Radiographic measurement of total lung capacity in acute asthma.

The thoracic cage appears to be large during attacks of asthma. Lung volume measurements by body plethysmography and helium dilution have suggested that total lung capacity may be increased during an acute attack of asthma, but doubt has been cast on the accuracy of these measurements in the presence of airflow obstruction. The change in total lung capacity has therefore been investigated during and after an acute attack of severe asthma in 32 patients by a radiographic technique. There was a small decrease (0.29 l) in mean total lung capacity between admission and follow up, though a quarter of the subjects showed a slight increase. There was no correlation between change in total lung capacity and change in expiratory flow rates, arterial carbon dioxide tension on admission, body mass index, and length of stay in hospital. Our findings agree with previous reports of a decrease in total lung capacity with improving airway obstruction, but the changes were small and inconsistent.     

Health status measurement in chronic obstructive pulmonary disease

Health status measurement is a common feature of studies in chronic obstructive pulmonary disease (COPD). This review assesses recent evidence for the validity of these measurements and their role as measures of the overall impact of the disease on the patient's daily life and wellbeing. It reviews the mostly widely used COPD specific questionnaires and examines the contribution that they make to an assessment of the overall effect of treatment. Finally, it addresses the question of how symptomatic benefit may be assessed in individual patients in routine practice.     

Effects of regular salmeterol on lung function and exercise capacity in patients with chronic obstructive airways disease.

BACKGROUND: The aim of this study was to evaluate the effects of single and chronic dosing with salmeterol on exercise capacity and lung function in patients with chronic obstructive pulmonary disease. METHODS: Twenty nine patients of mean (SE) age 64 (1.5) years, forced expiratory volume in one second (FEV1) 42(3)% of predicted, and 5-15% reversibility to salbutamol 200 micrograms were randomised to receive four weeks treatment with salmeterol 50 micrograms twice daily or placebo in a double blind crossover fashion with a one week washout period in between. Measurements of spirometric parameters, static lung volumes, and exercise capacity were made one and six hours after a single dose, and six hours after the final dose of salmeterol or placebo. RESULTS: Salmeterol produced a small increase in FEV1 at one and six hours after a single dose, and this was maintained after chronic dosing (mean difference and 95% CI versus placebo): single dosing at one hour 0.07 (95% CI 0.02 to 0.11) 1, single dosing at six hours 0.16 (95% CI 0.09 to 0.22) 1, chronic dosing at six hours 0.11 (95% CI 0.03 to 0.19) 1. The increase in forced vital capacity (FVC) was greater with salmeterol than with placebo six hours after single but not chronic dosing: single dosing at six hours 0.17 (95% CI 0.04 to 0.29) 1, chronic dosing at six hours 0.02 (95% CI -0.18 to 0.22) 1. Slow vital capacity was increased after treatment with salmeterol compared with placebo one and six hours after single but not after chronic dosing. There were no significant differences in static lung volumes or exercise capacity after single or chronic dosing with salmeterol compared with placebo. Patients reported a significantly lower Borg score for perceived exertion following the six minute walk after chronic treatment with salmeterol compared with placebo. CONCLUSIONS: Salmeterol produced a small improvement in spirometric values compared with placebo consistent with the degree of reversibility originally shown by the subjects to salbutamol 200 micrograms. This was not associated with improvements in static lung volumes or exercise capacity, but there was some symptomatic benefit in that patients were able to walk the same distance in six minutes with less perceived exertion.     

Effects of corticosteroids on bronchodilator action in chronic obstructive lung disease.

