Background: Fraction of exhaled nitric oxide (FENO) and blood eosinophil count (B-Eos) values, markers of local and systemic eosinophilic inflammation, respectively, are increased in asthmatic patients. Little is known about the relation of these markers to reported wheeze and asthma events in a random population sample. Objectives: We sought to determine the individual and independent values of B-Eos and FENO in relation to wheeze, asthma diagnosis, and asthma events in a cross-sectional study. 3 ) values rendered an adjusted odds ratio of 4.5 of having wheeze, 5.1 of having asthma, 5.4 for asthma attacks, and 2.9 for asthma-related ED visits compared with normal FENO (<25 ppb) and B-Eos (<300 cells/mm

ObjectiveThe best combination of questions to define asthma in epidemiological asthma studies is not known. We summarized the operational definitions of asthma used in prevalence studies and empirically assess how asthma prevalence estimates vary depending on the definition used.MethodsWe searched the Thomson Reuters ISI Web of knowledge and included (1) cross-sectional studies (2) on asthma prevalence (3) conducted in the general population and (4) containing an explicit definition of asthma. The search was limited to the 100 most-cited papers or published since January 2010. For each paper, we recorded the asthma definition used and other variables. Then we applied the definitions to the data of the Portuguese National Asthma survey (INAsma) and of the 2005–2006 National Health and Nutrition Examination Survey (NHANES) computing asthma prevalence estimates for the different definitions.ResultsOf 1738 papers retrieved, 117 were included for analysis. Lifetime asthma, diagnosed asthma and current asthma were defined in 8, 12 and 29 different ways, respectively. By applying definitions of current asthma on INAsma and NHANES data, the prevalence ranged between 5.3%-24.4% and 1.1%-17.2%, respectively.ConclusionsThere is considerable heterogeneity in the definitions of asthma used in epidemiological studies leading to highly variable estimates of asthma prevalence. Studies to inform a standardized operational definition are needed. Meanwhile, we propose a set of questions to be reported when defining asthma in epidemiological studies.

Asthma frequently occurs in association with allergic rhinitis and a combined management approach has been suggested. The Control of Allergic Rhinitis and Asthma Test (CARAT) is the first questionnaire to assess control of both diseases concurrently. However, to have an impact on healthcare it needs to be disseminated and adopted. In this paper we discuss the dissemination of CARAT in different countries and its possible applications in primary care. At present, the adaptation of CARAT for use in different languages and cultures is being led by volunteer researchers and clinicians in 15 countries. Website and smartphone applications have been developed, and a free open model of distribution was adopted to contribute to the dissemination of CARAT. Examples of dissemination activities include distribution of leaflets and posters, educational sessions on the use of the questionnaire in the follow-up of patients, development of

BackgroundAsthma is a frequent chronic respiratory disease in both children and adults. However, few data on asthma prevalence are available in Portugal. The Portuguese National Asthma Survey is the first nationwide study that uses standardized methods. We aimed to estimate the prevalence of current asthma in the Portuguese population and to assess the association between ‘Current asthma’ and comorbidities such as upper airways disease.MethodsA cross-sectional, population-based, telephone interview survey including all municipalities of Portugal was undertaken. Participants were randomly selected to answer a questionnaire based on the Portuguese version of the GA2LEN survey. ‘Current asthma’ was defined as self-reported lifetime asthma and at least one of 3 symptoms in the last 12 months: wheezing, waking with breathlessness or having an asthma attack.ResultsData were obtained for 6 003 respondents, with mean age of 38.9 (95%CI 38.2-39.6) years and 57.3% females. In the Portuguese population, the prevalence of ‘Current asthma’ was 6.8% (95%CI 6.0-7.7) and of ‘Lifetime asthma’ was 10.5% (95%CI 9.5-11.6) Using GA2LEN definition for asthma, our prevalence estimate was 7.8% (95%CI 7.0-8.8). Rhinitis had a strong association with asthma (Adjusted OR 3.87, 95%CI 2.90-5.18) and the association between upper airway diseases and asthma was stronger in patients with both rhinitis and sinusitis (Adjusted OR 13.93, 95%CI 6.60-29.44).ConclusionsCurrent asthma affects 695 000 Portuguese, with a prevalence of 6.8%. People who reported both rhinitis and sinusitis had the highest risk of having asthma.

It is not fully understood how the fraction of exhaled nitric oxide (FeNO) varies with age and gender in healthy individuals. We aim to describe the evolution of FeNO with age, giving special regard to the effect of gender, and to relate this evolution to natural changes in the respiratory tract.We studied 3081 subjects from NHANES 2007-08 and 2009-10, aged 6-80 years, with no self-reported diagnosis of asthma, chronic bronchitis or emphysema, and with normal values of blood eosinophils and C-reactive protein. The relationship of the mean values of FeNO to age, in all participants and divided by gender, was computed, and compared with changes in anatomic dead space volume and forced vital capacity. A change-point analysis technique and subsequent piecewise regression was used to detect breakpoints in the evolution of FeNO with age.Three distinct phases in the evolution of FeNO throughout the age range 6-80 years can be seen. FeNO values increase linearly between 6-14 years of age in girls and between 6-16 years of age in boys, in parallel with somatic growth. After that, FeNO levels plateau in both genders until age 45 years in females and age 59 years in males, when they start to increase linearly again. This increase continues until age 80.Our data clearly show a triphasic evolution of FeNO throughout the human age range in healthy individuals. This should be accounted for in development of reference equations for normal FeNO values.

