| 1. |
- Amaral, Rita, et al.
(författare)
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Comparison of hypothesis- and data-driven asthma phenotypes in NHANES 2007-2012 : the importance of comprehensive data availability
- 2019
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHalf of the adults with current asthma among the US National Health and Nutrition Examination Survey (NHANES) participants could be classified in more than one hypothesis-driven phenotype. A data-driven approach applied to the same subjects may allow a more useful classification compared to the hypothesis-driven one.AimTo compare previously defined hypothesis-driven with newly derived data-driven asthma phenotypes, identified by latent class analysis (LCA), in adults with current asthma from NHANES 2007-2012.MethodsAdults (18years) with current asthma from the NHANES were included (n=1059). LCA included variables commonly used to subdivide asthma. LCA models were derived independently according to age groups: <40 and 40years old.ResultsTwo data-driven phenotypes were identified among adults with current asthma, for both age groups. The proportions of the hypothesis-driven phenotypes were similar among the two data-driven phenotypes (p>0.05). Class A <40years (n=285; 75%) and Class A 40years (n=462; 73%), respectively, were characterized by a predominance of highly symptomatic asthma subjects with poor lung function, compared to Class B <40years (n=94; 25%) and Class B 40years (n=170; 27%). Inflammatory biomarkers, smoking status, presence of obesity and hay fever did not markedly differ between the phenotypes.ConclusionBoth data- and hypothesis-driven approaches using clinical and physiological variables commonly used to characterize asthma are suboptimal to identify asthma phenotypes among adults from the general population. Further studies based on more comprehensive disease features are required to identify asthma phenotypes in population-based studies.
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| 2. |
- Amaral, Rita, et al.
(författare)
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Having concomitant asthma phenotypes is common and independently relates to poor lung function in NHANES 2007-2012
- 2018
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Ingår i: Clinical and Translational Allergy. - : BIOMED CENTRAL LTD. - 2045-7022. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence 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. Methods: Data 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/mm(3)]; FeNO-high (FeNO >= 35 ppb); B-Eos&FeNO-low (B-Eos < 150/mm(3) and FeNO < 20 ppb); asthma with obesity (AwObesity) (BMI >= 30 kg/m(2)); and asthma with concurrent COPD. Data were weighted for the US population and analyses were stratified by age (< 40 and >= 40 years old). Results: Of 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. Conclusions: A 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.
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| 3. |
- Amaral, Rita, et al.
(författare)
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The influence of individual characteristics and non-respiratory diseases on blood eosinophil count
- 2021
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Ingår i: Clinical and Translational Allergy. - : John Wiley & Sons. - 2045-7022. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBlood eosinophil (B-Eos) count is an emerging biomarker in the management of respiratory disease but determinants of B-Eos count besides respiratory disease are poorly described. Therefore, we aimed to evaluate the influence of non-respiratory diseases on B-Eos count, in comparison to the effect on two other biomarkers: fraction of exhaled nitric oxide (FeNO) and C-reactive protein (CRP), and to identify individual characteristics associated with B-Eos count in healthy controls.MethodsChildren/adolescents (<18 years) and adults with complete B-Eos data from the US National Health and Nutritional Examination Surveys 2005–2016 were included, and they were divided into having respiratory diseases (n = 3333 and n = 7,894, respectively) or not having respiratory disease (n = 8944 and n = 15,010, respectively). After excluding any respiratory disease, the association between B-Eos count, FeNO or CRP, and non-respiratory diseases was analyzed in multivariate models and multicollinearity was tested. After excluding also non-respiratory diseases independently associated with B-Eos count (giving healthy controls; 8944 children/adolescents and 5667 adults), the independent association between individual characteristics and B-Eos count was analyzed.ResultsIn adults, metabolic syndrome, heart disease or stroke was independently associated with higher B-Eos count (12%, 13%, and 15%, respectively), whereas no associations were found with FeNO or CRP. In healthy controls, male sex or being obese was associated with higher B-Eos counts, both in children/adolescents (15% and 3% higher, respectively) and adults (14% and 19% higher, respectively) (p < 0.01 all). A significant influence of race/ethnicity was also noted, and current smokers had 17% higher B-Eos count than never smokers (p < 0.001).ConclusionsNon-respiratory diseases influence B-Eos count but not FeNO or CRP. Male sex, obesity, certain races/ethnicities, and current smoking are individual characteristics or exposures that are associated with higher B-Eos counts. All these factors should be considered when using B-Eos count in the management of respiratory disease.
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| 4. |
- Cunha, Francisco, et al.
