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The aim of this work was to study the effect of gas microbubbles on the production of particles suitable for inhalatory administration by a spray drying technology. An antiasthmatic model drug (sod...

Severe traumatic brain injury (TBI) results in significant functional disturbances in the hippocampus. Studies support that sodium cromoglycate (CG) induces neuroprotective effects. This study focused on investigating the effects of post-TBI subchronic administration of CG on hippocampal hyperexcitability and damage as well as on sensorimotor impairment in rats. In contrast to the control group (Sham+SS group), animals undergoing severe TBI (TBI+SS group) showed sensorimotor dysfunction over the experimental post-TBI period (day 2, 55%

Purpose . To study the effectiveness and tolerability of sodium cromoglycate (Uzbekistan) in the treatment of allergic conjunctivitis. Material and methods . 60 patients (120 eyes) with allergic conjunctivitis aged 18 to 60 years (28 men and 32 women), were divided into two homogeneous groups with similar clinical manifestations. The main group (30 patients), in addition to basic treatment, received instillations of sodium cromoglycate, 2 drops 4 times a day for 4 weeks. The control group (30 patients) received a foreign medication of the same group, instilled in the same way. Results . The patients of both groups revealed a comparable therapeutic effect. By the end of the treatment course, substantial positive changes were observed and the symptoms of allergic inflammation disappeared. The treatment effectiveness was 95.9 and 97.6 % in the main and the control groups, respectively. Conclusion . The use of domestic medication of the sodium cromoglycate group reduces the patients’ subjective complaints and helps achieve a maximum therapeutic effect at a price affordable by the patient and the clinic. No side effects or cases of intolerance to the drug of sodium cromoglycate group used have been revealed.

A simple technique to produce spray-dried porous particles for inhalatory administration was developed. The particles were produced using water as solvent, Sodium Cromoglycate as model drug and ammonium bicarbonate as pore forming agent. A central composite design was employed to study the influence of the: pore-forming agent concentration (in the drug aqueous solution fed to the spray dryer) and air inlet temperature on: process yield and powder properties. The powder particle size distribution, moisture content, densities and estimated aerodynamic diameters were studied. Also, particles morphology, hygroscopicity, surface area, in vitro aerosolization properties, dissolution rate and stability were evaluated for some selected samples. In addition, a novel friability test was proposed for mechanical resistance evaluation of the porous materials. A pore forming agent concentration of 1.25% (w/w) and an air inlet temperature of 170 °C were the optimal process parameters to produce porous particles suitable for inhalatory administration. The process yield was high and it was demonstrated that the particles were free of ammonium bicarbonate. The porous powder, obtained by a simple and scalable technique, exhibited low tap density, good stability even at long storage periods (12 months), appropriate mechanical resistance, high initial dissolution rate and excellent aerosolization performance. Fil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Ramírez Rigo, María Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Bucala, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentina

Fluorometholone (FLM) and Sodium Cromoglycate (CMG) are co-formulated in ophthalmic preparation and showed marked instability under different conditions. Two specific, sensitive and precise stability-indicating chromatographic methods have been developed and validated for their determination in the presence of their degradation products and FLM impurity. Ten components were efficiently separated by them. The first method was HPTLC-spectrodensitometry, where the separation was achieved using silica gel 60 F254 HPTLC plates and developing system of ethyl acetate: methanol (9:1, v/v). The second method was a reversed phase HPLC associated with kinetic study of the degradation process and was successfully applied for determination of the studied compounds in spiked rabbit aqueous humor. The mobile phase was acetonitrile: methanol: 0.05 M potassium dihydrogenphosphate (0.1% trimethylamine); pH 2.5, adjusted with orthophosphoric acid (20: 30: 50, by volume). In both methods, the separated components were detected at 240 nm and system suitability was checked. Good correlation was obtained in the range of 0.10–24.00 and 0.20–48.00 µg band−1, for FLM and CMG by HPTLC. While for HPLC, the linearity ranges from 0.01–50.00 and 0.05–50.00 µg mL−1 for both drugs. The methods were applied in pharmaceutical formulation, where they were compared to the reported method with no significant difference.

Remodeling of pulmonary resistance arteries in rats due to 4-day hypoxia could be successfully suppressed by sodium cromoglycate. In this study, we tested the difference in the suppression between two distinct time patterns of cromoglycate administration during 21-day hypoxia. In the experiment, we focused on some details in both smooth muscle cells and extracellular matrix of pulmonary arterial walls.During 21-day hypoxia, rats were treated with sodium cromoglycate either in the first four days or in the last four days. The first four days were chosen to test efficiency of an initial pulse of cromoglycate to suppress pulmonary vascular remodeling. The last four-day administration tested possibility to block remodeling post hoc.Initial pulse reduced and modified remodeling in all levels of pulmonary arteries, which comprises neomuscularization of prealveolar arteries, asymmetrical hypertrophy of tunica media in muscular pulmonary arteries and hypertrophy of tunica media and tunica adventitia in large conduit arteries. Terminal pulse had only negligible effect.Only the initial cromoglycate therapy led to significant morphological suppression of remodeling. We therefore assume important role of initial remodeling influencing during long time hypoxia experiment.

