Time course of response to prednisolone in chronic airflow obstruction.

Nineteen patients with chronic airflow obstruction measured their morning and evening peak expiratory flow (PEF) daily for 28 days. A placebo was taken for the first week and prednisolone 20 mg twice daily was taken for the last three weeks. The mean PEF in 13 patients who responded to prednisolone reached a maximum after eight days' treatment. The majority of the 19 patients had asthma and were thought to represent a typical cross section of patients who would be considered for a trial of oral corticosteroids. Most responsive patients will achieve a maximum response within eight days.     

Cardiopulmonary response to oxygen therapy in hypoxaemic chronic airflow obstruction.

The acute change in pulmonary artery pressure in response to oxygen may have prognostic value for patients with chronic obstructive pulmonary disease treated with long term domiciliary oxygen. A study was carried out to elucidate the mechanism of the acute cardio-respiratory response to oxygen in such patients and to determine whether it can be quantified non-invasively. The effects of acute oxygen administration (100% for 20 minutes and 28% oxygen for 24 hours) were assessed by non-invasive means and right heart catheterisation in 17 patients with severe stable hypoxaemic chronic obstructive pulmonary disease. Measurements included change in the ratio of dead space to tidal volume (VD/VT), effective pulmonary capillary blood flow (by rebreathing and single breath soluble gas uptake: QRB, QSB), left ventricular ejection fraction (radionuclide ventriculography), and M mode echocardiographic estimates of ventricular diameters and fractional shortening. These values were compared with those obtained from right heart catheter measurements of pulmonary artery pressure, cardiac index (thermodilution and direct carbon dioxide Fick: QTD, QFICK), and pulmonary vascular resistance. Oxygen administration resulted in a significant fall in pulmonary artery pressure, QTD, and QRB and a significant increase in VD/VT. The fall in QRB after 100% oxygen breathing for 20 minutes correlated strongly with the fall in pulmonary artery pressure (r = 0.86). There was no correlation between the fall in pulmonary artery pressure and the fall in QSB or the risen in VD/VT. Left ventricular ejection fraction did not change significantly. Echocardiography was technically unsatisfactory because of lung hyperinflation. Apart from a possible relation between VO2max and fall in pulmonary artery pressure after 24 hours of 28% oxygen breathing (r = 0.49, p less than 0.1) none of the baseline respiratory function measurements predicted the fall in pulmonary artery pressure or QRB. It is concluded that the cardiopulmonary response to acute oxygen breathing in patients with hypoxic chronic obstructive pulmonary disease includes a reduction in pulmonary artery pressure and cardiac output and a redistribution of pulmonary blood flow, and that rebreathing measurements of effective pulmonary blood flow can be used to quantify this response non-invasively.     

Assessment of reversibility of airway obstruction in patients with chronic obstructive airways disease.

Spirometry before and after an inhaled beta agonist or a course of oral prednisolone is widely used to detect reversible airflow limitation in patients with chronic obstructive lung disease. How many of these patients have a response and how the response to beta agonists relates to the response to corticosteroids is not clear. In 127 outpatients (mean (SD) FEV1 0.92 (0.38) 1) who had a clinical diagnosis of chronic obstructive lung disease (continuous breathlessness for more than six months and an FEV1/forced vital capacity (FVC) ratio less than 60%) and who appeared to be stable, the change in FEV1 was measured after salbutamol 200 micrograms from a metered dose inhaler and 5 mg from a nebuliser. Symptoms and spirometric values were recorded before and after two weeks of oral prednisolone 30 mg. Reversibility was defined as a response in FEV1 of 15% or more from baseline alone and as a 15% change and a minimum increase of at least 200 ml. The latter gave results that showed greater internal consistency between the drug regimens. On the basis of this criterion 56 patients (44%) had no response to salbutamol or prednisolone, 71 responded to salbutamol (including all 27 steroid responders), and 25 patients had a response to salbutamol 5 mg but not to 200 micrograms. In general, the largest increase in FEV1 after salbutamol occurred in the subjects with greatest improvement after prednisolone. Subjects showing a response in FEV1 after two weeks' prednisolone had a fall in total symptom score, unlike those who had no response to any treatment or a response to salbutamol only. These data show that reversibility in response to beta agonists is common in patients diagnosed on clinical grounds as having stable chronic obstructive lung disease, that it can be substantial, and that it is best detected by using a larger dose of salbutamol. Salbutamol responders were those most likely to improve after a trial of oral prednisolone. Allowance should be made for the variability of FEV1 in the calculation of the percentage response at low baseline values (less than 1 litre).     

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.     

Time course of response to oral and inhaled corticosteroids in non-asthmatic chronic airflow obstruction.

