Global burden of pediatric asthma and rhinitis - what we have recently learned from epidemiology.

PURPOSE OF REVIEW: To analyze and present recently published information on the factors that modify the burden of asthma and rhinitis in pediatric ages, such as ecological determinants; highlighting access and adherence to medications, exposure to pollutants and climate change. In addition to individual determinants such as obesity, protective & risk factors and comorbidities. RECENT FINDINGS: Asthma and rhinitis continue to have a significant impact worldwide on the health of affected patients, primarily children. The burden of asthma is greatest in developing countries and vulnerable populations, resulting in increased morbidity, potentially preventable asthma deaths and socioeconomic consequences. SUMMARY: A better understanding and representation of the burden of asthma and rhinitis in children can contribute to prevention strategies and improvements in the care of pediatric patients.

Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study.

BACKGROUND: Asthma is the most common chronic disease in children globally. The Global Asthma Network (GAN) Phase I study aimed to determine if the worldwide burden of asthma symptoms is changing. METHODS: This updated cross-sectional study used the same methods as the International study of Asthma and Allergies in Childhood (ISAAC) Phase III. Asthma symptoms were assessed from centres that completed GAN Phase I and ISAAC Phase I (1993-95), ISAAC Phase III (2001-03), or both. We included individuals from two age groups (children aged 6-7 years and adolescents aged 13-14 years) who self-completed written questionnaires at school. We estimated the 10-year rate of change in prevalence of current wheeze, severe asthma symptoms, ever having asthma, exercise wheeze, and night cough (defined by core questions in the questionnaire) for each centre, and we estimated trends across world regions and income levels using mixed-effects linear regression models with region and country income level as confounders. FINDINGS: Overall, 119 795 participants from 27 centres in 14 countries were included: 74 361 adolescents (response rate 90%) and 45 434 children (response rate 79%). About one in ten individuals of both age groups had wheeze in the preceding year, of whom almost half had severe symptoms. Most centres showed a change in prevalence of 2 SE or more between ISAAC Phase III to GAN Phase I. Over the 27-year period (1993-2020), adolescents showed a significant decrease in percentage point prevalence per decade in severe asthma symptoms (-0·37, 95% CI -0·69 to -0·04) and an increase in ever having asthma (1·25, 0·67 to 1·83) and night cough (4·25, 3·06 to 5·44), which was also found in children (3·21, 1·80 to 4·62). The prevalence of current wheeze decreased in low-income countries (-1·37, -2·47 to -0·27], in children and -1·67, -2·70 to -0·64, in adolescents) and increased in lower-middle-income countries (1·99, 0·33 to 3·66, in children and 1·69, 0·13 to 3·25, in adolescents), but it was stable in upper-middle-income and high-income countries. INTERPRETATION: Trends in prevalence and severity of asthma symptoms over the past three decades varied by age group, country income, region, and centre. The high worldwide burden of severe asthma symptoms would be mitigated by enabling access to effective therapies for asthma. FUNDING: International Union Against Tuberculosis and Lung Disease, Boehringer Ingelheim New Zealand, AstraZeneca Educational Grant, National Institute for Health Research, UK Medical Research Council, European Research Council, and Instituto de Salud Carlos III.

Parental Education and the Association between Fruit and Vegetable Consumption and Asthma in Adolescents: The Greek Global Asthma Network (GAN) Study.

