Transfer of innovation on allergic rhinitis and asthma multimorbidity in the elderly (MACVIA-ARIA) - EIP on AHA Twinning Reference Site (GARD research demonstration project).

The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults.

Do HLA class II genes protect against pulmonary tuberculosis? A systematic review and meta-analysis.

Pulmonary tuberculosis (PTB) develops by a complex combination of environmental, immunological and socioeconomic factors and genetic susceptibility. The human leukocyte antigen (HLA) is the most polymorphic biological system and plays an essential role in the immune response against PTB. The aim of this study was to carry out a systematic review and meta-analysis evaluating the relationship between HLA-DRB1, HLA-DQB1 and HLA-DQA1 gene polymorphisms as possible risk or protective factors for PTB. A systematic search of the PubMed and Scopus databases was conducted following the guidelines described in the PRISMA statement. Fifty-six alleles were included in the meta-analysis. In the total pooled results, HLA-DRB1*08:03 (OR 1.95, CI 1.29-2.96), HLA-DQB1*06:01 (OR 1.78, CI 1.39-2.28), HLA-DQB1*06:09 (OR 2.27, 95 % CI 1.04-4.96) and HLA-DQA1*01:01 (OR 2.12, CI 1.11-4.03) genes were related to higher susceptibility to PTB. Conversely, the presence of the genes HLA-DRB1*07:01 (OR 0.74, CI 0.56-0.97), HLA-DQB1*03:01 (OR 0.77, CI 0.61-0.97), HLA-DQB1*04:02 (OR 0.57, CI 0.39-0.83), HLA-DQA1*04:01 (OR 0.50, CI 0.26-0.95) and HLA-DQA1*05:01 (OR 0.66, CI 0.48-0.92) demonstrated protection against PTB. In an analysis by ethnic subgroups, we found more genetic associations in Caucasians than in Asians. These findings suggest that HLAs may be used as markers for acquisition and development of PTB. To strengthen PTB susceptibility/resistance, we recommend further multicentric studies in different geographic regions, with certainty of controls' exposure to M. tuberculosis by use of marker of latent or active PTB, with analysis stratified by ethnic groups, with descriptions of specific alleles and carrying out immunological functionality tests.

Integrated care pathways for airway diseases (AIRWAYS-ICPs).

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper.

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.

Reference values for peak nasal inspiratory flow in children and adolescents in Brazil.

STATEMENT OF THE PROBLEM: Allergic rhinitis is a global public health issue. Peak nasal inspiratory flow (PNIF) can help in the assessment of patients with allergic rhinitis. However, reference values in the literature for PNIF in school children and adolescents are limited. THE AIM OF THIS STUDY was to identify reference values of PNIF among children and adolescents. METHODS: We conducted a cross-sectional study to identify reference values of PNIF among healthy school children and adolescents aged from eight to fifteen years old, selected from 14 randomly selected public schools. Participants performed measurements of PNIF using the In-check-inspiratory flow meter (Clement Clarke, Harlow, England). PNIF values were correlated to gender, age, height, weight and body mass index. RESULTS: A total of 526 subjects participated in the study. The final linear regression model for PNIF allowed obtaining the following equation for subjects aged from eight to 15 years old: PNIF (l/m) = height (centimeters) x 0.7 + 11.2, for boys and PNIF (l/m) = height (centimeters) x 0.7, for girls. CONCLUSION: the equations of the final regression model resulted in a simple formula to obtain reference values of PNIF for subjects aged from 8 to 15 years old.

A pediatric asthma management program in a low-income setting resulting in reduced use of health service for acute asthma.

BACKGROUND: The effectiveness of pediatric asthma management programs in reducing health services utilization during exacerbations in developing countries is not widely studied. This study was carried out to assess the effectiveness of an asthma management program to reduce the overall health services utilization by acute asthma in children and adolescents. METHODS: In this historical population-based real-life cohort study, we selected 582 patients with asthma aged 4-15 living in deprived areas in the town of Itabira, Brazil, of which 470 cases were assisted by the asthma management program and 112 were controls. The end point was the first physician-diagnosed asthma exacerbation occurring after study enrollment and within 12 months after admission. All 470 cases received a written plan about exacerbation self-management, including the use of inhaled albuterol at home. Three hundred and seventeen out of 470 cases (67.4%) were also treated with beclomethasone diproprionate (BDP). RESULTS: Both groups were comparable regarding gender, age group, and place of residence. At the end of the study, only 5% of cases vs 34% of controls did seek health services because of acute asthma (P < 0.01). Statistical difference also remained when comparing the 112 controls with the 153 cases not treated with com BDP (Hazard Ratio = 0.04, 95% CI, 0.01-0.14, P < 0.01). CONCLUSIONS: Results have demonstrated the effectiveness of the pediatric asthma management program in reducing dependence on the health services for acute asthma. Effectiveness was also observed in subjects with no use of BDP.

