Theophylline and salbutamol improve pulmonary function in patients with irreversible chronic obstructive pulmonary disease. Theophylline improves gas exchange during rest, exercise, and sleep in severe chronic obstructive pulmonary disease. A randomized, controlled trial of theophylline in patients with severe chronic obstructive pulmonary disease. Effect of theophylline on exercise performance in patients with severe chronic obstructive pulmonary disease. The usefulness of theophylline in nonasthmatic airway obstruction. Physiological and neuropsychological effects of theophylline in chronic obstructive pulmonary disease. The additive effect of theophylline on a high-dose combination of inhaled salbutamol and ipratropium bromide in stable COPD. Intravenous aminophylline in the treatment of acute bronchospastic exacerbations of chronic obstructive pulmonary disease. Long-term, double-blind comparison of controlled-release albuterol versus sustained-release theophylline in adolescents and adults with asthma. Sustained-release theophylline reduces dyspnea in nonreversible obstructive airway disease. Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow-release theophylline in the treatment of COPD. Is oral theophylline effective in combination with both inhaled anticholinergic agent and inhaled beta 2-agonist in the treatment of stable COPD? Efficacy of intravenously administered theophylline in children hospitalized with severe asthma. Aminophylline for acute exacerbations of chronic obstructive pulmonary disease. A controlled trial. Dose response relation to oral theophylline in severe chronic obstructive airways disease. Effects of muliple doses of metoprolol and propranolol on ventilatory function in patients with chronic obstructive lung disease.
To investigate the efficacy of bronchodilators in patients with irreversible chronic obstructive pulmonary disease (COPD), we conducted a double-blind, randomized, four-phase, crossover comparison between placebo, oral theophylline, inhaled salbutamol, and a combination of both drugs in 12 patients with stable COPD (mean age, 63 years) whose increase in forced expiratory volume in 1 s (FEV1) was less than or equal to 15 percent following 200 micrograms of inhaled salbutamol. Patients received two weeks of therapy with each of the test regimens. Both theophylline and salbutamol resulted in statistically significant improvement in FEV1, forced vital capacity (FVC), slow vital capacity (SVC), residual volume (RV), airway resistance (Raw), and maximum expiratory flow rate at 50 percent of vital capacity (V50). In most instances, there were no significant differences between theophylline and salbutamol. Combination therapy produced significantly greater improvement in FEV1, FVC, V50, Raw, and RV than either agent alone. The two drugs interacted in an additive fashion. Neither of the drugs, used singly, significantly reduced the severity or incidence of symptoms. The reduction in dyspnea and wheeze during combination therapy approached statistical significance (p = 0.06) and patient preference was significantly in favor of the combination regimen. None of the active treatments produced significantly more side effects than placebo. We conclude that theophylline and inhaled salbutamol produce significant, and approximately equal, improvement in pulmonary function in patients traditionally classified as suffering from "irreversible" COPD. The combination of theophylline and inhaled salbutamol generally results in additional improvement over that obtained with either drug used alone and this improvement is reflected by reduced symptomatology and treatment preference. The effects of theophylline on pulmonary function and gas exchange during rest, sleep, and exercise were assessed in 10 patients with severe but stable chronic obstructive pulmonary disease (COPD; median FEV1, 31% of predicted). The study was randomized, double blind, placebo controlled, and crossover in design, with each study period lasting 3 wk, and all other usual bronchodilator therapy was continued unchanged. All patients had detailed pulmonary function tests, in addition to exercise testing and overnight sleep studies by standard polysomnography. Theophylline significantly improved gas exchange during rest, exercise, and sleep. Awake resting arterial blood gases showed a higher PaO2 on theophylline (78 [53 to 93] mm Hg, median [range]) than placebo (72 [47 to 83] mm Hg; p < 0.01 by ANOVA), and PaCO2 was lower on theophylline (42 [38 to 54]) compared with placebo (45 [40 to 51], p < 0.05 by ANOVA). Arterial oxygen saturation (SaO2) was significantly higher on theophylline than placebo during exercise and sleep (p < 0.01), and transcutaneous CO2 was lower during sleep (p < 0.05). Theophylline also resulted in significantly improved pulmonary function and reduced trapped gas volume (p < 0.05). Exercise performance was no different during theophylline or placebo phases of the study. Sleep quality, however, was significantly impaired on theophylline. We conclude that theophylline has clinically significant benefits in patients with severe COPD. To assess the effects of theophylline in chronic obstructive pulmonary disease, we conducted a randomized, placebo-controlled, double-blind, crossover trial in 60 patients with severe but stable disease. The patients (mean age, 61 years) were studied before and after two months of placebo and two months of treatment with a sustained-release preparation of theophylline (10 mg per kilogram of body weight per day), administered orally. The two treatments were administered in a random order and separated by an eight-day washout period. After taking theophylline for two months (mean plasma concentration, 14.8 mg per liter), as compared with the two months of placebo, the patients had significant