Prevalence of airflow limitation in subjects undergoing comprehensive health examination in Japan: Survey of Chronic Obstructive pulmonary disease Patients Epidemiology in Japan.

PURPOSE: There are still evidence gaps on the prevalence of airflow limitation in Japan. The purpose of this survey was to estimate the prevalence of airflow limitation among healthy subjects in Japan and to show what proportion of subjects with airflow limitation had been diagnosed with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: This was an observational, cross-sectional survey targeting multiple regions of Japan. Subjects aged 40 years or above who were undergoing comprehensive health examination were recruited from 14 centers in Japan. Airflow limitation was defined as having forced expiratory volume in 1 second/forced vital capacity less than 70%. RESULTS: In a total of 22,293 subjects, airflow limitation was most prevalent in subjects aged over 60 years (8.7%), but was also observed in subjects aged 50-59 years (3.1%) and 40-49 years (1.7%). Overall prevalence was 4.3%. Among subjects with smoking history (n=10,981), the prevalence of airflow limitation in each age group (12.8% in those aged over 60 years, 4.4% in those aged 50-59 years, and 2.2% in those aged 40-49 years) and overall prevalence (6.1%) were higher than that of total subjects. Of the smokers with airflow limitation, 9.4% had been diagnosed with COPD/emphysema and 27.3% with other respiratory diseases. CONCLUSION: Among smokers undergoing comprehensive health examination, prevalence of airflow limitation reached 12.8% in those aged over 60 years and airflow limitation was observed in subjects aged 40-59 years as well, though their prevalence was lower than that in subjects aged over 60 years. We demonstrated that a significant proportion of smokers with airflow limitation had not been diagnosed with COPD/emphysema, suggesting that some of them can be diagnosed with COPD or other respiratory diseases by a detailed examination after comprehensive health examination. Screening for subjects at risk of COPD by spirometry in comprehensive health examination starting at 40 years of age, followed by a detailed examination, may be an effective approach to increase the diagnosis of COPD.

The relationship between the COPD Assessment Test score and airflow limitation in Japan in patients aged over 40 years with a smoking history.

BACKGROUND: A large number of chronic obstructive pulmonary disease (COPD) patients in Japan remain undiagnosed, primarily due to the underuse of spirometry. Two studies were conducted to see whether the COPD Assessment Test (CAT) in primary care has the potential to identify those patients who need spirometry for a diagnosis of COPD and to determine whether patients with cardiovascular disease had airflow limitation, which could be detected by CAT. MATERIALS AND METHODS: Two multicenter, noninterventional, prospective studies (studies 1 and 2) were conducted across Japan. Patients in both studies were ≥40 years old with a smoking history. Those in study 1 were seen in primary care and had experienced repeated respiratory tract infections, but had no diagnosis of COPD. Patients in study 2 were identified in cardiovascular disease clinics when routinely visiting for their cardiovascular disease. All patients completed the CAT prior to lung-function testing by hand-held spirometry. The presence of airflow limitation was defined as a forced expiratory volume in 1 second (FEV1)/FEV6 ratio<0.73. RESULTS: A total of 3,062 subjects completed the CAT (2,067 in study 1, 995 in study 2); 88.8% were male, and the mean age (±standard deviation) was 61.5±11.6 years. Airflow limitation was found in 400 (19.4%) patients in study 1, and 269 (27.0%) in study 2. The CAT score in patients with airflow limitation was significantly higher than in patients without airflow limitation in both studies: 8.6 (95% confidence interval [CI] 7.9-9.2) versus 7.4 (95% CI 7.1-7.6) in study 1, and 8.3 (95% CI 7.5-9.2) versus 6.4 (95% CI 6.0-6.8) in study 2 (both P<0.001). CONCLUSION: These findings suggest that the CAT has the potential to identify patients with cardiovascular disease or a history of frequent chest infections who need spirometry to diagnose COPD.

Prevalence of airflow limitation in outpatients with cardiovascular diseases in Japan.

