A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population.

The genetics of asthma and atopy have been difficult to determine because these diseases are genetically heterogeneous and modified by environment. The pedigrees in our study (n=86) originate in eastern central Finland (Kainuu province). According to census records, this region had only 200 households (2,000 inhabitants) in the mid sixteenth to mid seventeenth centuries. The current population of 100,000 represents the expansion of these founders within the past 400 years. Because this population is relatively homogeneous, we hypothesized that the molecular genetic mechanisms underlying asthma might also have reduced heterogeneity and therefore be easier to dissect than in mixed populations. A recent twin family study supported a strong genetic component for asthma in Finland. We carried out a genome-wide scan for susceptibility loci in asthma in the Kainuu subpopulation. We identified two regions of suggestive linkage and studied them further with higher-density mapping. We obtained evidence for linkage in a 20-cM region of chromosome 7p14-p15 for three phenotypes: asthma, a high level of immunoglobulin E (IgE; atopy) and the combination of the phenotypes. The strongest linkage was seen for high serum IgE (non-parametric linkage (NPL) score 3.9, P=0.0001), exceeding the threshold for genome-wide significance based on simulations. We also observed linkage between this locus and asthma or atopy in two independent data sets.

Smoking strongly predicts disability retirement due to COPD: the Finnish Twin Cohort Study.

No previous studies on the association of smoking behaviour with disability retirement due to register verified chronic obstructive pulmonary disease (COPD) exist. This 30-yr follow-up study examined how strongly aspects of cigarette smoking predict disability retirement due to COPD. The study population consisted of 24,043 adult Finnish twins (49.7% females) followed from 1975 to 2004. At baseline the participants had responded to a questionnaire. Information on retirement was obtained from the Finnish pension registers. Smoking strongly predicted disability retirement due to COPD. In comparison to never-smokers, age adjusted hazard ratio (HR) for current smokers was 22.0 (95% CI 10.0-48.5) and for smokers with ≥ 12 pack-yrs was 27.3 (95% CI 12.6-59.5). Similar estimates of risk were observed in within-pair analyses of twin pairs discordant for disability retirement due to COPD. Among discordant monozygotic pairs those with disability pension due to COPD were more often current smokers. The effect of early smoking onset (< 18 yrs) on the risk of disability retirement due to COPD remained after adjustment for the amount smoked (HR 1.70, 95% CI 1.08-2.68). Smoking strongly predicts disability retirement due to COPD. Preventive measures against disability retirement and other harmful consequences of tobacco smoking should receive greater emphasis.

Chronic bronchitis and chronic obstructive pulmonary disease. The Finnish Action Programme, interim report.

The Finnish National Prevention and Treatment Programme for Chronic Bronchitis and COPD, launched in 1998, has, to date, been running for 6 years (2003). The goals of this action programme were to reduce the incidence of COPD and the number of moderate and severe cases of the disease, and to reduce both the number of days of hospitalisation and treatment costs. A prevalent implementation of over 250 information and training events started. Health centres and pharmacies appointed a person in charge of COPD patients. In order to improve the cooperation between primary and specialised care, two thirds of hospital districts created local COPD treatment chains. The early diagnosis of COPD by spirometric examination was activated during the programme. Number of health centres with available spirometric services increased to 95%. Before the start of the programme, approximately 5-9% of the adult population had COPD. During the whole programme, the proportion of male and female smokers decreased from 30% to 26% and from 20% to 19%, respectively. The total number of hospitalisation periods and days due to COPD decreased by 15% and 18%, respectively. Both the number of pensioners and daily sickness days due to COPD also decreased by 18%. Registered COPD induced deaths remained at their previous levels during the monitoring period, i.e. around 1000 deaths out of 5.2 millions annually. The measures recommended by the programme have been widely introduced but they need to be still more effective.

Predictors of lung function and its decline in mild to moderate COPD in association with gender: results from the Euroscop study.