improvements in dyspnea, pulmonary gas exchange (partial pressure of arterial oxygen, 66 vs. 61 mm Hg [P less than 0.0001]; partial pressure of arterial carbon dioxide, 44 vs. 49 mm Hg [P less than 0.0001]), vital capacity (63 percent vs. 58 percent of the predicted value [P less than 0.0001]), and forced expiratory volume in one second (36 percent vs. 32 percent of the predicted value [P less than 0.0001]), with no significant change in airway resistance or functional residual capacity. Minute ventilation increased by a mean of 18 percent (P less than 0.0001) in the patients taking theophylline because of increased tidal volume, with no change in respiratory frequency. The respiratory-muscle performance of the patients taking theophylline improved by approximately 29 percent (P less than 0.0001), as indicated by a decline in the ratio of inspiratory pleural pressure during quiet breathing to maximal pleural pressure. We conclude that theophylline improves respiratory function and dyspnea in patients with severe chronic obstructive pulmonary disease and that these improvements are probably due to better respiratory-muscle performance. Theophylline is a well known bronchodilator which has been used for more than 50 years in the treatment of obstructive pulmonary diseases. In patients with severe chronic obstructive pulmonary disease whose cardiopulmonary performance is limited by their ventilatory capacity the administration of theophylline may improve exercise performance.
                A randomised, placebo controlled, double blind, crossover trial was conducted in 22 patients with severe but stable disease. The patients (mean age 68 years) were studied before and after one month of placebo and one month of treatment with a sustained release preparation of theophylline administered orally. The theophylline dose was adjusted until a blood level above 55.5 mumol/l was achieved. The two treatments were administered in random order and separated by a two week washout period. After theophylline was administered for one month a mean level of 68.2 mumol/l was achieved. Pulmonary function tests, arterial blood gas measurements, maximal voluntary ventilation (MVV), and an incremental exercise test were performed before (baseline) and at the end of the first and second month of treatment.
                Pulmonary function tests showed no improvement in the flow parameters but showed an improvement in MVV after treatment with theophylline. Pulmonary gas exchange was improved after theophylline (resting arterial PO2 8.91 v 8.59 kPa, PCO2 5.38 v 5.56 kPa). The incremental exercise study showed improvement in maximal work rate (86.5 v 75.0 watts) and maximal ventilation (VEmax) (46.7 v 43.01/min). The dyspnoea index on maximal effort (VEmax/MVV), anaerobic threshold, and oxygen pulse remained unchanged. Resting and exercise heart rate were higher after theophylline.
                Theophylline improved cardiorespiratory performance in these patients with severe chronic obstructive pulmonary disease mainly by increasing the ventilatory capacity. This study evaluated the effectivness of oral bronchodilator therapy using theophylline in patients with nonreversible chronic obstructive pulmonary disease. Twelve chronic obstructive pulmonary disease patients were entered into a doubleblind crossover study using either active drug theophylline in 200 mg capsules (Elixophyllin) or placebo for 3 months, followed by 3 months of the alternate capsule. At baseline and monthly visits, data were recorded, including history, physical examination, and pulmonary function testing. Clinically, 7 of 11 patients responded favorably to theophylline, 3 were unchanged, and 1 improved on placebo. Comparison of each sign and symptom individually revealed no statistically significant differences. Pulmonary function (FEV1 and FVC) showed slight deterioration with placebo, but not with active drug therapy. These findings suggest that nonasthmatic patients may improve clinically during theophylline therapy whereas their pulmonary function may deteriorate during placebo therapy. The effect of oral theophylline on clinical course, exercise, neuropsychological performance and bronchial reactivity was studied in chronic airflow obstruction. Twelve patients with chronic obstructive pulmonary disease (COPD) [mean age 62.4 +/- 1.6 years (SE), and forced expiratory volume in 1 sec of 1.15 +/- 0.1 l] were randomized to 4 weeks treatment with oral theophylline followed by 4 weeks of placebo, in a double-blind fashion. During each period, patients underwent clinical evaluation, incremental exercise, a battery of neuropsychological tests measuring a wide range of cognitive functions, and an inhaled methacholine provocation. On the active drug (levels 9.5 +/- 1 mg/l), vital capacity and maximal breathing capacity were 16 +/- 7% and 20 +/- 7% respectively, higher relative to placebo (P < 0.04). Exercise capacity, as reflected by peak O2 uptake and the anaerobic threshold, improved 14 +/- 5% and 18 +/- 5% (P < 0.04). In contrast, bronchial responsiveness to inhaled methacholine and the mean scores on the neuropsychological tests were not significantly altered by the drug. Clinical symptoms were unaltered, but mild side effects were more common on theophylline. We concluded that in moderate to severe COPD, theophylline treatment, at the low range of the therapeutic dose, improves lung function and exercise capacity. This improvement is achieved with no detectable alteration of bronchial reactivity to methacholine and with no deleterious effect on cognitive functions. To determine the additive effect of oral theophylline in patients with stable COPD who received both inhaled salbutamol, 400 micrograms, and ipratropium bromide, 80 micrograms, four times daily administered with a metered-dose inhaler.
