Seppo Saarelainen

Randomised comparison of guided self management and traditional treatment of asthma over one year

Abstract Objective: To compare the efficacy of self management of asthma with traditional treatment. Design: 12 month prospective randomised trial. Setting: Outpatient clinics in Finland. Subjects: 115 patients with mild to moderately severe asthma. Interventions: Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements. Main outcome measures: Unscheduled admissions to hospital and outpatient visits, days off work, courses of antibiotics and prednisolone, lung function, and quality of life. Results: The mean number of unscheduled visits to ambulatory care facilities (0.5 v 1.0), days off work (2.8 v 4.8), and courses of antibiotics (0.4 v 0.9) and prednisolone (0.4 v 1.0) per patient were lower and the quality of life score (16.6 v 8.4 at 12 months) higher in the self management group than in the traditionally treated group. In both groups admissions for asthma were rare. Conclusions: Self management reduces incidents caused by asthma and improves quality of life. Key messages Key messages This trial of 115 patients with mild to moderately severe disease randomised half to a traditional care and half to a self management programme consisting of education about asthma and daily peak flow readings Intervention thresholds of < 85% of the optimal peak flow for doubling the dose of inhaled steroid for two weeks and of < 70% of the optimal peak flow for starting a course of oral steroids worked well The self management group had fewer incidents (consultations, days off work, courses of prednisolone or antibiotics) than the traditionally treated group and better quality of life scores Adherence of patients to the self management instructions was better than expected

Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms.

Nocturnal asthma symptoms and impaired lung function at night are related to inflammatory activity in the peripheral lung compartment. Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates can be used to separately assess alveolar and bronchial NO production and inflammation. The authors hypothesised that asthmatic patients with nocturnal symptoms have a higher alveolar NO concentration than those with only daytime symptoms. The authors asked 40 patients with newly-diagnosed steroid-naïve asthma about their nocturnal asthma symptoms through the use of a written questionnaire. Alveolar NO concentration and bronchial NO flux were assessed in the 40 asthmatics and 40 healthy controls. Nineteen of the 40 patients reported nocturnal symptoms. Patients with nocturnal symptoms had a higher alveolar NO concentration (1.7±0.3 (mean±sem) parts per billion (ppb)) than patients without nocturnal symptoms (0.8±0.3 ppb, p=0.012) or healthy controls (1.0±0.1 ppb, p=0.032). Bronchial NO flux was higher both in patients with (2.4±0.4 nL·s−1, p<0.001) and without (2.6±0.4 nL·s−1, p<0.001) nocturnal symptoms, compared to controls (0.7±0.1 nL·s−1). Nocturnal symptoms in asthmatic patients are related to a higher alveolar nitric oxide concentration. The results suggest that assessment of alveolar nitric oxide concentration can be used to detect the parenchymal inflammation in asthmatic patients with nocturnal symptoms.

Inhaled fluticasone decreases bronchial but not alveolar nitric oxide output in asthma

Exhaled nitric oxide (NO) concentration is a noninvasive measure of airway inflammation and is increased in asthma. Inhaled glucocorticoids decrease exhaled NO concentration, but the relative contributions of alveolar and bronchial levels to the decrease in exhaled NO concentration are unknown. Alveolar NO concentration and bronchial NO flux can be separately approximated by measuring exhaled NO at several exhalation flow rates. The effect of steroid treatment on alveolar and bronchial NO output in asthma was studied. Alveolar NO concentration and bronchial NO flux were assessed in 16 patients with asthma before and during treatment with inhaled fluticasone for 8 weeks and in 16 healthy controls. Before the treatment, asthmatics had increased bronchial NO flux (mean+/-SEM: 3.6+/-0.4 versus 0.7+/-0.1 nL x s(-1), p<0.001) but normal alveolar NO concentration (1.2+/-0.5 versus 1.0+/-0.2 parts per billion (ppb), p>0.05) compared with controls. Inhaled fluticasone decreased bronchial NO flux from 3.6+/-0.4 to 0.7+/-0.1 nL x s(-1) (p<0.01) but had no effect on alveolar NO concentration (before: 1.2+/-0.5; after: 1.2+/-0.1 ppb, p>0.05). The forced expiratory volume in one second improved, whereas asthma symptom score and serum levels of eosinophil cationic protein and eosinophil protein X decreased during the treatment. In conclusion, inhaled fluticasone decreases bronchial but not alveolar nitric oxide output simultaneously with clinical improvement in patients with asthma.

Circulating Endothelin-1 in Obstructive Sleep Apnea

Endothelin (ET)-1 is a potent vasoconstrictive and mitogenic peptide produced by endothelial cells and degraded predominantly in pulmonary vasculature. We measured ET-1 in 9-normotensive and 14 hypertensive men with obstructive sleep apnea. The ET-1 levels were higher in both normotensive (mean +/- SD, 6.3 +/- 2.8 pg/ml) and hypertensive (7.8 +/- 3.0 pg/ml) groups than in 66 healthy controls (2.9 +/- 1.2 pg/ml). Ten patients were restudied after three months of nCPAP treatment. No decrease in ET-1 was observed.

