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Highlights from the 14th Annual Congress of the European Respiratory Society in Glasgow, September 2004

By Dr Hetty van Dijk, IPCRG web editor
September 2004

Pneumonia contracted in the community: big disparities in hospitalisation costs in France, Germany, Japan and the USA
With the explosion in healthcare costs facing developed countries, it makes sense to analyse factors affecting healthcare costs in different countries. This was the task undertaken by a multinational team led by Albrecht Neiss of Munich Technical University (Germany), for a specific respiratory condition, namely community-acquired pneumonia (contracted outside hospital), which affects between five and eleven adults per 10,000 in the USA and is a major cause of morbidity and mortality worldwide. The study analysed retrospectively, over a one-year period, data on 2,183 patients hospitalised for the condition in France, Germany, Japan and the USA.

The figures Neiss presented in Glasgow do show a substantial disparity in hospitalisation costs for the different countries, since the average cost of the hospital stay was almost four times as much in one country as in another. One should bear in mind, though, that direct comparison of these costs must be interpreted carefully as each countries allocation and use of healthcare resources vary dramatically.

Since the length of the hospital stay varies, one could first think that there is a connection between average cost and average duration. On the contrary, the USA, which is highest in terms of cost (with an average stay costing the equivalent of 14,347 euros), is also the country with the shortest average stay (at 8.7 days). Conversely, the average cost of a hospital stay is lowest in Germany, at 3,892 euros, though Germany also has one of the longest average stays, lasting 14.0 days. Japan beats it on that score, though, since the average stay there is no less than 17.2 days, costing the equivalent of 6,637 euros on average. As to France, where the average length of stay at 11.2 days is the shortest after the USA, the average cost is only half that across the Atlantic, at 5,923 euros.

"Given the differences in reimbursement of medical costs in the different countries, we cannot completely explain such large differences", Neiss cautioned in Glasgow. "But when we analyse ward data for the hospitals where the patients where admitted, this might provide an interesting clue. It's the USA and France, the two countries with the highest daily costs, that keep their patients in the emergency room or in the intensive care unit the longest, and those wards are probably the most costly". Conversely, we see that most of the hospital stays in Japan and Germany were on general wards, which have lower daily costs.

The international team, which included researchers from each of the countries in the study, also examined the influence that risk factors could have on hospitalisation costs. Here, Neiss and his colleagues focused on Japan and Germany, two countries where reimbursement by social security depends on the seriousness of the illness and its development over the course of the hospital stay, and not simply on the admission diagnosis, like fixed-sum reimbursement schemes.

They identified three factors that tended to increase cost: the existence of other conditions (co-morbidity), recourse to a combination of several antibiotics and above all, initial prescription of an inappropriate antibiotic. "Prescription of a suitable antibiotic from the start can cut hospitalisation costs considerably", Neiss emphasised in Glasgow. "We show that this factor is systematically associated with shorter hospital stays".

In conclusion, Neiss explained that the prescribed antibiotic treatment needs to cover the entire range of pathogens known to be responsible for community-acquired pneumonia, including resistant strains. And, on the subject of resistance, it is essential that the first choice of antibiotic take into account local rates of resistance to commonly prescribed antibiotics, and that guidelines from infectious disease specialists are implemented.

Atherosclerosis is exacerbated by sleep apnoea
Two clinical studies, conducted in Slovakia and Italy, may explain the link between sleep breathing disturbances and cardiovascular disease.

Primary preventive cardiac health care is increasingly resorting to ultrasound measurement of the thickness of arterial walls, principally in the carotid and femoral arteries. It is known that the thickness of the internal layers (intima-media) of the arteries provides a reliable reflection of the size of the fatty deposits typically found in atherosclerosis and thus represents a good indicator for this cardiovascular risk factor.

This non-invasive and relatively inexpensive test has also been found to fit with several emerging cardiovascular risk factors (such as stress, homocysteinemia and a sedentary lifestyle), and so it is now considered an integral part of quality cardiovascular screening.

Moreover, sleep apnoea - characterised by frequent nocturnal interruptions to breathing - has been found often to be associated with an exacerbation of cardiovascular disease and even to increase mortality rates among affected stroke victims. The two studies, showing that apnoea is more frequently found in combination with arterial deposits, could prove an explanation for this link between sleep apnoea and cardiovascular disease.

The first study was undertaken by a team led by Viliam Donic, of Kosice University Hospital, Slovakia. It included 78 patients, of whom 52 presented with moderate sleep apnoea. The apnoea was identified objectively using classical nocturnal polysomnography, the current golden standard, which involves simultaneous recording of respiratory, cardiac, brain and blood parameters. The thickness of the intima-media was measured by standard Doppler ultrasound scanning of the carotid arteries, on both sides of the neck.