BACKGROUND AND OBJECTIVES: Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) commonly coexist and share common risk factors. The prevalence of COPD in outpatients with a smoking history and CVD in Japan is unknown. The aim of this study was to determine the proportion of Japanese patients with a smoking history being treated for CVD who have concurrent airflow limitation compatible with COPD. A secondary objective was to test whether the usage of lung function tests performed in the clinic influenced the diagnosis rate of COPD in the patients identified with airflow limitation. METHODS: In a multicenter observational prospective study conducted at 17 centers across Japan, the prevalence of airflow limitation compatible with COPD (defined as forced expiratory volume (FEV)1/FEV6 <0.73, by handheld spirometry) was investigated in cardiac outpatients ≥40 years old with a smoking history who routinely visited the clinic for their CVD. Each patient completed the COPD Assessment Test prior to spirometry testing. RESULTS: Data were available for 995 patients with a mean age of 66.6±10.0 years, of whom 95.5% were male. The prevalence of airflow limitation compatible with COPD was 27.0% (n=269), and 87.7% of those patients (n=236) did not have a prior diagnosis of COPD. The prevalence of previously diagnosed airflow limitation was higher in sites with higher usage of lung function testing (14.0%, 15.2% respectively) compared against sites where it is performed seldom (11.1%), but was still low. CONCLUSION: The prevalence of airflow limitation in this study indicates that a quarter of outpatients with CVD have COPD, almost all of whom are undiagnosed. This suggests that it is important to look routinely for COPD in CVD outpatients.

A study to assess COPD Symptom-based Management and to Optimise treatment Strategy in Japan (COSMOS-J) based on GOLD 2011.

BACKGROUND AND OBJECTIVE: The Global initiative for chronic Obstructive Lung Disease (GOLD) Committee has proposed a chronic obstructive pulmonary disease (COPD) assessment framework focused on symptoms and on exacerbation risk. This study will evaluate a symptom and exacerbation risk-based treatment strategy based on GOLD in a real-world setting in Japan. Optimal management of COPD will be determined by assessing symptoms using the COPD Assessment Test (CAT) and by assessing the frequency of exacerbations. METHODS: This study (ClinicalTrials.gov identifier: NCT01762800) is a 24-week, multicenter, randomized, double-blind, double-dummy, parallel-group study. It aims to recruit 400 patients with moderate-to-severe COPD. Patients will be randomized to receive treatment with either salmeterol/fluticasone propionate (SFC) 50/250 µg twice daily or with tiotropium bromide 18 µg once daily. Optimal management of patients will be assessed at four-weekly intervals and, if patients remain symptomatic, as measured using the CAT, or experience an exacerbation, they have the option to step up to treatment with both drugs, ie, SFC twice daily and tiotropium once daily (TRIPLE therapy). The primary endpoint of the study will be the proportion of patients who are able to remain on the randomized therapy. RESULTS: No data are available. This paper summarizes the methodology of the study in advance of the study starting. CONCLUSION: The results of this study will help physicians to understand whether TRIPLE therapy is more effective than either treatment strategy alone in controlling symptoms and exacerbations in patients with moderate-to-severe COPD. It will also help physicians to understand the GOLD recommendation work in Japan.

The natural history of community-acquired pneumonia in COPD patients: a population database analysis.

BACKGROUND: Patients with Chronic Obstructive Pulmonary Disease (COPD) are at higher risk of developing Community-Acquired Pneumonia (CAP) than patients in the general population. However, no studies have been performed in general practice assessing longitudinal incidence rates for CAP in COPD patients or risk factors for pneumonia onset. METHODS: A cohort of COPD patients aged ≥ 45 years, was identified in the General Research Practice Database (GPRD) between 1996 and 2005, and annual and 10-year incidence rates of CAP evaluated. A nested case-control analysis was performed, comparing descriptors in COPD patients with and without CAP using conditional logistic regression generating odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The COPD cohort consisted of 40,414 adults. During the observation period, 3149 patients (8%) experienced CAP, producing an incidence rate of 22.4 (95% CI 21.7-23.2) per 1000 person years. 92% of patients with pneumonia diagnosis had suffered only one episode. Multivariate modelling of pneumonia descriptors in COPD indicate that age over 65 years was significantly associated with increased risk of CAP. Other independent risk factors associated with CAP were co-morbidities including congestive heart failure (OR 1.4, 95% CI 1.2-1.6), and dementia (OR 2.6, 95%CI 1.9-3.). Prior severe COPD exacerbations requiring hospitalization (OR 2.7, 95% CI 2.3-3.2) and severe COPD requiring home oxygen or nebulised therapy (OR 1.4, 95% CI 1.1-1.6) were also significantly associated with risk of CAP. CONCLUSION: COPD patients presenting in general practice with specific co-morbidities, severe COPD, and age >65 years are at increased risk of CAP.

