Randomised controlled trial of the efficacy of a metered dose inhaler with bottle spacer for bronchodilator treatment in acute lower airway obstruction.

BACKGROUND: Inhaled bronchodilator treatment given via a metered dose inhaler (MDI) and spacer is optimal for relief of bronchoconstriction. Conventional spacers are expensive or unavailable in developing countries, but there is little information on the efficacy of low-cost spacers in young children. OBJECTIVE: To compare the response to bronchodilator treatment given via a conventional or a low-cost bottle spacer METHODS: A randomised controlled trial of the efficacy of a conventional spacer compared with a bottle spacer for bronchodilator treatment in young children with acute lower airway obstruction. Bronchodilator treatment was given from an MDI via an Aerochamber or a bottle spacer. Clinical score and oximetry recording were carried out before and after 15 min of treatment. MDI-spacer treatment was repeated up to three times, depending on clinical response, after which nebulisation was used. The primary outcome was hospitalisation. RESULTS: 400 children, aged (median (25th-75th centile)) 12 (6-25) months, were enrolled. The number of children hospitalised (n = 60, 15%) was identical in the conventional and bottle spacer groups (n = 30, 15% in each). Secondary outcomes including change in clinical score (-2 (-3 to -1)), oxygen saturation (0 (-1 to 1)) and number of bronchodilator treatments (2 (1 to 3)) were similar in both groups. Oral corticosteroids, prescribed for 78 (19.5%) children, were given to a similar number in the conventional (37 (18.5%)) and bottle spacer groups (41 (20.5%)). CONCLUSION: A low-cost bottle spacer is as effective as a conventional spacer for bronchodilator treatment in young children with acute obstruction of the lower airways.

Socioeconomic status and prevalence of allergic rhinitis and atopic eczema symptoms in young adolescents.

Environmental factors are known to influence the development of allergic rhinitis and atopic eczema in genetically susceptible individuals. Socioeconomic status (SES) may be an important indicator of risk for these conditions. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase 1 written questionnaire was used to determine the prevalence and severity of allergic rhinoconjunctivitis and atopic eczema symptoms in 4947 pupils aged 13-14 years attending 30 schools in socioeconomically diverse areas of Cape Town. Home addresses were used to stratify participants into five SES bands. Relationships between symptom prevalence and severity, and SES, recent urbanization and upward socioeconomic mobility were examined. Logistic regression was used to generate odds ratios (OR) and 95% confidence intervals (CI) in order to assess overall trends by SES. The prevalences of self-reported allergic rhinitis symptoms and recurrent itchy rash in the past year were 33.2% and 11.9% respectively. Girls had a significantly higher prevalence of all symptoms than boys. The prevalence of allergic rhinitis symptoms increased from lowest to highest SES (overall OR for rhinitis symptoms in past year = 1.16, 95% CI 1.11-1.21). There was no significant trend in reported eczema symptoms by SES other than for the question, 'Have you ever had eczema' (OR = 0.88, 95% CI 0.83-0.93). Longer period of urbanization was weakly associated only with recurrent itchy skin rash (OR = 1.05, 95% CI 1.01-1.09). 'Socially mobile' pupils, i.e. those resident in the lowest SES areas but attending highest SES schools showed significantly higher prevalences of eczema and some rhinitis symptoms than pupils attending lowest SES schools. These findings may reflect differences in reporting related to language, culture and access to medical care rather than real differences in prevalence.

Acute and maintenance treatment of atopic dermatitis in children - two comparative studies with fluticasone propionate (0.05%) cream.

BACKGROUND: Two multicentre, randomised, parallel group, double-blind, comparative studies in children (2-14 yr) evaluated fluticasone propionate (FP) 0.05% cream for both acute and maintenance treatment of moderate to severe atopic dermatitis (AD). METHODS: One study compared FP with hydrocortisone (HC) 1% cream (FP 70, HC 67) and the other with hydrocortisone butyrate (HCB) 0.1% cream (FP 67, HCB 62). Treatments were applied twice daily, for 2-4 weeks until the AD was stabilised, and thereafter intermittently ('as required') for up to 12 weeks. RESULTS: The primary outcome measure, Total AD Score, recorded at the end of the acute and maintenance phases, was significantly lower (indicating improvements in disease severity) following treatment with FP compared with either HC or HCB (acute phase difference vs. HC, -2.39, 95%CI -3.47, -1.31; p<0.001 and vs. HCB, -1.25, 95%CI -2.46, -0.05; p=0.042) and (maintenance phase difference vs. HC, -1.88, 95%CI -3.20, -0.56; p=0.006 and vs. HCB, -1.39, 95%CI -2.72, -0.05; p=0.042). In both studies treatments were equally well tolerated with no visible signs of skin atrophy. CONCLUSION: In both the acute and longer term management of AD in children, FP demonstrated a high level of efficacy and maintenance of disease control with a tolerability similar to HC 1%, a lower potency corticosteroid.

