Effect of sodium cromoglycate and nifedipine on adenosine-induced bronchoconstriction

Inhaled adenosine causes bronchoconstriction in asthmatic patients. In 7 symptom-free asthmatics a study was performed to investigate the effect of sodium cromoglycate and nifedipine on adenosine-induced bronchoconstriction. All patients were challenged with increasing doses (from 0.03 to 2 mg) of nebulized adenosine to assess airway reactivity. The same procedure was repeated on different days at the same time each morning after administration of placebo and drugs in a randomized double-blind study. Airway response was measured as the forced expiratory volume in 1 s (FEV1). The PD20 value and the fall of FEV1 at the provocative dose were calculated. The PD20 data were modified in log values and the statistical analysis was performed by two-way analysis of variance. Mean decrease of FEV1 after adenosine challenge was 26.02 and 28.87% with placebo sodium cromoglycate and placebo nifedipine, respectively. Sodium cromoglycate and nifedipine gave a mean decrease of FEV1 of 6.44% (p less than 0.05) and 22.22%, respectively. PD20 values (geometric mean) after adenosine inhalation were 0.72 and 0.74 mg for placebo sodium cromoglycate and placebo nifedipine and 0.86 mg for nifedipine. Sodium cromoglycate gave a significant protection against adenosine in all subjects and in no case did the maximum dose used (2 mg) result in a fall in FEV1 value greater than 20%. Adenosine antagonism could be considered as a possible factor contributing to the pharmacologic efficacy of sodium cromoglycate in asthmatic patients. No protective effect was noticed with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dissociation in the effect of nedocromil on mannitol-induced cough or bronchoconstriction in asthmatic subjects

OBJECTIVE: Inhaled mannitol induces both bronchoconstriction and cough. Nedocromil sodium greatly attenuates mannitol-induced bronchoconstriction. Knowledge about the effect of nedocromil on mannitol-provoked cough might, therefore, clarify the mechanisms of this response. METHODOLOGY: Inhalation challenges with mannitol powder were performed after inhalation of 8 mg of nedocromil or its placebo in 24 subjects with asthma. The study was double-blind, randomised, and placebo-controlled. The mannitol-provoked coughs were manually recorded and the mannitol-induced bronchoconstriction was measured with a spirometer. RESULTS: The cumulative dose of mannitol that provoked at least two coughs tended to be higher on the nedocromil day than on the placebo day (34 (22--53) mg vs 26 (18--37) mg, P=0.051). The cumulative number of coughs per dose of mannitol was slightly, but significantly, lower on the nedocromil than on the placebo day (4.2 (2.8--6.3) coughs/100 mg vs 6.1 (4.0--9.4) coughs/100 mg, P=0.037). However, when analysed on a constant-dose basis, nedocromil provided no protection for coughing (-1% protection), whereas the protection for bronchoconstriction was clear (55% protection). CONCLUSIONS: Nedocromil strongly attenuates mannitol-induced bronchoconstriction but has a negligible effect on mannitol-provoked cough. Therefore, these responses seem to have different pathways in asthma. Recording of both provoked coughs and induced bronchoconstriction during mannitol challenge may provide supplementary information about a patient's disease.     

Effect of nedocromil sodium and sodium cromoglycate against bronchoconstriction induced by inhaled adenosine 5'-monophosphate