Randomised comparison of cost effectiveness of guided self management and traditional treatment of asthma in Finland

In many countries the cost of caring for patients with asthma is high.1 Guidelines have recommended guided self management for the treatment of asthma. 2 3 We recently compared the efficacy of guided self management with traditional treatment for asthma4 and here report the cost effectiveness of the two treatments. One hundred and fifteen patients with mild to moderately severe asthma were randomly allocated guided self management or traditional treatment. The 56 patients allocated guided self management were given personal education and they were taught to measure their peak expiratory flow rate every morning for a year. If the value fell below 85% of their predetermined optimal value on any morning they were instructed to double their dose of inhaled corticosteroid for 2 weeks. If the value fell below 70% of the optimal value on any morning they were to take oral prednisolone (40 mg/day) for 7 days and immediately contact their nurse or doctor. The 59 patients allocated traditional …

Effect of nasal CPAP treatment on insulin sensitivity and plasma leptin

There have been reports indicating that obstructive sleep and gave their consent. The protocol was approved by the Ethical Committee of the Tampere University Hospital. apnoea (OSA) may affect glucose metabolism (Brooks et al. 1994; Strohl et al. 1994) and insulin sensitivity (Tiihonen et al. All-night recordings were performed on eight subjects with an Alice 3⊂ digital polysomnograph (Healthdyne, Belgium) and 1993). However, two recent studies suggest that the relationship between glucose metabolism (Davies et al. 1994) or insulin on two subjects with a Static Charge Sensitive Bed (Biomatt⊂, Biorec, Finland). The sleep studies, adjusting the CPAP level resistance (Stoohs et al. 1996) and OSA is mediated through obesity. and compliance monitoring have been described earlier (Saarelainen et al. 1996). Resistance to insulin-stimulated glucose uptake is present in 25% of nonobese individuals with normal oral glucose After fasting for 12 h euglucaemic hyperinsulinaemic clamp (as described by Lahtela et al. 1985) was started at 07.00 hours tolerance, and in the majority of patients with non-insulin dependent diabetes. Insulin resistance is associated with using a constant intravenous insulin infusion of 40 mU/m/ min. Samples for plasma leptin (Human leptin RIA kit, Linco hyperinsulinemia, glucose intolerance, increased plasma triglyceride, decreased HDL-cholesterol and hypertension, all Research Inc., St. Charles, MO), cholesterol, HDL-cholesterol and triglyceride measurements were collected before the clamp. risk factors for coronary heart disease (Reaven 1988). We have performed an euglucaemic hyperinsulinaemic clamp The patients were instructed to keep their diet and physical activity constant until metabolic studies were repeated after on 10 nondiabetic patients referred to our sleep laboratory because of OSA. No control group was included. The patients 3 mo of nCPAP treatment. Table 1 gives the main characteristics of the group studied were randomly selected excluding all patients with other chronic diseases and current smokers. A detailed history and physical and the results before and after nCPAP treatment. Patients 1–6 used nCPAP 4.0–6.9 h per night (mean 5.6 h). Patient 7 examination were performed. It was confirmed that Hb, serum transaminases, glucose, creatinine and thyroxin were within had breaks in nCPAP treatment, but used it regularly during the week before control measurements. Patient 8 used a nCPAP normal limits. All patients were informed of the study protocol

Increased bronchial nitric oxide production in patients with asthma measured with a novel method of different exhalation flow rates

The concentration of nitric oxide (NO) in exhaled air is increased in patients with asthma, suggesting that measuring fractional exhaled NO concentration (FENO) may be used to monitor asthmatic airway inflammation. However, increased FENO is not specific for asthma, as other inflammatory lung diseases may also increase FENO. To augment the specificity of FENO measurement, we tested a novel theoretical modelling of pulmonary NO dynamics that allows the approximation of alveolar NO concentration and bronchial NO flux separately by measuring FENO at several exhalation flow rates. We measured FENO at four exhalation flow rates in 10 steroid-naive asthmatics, 5 patients with extrinsic allergic alveolitis, and in 10 healthy controls. Both the asthmatics and the patients with alveolitis had significantly higher FENO than the healthy controls. The increased NO concentration originated from the bronchial level in the asthmatics and from the alveolar level in the patients with alveolitis. In the second part of the study we assessed the repeatability of FENO test, within-day and day-to-day (during two weeks) variation in FENO, and the effects of mouth pressure and cigarette smoking on FENO in healthy volunteers. Repeatability of 10 subsequent measurements was high (coefficient of variation (CV) 4.6% ± 0.4%), and no diurnal variation was found. The day-to-day variation during a 2-week period gave a CV of 10.6% ± 1.0%. The magnitude of mouth pressure (5-20 cmH2O in adults, 5-40 cmH2O in children) during measurement had no effect on FENO. Smoking a cigarette caused a small and transient but statistically significant increase in FENO at 1 and 5 min after smoking. In conclusion, FENO measurement is highly repeatable with low day-to-day variation among healthy subjects. Our results also suggest that the present novel method of measuring FENO at several exhalation flow rates can be used to approximate alveolar and bronchial contributions to FENO separately and thus increase the clinical value of this test.