BACKGROUND: There is increasing appreciation of gender differences in COPD but scant data whether risk factors for low lung function differ in men and women. We analysed data from 3 years follow-up in 178 women and 464 men with COPD, participants in the Euroscop Study who were smokers unexposed to inhaled corticosteroids. METHODS: Explanatory variables of gender, age, starting age and pack-years smoking, respiratory symptoms, FEV(1)%FVC and FEV(1)%IVC (clinically important measures of airway obstruction), body mass index (BMI), and change in smoking were included in multiple linear regression models with baseline and change in post-bronchodilator FEV(1) as dependent variables. RESULTS: Reduced baseline FEV(1) was associated with respiratory symptoms in men only. Annual decline in FEV(1) was not associated with respiratory symptoms in either men or women, and was 55 ml less in obese men (BMI 30 kg/m(2)) than men having normal BMI, an effect not seen in women. It was 32 ml faster in women with FEV(1)%FVC

Effect of posture on spontaneous and thermally stimulated cardiovascular oscillations.

STUDY OBJECTIVE: The aim of the study was to investigate the effect of posture on thermally stimulated cardiovascular oscillations. DESIGN: The effect of increased gravitational stress (rising from sitting to standing position) on the thermally stimulated cardiovascular oscillations was measured in young male volunteers. Extensive cardiovascular function data were obtained using a cardiovascular investigation protocol. SUBJECTS: The volunteers were five fit young men, aged 20-21 years. EXPERIMENTS AND MAIN RESULTS: Cardiovascular changes from sitting to standing indicated increased sympathetic and decreased parasympathetic influence on heart and skin blood vessels; mean heart rate increased, beat to beat heart rate variability diminished, high frequency periodic heart rate variability decreased, low frequency heart rate oscillations and ratio of low frequency to high frequency heart rate variability increased, mean skin blood flow and oscillations of skin blood flow decreased (all p less than 0.05). Thermal skin stimulation at 0.01-0.10 Hz frequency increased both sitting and standing 0.10 Hz periodic heart rate variability (p less than 0.05), and 0.10 Hz thermal stimulation entrained the heart rate oscillations in sitting and standing subjects (p less than 0.05). In contrast, skin blood flow oscillations in sitting subjects decreased, while in standing subjects it increased during 0.10 Hz thermal stimulation compared to the corresponding prestimulus values (p less than 0.04). CONCLUSIONS: On the basis of previous physiological experiments, these results suggest coupling between thermoregulatory and 0.10 Hz reflex activities.

Clinical testing of thermally stimulated cardiovascular oscillations in man.

STUDY OBJECTIVE: The study assessed the physiological validity of an automatic thermal stimulation method to induce synchronised oscillations in the neural cardiovascular control system. DESIGN: Automatic alternating rhythmic warm and cool immersion of different skin areas of 18 males was done at different frequencies and water temperatures. The neurally mediated responses to the periodic thermal stimulation were measured from skin blood flow and heart rate and compared to those of a sham stimulation. Respiration was monitored for control purposes. The reproducibility of the stimulation and responses was examined. SUBJECTS: 18 young males volunteered for the study. MEASUREMENTS AND MAIN RESULTS: The water bath method produced reproducible thermal stimulation and responses of skin blood flow and heart rate. Rhythmic thermal stimulation at 0.013-0.096 Hz synchronised the oscillations of the forearm skin blood flow when the thermal stimulus amplitude exceeded 10 degrees C. The increase in the stimulus amplitude or enlargement of the stimulus area did not further increase the oscillatory response of skin blood flow. Sham stimulation or mean temperature of the periodic thermal stimulation in the range 23-33 degrees C did not influence the oscillations of skin blood flow. Local cooling of the stimulated lower legs attenuated the response of skin blood flow. Both thermal stimulation and sham stimulation affected heart rate, but no stable synchronisation of the periodic heart rate variability was found at supine rest. Thermal stimulation of the sitting subjects' forearm instead of legs increased the synchronisation of the periodic heart rate variability. CONCLUSIONS: The response of skin blood flow agreed with the theory of the thermal entrainment. In a supine man, both thermal stimulation and non-specific central nervous influences induced significant and reproducible interactions with periodic heart rate variability and respiration.

A non-invasive method for testing neural circulatory control in man.

