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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.

Sodium cromoglycate (SC) is an antiasthmatic and antiallergenic drug commonly used for chronic inhalation therapy, however many daily intakes are required due to the fast drug clearance from airways. For these reasons, SC polymeric particles for inhalatory administration with adequate aerosolization and mucoadhesive properties were designed to prolong the drug residence time in the site of action. Sodium carboxymethylcellulose (CMCNa), sodium hyaluronate and sodium alginate were selected to co-process SC by spray drying. The influence of these polysaccharides on the spray drying process and powder quality were evaluated (among others, morphology, size, moisture content, hygroscopicity, flowability, densities, liquid sorption and stability). In vitro aerosolization, drug release and mucoadhesion performance were also studied. Particularly, a novel method to comparatively evaluate the interaction between formulations and mucin solution (mucoadhesion test) was proposed as a rapid methodology to measure adhesion properties of inhalable particles, being the results as indicative of clearance probability. Among all the studied formulations, the powder based on SC and CMCNa exhibited the best mucoadhesion and aerosolization performance, the highest process yield and adequate moisture content, hygroscopicity and stability. SC-CMCNa formulation arose as a promising inhalatory system to reduce the daily intakes and to increase the patient compliance. 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 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 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

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.

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.

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

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.

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.

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.

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.

Despite international consensus and clearly written guidelines urging wider use of corticosteroids or combinations of inhaled short- and long-acting β-agonists (SABA and LABA) and corticosteroids in persistent asthma, prescribing patterns and compliance rates fall far short of recommendations. The failure to use steroids more aggressively is due, in part, to their side effects, even with inhaled forms of the drug. There is a role for expanded use of sodium cromolyn in asthma. Its potent anti-inflammatory effects, lack of side effects, and acceptable dosing and method of delivery, as well as its special role in exercise-induced asthma, make it a very suitable choice in the initial therapy for control of asthma. Compared to SABA and LABA, cromoglycates alone are unsuspicious of being used to enhance physical performance.

The mechanism of action of the antiasthmatic drug sodium cromoglycate (SCG) is unclear. One possibility is that SCG antagonizes the effects of the tachykinin substance P (SP), an agent known to cause airway edema. However, when SP is inhaled by humans, it has no demonstrable effect on airway function; therefore, the possibility that SCG prevents SP-induced changes in microvascular permeability was examined in human skin in vivo where potent edema-producing effects are seen. SCG (5–500 nmol) caused significant (P < 0.05) dose-dependent inhibition of SP-induced edema (wheal) formation when coadministered by intradermal injection. There was no effect on the nonreceptor-mediated flare response. SCG also significantly (P < 0.05) inhibited the wheal response to the related tachykinin neurokinin B but had no inhibitory effect on the cutaneous responses to histamine and prostaglandin E2. In addition, SCG (0.1–10 mM) caused dose-dependent inhibition of binding of SP labeled with 125I-labeled Bolton-Hunter to a number of tissues known to contain SP binding sites, as assessed by autoradiography. These concentrations were equivalent to the final concentrations of SCG found to inhibit the wheal response in the skin. The possibility that SCG interacted with SP was investigated both by gel filtration and high-performance liquid chromatography. No strong interaction was demonstrated with an 8,000 M excess of SCG under both hydrophobic and hydrophilic conditions. These results raise the possibility that SCG may have tachykinin antagonist properties.

Three cases of diffuse cutaneous mastocytosis (DCM) were at first incorrectly diagnosed as staphylococcal scalded-skin syndrome. In the first patient, at age 1 day the disease was recognized promptly by simple techniques such as Darier's sign and Tzanck smear. Much delay in making the diagnosis occurred in the other two patients, however: almost 1 year and 15 years, respectively. Bullous manifestations in mastocytosis occur only in the first two or three years. In the first months the disease can be dangerous and life threatening. To distinguish mastocytosis from vesicular and bullous neonatal disorders, one should perform Darier's sign and a Tzanck smear. The diagnosis is confirmed by histopathologic studies. Treatment of the bullous manifestations is symptomatic, with zinc oxide paste and oral antihistamines, which may provide some relief. In addition, cimetidine and sodium cromoglycate may be beneficial. At a later age psoralen plus ultraviolet A therapy may also relieve the symptoms. Particular foods and medicines can liberate histamine and should be restricted as much as possible in extremely affected patients. Special care should be taken when these patients are to undergo anesthesia. The risk of complications during and after anesthesia is also present in other forms of mastocytosis.