Background:The values obtained when the fraction of exhaled nitric oxide (FeNO) is measured are affected by several factors that are specific to the individual patient, making interpretation difficult, especially in the initial assessment of patients with respiratory symptoms. Methods: Systematic review of studies on FeNO reference values and individualspecific factors that influence them. Results: From 3739 references, 15 studies were included. Four studies included children and adolescents. In nine studies, samples were selected from the general population. Most studies reported objective measures for atopy (nine studies), but not for smoking status (one). Significant determinants of FeNO values reported were age and height (seven studies), atopy (six), smoking (four), weight (four), sex (three) and race (three). Additional factors were included in eight studies. R 2 was reported in only five studies. The logarithmic transformation of FeNO was inadequately described in seven studies. Conclusion:There are several equations for FeNO reference values that may be used in clinical practice, although the factors they include and the statistical methods they use vary considerably. We recommend the development of standard methods for the evaluation of normal FeNO data and that reference equations should be formulated based on a predetermined physiological model. Please cite this paper as: Jacinto T, Alving K, Correia R, Costa-Pereira A and Fonseca J. Setting reference values for exhaled nitric oxide: a systematic review. Clin Respir J 2013; 7: 113-120. Key words exhaled nitric oxide -reference valuessystematic reviewCorrespondence

BackgroundEvidence for distinct asthma phenotypes and their overlap is becoming increasingly relevant to identify personalized and targeted therapeutic strategies. In this study, we aimed to describe the overlap of five commonly reported asthma phenotypes in US adults with current asthma and assess its association with asthma outcomes.MethodsData from the National Health and Nutrition Examination Surveys (NHANES) 2007–2012 were used (n = 30,442). Adults with current asthma were selected. Asthma phenotypes were: B-Eos-high [if blood eosinophils (B-Eos) ≥ 300/mm3]; FeNO-high (FeNO ≥ 35 ppb); B-Eos&FeNO-low (B-Eos < 150/mm3 and FeNO < 20 ppb); asthma with obesity (AwObesity) (BMI ≥ 30 kg/m2); and asthma with concurrent COPD. Data were weighted for the US population and analyses were stratified by age (< 40 and ≥ 40 years old).ResultsOf the 18,619 adults included, 1059 (5.6% [95% CI 5.1–5.9]) had current asthma. A substantial overlap was observed both in subjects aged < 40 years (44%) and ≥ 40 years (54%). The more prevalent specific overlaps in both age groups were AwObesity associated with either B-Eos-high (15 and 12%, respectively) or B-Eos&FeNO-low asthma (13 and 11%, respectively). About 14% of the current asthma patients were “non-classified”. Regardless of phenotype classification, having concomitant phenotypes was significantly associated with (adjusted OR, 95% CI) ≥ 2 controller medications (2.03, 1.16–3.57), and FEV1 < LLN (3.21, 1.74–5.94), adjusted for confounding variables.ConclusionsA prevalent overlap of commonly reported asthma phenotypes was observed among asthma patients from the general population, with implications for objective asthma outcomes. A broader approach may be required to better characterize asthma patients and prevent poor asthma outcomes.Electronic supplementary materialThe online version of this article (10.1186/s13601-018-0201-3) contains supplementary material, which is available to authorized users.

BackgroundAtopy and rhinitis are among the factors affecting exhaled nitric oxide (FeNO) values and may contribute to difficulties in the clinical interpretation of FeNO measurements. However, data assessing their effects on FeNO values had never been summarized. This review aims to evaluate the effect of atopy and rhinitis in FeNO values in otherwise healthy individuals.MethodsA systematic review was performed in Pubmed, Scopus and ISI Web of Knowledge. A two-step selection process was completed, and from 2357 references 19 were included. The inclusion criteria were: participants without known diseases other than rhinitis; atopy assessement by SPT or Specific IgE; and FeNO measurements according to ATS/ERS recommendations.ResultsThe 8 articles measuring FeNO in children showed higher values in both allergic rhinitis and atopic children when compared with healthy children. The 11 articles performed in adults observed higher FeNO in AR patients comparatively with either healthy or atopic individuals. However, adult healthy and atopic individuals had similar FeNO values.ConclusionsFeNO values are higher in individuals with rhinitis and/or atopy without other health problems. These effects are small, seem to be independent and should be further studied using multivariate models. The effect of atopy was observed only in children. The combined effect of atopy and rhinitis produced higher FeNO values in adults. These results support that both atopy and rhinitis should be considered when interpreting or when defining FeNO reference values.