Purpose of review Many patients with interstitial lung diseases (ILDs), especially fibrotic ILDs, experience chronic cough. Cough has a major impact on wellbeing, affecting both physical and psychological aspects of life. The pathophysiology of cough in ILDs is poorly understood and currently no good antitussive therapy exists. Recent findings Research on cough in ILDs is increasing. A recent proof-of-concept study with nebulized sodium cromoglycate for patients with idiopathic pulmonary fibrosis (IPF)-related cough showed a promising effect on cough. Observational data suggest that antifibrotic pirfenidone might reduce cough in IPF. Studies on the effect of acid inhibition on cough in ILDs show contradicting results. Summary The first steps in analyzing new treatment options for chronic cough in patients with ILDs, especially in IPF, have been taken, but an effective treatment is still lacking.

Background Recurrent cow's milk (CM) aspiration is often associated with gastroesophageal reflux in infants and toddlers and it seems to be implicated in the etiology of different inflammatory lung disorders. This study aimed to investigate ex vivo the impact of CM aspiration on human airways and whether treatment with beclomethasone dipropionate (BDP) or sodium cromoglycate (SCG) may prevent the potential CM-induced airway hyperresponsiveness (AHR). Methods Human isolated bronchi were contracted by electrical field stimulation (EFS10Hz) to mimic the contractile tone induced by the parasympathetic activity and challenged with CM, fat/lactose-free CM, or human breast milk (HM). The effect of pre-treatment with beclomethasone dipropionate (BDP) and sodium cromoglycate (SCG) was also investigated on the AHR induced by CM. Results After a 60 min-challenge with CM 1:10 v/v and fat/lactose-free CM 1:10 v/v, ASM significantly (P ​, Graphical abstract Image 1, Highlights • Cow's milk aspiration seems to be associated with some inflammatory lung diseases. • Cow's milk aspiration induces human airway hyperresponsiveness. • Beclomethasone and sodium cromoglycate protect against cow's milk hyperresponsiveness in vitro. • Inhaled sodium cromoglycate might be suitable in children at risk of cow's milk aspiration.

Background: Allergic eye diseases are the commonest causes of ocular morbidity worldwide. To choose the best therapy in allergic conjunctivitis, understanding of underlying mechanisms implicated in triggering the allergy is very important. Olopatadine with a wide spectrum has proven to be very effective in allergic conjunctivitis. The objective of the study was to compare the efficacy and safety of ophthalmic solutions of olopatadine 0.2% once daily, olopatadine 0.1% twice daily and sodium cromoglycate 2% four times daily in allergic conjunctivitis for 3 weeks. Methods: This was a prospective, single centre study enrolling 304 patients with allergic conjunctivitis attending ophthalmology clinics. Subjects were assessed for ocular signs and symptoms at 3 visits-baseline, week 2, week 3. The change from baseline in the mean scores of itching and redness at 3 weeks was primary outcome variable. Results: The reduction in signs and symptoms were statistically significant in all the three groups (p

Background/Aims: Ulcerative colitis (UC) is a type of inflammatory bowel disease that mainly involves the colon. Thus far, glucocorticoids and amino-salicylate have been the main treatment. Methods: To assess drugs with fewer side effects, this study evaluated the effects of sodium cromoglycate (SCG) on acetic acid-induced UC in rats. The treatment groups included SCG receivers (50 and 100 mg/kg, intra-orally) and sulfasalazine (SSZ) receivers (100 mg/kg, intra-orally). The colonic mucosal injury was assessed by clinical, macroscopic, and histopathological examinations. Results: In the treatment groups with 50 and 100 mg/kg of SCG, the clinical activity score decreased to 2.67+/-0.18 and 1.73+/-0.21 (p

Sodium cromoglycate (SCG) and oxymetazoline hydrochloride (OXMT) are administered in combination for effective treatment of nasal congestion and allergy. In this work, SCG was determined using direct spectrophotometry by measuring its zero order absorption spectra at its λ max 320.6 nm where OXMT showed zero absorbance. On the other hand, four simple, sensitive and precise spectrophotometric methods were developed and validated for the determination of OXMT in the presence of SCG in their laboratory prepared mixtures and pharmaceutical formulation, without preliminary separation; Method A: first derivative spectrophotometric method [ 1 D], Method B: first derivative of ratio spectra method [ 1 DD], Method C: ratio difference spectrophotometric method [RDSM] and Method D: ratio subtraction method [RSM]. Ratio manipulating methods (Method B, C and D) were done using divisor of 10.00 µg/mL SCG. Linear correlation was obtained in range 4-22 µg/mL for OXMT by methods A, B and D and 6-22 µg/mL for method C. All methods were validated in compliance with the International Conference on Harmonization (ICH) guidelines and satisfactory results were obtained. No significant difference was noted between the developed methods and the official one with respect to accuracy and precision.