One of the many areas of clinical practice in which GPs are accused of failing to keep up with modern methods is in the management of allergies. It seems that every couple of years some elite medical body documents the woeful state of standards in primary care and insists on the urgent need for more training for GPs as well as demanding the provision of more specialist services. So when patients ask for a referral for skin tests or other forms of expert investigation and treatment, I duly oblige. It is always something of an anticlimax when they return with a recommendation for a prescription for some combination of an antihistamine, a steroid cream, inhaler or nasal spray, and sodium cromoglycate eye drops. I used to …

The circumstances surrounding the death of all patients who died from asthma in the State of Victoria over a 12-month period from May 1, 1986 were investigated. Data were collected using an interviewer-administered questionnaire as soon as practicable after registration of the death. In 168 cases asthma was considered to be the cause of death and adequate data were obtained in 163; 75 of these were male (74 over 60 years of age). Thirteen per cent had a history of trivial or mild asthma, 22% of moderate and 65% of severe asthma. Thirty-four per cent had not been limited at all or only by active sport, while 39% had had no previous hospital admission for asthma. In only 18% had there been a previous admission to an intensive care unit. Forty-seven per cent were taking inhaled beclomethasone or sodium cromoglycate regularly and 27% were taking corticosteroids by mouth regularly. Death occurred outside hospital in 150 of 163 subjects. In the final attack 58% had a sudden onset and collapsed within minutes, 20% were found dead and 27% had an acute progression of an established attack. Twenty-nine per cent of the deaths were assessed as preventable: preventable factors included inadequate assessment or therapy of prior asthma (35%), poor compliance with therapy (33%) and delay in seeking help (43%). As a significant number of subjects in this survey could not be classified as "high risk", it is important that clinicians ensure that all patients are aware of optimal maintenance management and have a clear individualized plan of what to do in the event of deteriorating asthma.

This year is the 50th anniversary of the introduction into clinical use of the first modern inhaler for the management of asthma — the pressurised metered-dose inhaler (pMDI). The pMDI was initially used for the administration of the non-selective beta-agonists adrenaline and isoprenaline. However, the epidemic of asthma deaths which occurred in the 1960s led to these drugs being superseded by the selective short-acting beta-agonist salbutamol, and the first inhaled corticosteroid (ICS) beclomethasone. At the same time, sodium cromoglycate was introduced, to be administered via the first dry-powder inhaler — the Spinhaler — but owing to its relatively weak anti-inflammatory action its use is now very limited. Over the last 10 years, the long-acting beta-agonists (LABAs) have become an important add-on therapy for the management of asthma, and they are now often used with ICS in a single ICS/LABA combination inhaler.

Purpose. To investigate the interaction and compatibility between a soft contact lens (SCL) and an ophthalmic drug. Methods. Samples were prepared with the nonionic SCL (groups I and II), the anionic SCL (group IV), and the zwitter ionic SCL (group IV). Chlorpheniramine maleate and sodium cromoglycate were used to measure the drug uptake into the SCL. Results. The results showed the largest drug uptake into the anionic SCL accompanied with dimensional changes and lower drug uptakes into the nonionic and the zwitter ionic SCL with dimensional stability. The cell permeability of the substances when instilled in the eye over the SCL was also measured. The zwitter ionic SCL allowed cell permeability comparable to that by oral administration. Conclusions. These results indicated the possibility for the zwitter ionic SCL as a lens to be worn concomitantly with ophthalmic drug instillation.

Epidemiological studies in many countries strongly suggest an increase in the prevalence of seasonal allergic rhinitis, particularly in urban communities. The mechanisms of allergic rhinitis have been the subject of much research, elucidating symptomatology and improving the focus of therapeutic strategies. Ideally, avoidance of the offending allergen may be undertaken but is often incompatible with normal activity. Thus, active therapy is usually required, selected from a range of pharmacologic agents. Choice is determined by the severity of the symptoms, the age and individual circumstances of the patients, and may vary considerably from country to country. The menu will primarily include rapid onset, oral non-sedating H1 antihistamines, topical nasal steroids and topical sodium cromoglycate to the nose, eyes or both. These medications may be given alone or in combination, usually under the direction of the primary care physician, and should be commenced in advance of exposure to the seasonal allergen. If this proves ineffective, specialist referral should be made for further management.

In the management of food allergic conditions orally administered sodium cromoglycate can be used in a supportive role to an elimination diet. It can either be used in addition to a diet when this does not provide complete control of symptoms or to provide cover against short-term breaks in the diet.

