Effects of weight loss on peak flow variability, airways obstruction, and lung volumes in obese patients with asthma.

STUDY OBJECTIVES: To clarify the pathophysiologic features of the relation between asthma and obesity, we measured the effects of weight reduction on peak expiratory flow (PEF) variability and airways obstruction, compared to simultaneous changes in lung volumes and ventilatory mechanics in obese patients with stable asthma. METHODS: Fourteen obese asthma patients (11 women and 3 men; aged 25 to 62 years) were studied before and after a very-low-calorie-diet period of 8 weeks. PEF variability was determined as diurnal and day-to-day variations. FEV(1) and maximal expiratory flow values were measured with a flow-volume spirometer. Lung volumes, airways resistance (Raw), and specific airways conductance were measured using a constant-volume body plethysmograph. Minute ventilation was monitored in patients in supine and standing positions. RESULTS: As patients decreased their body mass index (SD) from 37.2 (3.7) to 32.1(4.2) kg/m(2) (p < 0. 001), diurnal PEF variation declined from 5.5% (2.4) to 4.5% (1.5) (p = 0.01), and day-to-day variation declined from 5.3% (2.6) to 3. 1% (1.3) (p < 0.005). The mean morning PEF, FEV(1), and FVC increased after weight loss (p = 0.001, p < 0.005, and p < 0.05, respectively). Flow rate at the middle part of FVC (FEF(25-75)) increased even when related to lung volumes (FEF(25-75)/FVC; p < 0. 05). Functional residual capacity and expiratory reserve volume were significantly higher after weight loss (p < 0.05 and p < 0.005, respectively). A significant reduction in Raw was found (p < 0.01). Resting minute ventilation decreased after weight loss (p = 0.01). CONCLUSION: Weight loss reduces airways obstruction as well as PEF variability in obese patients with asthma. The results suggest that obese patients benefit from weight loss by improved pulmonary mechanics and a better control of airways obstruction.

Immediate and long term effects of weight reduction in obese people with asthma: randomised controlled study.

OBJECTIVE: To investigate the influence of weight reduction on obese patients with asthma. DESIGN: Open study, two randomised parallel groups. SETTING: Private outpatients centre, Helsinki, Finland. PARTICIPANTS: Two groups of 19 obese patients with asthma (body mass index (kg/m(2)) 30 to 42) recruited through newspaper advertisements. INTERVENTION: Supervised weight reduction programme including 8 week very low energy diet. MAIN OUTCOME MEASURES: Body weight, morning peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)); and also asthma symptoms, number of acute episodes, courses of oral steroids, health status (quality of life). RESULTS: At the end of the weight reducing programme, the participants in the treatment group had lost a mean of 14.5% of their pretreatment weight, the controls 0.3%. The corresponding figures after one year were 11.3% and a weight gain of 2.2%. After the 8 week dieting period the difference in changes in percentage of predicted FEV(1) from baseline in the treatment and control groups was 7.2% (95% confidence interval 1.9% to 12.5%, P=0. 009). The corresponding difference in the changes in FVC was 8.6% (4. 8% to 12.5%, P<0.0001). After one year the differences in the changes in the two groups were still significant: 7.6% for FEV(1) (1. 5% to 13.8%, P=0.02) and 7.6% for FVC (3.5% to 11.8%, P=0.001). By the end of the weight reduction programme, reduction in dyspnoea was 13 mm (on a visual analogue scale 0 mm to 100 mm) in the treatment group and 1 mm in the control group (P=0.02). The reduction of rescue medication was 1.2 and 0.1 doses respectively (P=0.03). After one year the differences in the changes between the two groups were -12 for symptom scores (range -1 to -22, P=0.04) and -10 for total scores (-18 to -1, P=0.02). The median number of exacerbations in the treatment group was 1 (0-4) and in the controls 4 (0-7), P=0.001. CONCLUSION: Weight reduction in obese patients with asthma improves lung function, symptoms, morbidity, and health status.

Salbutamol inhalation has no effect on myocardial ischaemia, arrhythmias and heart-rate variability in patients with coronary artery disease plus asthma or chronic obstructive pulmonary disease.

