5.8.3. Data description and analysis

 

This section addresses incidence, prevalence and mortality associated with COPD. It covers co-morbidity problems and the economic burden associated to these disorders.

 

Incidence

 

There are limited comparable data on the incidence of COPD in the EU, mainly deriving from isolated studies in Scandinavian countries and Ireland. In a study by Lindberg et al. (2005), in a symptomatic cohort of patients born in 1919 to 1929, 1934 to 1935 and 1949 to 1950 in Northern Sweden, a 10-year cumulative incidence rate according to a 9-4% GOLD criteria27 in persistent never smokers was reported. In another study by the same authors, an age-stratified general population sample of middle-aged and elderly individuals was considered: the 7-year cumulative incidence of COPD was 11.0% according to the GOLD criteria (Lindberg et al 2006). This was significantly higher in smokers (18.8%).

 

A study by Johannessen et al (2005) reported cumulative incidence rates of GOLD-defined COPD of 1.8% in never smokers, in a 9-year follow-up of a general population sample in Bergen (Norway).

 

Among 1711 middle-aged men of two rural Finnish cohorts, which were monitored within the framework of the Seven Countries Study, the 30-year cumulative incidences of chronic bronchitis and COPD were assessed at 22% and 12% in never-smokers (Pelkonen et al, 2006).

 

In another study performed in Copenhagen, Denmark, 8045 men and women aged 30-60 with normal lung function at baseline were followed for 25 years (Lokke et al, 2006). Abnormal lung function was observed in 4% for male never smokers (9% in women). The 25-year cumulative incidence of moderate and severe COPD was 1% in never smokers, with no significant differences between men and women.

 

Prevalence and disease severity

 

Since 2000, many studies on COPD prevalence have been published (Chapman et al, 2006). The variability of prevalence rates according to different diagnostic criteria were frequently underlined: a study reported rates ranging from 0.23 to 18.3%, the lowest ones (0.2 to 2.5%) being based on WHO expert opinions (Halbert et al, 2003). Recently, a meta-analysis (Halbert et al, 2006) estimated a prevalence of 9.2% using a spirometric definition in adults over 40 years of age. A total of 62 studies reported 101 overall prevalence estimates from 28 different countries, 17 of which were European. Prevalence did not vary significantly among WHO regions, although these results should be interpreted with caution since only the European region has more than four estimates (Table 5.8.1)

 

Table 5.8.1. Prevalence estimates for COPD per different variables

 

An example of the variability of estimates caused by different definitions of airways obstruction (AO) is provided by Viegi et al (2000). For example, in a general population sample of 25-73 year old patients from Northern Italy, AO prevalence rates ranged from 11.0% with the ERS criterion (forced expiratory volume in one second (FEV1)/vital capacity (VC) % <88th percentile in men, < 89th percentile in women) to 18.3% with the “clinical” criterion (GOLD Stage I+).

 

The Northern Ireland Cost and Epidemiology of Chronic Obstructive Pulmonary Disease (NICECOPD) study, assessed the prevalence of obstructive lung disease in 40-69 year olds to 14.4% (6.3% COPD) (Murtagh et al, 2005).

 

The WHO’s Large Analysis and Review of Housing and Health Status Study (WHO LARES) reported a prevalence of 6.2% of chronic bronchitis and emphysema in the past year among adults in seven EU cities (Angers, Bonn, Bratislava, Budapest, Ferreira, Forlì and Vilnius), with values ranging from about 4% in Forlì (Italy) and Bratislava (Slovak Republic) to about 11% in Vilnius (Lithuania) (Boutin-Forzano et al, 2007).

 

The IBERPOC study, carried out in 7 geographical areas with nearly 5 000 patients, has estimated that the prevalence of COPD in the general Spanish population aged between 40 and 69 years is 9.1% (Sobradillo Pena et al, 2000).

 

WHO-HFA database provides data for a few EU Countries, collected by national sources with different methodologies. Although, as already discussed, comparisons between countries may not be appropriate, the available data indicate a steady trend to increased prevalence in Finland, Slovakia, Romania, Hungary (Figure 5.8.1).