                Twenty-four male patients with stable COPD (FEV1, 0.96 +/- 0.43 L; 36.8 +/- 17.0 percent predicted [% pred]) completed a randomized, double-blind, placebo-controlled crossover trial with oral theophylline for 4 weeks.
                The average serum theophylline level was 15.0 +/- 5.5 micrograms/mL during treatment. On the whole, without inhalation of bronchodilators, FEV1 was 0.93 +/- 0.42 L during the placebo period and 1.00 +/- 0.43 L (significantly different from placebo; p < 0.01) during the theophylline period. At 15 and 60 min after inhalation of salbutamol, 400 micrograms, and ipratropium, 80 micrograms, the FEV1 with placebo was 1.12 +/- 0.43 L and 1.14 +/- 0.46 L, respectively, and the FEV1 with theophylline was 1.18 +/- 0.45 L (p < 0.01) and 1.20 +/- 0.47 L (p < 0.01), respectively. Daily peak expiratory flow rate also improved. Daily symptom scores were not significantly different between theophylline and placebo periods. Nevertheless, eight patients reported a subjective benefit during the theophylline administration period, and they were thus considered subjective responders. While FEV1 after inhalation was significantly improved during the theophylline periods in subjective responders (change in FEV1 between theophylline and placebo treatment 15 min after inhalation, 3.1 %pred; 60 min, 3.5 %pred), postbronchodilator FEV1 was not significantly different between the placebo and theophylline periods in subjective nonresponders (15 min, 1.7 %pred; 60 min, 1.6 %pred).
                On the whole, theophylline has a small bronchodilating effect but does not improve the symptoms of patients with stable COPD. However, one third of patients with COPD may respond subjectively to theophylline. The additive bronchodilating effect of theophylline may be related to the symptomatic improvement in subjective responders. Often chronic obstructive pulmonary disease (COPD) patients treated for acute exacerbations receive intravenous (IV) aminophylline in addition to inhaled bronchodilators that may raise serum levels of theophylline into the toxic range. A double-blind, randomized study of 52 men with COPD who came to the emergency department for treatment of exacerbations was initiated to establish the efficacy and safety of this common practice. After history and physical examination, patients were treated with 28% oxygen by Venturi mask and 0.3 cc metaproterenol sulfate in 2.5 cc saline by nebulizer; an IV line was started and patients received either aminophylline or D5W. Measurements included baseline and two-hour serum theophylline levels, pulmonary function tests, and symptom questionnaires. Mean values from the entire group showed decreases in respiratory rate, cardiac rate, and pulsus paradoxus, and increases in forced expiratory volume in one second (FEV1) and vital capacity (VC) over a two-hour treatment period (P less than .01). Despite the increase in serum theophylline in the treatment group, the demographic, clinical, pulmonary function, and outcome data were found to have no statistically significant differences when compared to control patients. The data were then analyzed according to serum theophylline levels. Theophylline level greater than 20 micrograms/mL occurred in 15 patients with no untoward effects; premature ventricular contractions (PVCs) were no more frequent in this group than in those with lower serum theophylline levels. A theophylline level greater than 10 micrograms/mL after two hours of treatment resulted in the following differences, which were not statistically significant: mean FEV1 response less than or equal to 10 micrograms/mL vs greater than 10 micrograms/mL, 20% vs 28%; mean VC change, 17% vs 30%; or mean emergency department returns in one week, 0.1 vs 0.26. In our experience, oxygen and inhaled metaproterenol are effective treatment for exacerbations of COPD. This parallel-group study compared the safety and efficacy of controlled-release albuterol versus sustained-release theophylline, both administered every 12 hours. One hundred twenty-four adolescent and adult patients with asthma and with chronic reversible obstructive airway disease were studied. All patients qualified with an FEV1 less than or equal to 80% of predicted (not receiving treatment) and greater than or equal to 15% reversibility in FEV1 or greater than or equal to 25% reversibility in FEF25-75% after inhaled isoproterenol. All patients were known to be able to take theophylline