Association between socioeconomic status, sex, and age at death from cystic fibrosis in England and Wales (1959 to 2008): cross sectional study

Limitations

The findings of this study depend on the accuracy of the initial diagnosis of cystic fibrosis and satisfactory completion of death certificates including the documentation of a diagnosis of cystic fibrosis. The extent of under-diagnosis of cystic fibrosis in the early years of this study is not clear. In addition, improved diagnostic techniques have led to increased recognition of milder phenotypes which will affect the outcome variable measured. From 1959 to 1967, the International Classification of Diseases category applying to cystic fibrosis included other disease of the pancreas and might therefore include deaths without a diagnosis of cystic fibrosis.29 However, we have previously estimated that less than 2% of deaths are probably misclassified in this way, and this proportion is therefore unlikely to affect the overall findings of our study.1 The consistency of the associations observed supports this estimate. Furthermore, improved diagnostic techniques in the later study years may have enhanced the recognition of mild phenotypes of cystic fibrosis, which could have contributed to the increased rate of survival observed, although this factor probably does not account for the differences in sex or socioeconomic status.

Due to confidentiality constraints, we used age at death as the midpoint of every five year age band, which could have underestimated the association between socioeconomic status and sex with median age at death. The use of the median age of death was necessary for statistical comparisons between groups, but this is a broad summary statistic that will not reflect a wide spread in ages at death within each year. The data available to us did not provide sufficient power to compare the interaction by study decade of death on the association between age of death and socioeconomic status or sex. However, the similar odds ratios with overlying confidence intervals for the first and last study decades indicate that the magnitude of these associations does not appear to have reduced substantially over time.

We defined socioeconomic status according to occupation from 1959 to 2000 using the Registrar General’s Social Class. In 2001, implementation of the internationally recognised and validated35 National Statistics Socioeconomic Classification made longitudinal trend comparisons difficult. The availability of socioeconomic status data also varied throughout the study period, with over half of deaths (51%) between 2001 and 2008 coded as unclassified, compared with 28% between 1959 and 2000 (when socioeconomic data were available). Since the definition of unclassified socioeconomic status encompasses a broad cross section of society, such as those adults who were permanently sick, were in long term unemployment, or had never worked to adults in full time education, this represents a limitation of our data.

We saw an increased risk of death above the annual median age of death for the unclassified socioeconomic group from 1959 to 1989; after this time the risk decreased, suggesting that the composition of this group changed over the past half century and possibly reflecting societal change. However, we do not consider that this finding changes the validity of our comparisons between those individuals who could be allocated to a defined social category. We have presented the raw data in two ways, as graphical representations of the annual data and as statistical comparisons of survival by sex and socioeconomic status using data roughly stratified in decades to permit sufficient numbers for comparison. The annual data can show trends over time, although relatively small numbers of events per year prevent conclusions being drawn over short periods of time. Finally, owing to improved survival, the lag time between the implementation of healthcare changes and median age at death is inevitably increasing. Consequently, these results reflect historical healthcare management, and the results of current healthcare strategies, particularly those aimed at younger patients, will not have filtered into the mortality figures yet.

Sex

Most studies have shown that females are associated with worse outcomes than their male counterparts.24 25 27 28 However, the cause of the sex gap remains unclear. Several studies suggest that female preponderance for early acquisition of P aeruginosa might have a role.20 26 Demko and colleagues20 showed that females became infected with chronic mucoid P aeruginosa an average of 1.7 years earlier than their male counterparts. Other studies have suggested that increased occurrence of cystic fibrosis-related diabetes,36 reduced activity levels,37 poor mental health,38 poor nutritional status,27 and oestrogens39 40 could contribute to the difference between males and females.