The relative lung bioavailability of sodium cromoglycate following inhalation has been evaluated using urinary drug excretion in nine healthly volunteers. Each inhaled four 5 mg sodium cromoglycate doses from a generic metered dose inhaler (MDI) and when it was attached to large volume spacer (MDI + VOL). A breath-actuated MDI was also evaluated either used on its own (EB) or attached to a small volume spacer tube (EBO). The mean (SD) urinary excretion of sodium cromoglycate in the first 30 min post-inhalation was 34.1 (20.2), 211.7 (123.5), 29.3 (19.5) and 52.8 (36.0) μg following MDI, MDI+VOL, EB and EBO, respectively. The cumulative mean (SD) urinary excretion of sodium cromoglycate over the 24 h post-inhalation was 364.7 (266.2), 1227.1 (459.0), 280.2 (155.4) and 429.5 (176.7) μg. A metered dose inhaler attached to a large volume spacer delivers more sodium cromoglycate to the lungs than any other inhalation method.

Background: Pyoderma gangrenosum is an uncommon skin disease usually treated with systemic drugs, most frequently corticosteroids. Isolated topical treatment is usually considered unsatisfactory. Objective: To evaluate the effect of topical 1% sodium cromoglycate solution on pyoderma gangrenosum in 5 patients 25–30 years of age. Methods: 5 patients, including 2 under systemic steroid treatment, hospitalized in our department from 1992 to 1993 because of pyoderma gangrenosum, were treated with topical 1% sodium cromoglycate solution. Systemic corticosteroids were further added in 2 patients whose initial improvement was inadequate. Results: Initial improvement was noted in all 5 patients after 3–7 days of sodium cromoglycate treatment. Complete healing of the ulcers occurred within 5–8 weeks. Conclusions: Topical treatment with sodium cromoglycate can be effective as adjunctive or sole treatment in pyoderma gangrenosum.

The long-term treatment modalities of bronchial asthma were studied in children from a defined Finnish population from 1985 to 1993, with special reference to changes during the study period. The data on maintenance drugs in children with asthma from five years (1985, 1987, 1989, 1991 and 1993) were retrospectively retrieved from the computerized registers. The reliability of the data for the diagnosis and basic treatment of asthma was checked by one of the authors, who compared the data with the patient cards from the hospital. The number of children with doctor-diagnosed asthma increased continuously during the surveillance period. The proportion of children receiving preventive medication increased concomitantly; this increase was most pronounced between 1987 and 1989. The most common preventive drug was sodium cromoglycate; its use increased from 14% in 1985 to 58% in 1993. The use of inhaled steroids remained stable at 17-19% in all surveillance years. Our treatment policy is in accordance with the international consensus statement published in 1989; however, the change towards preventive medication occurred before its publication.

Obvious precipitating factors should be sought and avoided when practicable. This is possible for specific allergens such as animals and foods, but is not usually feasible with more widespread allergens such as pollens and house dust mites. A common non-specific stimulus is cigarette smoking. Up to a fifth of asthmatics continue to smoke andstrenuous efforts should be made to discourage smoking in both asthmatic patients and their families. Precipitating factors should be carefully explored on one of the first visits but they should also be reassessed periodically. Fortunately most asthmatic patients can have their disease controlled by safe drug treatment with minimal side effects. Education of the patient in understanding the disease and treatment is often helped by home peak flow recording and written explanations of the purpose and practical details of treatment. In particular, the differences between symptomatic bronchodilator treatment and regular maintenance treatment must be emphasised. It is all too common to find asthmatic patients using their dose of inhaled steroid or sodium cromoglycate only to treat an acute attack. Trained nurses can be helpful in continuing education and supervision. Many hospitals have concentrated their patients into specific asthma clinics for …

Sodium cromoglycate is manufactured by a seven-stage synthetic process. There has been no previous documentation of toxicological effects of the intermediate compounds in its synthesis. This paper describes the health effects of acute exposure to the intermediates on the skin, eye and respiratory tract. With the exception of the product of the fourth stage, 2,6-dihydroxyacetophenone, no significant local effects arise at exposures of 10 mg m−3. Inhalation of dried 2,6-dihydroxyacetophenone produces nasal irritation and sneezing at short-term exposures of around 1 mg m−3.

Nedocromil sodium (Ned) 4 mg, sodium cromoglycate (SCG) 10 mg, and placebo were compared for their efficacy in preventing exercise-induced asthma. Nineteen asthmatic children aged six to 15 years performed a treadmill exercise test before and 20' after a single dose of drug in a double-blind trial. Both active drugs performed significantly better than placebo; in fact the exercise challenge resulted in a mean maximum fall in FEV1 of 26.1 +/- 14.9% after placebo, but only of 14.6 +/- 11.5% after SCG (P < 0.05), and 11.0 +/- 12.4% after Ned (p < 0.01). Measurements of PEFR gave similar results, while the effect of treatment on FEF 25-75 was significant for Ned alone (p < 0.05). Direct comparison between Ned and SCG at different time points demonstrated significant differences in FEV1 at 1 min (p < 0.05) with a better overall performance of Ned. In individual patients, complete protection was provided in 9 patients with SCG, in 14 patients with Ned and in 2 with placebo. No side effects were observed. This study suggests that at the dosages used there are only slight differences between SCG and Ned activity in the prevention of exercise-induced asthma.

