subtype with a p < 0.10 in univariate analysis were included in a multivariate logistic regression model to identify variables independently associated with CB. Statistical analysis was performed with Microsoft Excel version 2007 and Medcalc version 8.2.1.0 software (MedCalc Software, Mariakerke, Belgium). A p-value of 0.05 was considered statistically significant.
Results Population characteristics and prevalence of chronic bronchitis Data from 976 subjects were collected, 625 from the Flemish part and 311 patients from the French part of Belgium, and 38 patients from Luxembourg. Two
patients were excluded from the analysis because the minimal criteria for analysis were not met. Thus, data analysis was performed for 974 subjects. The characteristics of the study population are summarised in Table 1. Patients in this study were on average 67.8 9.6 years old, 72% were male and mean FEV1 was 52.5 15.8% of predicted. The prevalence of CB was 64% (CB present in 622/974 patients).
Comparison of COPD patients with and without chronic bronchitis No significant difference was observed between patients with and without CB for age, gender, smoking status, body mass index (BMI) (Table 1) and prevalence of most comorbidities (asthma, allergy, cardiovascular disease, osteoporosis, anaemia, lung cancer, depression and diabetes) (Table 2). Chronic respiratory failure, cachexia and skeletal muscle wasting, however, were more frequently present in the group with CB. The number of pack-years and COPD duration were higher, and both FEV1% predicted and FEV1/VC% were lower in patients with CB. The proportion of patients with CB increased with GOLD stage (Figure 1) and the prevalence of CB was higher in patients with emphysema and in patients exposed to occupational risk factors.
Chronic bronchitis and COPD exacerbations The overall number of exacerbations per patient per year was significantly higher in patients with CB (2.08 2.78 vs. 1.05 1.71; p < 0.001), as were the numbers of mild (0.7 1.9 vs. 0.3 0.9; p = 0.002), moderate (1.1 1.4 vs. 0.5 0.9; p < 0.0001) and severe (0.3 0.8 vs. 0.2 0.6; p = 0.0185) exacerbations per patient per year (Table 3). The percentage of patients with frequent (moderate or severe) exacerbations (defined as two or more per patient per year) was higher in the CB group than in the group without CB (37.3% vs. 14.2% of patients; p < 0.0001). The percentage of patients who experienced mild, moderate or severe exacerbations over the last year was higher in the CB group (Figure 2). More hospitalisations and more COPD-related hospitalisations without stay at the intensive care unit were observed for COPD patients with CB (Table 4).
COPD treatment in patients with and without chronic bronchitis Chronic obstructive pulmonary disease patients with CB are treated more often with theophyllines, antibiotics and smoking cessation therapy, but less frequently used long-acting muscarinic antagonist (LAMA) monotherapy than COPD patients without ª 2013 John Wiley & Sons Ltd Int J Clin Pract, December 2013, 67, 12, 1294–1301
Chronic bronchitis in COPD patients
Table 1 Population characteristics and comparison of chronic obstructive pulmonary disease patients with (CB+) and without (CB ) chronic bronchitis
Total N = 974
Age (years) Gender (% female) Disease duration (years) FEV1 (% predicted)† FEV1/VC (%)† Smoking status, % (n) Never smoked Former smoker Current smoker Unknown Number of pack years, % (n)‡ 20 years Unknown Body mass index (kg/m²) Emphysema, % (n) Present Absent Unknown Occupational risk factors, % (n) Present Absent Unknown
9.63
CB+ N = 622
CB N = 352
p-value
67.02 9.93 29.0 6.37 5.87 55.3 15.2 53.7 10.8
0.0768* 0.6733 0.0003*