In this randomized, double-blind, placebo controlled study, the effect of prior inhalation of nebulized sodium cromoglycate (SCG) (7.3 +/- 0.6 mg) and nedocromil sodium (NED) (7.5 +/- 0.6 mg) was observed on adenosine 5'-monophosphate (AMP)-induced bronchoconstriction in 11 non-atopic asthmatic subjects. The geometric mean provocation doses of methacholine and AMP required to produce a 20% decrease in forced expiratory volume in one second (FEV1) (PD20FEV1) were 0.6 (0.1-18.8) and 5.1 (0.8-130.7) mumole respectively. The repeatability of the AMP challenge procedure for PD20FEV1 was within one doubling dose difference. SCG and NED, administered 30 min prior to bronchoprovocation with AMP, displaced the AMP dose-response curve to the right by 9.6 (1.5-41.6) (p less than 0.01) and 22.2 (3.7-89.1) (p less than 0.01)-fold, respectively, the difference between the two drugs being significant (p less than 0.05). There was a significant correlation (r = 0.7, p = 0.02) between the log dose ratios for PD20FEV1 for SCG and NED. We conclude that both SCG and NED protect against AMP-induced bronchoconstriction, NED being at least 2.3 (0.7-11.5)-fold more potent than SCG, and that they achieve this effect by a similar mechanism(s).     

Nedocromil sodium inhibits the early and late asthmatic response to exercise.

A double-blind, crossover study was carried out to investigate the effect of nedocromil sodium on the dual asthmatic response to exercise challenge. Nineteen patients with a late response to bicycle exercise were randomly treated on two study days with 4 mg nedocromil sodium or a matched placebo aerosol, 30 min before commencing exercise. Peak flow was measured before exercise, at intervals up to 60 min after exercise, then hourly for up to 13 h. In 12 of the 19 patients an early reaction to exercise occurred. In 8 of these 12 patients the early reaction could be inhibited by nedocromil sodium (p less than 0.01) although in half of these patients placebo was also shown to be protective. In the case of the late reaction after exercise challenge, 4-13 h after exercise challenge, nine patients were clearly protected by pretreatment with nedocromil sodium (p less than 0.01) when the fall in peak expiratory flow rate was related to the pre-exercise baseline, four patients showed an equal protective effect of placebo and nedocromil sodium, whilst the others were not protected. When the late asthmatic response (fall in peak expiratory flow rate) after exercise challenge was related to control diurnal peak flow values, the number of responses was reduced; the protective effect of nedocromil sodium remained.     

Nedocromil sodium inhibits the increase in airway reactivity induced by platelet activating factor in humans.

To investigate the effect of nedocromil sodium on changes in airway reactivity to methacholine induced by platelet activating factor, we studied 12 nonasthmatic, nonatopic subjects (24 to 41 years) in a double-blind trial. The FEV1 and airflow at 30 percent of vital capacity from a partial forced expiration (V30p) were used to assess changes in airway caliber. Two concentration-response curves to doubling concentrations of MCh (from 0.3 mg/ml) were performed 48 h apart. The concentrations of MCh causing a 20 percent fall in FEV1 (PC20FEV1) or a 40 percent fall in V30p (PC40V30p) were calculated. After the first MCh challenge, subjects were matched by airway reactivity and randomly assigned to nedocromil sodium (two puffs qid 2 mg/puff) or placebo treatment. Two days after the second MCh challenge, PAF was inhaled, and changes in airway caliber were recorded. Administration of either nedocromil sodium or placebo was ended at this time and airway response to MCh was assessed two days after PAF. The two concentration-response curves to MCh obtained before PAF exposure were superimposable. The PAF caused a dose-related bronchoconstriction in both groups; the maximal fall in V30p was 27.6 +/- 6.6 percent (mean +/- SE) in the nedocromil sodium group and 37.4 +/- 4.6 percent in the placebo group. Two days after PAF, the PC20FEV1 did not change in subjects who received nedocromil sodium (4.86 vs 4.32 mg/ml; geometric mean), but it fell from 6.59 to 1.12 mg/ml (p less than 0.05) in placebo-treated subjects. These results indicate that nedocromil sodium inhibits PAF-induced increase in airway reactivity.     