Development and implementation of guidelines in allergic rhinitis ­ an ARIA-GA2LEN paper.

The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.

Monitoring adherence to beclomethasone in asthmatic children and adolescents through four different methods.

BACKGROUND: Suboptimal adherence to inhaled steroids is a known problem in children and adolescents, even when medications are administered under parental supervision. This study aimed to verify the adherence rate to beclomethasone dipropionate (BDP) by four currently available methods. METHODS: In this concurrent cohort study, 102 randomly selected asthmatic children and adolescents aged 3-14 years were followed for 12 months. Adherence rate was assessed every 2 months by self and/or parent report, pharmacy dispensing data, electronic device (Doser); Meditrack Products, Hudson, MA, USA) monitor, and canister weight. RESULTS: Mean adherence rates to BDP by self and/or parent report, pharmacy records, Doser, and canister weight were 97.9% (95% CI 88.0-98.6), 70.0% (95% CI 67.6-72.4), 51.5% (95% CI 48.3-54.6), and 46.3% (95% CI 44.1-48.4), respectively. Agreement analysis between (Doser) and canister weight revealed a weighted kappa equal to 0.76 (95% CI 0.65-0.87). CONCLUSIONS: Adherence was a dynamic event and rates decreased progressively for all methods over the 12-month follow-up. Canister weight and electronic monitoring measures were more accurate than self/parent reports and pharmacy records. Rates obtained by these two methods were very close and statistical analysis also showed a substantial agreement between them. As measurements by canister weight are less costly compared with currently available electronic devices, it should be considered as an alternative method to assess adherence in both clinical research and practice.

Adherence rate to inhaled corticosteroids and their impact on asthma control.

BACKGROUND: Poor asthma control is associated to high morbidity. The objective of this study was to assess the association between adherence rates to beclomethasone dipropionate (BDP) and the degree of asthma control. METHODS: A cohort concurrent study was carried out for 12 months with 122 asthmatic patients, aged 3-12 years, randomly selected in a pediatric pulmonology outpatient clinic, who received BDP free of charge. Adherence rates were verified by pharmacy records. Clinical control was assessed through a scoring system comprised four variables (nocturnal and morning symptoms, limitation of physical activities and exacerbations). Total score was 16 points. Patients whose score was below or equal to two were considered controlled (group 1), and patients whose score was above or equal to three were considered uncontrolled (group 2). For patients able to perform spirometry, we considered as controlled the patients with forced expiratory volume in 1 s (FEV(1)) equal to or above 80% of the predicted value, and as uncontrolled the patients with FEV(1) below 80%. RESULTS: Fewer than half (40.3% maximum) of the 122 patients maintained asthma control. Median adherence rate of groups 1 and 2 were 85.5% and 33.8%, (P < 0.001) in the 4th month, 90.0% and 48.0% (P < 0.001) in the 8th month and 84.4% and 47.0% in the 12th month (P < 0.001), respectively. CONCLUSION: In all periods, there were statistically significant differences in adherence rates for maintaining or not maintaining the asthma control. Optimal asthma control entailed adherence rate higher than 80%. Strategies for reducing asthma morbidity should include a regular monitoring of adherence to inhaled steroids.

Prophylactic regimens with fluconazole for candidiasis in neonates under 1.500g: A retrospective chart review of two cohorts.