A sensitive and simple analytical strategy for the detection of sodium cromoglycate (SCG) has been established based on a readily detectable fluorescence quenching effect of SCG for glutathione-capped (GSH-capped) CdTe quantum dots (QDs). The fluorescence of GSH-capped CdTe QDs could be efficiently quenched by SCG through electron transfer from GSH-capped CdTe QDs to SCG. Under optimum conditions, the response was linearly proportional to the concentration of SCG between 0.6419 and 100 µg/mL, with a correlation coefficient (R) of 0.9964; the detection limit (3δ/K) was 0.1926 µg/mL. The optimum conditions and the influence of coexisting foreign substances on the reaction were also investigated. The very effective and simple method reported here has been successfully applied to the determination of SCG in synthetic and real samples. It is believed that the established approach could have good prospects for application in the fields of clinical diseases diagnosis and treatment.

Background Ocular allergies frequently present in pharmacy practices. However, research into the actual management of ocular allergy in pharmacies is lacking. Objective To determine and quantify history and symptom questioning of a patient with presumed allergic conjunctivitis and management strategies employed by pharmacy staff in the UK. Method A mystery shopper technique was used to simulate an episode of allergic conjunctivitis in 100 community pharmacies across the UK. Results The mean number of questions asked by pharmacy staff to the patient was 3.5 ± 2.6, with a range of 0-10. The most common question was whether the patient had a history of allergies (45 %).Ninety-one percent advised on treatment, with the remaining 9 % directly referring to the patient's general practitioner (n = 4) or pharmacist(n = 4), but only two to their optometrist. The most common treatment suggested was sodium cromoglycate 2 % (50 %). However, many pharmacies advising treatment did not ask the patient's age (37 %), if they wore contact lenses (43 %), or gave dosage advice (43 %). Only 5 % of pharmacies advised follow up and 14 % suggested visiting a general practitioner and 1 % an optometrist if symptoms did not resolve with treatment. Conclusion There is a need for improved ophthalmological training for pharmacy staff with respect to the management of allergic conjunctivitis. © Springer Science+Business Media Dordrecht 2012.

Background: The concentration of exhaled carbon monoxide (eCO) in young children with stable asthma and during acute asthma attack is not known. Methods: A sampling bag was developed to collect the exhaled air of preschool children. A total of 257 preschool-age children (≥3 years and ≤6 years old) were studied; 111 had a diagnosis of asthma (43 suffering a mild asthma attack and 68 without active asthmatic symptom), 99 had upper respiratory infection (URI) and 47 were healthy. Results: In preschool-age children, eCO levels of those with asthma attacks (mean ± SE, 2.7 ± 0.3 p.p.m., n= 43) were significantly higher than those of subjects with asymptomatic asthma (0.5 ± 0.1 p.p.m., P < 0.05), URI (0.8 ± 0.1 p.p.m., P < 0.05) and healthy children (0.4 ± 0.1 p.p.m., P < 0.05). A multivariate linear regression model showed that eCO was higher in children with asthma attacks independent of age and gender. In 33 asthmatic children followed before and after treatment, eCO levels during asthma attacks significantly decreased after inhalation therapy with a combination of salbutamol and sodium cromoglycate (before therapy, 2.9 ± 0.4 p.p.m.; after therapy, 0.6 ± 0.1 p.p.m., P < 0.0001). Conclusions: The measurement of eCO using a novel collecting system is useful in the recognition of asthma in preschool children.

Fluorometholone and Sodium Cromoglycate are used in the treatment of allergic conjunctivitis. A validated HPLC method was developed for the assay of them. The method was performed on BDS HYPERSIL C18 column (250x4.6 mm, 5μ) and the mobile phase consisted of potassium dihydrogen phosphate (pH 4.5, 0.025M) - Acetonitrile (40:60, V/V) which pumped at a flow rate 1.0 ml/min at ambient temperature. 20 μl of drugs sample solutions were monitored at two fixed wavelengths (lambda = 240.0 nm for Sodium Cromoglycate and 330.0 nm for Fluorometholone). The proposed method was validated in terms of linearity, accuracy, precision and limits of detection and quantitation according to ICH

Background and objective: Dry powder mannitol has the potential to be used to enhance clearance of mucus in subjects with bronchiectasis. A reduction in FEV1 has been recorded in some subjects with bronchiectasis after inhaling mannitol. The aim of this study was to investigate if pre-medicating with either sodium cromoglycate (SCG) or eformoterol could inhibit this reduction in FEV1. Methods: A double-blind, placebo-controlled, randomized cross-over study was conducted. Lung function and airway response to mannitol was assessed on a control day and then re-assessed after pre-medication with placebo, SCG and eformoterol in nine subjects. Sensitivity to mannitol, expressed as the dose required to induce a 15% fall in FEV1 (PD15), and reactivity to mannitol, expressed as the % fall in FEV1 per mg of mannitol (response–dose ratio, RDR), are reported. Results: Subjects had an FEV1 of 68 ± 14% predicted, FVC of 97 ± 15% predicted and FEV1/FVC of 71 ± 8%. They were mildly hypoxemic and the SpO2 was 95 ± 2%.They had a PD15 to mannitol of 235 mg (95% CI: 150–368 mg) and a RDR of 0.057% fall in FEV1 per mg (95% CI: 0.038–0.085). After pre-medication with SCG, PD15 increased (773 mg, P

This paper, which was presented at the 17th JMRC 'John Robert Vane Memorial' Symposium, describes some recent work from the authors' laboratory that provides a tentative explanation for the anti-inflammatory effects produced by the cromoglycate-like anti-allergic drugs. Some of the implications of this finding are discussed.