BACKGROUND: Evidence suggests that nutritional factors, such as consumption of fruits and vegetables, along with socioeconomic factors such as parental education level, are associated with asthma prevalence. Our study examined the role of parental education in the association between fruit and vegetable consumption and adolescent asthma. METHODS: 1934 adolescents (mean age: 12.7 years, standard deviation: 0.6 years, boys: 47.5%) and their parents were voluntarily enrolled and completed a validated questionnaire assessing current asthma status, fruit and vegetable consumption and parental educational level. Participants were categorized as high or low intake for five food groups: fruits, cooked vegetables, raw vegetables, all vegetables (cooked and raw), and all three food groups together (fruits and all vegetables). RESULTS: Adolescents who were high consumers of all three food groups (fruits, cooked and raw vegetables) were less likely to have asthma, adjusted for several confounders (adjusted odds ratio (aOR): 0.53, 95% confidence interval (CI): 0.25-0.97). Moreover, in adolescents who had parents with tertiary education and were in the high consumption of all three food groups, the inverse association was almost twofold higher than the one for adolescents with parents of primary/secondary education (aOR: 0.35, 95% CI: (0.21-0.89) and aOR: 0.61, 95% CI: (0.47-0.93) respectively). CONCLUSIONS: Our findings highlight the importance of the adoption of a diet rich in fruits and vegetables for all asthmatic adolescents and emphasize the important role of parental influences in this association.

Improving lung health in low-income and middle-income countries: from challenges to solutions.

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.

Risk factors for wheezing in primary health care settings in the tropics.

BACKGROUND: The International Study of Wheezing in Infants (EISL) is a cross-sectional, population-based study, based on ISAAC (http://www.isaac.auckland.ac.nz). It uses a validated questionnaire on early wheezing and risk/protective factors. OBJECTIVE: To apply the EISL questionnaire regarding wheezing events in 0- to 12-month-old infants with or without atopic background searching for risk factors in the tropics. METHODS: The population was toddlers coming in for a checkup or 12-months' vaccination in primary health care clinics of a tropical city. Apart from child factors (eg, daycare attendance), we evaluated home factors (eg, air conditioning, bathroom, carpet, >6 persons, pollution) and mothers' factors (eg, education level, employment, cellphone). Data analysis was descriptive and case-control, with as cases atopic (AW) or non-atopic (NAW) wheezing children vs healthy controls. Wheezing-associated factors were evaluated using multivariate analysis, adjusted for the relation of AW/NAW with factors that were significant in prior univariate analysis. RESULTS: The study included 999 toddlers. Any wheeze: 31.3%, recurrent wheeze (≥3 episodes): 12.1%. Major risk factors for AW (OR; 95%CI) included smoking (11.39; 2.36-54.99), common cold before 3 months of life (3.72; 2.59-5.36), mold (3.48; 2.28-5.30), kitchen indoors (2.40; 1.27-4.54), and pets (1.69; 1.09-2.62); breastfeeding was almost protective. For NAW, common cold and pets were risk factors, but cesarean section (0.44; 0.23-0.82), more than 1 sibling (0.33; 0.18-0.61), and breastfeeding for longer than 3 months (0.50; 0.28-0.91) were protective. CONCLUSION: Wheezing is a health care burden. We found potential new risk factors for AW, some possibly unique for tropical climates. We suggest testing several hypotheses: could early AW be reduced in the tropics by attacking mold growth? Enhancing cooking place ventilation? Keeping pets outside? Or by postponing daycare attendance until after 4 months of age and avoiding (passive) smoking during pregnancy?

Combined impact of healthy lifestyle factors on risk of asthma, rhinoconjunctivitis and eczema in school children: ISAAC phase III.