OBJECTIVES: Inhaled beta-2 agonists raise heart rate, systolic blood pressure and contractility, all of which cause an increase in oxygen consumption of the heart. We performed a study on the influence of inhaled salbutamol on myocardial ischaemia, rhythm, and heart rate variability as assessed by Holter monitoring of 24 patients with coronary artery disease (CAD) and clinically stable asthma or chronic obstructive pulmonary disease (COPD). DESIGN: In hospital the patients received 0.2 mg (hour 1), 0.4 mg (hour 6), 0.8 mg (hour 13) of salbutamol with a metered-dose inhaler and a spacer, and 5 mg (hour 25) with a nebulizer; symptoms, peak expiratory flow (PEF), 30-h Holter monitoring, and blood pressure (BP) were recorded. The study parameters were compared for the hour preceding and following each dose of salbutamol. RESULTS: No cardiac symptoms were associated with salbutamol inhalation. PEF increased after all doses (P < 0.005). A dose of 0.2 mg salbutamol induced no changes in heart rate, whereas dose of 0.4 mg increased heart rate from a mean of 75 +/- 13 to 79 +/- 14 beats min-1 (P < 0.005), and a dose of 0.8 mg from 76 +/- 14 to 78 +/- 15 beats min-1 (P < 0.05). No changes in systolic BP appeared after any dose of salbutamol. The diastolic BP was lowered after 0.8 mg of salbutamol from 86 +/- 12 to 82 +/- 10 mmHg (P < 0.05). The 5 mg of nebulized drug provoked no significant changes in heart rate or BP. Myocardial ischaemia, heart rate variability and ventricular arrhythmias remained unaltered with all doses. CONCLUSIONS: The commonly used doses of inhaled or nebulized salbutamol induced no acute myocardial ischaemia, arrhythmias or changes in heart rate variability in patients with CAD and clinically stable asthma or COPD.

Acute asthma during pregnancy.

BACKGROUND: Acute asthma during pregnancy is potentially dangerous to the fetus. The aim of this study was to investigate the effect of an acute attack of asthma during pregnancy on the course of pregnancy or delivery, or the health of the newborn infant, and to identify undertreatment as a possible cause of the exacerbations. METHODS: Five hundred and four pregnant asthmatic subjects were prospectively followed and treated. The data on 47 patients with an attack of asthma during pregnancy were compared with those of 457 asthmatics with no recorded acute exacerbation and with 237 healthy parturients. RESULTS: Of 504 asthmatics, 177 patients were not initially treated with inhaled corticosteroids. Of these, 17% had an acute attack compared with only 4% of the 257 patients who had been on inhaled anti-inflammatory treatment from the start of pregnancy. There were no differences between the groups as to length of gestation, length of the third stage of labour, or amount of haemorrhage after delivery. No differences were observed between pregnancies with and without an exacerbation with regard to relative birth weight, incidence of malformations, hypoglycaemia, or need for phototherapy for jaundice during the neonatal period. CONCLUSIONS: Patients with inadequate inhaled anti-inflammatory treatment during pregnancy run a higher risk of suffering an acute attack of asthma than those treated with an anti-inflammatory agent. However, if the acute attack of asthma is relatively mild and promptly treated, it does not have a serious effect on the pregnancy, delivery, or the health of the newborn infant.

Controlled trial of methotrexate in patients with severe chronic asthma.

The aim of this study was to investigate the efficacy and adverse effects of methotrexate (MTX) in the treatment of severe chronic asthma in 12 patients with severe asthma requiring continuous treatment with oral steroids at the Outpatient Department of Helsinki University Central Hospital. The study was a randomised, double-blind placebo-controlled trial of methotrexate treatment 15 mg weekly on a crossover basis over 24 weeks. During the 2 weeks baseline phase the mean dose of oral steroids administered was 10.9 (3.2-28) mg.day-1, and the mean dose of inhaled steroids administered was 2.3 (1.6-3.2) mg budesonide or beclomethasone. The average dose of oral steroids administered was 12.8 mg.day-1 during the last 2 placebo weeks but only 7.9 mg.day-1 during the last 2 weeks with MTX treatment. The reduction in daily dose of oral steroids was 38%, while daily bronchodilator use was reduced by 22%. During MTX treatment the patients experienced significantly less wheezing, dyspnoea and coughing. Nine out of 12 patients reported better asthma control during MTX treatment. The peak expiratory flow rate (PEF) 1-s forced expiratory volume (FEV1) values did not differ between MTX and placebo treatments. There was no statistical correlation between serum MTX concentration and clinical improvement. No serious adverse effects of MTX were found during the study. It was concluded that low-dose MTX may be beneficial for severe chronic asthma and that this therapy is well tolerated by patients.

Slow-release theophylline in pregnant asthmatics.