Reported pneumonia in patients with COPD: findings from the INSPIRE study.

BACKGROUND: Pneumonia is an important complication of COPD and is reported more often in patients receiving inhaled corticosteroids (ICSs). Little is known about the clinical course and factors predisposing to pneumonia in patients with COPD. We investigated patient characteristics and symptoms occurring before pneumonia reports in the Investigating New Standards for Prophylaxis in Reduction of Exacerbations (INSPIRE) study. METHODS: This was a 2-year, double-blind, double-dummy parallel study of 1,323 patients randomized to salmeterol/fluticasone propionate 50/500 µg bid (SFC) or tiotropium 18 µg once daily (Tio). Baseline demographics, including serum C-reactive protein (CRP) levels, were measured, and daily record cards (DRCs) were completed. RESULTS: We identified 87 pneumonia reports from adverse event records (SFC=62; Tio=25) in 74 patients (SFC=50; Tio=24), compared with 2,255 exacerbations (SFC=1,185; Tio=1,070). Pneumonia was more common in patients with severe dyspnea and in those with a baseline CRP level>10 mg/L. Numbers of de novo pneumonias (events that were not preceded by symptoms of an exacerbation) were similar between treatment groups, but pneumonia was more likely after either a treated or untreated unresolved exacerbation in patients receiving ICSs (SFC=32; Tio=7). Similar results were seen when analysis was confined to radiologically confirmed events. CONCLUSIONS: Pneumonia is much less frequent than exacerbation in COPD. The excess of events with ICS treatment appears to be associated with protracted symptomatic exacerbations. Earlier identification and treatment of these events to prevent pneumonia merits further investigation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00361959; Study No.: SC040036; URL: clinicaltrials.gov.

Prevalence of airflow obstruction in patients attending a rapid access chest pain clinic.

BACKGROUND: Many UK hospitals have set-up specialised chest pain clinics to deal promptly and efficiently with cases of possible cardiac chest pain. It is possible that a proportion of patients attending these clinics will have a respiratory cause for their chest pain, or respiratory disease in addition to their cardiac pain. This study aimed to determine the prevalence of airflow obstruction, ischaemic heart disease and dual pathology in such patients. METHODS: Spirometry was performed on patients referred to a rapid access chest pain clinic over a 12-month period (target population of 400 patients). The main outcome measure was the prevalence of airflow obstruction (defined using spirometry), ischaemic heart disease and dual pathology. RESULTS: 405 subjects participated in the study. Abnormal spirometry was detected in 21% of patients (n=85). Airflow obstruction was the predominant lung function abnormality and was detected in 60 patients. Ischaemic heart disease was diagnosed in 21% of patients (n=85). Dual pathology was found in 4% of patients (n=17). CONCLUSIONS: Previous studies have reported a link between impaired lung function and future cardiovascular morbidity and mortality. This study suggests that airflow obstruction is an important alternative differential diagnosis in patients referred to a rapid access chest pain clinic. The identification of abnormal spirometry may help to better risk-stratify patients for future cardiovascular events and allow interventions to be instituted.

The prevention of COPD exacerbations by salmeterol/fluticasone propionate or tiotropium bromide.