Peak expiratory flow rate and symptom self-monitoring of asthma initiated from community pharmacies.

OBJECTIVE: To compare the use of patient-performed peak expiratory flow (PEFR) and symptom monitoring as asthma self-management tools initiated from community pharmacies. DESIGN AND SETTING: 110 patients over 6 years of age were recruited from five private-sector community pharmacies. Patients were identified from pharmacist recall as having 'asthma'. Information on the frequency of their asthma symptoms, medication use, level of physical activity, school or work attendance and lung function was obtained using a questionnaire to classify patients as either mild, moderate or severe. Each patient was alternately assigned to either the symptom or PEFR monitoring procedure in the order they were recruited. Patients performing symptom monitoring used a visual analogue scale to assess symptoms, whereas those in the PEFR monitoring group assessed symptoms and used a pocket-size peak flow meter to measure lung function. Both self-monitoring groups were required to adhere to an individualized management plan based on guideline recommendations and to record their monitored data in a diary card for 2 months. Data from the diary cards were reviewed, collated, transcribed and analysed using the Student t and Mann-Whitney tests. OUTCOME MEASURES: The average monthly frequency of appropriate patient responses determined from their adherence to the self-management plan was used to compare the usefulness of symptom and PEFR self-monitoring. In particular, appropriate use of medication and need for medical consultation was compared. RESULTS: 21 symptom and 40 PEFR-assigned patients completed 2 months' monitoring. The average monthly frequency of appropriate responses in patients using PEFR (0.76) was significantly higher than that of patients using symptom monitoring (0.53, P < 0.006). Patients applying symptom monitoring had a higher monthly frequency (0.39) of inappropriate medication use compared to the PEFR group (0.14). Furthermore, the patients' mean daily symptom scores (2.85) were significantly lower than that estimated by the researcher (4.12, P < 0.03). For all three asthma severity groups a higher monthly average of appropriate responses was observed in patients using PEFR monitoring compared to those who used symptom monitoring. CONCLUSION: PEFR self-monitoring proved to be a more useful asthma tool than symptom self-monitoring. Patients applying symptom monitoring tend to underestimate the severity of their condition and use medication inappropriately. Active involvement of community pharmacists in facilitating and reinforcing out-patient self-monitoring would help to optimize asthma management.

Guideline for the management of chronic asthma in children--2000 update. Allergy Society of South Africa Working Group.

OBJECTIVE: To increase awareness of asthma and diagnose asthma early in children. To make recommendations regarding management of chronic childhood asthma in a country with diverse cultural, socio-economic and educational characteristics. The guideline should be used by health professionals involved in the treatment of asthma at all levels of care. OPTIONS: Various management options were considered. Ideal treatment includes use of the new generation inhaled corticosteroids (fluticasone, budesonide), housedust mite intervention for asthma control using impermeable covers for pillows and mattresses, and if needed use of inhaled long-acting beta 2 agonists (LABAs) and leukotriene receptor antagonists (LRAs). Alternative therapeutic approaches for situations where resources are limited include simple housedust mite control measures (e.g. airing mattresses and bedding), avoidance of exposure to passive smoking, use of lower doses of beclomethasone than recommended by other guideline documents and/or sustained-release (SR) theophylline as preventer treatment and use of plastic bottles as cheap spacer devices. OUTCOMES: The main potential outcomes considered were: to reduce morbidity and mortality by correct diagnosis of asthma, to achieve the best quality of life for the child with asthma, to minimise side-effects from medication and to prevent development of permanently abnormal lung function. EVIDENCE: Current international guideline documents for diagnosis and management of childhood asthma were evaluated. Clinical studies before 1998 pertaining to the various aspects of management of childhood asthma were reviewed, including controlled studies on the use of inhaled corticosteroids in children with asthma, randomised controlled trials on the use of LRAs and two studies evaluating the efficacy of LABAs. Current data on the anti-inflammatory effects of SR theophylline were also reviewed as well as a randomised controlled trial on the benefits of SR theophylline as adjunct treatment in childhood asthma. The benefit of simple spacer devices, based on well-conducted local studies (published in an international peer-reviewed journal) was also considered. VALUES: The South African Childhood Asthma Working Group (SACAWG) committee members, appointed by the Allergy Society of South Africa (ALLSA), were selected to represent the interests of health professionals involved in the care of childhood asthma and to co-opt other colleagues with expertise relevant to the guideline. The committee was divided into six task groups headed by a chairperson--each task group had to review critically the previous SACAWG guideline (for deficiencies and obstacles to implementation), review current trends in asthma management (evidence-based where available) and submit proposals and recommendations to their respective chairperson. The chairperson then compiled a report for discussion by the SACAWG executive committee. The executive group convened a meeting to discuss the recommendations and obtain consensus. An editorial board was appointed to compile the final report. Cultural factors, patient preferences, cost, availability and education were considered important. BENEFITS, HARMS AND COSTS: Proper treatment should enable most children with asthma to lead normal or near-normal lives. The guideline could be implementable at all levels of care. The risk of systemic effects due to inhaled corticosteroids should be minimised in children with mild to moderate persistent asthma (risk of systemic effects is more likely at daily beclomethasone doses exceeding 400 micrograms or the equivalent dose of other inhaled corticosteroids). Promotion of simple environmental control measures and use of inhaled beclomethasone and/or SR theophylline should make treatment more widely available and more affordable and improve adherence to treatment. Alternative cheap plastic bottle spacer devices will increase availability and assist with overcoming the problem of incorrect inha