STUDY OBJECTIVE: Oral theophylline treatment may be helpful in controlling severe asthma during pregnancy. This treatment, however, has been suspected of causing both complications and malformations. The objective of this investigation was to study the influence of theophylline treatment on the course of pregnancy and delivery and on maternal and infant health. SETTING: Respiratory unit, antenatal outpatient departments, and labor and delivery rooms. DESIGN: Case-control study. PATIENTS: The data of 212 pregnant asthmatics with theophylline treatment (AT) were compared with findings in 292 pregnant asthmatics without theophylline (A) and 237 nonasthmatic pregnant control subjects (C). RESULTS: There were no significant differences among groups as to age, height, age of onset of asthma, lung function, parity, or smoking. In the AT group, 19% were treated for acute exacerbations of the asthma as compared with 6% in the A group (p < 0.001). The incidence of preeclampsia was higher in the AT (15.6%) than in the C (6.4%) group (p < 0.03). Theophylline treatment at term was not associated with premature contractions or premature rupture of membranes, hemorrhage, placenta previa, abruption of the placenta, abnormal fetus position, frequent induction or augmentation of labor, prolonged third phase of delivery, or increased hemorrhage post partum. No differences among groups were seen with regard to gestational age, birth weight, Apgar scores, or perinatal deaths. Jaundice in the newborn, necessitating treatment with blue light, was more common in the AT (15.0%) than in the C group (7.8%) (p < 0.05). Three infants of 121 patients treated with theophylline during the first trimester were born with malformations; in the 91 patients treated with theophylline only during the second and third trimester, and the asthmatic control group, the corresponding figures were 4 and 3. CONCLUSIONS: During the second and third trimesters until term, theophylline treatment using moderate doses can be considered safe. The safety of theophylline treatment during the first trimester with regard to teratogenicity remains to be determined.

Evaluation of a new spacer device for drug inhalation.

We have studied the efficacy and acceptability of a new inhalation spacer device. The functional principle of the device, differing from that of conventional spacers, is based on evaporation of the propellant during circular movement of the aerosol in a small spherical chamber. We assessed the bronchodilating effect of salbutamol (Salbuvent) inhaled with the new spacer (Rondo) compared with salbutamol (Ventoline) inhaled with the spacer Volumatic and with salbutamol (Salbuvent) inhaled with a conventional metered dose actuator using a double-blind cross-over arrangement. Fifteen asthmatic patients were treated over a period of 4 weeks. They used each of the three different devices for 2-3 days every week. Peak expiratory flow rates were recorded every morning after one and after two puffs of the study drugs. The bronchodilator responses to the three treatments were similar within narrow ranges of estimate. By visual analogue scale assessment the new spacer was significantly easier to handle (P < 0.05) and more convenient to carry around (P < 0.01) than Volumatic.

Fire-eater's lung.

Acute pneumonitis following aspiration of petroleum products is usually related to accidental poisonings in children. We describe here two cases of hydrocarbon pneumonitis in fire-eaters, caused by accidental aspiration of petroleum during the performance of fire-eating. Both patients had cough, dyspnoea, chest pain and fever. Chest X-rays showed basal lung infiltrates and, 2 weeks later, pneumatocele formations. Reversible bronchial hyperresponsiveness and restrictive ventilatory limitation were demonstrated in one of the patients. The bronchoalveolar lavage specimen showed cytoplasmic vacuolation of the macrophages and neutrophilia. After treatment with antibiotics and corticosteroids the symptoms disappeared and the lung function values returned to normal within 2-3 weeks. Radiological resolution of the pneumatoceles occurred within 2-12 months.

Effects of captopril on blood pressure and respiratory function compared to verapamil in patients with hypertension and asthma.

Seventeen adult patients with moderate and stable bronchial asthma and established essential hypertension (WHO I or II) were evaluated in a randomized, double-blind, crossover study of the effects of captopril (50-100 mg/day) and verapamil (160-240 mg/day) on blood pressure, orthostatic reactions, respiratory function, and asthmatic symptoms. The effect of both drugs on blood pressure was significant. Blood pressure (mean of 161/98 mm Hg initially) decreased to a mean of 147/90 and 160/91 mm Hg on captopril and verapamil, respectively, with normal orthostatic changes. There were no significant differences in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal expiratory flow at 50% of FVC (MEF50), or peak expiratory flow (PEF) measurements at the end of each treatment period. The subjective severity of asthma did not change significantly during the trial. No significant cough symptoms were reported on captopril.

Evening primose oil and fish oil are ineffective as supplementary treatment of bronchial asthma.

