Clinical standards for the diagnosis and management of asthma in low- and middle-income countries.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2.

BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. RESULTS: Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. CONCLUSIONS: Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.

How well do questionnaires perform compared with physical examination in detecting flexural eczema? Findings from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two.

BACKGROUND: Questionnaires are widely used in epidemiological studies to measure eczema symptom prevalence, but there are concerns regarding their accuracy if used as a diagnostic tool. OBJECTIVES: To compare the performance of a validated eczema symptom questionnaire and a standardized skin examination protocol employed in the second phase of the International Study of Asthma and Allergies in Childhood (ISAAC). METHODS: A total of 30,358 schoolchildren aged 8-12 years from 18 countries were examined for flexural eczema. Parents also completed an eczema symptom questionnaire. We compared prevalence estimates at the population level based on the questionnaire vs. physical examination. We also compared the skin examination and the ISAAC questionnaire in making a diagnosis of flexural eczema. RESULTS: The point prevalences for flexural eczema at centre level based on a single examination were lower than the questionnaire-based 12-month period prevalences (mean centre prevalence 3.9% vs. 9.4%). Correlation between prevalences of both outcome measures was high (r = 0.77, P < 0.001). At the individual level, questionnaire-derived symptoms of 'persistent flexural eczema in the past 12 months' missed < 10% of cases of flexural eczema detected on physical examination. However, between 33% and 100% of questionnaire-based symptoms of 'persistent flexural eczema in the past 12 months' were not confirmed on examination. CONCLUSIONS: ISAAC questionnaire-derived symptom prevalences are sufficiently precise for comparisons between populations. Where diagnostic precision at the individual level is important, questionnaires should be validated and potentially modified in those populations beforehand, or a standardized skin examination protocol should be used.

Asthma and allergic symptoms in relation to house dust endotoxin: Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II).

BACKGROUND: Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent. OBJECTIVES: To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries. METHODS: Data were collected within the International Study on Asthma and Allergies in Childhood Phase Two, a multi-centre cross-sectional study of 840 children aged 9-12 years from six centres in the five countries of Albania, Italy, New Zealand, Sweden and the United Kingdom. Living room floor dust was collected and analysed for endotoxin. Health end-points and demographics were assessed by standardized questionnaires. Atopy was assessed by measurements of allergen-specific IgE against a panel of inhalant allergens. Associations between house dust endotoxin and health outcomes were analysed by logistic regression. Odds ratios (ORs) were presented for an overall interquartile range increase in exposure. RESULTS: Many associations between house dust endotoxin in living room floor dust and health outcomes varied between countries. Combined across countries, endotoxin levels were inversely associated with asthma ever [adjusted OR (95% confidence interval (CI)) 0.53 (0.29-0.96) for endotoxin levels per m(2) of living room floor] and current wheeze [adjusted OR (95% CI) 0.77 (0.64-0.93) for endotoxin levels per gram of living room floor dust]. There were inverse associations between endotoxin concentrations and atopy, which were statistically significant in unadjusted analyses, but not after adjustment for gender, parental allergies, cat and house dust mite allergens. No associations were found with dust quantity and between endotoxin exposure and hayfever. CONCLUSION: These findings suggest an inverse association between endotoxin levels in living room floor dust and asthma in children.

A multinational study of treatment failures in asthma management.

SETTING: Emergency rooms. OBJECTIVE: To assess quality of care and its determinants for asthma patients before emergency room treatment. DESIGN: Consecutive patients with acute severe asthma attending emergency rooms were questioned about the severity of their disease and treatment in the previous 4 weeks. Prescriptions of inhaled corticosteroids were recorded. Other outcomes included self-reported adherence to treatment and loss of work. RESULTS: Thirteen centres in 11 countries recruited 1156 patients. Only 36% of patients with persistent asthma had been prescribed an adequate dose of inhaled corticosteroids. This percentage improved in those receiving regular care from the same doctor (OR 2.86, 95%CI 1.38-5.96), and was at least as good for the 10% of patients receiving 'private' health care (OR 3.08, 95%CI 1.69-5.62). Forty-four per cent of patients had health insurance covering some asthma medications. These patients were more likely to be receiving adequate inhaled corticosteroids (OR 1.74, 95%CI 1.17-2.58), and reported better adherence than those without insurance (OR 3.00, 95%CI 1.64-5.50). Of those on adequate inhaled corticosteroids, 18% had lost work in each of the 4 previous weeks compared with 59% among those more than one treatment step below the recommended dose. CONCLUSIONS: Access to adequate treatment is critical for better management of asthma.

Factors associated with frequent emergency room attendance by asthma patients in Palestine.

SETTING: The emergency room (ER) of Alia Governmental Hospital in Hebron city, in the southern part of the West Bank. OBJECTIVE: To investigate the role of asthma severity, health services utilisation and medication use in frequent ER attendance for asthmatics in Palestine. DESIGN: A cross-sectional study using a previously developed questionnaire. RESULTS: Of 121 asthma patients, 73.5% were frequent ER attendees during the previous year, with a mean 6.7 visits (standard error 0.75). Moderate/severe asthma and hospital admissions in the previous year due to asthma were the strongest predictors for frequent attendees (adjusted OR [aOR] 6.92, 95%CI 2.44-19.62 and 11.16, 95%CI 4.37-28, respectively). Frequent attendees reported more difficulties in using asthma inhalers compared to one-time ER attendees (aOR 2.49, 95%CI 1.04-5.99). Inhaled short-acting beta(2)-agonists were reported to be used regularly, on most days, by frequent attendees (>or=1 canister/month) compared to one-time attendees (aOR 4.4, 95%CI 1.28-15 and 4.05, 95%CI 1.33-12, respectively). CONCLUSIONS: Lack of proper use of inhalers and an over-reliance on reliever therapy contributes to asthma morbidity in Palestine. We recommend an intervention programme at the professional and patient levels.