BACKGROUND: Asthma is not the key focus of prevention strategies. A Healthy Lifestyle Index (HLI) was developed to examine the combined effect of modifiable lifestyle factors on asthma, rhinoconjunctivitis and eczema using data from the International Study of Asthma and Allergies in Childhood (ISAAC) phase III. METHODS: Information on symptoms of asthma, rhinoconjunctivitis, eczema and several lifestyle factors was obtained from children aged 6-7 years through written questionnaires. The HLI combined five lifestyle factors: no parental smoking, child's adherence to Mediterranean diet, child's healthy body mass index, high physical activity and non-sedentary behaviour. The association between the HLI and risk of asthma, rhinoconjunctivitis and eczema was evaluated using multilevel mixed-effects logistic regression models. FINDINGS: Data of 70 795 children from 37 centres in 19 countries were analysed. Each additional healthy lifestyle factor was associated with a reduced risk of current wheeze (OR 0.87, 95% CI 0.84 to 0.89), asthma ever (OR 0.89, 95% CI 0.87 to 0.92), current symptoms of rhinoconjunctivitis (OR 0.95, 95% CI 0.92 to 0.97) and current symptoms of eczema (OR 0.92, 95% CI 0.92 to 0.98). Theoretically, if associations were causal, a combination of four or five healthy lifestyle factors would result into a reduction up to 16% of asthma cases (ranging from 2.7% to 26.3 % according to region of the world). CONCLUSIONS: These findings should be interpreted with caution given the limitations to infer causality from cross-sectional observational data. Efficacy of interventions to improve multiple modifiable lifestyle factors to reduce the burden asthma and allergy in childhood should be assessed.

The Global Asthma Network rationale and methods for Phase I global surveillance: prevalence, severity, management and risk factors.

The Global Asthma Network (GAN), established in 2012, followed the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC Phase One involved over 700 000 adolescents and children from 156 centres in 56 countries; it found marked worldwide variation in symptom prevalence of asthma, rhinitis and eczema that was not explained by the current understanding of these diseases; ISAAC Phase Three involved over 1 187 496 adolescents and children (237 centres in 98 countries). It found that asthma symptom prevalence was increasing in many locations especially in low- and middle-income countries where severity was also high, and identified several environmental factors that required further investigation.GAN Phase I, described in this article, builds on the ISAAC findings by collecting further information on asthma, rhinitis and eczema prevalence, severity, diagnoses, asthma emergency room visits, hospital admissions, management and use of asthma essential medicines. The subjects will be the same age groups as ISAAC, and their parents. In this first global monitoring of asthma in children and adults since 2003, further evidence will be obtained to understand asthma, management practices and risk factors, leading to further recognition that asthma is an important non-communicable disease and to reduce its global burden.

Towards a comprehensive global approach to prevention and control of NCDs.

BACKGROUND: The "25×25" strategy to tackle the global challenge of non-communicable diseases takes a traditional approach, concentrating on a few diseases and their immediate risk factors. DISCUSSION: We propose elements of a comprehensive strategy to address NCDs that takes account of the evolving social, economic, environmental and health care contexts, while developing mechanisms to respond effectively to local patterns of disease. Principles that underpin the comprehensive strategy include: (a) a balance between measures that address health at the individual and population level; (b) the need to identify evidence-based feasible and effective approaches tailored to low and middle income countries rather than exporting questionable strategies developed in high income countries; (c) developing primary health care as a universal framework to support prevention and treatment; (d) ensuring the ability to respond in real time to the complex adaptive behaviours of the global food, tobacco, alcohol and transport industries; (e) integrating evidence-based, cost-effective, and affordable approaches within the post-2015 sustainable development agenda; (f) determination of a set of priorities based on the NCD burden within each country, taking account of what it can afford, including the level of available development assistance; and (g) change from a universal "one-size fits all" approach of relatively simple prevention oriented approaches to more comprehensive multi-sectoral and development-oriented approaches which address both health systems and the determinants of NCD risk factors. SUMMARY: The 25×25 is approach is absolutely necessary but insufficient to tackle the the NCD disease burden of mortality and morbidity. A more comprehensive approach is recommended.

Pediatricians' attitudes and costs of bronchiolitis in the emergency department: a prospective multicentre study.