BACKGROUND: Short term treatment with corticosteroids does not usually reduce airflow limitation and airway responsiveness in patients with chronic obstructive lung disease. We investigated whether corticosteroids modulate the effects of inhaled salbutamol and ipratropium bromide. METHODS: Ten non-allergic subjects with stable disease were investigated; eight completed the randomised, double blind, three period cross over study. Treatment regimens consisted of 1.6 mg inhaled budesonide a day for three weeks, 40 mg oral prednisone a day for eight days, and placebo. After each period cumulative doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo were administered on separate days until a plateau in FEV1 was reached. A histamine challenge was then performed. RESULTS: At the end of placebo treatment mean FEV1 was 55.5% predicted after inhaled placebo, 67.9% predicted after salbutamol and 64.0% predicted after ipratropium. Compared with the results after the placebo period the FEV1 with salbutamol increased by 0.7% predicted after treatment with budesonide and by 0.7% predicted after treatment with prednisone; the FEV1 with ipratropium increased by 0.7% predicted after budesonide and by 4.8% predicted after prednisone; none of these changes was significant. After placebo treatment the geometric mean PC20 was 0.55 mg/ml after placebo, 1.71 mg/ml after salbutamol and 0.97 mg/ml after ipratropium. Compared with the placebo period the PC20 with salbutamol was increased by 0.86 doubling concentrations after treatment with budesonide, and by 0.67 doubling concentrations after prednisone; the PC20 with ipratropium increased by 0.03 and 0.34 doubling concentrations after budesonide and after prednisone respectively compared with placebo; none of these changes was significant. CONCLUSIONS: In non-allergic subjects with chronic obstructive lung disease short term treatment with high doses of inhaled or oral corticosteroids does not modify the bronchodilator response to salbutamol or ipratropium or the protection provided by either drug against histamine. Salbutamol produces greater protection from histamine induced bronchoconstriction than ipratropium.     

Morphometry of pulmonary arteries from angiograms in chronic obstructive lung disease.

The application of morphometric techniques based on Strahler orders to the study of pulmonary angiograms is described. When the pulmonary arterial tree is ordered by Strahler's method, peripheral branches have the lowest orders and the main pulmonary artery the highest order. The mean diameter of vessels in each order can then be determined. Pulmonary angiograms were obtained from 16 patients, 10 of whom had chronic obstructive lung disease (COLD), the other six having normal angiograms. Six orders of branching were found in vessels of 1 mm diameter or greater, and a plot of log mean diameter versus order from the normal angiograms was linear. The mean diameters of orders 2, 3, and 4 (diameter 2 to 7 mm) from COLD patients were significantly reduced ((p less than 0.01) and the log mean diameter versus order plot was concave upwards. These changes were more marked when TLC was raised than when it was normal. Plots of diameters of vessels from zones of the lung in which the pathology was well advanced (as judged by radiological changes) showed even greater reduction in the middle orders. These changes are probably the result of stretching of vessels in emphysematous lesions and diminution of blood flow from loss of capillary bed.     

Vertebral compression fractures and mineral metabolism in chronic obstructive lung disease.

Chronic obstructive lung disease has been reported as a cause of osteoporosis, though whether this association is due to the disease itself or to corticosteroid treatment has not been elucidated. We studied 44 male patients with chronic obstructive lung disease (mean (SD) FEV1 39% (14%) of predicted normal) who were not having long term corticosteroids. No differences in a vertebral deformity score or in metacarpal index were found between them and a control group of similar age. Indices of bone formation (serum osteocalcin) and bone resorption (urinary hydroxyproline) were normal and parathyroid hormone and 1,25-dihydroxyvitamin D were also normal. Serum 25-hydroxyvitamin D was decreased, indicating depleted vitamin D. Calcitonin concentrations were higher in the patient than in the control group of the same age. There was no increase in the prevalence of osteoporosis in patients with chronic obstructive lung disease who had not received long term corticosteroid treatment. Increased concentrations of calcitonin may protect the skeleton from the detrimental effect of hypovitaminosis D.     

Blood volume studies in chronic obstructive non-specific lung disease

Blood volume studies in chronic hypoxic lung disease have produced conflicting results. Some have demonstrated that the red cell volume-hypoxic relationship is similar to that in normal subjects, whereas others have found that it is subnormal. Plasma volume has not been shown to be related to hypoxia. To elucidate this further, 45 patients with chronic obstructive bronchitis were studied. They were on average hypoxic at rest and on exertion, but mean values of red cell volume, plasma volume, venous haematocrit, red cell count, and haemoglobin concentration were normal. Red cell volume was linearly related to the degree of hypoxia, but the response was subnormal. Arterial oxygen saturation rather than tension was the main determinant of red cell volume, and resting values correlated better than exercise values with red cell volume. The best correlations were obtained when red cell volume was expressed as a function of the lean body mass rather than the total body weight. Red cell volume was also linearly related to arterial Co₂ tension. Plasma volume did not correlate with any of the blood gases. The subnormal polycythaemic response to hypoxia may have been caused partially by latent iron deficiency and chronic infection; but severe hypoxia, hypercapnia, and gastrointestinal bleeding were not aetiological factors. The importance of tissue hypoxia in the regulation of the erythropoietic response and the reasons why previous blood volume studies have produced conflicting results are discussed.     