Food-dependent exercise-induced anaphylaxis (FDEIA) was prevented from recurring in 2 children by sodium cromoglycate (SCG) before intake of the causative food. Case 1: A 14-year-old girl who had suffered recurrent symptoms of anaphylaxis when she exercised after lunch. Radioallergosorbent test (RAST) was 1.49 UA/mL for wheat. She was advised to take SCG before lunch. In 2007, she ate bread at lunchtime without taking SCG and developed anaphylaxis. After this, she always took SCG and did not develop anaphylaxis. Case 2: A 9-year-old boy who had recurrent symptoms of anaphylaxis when he exercised after lunch. RAST was 0.46 UA/mL for wheat. He started taking SCG before lunch. In June 2008, he forgot to take SCG and ate fu (a food made from wheat). He exercised after lunch and developed anaphylaxis. Since then, he has always taken SCG and has not developed anaphylaxis. Conclusion: Our findings suggest that SCG prevents FDEIA caused by wheat allergy.

A multicentre, group comparative open study was carried out on 68 patients to compare the effects of 2% sodium cromoglycate eyedrops and an oral antihistamine, terfenadine, on acute symptoms of seasonal allergic conjunctivitis. The study was continued for one week after the onset of acute symptoms. Both medications were equally efficient in reducing symptoms during the first hour of observation. During the one-week follow-up both medications reduced symptoms to a low level, and both medications were equally effective for allergic symptoms, except that terfenadine was more effective in reducing the watering of eyes.

To compare pulmonary deposition after inhalation with three different nebulisers in preterm infants under conditions relevant to practice.The relative lung deposition (bioavailability) was estimated by inhalation of the marker substance, sodium cromoglycate (SCG), and measurement of urinary excretion of SCG. Seventeen spontaneously breathing preterm infants received 20 mg of SCG as nebuliser solution by means of (a) an LC Star jet nebuliser; (b) an LS 290 ultrasonic nebuliser; and (c) a Projet ultrasonic nebuliser in a randomised three-period, crossover design. Serial urine samples were collected until about 12 hours after inhalations, and the excreted SCG was determined by high-performance liquid chromatography.The mean (SD) total amounts of SCG excreted in urine measured after inhalation with the LC Star nebuliser (0.089 (0.036) mg) were significantly higher than those obtained with the LS 290 (0.055 (0.019) mg) or the Projet nebuliser (0.046 (0.025) mg). The average pulmonary deposition after inhalation using the LC Star, LS 290 and Projet devices was estimated as 0.89%, 0.55% and 0.46% of the nominal dose, respectively.Inhalation with the LC Star jet nebuliser producing the greatest proportion of droplets2 mum yielded a higher lung deposition in preterm infants than the LS 290 and Projet ultrasonic nebulisers.

Two stability-indicating reversed-phase liquid chromatographic methods were developed and validated for the determination of fluorometholone (FLU) in its mixtures with sodium cromoglycate (SCG) and tetrahydrozoline hydrochloride (THZ). The first HPLC method (Method 1) was based on isocratic elution of FLU and SCG along with their alkaline degradation products on a reversed phase C18 column (250 × 4.6 mm id)-ACE Generix 5, using a mobile phase consisting of methanol-water (70 : 30, v/v), pH adjusted to 2.5 using orthophosphoric acid at a flow rate of 1.2 mL min(-1) Quantitation was achieved with UV detection at 240 nm. The second HPLC method (Method 2) was based on isocratic elution of FLU, its alkaline degradation product and THZ on a reversed phase C8 column (250 × 4.6 mm)-ACE Generix 5, using a mobile phase consisting of acetonitrile-50 mM potassium dihydrogen orthophosphate (40 : 60, v/v) at a flow rate of 2 mL min(-1) Quantitation was achieved by applying dual-wavelength detection, where FLU and its alkaline degradation product were detected at 240 nm and THZ was detected at 215 nm at ambient temperatures. Linearity, accuracy and precision were found to be acceptable over the concentration range of 5-50 and 10-500 μg mL(-1) for FLU and SCG (Method 1) and over the concentration range of 5-80 and 5-60 μg mL(-1) for FLU and THZ (Method 2), respectively. Besides, the FLU alkaline degradation product was verified using IR, NMR and LC-MS spectroscopy. The two proposed methods could be successfully applied for the routine analysis of the studied drugs either in their pure bulk powders or in their pharmaceutical preparations without any preliminary separation step.