Exaggerated cardiovascular responsiveness is common in young men and may cause non-specific symptoms and poor performance. Conventional autonomic function tests are not clinically useful. We have therefore designed a thermal entrainment method to evaluate sympathetic and parasympathetic cardiovascular function in subjects with dystonic symptoms and orthostatic intolerance. Oscillations of thermal gradient in the skin were produced by standardised periodic stimulation of the lower part of the arm with warm and cool water. Vasomotor activity of the skin induced oscillations of arterial blood pressure which were thought to be regulated by sympathetic and parasympathetic heart rate control and by oscillation of the sympathetically controlled peripheral vascular resistance. We tested the method in subjects with cardiovascular symptoms (n = 7) and controls (n = 7). At supine rest, the frequency response of the heart rate variability to the thermal stimulation at frequencies of 0.01, 0.02, 0.03 and 0.1 Hz was significantly different (p = 0.008) between symptomatic subjects and controls. The gain of the heart rate control was increased to 0.03 Hz [-1.3(SEM 0.5) dB v -3.8(0.8) dB, p = 0.068] and decreased at 0.1 Hz [-3.9(1.1) dB v -1.5(0.6) dB, p = 0.076] in the test group compared to the control group. At stimulus frequencies of less than 0.03 Hz the individual overall heart rate variability of the subjects with symptoms stayed below the mean control value, at 60(6) ms v 79(15) ms, p = 0.16. The cutaneous temperature oscillations at the site of stimulation, frequency response of the oscillations of the skin blood flow and respiration to the thermal stimulation, and mean heart rate were similar in the both groups. The results show that this thermal entrainment method quantifies the increased sympathetic and decreased parasympathetic cardiac control of subjects with dystonic symptoms.

The IL9R region contribution in asthma is supported by genetic association in an isolated population.

Interleukin 9 (IL9) is involved in mast cell maturation and the enhancement of IgE production by B cells. Furthermore, linkage data in human and mice have suggested that IL9 may contribute to asthma. Since our genetic analysis of the 5q cytokine cluster did not support a genetic role for the IL9 gene, we became interested in the IL9 receptor gene (IL9R) in the pseudoautosomal region. We genotyped markers sDF2 and sDF1 close to the IL9R gene among 289 affected and 368 family-based controls. The results were studied by using linkage, transmission disequilibrium, association and homozygosity analyses. Linkage analyses remained negative, presumably because of our low power for linkage study. However, all the other analyses yielded evidence that the IL9R gene region may have a role in the development of asthma. The sDF2*10 allele was more frequently transmitted than untransmitted to asthmatic offspring (34 vs 16, pchi2 < or = 0.01), and it was found homozygotic among asthma patients more often than expected (Psimul2 = 0.009). Also, a specific X chromosomal haplotype, sDF2*10-sDF1*6 associated with asthma (40 vs 7, Pchi2 < 0.005, Psimul1 = 0.04).

Exercise alters the pharmacokinetics of midazolam.

Six healthy volunteers received 15 mg midazolam, 50 mg ephedrine, or placebo orally before a 50-minute aerobic treadmill exercise and in a control session. Plasma drug concentrations for pharmacokinetic calculations were estimated from samples drawn up to 24 hours after drug intake. Heart rate, blood pressure, critical flicker fusion test, Maddox wing test, and visual analog scales relating to mood and feelings of tiredness were included in the sessions as pharmacodynamic measures. These tests were made at 35, 55, and 75 minutes and at 2, 2 1/2, 3 1/2, and 5 hours after drug intake. Exercise impaired the absorption of midazolam and counteracted the midazolam-induced decrement in flicker fusion threshold. Whether the effect on flicker fusion was caused mainly by the pharmacokinetic changes or by a general alerting effect of exercise cannot be verified by this experiment. The kinetics of ephedrine was not affected by exercise, but exercise enhanced the tachycardic response to ephedrine and abolished its pressor effect.

Plasma high density lipoproteins HDL2, HDL3 and postheparin plasma lipases in relation to parameters of physical fitness.