One hundred and twenty one patients considered on clinical grounds to have non-asthmatic chronic airflow obstruction completed a double blind, crossover trial comparing oral prednisolone 40 mg per day with inhaled beclomethasone dipropionate 500 micrograms thrice daily, each given for 14 days, with a 14 day washout period between treatments. The time course of response was analysed for the 57 occasions where there was a significant increase in mean daily peak expiratory flow (PEF) over the treatment period. Mean daily PEF was still rising at day 14 on 12 occasions. After withdrawal of treatment mean daily PEF remained above pretreatments levels for more than two weeks in half the responses analysed. The peak response occurred earlier with inhaled beclomethasone (median 9.5 (range 3-14) days) than with oral prednisolone (median 12 (range 1-14) days), though both treatments produced a response that was sustained for a similar period. The results suggest that a trial of treatment with corticosteroids in this group of patients should last more than 14 days, and that in a study with a crossover design the washout period should be longer than two weeks.     

Validity of peak expiratory flow measurement in assessing reversibility of airflow obstruction.

BACKGROUND: Assessing the reversibility of airflow obstruction by peak expiratory (PEF) measurements would be practicable in general practice, but its usefulness has not been investigated. METHODS: PEF measurements were performed (miniWright peak flow meter) in 73 general practice patients (aged 40 to 84) with a history of asthma or chronic obstructive lung disease before and after 400 micrograms inhaled sulbutamol. The change in PEF was compared with the change in forced expiratory volume in one second (FEV1). Reversible airflow obstruction was analysed in two ways according to previous criteria. When defined as a 9% or greater increase in FEV1 expressed as a percentage of predicted values reversibility was observed in 42% of patients. Relative operating characteristic analysis showed that an absolute improvement in PEF of 60 l/min or more gave optimal discrimination between patients with reversible and irreversible airflow obstruction (the sensitivity and specificity of an increase of 60 l/min in detecting a 9% or more increase in FEV1 as a percentage of predicted values were 68% and 93% respectively, with a positive predictive value of 87%). When defined as an increase of 190 ml or more in FEV1, reversible airflow obstruction was observed in 53% of patients. Again an absolute improvement in PEF of 60 l/min or more gave optimal discrimination between patients with reversible and irreversible airflow obstruction (sensitivity 56%, specificity 94%, and positive predictive value 92%). CONCLUSION: Absolute changes in PEF can be used as a simple technique to diagnose reversible airflow obstruction in patients from general practice.     

Diurnal variation in airflow obstruction in chronic bronchitis.

Twelve patients fulfilling strict criteria for chronic obstructive bronchitis recorded serial peak expiratory flow rates (PEFR) five times daily for a two-week period. Despite a 9.2% improvement in forced expiratory volume in one second (FEV1) with ipratropium bromide, and an 11.3% improvement with ipratropium bromide plus salbutamol, the inherent diurnal variation in PEFR while on no medication was greater than the improvement caused by either bronchodilator. In the group as a whole, the difference between the highest and the lowest daily PEFR over the two weeks was 24% of the mean daily value. Using cosinor analysis, 10 of the 12 patients showed a significant rhythm in PEFR with a computed mean amplitude between highest and lowest readings of 8.6% of the mean daily value. This is no greater than that found in normal subjects, but is considerably less than the variation in PEFR in patients with bronchial asthma.     

Carbimazole and exercise tolerance in chronic airflow obstruction.

Ten patients with severe dyspnoea and chronic airflow obstruction entered a randomised double-blind crossover trial comparing the effect of carbimazole 80 mg daily for two months with that of placebo. Assessment of thyroid function, lung function, and exercise tolerance was performed monthly. The mean free thyroxine index after two months of carbimazole was significantly lower at 64.1 (+/- 10.5, SEM) than the 89.1 (+/- 3.8) while on placebo. Serum tri-iodothyronine was reduced and thyroid stimulating hormone raised while on the active drug. There was no significant difference in the 12-minute walking distance (TMD), the rating of perceived exertion during the TMD, the oxygen cost score, the dyspnoea grade, the resting arterialised capillary blood gas tensions or the resting minute ventilation. During a progressive exercise test to exhaustion on a cycle ergometer, there was no significant difference in the minute ventilation, heart rate, blood gas tensions at exhaustion, or the total work done. There were no symptoms or signs of hypothyroidism. Lung function (FEV1, FVC, TLC, KCO) was unchanged. Thus a 28% reduction in the free thyroxine index produced no symptomatic or objective benefit in exercise tolerance in patients with severe airflow obstruction. These results provide no support for the use of carbimazole in chronic airflow obstruction.