Purpose. The aim of the study was to evaluate the concentration - in-vitro release relationship for topical semisolid formulations of sodium cromoglycate. Materials / Methods. According to usual pharmaceutical compounding practice, commercially available cosmetic emulsions were used as vehicles for topical semisolid dosage forms containing 0.5, 2, 4 and 10% disodium cromoglycate (CS). The in-vitro release profiles and structural parameters of the resulting formulations was evaluated in a correlated manner, in order to reveal potential differences in the in-vivo performance. Results. Depending on the hydro-lipophilic characteristics of the vehicle and on the quantity of drug dissolved or dispersed, the structure and the release kinetics are distinct. Conclusions. The results suggested that current lack of an unitary approach for the compounding of semisolid dosage forms of CS, resulting from the lack of widely available, standardized dosage form could be a reasonable explanation for the apparent discrepancy in the reports of clinical outcome after topical administration.

This study estimated the health economic impact of olopatadine (Opatanol) compared to branded cromoglycate (Opticrom) and generic sodium cromoglycate in the treatment of seasonal allergic conjunctivitis (SAC) in the UK.This was a modelling study performed from the perspective of the UK's National Health Service (NHS).A decision model was constructed depicting the management of SAC sufferers who are 4 years of age or above over a typical allergy season of 4 months and considers the decision by a GP to initially treat a patient with olopatadine, branded or generic cromoglycate. The analysis assumed both drugs to be equally effective. Consequently, a cost-minimisation analysis was performed to identify the least costly alternative.Starting treatment with olopatadine is expected to lead to a healthcare cost of 92 pounds sterling (95% CI: 46 pounds sterling; 150 pounds sterling) over 4 months compared to 109 pounds sterling (95% CI: 65 pounds sterling; 166 pounds sterling) with branded cromoglycate and 95 pounds sterling (95% CI: 51 pounds sterling; 152 pounds sterling) with generic cromoglycate, resulting in a 16% and 3% reduction in healthcare costs respectively over 4 months of treatment. This cost-difference is primarily due to fewer GP visits among olopatadine-treated patients.Use of olopatadine instead of branded or generic cromoglycate affords an economic benefit to the NHS. Hence, within the limitations of the model, olopatadine is the preferred first-line treatment for use in SAC sufferers, since it is expected to lead to fewer GP visits, thereby releasing healthcare resources for alternative use.

To determine the efficacy of forskolin in preventing asthma attacks, we performed a single-blinded clinical study in children and adult out-patients at a public hospital in Mexico. Forty patients of either sex with mild persistent or moderate persistent asthma were assigned randomly to 6 months of treatment with forskolin at 10 mg/day orally (capsules) or with two inhalations of sodium cromoglycate every 8 h, i.e. three times a day. The number of patients who had asthma attacks during the treatment period was significantly lower among those receiving forskolin (8/20, 40%) than among those receiving sodium cromoglycate (17/20, 85%). Values of forced expiratory volume in 1 s and forced expiratory flow, mid-phase, were similar in the two groups during the treatment period. We conclude that forskolin is more effective than sodium cromoglycate in preventing asthma attacks in patients with mild persistent or moderate persistent asthma.

When the expected effect of an inhaled drug is not achieved, the cause could be poor inhalation technique and consequently a low pulmonary dose. A simple in vivo test to evaluate the pulmonary dose would be a benefit. This study evaluates the relative and systemic bioavailability following inhalation of nebulized sodium cromoglycate (SCG) in healthy subjects. Blood samples were collected during 240min and urine was collected in two portions, up to 6h post-inhalation. Two exposures were performed and comparisons based on the quantification of drug in plasma and urine by a high-performance liquid chromatography (HPLC) procedure were done. In one of the exposures, a pulmonary function test was performed to study if an expected effect of increased absorption could be detected. There was a good correlation between the two exposures shown in the plasma concentrations, but not in the urine analyses. The forced exhaled volume manoeuvres were associated with a higher Cmax and plasma concentrations up to 60min post-inhalation (P

The aim of this study was to determine the delivery of two different drugs from spacer devices of different lengths and diameter. Spacer devices were prepared from lengths of plastic tubing of length 5, 10, 20, 50 and 100 cm, and diameter 30, 50 and 100 mm. Metered dose inhalers of sodium cromoglycate and budesonide were actuated into the spacers and drug output and particle size were measured using a glass multistage liquid impinger. To determine the effect of delay on the recovery of drug from the spacers, budesonide was actuated into spacers and output measured after a delay of 5, 10 or 20 s. For both drugs, increasing spacer length up to 20 cm increased drug recovery. There was no further increase or reduction with longer spacers. Increasing spacer diameter also increased drug recovery, although the increase was greater for sodium cromoglycate than budesonide. Budesonide delivery was greatest for spacers with a volume of 300 mL or greater, whereas maximum sodium cromoglycate delivery was from spacers with a volume of 1000 mL or greater. Drug half-life was also longer in larger spacers, being 6 s in a 10 cm length spacer (196 mL volume) and 15 s in a 20 cm length spacer (392 mL volume). The optimum spacer size was different for the two drugs. Sodium cromoglycate is best delivered from a larger spacer than budesonide. Conclusions from studies with one drug and spacer combination cannot be applied to another.

