Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood.

BACKGROUND: Associations of larger families with lower prevalences of hay fever, eczema and objective markers of allergic sensitization have been found fairly consistently in affluent countries, but little is known about these relationships in less affluent countries. METHODS: Questionnaire data for 210,200 children aged 6-7 years from 31 countries, and 337,226 children aged 13-14 years from 52 countries, were collected by Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations of disease symptoms and labels of asthma, rhinoconjunctivitis and eczema were analysed by numbers of total, older and younger siblings, using mixed (multi-level) logistic regression models to adjust for individual covariates and at the centre level for region, language and national affluence. RESULTS: In both age groups, inverse trends (P < 0.0001) were observed for reported 'hay fever ever' and 'eczema ever' with increasing numbers of total siblings, and more specifically older siblings. These inverse associations were significantly (P < 0.005) stronger in more affluent countries. In contrast, symptoms of severe asthma and severe eczema were positively associated (P < 0.0001) with total sibship size in both age groups. These associations with disease severity were largely independent of position within the sibship and national GNI per capita. CONCLUSIONS: These global findings on sibship size and childhood asthma, rhinoconjunctivitis and eczema suggest at least two distinct trends. Inverse associations with older siblings (observations which prompted the 'hygiene hypothesis' for allergic disease) are mainly a phenomenon of more affluent countries, whereas greater severity of symptoms in larger families is globally more widespread.

Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs.

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

International consensus on (ICON) pediatric asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

Exposure to combustion of solid fuel and tuberculosis: a matched case-control study.

The present study was conducted in Benin to ascertain the association between exposure to combustion of solid fuel (coal and biomass) and tuberculosis. Cases were consecutive, sputum smear-positive tuberculosis patients never previously treated for tuberculosis for as long as 1 month. Two controls were selected from the neighbourhood of each case, matched by age and sex by a predefined procedure. A total of 200 new smear-positive cases and 400 neighbourhood controls were enrolled. In univariate analysis, using solid fuel for cooking (OR 1.7, 95% CI 1.1-2.8), ever smoking (OR 5.5, 95% CI 3.1-9.8), male sex (OR 10.5, 95% CI 1.6-71.1), daily use of alcoholic beverages (OR 2.3, 95% CI 1.2-4.2) and having a family member with tuberculosis in the previous 5 yrs (OR 30.5, 95% CI 10.8-85.8) were all significantly associated with tuberculosis cases. When all significant variables were entered into a multivariate conditional logistic regression model, the association between using solid fuel for cooking and tuberculosis cases was no longer statistically significant (adjusted OR 1.4, 95% CI 0.7-2.7). In conclusion, the association between exposure to combustion of solid fuel and tuberculosis was relatively weak and not statistically significant.

Global analysis of breast feeding and risk of symptoms of asthma, rhinoconjunctivitis and eczema in 6-7 year old children: ISAAC Phase Three.

BACKGROUND: In Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC), we investigated the relationship between breast feeding in infancy and symptoms of asthma, rhinoconjunctivitis and eczema in 6-7 year old children. METHODS: Parents or guardians of 6-7 year old children completed written questionnaires on current symptoms of asthma, rhinoconjunctivitis and eczema, and on a range of possible asthma risk factors including a history of breast feeding ever. Prevalence odds ratios were estimated using logistic regression, adjusted for gender, region of the world, language, per capita gross national income, and other risk factors. RESULTS: In all 206,453 children from 72 centres in 31 countries participated in the study. Reported breast feeding ever was not associated with current wheeze, with an odds ratio (adjusted for gender, region of the world, language, per capita gross national income, and factors encountered in infancy) of 0.99 (95% CI 0.92-1.05), current rhinoconjunctivitis (OR 1.00, 95% CI 0.93-1.08), current eczema (OR 1.05, 95% CI 0.97-1.12), or symptoms of severe asthma (OR 0.95, 95% CI 0.87-1.05). Breast feeding was however associated with a reduced risk of severe rhinoconjunctivitis (OR 0.74, 95% CI 0.59-0.94) and severe eczema (OR 0.79, 95% CI 0.66-0.95). CONCLUSIONS: There was no consistent association between breast feeding use in the first year of life and either a history or current symptoms of wheezing, rhinoconjunctivitis or eczema in 6-7 year old children, but possibly an effect on severe symptoms of the latter two conditions.