The long-term effects of nedocromil sodium and beclomethasone dipropionate on bronchial responsiveness to methacholine in nonatopic asthmatic subjects

We investigated the effects of long-term treatment with two anti-inflammatory drugs, nedocromil sodium and beclomethasone dipropionate, on airway hyperresponsiveness to methacholine (PC20), on baseline FEV1 and on the bronchodilating effect of a deep breath in 25 nonsteroid-dependent nonatopic asthmatic adults. In all subjects the prestudy PC20 was less than 8 mg/ml, the postbronchodilator FEV1 was greater than 75% predicted, and skin prick tests and RAST to 13 common allergens were negative. After 2 months run-in, the subjects were randomly allocated into 3 parallel treatment groups to inhale double-blind either 4 mg nedocromil (n = 9) or 100 micrograms beclomethasone (n = 8) or placebo (n = 8) 4 times daily for 4 months. PC20 was measured using the 2-min tidal breathing method. The effect of a deep breath was measured during methacholine-induced bronchoconstriction by standardized maximal and partial expiratory flow-volume curves and was expressed as a flow ratio (M/P ratio). Pretreatment values of FEV1, PC20, and M/P ratio were not different between the 3 groups. PC20 did not change in the placebo group, but increased significantly by a factor of 3 after 8 wk of treatment with beclomethasone or nedocromil (p less than 0.001). FEV1 did not change after treatment with placebo or nedocromil (p greater than 0.2), but increased (mean change 0.2 L, SD 0.2) after 4 wk of treatment with beclomethasone (p less than 0.05). Geometric mean M/P ratio increased from 1.98 to 2.66 after 4 wk of beclomethasone (p less than 0.01), but not after nedocromil or placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

BRL10833 in inhibiting exercise-induced bronchoconstriction in asthmatic children.

A double-blind controlled exercise challenge study has been performed in 16 asthmatic chlidren to show the effectiveness of BRL10833 in inhibiting exercise-induced bronchoconstriction. The children attended the respiratory laboratory on four occasions within the space of two weeks; on each occassion a routine 6-min exercise test was performed. At the first visit no drugs were given before the exercise test and all the children demonstrated abnormal exercise-induced bronchoconstriction as measured by peak expiratory flow rate (PEFR), forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC). On the other three occasions the children were given sodium cromoglycate, BRL10833 or placebo medications before the exercise test. After sodium cromoglycate administration four children showed complete blocking and four showed partial blocking of exercise-induced bronchoconstriction. After BRL10833 four children showed complete blocking and six showed partial blocking of exercise induced bronchoconstriction. Placebo administration produced complete blocking of exercise-induced bronchoconstriction in three and partial blocking in two children. The results indicated that BRL10833 was almost as effective as sodium cromoglycate in inhibiting exercise-induced bronchoconstriction and placebo, although less effective than the two preparations, did afford protection from exercise-induced bronchoconstriction in some of the children.     

The effect of nedocromil sodium and cromolyn sodium on antigen-induced responses in allergic sheep in vivo and in vitro

We studied the effects of nedocromil sodium and cromolyn sodium on early and late bronchial responses to inhaled Ascaris suum antigen in allergic sheep in vivo, and the antigen-induced contractile responses of sheep tracheal smooth muscle in vitro. For the in vivo studies the sheep were pretreated with aerosols of placebo (buffered saline solution), 20 mg of nedocromil sodium, or 20 mg of cromolyn sodium (both dissolved in 3 ml of buffered saline solution) and then challenged with aerosol antigen. Specific pulmonary resistance (SRL) was measured before and after challenge to document the responses of the airways. In the trial with placebo, challenge with antigen resulted in significant early and late increases in SRL. Treatment with nedocromil sodium significantly reduced the early response to antigen and blocked the late response. Cromolyn sodium gave the same results; there were no statistical differences between the responses of the airways for the two dogs. In vitro nedocromil sodium at doses of 10(-6)M and 10(-5)M inhibited significantly the contractile responses of sheep tracheal smooth muscle to A suum. Cromolyn sodium only showed efficacy at 10(-5)M. These results suggest that nedocromil sodium may be potentially useful in the treatment of reversible allergic disease of the airways.     

