Biomedical subjects
Publications and source records attributed to G Boman.
Knowledge of the pathophysiology and aetiology of asthma has expanded greatly during recent years, and hopes are strong that within the foreseeable future it will be possible to alleviate asthmatic symptoms even more effectively. This review covers some of this new knowledge, and presents viewpoints on the practical clinical management of asthma patients.
We have analysed the predictors of survival in patients starting long-term domiciliary oxygen therapy (LTO) for chronic hypoxia caused by parenchymal lung disease. In 240 patients (136 males) LTO was started at a mean age of 70 yrs. Survivors have been followed up for a minimum of 28 months (range 28-57 months). Interstitial fibrosis was the sole cause of hypoxia in 51 patients, and late sequelae of pulmonary tuberculosis in 48 patients. More than one (mixed) disease caused hypoxia in 124 patients. Patients with tuberculosis (TB) started LTO with significantly higher values of arterial carbon dioxide tension (PaCO2) and markedly lower spirometry volumes than patients with interstitial fibrosis. In the total patient group survival was correlated in the univariate analysis to cause(s) of hypoxia, performance status and PaCO2 when breathing air. TB had a relatively good prognosis, whilst interstitial fibrosis implied a poor long-term survival. A PaCO2 of below 5.5 kPa and a poor performance class was associated with increased mortality rates. In TB patients, survival was better when thoracic deformity contributed to hypoxia. In patients with interstitial fibrosis, a forced vital capacity of below 2.1 l was associated with increased mortality. Concomitant chronic obstructive pulmonary disease was associated with better survival than interstitial fibrosis alone. In the multivariate analysis, survival was found correlated to performance status, presence or absence of thoracic deformity and forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
In a double-blind cross-over study comparing the duration of action of 12 micrograms and 24 micrograms formoterol, 500 micrograms terbutaline and placebo, lung function tests were performed in 12 never-smokers with non-allergic bronchial asthma. All the patients were hyperreactive to methacholine, had normal serum IgE level, and negative skin or RAST results. The lung function tests were carried out over an 11-h period and included measurements of lung volumes, airway resistance, dynamic spirometry, nitrogen single breath wash-out test and single breath diffusion capacity for CO. The airway resistance and maximal forced expiratory flow tests indicated a pronounced bronchodilator effect without adverse effects of 12 micrograms and 24 micrograms formoterol on both large and peripheral airways. Improved intrapulmonary gas distribution measured by the nitrogen wash-out test and more even distribution of the lung volumes indicating more homogeneous ventilation was seen for approx. 3 h after terbutaline and approx. 11 h after 24 micrograms formoterol. Measurement of the CO diffusion capacity indicates more effective gas diffusion and a better ventilation-perfusion ratio for at least 11 h, especially after inhalation of 24 micrograms formoterol.
The effect of i.v. theophylline after high-dose beta 2-agonist treatment in severe acute asthma was studied in 30 patients from a multicentre study who reported not having taken theophylline during the last 24 hours. One hour after the start of inhaled or i.v. salbutamol treatment, all patients received 6 mg/kg of i.v. theophylline. The plasma concentration 30 minutes after the start of the theophylline infusion was 78 +/- 13 mumol/l (mean +/- SD). The mean change (delta) in peak expiratory flow (PEF) was 8 +/- 6% of the predicted 30 minutes after the theophylline infusion and 7 +/- 5% 60 minutes after it. The increase in PEF was greater in this patient group than in a group of 101 patients from the same multicentre study who were on theophylline medication and were therefore given a reduced dose (3 mg/kg) (7 +/- 5 vs. 4 +/- 6% of the predicted value, p < 0.01). The proportion of patients with an increase in PEF of > or = 10% of the predicted at discharge was 27% (8/30) in the patient group in this investigation and 14% (14/101) in the group who was on theophylline treatment.