PBMCs from both atopic asthmatic and nonatopic children show a TH2 cytokine response to house dust mite allergen.

BACKGROUND: The hypothesis that in atopic diseases the T-helper response is skewed toward a T(H)2-type cytokine response was based on studies with mitogen stimulation, T-cell clones, or both. OBJECTIVE: Using primary cultures, we investigated (1) whether atopic asthmatic patients have a T(H)2 response and nonatopic subjects have a T(H)1 response to allergen and (2) whether atopic patients have a decreased ability to mount T(H)1 immune responses to mycobacterial antigens. METHODS: The responses of PBMCs to allergen (house dust mite [HDM]) or purified protein derivative of Mycobacterium tuberculosis (PPD) stimulation from 10 severely and 14 moderately asthmatic patients (all allergic to HDM) were compared with those of 17 nonatopic healthy black (Xhosa) children. RESULTS: HDM-stimulated proliferation, IL-5 release, and the IL-5/IFN-gamma ratio were significantly increased in subjects with atopic asthma, whereas IFN-gamma release was not significantly different. IL-4 levels were below the level of detection. PPD-stimulated proliferation, IL-5 release, IFN-gamma release, and the IL-5/IFN-gamma ratio were not significantly different among the groups. Each group had a significantly higher IL-5/IFN-gamma ratio in response to HDM than to PPD (a T(H)1 stimulus). CONCLUSION: Our study, which used primary cultures to investigate the hypothesis that nonatopic subjects have a T(H)1 response to allergens, indicates that HDM stimulates a T(H)2 cytokine response in both atopic and nonatopic subjects but that the response is enhanced in atopic patients. Our results with PPD suggest that normal and atopic asthmatic subjects can have a T(H)1 cytokine response to mycobacteria, but there is a subgroup of atopic subjects that have a T(H)2 response.

Lung deposition of aerosol--a comparison of different spacers.

AIMS: To investigate (1) aerosol lung deposition obtained from two small volume conventional spacers (Babyhaler and Aerochamber) and a home made spacer (modified 500 ml plastic cold drink bottle); (2) the effect of using a face mask or mouthpiece; and (3) the relation between age and pulmonary deposition. METHODS: Lung deposition of aerosolised technetium-99m DTPA inhaled via spacer was measured in 40 children aged 3-7 years with stable asthma. Each patient performed sequential randomly assigned inhalations using two spacers. Three studies were performed: Babyhaler compared to Aerochamber (with facemasks); Babyhaler with facemask compared to Babyhaler with mouthpiece; and Babyhaler with mouthpiece compared to a 500 ml bottle. RESULTS: Median lung aerosol deposition from a Babyhaler and Aerochamber with masks were similar (25% v 21%, p = 0.9). Aerosol lung deposition from a Babyhaler with mask compared to a Babyhaler with mouthpiece was equivalent (26% v 26%, p = 0.5). Lung deposition was higher from a 500 ml bottle compared to a Babyhaler in both young (25% v 12.5%, p = 0.005) and older children (42% v 22.5%, p = 0.003). A notable reduction in pulmonary deposition occurred at 50 months of age. CONCLUSION: A Babyhaler or Aerochamber produce equivalent lung deposition of aerosol. There is no difference in lung deposition when a mask or mouthpiece is used. A modified 500 ml plastic bottle produces greater pulmonary aerosol deposition than a conventional small volume spacer.