 

Figure 5.8.1. Chronic obstructive pulmonary disease prevalence, in % in EUGLOREH countries

 

In two model studies carried out with data of the Dutch population, the prevalence of COPD was estimated to increase by 40% in males and 140% in females between 1994 and 2015 (Feenstra et al, 2001) and by 50% (from 1.9 to 2.9 per 1 000) in males and by 90% in females (from 1.0 to 2.9 per 1 000) from 2000 to 2025 (Hoogendoorn et al, 2005). As regards the measurement of disease severity, data from 18 000 young adults (20–44 years) enrolled between 1991 and 1993 in 35 centres of 16 countries (13 EU and EFTA countries) collected for the European Community Respiratory Health Survey (ECRHS), were used to assess the prevalence of COPD severity stages, as defined in the GOLD guidelines (De Marco et al, 2004). These results are reported in Figure 5.8.2.

 

Figure 5.8.2. Prevalence of the GOLD severity stages* for the countries participating in the European Community Respiratory Health Survey

 

 

The Po Delta survey assessed the prevalence of GOLD-COPD in men and women respectively to: mild 12.3 and 7.3%, moderate 4.5 and 2.2%, severe-very severe 0.4 and 0.3% (Zielinski et al, 2006). People with chronic cough or phlegm ranged from 20-30% in mild to about 80% in the severe to very severe category.

 

Recently, the results of the Burden of Obstructive Lung Disease (BOLD) studies (12 centres; 5 European centres) suggested COPD GOLD stage II was 10.1% overall, 11.8% for men, and 8.5% for women (Buist et al, 2007). In Salzburg (Austria), the overall prevalence of COPD at stage I or higher was estimated at 26.1%, regardless of gender, and at stage II or higher at 10.7%. A doctor diagnosis of COPD was reported only by 5.6% of participants (Schirnhofer et al, 2007).

 

The Obstructive Lung Disease in Northern Sweden (OLIN) found that the prevalence of mild British Thoracic Society (BTS)-COPD was 5.3%, moderate 2.2%, and severe 0.6% (GOLD-COPD: mild 8.2%, moderate 5.3%, severe 0.7%, and very severe 0.1%) (Lindberg et al 2006). All subjects with severe COPD were symptomatic.

 

Prevalence (per 1 000 in Dutch population) reported for the Netherlands was 6.5. for mild, 13.3 for moderate, 3.7 for severe and 0.6 for very severe COPD (Hoogendoorn et al, 2005) in males and 3..9, 8.1, 2.3, 0.4, respectively, in females.

 

Mortality.

 

Although there are some problems regarding the accuracy of COPD mortality data, the limited data available indicate that mortality due to COPD increases with age and is greater in men than in women. Moreover, it is clear that COPD is one of the most important causes of death in most countries. The Global Burden of Disease Study (Murray and Lopez, 1997) has estimated that COPD, which was the sixth cause of death in 1990, will become the third cause of death worldwide and the ninth cause of death in developed countries by 2020. The reasons for this increase are attributable to the larger spread of the smoking habit and the fact that, in general, the population lives longer.

 

Despite statistics are greatly affected by terminology, awareness of the disease and potential gender bias in its diagnosis, the trends in mortality rates over time provide some important information. COPD mortality trends generally track several decades behind smoking trends. Trends in age-standardized death rates for the six leading causes of death in the United States from 1970 through 2002 show that COPD mortality increased over that period, while mortality from other chronic conditions declined (Chapman et al, 2006).

 

Interesting data are available on the WHO web site (http://data.euro.who.int).

 

 

Co-morbidity.

 

Elderly patients frequently have multiple chronic health conditions. The severity of co-morbid conditions and their impact on patients vary among patients and in the same patient over time. Co-morbidities can be categorized to provide a better understanding of their impact on the patient and disease management:

• Common pathway co-morbidities: diseases with a common patho-physiology, for instance, in the case of COPD, other smoking-related diseases

• Complicating co-morbidities: conditions that arise as a complication of a specific pre-existing disease—in the case of COPD, pulmonary hypertension and consequent heart failure.