BACKGROUND: The incidence rate of invasive candidiasis in newborns with birth weight below 1,500 g ranges from 2% to 8%, and fluconazole prophylaxis in neonatal units is recommended when the incidence of invasive candidiasis is higher than 5%. This study aimed to compare the effectiveness of targeted prophylaxis and universal prophylaxis with fluconazole in the prevention of invasive candidiasis. METHODS: This was a historical cohort comparing the targeted prophylaxis for newborns weighing less than 1,500 g and the universal prophylaxis for newborns weighing less than 1,000 g. RESULTS: The overall incidence rate of invasive candidiasis was 5.25% and was reduced from 7.1% to 3.72% with universal prophylaxis (p = 0.04). In a multivariate analysis, the significant factors associated with the development of candidiasis were birth weight less than 1,000 g, prolonged hospitalization, previous surgery, prolonged use of mechanical ventilation, prior exposure to antimicrobial treatments, and use of targeted prophylaxis. CONCLUSIONS: Universal prophylaxis had lower incidence of invasive candidiasis, and preventive measures considering the risk factors are mandatory to reduce the incidence of invasive candidiasis.

Incidence rate and factors related to post-bronchoalveolar lavage fever in children.

BACKGROUND: Post-bronchoscopy and bronchoalveolar lavage (BAL) fever in children has been described by several authors. OBJECTIVES: This study aimed at assessing the occurrence of fever after these examinations and associated risk factors. METHODS: The study was performed in the Bronchoscopy Unit of Hôpital Necker-Enfants Malades, Paris, France, from June 2004 to July 2005. 148 children who underwent fiberoptic bronchoscopy and BAL, and remained in the Unit for 24 h, were included. RESULTS: 37.8% of the patients presented post-BAL fever. In the multivariate analysis of the selected factors (age, immunodeficiency, general or local anesthesia, mucosal biopsy, inflammation and suppuration at the moment of the examination, abnormal bronchoalveolar fluid cellularity and infection), only age <2 years and presence of infection remained associated with fever. CONCLUSIONS: The occurrence of fever is a frequent event in children who underwent BAL. In order to reduce post-BAL fever, antibiotic strategies should be devised based on prospective studies assessing identification of predictive air-way infection criteria and/or rapid bacteriological result analysis.

Correlations between pulse oximetry and peak expiratory flow in acute asthma.

Few studies are available concerning correlations between pulse oximetry and peak expiratory flow in children and adolescents with acute asthma. Although the Global Initiative for Asthma states that measurements of lung function and oximetry are critical for the assessment of patients, it is not clear if both methods should necessarily be included in their evaluation. Since there is a significant difference in cost between pulse oximetry equipment and peak expiratory flow devices, we determined whether clinical findings and peak expiratory flow measurements are sufficient to determine the severity of acute asthma. The present prospective observational study was carried out to determine if there is correlation between pulse oximetry and peak expiratory flow determination in 196 patients with acute asthma aged 4 to 15 years diagnosed according to the Global Initiative for Asthma criteria. Patients experiencing their first or second wheezing episode, with fever, related acute or chronic diseases, and unable to perform the peak expiratory flow maneuver were excluded. Measurements of peak expiratory flow and pulse oximetry were performed at admission and after 15 min of each inhaled salbutamol cycle. Correlations obtained by linear regression using the Pearson correlation coefficients (r) were 0.41 (P < 0.0001), 0.53 (P < 0.0001), 0.51 (P < 0.0001), and 0.61 (P < 0.0001) at admission and after the first, second and third cycles of salbutamol, respectively. These correlations showed that one measure cannot substitute the other (Pearson's coefficient <0.7), probably because they evaluate different aspects in the airways, suggesting that peak expiratory flow should not be used alone in the assessment of acute asthma in children and adolescents.

CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: a SUNFRAIL report.

A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.

Primary care physicians' ability to diagnose the most prevalent respiratory diseases.

BACKGROUND: There are few reports on the ability of primary care physicians (PCPs) to diagnose acute and chronic respiratory diseases. We assessed the agreement between PCPs and pulmonologists in diagnosing pulmonary tuberculosis (TB), chronic obstructive pulmonary disease (COPD), asthma and acute respiratory infections (ARI). SETTING: Metropolitan Region of Belo Horizonte, State of Minas Gerais, Brazil. METHODS: PCPs filled out a symptom-based questionnaire for adult patients presenting with respiratory symptoms. Their diagnoses were compared to those of three pulmonologists who reviewed the data independently without seeing the patients. Agreement between PCP decisions and those of the pulmonologists was assessed. RESULTS: Among a total of 554 patients, 60 PCPs correctly diagnosed 42.4% as having ARI, 17.3% asthma, 15.7% COPD and 12.4% suspected TB. Agreement between the PCPs and the pulmonologists was as follows: 0.53 for asthma (95%CI 0.45-0.60), 0.53 (95%CI 0.46-0.60) for ARI, 0.45 (95%CI 0.34-0.57) for TB and 0.40 (95%CI 0.29-0.50) for COPD. CONCLUSION: Only reasonable to moderate agreement was found between PCPs and pulmonologists in diagnosing the most prevalent respiratory conditions. This result emphasises the need to adopt measures and provide tools to improve the diagnostic skills of PCPs for patients presenting with respiratory symptoms.

