Physician-Diagnosed COPD Global Initiative for Chronic Obstructive Lung Disease Stage IV in Östersund, Sweden*

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1 Original Research COPD Physician-Diagnosed COPD Global Initiative for Chronic Obstructive Lung Disease Stage IV in Östersund, Sweden* Patient Characteristics and Estimated Prevalence Nikolai Stenfors, MD, PhD Background: The prevalence of COPD is estimated to 4 to 14%. According to the Global Initiative for Chronic Obstructive Lung Disease guidelines, COPD is divided into four stages. Patients with stage IV disease (very severe) have FEV 1 < 30% of predicted values and/or respiratory insufficiency. The few studies that exist have reported a stage IV disease prevalence of 0.1 to 0.2% but provide limited additional patient characteristics. The present study estimated the prevalence of physician-diagnosed stage IV COPD in the city of Östersund, Sweden, and characterized the patients. Methods: Due to the regional integrated care pathway, patients in whom severe COPD is diagnosed are under surveillance by the Respiratory Department at Östersund Hospital. Among these patients and all others in whom COPD has been diagnosed at Östersund Hospital from 2000 to 2004, all those with an FEV 1 of < 40% predicted were examined. Results: A total of 76 patients fulfilled the criteria for stage IV COPD. The mean age was 71 years, 59% were women, and 40% were receiving long-term oxygen therapy. Sixty-five percent of the patients lived independently at home, 9% were present smokers, and 75% used inhaled corticosteroids daily. Sixty-seven percent of the patients had received vaccination against influenza the previous year. During 2004, 48% of the patients had at least one COPD-related hospitalization, and 11% had made at least one visit to the hospital for emergency care. Conclusions: The present study indicated that 0.13% of the population in Östersund in 2004 had physician-diagnosed stage IV COPD. This is probably an underestimation of the true prevalence. Patients with stage IV COPD appear to require periods of hospitalization more often than intermittent emergency department visits. (CHEST 2006; 130: ) Key words: COPD; description; Global Initiative for Chronic Obstructive Lung Disease; prevalence; stage IV Abbreviation: GOLD Global Initiative for Chronic Obstructive Lung Disease COPD was the sixth most common cause of death worldwide in 1990 and is predicted to be the third most common cause by The prevalence of COPD is estimated to 4 to 10%, 2,3 and 4 to 14% in the Scandinavian countries. 4 9 *From the Department of Respiratory Medicine & Allergy, Östersund Hospital, Östersund, Sweden. The author has reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. This work was generously supported by grants from Syskonen Perssons Donationsfond, Jämtlands Läns Landstings anslag för Forskning och Utveckling, Medicinsk forskning inom länsjukvården Jämtlands Läns Landsting, and Hjärt-och Lungsjukas Länsförening i Jämtland. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, 10 COPD can be staged on the basis of FEV 1 as follows: mild (stage I); moderate (stage II); severe (stage III); and very severe disease (stage IV). Patients with stage IV disease have an FEV 1 of 30% predicted Manuscript received December 20, 2005; revision accepted March 2, Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( org/misc/reprints.shtml). Correspondence to: Nikolai Stenfors, MD, PhD, Consultant, Department of Respiratory Medicine & Allergy, Östersund Hospital, Östersund, Sweden; nikolai.stenfors@jll.se DOI: /chest Original Research

2 or 50% predicted with respiratory insufficiency. Respiratory insufficiency is defined as a Pao 2 of 60 mm Hg and/or a Pco 2 of 50 mm Hg. Patients with an FEV 1 of 30 to 50% predicted and right heart failure (cor pulmonale) are also considered as having stage IV disease. Epidemiologic studies 6,11,12 have reported that 0.1 to 1.5% of individuals in the population have severe obstructive lung disease, defined as an FEV 1 of 50% predicted. For COPD, few epidemiologic studies exist on the prevalence of GOLD stage IV disease. A prevalence of 0.1 to 0.2% has been reported from Sweden, Japan, Korea, and Denmark. 6,8,13,14 Stage IV disease was not evident in young adults aged 20 to 44 years in a European health survey. 15 In these studies, the diagnosis of stage IV COPD was based mainly on questionnaires and spirometry findings, with limited additional data on patient characteristics in two studies. 