Although infants and children are affected by many acute and chronic diseases, nearly 80% of the drugs approved in the US for use in adults have not been labelled for paediatric use. This leads to the 'off-label' use of drugs which may produce suboptimal efficacy or harmful effects. Recent regulations proposed by the US Food and Drug Administration (FDA) require the industry to conduct paediatric studies in certain situations. However, some incentives will be provided to the industry to seek paediatric labelling. Paediatric practitioners and researchers will play an active role in conducting research and disseminating data about medication use in infants and children. However, increased funding is required for paediatric research. Industry, government, associations, academia and the public should work together to develop an agenda for action, with the goal of improving clinical outcomes and quality of life in infants and children.

Earlier guidelines recommended the use of bronchodilators, such as β2-agonists, in patients with mild asthma (defined as having symptoms present on ≤3 days per week), the use of sodium cromoglycate in moderately severe asthma patients (symptoms present on >3 days per week), and inhaled corticosteroids in those not satisfactorily controlled by sodium cromoglycate (severe asthma). A retrospective study was performed to evaluate the effect of such a stepwise approach on the long-term outcome of the disease. A group of 175 children were followed for a mean of 8.4 years (range, 2–16 years) and divided into mild (treated with “as-needed” bronchodilators, usually β2-agonists), moderate (treated with sodium cromoglycate), and severe asthmatics (treated with inhaled corticosteroids). Treatment was altered if patients deteriorated or improved. The clinical improvement (as determined by days with symptoms present, emergency room visits, and hospitalizations) of patients being treated with anti-inflammatory agents (sodium cromoglycate or inhaled corticosteroids) was significantly greater than for those receiving bronchodilators. Delay in starting sodium cromoglycate, but not inhaled corticosteroids, had a negative effect on both clinical outcome and pulmonary function. Spirometry showed a significant worsening in the mild group but improvements in the moderate and severe groups. Thus, treatment with anti-inflammatory drugs improves the long-term prognosis and at least partially reverses the natural history of the disease; however, sodium cromoglycate should be started in milder patients than those recommended by the earlier guidelines. The new Global Initiative guidelines have recommended moving the indication for the start of non-steroidal anti-inflammatory drugs from having symptoms on >3 days per week to having symptoms on >1 day per week. Considering the fact that inhaled corticosteroids have some side effects even at standard doses, especially in patients with milder asthma, it would appear that a stepwise approach, starting with non-steroidal anti-inflammatory drugs is the most appropriate therapy for patients with mild-to-moderate asthma. Pediatr. Pulmonol. 1997; Supplement 15:34–39. © 1997 Wiley-Liss, Inc.

Objective A study was made to assess the proportion of 17-year-old students who consider themselves to have allergic rhinoconjunctivitis and to find out how they treat themselves. Method The study was performed outside the pollen season in 1993 and 1994 and 5,938 first-year secondary school students in eight different cities were asked to answer a questionnaire during class. Results A total of 1,458 students (24%) claimed that they suffered from allergic rhinoconjunctivitis after being given a description of the disease. Sixty-five percent had had symptoms for 3 or more years and most of the sufferers, 71% had had symptoms during the spring and/or summer. In 32% of the sufferers, the causative agent was unknown. Seventy-six percent (n = 1,103) of the sufferers treated themselves with drugs. The most commonly used drugs for a systemic effect were nonsedating antihistamines and for a local effect, sodium cromoglycate. Of those who used nasal drugs (sodium cromoglycate and/or steroids, n=545), only 14% used them daily, 51% always when having symptoms, and 35% occasionally when having symptoms. The reasons for not using nasal sprays daily were inconvenience and embarrassment. Twenty-five percent had bought the drug over-the-counter in 1992, the first year when allergy drugs could be purchased without a prescription. The use of over-the-counter treatment increased in the following year to 33% ( P Conclusion We conclude that many young people perceive themselves as having allergic rhinoconjunctivitis and that the treatment can be much improved for the group as a whole.

The influence of sodium-cromoglycate (cromolyn) on the binding and ingestion of sheep erythrocytes (SRBC) by elicited rat peritoneal macrophages (M phi) was studied using unsensitized SRBC. SRBC sensitized by homologous IgG or by IgM and complement as target cells. Preincubation of M phi with the drug (1 nM/1-2 mM/1) markedly enhanced both binding and ingestion of uncoated SRBC. The IgG-related increment in binding and phagocytosis was not significantly influenced by the drug. When target cells were coated by IgM and complement cromolyn pretreatment was ineffective. Preincubation of M phi by bovine brain gangliosides (BBG) diminished the cromolyn-induced enhancement of target cell binding and phagocytosis. When SRBC were pretreated by BBG, an increase of binding and phagocytosis was observed. These data suggest that cromoglycate may enhance the capacity of M phi to bind erythrocytes via ganglioside structures. Coating SRBC by complement components appears to interfere with binding of erythrocytes to M phi ganglioside receptors.