Prioritised research agenda for prevention and control of chronic respiratory diseases.

The 2008-2013 World Health Organization (WHO) action plan on noncommunicable diseases (NCDs) includes chronic respiratory diseases as one of its four priorities. Major chronic respiratory diseases (CRDs) include asthma and rhinitis, chronic obstructive pulmonary disease, occupational lung diseases, sleep-disordered breathing, pulmonary hypertension, bronchiectiasis and pulmonary interstitial diseases. A billion people suffer from chronic respiratory diseases, the majority being in developing countries. CRDs have major adverse effects on the life and disability of patients. Effective intervention plans can prevent and control CRDs, thus reducing morbidity and mortality. A prioritised research agenda should encapsulate all of these considerations in the frame of the global fight against NCDs. This requires both CRD-targeted interventions and transverse NCD programmes which include CRDs, with emphasis on health promotion and disease prevention.

Global map of the prevalence of symptoms of rhinoconjunctivitis in children: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three.

BACKGROUND: Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global patterns of prevalence and severity of symptoms of rhinoconjunctivitis in children in 1993-1997. METHODS: International Study of Asthma and Allergies in Childhood Phase Three was a cross-sectional survey performed 5-10 years after Phase One using the same methodology. Phase Three covered all of the major regions of the world and involved 1 059 053 children of 2 age groups from 236 centres in 98 countries. RESULTS: The average overall prevalence of current rhinoconjunctivitis symptoms was 14.6% for the 13- to 14-year old children (range 1.0-45%). Variation in the prevalence of severe rhinoconjunctivitis symptoms was observed between centres (range 0.0-5.1%) and regions (range 0.4% in western Europe to 2.3% in Africa), with the highest prevalence being observed mainly in the centres from middle and low income countries, particularly in Africa and Latin America. Co-morbidity with asthma and eczema varied from 1.6% in the Indian sub-continent to 4.7% in North America. For 6- to 7-year old children, the average prevalence of rhinoconjunctivitis symptoms was 8.5%, and large variations in symptom prevalence were also observed between regions, countries and centres. DISCUSSION: Wide global variations exist in the prevalence of current rhinoconjunctivitis symptoms, being higher in high vs low income countries, but the prevalence of severe symptoms was greater in less affluent countries. Co-morbidity with asthma is high particularly in Africa, North America and Oceania. This global map of symptom prevalence is of clinical importance for health professionals.

Isoniazid preventive therapy for people living with HIV: public health challenges and implementation issues.

Isoniazid preventive therapy (IPT) is recognised as an important component of collaborative tuberculosis (TB) and human immunodeficiency virus (HIV) activities to reduce the burden of TB in people living with HIV (PLHIV). However, there has been little in the way of IPT implementation at country level. This failure has resulted in a recent call to arms under the banner title of the 'Three I's' (infection control to prevent nosocomial transmission of TB in health care settings, intensified TB case finding and IPT). In this paper, we review the background of IPT. We then discuss the important challenges of IPT in PLHIV, namely responsibility and accountability for the implementation, identification of latent TB infection, exclusion of active TB and prevention of isoniazid resistance, length of treatment and duration of protective efficacy. We also highlight several research questions that currently remain unanswered. We finally offer practical suggestions about how to scale up IPT in the field, including the need to integrate IPT into a package of care for PLHIV, the setting up of operational projects with the philosophy of 'learning while doing', the development of flow charts for eligibility for IPT, the development and implementation of care prior to antiretroviral treatment, and finally issues around procurement, distribution, monitoring and evaluation. We support the implementation of IPT, but only if it is done in a safe and structured way. There is a definite risk that 'sloppy' IPT will be inefficient and, worse, could lead to the development of multidrug-resistant TB, and this must be avoided at all costs.