The Slovakian team then correlated the severity of the subjects' atherosclerosis with the presence or absence of apnoea. The results show clearly that subjects who already suffered either from hypertension or from cardiovascular disease had markedly more severe atherosclerosis when they had also sleep apnoea (0.9mm compared to 0.8mm). "An intima-media of more than 0.85mm is considered to represent coronary sclerosis", emphasised Donic. More alarmingly still, when Donic and his colleagues compared patients with no apparent cardiovascular disease, they found an even greater difference between apnoeic and non-apnoeic subjects (0.83mm compared to 0.67mm).

The Italian team working under Flaminio Mormile, of the Catholic University of the Sacred Heart in Rome, has reached similar conclusions following a study that conducted carotid ultrasound on 29 patients newly diagnosed with sleep apnoea who had not yet been treated for the condition. Mormile presented results showing that in these patients atheromatous deposits over 1.22mm were associated with a large number of nocturnal interruptions to breathing (apnoea-hypopnoea index of 47.2 +/-24) while cases with an intima-media of 1.05mm or less had, on average, less severe sleep apnoea (29.3 +/-11) once other cardiovascular risk factors were taken into account. "An interesting but surprising fact", Mormile noted, "is that patients who, in our study, presented this strong link between apnoea and atherosclerosis, were found to have a normal blood oxygen concentration".

Whatever the reason, and even though the mechanisms linking atherosclerosis to severity of apnoea remain hypothetical (possibly activation of the sympathetic nervous system, oxidative stress or excessively sudden changes in blood oxygen concentration), these two studies are sure to lead to a practical outcome.

As regards prevention, they can be expected to lead to more active investigation of sleep apnoea in everyday practice and, for sufferers, to ultrasound measurement of the degree of atherosclerosis in the carotid or femoral arteries.

On the treatment level, meanwhile, they open up possibilities for apnoea treatment (for example, using positive pressure ventilation, now established as the standard) to provide an additional benefit by limiting atherosclerosis and its consequences.

The neonatal period, asthma and obesity
Asthma and obesity, which are often associated, may have a common origin in the neonatal period, according to a British team. And a prospective study from the Netherlands shows that 19-year-olds who were born prematurely or with low birth weight are more frequently affected by respiratory problems than those who were carried to term.

A team led by Jane Lucas, of Southampton University, may have found the key to why asthma and obesity so often present together. The British team measured various lung function parameters in 131 children, 66 boys and 65 girls aged from five to fourteen weeks, carried to term but some of them with a birth weight below the norm. They also recorded the speed with which the babies gained weight.

By comparing the various values, adjusted for age and sex, Lucas and her colleagues discovered that it was the speed with which babies gained weight, rather than low birth weight, was associated with reduced respiratory capacities. The babies' expiratory function dropped by 11% every time that the baby's weight increased by a standard deviation, while respiratory frequency simultaneously increased by 5.1%.

"This is the first time that such a link has been identified between weight gain in the weeks following birth and deterioration in lung function", announced Lucas in Glasgow. It is unlikely that different types of feeding could be responsible for this effect, since similar lung function was found in breast-fed and bottle-fed babies. "We are more inclined to think that the post-natal weight gain of some babies could represent a catching-up process, a consequence of growth retardation in the later months of pregnancy.

That would mean that the foetus' lungs had not reached their normal dimension, which would contribute to damaging lung function", Dr. Lucas stated. It is also possible that the post-natal weight gain itself affects babies' lung function. That would fit with the fact that obesity and asthma are often associated and babies with a low birth weight gain weight more quickly than others and are more prone to subsequent obesity.

The same catch-up effect is at the centre of the second study, presented by Elianne Vrijlandt and her team, of the Beatrix Children's Hospital in Groningen (Netherlands). This wide-ranging prospective study, undertaken over an exceptional period of 19 years, from 1983, covered 690 babies born at less than 32 weeks' gestation or whose birth weight was below 1.5kg. This cohort represented almost three-quarters of the premature babies born that year in the Netherlands who survived the initial hospital stay.

The results of this study show that, in addition to conditions directly related to prematurity such as neonatal respiratory distress syndrome (RDS), babies born prematurely had a significant reduced respiratory health in adult life.

"Our study shows that those born prematurely are more frequently afflicted by wheezing than other young adults (25.3% against 20.4%), particularly when they have a cold, and they are more likely to complain of shortness of breath on exertion (20.8% against 13.1%)", explained Vrijlandt. "But the comparisons are particularly striking where asthma is concerned. Both for asthma attacks in the past 12 months and for the general prevalence of asthma, the rates are approximately three times higher among people born prematurely".

This increased vulnerability among those born prematurely could be connected with a poorer development of the respiratory tract in the first weeks of life. Airway diameter could be smaller in that group, which would favour bronchial constriction and hyperreactivity.

Yet people born prematurely seem to have a very strong protection against allergy-related conditions: they were found to be only half as likely to have hay fever as the control subjects (8.7% against 18.7%) and less than a quarter as likely to have eczema (8.9% against 36.2%). The Netherlands team explains this by reference to what has become known as the hygiene hypothesis: the premature babies probably suffered more infections in their early years because of their fragile immune systems. This fragility, paradoxically, may have contributed to protecting them against the development of certain allergic conditions.

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