without unacceptable adverse effects. Theophylline was titrated for patients to receive, unblinded, theophylline serum concentrations of 10 to 20 micrograms/ml. With subsequent randomization, 62 patients continued to receive theophylline and 62 patients started taking albuterol in the 12-week, double-blind, double-dummy portion of the study. Pulmonary function was measured during a pretreatment visit (unmedicated) and serial assessment was made starting just before the morning dose and continuing for 12 hours after the dose at the end of 1, 6, and 12 weeks of treatment. Both treatment groups exhibited statistically significant increases in FEV1 from the pretreatment visit to all times of observation at weeks 1, 6, and 12. The increases in FEV1 were not significantly different between albuterol and theophylline administration. There was no evidence of tolerance to the bronchodilatory effect during 12 weeks in either treatment group. Only one patient in the study stopped treatment because of an adverse effect. This patient had tremor during albuterol administration. All other adverse events were tolerated or resolved during treatment.(ABSTRACT TRUNCATED AT 250 WORDS) Although orally administered theophylline has been prescribed widely in patients with nonreversible airway obstruction, symptomatic benefit has not been established. To assess the effects of orally administered theophylline on dyspnea, we performed a randomized, double-bind, crossover, placebo-theophylline clinical trial in 12 ambulatory male patients with moderate to severe nonreversible airway obstruction. Dyspnea was rated using 2 clinical indexes based on 3 components affecting breathlessness: functional impairment, magnitude of task that evokes dyspnea, and the associated magnitude of effort. Dyspnea and physiologic parameters were measured on 4 occasions: at baseline, 4 wk after initial treatment, a second baseline after a 2-wk washout period, and 4 wk after the second medication. For the 12 patients, mean age (+/- SD) was 60 +/- 7 yr, forced expiratory volume in one second was 1.36 +/- 0.67 L (mean, 40% of predicted), and arterial oxygen tension was 71 +/- 10 mmHg. During the treatment phase, all patients had a therapeutic theophylline blood level (range, 12 to 19 micrograms/ml). Theophylline significantly decreased the components of functional impairment (p = 0.02) and magnitude of task (p = 0.02) relating to dyspnea, as well as the overall dyspnea rating (p = 0.01). There were no significant differences between placebo and theophylline therapy for spirometry, arterial blood gas tensions, and the 12-min walking distance. Thus, sustained-release theophylline significantly reduced dyspnea in these ambulatory patients with moderate to severe nonreversible airway obstruction without altering lung function, gas exchange, or exercise performance. To compare the efficacy, tolerability, and safety of therapy with formoterol and oral slow-release theophylline (THEO) in patients with COPD.
                A randomized, parallel-group study, with double-blind arms for formoterol and placebo (PL) and an open arm for oral slow-release THEO administered in individual doses on the basis of plasma concentrations.
                Eighty-one centers worldwide.
                Eight hundred fifty-four patients with symptomatic COPD.
                Comparison of twice-daily inhaled formoterol dry powder (12 or 24 microg), PL, and THEO (individualized doses) over 12 months.
                Compared to PL, doses of formoterol and THEO both significantly improved the area under the curve for FEV(1) measured over a period of 12 h following the morning dose of study medication at 3 and 12 months (p < 0.001 for all comparisons). Therapy with formoterol, 12 microg, was significantly more effective than that with THEO (p < or = 0.026). Formoterol significantly reduced the percentage of "bad days" (i.e., days with at least two individual symptom scores > or = 2 and/or a reduction in peak expiratory flow from a baseline of > 20%; p < or = 0.035 vs. PL and THEO), and the use of salbutamol rescue medication (p < or = 0.003 vs PL) over the whole treatment period, while the effect of THEO was similar to that of PL. Therapy with formoterol and THEO was more effective than PL at improving quality of life for > 12 months (p < or = 0.030). Treatment-related adverse events and discontinuations were more frequent among patients receiving THEO than among those receiving formoterol.