Inhaled nedocromil sodium as additional treatment to high dose inhaled corticosteroids in the management of bronchial asthma.

Thirty five asthmatic patients were included in a randomized, double-blind, placebo-controlled, parallel group study of inhaled nedocromil sodium (4 x 4 mg daily) as an additional treatment to high dose (greater than or equal to 1,000 micrograms) inhaled corticosteroids in the management of bronchial asthma. Following a four week baseline, patients received nedocromil sodium (17) or placebo treatment (18) for eight weeks. Five patients (four in the group subsequently randomized to nedocromil sodium) used short course oral corticosteroid therapy during the baseline and four placebo treated patients used oral steroid therapy during treatment. Fifteen patients (11 nedocromil sodium) reported unusual symptoms. Two nedocromil sodium treated patients were withdrawn owing to treatment taste and vomiting. Statistically significant treatment differences in favour of nedocromil sodium were seen for daytime symptoms (p = 0.03) and morning peak expiratory flow (PEF) (p = 0.012) during weeks 5-8, and for clinician opinion (p = 0.02). Patient opinion (p = 0.053) and evening PEF (p = 0.08) failed to reach statistical significance. Eight out of fifteen and three out of seventeen patients considered nedocromil sodium and placebo, respectively, to be very or moderately effective. The results indicate that the addition of nedocromil sodium (4 mg four times daily) to moderate to severe asthmatics not fully controlled on a regimen of greater than or equal to 1,000 micrograms inhaled corticosteroids and inhaled bronchodilators can produce improvements in symptoms and pulmonary function.     

Effects of nedocromil and salbutamol on airway reactivity in children with asthma.

Nedocromil and salbutamol are effective drugs in preventing exercise-induced asthma (EIA). The aim of this study was to compare the protective effects of both drugs and a combination of both drugs against cold dry air-induced bronchoconstriction, using cold dry air challenges (CACh) as a surrogate for exercise. Twenty-five atopic children (mean age 13.7, range 8-18 yrs) with EIA participated in the study. Lung function tests were performed before medication, 30 min after medication and just before CACh, and 3 and 15 min after the challenge on four consecutive days. CACh consisted of a 4-min isocapnic hyperpnoea of -10 degrees C, absolutely dry air. Treatment consisted of nedocromil (two puffs of 2 mg) plus placebo, salbutamol (two puffs of 100 microg) plus placebo, the combination of both drugs, and placebo alone, in a random order. Both active drugs were significantly more protective than placebo and the combination showed an additive effect. Mean maximum postchallenge decrease in forced expiratory volume in one second after placebo was 27+/-8.1%, 12+/-9.5% after nedocromil, 8+/-10.4% after salbutamol, and 4.5+/-6.71% after the combination of both drugs, respectively. These results suggest that both drugs protect against exercise-induced asthma. Although not as effective as salbutamol and combined medication, nedocromil can give sufficient protection for many patients.     

Nedocromil sodium vs. Sodium cromoglycate pressurized aerosol in the prevention of bronchoconstriction induced by ultrasonic nebulized distilled water in asthmatic children

To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG), administered by metered dose inhaler (MDI) with a 700 mL holding chamber (Fisonair Fisons UK) in preventing bronchoconstriction induced by inhalation of ultrasonically nebulized distilled water (UNDW), 12 asthmatic children were studied in a randomized, double-blind, placebo-controlled, intrapatient study. Following a baseline challenge with UNDW, the protective effect of NS, SCG, or placebo was evaluated in each subject. Cumulative doses of delivered nebulized water producing a 20% fall in forced expiratory volume in 1 sec (PD₂₀ UNDW) was measured. Mean (± SD) PD₂₀, UNDW was 4.83 (± 4.84), 10.16 (± 7.05), 15.8 (± 0.5), and 15.93 (± 0.23) respectively, for baseline, and placebo, SCG, and NS-treated groups. A significant (P < 0.05) protection from UNDW induced bronchoconstriction by NS was observed in comparison with placebo, while no such effect was evident when the children were treated with SCG. Pediatr Pulmonol. 1993; 16:243–247. © 1993 Wiley-Liss, Inc.     

