Læknablaðið : fylgirit - 01.08.2002, Qupperneq 28

ABSTRACTS / 21 ST NORDIC CONGRESS OF ALLERGOLOGY
in infected animals and enabling survival due to slower immune
response. This immunosuppression could also account for the effect
on autoimmune reactions. The effect on different infectious agents
and the possible pathophysiological effect on the leukotriene meta-
bolism needs still further investigation.
R 4 - Linkage of asthma to chromosome 14q24:
“asthma gene one”
Hákonarson H, Björnsdóttir US, Stefánsson K
Asthma is a complex genetic disorder with a heterogeneous pheno-
type, largely attributed to the interactions among many genes and
between these genes and the environment. Numerous loci and
candidate genes have been reported to show linkage and associa-
tion to asthma and atopy. While some studies reporting these
observations are compelling, no asthma gene conferring high risk
has been mapped such that it meets stringent criteria for genome-
wide significance. We have performed a genome-wide scan with
976 microsatellite markers using 175 extended Icelandic families
with 596 asthma patients. The families were identified by cross-
matching a list of asthma patients from the Allergy/ Pulmonary
Divisions of the National University Hospital of Iceland with a
genealogy database of the entire Icelandic nation. We detected
linkage of asthma to chromosome 14q24 with an allele-sharing lod
score of 2.66. After increasing the marker density within the locus
to a microsatellite every 0.2 cM on the average, the lod score rose to
4.00. We designate this locus, asthma locus one (ASl). Taken
together, these results provide evidence for a novel susceptibility
gene for asthma on chromosome 14q24.
R 5 - Asthma - Gastroesophageal Reflux, Sleep
and Obesity
Gíslason Þ
Based on recent epidemiological data from the European Com-
munity Respiratory Health Survey (ECRHS) newly developed
asthma is often associated with female gender and obesity. Similar
results have been reported from Canada (1) and decreased physical
activity does not explain the association of new asthma to weight
gain (2).
Both gastroesophageal reflux (GER) and obstructive sleep
apnea syndrome (OSAS) increase in prevalence with increased
body weight. GER has been associated with respiratory symptoms
and many studies have shown a high prevalence of GER among
patients with asthma (3,4). In a recent report even asthmatics with-
out reflux symptoms had a high prevalence (62%) of abnormal 24-h
esophageal tests (5). The relationship between GER and respiratory
symptoms has primarily been assessed in highly selected popula-
tions at secondary or tertiary referral hospitals. There are few epi-
demiological studies in the general population and little is known
about a possible association between sleep, GER and respiratory
symptoms in an unselected random population.
Between 1990 and 1993 the ECRHS was conducted in different
centers throughout the world (6). In four of the parlicipating
centers - Reykjavik Iceland, Uppsala and Göteborg, Sweden, and
Antwerp, Belgium - a questionnaire relating to sleep disturbances
was added to the second part of the ECRHS study (7-9). Altogether
2,202 subjects (20-48 years) were randomly selected from the
general population in addition to 459 with reported asthma (10).
The investigation also included a structured interview, spirometry,
methacholine challenge, peak flow diary and skin prick tests. In the
random population sample, 101 (4.6%) subjects reported GER
defined as heartburn or belching after retiring to bed at least once
per week. Subjects with GER were more often overweight and had
more frequent symptoms of sleep disordered breathing than
participants not reporting GER. Participants with GER were more
likely to report wheezing (adjusted odds ratio [OR] = 2.5), breath-
lessness at rest (OR = 2.8), nocturnal breathlessness (OR = 2.9) and
had increased peak flow variability compared to the subjects
without GER. Physician diagnosed current asthma was reported by
9% of subjects with GER compared to 4% of those not reporting
GER (p<0.05). Subjects with the combination of asthma and GER
had a higher prevalence of sleep-related symptoms like snoring,
daytime sleepiness etc than subjects with asthma alone (10).
Based on available data, it is possible that episodes of upper
airway obstruction during sleep are associated with large intra-
thoracic/esophageal negative pressures swings (11), which result in
an increased transdiaphragmatic pressure gradient, and may, at
least in theory, lead to regurgitation of gastric acid into the eso-
phagus. Such sleep-related GER could potentially cause respira-
tory dysfunction, bronchoconstriction, coughing, wheezing, laryn-
gospasm and sleep disturbance. If the strong association we find
between OSAS and GER is confirmed by others, traditional
evaluation and treatment of asthmatic/OSAS patients may change.
Therapeutic trials with continuous positive airway pressure (CPAP)
may be indicated. This is especially true in complex cases with
combined OSAS, GER and resistant respiratory symptoms. Recent
studies reporting that CPAP reduces GER in OSAS (12), that
swallowing reflex is improved after CPAP (13) and that CPAP even
improves the control of asthma (14) support this approach. A
therapeutic trial with a potent proton inhibitor should be con-
sidered in patients with resistant asthma, even in subjectsnot having
GER or OSAS symptoms.
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