Rationale: Exacerbations are key drivers of morbidity and mortality in chronicobstructive pulmonary disease (COPD).Objectives: We compared the relative efficacy of the long-acting inhaledbronchodilator/anti-inflammatory combination (salmeterol/fluticasone propionate) 50/500mcg bd and the long-acting bronchodilator (tiotropium) 18mcg od in preventing exacerbations and related outcomes in moderate severe COPD Methods: 1323 patients (mean age 64yr, forced expiratory volume in 1sec 39 per cent predicted) were randomized in 2-year, double blind, double-dummy, parallel study.Measurements and Main Results: Primary endpoint was healthcare utilization exacerbation rate. Other endpoints included health status measured by St. Georges Respiratory Questionnaire (SGRQ), mortality, adverse events and study withdrawal.Probability of withdrawing from the study was 29 per cent greater with tiotropium than salmeterol/fluticasone propionate (p=0.005). The modelled annual exacerbation rate was 1.28 in the salmeterol/fluticasone propionate group and 1.32 in the tiotropium group (rate ratio 0.967 [95 per cent CI: 0.836 to 1.119]; p=0.656). The SGRQ total score was statistically significantly lower at 2 years on salmeterol/fluticasone propionateversus tiotropium (difference 2.1 units, 95 per cent CI: 0.1 to 4.0, p=0.038). Mortality was significantly lower in the salmeterol/fluticasone propionate group; 21 (3 per cent of patients in this group died compared to 38 (6 per cent) in the tiotropium group (p=0.032). Morepneumonias were reported in the salmeterol/fluticasone propionate group relative to tiotropium (p=0.008).Conclusions: We found no difference in exacerbation rate between salmeterol/fluticasone propionate and tiotropium. More patients failed to complete the study receiving tiotropium. A small statistically significant beneficial effect was found on health status, with an unexpected finding of lower deaths in salmeterol/fluticasone propionate treated patients.

The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide.

RATIONALE: Exacerbations are key drivers of morbidity and mortality in chronic obstructive pulmonary disease (COPD). OBJECTIVES: We compared the relative efficacy of the long-acting inhaled bronchodilator/antiinflammatory combination (salmeterol/fluticasone propionate) 50/500 microg twice daily and the long-acting bronchodilator (tiotropium) 18 microg once daily in preventing exacerbations and related outcomes in severe and very severe COPD. METHODS: A total of 1,323 patients (mean age, 64 yr, post-bronchodilator FEV1, 39% predicted) were randomized in this 2-year, double-blind, double-dummy parallel study. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was health care utilization exacerbation rate. Other endpoints included health status measured by St. George's Respiratory Questionnaire (SGRQ), mortality, adverse events, and study withdrawal. Probability of withdrawing from the study was 29% greater with tiotropium than salmeterol/fluticasone propionate (P = 0.005). The modeled annual exacerbation rate was 1.28 in the salmeterol/fluticasone propionate group and 1.32 in the tiotropium group (rate ratio, 0.967; 95% confidence interval [CI], 0.836-1.119]; P = 0.656). The SGRQ total score was statistically significantly lower at 2 years on salmeterol/fluticasone propionate versus tiotropium (difference 2.1 units; 95% CI, 0.1-4.0; P = 0.038). Mortality was significantly lower in the salmeterol/fluticasone propionate group; 21 (3%) of patients in this group died compared with 38 (6%) in the tiotropium group (P = 0.032). More pneumonias were reported in the salmeterol/fluticasone propionate group relative to tiotropium (P = 0.008). CONCLUSIONS: We found no difference in exacerbation rate between salmeterol/fluticasone propionate and tiotropium. More patients failed to complete the study while receiving tiotropium. A small statistically significant beneficial effect was found on health status, with an unexpected finding of lower deaths in salmeterol/fluticasone propionate-treated patients. Clinical trial registered with www.clinicaltrials.gov (NCT 00361959).

The relationship between inflammatory markers and disability in chronic obstructive pulmonary disease (COPD).

AIMS: To examine relationships between markers of systemic inflammation and functional status in patients with chronic obstructive pulmonary disease (COPD). METHODS: 41 COPD patients were stratified using the Medical Research Council (MRC) dyspnoea scale. Six-minute walking distance (6MWD), Quadriceps (% body weight) (QBW), St George's Hospital Respiratory Questionnaire (SGRQ), London Chest Activity of Daily Living Scale (LCADL), C-reactive protein (CRP), interleukin 6 (IL6), tumour necrosis factor alpha, and neopterin were measured. Relationships between variables and differences in inflammatory markers between MRC categories were tested. RESULTS: Inflammation increased with MRC grade and was significantly different across grades; CRP (p=0.002) and IL6 (p=0.04). Relationships were evident between CRP, 6MWD, LCADL and SGRQ, r=-0.47, 0.50, 0.43 (all p<0.01) respectively, and between IL6, QBW and LCADL, rho=-0.36, 0.51 (p<0.05). CONCLUSIONS: Measures of systemic inflammation, and in particular CRP, may prove to be useful markers in the assessment of COPD severity in primary care.