Value of theophylline treatment in patients handicapped by chronic obstructive lung disease.

BACKGROUND: It is still not certain whether it is worth using theophylline in addition to inhaled bronchodilators and corticosteroids to treat obstructive airways disease. This trial was designed to test whether the addition of prescribed theophylline in doses sufficient for sustained optimal steady state plasma concentrations would produce any detectable additional advantage in spirometric or functional variables in these handicapped patients. METHODS: A randomised, double blind, placebo controlled, crossover study of added theophylline treatment was aimed at steady state plasma concentrations of 10 and 17 mg/l, the dose being calculated individually by Bayesian parameter estimation and maintained for six weeks along with the patient's previously prescribed bronchodilators and steroids. Of 20 patients sequentially recruited, 15 provided data that could be analysed. All had chronic obstructive lung disease with a mean forced expiratory volume in the first second (FEV1) up to about 30% of the predicted value and gave no history of being treated with theophylline. The protocol included spirometry, whole body plethysmography, and treadmill exercise. Measurements also included steady state plasma theophylline concentrations and trapped gas volume. Quality of life was assessed by an established questionnaire method covering breathlessness in everyday activities, fatigue, emotional function, and control over the disease. RESULTS: Both target plasma concentrations were achieved. Improvements in peak flow (PEF; mean 20%), trapped gas volumes (38%), two stage vital capacity (15%), distances walked (48%), breathlessness in everyday activities (32%), and fatigue (18%) were found at the higher plasma concentration only. FEV1, forced vital capacity (FVC), emotional function, and control did not change. CONCLUSION: Theophylline treatment with sustained steady state concentrations about 17 mg/l provides worthwhile objective and subjective further benefits for patients handicapped by chronic obstructive lung disease when it is added to bronchodilators and corticosteroids.     

Prediction of oxygenation during sleep in patients with chronic obstructive lung disease.

The accuracy of a prediction equation for assessing the lowest arterial oxygen saturation (SaO2) during sleep was determined in 24 consecutive patients with chronic obstructive lung disease referred for assessment for home oxygen therapy. Subjects had a mean (SD) FEV1 of 0.81 (0.31) litre and an FEV1/FVC of 37% (12%). There was reasonable agreement between predicted and measured values (mean difference [predicted-measured] = -2.5%) but the prediction was not precise as the 95% confidence interval for the difference was +8% to -13%. The duration of arterial oxygen desaturation, defined as the percentage of total sleep time spent below a given SaO2, was not predicted accurately. It is concluded that nocturnal arterial oxygen desaturation in individual patients with chronic obstructive lung disease cannot be predicted from "awake" measurements with sufficient accuracy to be clinically useful.     

Exercise capacity after lobectomy in patients with chronic obstructive pulmonary disease

The aim of this study is to clarify whether patients with chronic obstructive pulmonary disease (COPD) lose less exercise capacity after lobectomy than do those without COPD, to the same extent as ventilatory capacity and lobectomy for selected patients with severe emphysema improve exercise capacity like ventilatory capacity. Seventy non-COPD patients (N group), 16 mild COPD patients (M group), and 14 moderate-to-severe COPD patients (S group) participated. Pulmonary function and exercise capacity tests were performed on the same day preoperatively and six months to one year after lobectomy. The S group lost significantly less FEV(1) (forced expiratory volume in 1 s) after lobectomy than did the N or M group (P<0.0001 and P<0.005). However, their loss of exercise capacity was equivalent to that for the N and M groups. For the S group, there was a significant, negative correlation between preoperative FEV(1) % of predicted and percentage change in FEV(1) and maximum oxygen consumption (VO2 max) after lobectomy (r=-0.93, P<0.0001 and r=-0.64, P=0.01). In moderate-to-severe COPD patients, patients with a lower preoperative FEV(1) % of predicted experienced a smaller decrease in FEV(1) and VO2 max after lobectomy.     