We conducted a double-blind parallel-group study to compare the efficacy of inhaled nedocromil sodium and inhaled sodium cromogylcate in patients aged 50 years or over with asthma. Seventy-seven patients were randomized, 38 to receive nedocromil sodium (4 mg q.d.s.) and 39 to receive sodium cromoglycate (10 mg q.d.s.) over a 16-week period. Eight patients withdrew from the study. Both patient groups showed a reduction in inhaled bronchodilator usage during the treatment period. No statistically significant differences were seen in diary card PEF recordings or symptom scores. Both clinic PEF and FEV1 were significantly greater (P0.05) in the sodium cromoglycate group at week 12. Patients considered the treatment to be very or moderately effective in 59% of the nedocromil sodium group and 50% of the sodium cromoglycate group. Thus, the study suggests that there is no difference in response to nedocromil sodium or sodium cromoglycate in this older group of patients with asthma who are already on moderate doses of inhaled steroids.

BACKGROUND--Aerosols generated from metered dose inhalers may be highly charged. The aim of this study was to determine whether lining the walls of a polycarbonate spacer device with an antistatic agent would result in an increase in drug output. The effects of multiple actuations of drug into the spacer device and increasing residence time of drug within the spacer were also determined. METHODS--The amount of sodium cromoglycate contained in particles of various size available for inhalation (per 5 mg actuation) from a 750 ml polycarbonate spacer was determined by impinger measurement and spectrophotometric assay. RESULTS--Lining the spacer with an antistatic agent increased the mean (SD) amount of sodium cromoglycate in particles < 5 microns available for inhalation (per 5 mg actuation) by 244% from (0.59 (0.03) to 1.44 (0.2) mg). When there was a 20 second interval between actuation into the spacer device and inhalation, sodium cromoglycate available for inhalation in particles < 5 micrograms decreased by 67% (from 0.59 (0.03) mg to 0.2 (0.01) mg). Use of the spacer device increased sodium cromoglycate available for inhalation in respirable particles (< 5 microns) by 18% compared with direct delivery by metered dose inhaler. Multiple actuations into the spacer decreased the amount of sodium cromoglycate available for inhalation in particles < 5 microns by 31% after two actuations and 56% after three acutations. CONCLUSIONS--Multiple actuations of sodium cromoglycate into a spacer device before inhalation should be avoided, and inhalation from spacer devices should take place immediately after actuation to ensure maximum dose. Lining of a standard spacer device with an antistatic agent significantly increased output of sodium cromoglycate. This may have implications for improved therapeutic response and drug cost.

Previous reviews of pediatric asthma mortality have mostly been from hospital-based clinic populations and suggest that only those with severe asthma are most at risk. This report summarizes an investigation, by interviewer-administered questionnaire, into the circumstances surrounding the death in all patients aged 20 years or less who died from asthma in the State of Victoria over a 3 year period from May 1, 1986. During this period, 51 deaths due to asthma were reported. Thirty-three percent of these were judged to have a history of trivial or mild asthma, and 32% had no previous hospital admission for asthma. However, 36% were judged to have had severe asthma, 43% were taking regular inhaled beclomethasone or sodium cromoglycate, and 10% were taking regular oral steroids. Twenty-two percent had a previous admission to an ICU. Death occurred outside hospital in 40 (78%) subjects. In the final attack 63% had sudden onset and collapse within minutes, 12% were found dead, and 25% had acute progression of an established attack. The investigators assessed 39% of the deaths to have had potentially preventable elements. The preventable factors included: inadequate assessment or therapy of prior asthma (68%), poor compliance with therapy (53%), and delay in seeking help (47%). The majority of subjects in this survey could not be classified as "high risk." Therefore, clinicians should ensure that all young patients with asthma are aware of optimal maintenance management, can recognize deteriorating asthma, and follow a clear individualized crisis plan.