Outcome definitions for multidrug-resistant tuberculosis treated with shorter treatment regimens.

To assess whether the revised 2013 World Health Organization (WHO) definitions for multidrug-resistant tuberculosis (MDR-TB) treatment outcomes apply to shorter treatment regimens in low- and middle-income countries and to propose modified criteria. Criteria for 'failure' and 'cure' outcomes were assessed using data on 1006 patients enrolled in an observational study on the standardised 9-11 month shorter MDR-TB regimen in Africa. Absence of conversion in the intensive phase, a WHO criteria for failure, was the worst performing criterion; reversion had low sensitivity and other criteria provided limited added value. Based on our study results, we propose new definitions for 'treatment failure' as treatment termination or the permanent discontinuation of 2 anti-tuberculosis drugs due to 1) positive culture after 6 months of treatment (except for one isolated positive culture) or 2) at least two consecutive grade 2+ positive sputum smears after 6 months of treatment if culture is not available; and for 'cure' as treatment completion without proof of failure AND two consecutive negative cultures taken 30 days apart, one of which should be after 6 months of treatment. The proposed new definitions are applicable to shorter regimens in low- and middle-income countries, and should also work for the newly recommended longer regimens. .

Challenges and opportunities to prevent tuberculosis in people living with HIV in low-income countries.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

COPD management. Part II. Relevance for resource-poor settings.

Chronic obstructive pulmonary disease (COPD) is a preventable disease and its prevalence, already high in middle- and low-income countries, is expected to increase in the next decade. Global initiatives, including those against the tobacco industry to stop the tobacco epidemic, are fundamental to reduce the expected morbidity and mortality due to COPD. National health expenditure is generally low in the majority of developing countries, where financial and human resources are lacking and are primarily devoted to infectious diseases. To face these challenges, it is essential to strengthen political commitment to prioritising resource allocation to discourage tobacco use and to implement cost-effective standardised case management. The management of COPD could be more affordable in resource-poor countries if the cheaper spirometers currently on the market were made available and by the use of generic essential drugs. The organisation within clinical services of integrated management of respiratory diseases, including tuberculosis, as recommended by the World Health Organization in its Practical Approach to Lung Health, and by the International Union Against Tuberculosis and Lung Disease in its Comprehensive Approach to Lung Health, would help to improve health systems and skills of health personnel, reduce health costs and improve the quality of care of patients with chronic respiratory diseases.

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.

Treating the patient with asthma.

Treatment of patients with asthma, although straight-forward, is a challenge. The treatment is prolonged, often for life, and must be taken regularly. For low-income countries, the treatment must be efficient and feasible. Two drugs are indicated: one to reduce the inflammation and one to relieve the airflow obstruction. The treatment and its goals need to be explained to the patient with asthma and to family members, as the success of treatment is dependent on their cooperation. The medications that reduce inflammation are corticosteroids. Inhaled beclomethasone 250 microg per puff is indicated for every patient who has persistent asthma. The medication recommended for relief of airflow obstruction is inhaled salbutamol/100 microg per puff. A four-step approach to treatment is indicated, starting with the dose of medication indicated by the degree of severity of the asthma, and periodically adjusted. When the condition improves and remains stable for at least 3 months, the dose of medication may be reduced to fit the grade of severity assessed at that time. In the event the condition worsens, the treatment is increased stepwise. This approach to treatment has every promise to improve the life and health of patients with asthma.

How to diagnose asthma and determine the degree of severity of the disease.

Asthma care begins with establishing the diagnosis and determining the severity of the disease. The key elements are the history of the disease and the measurements of peak expiratory flow (PEF). The characteristic of asthma is variability. A history of chest symptoms that are variable is typical of asthma. Demonstrating a variation of PEF > or = 20% establishes a definite diagnosis of asthma. This variability is demonstrated either, in patients with normal PEF when they are well, by measuring a decrease in PEF during a period when the patient has symptoms of asthma or, in patients with PEF < normal, an improvement after inhalation of salbutamol or after a period of treatment. Classifying the severity of asthma is also based on history and lung function measurement. Patients with PEF <60% or continuous symptoms are classified as severe persistent. Those with PEF 60-79% or daily symptoms (not continuous) are classified as moderate persistent. Those with symptoms more than once per week but less than daily and PEF > or = 80% are classified as mild persistent. Those with symptoms less than once per week and PEF > or = 80% are classified as intermittent. Establishing the diagnosis and assessing the severity are crucial to high quality care.