A number of studies has shown that the plasma levels of high density lipoprotein (HDL) are increased by regular aerobic exercise. The plasma HDL, particularly HDL2, is regulated by the activity of 2 endothelial lipases, viz. lipoprotein lipase (LPL) and hepatic lipase (HL), which both can be assayed in postheparin plasma. In the present study the plasma levels of HDL2 and HDL3 cholesterol and the postheparin plasma lipase activities were related to parameters of physical fitness obtained from a pulse conducted maximal bicycle ergometer test. There was a significant positive correlation between HDL2 cholesterol and physical fitness (r = 0.52, P less than 0.01). On the other hand, the postheparin plasma hepatic lipase activity showed a significant negative correlation to physical fitness (r = -0.57, P less than 0.01). The HDL2 cholesterol was inversely correlated with the HL activity (r = 0.57, P less than 0.001). Application of partial correlation analysis to the data showed that the relationship between HDL2 cholesterol and fitness disappeared by keeping the HL activity constant whereas the correlation between HDL2 and HL was not influenced by fitness. The relation of HDL2 to fitness was independent in body fat and basal plasma insulin level; in addition the relationship between HL and fitness was not accounted for by body fatness. No relationship was found between physical fitness and LPL activity or between HDL3 and fitness. The results support the hypothesis that hepatic endothelial lipase has a role in the regulation of plasma HDL2 cholesterol and that the activity of this enzyme decreases upon increase of physical fitness.

Dose-related effects of pharmacological mediators on tracheal vascular resistance in dogs.

1 Various doses of mediators were tested on tracheal vascular resistance in dogs anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures. 2 All drugs produced dose-related changes in vascular resistance. 3 The peptides bradykinin, substance P and vasoactive intestinal peptide (VIP) each had similar vasodilator potencies and were much more powerful than histamine, methacholine and salbutamol. 4 Platelet activating factor (Paf) was a weaker dilator than the peptides. Prostaglandins D2, E1 and F2 alpha had wide dilator potency ranges, PGE1 being very effective even at low concentrations. 5 Phenylephrine, an alpha-adrenoceptor agonist, was the only drug tested that always increased vascular resistance. 6 All the drugs studied also had effects on the contralateral tracheal vascular resistance.

Incidence and prevalence of asthma among adult Finnish men and women of the Finnish Twin Cohort from 1975 to 1990, and their relation to hay fever and chronic bronchitis.

STUDY OBJECTIVES: To examine the prevalence of asthma and hay fever, and the incidence and temporal relationships of asthma, hay fever, and chronic bronchitis among adult twins during a 15-year period. DESIGN: Prospective cohort study. PARTICIPANTS: A population of 11,540 Finnish adult men and women, initially 18 to 45 years of age, who returned a health questionnaire in 1975, 1981, and 1990 as part of the Finnish Twin Cohort study. METHODS: Age-standardized prevalences and cumulative incidences among individuals were calculated for asthma, hay fever, and chronic bronchitis. The incidence of asthma among subjects with and without hay fever or chronic bronchitis was analyzed in the entire cohort as well as in twin pairs discordant for incident asthma. RESULTS: The prevalence of asthma increased slightly from 1975 (2.0% in men and 2.2% in women) to 1990 (2.9% in men and 3.1% in women). The prevalence of hay fever showed a larger increase in men and women (from 6.8% and 9.8% to 11.8% and 15.3%, respectively). Compared with figures for 1976 to 1981, no significant increase in asthma incidence occurred from 1982 to 1990, whereas the incidence of hay fever was lower during the latter period among men (incidence rate ratio, 0.7; 95% confidence interval, 0.6 to 0.9) as was the incidence of chronic bronchitis among women (incidence rate ratio, 0.7; 95% confidence interval, 0.6 to 0.9). Hay fever and chronic bronchitis were usually diagnosed before asthma. Both diseases increased the risk of asthma significantly on the basis of analyses of all individuals and of discordant twin pairs. CONCLUSIONS: The pattern of increase in asthma and hay fever prevalence with time was similar, and hay fever was a strong predictor of asthma. These diseases showed no significant increase in incidence.

Sleep-related disordered breathing during pregnancy in obese women.