6,8 According to the regional integrated care pathway for COPD, in Östersund, Sweden, the Respiratory Department at Östersund Hospital has the responsibility for the continuing medical evaluation of patients with an FEV 1 of 40%. The aim of the present study was to estimate the prevalence of physician-diagnosed GOLD stage IV COPD in the city of Östersund, Sweden, and to characterize the patients regarding health status, social conditions, medication, and COPD-related health-care consumption. Materials and Methods In 2004, the city of Östersund had 58,459 inhabitants, with 17% of them 65 years of age. The city has seven primary health care centers and one hospital, with 393 beds. According to the regional integrated care pathway for COPD that was established in the late 1990s, patients with an FEV 1 40% predicted should be referred to the Respiratory Department for assessment. These patients are thereafter followed up at least once annually by a respiratory physician. In addition, they can directly contact the Respiratory Department when they experience a worsening of their respiratory status. The study design is presented in Figure 1. A computerized scan of patient records identified 326 patients with a diagnosis of COPD and/or emphysema (International Classification of Diseases, 10th revision, codes J43-J44) who had attended the Departments of Internal Medicine or Respiratory Medicine & Allergology from 2000 to 2004 and were resident in Östersund on December 31, From this group, 105 patients with an FEV 1 of 40% predicted and respiratory insufficiency or suspected cor pulmonale who were in stable clinical condition were identified and assessed in the spring of In addition to a thorough medical and social history, physical examination, postbronchodilator therapy spirometry 16,17 (Microplus; Levimed AB; Höganäs, Sweden), and ECG, were performed, and radial artery blood samples were obtained for acid-base and oxygenation status determination. Clinical signs of cor pulmonale were defined as a distended internal jugular venous pressure measured 2cm above the clavicle, leg edema, or p-pulmonale seen on ECG. Data on current medication, Medical Research Council dyspnea score, and comorbidity using the Charlson comorbidity index, as well as COPD-related hospital admissions, emergency care visits, and elective outpatient visits at the Departments of Internal Medicine or Respiratory Medicine were also registered. One patient with GOLD stage III disease in 2004 was unable to perform a proper spirometry and was excluded. Figure 1. Study design. *Patients in whom COPD/emphysema was diagnosed (International Classification of Diseases, 10th revision, J43-J44) at the Departments of Internal and Respiratory Medicine, Östersund Hospital, from 2000 to 2004 during a hospitalization, emergency visit, or elective outpatient visit. The medical records revealed that eight patients in whom COPD had been diagnosed in fact had pure asthma and had never smoked. Estimation of COPD stage based on medical records from 2000 to CHEST / 130 / 3/ SEPTEMBER,

3 All patients fulfilling the GOLD criteria for stage IV disease based on spirometry findings, respiratory insufficiency, or cor pulmonale were informed about the study. None declined inclusion. The Regional Ethics Committee at Umeå University approved the study. Statistical Analysis Descriptive statistics are presented as the mean (SD), unless otherwise stated. Results Table 1 GOLD Stage IV COPD Disease Based on Spirometry and/or Respiratory Insufficiency Criteria* Variables No LTOT (n 42) LTOT (n 28) Total (n 70) Female gender, No Age, yr (range) 68 (43 87) 74 (57 86) 71 (43 87) VC, % predicted 41.8 (11.7) 48.5 (19.2) 44.2 (15.2) FEV 1, % predicted 23.6 (6.2) 28.9 (14.6) 25.5 (10.4) BMI, kg/m (5.4) 22.8 (2.9) 23.1 (4.7) Po 2,mmHg 60.9 (7.5) Pco 2,mmHg 42.9 (0.1) MRC dyspnea score 4.4 (1.0) 4.9 (3.8) 4.6 (0.9) *Values are given as the mean (SD), unless otherwise indicated. LTOT long-term oxygen therapy; BMI body mass index; VC vital capacity; MRC Medical Research Council. Patients with and without oxygen when peripheral arterial blood samples were taken. A total of 76 patients fulfilled the GOLD criteria for COPD stage IV disease. Of these, 70 patients fulfilled the criteria based on spirometry and/or respiratory insufficiency (Table 1). The remaining six patients fulfilled the criteria based on signs of cor pulmonale only (Table 2). All six patients had an FEV 1 of 30% predicted and no evidence of respiratory insufficiency. They were included in the estimation of prevalence but not in the subsequent description. Thus, the estimated prevalence of physician-diagnosed stage IV COPD in Östersund as of December 31, 2004, was 0.13%, and was 0.26% among individuals in the population who were 40 years of age. Forty-five patients lived independently at home. Of these patients, 14 lived alone. Fifteen patients lived at home with community assistance or medical home care, and of these