                Long-term treatment with inhaled formoterol dry powder is more effective and better tolerated than treatment with therapeutically appropriate doses of oral slow-release THEO in symptomatic patients with COPD. To investigate the additive effect of oral theophylline on combined inhaled anticholinergic agent and beta 2-agonist therapy, 12 patients with stable COPD (64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial of oral theophylline for a 4-week period (400 mg for 2 weeks, followed by 600 mg for 2 weeks). All of the patients continued to inhale both salbutamol, 200 micrograms, and ipratropium bromide, 40 micrograms, using a metered-dose inhaler four times a day. Spirometry was assessed before, and 15 and 60 min after the inhalation of bronchodilators at 2-week intervals. Even after the inhalation of salbutamol and ipratropium, theophylline significantly improved FEV1 and daily peak expiratory flow rate compared with the placebo. No significant improvement in the daily symptom scores for cough, sputum, wheezing, or shortness of breath was observed throughout the different phases of treatment. This study shows that the additive bronchodilating effect of theophylline, when used in combination with salbutamol, 200 micrograms, and ipratropium, 40 micrograms, is significant but small in stable COPD. The addition of theophylline did not significantly improve the patient's symptoms. Oral theophylline, when used in combination with an inhaled anticholinergic agent and an inhaled beta 2-agonist, may be of limited value in the treatment of stable COPD. To determine whether intravenously administered theophylline, when added to frequently nebulized albuterol and intravenously administered methylprednisolone, benefits children hospitalized with severe asthma.
                Prospective, randomized, placebo-controlled, parallel-group, double-blind study.
                Inpatient pediatric service at a tertiary-care teaching hospital.
                Twenty-one children 5 to 18 years of age.
                All patients received 2.5 to 5.0 mg of nebulized albuterol every 20 minutes to every 6 hours, intravenously administered methylprednisolone (1 mg/kg every 6 hours), and either intravenously administered theophylline (as aminophylline) or placebo for 36 hours. Serum theophylline concentrations were maintained between 55 and 110 mumol/L (between 10 and 20 micrograms/ml) by adjusting loading doses and continuous infusion rates.
                Forced expired volume in 1 second (FEV1) and clinical score were measured at 0, 1, 3, 6, 12, 24, and 36 hours after the start of each individual study. The total number of nebulizations, total albuterol dosage, adverse effects, and duration of hospital stay were recorded. Twelve children received theophylline and nine received placebo. The two groups did not differ significantly in age, sex, or baseline FEV1. In both groups, clinical score significantly improved from baseline by 12 hours, and FEV1 by 24 hours (p < 0.05). There were no significant differences between the groups in FEV1 or clinical score at any of the measured time points. There were no significant differences in rate of improvement in FEV1, total number of nebulizations, total albuterol dosage, or duration of hospital stay. Adverse effects were mild and infrequent and did not differ significantly between the two groups.
                Theophylline, at therapeutic concentrations, did not additionally benefit children hospitalized with severe asthma who were being treated frequently with nebulized albuterol and with methylprednisolone intravenously. Study Objective: To determine the efficacy of intravenous aminophylline in the treatment of patients hospitalized for exacerbation of chronic obstructive pulmonary disease. Design: Randomized, double-blind, placebo-controlled trial during the first 72 hours of hospitalization. Patients: Thirty patients admitted from the emergency room or walk-in clinic with the primary diagnosis of an exacerbation of chronic obstructive pulmonary disease. Twenty-eight patients completed the study; 2 patients, 1 receiving placebo and 1 receiving aminophylline, were removed from the study because of respiratory failure requiring mechanical ventilation. Interventions: Patients received either intravenous aminophylline or placebo, in addition to nebulized, inhaled 0.3 mL of a 5% solution every 6 hours; methylprednisolone, 0.5 mg/kg body weight every 6 hours intravenously; ampicillin, 500 mg orally every 6 hours (tetracycline or trimethoprim-sulfamethoxazole were substituted in penicillin-allergic patients); and supplemental oxygen as needed. Aminophylline infusion rates were adjusted by an unblinded investigator to achieve theophylline levels of 72 to 83 mumol/L. Changes were also made in placebo infusion rates to maintain the double-blind design. Measurements and Main Results: The forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) before and after metaproterenol inhalation were measured twice daily by a blinded investigator, who also administered a verbal dyspnea index with a scale of 1 to 10 and questioned patients regarding possible side effects of treatment (tremor, palpitations, nausea, or vomiting). Arterial blood gas measurements at 72 hours were compared with those obtained on admission. Significant improvements in FEV1 and FVC measured before and after metaproterenol treatment and in dyspnea occurred over time in both treatment groups (p less than 0.05 for all measurements). However, there were no significant differences between the placebo and aminophylline groups in any of the spirometric measurements or the dyspnea indices (p greater than 0.5 in all five analyses). The mean increases (+/- SE) in Po2 of 1.9 (+/- 0.5) kPa with placebo and 1.7 (+/- 0.7) kPa with aminophylline and the mean decreases in PCO2 of 0.5 (+/- 0.4) kPa with placebo and 1.2 (+/- 0.4) kPa with aminophylline were not significantly different (p greater than 0.6 for PO2, p greater than 0.2 for PCO2).(ABSTRACT TRUNCATED AT 400 WORDS) To evaluate measurement of the trapped gas volume as a measure of respiratory function in patients with chronic obstructive airways disease and their response to treatment with theophylline.