STUDY OBJECTIVES: This study was designed to evaluate sleep-related disordered breathing in obese women during pregnancy. Obesity is known to predispose to sleep-related breathing disorders. During pregnancy, obese mothers gain additional weight, but other mechanisms may counteract this effect. DESIGN: A case-control study to compare sleep-related breathing in obese pregnant women (mean prepregnancy body mass index [BMI] > 30 kg/m(2)) with pregnant women of normal weight (mean BMI, 20 to 25 kg/m(2)). SETTING: University teaching hospital with a sleep laboratory. PARTICIPANTS: We recruited 11 obese women (BMI, 34 kg/m(2); mean age 31 years) and 11 control women (BMI, 23 kg/m(2); mean age 32 years). INTERVENTIONS: Overnight polysomnography was performed during early (after 12 weeks) and late (after 30 weeks) pregnancy. MEASUREMENTS AND RESULTS: During pregnancy, obese mothers gained 13 kg and control women gained 16 kg. Sleep characteristics did not differ between the groups. During late pregnancy, the women in both groups slept more poorly and slept in supine position less. During early pregnancy, their apnea-hypopnea indexes (1.7 events per hour vs 0.2 events per hour; p < 0.05), 4% oxygen desaturations (5.3 events per hour vs 0.3 events per hour; p < 0.005), and snoring times (32% vs 1%, p < 0.001) differed significantly. These differences between the groups persisted in the second polysomnography, with snoring time further increasing in the obese. Preeclampsia and mild obstructive sleep apnea were diagnosed in one obese mother. One obese mother delivered a baby showing growth retardation (weight - 3 SD). CONCLUSIONS: We have shown significantly more sleep-related disordered breathing occurring in obese mothers than in subjects of normal weight, despite similar sleeping characteristics.

Relationship between tracheal mucosal thickness and vascular resistance in dogs.

We have measured changes in tracheal mucosal thickness and tracheal vascular resistance in the dog. A probe was used to detect changes in height with time of the tracheal epithelium relative to an underlying cartilage. Tracheal vascular resistance was determined by perfusing a cranial tracheal artery at constant flow and measuring inflow pressure. Various drugs injected close-arterially were tested in 20 greyhounds anesthetized with pentobarbital sodium. Bradykinin, histamine, and methacholine significantly (P less than 0.01) decreased vascular resistance (-39.3 +/- 3.7, -47.3 +/- 4.2, and -22.5 +/- 5.2%, respectively) and increased the thickness of the mucosa (119.0 +/- 25.0, 61.9 +/- 25.0, and 46.3 +/- 6.4 micron). Substance P, vasoactive intestinal peptide, prostaglandin F2 alpha, and prostaglandin E, had large vasodilator actions (-31.4 +/- 5.0, -34.3 +/- 2.2, -21.9 +/- 2.8, and -31.5 +/- 2.4%) but only small effects on mucosal thickness (12.3 +/- 3.9, 13.0 +/- 3.4, 16.7 +/- 6.5, and 8.7 +/- 2.9 micron, respectively). Phenylephrine hydrochloride increased vascular resistance (19.8 +/- 1.7%) and decreased mucosal thickness (-23.9 +/- 3.1 micron). Thus airway vascular resistance and mucosal thickness always change in opposite directions, but drugs have different relative actions on the two variables. Even with large vasodilatations, the absolute changes in mucosal thickness were small and were unlikely to have an appreciable effect on tracheal airway resistance.

Budesonide inhibits plasma extravasation induced by capsaicin and by substance P in the rat nasal mucosa.

We studied the effect of the locally administered glucocorticoid budesonide on plasma extravasation induced by capsaicin and by substance P (SP) in the nasal mucosa of pathogen-free rats. Using Evans blue dye as a tracer, we measured plasma extravasation induced by capsaicin (150 micrograms kg-1 i.v.) or SP (0.5 and 2.5 micrograms kg-1 i.v.) in the rat naso- and maxilloturbinates after pretreatment with budesonide (0.1-50 micrograms twice/day for 2 days in the right nostril; 50 micrograms only for SP) or its vehicle. We found that budesonide inhibits plasma extravasation induced by capsaicin in a dose-dependent fashion in the nasal cavity. After the highest dose (50 micrograms) of budesonide, the values of Evans blue in the nasal mucosa were not different from the values observed after capsaicin vehicle alone. Budesonide also reduced plasma extravasation induced by capsaicin in the trachea and the urinary bladder of the rats in a dose-dependent fashion. Budesonide (50 micrograms) delivered to the nose inhibited the plasma extravasation caused by 0.5 but not by 2.5 micrograms SP kg-1 in the nasal mucosa. We conclude that the postjunctional part of the neurogenic pathway is a target for glucocorticoid antiinflammatory action in the nasal mucosa, at least of the rat. Budesonide's effect on organs other than the nose can be explained by systemic absorption.