Management of asthma: the essentials of good clinical practice.

Asthma is a condition that affects all countries worldwide. It is a chronic, disabling condition that diminishes the quality of life and the economic prosperity of those who live with it. The majority of persons living with asthma are from developing countries. Asthma management necessitates long-term treatment that is expensive, making it less accessible to poor people. The cost of medications is the key factor preventing people living with asthma from having access to care that has the potential to relieve their suffering, improve their quality of life and enhance their economic status. Asthma is a disease caused by environmental exposures. Genetic factors predispose certain people to developing asthma once they are exposed to the causative agents, and certain factors can trigger symptomatic episodes of asthma in those who have already developed the disease. Certain clinical characteristics differentiate asthma from other chronic lung conditions. The most important of these is that the symptoms and functional disability caused by asthma vary from one occasion to another. In those with less severe asthma, they may be present on some occasions and not others; in those with more severe asthma, their degree of severity varies from one time to another.

Dissemination and implementation of guidelines for the treatment of asthma.

Asthma remains a serious global health problem that affects people of all ages. Many asthma management guidelines, both national and international, are available, but they are seldom implemented. The implementation of guidelines remains a challenge worldwide, as barriers exist at several levels. These barriers are generic, such as poverty, inadequate resources and poor infrastructure, or specific, such as organisational, health care provider and patient factors. The barriers are, however, potentially correctable, and the goal of guideline implementation is to translate evidence-based asthma management recommendations into real-life practice to improve patient health. This state of the art article reviews the challenges and current status of and strategies for asthma dissemination and implementation globally, and highlights the specific strategies for such improvement in developing countries.

Ensuring the quality of asthma case management.

An evaluation based on recording the number of patients and evaluating their treatment outcomes provides the information necessary to plan the provision of care, determine the analysis of the situation and revise practice if the results are not satisfactory. The standardised tools proposed for this evaluation are: a district register for new persistent asthma patients, quarterly reports of case finding and an annual report of cohort patient follow-up. The main indicators of quality of care based on register information given by the cohort analysis are the percentage of defaulters and the percentage of patients whose asthma is controlled or well controlled after 1 year of follow-up. The services involved in asthma management should be adapted to the local situation in each country. In particular, the health service structure and national guidelines must be respected, and services involved in asthma management should be implemented in stages. Operational research within the services is essential to ensure that the services provided are appropriate. This type of research involves the health personnel responsible for patient management, provides them with new knowledge and helps them to resolve problems they are confronted with on a regular basis. It also inspires critical thinking, which is crucial to both research and practice.

Managing acute attacks of asthma.

Asthma patients may present to the health services with acute attacks. Assessment and management must be undertaken rapidly. The patient must be given oxygen and then assessed by measuring the peak expiratory flow rate (PEF) before and after salbutamol, and by questioning and examining the patient. Using the information gathered, the caregiver is able to assess the grade of severity of the attack and provide appropriate care according to the severity. Patients judged as having imminent respiratory arrest must be immediately transferred to intensive care after starting treatment. Patients judged as having a severe attack are given oxygen, salbutamol, systemic corticosteroids and are closely monitored. They must remain for a minimum of 6 h prior to being either hospitalised or sent home. Patients with moderate attacks are given salbutamol and oral prednisone and are kept under observation for a minimum of 2 h. If stable at least 1 h after last dose of salbutamol, they may be sent home. Patients with mild attacks are given inhaled salbutamol and kept under observation for a minimum of 2 h. If stable at least 1 h after the last dose of salbutamol, they may be sent home. Careful and correct follow-up after an attack is crucial.