                Patients able to produce consistent results on testing of respiratory function spent two weeks having dosage of theophylline adjusted to give individual pharmacokinetic data. This was followed by random assignment to four consecutive two month treatment periods--placebo and low, medium, and high dose, as assessed by serum concentrations of theophylline. Respiratory function and exercise performance was assessed at the end of each two month period.
                Chest unit in district hospital.
                Thirty eight patients with chronic bronchitis and moderate to severe chronic obstruction to airflow were recruited; 33 aged 53-73 years completed the study.
                Dosage of oral theophylline increased during two week optimisation period to 800 mg daily unless toxicity was predicted, when 400 mg was given. Targets for the steady state serum theophylline concentrations were 5-10 mg/l in the low dose period, 10-15 mg/l in the medium dose, and 15-20 mg/l in the high dose period.
                Respiratory function as measured by forced expiratory volume in one second, forced vital capacity, peak expiratory flow rate, slow vital capacity, and static lung volumes using helium dilution and body plethysmography from which trapped gas volume was derived. Exercise performance assessed by six minute walking test and diary cards using visual analogue scale.
                The forced expiratory volume in one second, forced vital capacity, and peak expiratory flow rate changed only slightly (about 13%) over the range of doses. There was a linear dose dependent fall of trapped gas volume from 1.84 l (SE 0.157) to 1.42 l (0.152), 1.05 l (0.128), and 0.67 l (0.102) during the placebo and low, medium, and high dose treatment periods. Mean walking distance increased by up to 55.6 m (20%). There was a modest improvement in dyspnoea as the dose of theophylline was increased. Side effects were mostly minor but they became more frequent as the dose was increased.
                The fall in trapped gas volume may reflect an improvement in peripheral ventilation (associated with treatment with theophylline) which is less apparent in the more common tests of lung function used in patients with chronic obstructive airways disease. The effect of metoprolol on pulmonary function was compared with that of propranolol and placebo in twelve patients with chronic obstructive lung disease. Propranolol caused a significant reduction in FEV1 compared with metoprolol and placebo. Metoprolol gave a slight reduction compared with placebo. FVC was not significantly influenced by metoprolol, but propranolol caused a significant depression compared both with metoprolol and placebo. The isoprenaline-mediated increase in FEV1 and FVC was not significantly altered after metoprolol compared with placebo. After propranolol the isoprenaline-mediated increases in FEV1 and FVC were 40 and 24% lower respectively than after metoprolol and placebo. Unwanted effects and pulmonary symptoms were at an acceptable level in all cases except in two patients who had to be given i.v. theophyllamine therapy during propranolol treatment. It is concluded that metoprolol exhibits a selective beta1-blocking action and thus may be given to patients with chronic obstructive lung disease provided that adequate beta2-stimulator treatment is given concomitantly.
Theophylline has a modest effect on FEV1 and FVC and slightly improves arterial blood gas tensions in moderate to severe COPD. These benefits were seen in participants receiving a variety of different concomitant therapies. Improvement in exercise performance depended on the method of testing. There was a very low dropout rate in the studies that could be included in this review, which suggests that recruited participants may have been known by the investigators to be theophylline tolerant . This may limit the generalisability of these studies.