Comparison of nedocromil sodium at two dosage frequencies with placebo in the management of chronic asthma.

Nedocromil sodium (4 mg b.d. or q.i.d.) was added to the therapy of 76 chronic asthmatic patients in a four-centre, double-blind cross-over, placebo-controlled trial. Patients had troublesome symptoms uncontrolled by high doses of inhaled corticosteroids (mean 1450 micrograms). In 54 patients who completed the study, nedocromil sodium was significantly more efficacious than placebo (P < 0.01) in relieving morning chest-tightness and cough, in reducing total diary card score and nocturnal bronchodilator usage, and in increasing morning and evening peak flow. Asthma severity at clinic visits decreased significantly (P = 0.001) following treatment with nedocromil sodium, which was globally rated more effective than placebo (P < 0.01). Treatment differences favored q.i.d. over b.d. dosage but without statistical significance. There were no serious adverse effects. Although the pulmonary function changes were small, these findings suggest that the addition of nedocromil sodium may benefit asthmatic patients who are inadequately controlled by high doses of inhaled corticosteroids.     

Attenuation of platelet-activating factor induced bronchoconstriction by nedocromil sodium.

We assessed the effect of nedocromil sodium on bronchoconstriction and airway responsiveness induced by platelet-activating factor (PAF) in eight normal subjects, in a double-blind, placebo-controlled cross-over study. Subjects inhaled PAF by a dosimeter method in 5 doses of 18 micrograms each, separated by an interval of 15 min, (total dose of 90 micrograms). Airway calibre was measured by partial expiratory flow at 30% of vital capacity (Vp30) before and at 1, 3, 5, 10 and 15 min after each dose of PAF. The bronchoconstrictor response was assessed by measuring the area under the curve of the percentage fall in Vp30 over time. There was a significant reduction in PAF-induced bronchoconstriction after nedocromil sodium (1,225 +/- 392 arbitrary units; mean +/- SEM) compared to placebo (2,395 +/- 598; p < 0.01). There was no significant difference in the fall in peripheral neutrophil count measured at 5 min after PAF with nedocromil sodium (48.5 +/- 9.5%) compared to placebo (43.3 +/- 6.8%). In conclusion, nedocromil sodium significantly attenuates PAF-induced bronchoconstriction but not the peripheral neutropenia in normal subjects. Since PAF is not a direct constrictor of human airway smooth muscle, this effect of nedocromil sodium may indicate inhibition of release of bronchoconstrictor mediators.     

Nedocromil sodium and placebo in the treatment of bronchial asthma. A multicenter, double-blind, parallel-group comparison

The efficacy of nedocromil sodium (4 mg twice daily by inhalation) in treating bronchial asthma was assessed by double-blind, placebo-controlled group comparison in 69 adults from three centers. The patients (34 active, 35 placebo) had a history of bronchial asthma with at least 15 percent reversibility. Inhaled corticosteroids, used by 22 and 24 subjects in the active and placebo groups respectively, were discontinued before the study, in which a two-week baseline was followed by six weeks of treatment. Two-weekly clinic assessments of lung function, symptoms and final opinions of treatment were significantly (p less than 0.05 p less than 0.001) in favor of nedocromil sodium. Daily diary cards showed a similar trend with significant drug effects seen after the third week. Blood and urine samples showed no abnormalities and the majority of patient withdrawals (five from nedocromil sodium and six from placebo treatment) were due to worsening asthma. Overall, we found nedocromil sodium to be well tolerated and effective in the management of bronchial asthma.     