No relation between apolipoprotein E alleles and obstructive sleep apnea.

Apolipoprotein E (ApoE) is a genetic risk factor influencing the development of cardiovascular diseases and Alzheimers disease. Patients with obstructive sleep apnea (OSA) suffer an excess mortality and morbidity from cardiovascular diseases. The frequencies of ApoE alleles were determined in 291 patients with OSA and 728 controls. The distribution of ApoE alleles and genotypes showed no difference between OSA and controls.

Increased alveolar nitric oxide concentration and high levels of leukotriene B4 and 8-isoprostane in exhaled breath condensate in patients with asbestosis

Background: Inhaled asbestos fibres can cause inflammation and fibrosis in the lungs called asbestosis. However, there are no non-invasive means to assess and follow the severity of the inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess the alveolar NO concentration and bronchial NO flux, which reflect inflammation in the lung parenchyma and airways, respectively. The aim of the present study was to investigate whether exhaled NO or markers in exhaled breath condensate could be used to assess inflammation in asbestosis. Methods: Exhaled NO and inflammatory markers (leukotriene B4 and 8-isoprostane) in exhaled breath condensate were measured in 15 non-smoking patients with asbestosis and in 15 healthy controls. Exhaled NO concentrations were measured at four constant exhalation flow rates (50, 100, 200 and 300 ml/s) and alveolar NO concentration and bronchial NO flux were calculated according to the linear model of pulmonary NO dynamics. Results: The mean (SE) alveolar NO concentration was significantly higher in patients with asbestosis than in controls (3.2 (0.4) vs 2.0 (0.2) ppb, p = 0.008). There was no difference in bronchial NO flux (0.9 (0.1) vs 0.9 (0.1) nl/s, p = 0.93) or NO concentration measured at ATS standard flow rate of 50 ml/s (20.0 (2.0) vs 19.7 (1.8) ppb, p = 0.89). Patients with asbestosis had increased levels of leukotriene B4 (39.5 (6.0) vs 15.4 (2.9) pg/ml, p = 0.002) and 8-isoprostane (33.5 (9.6) vs 11.9 (2.8) pg/ml, p = 0.048) in exhaled breath condensate and raised serum levels of C-reactive protein (2.3 (0.3) vs 1.1 (0.2) μg/ml, p = 0.003), interleukin-6 (3.5 (0.5) vs 1.7 (0.4) pg/ml, p = 0.007) and myeloperoxidase (356 (48) vs 240 (20) ng/ml, p = 0.034) compared with healthy controls. Conclusions: Patients with asbestosis have an increased alveolar NO concentration and high levels of leukotriene B4 and 8-isoprostane in exhaled breath. Measurement of exhaled NO at multiple exhalation flow rates and analysis of inflammatory markers in exhaled breath condensate are promising non-invasive means for assessing inflammation in patients with asbestosis.

Peripheral inflammation in patients with asthmatic symptoms but normal lung function.

Some patients with asthmatic symptoms and eosinophilic airway inflammation have normal lung function and thus do not meet the current diagnostic criteria of asthma. Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates can be used to assess alveolar and bronchial NO output and inflammation. We tested whether alveolar or bronchial NO output is increased in subjects having asthmatic symptoms but normal lung function. Exhaled NO concentration was measured at three exhalation flow rates (100, 175, and 370 mL/s) to assess alveolar NO concentration and bronchial NO flux in 23 patients with asthmatic symptoms but normal lung function (“asthmatic symptoms group”), 40 patients with asthma, and 40 healthy control subjects. The asthmatic symptoms group had increased bronchial NO flux (1.7 ± 0.3 nL/s, p = 0.016) and alveolar NO concentration (1.8 ± 0.2 parts per billiant (ppb), p = 0.010) compared with healthy controls (0.7 ± 0.1 nL/s and 1.0 ± 0.1 ppb, respectively). Patients with asthma had even higher bronchial NO flux (2.5 ± 0.3 nL/s, p = 0.024) but normal alveolar NO concentration (1.1 ± 0.2 ppb, p = 0.664). In asthmatic symptoms group, alveolar NO concentration correlated positively with blood eosinophil count and negatively with small airway function (FEF50% and FEF75%). In conclusion, patients with asthmatic symptoms but normal lung function have increased alveolar NO concentration and mildly elevated bronchial NO flux suggesting a more peripheral inflammation than in patients with asthma.