The effect of daily dietary supplementation with 15 to 20 mL of evening primrose seed oil or fish oil was assessed by comparison with olive oil as placebo in a cross-over study in 29 asthmatics. During 10 weeks of each regimen, the patients kept record of symptoms, peak expiratory flow rates and medication. Plasma and urine TxB2, PGE2, PGF2 alpha and 6 keto-PGF1 alpha and plasma fatty acid composition of plasma cholesterol esters were measured at the end of each treatment period. There were no differences between regimes with regard to peak flow rates, symptoms, or drug consumption. Plasma PGE2 levels increased during the fish oil treatment but there were no changes in other prostanoids in plasma or urine. The fatty acid pattern of plasma cholesterol esters showed significant differences between the supplementation periods. We conclude that moderate doses of evening primrose oil or fish oil are ineffective as a supplementary treatment of bronchial asthma.

The reducing effects of tazifylline on histamine-induced bronchoconstriction in atopic asthmatics.

Percentage reductions in the peak flow rates to a standardized number of histamine inhalations were compared after 7 days of treatment with 10 mg bd tazifylline and after 7 days of placebo in a randomized crossover study in 11 male seasonal atopic asthmatics. After tazifylline, mean % reductions in peak flow rates were significantly lower than after placebo (p = 0.03). The effects of tazifylline had disappeared within 7 days of stopping treatment. Using a 50% decrease in bronchial reactivity as the criteria of "protection", 7 of the subjects were "protected" by tazifylline only and none by placebo only (p = 0.03).

Influence of terbutaline on natural killer cell activity.

Studies on the effect of cAMP-inducing agents on NK activity have been contradictory. The aim of this study was to investigate the acute effects of beta-agonists on NK activity in vivo in 15 asthmatics and 3 healthy volunteers. Blood samples of NK activity were taken at regular intervals after placebo and after subcutaneous injection of 7 micrograms/kg of terbutaline. NK activity was measured by the standard 4-h Chromium51 release assay against the leukemic line K 562 at a 50:1 effector/target cell ratio. Compared with placebo, terbutaline induced within 30-60 min a significant increase in NK activity which lasted less than 2 h. Further studies are necessary to investigate the effect of long-term beta-agonist treatment on NK activity.

Asthma and pregnancy: a prospective study of 198 pregnancies.

A study was designed to investigate whether asthma, when carefully managed, is associated with an increased risk of complications in connection with pregnancy. One hundred and eighty one asthmatic women were monitored during 198 pregnancies. Antiasthmatic treatment consisted of inhaled beta 2 adrenergic drugs, beclomethasone, sodium cromoglycate, oral theophylline, and systemic corticosteroids as needed. Postpartum information on asthmatic symptoms and infant feeding was collected by means of a questionnaire. A control group of 198 non-asthmatic pregnant women was matched for age and parity. Atopic women had less severe asthma than non-atopic women. During pregnancy 40% of the patients were managed with the same antiasthmatic medication as before pregnancy; 18% needed less and 42% more medication. Pre-eclampsia occurred more often in asthmatic than control subjects, especially in patients with severe asthma. Hypoglycaemia occurred more often in infants of mothers with severe asthma than in infants of mothers with less severe disease. Theophylline medication at term did not influence labour or delivery. Asthma caused no emergencies during labour. Among the asthmatic subjects 28% of babies were delivered by caesarean section compared with 17% in the control group. There was no difference between asthmatic and control subjects with regard to length of gestation, birth weight, incidence of perinatal deaths, low Apgar scores, neonatal respiratory difficulties, hyperbilirubinaemia, or malformations. It is concluded that severe asthma or systemic corticosteroid treatment (or both) during pregnancy seems to increase the incidence of mild pre-eclampsia in the mother and hypoglycaemia in the infant. The findings suggest that careful supervision of asthma during pregnancy and labour by obstetricians and chest physicians working in close collaboration should prevent most of the serious obstetric and neonatal complications of asthma in pregnancy reported by previous authors.

The role of infection in asthma.

The possible role of bacterial, viral and fungal infections in the development, exacerbation and treatment of asthma are discussed. Although bacterial allergy has in the past been advocated as an important etiologic factor for asthma, the evidence is inconclusive. Hyposensitization with bacterial antigens is no longer an accepted treatment. Bacterial infection of the nasal sinuses and bronchi may exacerbate an asthmatic attack and in some cases patients benefit from antibiotic therapy. However, bacterial infections in asthma and allergic rhinitis do not always require treatment and if treated this is not sufficient alone to reverse symptoms. Opinions vary as to the importance of viral infections. There is evidence that the immunologic consequences of intrabronchial infection with Aspergillus fumigatus may cause exacerbations of asthma.