BACKGROUND: How pediatricians manage bronchiolitis and the derived total costs (direct and indirect) in the emergency department (ED) have not been fully characterized. The aim of the present study is to calculate those costs in a European country. METHODS: A prospective and observational study, including 10 EDs of tertiary hospitals throughout Spain and during the bronchiolitis season 2010-2011, was performed. Every ED recruited children on random days of the week (3 days per week; always including one non-working day per every week). Recruitment aimed at a total sample size of 600 children. Direct (diagnostic procedures, time spent in the ED and medication) and indirect costs (work hours lost by parents, babysitting, travels, and meals) were collected. Comparisons between bronchiolitis caused by respiratory syncytial virus (RSV) and non-RSV bronchiolitis, as well as costs across severity categories were performed with the Kruskal-Wallis test. A multiple regression model was built to assess the influence of several of the studied factors on the total costs, including a RSV positive test and episode severity as independent variables; and gender, age, attending nursery school, preterm birth, low birth weight, smoker mother during pregnancy, and current smoker father as covariates. RESULTS: From the 664 recruited children, direct mean costs were €213.2 ± 91.8 and indirect ones were €35.9 ± 55.3; the total costs being €249.2 ± 122.9. Costs were significantly higher in children positive to RSV and rose with increased severity. Those associations were maintained in the multiple regression analysis. CONCLUSIONS: Although relatively low at the individual level (€249.2, mean total cost) the costs for just the ED expenses of bronchiolitis in Spain would add up to about €20 million per year.

International prevalence of recurrent wheezing during the first year of life: variability, treatment patterns and use of health resources.

BACKGROUND: Recurrent wheezing (RW) during the first year of life is a major cause of respiratory morbidity worldwide, yet there are no studies on its prevalence at an international level. A study was undertaken to determine the prevalence of RW in infants during their first year of life in affluent and non-affluent localities. METHODS: This international population-based study was performed in random samples of infants aged 12-15 months from 17 centres in Latin America and Europe. It uses a validated questionnaire answered by parents at the primary care health clinics where infants attend for growth/development monitoring and/or vaccine administration. RESULTS: Among the 30,093 infants surveyed, 45.2% (95% CI 44.7% to 45.8%) had at least one episode of wheezing and 20.3% (95% CI 19.8% to 20.7%) had RW. The mean prevalence of RW in Latin American and European centres was 21.4% (95% CI 20.9% to 21.9%) and 15.0% (95% CI 14.0% to 15.9%), respectively (p<0.001). There was significant morbidity associated with RW in terms of severe episodes (59.4%), visits to the emergency department (71.1%) and hospital admissions (26.8%); 46.1% used inhaled corticosteroids. CONCLUSIONS: The prevalence of RW in infants during the first year of life is high and varies between localities. A significant proportion of infants progress to a more severe condition which results in high use of health resources (visits to emergency department and hospitalisations). The prevalence of RW is lower and less severe in European than in Latin American centres, suggesting there is a higher risk for the disease in developing areas.

Concordance of lateral flow and skin prick tests in the assessment of allergen sensitisation in the epidemiological field in children.

BACKGROUND: A new lateral flow test (LFT) for office use provides information about sensitisation to common allergens. Concordance between LFT and skin-prick test (SPT) has not been assessed in epidemiological studies. The aim of this study is to determine LFT-SPT concordance in this field. METHODS: Plasma samples (n = 270) from children aged 9-12 years previously SPT tested were used for the analysis. We selected 180 samples from children SPT positive to any of the 6 allergens which were common to SPT and LFT (cat, birch, timothy-grass, olive, pellitoryand Dermatophagoides pteronyssinus), and 90 samples from children SPT negative. The intensity of the LFT colour line which indicates a positive reaction was rated from 0 to 4. RESULTS: Only results on cat, olive and D. pteronyssinus were analysed, as only these had an acceptable number of individuals. When atopy was defined as at least 1 wheal with a mean diameter > or =3 mm, agreement was excellent (Cohen's kappa = 0.81) when a lightly visible line was considered positive in the LFT, and dropped substantially (Cohen's kappa = 0.68) when this value of LFT was considered negative. The correlation between the SPT wheal diameter and the intensity of the LFT line was 0.71 for cat, 0.81 for olive and 0.78 for D. pteronyssinus. CONCLUSIONS: As compared to SPT, LFT is a reliable method to screen for sensitisation to cat dander, olive pollen and D. pteronyssinus in the epidemiological field among schoolchildren. There is a good correlation between the SPT wheal diameter and the intensity of the LFT line.