• Co-incidental co-morbidities: Coexisting chronic conditions with unrelated pathogenesis that make COPD management more difficult.

• Inter-current co-morbidities: Acute illnesses that may have a more severe impact on patients with a given chronic disease. For example, upper respiratory tract infections have a more severe impact or require different treatment for patients with COPD (Rea et al 2004; GOLD 2006)

 

A relevant association among cardiovascular disease, lung cancer, asthma was found in a French study exploring deaths from COPD and the multiple underlying causes (Furhman et al, 2006). In this study, cardiovascular disease, ischemic heart disease, lung cancer and asthma were more likely to be the underlying cause of death when COPD was mentioned as an associated cause on the death certificate than when it was not. Cardiovascular disease (CVD) was described as a very common cause of death in patients with COPD in a study by Calverley and Scott (2006). The authors stated that, although smoking is a well-known risk factor for both COPD and CVD, CVD in patients with COPD is likely to be due to other factors in addition to smoking.

 

In another study, Gudmundsson et al (2007) performed an analysis of mortality in COPD patients discharged from hospital in Scandinavia, and highlighted that a lower health status (total SGRQ > 60) and diabetes have a negative effect on survival. In the WHO Large Analysis and Review of European Housing and Health Status (LARES) study by Boutin-Forzano et al (2007), different co-morbidities were found in association with reported chronic bronchitis and emphysema in the past year, namely: asthma, allergy, osteoporosis, hypertension, digestive ulcer, articular disorders, cataract, migraine, skin diseases, depression, up to diabetes, cerebral stroke, malignant tumour.

 

An increased incidence of a number of co-morbidities associated with COPD were reported also in a study of 45 966 COPD patients aged more than 39, with respect to an age- and gender-matched control group, in the framework of the Northern California Kaiser Permanente Medical Care Program, a comprehensive integrated health-care system (Sidney et al, 2005). These were diabetes, hypertension, obesity, stroke, hyper-lipidemia, ventricular tachycardia/ventricular fibrillation/cardiac arrest, atrial fibrillation, other arrhythmias, angina, MI, CHF, renal disease, pulmonary embolism (Table 5.8.2).

 

Table 5.8.2. Incidence of comorbidities in COPD patients with respect to a gender- and age-matched control group

 

 

In a study by Soriano et al (2005), the UK General Practice Research Database was used to compare incident COPD patients (physician diagnosed, n = 2,699) in 1998 with age, gender, time, and practice-matched cohorts . The total sum of diagnosis of incident COPD patients related to major organ systems was higher, and a frequency > 1% within the first year after diagnosis was pointed out for angina, cataracts, bone fractures, osteoporosis, pneumonia, and respiratory infections (RI). COPD patients were at high risk for pneumonia (relative risk (RR) = 16.0), osteoporosis (RR = 3.1), RI (RR = 2.2), MI (RR = 1.7), angina (RR = 1.7), fractures (RR = 1.6), and glaucoma (RR = 1.3) [all p < 0.05].

 

The Longitudinal Ageing Study Amsterdam by Kriegsman et al (2004), apart from observing that COPD was present in 10.4% of the 2497 subjects with different index diseases at baseline, showed that more than 2/3 of them (69.4%) reported one or more co-morbidity.

 

Moreover, a study on the prevalence of nutritional depletion (defined as body mass index (BMI) < 21 kg/m2 and/or fat-free mass index (FFMI) < 15 (females) or < 16 (males) kg/m2) in a large out-patient population of patients with COPD (389 patients) was performed in the Netherlands (Vermeeren et al, 2006). The results showed that the prevalence of nutritional depletion was high (27%), whereas the prevalence of normal BMI and low FFMI was 15%, and of low BMI and low FFMI 11%. Low BMI and low FFMI were significantly more frequent in female (18% and 40%) than in male COPD patients (10% and 20%). Moreover, depletion of FFM was associated to impaired peripheral muscle strength, irrespective of disease severity.