The aim of this investigation was to study whether certain patients benefit from adding theophylline to the beta 2-agonist treatment of acute asthma. The study group comprised 101 patients who were taking oral theophylline. The patients received inhaled salbutamol (albuterol) (0.15 mg/kg x 2) (n = 53) or IV salbutamol (5 micrograms/kg) (n = 48). Aminophylline (3 mg/kg) was infused intravenously 60 minutes after the start of the salbutamol treatment. The mean increase in peak flow (PEF) after the aminophylline infusion was 22 +/- 33 L/min or 4% +/- 6% of the predicted value (mean +/- SD). A change in PEF correlated negatively to plasma theophylline before treatment (P less than .01) and positively to a change in plasma-theophylline after treatment (P less than .05). All patients with an increase in PEF of more than 10% of the predicted value (n = 14) after the theophylline infusion had plasma-theophylline levels before treatment of below 7.5 mg/L (41 mumol/L). No significant difference in the change in PEF after the theophylline infusion was found between patients who had received inhaled or intravenous salbutamol. This investigation could indicate that IV theophylline as an additive to beta 2-agonist treatment should be reserved for patients who are either not taking theophylline or who have only taken a low dose before arriving for the emergency treatment of acute asthma.
We have measured the plasma levels of salbutamol, terbutaline and theophylline in 140 patients (70 men, mean age 57 yrs) arriving for emergency treatment with severe acute asthma. The aim of the study was to investigate how the measured plasma levels correlated with the reported bronchodilator intake and whether the pretreatment beta 2-agonist levels influenced the effect of emergency salbutamol treatment. We found a highly significant correlation between the reported 24 h dose and the measured plasma concentrations for all three drugs. A plasma concentration less than 40 mumol.l-1 was found in 63 of the 107 patients who had taken theophylline, while no patient had a plasma concentration greater than 110 mumol.l-1. A plasma concentration above the suggested therapeutic range was found in 23 of the 95 patients who had taken terbutaline (greater than 30 nmol.l-1) and in 12 of the 98 patients who had taken salbutamol (greater than 60 nmol.l-1). A significant negative correlation was found between the initial plasma beta 2-agonist levels and the bronchodilation after i.v. salbutamol treatment (5 micrograms.kg-1), while there was no clear indication that high plasma beta 2-agonist levels reduced the bronchodilator effect of a high dose of inhaled salbutamol (0.15 mg.kg-1 x 2). We conclude that some patients arriving with acute asthma have high blood concentrations of beta 2-agonists, which possibly limit the response to i.v. beta 2-agonist treatment, while the effect of high-dose inhaled beta 2-agonists appears to be related to a lesser degree to the drug concentration on arrival. In this study overtreatment with theophylline appears to be uncommon.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Five hundred and eighty persons who were heavy snorers filled in a questionnaire regarding symptoms on a 5-grade scale. Of these, 178 had a complete polysomnography investigation while 402 patients underwent oxymetric screening during the night only. On the basis of these investigations. 217 were classified as suffering from the obstructive sleep apnea syndrome (OSAS) and 363 as snorers without OSAS. The symptom scores differed between the two groups, but the range was wide and some persons with OSAS claimed only minor daytime sleepiness, somnolence, etc., while a high proportion of persons without OSAS frequently suffered from such symptoms. Thus, it was not possible to discriminate between patients with and without OSAS on the basis of their symptoms only. Furthermore, there are many persons who are "only" heavy snorers but who have symptoms that affect their career and social life and who so far have only received scant interest from the medical profession. Excessive daytime sleepiness and somnolence thus do not seem to be secondary to hypoxemia at night but rather to poor quality of sleep, which may be the case in association with heavy snoring even without appreciable deterioration of oxygen saturation.
A double-blind cross-over study was performed on 22 asthmatic patients receiving maintenance treatment with theophylline who, in a previous study, had reported sleep problems. In one of two three-week periods the theophylline medication was replaced by an equipotent dose of slow-release enprofylline. Analysis of sleep questionnaires answered after each treatment period, and sleep diaries filled in throughout the study, showed no significant differences in the quality of sleep between the treatments. Peak expiratory flow (PEF) in the morning did not differ between the treatment periods, but mean PEF in the evening was slightly higher (20 l/min) during theophylline treatment. It was concluded that replacement of theophylline by enprofylline did not improve the quality of sleep subjectively in this group of theophylline treated asthmatics. The results suggest that adenosine receptor antagonism may not be a significant cause of sleep disturbances in asthmatic patients who are receiving theophylline as maintenance treatment.