Atopic sensitization and the international variation of asthma symptom prevalence in children.

RATIONALE: Atopic sensitization has long been known to be related to asthma in children, but its role in determining asthma prevalence remains to be elucidated further. OBJECTIVES: To investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma. METHODS: Cross-sectional studies of random samples of 8- to 12-year-old children (n = 1,000 per center) were performed according to the standardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood (ISAAC). Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions, from rural Africa to urban Europe. Data were collected by parental questionnaires (n = 54,439), skin prick tests (n = 31,759), and measurements of allergen-specific IgE levels in serum (n = 8,951). Economic development was assessed by gross national income per capita (GNI). MEASUREMENTS AND MAIN RESULTS: The prevalence of current wheeze (i.e., during the past year) ranged from 0.8% in Pichincha (Ecuador) to 25.6% in Uruguaiana (Brazil). The fraction of current wheeze attributable to atopic sensitization ranged from 0% in Ankara (Turkey) to 93.8% in Guangzhou (China). There were no correlations between prevalence rates of current wheeze and atopic sensitization, and only weak correlations of both with GNI. However, the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI (Spearman rank-order coefficient rho = 0.50, P = 0.006, and rho = 0.74, P < 0.0001, respectively). In addition, the strength of the association between current wheeze and skin test reactivity, assessed by odds ratios, increased with GNI (rho = 0.47, P = 0.01). CONCLUSIONS: The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.

Benefit-risk assessment of antileukotrienes in the management of asthma.

Antileukotrienes are a relatively new class of anti-asthma drugs that either block leukotriene synthesis (5-lipoxygenase inhibitors) like zileuton, or antagonise the most relevant of their receptors (the cysteinyl leukotriene 1 receptor [CysLT1]) like montelukast, zafirlukast or pranlukast. Hence, their major effect is an anti-inflammatory one. With the exception of pranlukast, the other antileukotrienes have been studied and marketed in the US and Europe for long enough to establish that they are useful drugs in the management of asthma. Their effects, significantly better than placebo, seem more pronounced in subjective measurements (i.e. symptoms scores or quality-of-life tests) than in objective parameters (i.e. forced expiratory volume in 1 second or peak expiratory flow rate). Also, there is some evidence that these drugs work better in some subsets of patients with certain genetic polymorphisms - probably related to their leukotriene metabolism - or patients with certain asthma characteristics. There are a small number of comparative studies only, and with regard to long-term asthma control differences between the agents have not been evaluated. Nevertheless, their overall effect appears comparable with sodium cromoglycate (cromolyn sodium) or theophylline, but significantly less than low-dose inhaled corticosteroids. Antileukotrienes have been shown to have a degree of corticosteroid-sparing effect, but salmeterol appears to perform better as an add-on drug. Montelukast is probably the most useful antileukotriene for continuous treatment of exercise-induced asthma, performing as well as salmeterol without inducing any tolerance. All antileukotrienes are taken orally; their frequency of administration is quite different ranging from four times daily (zileuton) to once daily (montelukast). Antileukotrienes are well tolerated drugs, even though zileuton intake has been related to transitional liver enzyme elevations in some cases. Also Churg-Strauss syndrome (a systemic vasculitis), has been described in small numbers of patients taking CysLT1 antagonists. It is quite probable that this disease appears as a consequence of an 'unmasking' effect when corticosteroid dosages are reduced in patients with severe asthma once CysLT1 antagonists are introduced, but more data are needed to definitely establish the mechanism behind this effect. Overall, however, the benefits of antileukotrienes in the treatment of asthma greatly outweigh their risks.