patients, 12 lived alone. The remaining 10 patients were institutionalized. Sixtyfive patients were retired due either to age or disease. None of the remaining patients worked 50% part time. Sixty-two patients were ex-smokers, 6 patients were present smokers, and 2 patients had never smoked. Forty-seven patients had received a vaccination against influenza within the last year, and 24 patients were vaccinated against Streptococcus pneumoniae within past 5 years. The use of medications is presented in Table 3. The most common comorbidity was hypertension (16 patients). Nine patients had diabetes and left ventricular heart failure, eight patients had angina, and six patients had atrial fibrillation. In addition to their COPD, seven patients had asthma and three patients had 1 -antitrypsin deficiency. The group had a mean Charlson comorbidity index of 1.68 COPD-related hospital contacts (SD, 0.81 COPD-related hospital contacts) with physicians at the Departments of Internal Medicine or Respiratory Medicine, which are presented in Table 4. The patients had a mean of 1.3 hospitalizations (SD, 2.3 hospitalizations), 0.4 emergency department visits (SD, 1.5 emergency department visits), and 0.7 elective outpatient visits (SD, 0.8 elective outpatient visits) during The mean stay for each COPD-related hospitalization was 8.6 days (SD, 9.3 days). Discussion To the best of our knowledge, this is the first study that estimates the prevalence of physician-diagnosed stage IV COPD using the GOLD criteria. This approximation is possible due to an ongoing local integrated care pathway, in which patients in whom severe COPD had been diagnosed are under surveillance by the regional Respiratory Department. Within the present study design, the local prevalence of stage IV COPD was estimated to be 0.13% in the whole population of Östersund, and 0.26% in the population of individuals who were 40 years of age. This result should not be regarded as an indication of the true prevalence, as the reported prevalence is likely to be an underestimation. The perfect point-prevalence study of physician-diagnosed stage IV COPD would require the simultaneous screening of all patients with COPD in a community, a task that is practically impossible. The estimated prevalence of physician-diagnosed stage IV COPD in the present study appears to be in accordance with rates of stage IV COPD from epidemiologic studies using spirometry and questionnaires. In those studies, prevalence rates of 0.1% in adults 40 years of age have been reported from northern Sweden 8 and Japan, 13 and of 0.1% and 0.2% in subjects 18 years of age in Korea vs Denmark. 6,14 It is possible that the prevalence of stage IV disease in the present study may have been underestimated, as only 50 to 90% of patients with an FEV 1 of 40% predicted have been shown to 668 Original Research

4 Table 2 GOLD Stage IV COPD Based on Signs of Cor Pulmonale Only* Age, yr Gender FEV 1, % predicted Pao 2, mm Hg Paco 2, mm Hg Leg Edema JVP, cm P-Pulmonale Comorbidity 75 Female Yes 2 No Myocardial infarction, angina, cardiomyopathy, and aortic stenosis 78 Male No 4 No Myocardial infarction, angina, hypertension 58 Female Yes 0 No Varicose veins 79 Male Yes 1 No Myocardial infarction with left ventricular heart failure and angina 68 Female Yes 0 No Asthma 78 Female No 5 No *JVP jugular venous pressure. have a physician-diagnosed obstructive lung disease in Sweden. 8,18 Furthermore, the prevalence of physician-diagnosed COPD was based on a selected cohort of patients in whom COPD had been diagnosed at Östersund Hospital. On the other hand, previous epidemiologic studies have included subjects with asthma and have not included patients based on the presence of respiratory insufficiency or cor pulmonale. In all of the studies, the prevalence of COPD is strongly age-related. In contrast, 59% of the patients in the present study were women, compared to 0% and 21% in the Korean and Danish studies. 6,14 A total of 326 living patients were identified and were eligible for inclusion in the study. Of these, 76 patients (21%) had stage IV disease, which is a substantial but not unexpected proportion. Six of these patients fulfilled the stage IV criteria based only on clinical signs of cor pulmonale. These patients are presented separately, as these clinical signs have an unknown validity and probably significant interphysician variability. Furthermore, the patients had significant comorbidity that may have affected Table 3 Daily and As-Required Medication Use* Medication Daily As Required Oral corticosteroids 14 NA Inhaled glucocorticosteroid 29 NA Fixed-dose inhaled glucocorticosteroid and 24 NA long-acting 2 -agonist Long-acting 2 -agonist 22 4 Short-acting 2 -agonist 