Summary Despite their frequency, upper respiratory tract infections (URTIs) constitute an area with few, if any, effective treatment remedies. Asthma and airway allergies share similar pathogenetic mechanisms to URTIs and it is not surprising, therefore, that agents used to treat allergic disorders have also been studied in URTIs. Their possible effects, limitations and hypothetical modes of action in URTIs are reviewed. In controlled clinical trials of satisfactory scientific standard, symptom reductions in both experimental rhinovirus infections and natural colds have occurred with topical anticholinergics, oral antihistamines and topical chromones. Future treatment alternatives for URTIs may include the intranasal anticholinergic ipratropium bromide, new nonsedating antihistamines and sodium cromoglycate (cromolyn sodium). The latter has a record of safety and an absence of adverse effects that would make it an attractive alternative for this common but not particularly serious condition in otherwise healthy individuals.

An economic analysis was conducted comparing the cost effectiveness of fluticasone propionate with that of sodium cromoglycate (cromolyn sodium) in a group of children aged 4 to 12 years old with asthma, who required inhaled prophylactic therapy. Over an 8-week study period, 115 patients received sodium cromoglycate 20mg 4 times daily, via the spin operated dry powder inhaler, and 110 patients received fluticasone propionate 50 micrograms twice daily, via the Diskhaler (trademark held by the Glaxo Wellcome Group of Companies). Patient healthcare resource use was examined in terms of study medication, the use of rescue medication [salbutamol (albuterol) 200 micrograms] and the number of hospitalisations. The effectiveness of both treatments was examined over a range of success and failure criteria embracing peak expiratory flow rate (PEFR) improvement, symptom control and the level of adverse events related to the study medication. Results indicate that, for each UK pound spent, fluticasone propionate was associated with twice as many successfully treated patients as sodium cromoglycate, using a range of outcomes based on the goals of treatment defined in the British Thoracic Society's asthma guidelines. It is concluded that fluticasone propionate was more cost effective than sodium cromoglycate in improving PEFR and symptom control in this group of children with asthma who had a clinical requirement for prophylactic therapy.

Background Sodium cromoglycate was first introduced as an inhaled treatment for bronchial asthma in the late 1960s. Initially, it was presented as 20 mg of sodium cromoglycate (SCG) combined with 0.1 mg of isoprenaline sulphate in a capsule which was inhaled using a Spinhaler. Sodium cromoglycate without isoprenaline sulphate was introduced shortly afterwards and, subsequently, further formulations have been introduced. These include a 1% aqueous solution containing 20 mg SCG for nebulization, a metered dose inhaler (MDI) delivering I mg SCG per actuation, an MDI delivering 5 mg SCG per actuation and an MDI delivering I mg of SCG and 0.1 mg of salbutamol per actuation. The most commonly used form at present is the MDI delivering 5 mg per actuation.

Objective: To review treatment prescribed to asthmatic children in Great Britain during the 12 months after publication of the first guidelines and to assess effectiveness of prophylactic treatment. Design: Review of prescribing information from January 1990 to June 1991 in a representative sample of general practices in Great Britain with a Compufile/AAH Meditel computer. Subjects: 17846 children with asthma aged 4-17 years. Main outcome measures: Numbers of children prescribed different asthma treatments; estimated use of inhaled β agonists in those receiving prophylactic treatment. Results: From January to December 1990, 9362 (52.5%) children were prescribed preventive treatments. 16211 (90.8%) children were prescribed bronchodilators of some kind. 3055 (17.1%) were prescribed sodium cromoglycate, and the proportion decreased significantly during the study (from 19.5% (95% confidence interval 18.6% to 20.4%) to 17.2% (16.4% to 18.1%), P Conclusions: These results are useful baseline data for audit of the impact of published clinical guidelines, particularly in terms of reducing the need for short acting inhaled β agonists with prophylactic treatment.

An entire school year of 8-9 year old schoolchildren in Sheffield were surveyed using the core questions of the international study of asthma and allergies in childhood in order to assess the morbidity associated with diagnosed asthma. Of 5321 children surveyed, replies were obtained from 4539 (85.3%). A current diagnosis of asthma was reported in 466 (10.3%), and a further 6.4% reported symptoms compatible with significant undiagnosed asthma. A validated questionnaire was used to assess symptoms and perceived disability in 336 (72.1%) of the children with diagnosed asthma. One third reported symptoms every day or most days, while 15.3% reported frequent nocturnal symptoms. There was no significant difference in reported symptoms between those receiving inhaled steroids, sodium cromoglycate, or no prophylaxis. Despite this, parents of children receiving inhaled steroids perceived more disability, and worried more about their children's health. It is concluded that perceived symptoms and morbidity are high in children with diagnosed asthma, and speculate that level of treatment is determined by parental tolerance of symptoms as much as by the symptoms themselves.

Two cases with intractable bronchial athma were treated with extensive inhalation therapy. The inhalation constituted with sodium cromoglycate+beta2-stimulant+prednisolon was scheduled for 5-6 times a day extended to mid-night and early morning using specially designed inhalation equipment. This protocol of therapy was found to be effective for intractable asthmatic children to induce remissive state.Case 1: A 15 year-old boy who was diagnosed as bronchial asthma on 1 year old was admitted to our Children's Allergy Center when he was 10 year-old. He had previously experienced frequent hospitalization due to recurrent attacks of asthma, and treated intensively including steroids. After admission the extensive inhalation protocol was initiated, and within 1-2 months asthmatic attacks were almostly relieved.Case 2: A 15 year-old boy with intractable asthma for 13 and half years was treated with the same regimen. In a few weeks with the extensive inhalation therapy remissive state of asthmatic attacks was achieved.Thus, the extensive inhalation therapy was revealed effective for both patients with long-term intractable asthma.