Chronic bronchitis and chronic obstructive pulmonary disease: Finnish National Guidelines for Prevention and Treatment 1998-2007.

1. A national recommendation for the promotion of prevention, treatment and rehabilitation in relation to chronic bronchitis and COPD from 1998 to 2007 has been prepared on the basis of extensive collaboration by order of the Ministry of Social Affairs and Health. The Programme needs to be revised as necessary, because of rapid developments in medical knowledge, and in drug therapy in particular. 2. COPD is a disease characterized by slowly progressing, irreversible airways obstruction. Over 5% of the population suffer from symptomatic forms of the disease. It is estimated that a further 5% of the population may suffer from latent COPD. Most patients (75%) suffer from mild forms of the disease. The disease is often preceded by chronic bronchitis. A total of 400,000 Finns suffer from chronic bronchitis or COPD. Occurrence of these diseases in future will be particularly affected by decreased smoking by men, increased smoking by the young and by women, and aging of the population. 3. In 1997, the annual treatment costs of chronic bronchitis and COPD were estimated to be FIM 1.5 thousand million, total costs FIM 5 thousand million. Without intensification of measures to prevent and treat the diseases, costs will rise significantly. Costs arising from severe COPD (5% of patients with COPD) account for roughly 65% of costs overall and are primarily related to hospitalizations. 4. The goals of the Programme for the Prevention and Treatment of Chronic Bronchitis and COPD are as follows: (a) to decrease the incidence of chronic bronchitis; (b) to ensure that as many patients as possible with chronic bronchitis recover; (c) to maintain capacity for work and functional capacity of patients with COPD; (d) to reduce the percentage of patients with moderate to severe COPD; (e) to decrease the number of hospitalization days of COPD patients by 25% overall; and (f) to decrease annual costs per patient. 5. The following means are suggested for achieving the goals: (a) reduction in smoking; (b) reduction in work-related and outdoor air pollutants and improvement of quality of indoor air; (c) enhancement of knowledge about risk factors and treatment of the diseases is in key groups; (d) promotion of early diagnosis and active treatment, in smokers in particular; (e) improvement of guided self-care; (f) early commencement of rehabilitation, individual planning and implementation, primarily as an element in treatment; and (g) encouragement of scientific research. 6. COPD and exacerbation of its symptoms can be prevented through choices relating to life habits, such as not smoking, maintaining good general condition, and protection against exposure to dusts. The Programme gives examples of such measures and appeals to various authorities and voluntary organizations to increase their cooperation. Preventive methods should be individualized, and based on due consideration. 7. Chronic bronchitis and COPD should be diagnosed at early stages, and treated appropriately from the outset. Treatment consists of: (a) treatment according to causes, such as stopping smoking and work hygiene; (b) early rehabilitation such as patient education and guided self-care: (c) drug therapy; (d) hospital treatment; and (e) rehabilitation. 8. The hierarchy of referrals in the treatment of COPD should be revised to accord a greater role to the primary health care sector. Good exchanges of information and cooperation between the primary health care and specialized medical care sectors will all be necessary if this hierarchial model is to have the desired effect. 9. Hospital districts and health centres should ensure that different levels of the health-care system are capable of fulfilling the tasks assigned to them appropriately. One specialist in each hospital district should be given charge of prevention and assembly of know-how relating to treatment, and of quality of treatment at regional level. (ABSTRACT TRUNCATED)

Sleep apnoea: Finnish National guidelines for prevention and treatment 2002-2012.