29 9 Inhaled anticholinergics 50 8 Theophylline (oral or suppository) 6 2 Calcium-supplementation 37 NA *Values are given as the No. of patients. NA not applicable. Budesonide, beclometasone, or fluticasone. Salmeterol or formoterol. Salbutamol, terbutaline, or fenoterol. Ipratropium bromide or tiotropium bromide. Calcium supplementation or diphosphonates (alendronate). the signs of cor pulmonale. To include COPD patients based on these criteria would thus be a potential confounding factor in future studies. To the best of our knowledge, this is the first study with detailed characteristics of patients with physician-diagnosed stage IV COPD. Two previous epidemiologic studies 6,8 have presented some description of subjects with severe COPD. Lindberg et al 8 found that 8% of a random sample of 1,237 subjects living in northern Sweden had an FEV 1 of 40% predicted. All of these patients had respiratory symptoms, used airway medications, and were smokers or ex-smokers. 8 In the other study, Vestbo and Lange 6 presented information on 33 Danish patients with stage IV disease. They had a mean age of 62 years and a mean FEV 1 of 23% predicted, and 61% were current smokers. 6 In contrast, only 9% were current smokers in the present study, whereas 89% were ex-smokers. Moreover, with a mean body mass index of 23, stage IV COPD patients in Östersund were generally not undernourished. An additional positive finding was that 65% of patients lived at home without any community or health-care assistance. The patients used several daily medications. Unexpectedly, inhaled anticholinergic agents were the most common. Inhaled corticosteroids, alone or in combination, are recommended for treatment in patients with stage III-IV disease and frequent exacerbations In the present study, 75% of the patients used this medication. Patients with stage IV disease have several risk factors for osteoporosis. Despite this, only 53% of the patients used either Table 4 Number of Patients With COPD-Related Events During 2004 Events No Event One Event Two Events More Than Two Events Hospitalizations Emergency visits Elective visits CHEST / 130 / 3/ SEPTEMBER,

5 biphosphonates or calcium supplementation. Only 34% of the patients had received the vaccine against S pneumoniae, whereas 60% had been vaccinated against influenza. These numbers could probably be increased, but we all know that many patients avoid vaccination and medication out of fear of the side effects. Comorbidity can predict mortality in patients with COPD, 23,24 and the Charlson comorbidity index is one of the most extensively used scoring systems. 25,26 Antonelli Incalzi et al 23 found a comorbidity index of 1.38, and Almagro et al 24 found an index of 2.22 in patients who had been admitted to the hospital for an exacerbation of COPD, compared to 1.68 in the present study. The patients in these studies had slightly higher FEV 1 and Po 2 values than did the patients in the present study. Our clinical experience is that patients with severe COPD have frequent contacts with health care. Rennard et al 27 found that 14% of COPD patients in general required emergency care and that 13% were hospitalized yearly. It has also been shown 28 that the severity of COPD is correlated to exacerbations causing hospitalization. In the present study, 11% of the patients required one or more COPD-related emergency visits and 48% required at least one COPD-related hospitalization during Our data indicate that patients with very severe COPD require periods of hospitalization more often than intermittent emergency visits, compared to COPD patients in general. It is our clinical experience that patients with severe COPD presenting to the emergency department with an exacerbation are usually hospitalized rather than treated as outpatients. It is difficult to know whether the present results indicate high or low health-care consumption by patients with very severe COPD as, to the best of our knowledge, there have been no corresponding studies published. It is therefore also difficult to know whether the present results are regional findings that may not be applicable elsewhere. The present study indicated that 0.13% of the population in Östersund, Sweden, in 2004 had physician-diagnosed stage IV COPD. The real prevalence is probably slightly higher. Among the identified patients, 40% were receiving long-term oxygen therapy. During 2004, 48% of the patients had experienced at least one hospitalization and 11% had made at least one emergency visit due to COPD. A prospective study on the present cohort is planned to further describe health-care contacts, morbidity, and mortality in patients with stage IV COPD. ACKNOWLEDGMENT: The authors thank the staff at the