Among nonsteroidal anti-inflammatory drugs used in the treatment of adult asthma, sodium cromoglycate and nedocromil sodium are the most frequently prescribed. These medications have a similar efficacy profile in asthma although it has been suggested that nedocromil is more powerful than cromoglycate, particularly in its steroid sparing effects. Both drugs have been recommended as alternatives to steroids in the treatment of mild asthma. They are useful in the prevention of bronchospasm induced by exposure to allergens or to a variety of other stimuli. In comparison with theophylline or low dose inhaled steroids, cromoglycate and nedocromil have shown a similar antiasthmatic efficacy, although this is variable among patients.

Although the Spinhaler has been available for many years as a delivery device for sodium cromoglycate powder, the quantity of powder delivered to the lungs and the optimal mode of inhalation for this device have remained largely unknown. Lung deposition of 20 mg sodium cromoglycate powder (labelled with the radionuclide 99m Tc) from the Spinhaler has been measured in 10 healthy volunteers who inhaled by four carefully controlled inhalation modes, involving fast (120 l min −1 ) and slow (60 l min −1 ) peak inhaled flow rates, holding the head in the normal and tilted-back (60° to the horizontal) positions, and breath-holding pauses of 0 and 10 s. Inhalation at 60 l min −1 significantly ( P −1 . Among the inhalation modes tested, delivery to the lungs was optimised (mean 17.1% of the dose) when powder was inhaled at 120 l min −1 , with the head in the normal position, and with 10 s breath-holding.

In a double-masked group comparative study, 20 patients received 2% nedocromil sodium four times daily and 23 placebo eye drops, for treatment of perennial allergic conjunctivitis (PAC). All had at least a one-year diagnosis of bilateral PAC and remained symptomatic despite using 2% sodium cromoglycate eye drops four times daily for at least 14 days Symptom severity (0-4) during sodium cromoglycate monotherapy was then recorded in a one-week baseline prior to randomisation, a minimum total score of 11 being mandatory. During the trial, no eye medication was allowed other than the test treatment. Clinic examinations were made before and after baseline and after one, three and six weeks' treatment, and patients kept daily diary cards of eye symptom severity. Compared to placebo, nedocromil sodium significantly (p0.05) improved diary scores for itching (weeks 3, 4, 5, 6), total symptoms (weeks 5, 6) and general eye condition (week 6). Mean scores over the final four weeks, allowing a two-week washout, showed similar improvements in itching (p = 0.01), total symptoms (p = 0.05) and general eye condition (p = 0.04). Clinical assessments again favoured nedocromil sodium, which improved itching (week 3, p = 0.002), burning (week 6, p = 0.007), overall eye condition (weeks 3-6, p0.05). and conjunctival thickening and hyperaemia (weeks 3-6, p0.05). Finally, both patient (p = 0.02) and clinician (p = 0.0015) opinions of efficacy favoured nedocromil sodium over placebo. These results show nedocromil sodium to be effective in controlling symptoms of perennial allergic conjunctivitis which persisted during treatment with sodium cromoglycate.

Sodium cromoglycate (SCG) was given daily for 24 weeks to 13 children with bronchial asthma, and its acute and chronic actions were determined. SCG was found to increase the peak expiratory flow rate (PEFR) immediately after inhalation in 12 patients, an increase frequently observed in patients whose PEFR was less than 50% of the expected value. In addition, the mean PEFR was increased by 17% after the study compared with that deduced from the baseline before the study, and the difference was statistically significant. These results indicate both acute and chronic antagonistic effects of SCG for bronchoconstriction in childhood asthma.

In this paper we present data on the assessment and treatment of asthma in a large sample (13,899 subjects) representative of the population of young males living in four districts of the Tuscany region (Italy). In this group, 404 asthmatics (2.9%) were identified and 365 of the eligible patients were included in the study. A total of 323 asthmatics (88.5%) reported respiratory symptoms during the preceding year. A total of 162 asthmatics (44%) had previously had lung function tests to assess asthma, whereas in 89% of the patients the atopic component of asthma had been previously evaluated by prick tests. Fifty-seven percent of the patients in whom bronchial obstruction was observed and 38% of the asthmatics with severe bronchial hyperresponsiveness (BH) were receiving either no medication or treatment with only one drug. The drugs prescribed most frequently during the preceding year were beta agonists (56%) as opposed to sodium cromoglycate (22%) and inhaled steroids (17%); the latter two drugs were included in the therapy of 143 asthmatics (39%) and represented the treatment of choice in 16% of the subjects with bronchial obstruction and in 38% of the subjects with severe BH. We conclude that in our sample of young asthmatics the pulmonary function tests and the inhaled anti-inflammatory drugs were insufficiently utilized.