 

In another study, a small Danish population of patients affected by severe COPD was analysed and it was found that 68% of them had osteoporosis or osteopenia (Jorgensen et al, 2007). This increased prevalence of osteoporosis could not be explained by gluco-corticoid use alone, thus the Authors affirmed that a screening of patients with COPD would be helpful.

 

A study by Mikkelsen et al (2004) found that clinical significant symptoms of depression / anxiety are reported with prevalence rates reaching 47% . Moreover, in a study by Wagena et al (2004) smoker patients with asthma or COPD proved to be at higher risk of depression (OR 3.52, 95%CI 2.04 to 6.07) compared to non smokers..

 

COPD has some important negative effects on the health related quality of life (HRQoL) as shown in a Spanish population of about 10 700 COPD patients, with a mean age of 67 and an average FEV of 35.9 ± 10% (Carrasco Garrido, 2006). In a study by Sprenkle et al (2004), SF-36V was used in a large cohort of veterans who received care through the Upper Midwest Veterans’ Integrated Service Network with reported asthma or COPD. The results demonstrate that HRQoL is an independent predictor of mortality, hospitalization,and outpatient utilization in people with self-reported obstructive lung disease.

 

On these basis, some authors consider that COPD should no longer be judged as a disease only involving the lungs. Recently, Fabbri and Rabe (2007) proposed the additional term “chronic inflammatory syndrome” to underline the common pathogenetical substrates of COPD and its comorbidities.

 

Economic burden and health care utilization

 

Several studies focused on the economic aspect of COPD. The ERS European Lung White Book reported that the overall annual cost for COPD in Europe (excluding mortality and rehabilitation) was 38.7 billion Euro, of which 4.7 were for ambulatory care, 2.7 for drugs, 2.9 for inpatient care and 28.4 for lost work days (European respiratory Society, 2003). In EU15, 41 300 lost work days per 100 000 population are due to this disease; in Central and Eastern Europe lost work days due to COPD are 4300. with a global productivity loss of about €28.5 billion annually (European Respiratory Society, 2003).

 

 

The total costs of COPD in different countries (Spain, USA, Sweden, The Netherlands, Italy) were compared (Chapman et al 2006). It was shown that the estimates of direct annual costs per patient were about 1 200, 1 600 and 2 300 € in Spain and 150, 3 000, 3 900 in Italy, respectively for stage I, II and III of the diseases.

 

In the SCOPE study, performed in France, the average total medical cost of every COPD patient was estimated at 4,366 euro per year: 41% was directed to COPD follow-up, 25% to COPD complications and exacerbations, and 34% to other diseases, one-third of the total direct COPD cost was directed to hospitalisations and 31% to drug consumption (Detournay et al, 2004). Moreover, the costs increased in proportion to severity based on FEV1. The total medical cost for COPD patients in France was estimated at 3.5 billion euro, accounting for 3.5% of total medical expenditures. In other studies, average direct costs per patient were estimated to be 909€ in Spain (Masa et al, 2004) and 1 261€ in Italy.

 

An analysis of the Danish Patient Registry for patients admitted with COPD diagnoses in 1998-2002 showed that, considering the total cost for treatment of 40+ year patients, 10% was directed to treatment of COPD (Bilde et al, 2007). The net cost for COPD patients was 256 million euro (6% of the total). Only one third of these costs were due to the treatment of COPD as primary diagnosis, whilst the remaining two-thirds were mainly due to admissions for other diseases.

 

In Sweden, the largest expenditure for patients with FEV1 below 40% is represented by hospitalisation costs, accounting for about 60% of direct costs (Jansson et al, 2002).

 

A study on the burden of COPD and asthma was performed in the city of Dubrovnik during 2002-2006. COPD patients (446) were treated in hospital for 5073 days during a five-year period. The total cost was 544,547 Euro. Average length of stay in hospital was 11.37 days and the cost of treatment per patient was 1.017 Euro. It was found that all analysed parameters (number of patients, length of stay, cost of treatment) were higher for COPD than for asthma (Vrbica, 2007)..