(1) After negotiations with the Finnish Ministry of Social Affairs and Health, a national programme to promote prevention, treatment and rehabilitation of sleep apnoea for the years 2002-2012 has been prepared by the Finnish Lung Health Association on the basis of extensive collaboration. The programme needs to be revised as necessary, because of the rapid development in medical knowledge, and in appliance therapy in particular. (2) Sleep apnoea deteriorates slowly. Its typical features are snoring, interruptions of breathing during sleep and daytime tiredness. Sleep apnoea affects roughly 3% of middle-aged men and 2% of women. In Finland, there are approx. 150,000 sleep apnea patients, of which 15,000 patients have a severe disease, 50,000 patients are moderate and 85,000 have a mild form of the disease. Children are also affected by sleep apnea. A typical sleep apnea patient is a middle-aged man or a postmenopausal woman. (3) The obstruction of upper airways is essential in the occurrence of sleep apnoea. The obstruction can be caused by structural and/or functional factors. As for structural factors, there are various methods of intervention, such as to secure children's nasal respiration, to remove redundant soft tissue, as well as to correct malocclusions. It is possible to have an effect on the functional factors by treating well diseases predisposing to sleep apnoea, by reducing smoking, the consumption of alcohol and the use of medicines impairing the central nervous system. The most important single risk factor for sleep apnoea is obesity. (4) Untreated sleep apnoea leads to an increase morbidity and mortality through heart circulatory diseases and through accidents by tiredness. Untreated or undertreated sleep apnoea deteriorates a person's quality of life and working capacity. (5) The goals of the Programme for the prevention and treatment of sleep apnoea are as follows: (1) to decrease the incidence of sleep apnoea, (2) to ensure that as many patients as possible with sleep apnoea recover, (3) to maintain capacity for work and functional capacity of patients with sleep apnoea, (4) to reduce the percentage of patients with severe sleep apnoea, (5) to decrease the number of sleep apnoea patients requiring hospitalisation and (6) to improve cost effectiveness of prevention and treatment of sleep apnoea. (6) The following means are suggested for achieving the goals: (1) to promote prevention of obesity, weight loss and weight control; (2) to promote securing of nasal respiration in child patients and removal of obstructing redundant soft tissues; (3) to promote the correction of children's malocclusions, (4) to enhance knowledge about risk factors and treatment of sleep apnoea in key groups, (5) to promote early diagnosis and active treatment, (6) to commence rehabilitation early and individually as a part of treatment and (7) to encourage scientific research. (7) On the national level, the occurrence of sleep apnoea can be prevented, for example, by encouraging weight control. The programme gives examples of such measures and appeals to various authorities and voluntary organisations to reinforce their collaboration. Preventive measures should be individualised, and based on due consideration. (8) The efficacy of diagnosing sleep apnoea should be increased. Attention should be paid to the symptoms of risk group patients at different units of the primary and occupational health care. Even mild forms of the disease should be treated appropriately. Diagnosis and treatment of the disease involve cooperation between the primary and specialised health-care sectors. Methods of treatment are (1) treatment of obesity, (2) positional therapy, (3) reduction of the use of medicines impairing the central nervous system, (4) reduction of smoking and the consumption of alcohol, (5) devices affecting the position of the tongue and lower jaw, (6) treatment with Continuous Positive Airway Pressure (CPAP-treatment), (7) surgical methods of treatment and (8) rehabilitation. (9) The hierarchy of referrals in the prevention and treatment of sleep apnoea should be revised to accord a greater role to the primary health-care sector. Good exchanges of information and cooperation between the primary health care and specialised medical-care sectors should be developed. Hospitals districts in cooperation with provincial governments and municipalities should ensure that different levels of the health-care system are capable of fulfilling the tasks assigned to them appropriately. (10) Rehabilitation of sleep apnoea should be goal-orientated and cover all forms of rehabilitation: medical, occupational and social. Rehabilitation should prevent the effects caused by the disease. Thus, it is possible to support self-care, increase the patient's resources and improve quality of life. (11) Information and training should be directed primarily towards health-care personnel, patients and their families. Organisations should produce materials for health and patient education as well as organising training events. To support the activities. financing will be needed from organisations such as Finland's Slot Machine Association. The Social Insurance Institution should disseminate information about questions of social security. Regional direction and training will mainly be the responsibilities of hospital districts, provincial governments and local health centres. The media will play an important role in the dissemination in-depth information about prevention and treatment of sleep apnoea.

Verification of self-reported asthma and allergy in subjects and their family members volunteering for gene mapping studies.

