[Occupation and smoking as risk factors for obstructive lung disease].
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Biomedical subjects
Publications and source records attributed to J Boe.
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Retrospective case-control studies suggest a connection between chronic treatment with fenoterol and other beta-2-agonists and increased mortality from asthma. These studies are extremely difficult to assess from a methodological point of view. They raise important questions, however, and force us to critically reevaluate our present therapeutic approach. In the acute situation, beta-2-agonists might be life-saving, and we must therefore be cautious in readily accepting a causal relationship between beta-2-agonist treatment and death from asthma. Probably, retrospective case-control studies are inadequate to establish a clear-cut association between beta-2-agonist therapy and death from asthma. This will require prospective randomized studies including large asthma populations providing accurate information on both chronic and acute drug treatment, and the end-point is death from asthma.
Scoliosis can lead to respiratory failure and premature death. Alveolar hypoventilation is a dominant cause and artificial ventilation at home (AVH) is probably the treatment of choice. It has been suggested that long-term domiciliary oxygen therapy (LTO) is of little value because of the worsening of hypercapnia. We analyzed survival and predictors of death among 80 patients with scoliosis and other severe thoracic spine deformities receiving LTO for chronic hypoxia. The survival rate was higher in patients under the age of 65 (p = 0.01) and in patients without concomitant pulmonary or airways disease. Likewise, the survival rate was higher in patients with a PaCO2 of greater than 7.4 kPa than in patients with a lesser degree of hypoventilation and hypercapnia (p less than 0.05). The risk of developing life-threatening hypercapnia during well-controlled LTO appeared to be small. In younger patients without complicating disease, long-term survival was achieved with LTO, but with time, an increasing proportion of the patients changed to AVH, with or without LTO.
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.
Of 123 individuals hospitalized as children (aged 5-15 years) because of asthma over a 10-year period (1953-1962), four are dead of whom three died of asthma at follow-up 23-31 years later. Using a survey questionnaire, 64 (53%) of the 117 responders (response rate 98%) claimed to be completely symptom-free. The rest were still suffering from their disease. Of the 31 symptom-free individuals still living in the community, two had decreased lung volumes and seven had positive methacholine provocation tests at re-examination, thus indicating hyperreactivity. Twenty-five individuals showed both positive skin prick tests and Phadiatop allergy tests. Nineteen individuals were suffering from allergic rhinoconjunctivitis. So, of symptom-free adults hospitalized for asthma in childhood, nearly a quarter (23%) had hyperreactive airways. The occurrence of positive skin prick test/Phadiotop and rhinoconjunctivitis was, however, even higher (80% and 61% respectively), thereby indicating that the disappearance of allergy may not be a prerequisite for restoration to health in asthma.
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Twelve subjects relocated from aluminium potrooms due to work-related asthma were followed up for 2-27 months (median 23 months). Repeated post-relocation examinations (numbering 3-7, median 6) of methacholine challenge, forced expiratory volume in one second (FEV1), eosinophil cell count and respiratory symptoms were carried out at regular intervals. At the time of relocation, bronchial hyperresponsiveness (provoking concentration producing a 20% fall in FEV1 (PC20) less than or equal to 8.0 mg.ml-1) was found in eight of the subjects. During the follow-up period a twofold increase in PC20 was found in 7 of the 8 subjects who had PC20 less than 8.0 mg.ml-1 at the time of relocation. There was an improvement of symptoms but no improvement in FEV1 or decrease of eosinophils during the follow-up examinations.
In order to assess patients' preferences for different inhalation devices a questionnaire has been developed. The questionnaire consisted of items covering various aspects considered important for patients who regularly use inhalation devices. The questions were designed to be of a general character so any inhalation device could be evaluated. We evaluated the questionnaire in a multicenter, open crossover study comparing patients' opinions of MDI with and without spacer and of a dry powder inhaler, Turbuhaler. One hundred twenty-three patients with stable asthma confirmed by daily peak expiratory flow rate (PEF) measurements used for 2 weeks MDI only and MDI with spacer and for 2 weeks Turbuhaler. The order was randomized. The drugs were terbutaline inhaled via MDI and Turbuhaler and budesonide inhaled via MDI with spacer and turbuhaler. At the end of each evaluation period the patients answered a number of questions about their opinion by marking on a visual analogue scale. A factor analysis revealed that the different questions represent a few common factors important for evaluating opinion about inhalation devices. These factors are handling of the device, use, time to learn how to use the device properly, how confident the patients feel about the use of it, and taste/irritation. A standardized questionnaire of reduced size seems to be a suitable method for evaluating patient preference for different inhalation devices.
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.
Consecutive determinations of erythropoietin in serum (s-Epo) were made in ten patients with chronic hypoxia starting domiciliary long-term oxygen therapy (LTO). After 24 h of supplementary oxygen treatment there was a fall in the median s-Epo level from 11.3 to 4.4 IU.l-1 (p less than 0.01). The initial decrease in s-Epo in conjunction with oxygen treatment was not sustained after one and three months of LTO. S-Epo levels above the reference range (3.3-13.5 IU.l-1) were found in three patients before and during LTO and in another two patients during LTO. Markedly elevated s-Epo levels were found in two patients with hypoxia and hypercapnia at the time of blood sampling. A significant negative relationship was found between the arterial oxygen tension and the log value for the s-Epo level (r = 0.40, p less than 0.005). The s-Epo levels were found to be normal in half of the measurements in patients using oxygen less than 15 h daily, a fact that indicates that s-Epo measurements are probably not suitable as indicators of compliance with LTO.