Nedocromil sodium versus sodium cromoglycate in treatment of exercise-induced bronchoconstriction: a systematic review.

The objective of this review was to compare the effects of prophylactic doses of nedocromil sodium (NCS) and sodium cromoglycate (SCG) on postexercise lung function, in persons diagnosed with exercise-induced bronchoconstriction. Randomized controlled trials were identified from the Cochrane Airways Review Group Asthma Register, plus hand searching for trials in journals, bibliographies of relevant studies and review articles. Randomized controlled trials comparing NCS to SCG in prophylactic treatment of exercise-induced bronchoconstriction were eligible. Studies were pooled using odds ratios (OR) for dichotomous outcomes or weighted mean differences (WMD) with 95% confidence intervals (95% CI) for continuous outcomes. No significant differences were noted between NCS and SCG with respect to the maximum per cent decrease in forced expiratory volume in one second (WMD=-0.88; 95% CI -4.50-2.74), complete protection (OR=0.95; 95% CI 0.50-1.81), clinical protection (OR=0.71; 95% CI 0.36-1.39), unpleasant taste (OR=6.85; 95% CI 0.77-60.73), or sore throat (OR=3.46; 95% CI 0.32-37.48). Subgroup analyses based on age, dosages of medications and timing of exercise postinhalation were consistent with the overall pooled analyses. No significant differences were evident between the effects of nedocromil sodium and sodium cromoglycate during the immediate postexercise period in adults and children with exercise-induced bronchoconstriction, with regards to maximum per cent decrease in forced expiratory volume in one second, complete protection, or clinical protection. Side-effect profiles were similar.     

Nedocromil sodium inhibits responsiveness to inhaled mannitol in asthmatic subjects

Nedocromil sodium inhibits the response to exercise-induced asthma (EIA). Mannitol given as a powder by inhalation is an osmotic stimulus that identifies EIA. We studied the acute effect of nedocromil on airway responsiveness to mannitol in 24 asthmatic subjects. After a control day, nedocromil (8 mg) or its placebo was administered randomized, double blind, 10 min before a challenge with progressively increasing doses of mannitol. Nedocromil inhibited the response to mannitol and there was a significant increase in the dose of mannitol required to cause a 15% reduction in FEV(1) (PD(15)) after nedocromil 409 (316,503) mg compared with placebo 156 (106,229) mg (p < 0.001). In the presence of nedocromil 12 subjects no longer recorded a 15% decrease in FEV(1) in response to mannitol. The remaining 12 required a significantly greater dose of mannitol to achieve a 15% decrease in FEV(1) after nedocromil. Following nedocromil, a plateau in responsiveness to mannitol was observed in 14 subjects. Nedocromil significantly inhibits the responsiveness to inhaled mannitol in asthmatic subjects.     

Long-term treatment with sodium cromoglycate, nedocromil sodium and beclomethasone dipropionate reduces bronchial hyperresponsiveness in asthmatic subjects.

165 patients (106 males, 59 females) entered an open group comparative study of a 12-week test treatment on bronchial hyperresponsiveness (BHR) determined by methacholine challenge. Patients were randomly allocated to receive nedocromil sodium (4 mg q.i.d.), sodium cromoglycate (10 micrograms q.i.d.) and beclomethasone dipropionate (500 micrograms t.i.d.). At the end of the study, an 2.25-fold increase of the PD20FEV1 was noted in all the treated patients. No significant difference was noted among the treatments.     

Comparison of two different dose regimens of nedocromil sodium with placebo in the management of childhood asthma.

