Is the hypercapnic ventilatory respons in combination with the upper airway resistance of predictive value in COPD patients for having an OSAS?

Both obstructive sleep apnoea syndrome (OSAS) and chronic obstructive pulmonary
disease (COPD) are common diseases in the general population (2,3). Recent
epidemiological studies have shown that in developed countries the prevalence
of OSAS is about 4% of males and 2% of females in the age span of 30-60 years,
while COPD affects as much as 10% of the population above 30 years (7,13).
Previous studies reported prevalences of an airway obstruction in patients with
OSAS of 11- 41 % (12). In a study population of patients presented with COPD
the prevalence of OSAS was 10-15 % (12,13,23). These data suggest that an
overlap syndrome, first defined by Flenley to describe the association of OSAS
(apneu/hypopneu index > 20/hr) with COPD (FEV1/VC ratio < or = 70%), is widely
under diagnosed. One of the reasons for this may be the fact that in patient
with COPD the symptoms of their pulmonary disease mask the OSAS symptoms.
All healthy humans hypoventilate to a significant degree during normal sleep
and have diminished HCVR due to mechanical impairment. It is assumed that
central CO2 chemosensitivity remains unchanged (1,26).
De Backer et al have shown an increase in HCVR in patients with an overlap
syndrome and in normocapnic OSAS. In severe COPD however, chronic hypercapnia
is known to decrease CO2 chemosensitivity resulting in a diminished HCVR
(1,6,24,25,27).
We hypothesize that a diminished HCVR at rest is protecting against having an
OSAS. We postulate that patients with a mild COPD (FEV1 50-80%) and a normal or
increased HCVR are at risk for developing an OSAS.
A recent human study showed that circulating leptin, an adipocyte-derived
hormone,was elevated in hypercapnic patients and in patients with OSAS
(14,15,16,17). Recent animal studies suggest that leptin may be a powerfull
respiratory stimulant most likely by stimulation of central respiratory control
systems (HCVR) (15). Since we assume that COPD patients at risk for an overlap
syndrome have a normal or increased HCVR, we presume that they will have an
increased circulating leptin.
(Since there is a relationship between the decrease in leptin level and the
degree of improvement of nocturnal respiration, leptin could be a usefull
parameter for follow up (18,19).)
It is known that eucapnic OSAS patients have an increased airway resistance,
measured by IOS, only in supine position (20,21,22). We therefore think that
IOS is helpful in detecting the patients with COPD at risk for an OSAS. Mainly
by discriminating the upper airway resistance from the resistance in the lower
airways.

First question:
The first aim of this study is to test the following hypothesis:Is the
hypercapnic ventilatory respons in combination with the upper airway resistance
of predictive value for the risk of COPD patients to have an OSAS?
The second question:
Is there a difference in the beginning of the apnoe between the OSAS en overlap
group?

There will be three groups of 27 patients selected. Patients will be included
from out patients clinic.
One group will contain COPD Gold classification 2 or 3 , one group patients
with overlap syndrome en the third group will contain patients with OSAS.
For the first question the COPD group will be compared with the overlap group
to test the following hypothesis:
The HCVR and the UAR can predict the risk of a COPD patient to have an OSAS. We
expect the following differences:
-The HCVR is significant higher in the overlap population than in the COPD
group.
-The UAR measured by IOS and bodybox is significant higher in the overlap group.
For the second question the OSAS group will be compared with the overlap group
to test the following hypothesis:
The origin of an apnoe in a patient with overlap syndrome is significant more
central in comparison with the OSAS group.

The following investigations will be done:
-HVCR
-Lungfunction
-IOS
-Arterial bloodgas
-Leptine
-Questionnaires: ESS/Qol-RIQ, questions about professional situation
-polysomnography (somno-medics)
-weight, height, BMI, impedance measurement

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