Socioeconomic status

The association between poor socioeconomic status and increased mortality in individuals with a diagnosis of cystic fibrosis is well established.1 22 23 These socioeconomic health disparities have been shown in both the universal healthcare system in the United Kingdom and the predominantly private based care system in the United States. In 1998, Schechter and colleagues41 reported that Medicaid patients (a marker of low income in the United States) had worse lung function and lower body mass index and required more hospital admissions than their socioeconomically advantaged counterparts. In 2008, Balmer and colleagues42 found that socioeconomically disadvantaged children with cystic fibrosis in the United States had poorer growth, lower lung function, and more days off school than socioeconomically advantaged children. However, the cause of this socioeconomic health gap is poorly understood. Low socioeconomic status has been associated with increased environmental exposure to tobacco smoke,43 inadequate nutrition,22 little understanding of the underlying disease,44 45 and poor treatment adherence.41

It is difficult to determine what role these individual factors have because social class is a composite measure that incorporates income, education, and occupation. It is clear, however, that socioeconomic status may affect childhood health from an early age. Phenotypical differences between high and low socioeconomic groups have been found in children with cystic fibrosis as young as 6 years, and these disparities persist into adulthood.23 41 However, reverse causation could complicate the association between low socioeconomic status and increased mortality. Individuals with cystic fibrosis are more likely to leave school without any qualifications than the general population and therefore less likely to have professional occupations, and this difference is increased in individuals with severe underlying disease.46 Conversely, individuals with cystic fibrosis who are in employment are more likely to have non-manual occupations than the general population,46 perhaps because they are less able to fulfil more physically demanding work. Since our data from recent years cover deaths in a mainly adult population, we cannot exclude the possibility that these factors might contribute to our observations of differences in mortality between socioeconomic groups.

Provision of care

Over the past few decades, increasing awareness of the complexity of cystic fibrosis disease management has led to the formation of specialist centralised centres. Specialist treatment centres are widely considered to provide the best standard care for patients13 47 48 and are endorsed by regulatory bodies in the United Kingdom,49 50 United States,51 52 and Australia.53 Consequently, the proportion of patients accessing specialist care has risen over the past 20 years.54 55 However, direct evidence supporting improved clinical outcomes in specialist cystic fibrosis centres is limited and most studies have been confounded by sample size6 56 57 or by comparison with historical controls.58 Mahadeva and colleagues47 reported that patients who attended specialist centres in Manchester had higher body mass indexes, higher chest radiograph scores, and better pulmonary function than patients in Cambridge who did not receive any centralised care. However, direct comparisons between different regions may be confounded by environmental factors59 and socioeconomic status.1

Inequalities in access to specialist cystic fibrosis services have shown marked regional variations.4 Patients receiving care at specialist centres generally travel further than those attending local clinics and, although not a universal finding,23 41 60 some studies have shown that socioeconomically disadvantaged individuals have limited access to specialist care, particularly to adult services,4 61 in the United Kingdom. Accordingly, the proportion of patients from socioeconomically advantaged backgrounds is over-represented at some specialist centres.61

A possible interpretation of our data is that new specialist treatment centres in the United Kingdom might have been preferentially accessed by individuals with the highest socioeconomic status, which could account for some of the socioeconomic discrepancy seen during the late 1980s and early 1990s. Alternatively, the highest socioeconomic groups could be better informed and hence obtain better healthcare when attending clinic. The observation by Schechter and colleagues60 that children living in affluent areas or with well educated mothers were more likely to receive macrolides in 2004, one year after a landmark study was published,62 would support the latter hypothesis. Our data also showed that individuals in the unclassified socioeconomic group had a poorer outcome than any other category over the past two decades. This heterogeneous category included individuals who were permanently sick, long term unemployed, or receiving incapacity benefits. The severity of the underlying disease and reverse causation could have been contributing factors. However, this category might represent the lowest socioeconomic group in society, including individuals who struggle to access timely healthcare.

Summary

We report nationally representative data that suggest that the socioeconomic and sex differences in age at death from cystic fibrosis that we first reported in 1989 persist to the present day, in the context of a large improvement in survival in this patient group over the past half century. Healthcare workers should be aware that females and low socioeconomic status are associated with poorer outcomes than males and high socioeconomic status. Environmental factors or varying access to healthcare might account for some of these differences.