There is much interest in the use of holding chambers with an attached facemask to deliver aerosols from metered dose inhalers to infants. In order to study the influence of various design factors on the dose inhaled at different tidal volumes, a model was constructed in which a Starling ventilator was used to generate an inspiratory/expiratory cycle across a filter. Sodium cromoglycate was administered via a Nebuhaler and mask, Aerochamber and mask, and a coffee cup using tidal volumes of 25, 50, and 150 ml and the dose deposited upon the filter after six breaths was assayed using an ultraviolet spectrophotometric method. At the lowest tidal volume the high aerosol concentration in the smaller chamber enhanced drug delivery while at the highest tidal volume delivery was greatest from the larger chamber reflecting the larger dose available. Multiple breaths ensured that the dose inhaled per kilogram from each chamber was relatively large and also permitted significant drug delivery despite the introduction of a relatively large dead space between valve and filter. The dose delivered was increased by increasing the dose introduced into the chamber though not proportionately. These devices appear likely to deliver significant quantities of aerosol to infants, though drug delivery may be enhanced by the use of an appropriate valve.

It is well established that 2% Sodium Cromoglycate is an effective treatment for a number of allergic eye diseases. It has been shown to be non-toxic. It can be used longterm and in serious allergic problems it is a useful adjunctive therapy to steroids. The main problem with Sodium Cromoglycate is that the recommended dosage is a four times daily application and patient non-compliance is common. One of the main objectives of any therapy is to reduce the frequency of dosage and the current study has been designed to investigate the efficacy of a 4% solution of Sodium Cromoglycate, used twice daily, versus a 2% solution used four times daily in seasonal allergic conjunctivitis. A multicentre study, therefore, was carried out to assess the efficacy of both drugs and to assess any possibility of side effects. In addition, a unit dose was used, thus eliminating preservatives and it was used specifically in seasonal allergic conjunctivitis in the pollen season. This study showed that 4% Sodium Cromoglycate used twice daily was at least as affective as 2% Sodium Cromoglycate used four times daily.

The case of a 30-year-old wood-worker, with rhinitis and asthma induced by exposure to the dust of Pau Marfim wood (Balfourodendron riedelianum) is reported. Hypersensitivity to this wood was confirmed by positive skin test, bronchial challenge test and RAST. The bronchial response was inhibited by sodium cromoglycate. Unexposed persons did not exhibit reactivity to this wood in any of the tests. When electrophoretic analysis of proteins in polyacrylamide gel was applied to a crude (phosphate-buffered) extract, an homogeneous distribution of low MW material was detected, with no clearly defined bands, suggesting the presence of filamentous type proteins. To the best of the author's knowledge, this is the first reported case of occupational rhinitis and asthma due to Pau Marfim wood dust. A type I (IgE-mediated) hypersensitivity mechanism was demonstrated but the non-glomerular nature of the proteins precluded further identification of the antigens involved.

A randomized double blind cross over trial to compare nedocromil sodium and sodium cromoglycate with placebo in the prevention of exercise induced asthma was conducted. Twenty asthmatics received nedocromil sodium, sodium cromoglycate or placebo via metered dose inhalers on successive days 30 minutes before exercise in a randomized order. Nedocromil sodium and sodium cromoglycate gave sufficient protection (P less than 0.05) compared to placebo as assessed by the reduction in the maximum percentage fall in the forced expiratory volume in 1 second (FEV1). The protective effect of nedocromil sodium and sodium cromoglycate varied in individuals.

Wheezing in infants and children presents a difficult differential diagnosis contingent on the presenting symptoms and age of the child. A determination of the anatomy of the lower airway, combined with allergic, infectious, and noninfectious irritants, is requisite to a complete evaluation. The intervention strategies to decrease wheezing and bronchial hyperresponsiveness may include both nonpharmacologic and pharmacologic management. The nonpharmacologic management of asthma in children is contingent on aggressive treatment of dietary protein sensitivity and strict environmental control. The treatment of bronchial hyperresponsiveness with pharmacologic intervention in infants and children is relegated to the optimal use of sodium cromoglycate and inhaled corticosteroid.

Repeated bronchial histamine challenges before, during, and after the birch pollen season were performed in 22 allergic patients with bronchial hyperreactivity (BHR) treated for 6 wk with sodium cromoglycate (SCG), 20 mg, four times a day, or placebo in a double-blind, randomized group comparison. Clinical assessments of the asthmatic symptom score and peak expiratory flow revealed less symptoms and less use of bronchodilators in the SCG group. Responsiveness to histamine was significantly increased in the placebo group after 14 days with high pollen counts. After the season there was an immediate return to preseasonal value. There was no change in responsiveness in the SCG group, demonstrating significant protection against pollen-induced increase of BHR. The results support the hypothesis that inhibition of mediator release, which is demonstrated for SCG, leads to a reduction of the nonspecific BHR.