On January 1, 1987, 560 patients (267 male) were registered as using long-term domiciliary oxygen therapy (LTO) in Sweden. The duration of LTO before this date varied between 10 days and 11 yrs. During a two-year follow-up 12 patients had their LTO withdrawn because they were no longer hypoxic. In 139 patients the arterial oxygen tension (PaO2) on breathing air was registered three times. In seventeen (12%) of these patients the PaO2 exceeded 7.5 kPa on all three control occasions. The two year actuarial survival in all patients was 57%. The two year actuarial survival was 77% in patients with kyphoscoliosis, 56% in patients with sequelae of tuberculosis, 54% in patients with chronic obstructive pulmonary disease (COPD) and 39% in patients with fibrosis. In COPD patients survival was predicted by age, sex, current smoking habits, arterial carbon dioxide tension (PacO2) when breathing oxygen and oral steroid medication. A poor Zubrod performance score was associated with a high mortality rate in all patient groups.
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A double blind, parallel group study was carried out to investigate the effect of inhaled budesonide in a moderate (200 micrograms) and a low (100 micrograms) twice daily dosage compared with the effect of placebo in 103 adults with mild symptomatic asthma. Subjects recorded peak expiratory flow (PEF), asthma symptoms, and beta 2 agonist consumption at home for a period of seven weeks (a one week run in and six weeks' treatment). Morning baseline PEF (around 80% of predicted normal) increased non-significantly to 88% with 200 micrograms budesonide daily and to 90% (p less than 0.05) with 400 micrograms, compared with 81% with placebo. Evening PEF (around 94% of predicted normal) did not change significantly with active or placebo treatment. By comparison with placebo, there was a significant decrease in nocturnal asthma symptoms and beta 2 agonist consumption. The changes during the day were less pronounced and significant only for 400 micrograms budesonide daily. No significant differences between the two active treatments were detected. It is concluded that low doses of inhaled budesonide are effective in patients with mild symptomatic asthma, particularly for night time symptoms and early morning lung function. The early introduction of inhaled corticosteroids for patients with mild asthma and night time symptoms may improve their quality of life during the night and early morning.
In 62 consecutive cases of pneumothorax, suction treatment was applied by a new method using a recently-developed vacuum pump (Pleupump) allowing the quantification of the volume of air through the chest drain. The previous 62 cases of pneumothorax treated with standard suction equipment were used as a control group. The new technique resulted in a statistically significant reduction in the mean suction treatment time from 8.1 to 4.8 days in patients with spontaneous pneumothorax. The mean total number of days in hospital was reduced from 10.0 to 6.5. This was accomplished without an increase in the number of complications or recurrences of the pneumothorax.
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The dose-response effects of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) administered b.i.d. with the aid of metered dose aerosols were studied in 128 patients (67 men and 61 women, mean age 53 years) suffering from asthma bronchiale. The study was designed as a multi-centre, double-blind, four-period cross-over study, followed by a single-blind double placebo period. BDP was administered in doses of 400 and 1000 micrograms, and BUD in doses of 400 and 800 micrograms. The results in terms of peak expiratory flow (PEF) in the morning and evening, daily symptoms score and use of inhaled beta 2-agonists did not reveal any clinically significant differences between the drugs or between high (800 micrograms BUD, 1000 micrograms BDP) and low (400 micrograms BUD/BDP) doses. However, statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods. Adverse effects consisting mainly of oropharyngeal candidiasis, hoarseness and cough occurred in 54 of 468 treatment months (12%). The carry-over effects of inhaled steroids are longer lasting than was previously assumed.
A national register of patients undergoing long-term oxygen therapy in Sweden was started in 1987. Of the population of 8.4 million, 560 patients (267 males) were registered as undergoing domiciliary oxygen treatment on January 1, 1987. These registered patients, aged between 2-86 yrs (mean age 65 yrs), constituted some 90% of all patients receiving domiciliary oxygen therapy because of chronic hypoxaemia on that date. The chronic respiratory diseases leading to hypoxaemia (more than one diagnosis could be registered for each patient) were: chronic obstructive pulmonary disease (COPD) (393), sequelae from pulmonary tuberculosis (92), thoracic deformity (97), interstitial fibrosis (44), benign pleural disease (22) and others (84). Concentrators were used by 253 patients and high-pressure compressed gas cylinders by 307. Arterial blood gas analyses were registered for 547 patients. The mean arterial oxygen tension (PaO2) when breathing air was 6.5 +/- 1.1 kPa and 9.0 +/- 1.4 kPa when breathing oxygen. The mean arterial carbon dioxide tension (PaCO2) without oxygen was 6.5 +/- 1.5 kPa and 6.8 +/- 1.5 kPa with oxygen. The register forms a data-base which can be used for the evaluation of different home oxygen systems, regional differences in the access to treatment and treatment performance and decisions relating to health care economics.
In 1985 a survey questionnaire was sent to 119 individuals who had been hospitalized as children (aged 5-15) because of asthma over a ten-year period (1953-1962). Four patients out of 123 had died, three of them because of asthma. The response rate was 98% and the follow-up covered a time range from 23 to 31 years. The mean age at follow-up was 33 (range 26-43) and sixty-four individuals (55%) were free from symptoms. The severity of asthma was evaluated by means of a symptom-score divided into 5 degrees (no symptoms to continuous asthma). Symptom onset under the age of 4, the occurrence of atopic eczema and increased sensitivity to pollen, furry animals and respiratory tract infections correlated significantly (p less than 0.05, p less than 0.05 and p less than 0.01, respectively) with the occurrence of continuous adult asthma. A factor which appears to predict the development of adult asthma is a high level of medical care, expressed as the number of days of hospitalization during childhood.