Department of Respiratory Medicine and Allergy, Östersund Hospital, for support; my late father, Professor Lars-Eric Stenfors, for scientific and fatherly advice; and Dr. Malcolm Sue-Chu, Department of Respiratory Medicine, Trondheim University Hospital, Norway, for language revision and fruitful discussion. References 1 Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause : Global Burden of Disease Study. Lancet 1997; 349: Mannino DM. COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity. Chest 2002; 121(suppl):121S 126S 3 Halbert RJ, Isonaka S, George D, et al. Interpreting COPD prevalence estimates: what is the true burden of disease? Chest 2003; 123: Bakke PS, Baste V, Hanoa R, et al. Prevalence of obstructive lung disease in a general population: relation to occupational title and exposure to some airborne agents. Thorax 1991; 46: Larsson L, Boethius G, Uddenfeldt M. Differences in utilisation of asthma drugs between two neighbouring Swedish provinces: relation to prevalence of obstructive airway disease. Thorax 1994; 49: Vestbo J, Lange P. Can GOLD stage 0 provide information of prognostic value in chronic obstructive pulmonary disease? Am J Respir Crit Care Med 2002; 166: Lundback B, Lindberg A, Lindstrom M, et al. Not 15 but 50% of smokers develop COPD? Report from the Obstructive Lung Disease in Northern Sweden Studies. Respir Med 2003; 97: Lindberg A, Bjerg-Backlund A, Ronmark E, et al. Prevalence and underdiagnosis of COPD by disease severity and the attributable fraction of smoking: report from the Obstructive Lung Disease in Northern Sweden Studies. Respir Med Lindberg A, Jonsson AC, Ronmark E, et al. Prevalence of chronic obstructive pulmonary disease according to BTS, ERS, GOLD and ATS criteria in relation to doctor s diagnosis, symptoms, age, gender, and smoking habits. Respiration 2005; 72: update: global strategy for the diagnosis, management, and prevention of COPD. Available at: Accessed August 1, Viegi G, Pedreschi M, Pistelli F, et al. Prevalence of airways obstruction in a general population: European Respiratory Society vs American Thoracic Society definition. Chest 2000; 117(suppl):339S 345S 12 Mannino DM, Homa DM, Akinbami LJ, et al. Chronic obstructive pulmonary disease surveillance: United States, MMWR Surveill Summ 2002; 51: Fukuchi Y, Nishimura M, Ichinose M, et al. COPD in Japan: the Nippon COPD Epidemiology study. Respirology 2004; 9: Kim DS, Kim YS, Jung KS, et al. Prevalence of chronic obstructive pulmonary disease in Korea: a population-based spirometry survey. Am J Respir Crit Care Med 2005; 172: de Marco, Accordini S, Cerveri I, et al. An international survey of chronic obstructive pulmonary disease in young adults according to GOLD stages. Thorax 2004; 59: Hedenstrom H, Malmberg P, Agarwal K. Reference values for lung function tests in females: regression equations with smoking variables. Bull Eur Physiopathol Respir 1985; 21: Hedenstrom H, Malmberg P, Fridriksson HV. Reference values for lung function tests in men: regression equations with smoking variables. Ups J Med Sci 1986; 91: Lindstrom M, Jonsson E, Larsson K, et al. Underdiagnosis of 670 Original Research

6 chronic obstructive pulmonary disease in Northern Sweden. Int J Tuberc Lung Dis 2002; 6: Jones PW, Willits LR, Burge PS, et al. Disease severity and the effect of fluticasone propionate on chronic obstructive pulmonary disease exacerbations. Eur Respir J 2003; 21: Szafranski W, Cukier A, Ramirez A, et al. Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease. Eur Respir J 2003; 21: Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2003; 361: Calverley PM, Boonsawat W, Cseke Z, et al. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003; 22: Antonelli Incalzi R, Fuso L, De Rosa M, et al. Co-morbidity contributes to predict mortality of patients with chronic obstructive pulmonary disease. Eur Respir J 1997; 10: Almagro P, Calbo E, Ochoa de Echaguen A, et al. Mortality after hospitalization for COPD. Chest 2002; 121: de Groot, V, Beckerman H, Lankhorst GJ, et al. How to measure comorbidity. a critical review of available methods. J Clin Epidemiol 2003; 56: Sundararajan V, Henderson T, Perry C, et al. New ICD-10 version of the Charlson comorbidity index predicted inhospital mortality. J Clin Epidemiol 2004; 57: Rennard S, Decramer M, Calverley PM, et al. Impact of COPD in North America and Europe in 2000: subjects perspective of Confronting COPD International Survey. Eur Respir J 2002; 20: Tsoumakidou M, Tzanakis N, Voulgaraki O, et al. Is there any correlation between the ATS, BTS, ERS and GOLD COPD s severity scales and the frequency of hospital admissions? Respir Med 2004; 98: CHEST / 130 / 3/ SEPTEMBER,

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