Re-emergence of lead poisoning from contaminated flour in a West Bank Palestinian village.

Although contaminated flour was first described as an important source of endemic lead poisoning in the Middle East almost 20 years ago, the use of lead in community flour mills has not been eliminated and continues to represent a significant environmental risk. The authors describe an outbreak of lead poisoning in a West Bank Palestinian family and draw attention to this unusual but important source of lead exposure. All 13 members of the family (two children and 11 adults), were found to have lead poisoning following hospitalization for "gastroenteritis," headache, joint pain, weight loss, and vision difficulties. Seven females had low hemoglobin levels. Blood lead concentrations ranged from 42 to 84 microg/dL. Household flour samples obtained from a stone mill, previously closed because of lead contamination, contained 2,000 ppm lead. Flour from traditional stone mills reinforced with lead joints remains a potential source for lead poisoning.

Familial and environmental determinants for wheezing and asthma in a case-control study of school children in Palestine.

BACKGROUND: Our prevalence study on Palestinian school children aged 6-12 years showed lower rates for asthma and asthma symptoms than economically developed and industrialized countries. Reasons for such differences are largely unknown, and could possibly be related to different environmental and lifestyle factors. OBJECTIVE: To investigate familial, early life exposures and indoor environmental determinants for asthma in children in Palestine. METHODS: From the population of our previous study, a group of 273 children with wheeze in the past 12 months (of whom 99 children had physician-diagnosed asthma) were matched with an equal number of non-wheezing controls. This case-control study involved a parental questionnaire; skin prick testing (SPT) with mixed house dust mites, cat and dog dander, mixed grass, mixed trees pollen, Alternaria tenuis, olive tree and cockroach extracts; and serum for total and specific IgE for the same eight allergens. RESULTS: Paternal asthma and maternal hayfever significantly tripled the risk for their children to have wheezing. Previous diagnoses of bronchial allergy, bronchitis, pneumonia, or whooping cough, and positive SPT for house dust mites and cockroaches were significantly more likely among wheezing and asthmatic children than controls. Specific IgE levels for house dust mites and cat allergens showed significantly higher risk for reported wheezing. After adjustment for several environmental and sociodemographic factors using multivariate logistic regression analysis, paternal asthma, maternal hayfever, damp houses, cat and cockroach SPT positivity proved to be strong predictors for wheezing symptoms. CONCLUSION: Our study confirmed that familial 'atopic' diseases are significant predictors of childhood asthma in Palestinian children. Moreover, indoor environment such as presence of cats and domestic moulds also appear to play a role. Our findings are consistent with studies in Canada, New Zealand, Estonia and Sweden, and show promise to explore further gene-environment interaction in the genesis of asthma.

Asthma prevalence in children living in villages, cities and refugee camps in Palestine.

Previous studies have suggested that asthma prevalence is generally lower in the Middle East than in more developed countries. The aim of this study was to investigate the prevalence and severity of asthma and asthma symptoms in schoolchildren in the Ramallah District in Palestine. In the autumn of 2000, 3,382 schoolchildren aged 6-12 yrs were surveyed in 12 schools, using the International Study for Asthma and Allergies in Childhood (ISAAC)-phase III, parents-administered translated questionnaire. The crude prevalence rates for "wheezing-ever", "wheezing in the previous 12 months", and "physician-diagnosed asthma" were 17.1, 8.8 and 9.4% respectively, with urban areas having higher prevalence rates than rural areas. Within urban areas, refugee camps had higher prevalence rates than cities. Yet, within the rural areas, the 12-month prevalence was lower in the deprived villages than other residences. Place of residence remained significant for asthma and asthma symptoms, after adjusting for sex, age, and place of birth. To conclude, children from refugee camps appear to be at higher risk of asthma than children from neighbouring villages or cities. The prevalence of asthma and asthma symptoms in Palestine appears to be close to that of Jordan, but it is much lower than Israel, and lower than some other countries in the region, such as Kuwait and Saudi Arabia, and more developed countries. This initial study is a baseline for a study on lifestyle and environmental determinants for asthma among Palestinian children.

Concentrations of domestic mite and pet allergens and endotoxin in Palestine.

BACKGROUND: A few studies have compared indoor allergens and endotoxin levels between urban and rural settings as important determinants for asthma and atopy in children. However, no study was done in the Middle East or investigated refugee camps. METHODS: As part of a nested case-control study in Ramallah in 2001, we measured house dust mite and pet allergens, as well as endotoxin in dust collected from 110 children's mattresses and living room floors. RESULTS: Geometric mean (GM) concentrations of Dermatophagoides pteronyssinus (Der p1) antigen were 4.48 microg/g in mattress dust and 1.23 microg/g floor dust. The highest Der p1 levels were seen in refugee camps. Concentrations of Dermatophagoides farinae antigen (Der f1) were much lower (<0.08 microg/g dust). Concentrations of cat allergen (Fel d1) were highest in villages, and those of dog allergen (Can f1) were highest in mattresses from cities and in floor dust from refugee camps. GM of endotoxin levels were 25.7 EU/mg in mattress dust and 49 EU/mg dust in floor dust. CONCLUSIONS: Concentrations of Der p1 were high compared to Western European countries, but were lower compared to UK and Australia. Levels of pet allergens were lower than in Western Europe. Endotoxin levels were higher compared to developed countries. Indoor environmental factors such as dampness seemed to be important determinants for allergen and endotoxin, but living habits such as lack of mattress cover appeared unimportant.