Treatment preferences of adolescent patients with asthma.

The study objective was to assess whether asthmatic adolescents who were regular users of inhaled corticosteroids preferred treatment with zafirlukast tablets or inhaled beclomethasone dipropionate (BDP), and, secondarily, to assess adolescents' inhaler technique and their opinions about treatment. An open-label, randomized, two-period, crossover study was conducted in 18 centres (primary care to specialist asthma centres) in South Africa, the UK, Finland and the Czech Republic. One hundred and thirty-two adolescents aged 12-17 years with asthma for at least 1 year and FEV1 > or = 75% of predicted, treated with short-acting bronchodilators and inhaled corticosteroids, entered the study. Patients received oral zafirlukast tablets (Accolate) 20 mg b.i.d. or inhaled BDP 100 or 200 microg b.i.d., provided by a standard pressurized metered-dose inhaler, for 4 weeks each. One questionnaire was used to determine preference (the primary outcome measure) and a second questionnaire was used to determine patients' likes and dislikes of treatment. Investigators also scored inhaler technique. Of 113 adolescents, 79 (70%) preferred zafirlukast compared with 31 (27%) who preferred the BDP inhaler (p < 0.001); three had no preference. Only 35 (29%) of 122 adolescents could use their inhaler correctly at study entry. Seventy-six patients (65%) rated zafirlukast tablets as 'very easy' to use, compared with 35 (30%) for the BDP inhaler. Both treatments were well-tolerated. This study shows that asthmatic adolescents prefer zafirlukast tablets by a ratio of 2.6:1 over inhaled BDP, and these results may have implications for improving adolescent patient compliance with asthma therapy.

Urbanization and childhood asthma: an African perspective.

The increasing prevalence of childhood asthma in the developed world is a cause for concern. Much research is currently being conducted in an attempt to identify possible reasons for this occurrence. A so-called Western lifestyle has been the factor most commonly cited to explain this worrying increase in asthma prevalence. In essence, this implies a way of life where children are exposed from early infancy to a wide range of foods, infections, indoor and outdoor allergens, and irritants and to the effects of motor vehicle pollution. Until fairly recently, children in many African countries lived mainly in rural areas and were not exposed to the effects of a Western lifestyle. Early studies in a limited number of African countries showed a very low rural prevalence of childhood asthma, especially where children lived according to a traditional lifestyle. These same studies showed that asthma was not uncommon in urbanized African children. There has been an increasing tendency over the past 20 years for those in rural communities to move to the large urban centers. More recent childhood asthma prevalence studies, especially those from Kenya and Ghana, have confirmed the urban-rural differences but have shown a much narrower gap. In part this may be the result of exposure of rural children to agricultural pesticides and irritants as well as of an increasing tendency to adopt a more Westernized lifestyle such as the use of beds with mattresses, pillows, and blankets. These circumstances on the African continent provide a natural laboratory in the quest for factors that influence the development of asthma in susceptible children. Once more fully elucidated, it is possible that much valuable information will be available to combat the relentless increase in childhood asthma both here as well as in the developed world.

Home-made spacers for bronchodilator therapy in children with acute asthma: a randomised trial.