According to the recent guidelines, persistent asthma requires daily antiinflammatory treatment with either nedocromil sodium, cromolyn sodium or inhaled corticosteroids. In choosing the most appropriate drug, it is wise to weigh the therapeutic advantages against possible side effects, particularly in patients at the milder end of disease spectrum and in children. Cromolyn sodium and nedocromil sodium both have strong safety profiles, and nedocromil sodium has been reported to have a broader spectrum of efficacy than cromolyn sodium. In an attempt to provide data for the efficacy of two different dose regimens of inhaled nedocromil sodium in childhood asthma, a placebo-controlled, randomized, double-blind, double-dummy, parallel group study was conducted in 38 subjects with mild to moderate persistent asthma. After a 2-week run-in period, patients were randomly allocated into one of the three study groups and treated with either placebo or with two times daily (4 mg b.i.d.) or four times daily (4 mg q.i.d.) regimens of inhaled nedocromil sodium for 8 weeks. Symptom scores, bronchodilator requirements, FEV1, daily PEFs and methacholine hyperreactivity were evaluated at study entry, before randomization and at weeks 4 and 8 of treatment. In the four times daily treatment group, slight but significant increases were observed in FEV1, peak expiratory flows and symptom scores (p < 0.05 for each). However, there was no significant change in methacholine hyperreactivity and bronchodilator requirement. In the two times dose regimen and placebo groups, there were no improvements in any of the variables. The compliance, measured as the reduced weight of the canisters, was low, but was not different between the two nedocromil sodium treatment groups. The four times daily regimen of nedocromil sodium was effective in improving control of mild to moderate persistent asthma in children, whereas the two times daily regimen failed.     

A comparison of several agents with two delivery systems for the prevention of airway narrowing induced by nebulised pentamidine isethionate

Bronchial narrowing is the major side effect of inhaled nebulised pentamidine isethionate, used for the prophylaxis and treatment of Pneumocystis carinii pneumonia. Several agents and delivery systems were assessed for prophylaxis of bronchial narrowing in HIV-positive males receiving regular nebulised pentamidine isethionate. In a previous study we found the mean maximum fall in FEV1 with nebulised pentamidine alone to be 21%. FEV1 was measured before and after inhaling nebulised pentamidine, preceded by one of the following bronchodilator/immunoregulatory agents: Terbutaline metered dose inhaler (500 micrograms), nebulised salbutamol (5 mg), nebulised ipratropium bromide (500 micrograms), nebulised sodium cromoglycate (20 mg), and nedocromil sodium metered dose inhaler (4 mg). Each agent was administered once only to ten different subjects. Nebulised salbutamol gave most effective prophylaxis against bronchial narrowing induced by nebulised pentamidine (mean maximum fall in FEV1 = 5% vs. 21%, P less than 0.001). Terbutaline given by metered dose inhaler was significantly less effective than high dose terbutaline (10 mg) given by nebuliser, demonstrated in the previous study (mean maximum fall in FEV1 = 14% vs. 6%, P less than 0.05). Mean maximum falls in FEV1 for ipratropium bromide, sodium cromoglycate and nedocromil sodium were 16, 17 and 16%, respectively. High dose beta 2-agonists administered by nebuliser give more effective prophylaxis against nebulised pentamidine-induced bronchial narrowing than either lower doses given by metered dose inhaler, anticholinergics or immunoregulatory drugs.     

Comparative trial of sulphasalazine and oral sodium cromoglycate in the maintenance of remission in ulcerative colitis.

Patients with ulcerative colitis in remission were randomly allocated to treatment with sulphasalazine (2 g/day) or oral sodium cromoglycate (160 mg/day or 2 g/day), and the relapse rates in these treatment groups were compared during continued treatment for one year. The percentage cumulative relapse rate after 12 months' treatment was 30% in the 33 patients treated with sulphasalazine compared with 71% in the 25 treated with high dose sodium cromoglycate, a highly significant difference (P less than 0.01). Patients allocated low dose sodium cromoglycate were only treated for a maximum of six months, and the relapse rate in these 12 patients was similar to that in patients on the high dose. These results suggest that oral sodium cromoglycate is considerably less effective than sulphasalazine in maintaining remission, and by analogy with results in other trials may be no more effective than placebo tablets.