The prevalence of sleep complaints and sleep disturbances was studied prospectively in 98 consecutive adult asthmatic patients (mean age 45 years, 46% men) attending an out-patient clinic by means of questionnaires and sleep diaries. The results were compared with those from an age- and sex-matched group of 226 healthy individuals. The most common sleep disturbances among the asthmatic patients were early morning awakening (51%), difficulty in maintaining sleep (DMS; 44%) and daytime sleepiness (44%). With decreasing asthma control (i.e. increased number of acute asthmatic attacks) there was an increase of DMS, nocturnal wakefulness, nocturnal breathing problems and bronchodilator inhalations at night. A decrease in estimated sleep time (P less than 0.05) and increase in nocturnal wakefulness (P less than 0.05) was seen with decreasing daytime FEV1--measured as percentage of the predicted value (%FEV1). There was also significant correlation between increasing age and decreasing %FEV1 (P less than 0.01). Among the 26 patients who were only taking one oral bronchodilator, no definite difference regarding sleep quality was found between those treated with theophylline and those taking an oral beta 2-agonist. The prevalence rates of DIS, DMS and daytime sleepiness were about twice as high among the asthmatic patients than in the healthy population. It is concluded that impaired quality of sleep, with disturbed sleep during the night, early morning awakenings and daytime sleepiness, is common among patients with bronchial asthma.
Explore the source record for details and available documents.
In order to study effects of theophylline on sleep, a randomised double-blind cross-over study with slow release theophylline vs. placebo was performed on 13 healthy male volunteers (mean age 24 years), eight of whom were considered caffeine-sensitive and five caffeine-insensitive. A sleep diary was filled in during the entire period. At the end of each 2 week study period a sleep questionnaire was filled in and a sleep recording was conducted. Seven of the eight caffeine-sensitive persons reported that their sleep was disturbed during the theophylline period, while none of the five caffeine-insensitive experienced any difference between the periods. Analysis of the sleep diaries (mean +/- SD) revealed a significant increase in sleep latency (16 +/- 11 vs 4 +/- 7 min) and decrease in sleep efficiency (95 +/- 3 vs 98 +/- 3%) among the caffeine-sensitive persons during the theophylline period compared with the placebo period, while no such difference was found among the caffeine-insensitive. We conclude that theophylline seems to disturb sleep mainly in caffeine-sensitive persons.
The etiology of the SAS is unknown. To test whether endogenous opioids could be pathologically active in SAS, markers of opioid systems were measured in the CSF of 15 patients with SAS and in control subjects. Measured by receptor assay, the concentration of so-called fraction 1 opioid was higher in patients with SAS (3.0 +/- 1.5 pmol/ml; mean +/- SD) than in control subjects (1.1 +/- 0.5 pmol/ml) (p less than 0.01), whereas that of fraction 2 opioid was similar in the two groups. Beta-endorphin-like activity, measured by radioimmunoassay, was somewhat lower in patients with SAS (14.0 +/- 2.8 pmol/ml) than in control subjects (21.8 +/- 7.6 pmol/ml) (p less than 0.05). Six months after surgical treatment of the soft palate, new measurements were made in eight patients. Fraction 2 endorphin and beta-endorphin showed no consistent changes. A decrease in the level of fraction 1 from 4.1 +/- 1.5 pmol/ml to 2.3 +/- 1.0 pmol/ml (p less than 0.02) was noted in those six patients showing a successful clinical course. The data support the hypothesis that in SAS the opioid activity is increased.
The accuracy of transcutaneous CO2 monitoring (PtcCO2) was studied in 22 subjects suspected of having sleep-related breathing disorders, by comparison with arterial CO2 measurements (PaCO2). At rest 40 simultaneous sets of PaCO2 and PtcCO2 were obtained. The mean PaCO2 (+/-SD) was 5.3 +/- 0.9 kPa and PtcCO2 was 5.7 +/- 1.0 kPa (r = 0.79). The ventilatory response to CO2 was evaluated by a CO2 rebreathing method, and simultaneous measurements of PaCO2, PtcCO2 and end-tidal PCO2 (PETCO2) were made every min. Both PaCO2 and PETCO2 increased more during the first min of CO2 rebreathing than PtcCO2 (p less than 0.001). Between 1 to 5 min after the start of rebreathing there were no significant differences between the three methods. During sleep there was an increase in PtcCO2 (by 0.1-0.3 kPa) with each apneic event, the magnitude of the increase depending on the length and distribution of these events. With repeated long apneas there was a cumulative increase in PtcCO2, especially during REM sleep. Continuous PtcCO2 monitoring proved useful in monitoring and diagnosing sleep-related breathing disorders.