Assessment of the right ventricle by magnetic resonance imaging in chronic obstructive lung disease.

Right ventricular wall and chamber volume were measured by magnetic resonance imaging in 16 patients with stable chronic obstructive lung disease who subsequently underwent measurement of pulmonary haemodynamics by right heart catheterisation. The patients had a forced expiratory volume in one second of 0.7 (SD 0.3) litres, a forced vital capacity of 2.4 (1.0) l, an arterial oxygen tension (PaO2) of 6.5 (1.3) kPa, an arterial carbon dioxide tension (PaCO2) of 6.5 (1.0) kPa, and a mean pulmonary arterial pressure 30 (10) mm Hg. The mean right ventricular free wall volume was 57.1 (22.6) cm3, compared with a mean value of 115.0 (44.3) cm3 for the left ventricle and interventricular septal volume. The right ventricular chamber volume at end systole was 44.8 (23.4) cm3, whereas the left ventricular end systolic chamber volume was 51.1 (35.1) cm3. The right ventricular free wall volume correlated with the right ventricular chamber volume (r = 0.71), systolic (r = 0.74) and mean (r = 0.72) pulmonary arterial pressure, pulmonary vascular resistance (r = 0.67), and PaCO2 (r = 0.56). There was no significant correlation between the right ventricular free wall volume and PaO2 or the right ventricular ejection fraction, measured by radionuclide ventriculography. Assessment of the right ventricle by magnetic resonance imaging may help to better define patients with cor pulmonable and assess the long term effects of treatment in such patients.     

Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease

BACKGROUND: Muscle wasting and decreased muscle oxidative capacity commonly occur in patients with chronic obstructive pulmonary disease (COPD). Polyunsaturated fatty acids (PUFA) have been shown to mediate several inflammatory and metabolic pathways which may be involved in the pathogenesis of muscle impairment in COPD. The aim of this study was to investigate the effect of PUFA modulation on systemic inflammation, reversal of muscle wasting, and functional status in COPD. METHODS: Eighty patients with COPD (57 men) with forced expiratory volume in 1 second (FEV1) 37.3 (13.8)% predicted received 9 g PUFA or placebo daily in a double blind randomised fashion during an 8 week rehabilitation programme. Body composition (bioelectrical impedance), functional capacity (lung function, incremental cycle ergometry test, submaximal cycle test, isokinetic quadriceps strength) and inflammatory markers (C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha) were assessed at baseline and after 8 weeks. RESULTS: Both groups had similar increases in weight, fat-free mass (FFM), and muscle strength. The peak load of the incremental exercise test increased more in the PUFA group than in the placebo group (difference in increase 9.7 W (95% CI 2.5 to 17.0), p = 0.009) even after adjustment for FFM. The duration of the constant work rate test also increased more in patients receiving PUFA (difference in increase 4.3 min (95% CI 0.6 to 7.9), p = 0.023). The positive effects of PUFA could not be attributed to a decrease in systemic levels of CRP, IL-6 and TNF-alpha. CONCLUSIONS: This is the first study to show beneficial effects of PUFA on exercise capacity in patients with COPD.     

Exercise-induced airway obstruction in relation to chronic obstructive lung disease

Gimeno, F., Berg, W. Chr., Steenhuis, E. J., de Vries, K., Peset, R., and Sluiter, H. J. (1974).Thorax,29, 16-20. Exercise-induced airway obstruction in relation to chronic obstructive lung disease. Forty-two patients with chronic obstructive lung disease and clinically suspected exercise-induced airway obstruction were studied to ascertain whether those with proven exercise-induced airway obstruction had specific distinguishing features. Exercise-induced airway obstruction (defined as a fall of FEV₁ of at least 10% of the pre-exercise values) was detected in 20 of the 42 patients. These 20 were found to have a lower elastic recoil but were otherwise identical with the remainder as regards clinical and physiological abnormality. It is postulated that exercise-induced airway obstruction can be a manifestation of chronic obstructive lung disease.