BACKGROUND: A metered-dose inhaler (MDI) with spacer is the best way to deliver bronchodilator therapy for treatment of acute asthma. In developing countries, commercially produced spacers are generally unavailable or too costly. We tested the efficacy of home-made spacers (500 mL plastic bottle, polystyrene cup) compared with a conventional spacer for delivery of a beta2 agonist via MDI for children with acute asthma. METHODS: We studied children aged 5 to 13 years with acute asthma, stratified into those with mild airways obstruction (peak expiratory flow [PEF] 60-79% of predicted value) or moderate to severe airways obstruction (PEF 20-59% of predicted value). A beta2 agonist (fenoterol hydrobromide) was given via MDI and one of four randomly assigned spacers (conventional spacer, sealed 500 mL plastic bottle, unsealed 500 mL bottle, 200 mL polystyrene cup). Clinical score, pulmonary function tests, and oximetry were recorded at baseline and 15 min after treatment. If a second bronchodilator treatment was needed, nebulised fenoterol was given and the assessment repeated 15 min later. Primary outcome measures were changes in clinical score and pulmonary function, and need for and response to nebulisation. FINDINGS: 88 children were eligible for study. In 44 children with moderate to severe airways obstruction, a cup gave significantly less bronchodilation (median increase in: forced expiratory volume in 1 s [FEV1] 0%; PEF 12%) compared with the conventional spacer (37%; 59%), sealed bottle (33%; 36%), or unsealed bottle (18%; 21%, p<0.05 for difference between groups). Nebulisation was required by ten of 11 who had used a cup, nine of 11 who had used an unsealed bottle, eight of 11 who had used a sealed bottle, and only four of 11 who had used a conventional spacer. After nebulisation, improvement in FEV1 (15.5%) and PEF (26%) was more marked in children who had used a cup than in those who had used a conventional spacer (5.5% FEV1; 4% PEF), sealed bottle (3%; 0%), or unsealed bottle (7%; 9%). For 44 children with mild airways obstruction, response to bronchodilator was similar for all spacers and need for nebulisation was not associated with use of a particular spacer. INTERPRETATION: A conventional spacer and sealed 500 mL plastic bottle produced similar bronchodilation, an unsealed bottle gave intermediate improvement in lung function, and a polystyrene cup was least effective as a spacer for children with moderate to severe airways obstruction. Use of bottle spacers should be incorporated into guidelines for asthma management in developing countries.

An assessment of asthmatic patients at four Western Cape community pharmacies.

OBJECTIVES: To identify the profile of asthmatic patients visiting community pharmacies and to assess the appropriateness of their current asthma therapy. DESIGN: Patients were identified as either chronic, newly diagnosed or undiagnosed. Asthma status was assessed from their current symptom and medication profiles and from performance in an airways responsiveness test. Reversibility of > 15% was suggestive of probable airflow obstruction and such patients were referred to a medical practitioner. SETTING: Four community pharmacies located in different socio-economic areas, viz. Khayelitsha, Wynberg, Mitchell's Plain and Vrijzee, were selected. SUBJECTS: Participants over the age of 6 years, who suffered from recurrent cough, wheeze, chest tightness and/or breathlessness and used over-the-counter (OTC) and/or asthma medications, completed a questionnaire and participated in the airways responsiveness test. OUTCOME MEASURES: Effective control of asthma based on minimal symptoms, appropriate use of bronchodilator and anti-inflammatory therapies and absence of airflow obstruction. RESULTS: Of the 220 participants, 120 were identified as chronic, 7 as newly diagnosed and 93 as undiagnosed. Chronic asthmatics suffered daily symptoms and used inadequate prophylactic anti-inflammatory therapy. Many undiagnosed asthmatics were unaware of their symptoms and took OTC medication indiscriminately. Based on peak expiratory flow rate measurements, > 50% of the screened patients displayed a reversibility of > 15%. CONCLUSIONS: Chronic and many undiagnosed asthmatic patients frequent community pharmacies for their medication. Such patients suffer recurrent asthma symptoms and use medication inappropriately, which results in suboptimal lung function. Pharmacists should play a more participatory role in the detection and management of asthma in the community.

The efficacy of alternative spacer devices for delivery of aerosol therapy to children with asthma.

Spacer devices are important aids for use with metered dose inhalers in children with asthma. However, expense and unavailability of commercially produced spacers in developing countries have limited their use. Home-made spacers in the form of cups or bottles are widely used despite a lack of data confirming their efficacy. We investigated the relative efficacy of three spacers (a commercially available spacer, a modified 500-ml cold drink bottle and a polystyrene cup) for delivery of aerosolized drugs to asthmatic children older than 5 years. We also investigated the effect of leaks in the delivery system by comparing delivery via a sealed and an unsealed cold drink bottle. Lung deposition of aerosolized Tc-99m DTPA inhaled via spacer was measured in 30 patients. The median aerosol deposition in the lungs was significantly greater for the conventional spacer than for the cup (31.5% vs 9.5%; Z = -2.8, p = 0.005). Median aerosol deposition for the conventional spacer and sealed bottle were equivalent (40.5% vs 44%). Aerosol deposition from the sealed and unsealed bottle was significantly different (43.5% vs 24%; Z = -2.54, p = 0.01); however, the unsealed bottle was more efficient than the cup. We conclude that a modified 500-ml cold drink bottle is an efficient spacer. Leaks in this system are a major factor affecting the amount of drug deposited. The modified polystyrene cup is not an efficient spacer, delivering between a third and a fifth of the dose that other spacers were capable of delivering.