Studies which aim at mapping genes contributing to the development of asthma and atopy demand that hundreds of patients and their family members be assessed. In Finland, the Social Insurance Institution (SII) grants substantial reimbursement for medication to all patients who meet diagnostic criteria of asthma, which include a history of asthmatic symptoms and a measured reversibility of bronchial obstruction. To recruit a large number of asthma patients efficiently in a short period of time, we took advantage of the national reimbursement procedure and retrospectively collective data on patients' medical history and lung function test results at the time of diagnosis. First, we wanted to investigate if the reimbursements could be regarded as objective verification for self-reported asthma. Altogether 335 adult self-reported asthma patients were evaluated, 87% of them were verified as having chronic asthma. Reimbursement for medication showed a sensitivity of 95% and a specificity of 76% for verified asthma. Second, we were interested to see if self-reported nasal allergic symptoms or self-reported physician diagnosed allergic rhinitis were sensitive and specific measures of allergy. The self-reported allergic nasal symptoms had a poor specificity (31% in the proband group and 59% in the family members group) when compared to the allergy screening test (Phadiatop). The best verification for self-reported asthma was achieved by combining the information on self-reported disease, granted reimbursement by the SII and the medical records. For allergies, the specificity of self-reporting was far too low to be used alone, and a positive allergy screening test together with relevant symptoms was chosen as a marker of allergy.

Investigative bronchoscopy and endobronchial biopsy is well tolerated in hyperreactive asthma patients.

The tolerability of 57 non-smoking asthma patients inhaling salbutamol as needed (ATS, 18--60 years, 60% < or = FEV1 < or =100%, PD15FEV1 <0.4 mg histamine) to fibreoptic bronchoscopy (FOB) and endobronchial biopsy was studied. The FOB was done in local Lignocaine anaesthesia, and from five to eight biopsy specimens were taken from the bronchial mucosa of the right lung. The tolerability was measured as cough/bronchospasm during the procedure (from 0 = normal to 3 = interrupted procedure), success of the procedure, and untoward occurrences. Twenty-seven of the 57 patients (48%) had no cough or bronchospasm during the FOB (score 0). Few coughs of no importance (score 1) were documented in 23 patients (40%). Seven patients (12%) had cough and/or bronchospasm interfering with the FOB procedure (score 2). The FOB procedure was not interrupted because of cough and/or bronchospasm (score 3) in any patient. Scores of cough and/or bronchospasm diminished progressively with the increase of PD15FEV1 histamine. The success of the procedure was 100%. Two patients had untoward medical occurrences requiring additional rescue medication (3.5%). In conclusion, we found that hyperreactivity predicts cough and/or bronchospasm during the FOB. Cough and/or bronchospasm are frequently observed during the bronchial procedure, but they are mild and of minor clinical importance. An investigational endobronchial procedure can be successfully performed in mildly or moderately obstructive asthmatic patients, even in cases with severe bronchial hyperreactivity.

Airway inflammation and basement membrane tenascin in newly diagnosed atopic and nonatopic asthma.

Previous studies have shown both similar and distinct inflammatory changes in atopic and nonatopic asthma. This study was set to investigate the bronchial inflammatory cell infiltrate and subepithelial basement membrane (BM) tenascin deposition in subjects with newly diagnosed asthma and bronchial hyperresponsiveness (BHR). Seventy-nine asthmatic subjects (age 18-60 years) were recruited and 58 were atopic according to skin prick testing. The patients recorded asthma symptoms and peak flow measurements for 14 days. Lung function and BHR were measured by spirometry and histamine challenge. Serum eosinophil cationic protein (ECP) and blood eosinophils were assessed. Fiberoptic bronchoscopy was performed to obtain bronchial biopsies. Serum ECP was higher in the atopic group but eosinophil counts did not differ. There were no differences in inflammatory cells studied (activated eosinophils, T-lymphocytes, mast cells or macrophages) between nonatopic and atopic subjects. BM tenascin layer was significantly thicker in atopic compared with nonatopic subjects (7.6 vs 6.3 microm, P = 0.007). The thickness of tenascin correlated with eosinophil, T-lymphocyte, and macrophage counts, as well as with IL-4-positive cell counts and the correlation was seen only in atopic asthmatics. These findings suggest that inflammatory cells may have a regulatory role in tenascin expression in atopic asthma.