Investigating new standards for prophylaxis in reduction of exacerbations--the INSPIRE study methodology.

Bronchodilators, including long-acting beta(2)-adrenoceptor agonists and anticholinergic bronchodilators, are effective in the treatment of chronic obstructive pulmonary disease. Evidence suggests that the addition of a long-acting beta(2)-agonist to an inhaled corticosteroid is associated with a reduced rate of exacerbations compared with either treatment alone or placebo. However, it is not known whether a long-acting beta(2)-agonist/inhaled corticosteroid combination is more effective than an anticholinergic bronchodilator alone in reducing exacerbations. The Investigating New Standards for Prophylaxis In Reduction of Exacerbations (INSPIRE) trial will study salmeterol (a long-acting beta(2)-agonist) in combination with fluticasone propionate (an inhaled corticosteroid) compared with tiotropium bromide (an anticholinergic bronchodilator) in patients with moderate-to-severe chronic obstructive pulmonary disease. The INSPIRE study is a multicentre, randomised, double-blind, double dummy, parallel group study conducted over 104 weeks. This is the first study to use two parallel definitions of an exacerbation; an event-based exacerbation is defined as one that requires use of healthcare resources, including additional treatment and hospitalization, whereas a symptom-based exacerbation is defined as one that satisfies the 1987 Anthonisen criteria. It is also the first study to compare the long-term effects of salmeterol/fluticasone propionate with tiotropium bromide on the rate of event-based exacerbations. Endpoints include rate of exacerbations (primary endpoint), time to first exacerbation, and duration of exacerbations. Health outcomes will be assessed via the St George's Respiratory Questionnaire. If the innovative methodology of utilizing 2 definitions of exacerbation proves successful, it will set the benchmark for future studies in chronic obstructive pulmonary disease.

Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease.

IMPACT: This study explores the use of measuring plasma biomarkers at exacerbation of chronic obstructive pulmonary disease (COPD), providing insight into the underlying pathogenesis of these important events. RATIONALE: The use of measuring C-reactive protein (CRP) to confirm exacerbation, or to assess exacerbation severity, in COPD is unclear. Furthermore, it is not known whether there may be more useful systemic biomarkers. OBJECTIVE: To assess the use of plasma biomarkers in confirming exacerbation and predicting exacerbation severity. METHODS: We assessed 36 biomarkers in 90 paired baseline and exacerbation plasma samples from 90 patients with COPD. The diagnosis of exacerbation fulfilled both health care use and symptom-based criteria. Biomarker concentrations were related to clinical indices of exacerbation severity. Interrelationships between biomarkers were examined to gain information on mechanisms of systemic inflammation at exacerbation of COPD. MEASUREMENTS AND MAIN RESULTS: To confirm the diagnosis of exacerbation, the most selective biomarker was CRP. However, this was neither sufficiently sensitive nor specific alone (area under the receiver operating characteristic curve [AUC], 0.73; 95% confidence interval, 0.66-0.80). The combination of CRP with any one increased major exacerbation symptom recorded by the patient on that day (dyspnea, sputum volume, or sputum purulence) significantly increased the AUC to 0.88 (95% confidence interval, 0.82-0.93; p<0.0001). There were no significant relationships between biomarker concentrations and clinical indices of exacerbation severity. Interrelationships between biomarkers suggest that the acute-phase response is related, separately, to monocytic and lymphocytic-neutrophilic pathways. CONCLUSIONS: Plasma CRP concentration, in the presence of a major exacerbation symptom, is useful in the confirmation of COPD exacerbation. Systemic biomarkers were not helpful in predicting exacerbation severity. The acute-phase response at exacerbation was most strongly related to indices of monocyte function.