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle.

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

Latex particle agglutination test in the diagnosis of Haemophilus influenzae type B, Streptococcus pneumoniae and Neisseria meningitidis A and C meningitis in infants and children.

The knowledge of purulent meningitis etiology is essential in deciding the immediate therapy; in developing countries, however, the etiological agent identification does not reach 60% of the cases. A comparative study using the latex particle agglutination test (LPAT) in cerebrospinal fluid (CSF) for the diagnosis of meningitis due to Haemophilus influenzae type b, Streptococcus pneumoniae or Neisseria meningitidis A and C was carried out in Belo Horizonte MG, Brazil. CSF culture was used as a gold-standard. Two hundred and ninety-nine children, ranging from 3 months to 14 years of age, were included in the investigation. One hundred and forty-four presented a positive CSF culture for the above mentioned bacteria; the remaining presented meningitis due to other organisms (other bacteria or viral) or a normal CSF. The sensitivity and the specificity of LPAT was 95.7 and 100.0% for N. meningitidis C, 95.2 and 100.0% for H. influenzae type b and 86.5 and 100.0% for S. pneumoniae, respectively. When all three organisms were considered simultaneously, the sensitivity and the specificity was 93.0 and 100.0%, respectively. Taking into consideration a realistic estimate of disease prevalence in the community where the diagnostic test is being used, the positive predictive value and the posttest probability were estimated as 36.7 and 47.1% for children < 5 years and as 21.3 and 35.1% for children < 14 years of age, respectively. LPAT is a useful diagnostic test for meningitis due to the studied pathogens, especially in developing countries where laboratory facilities are limited.

Risk assessment for acquiring meningitis tuberculosis among children not vaccinated with BCG: a case-control study.

This case-control study was conducted to assess the risk, among children aged 0-12 years, of developing meningitis tuberculosis (MT) associated with a lack of intradermal BCG vaccination. Cases (45) of MT admitted for treatment at the Fundacao Benjamin Guimaraes Hospital (Belo Horizonte, MG, Brazil), from 1975 to 1981, were matched for age at hospitalization, date of hospitalization and nutritional status, with two types of controls--patients with acute diarrhoea (AD) and patients with acute non-tuberculous bacterial pneumonias (BP)--admitted to the same hospital. Vaccination status was ascertained from the patients' medical records. Results showed a risk for MT, estimated by the odds ratio, between BCG non-vaccinated and BCG vaccinated patients, of 6.7 (95% Cl 2.3-19.0) comparing cases and AD controls, of 4.0 (95% Cl 1.5-11.0) comparing cases and BP controls and 5.7 (95% Cl 2.3-14.0) comparing cases with both controls. When adjustments were made for place of residence (Metropolitan Region of Belo Horizonte and other regions of Minas Gerais State), the risks decreased to 5.2 (95% Cl 1.9-14.0) and 2.9 (95% Cl 1.2-7.3) comparing cases with AD and BP controls, respectively.

Blood stained cerebrospinal fluid responsible for false positive reactions of latex particle agglutination tests.

The accuracy of the latex particle agglutination test (LPAT) was assessed in blood stained cerebrospinal fluid (CSF) specimens from 166 paediatric patients, aged from three months to 13 years. A commercial LPAT kit was used to detect Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis A, B, and C soluble antigens. Culture of CSF specimens was used as the standard and all laboratory procedures were performed blind. The mean CSF erythrocyte count was 66,406 cells/mm3 in the cases and 11,560 cells/mm3 in the controls. The sensitivity and the specificity of LPAT were 83.8 and 94.0%, respectively, suggesting that LPAT is a useful diagnostic tool even in blood stained CSF specimens.