(författare)
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A Systematic Review of Asthma Phenotypes Derived by Data-Driven Methods
- 2021
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Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 11:4
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Forskningsöversikt (refereegranskat)abstract
- Classification of asthma phenotypes has a potentially relevant impact on the clinical management of the disease. Methods for statistical classification without a priori assumptions (data-driven approaches) may contribute to developing a better comprehension of trait heterogeneity in disease phenotyping. This study aimed to summarize and characterize asthma phenotypes derived by data-driven methods. We performed a systematic review using three scientific databases, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. We included studies reporting adult asthma phenotypes derived by data-driven methods using easily accessible variables in clinical practice. Two independent reviewers assessed studies. The methodological quality of included primary studies was assessed using the ROBINS-I tool. We retrieved 7446 results and included 68 studies of which 65% (n = 44) used data from specialized centers and 53% (n = 36) evaluated the consistency of phenotypes. The most frequent data-driven method was hierarchical cluster analysis (n = 19). Three major asthma-related domains of easily measurable clinical variables used for phenotyping were identified: personal (n = 49), functional (n = 48) and clinical (n = 47). The identified asthma phenotypes varied according to the sample's characteristics, variables included in the model, and data availability. Overall, the most frequent phenotypes were related to atopy, gender, and severe disease. This review shows a large variability of asthma phenotypes derived from data-driven methods. Further research should include more population-based samples and assess longitudinal consistency of data-driven phenotypes.
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| 5. |
- Jacinto, Tiago, et al.
(författare)
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Differential effect of cigarette smoke exposure on exhaled nitric oxide and blood eosinophils in healthy and asthmatic individuals
- 2017
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Ingår i: Journal of Breath Research. - : IOP Publishing. - 1752-7155 .- 1752-7163. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Background:Tobacco smoking affects both the fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count, two clinically useful biomarkers in respiratory disease that represent local and systemic type-2 inflammation, respectively.Objective:We aimed to study the influence of objectively measured smoke exposure on FeNO and B-Eos in a large population of subjects with and without asthma.Methods:We utilized the US National Health and Nutrition Examination Surveys 2007-2012 and included 10 669 subjects aged 6-80 years: 9869 controls and 800 asthmatics. Controls were defined as having no respiratory disease, no hay fever in the past year, and B-Eos count ≤0.3 × 109 l−1. Asthma was defined as self-reported current asthma and at least one episode of wheezing or an asthma attack in the past year, but no emphysema or chronic bronchitis. Tobacco use was collected via questionnaires and serum cotinine was measured with mass spectrometry.Results:Increasing cotinine levels were associated with a progressive reduction in FeNO in both controls and asthmatics. FeNO remained significantly higher in asthmatics than controls except in the highest cotinine decile, equivalent to an average reported consumption of 13 cigarettes/day. B-Eos count increased with cotinine in controls, but was unchanging in asthmatics. Interestingly, B-Eos count was significantly higher in presently non-exposed (cotinine below detection limit) former smokers than never smokers.Conclusion:Smoke exposure decreases FeNO and increases B-Eos count. These effects should be considered in the development of normalized values and their interpretation in clinical practice. The persistence of elevated B-Eos in former smokers warrants further studies.
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| 6. |
- Jacinto, Tiago, et al.
(författare)
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Evolution of exhaled nitric oxide levels throughout development and aging of healthy humans
- 2015
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Ingår i: Journal of Breath Research. - : IOP Publishing. - 1752-7155 .- 1752-7163. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Jacinto, Tiago, et al.
(författare)
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Exhaled NO reference limits in a large population-based sample using the Lambda-Mu-Sigma method
- 2018
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 125:5, s. 1620-1626
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Tidskriftsartikel (refereegranskat)abstract
- Absolute values are used in the interpretation of the fraction of exhaled nitric oxide (FeNO), but it has been suggested that equations to calculate reference values may be a practical and clinically useful approach. We hypothesize that the application of the Lambda-Mu-Sigma (LMS) method may improve FeNO reference equations and their interpretation. Our aims were to develop FeNO reference equations with the LMS method and to describe the difference between this method and the absolute fixed cut-offs of the current recommendations. We utilized the United States National Health and Nutrition Examination Surveys 2007-2012 and included healthy individuals with no respiratory diseases and blood eosinophils <300/mm(3) (n = 8,340). Natural log-transformed FeNO was modeled using the LMS method, imbedded in the generalized additive models for location, scale, and shape models. A set of FeNO reference equations was developed. The explanatory variables were sex, age, height, smoking habits, and race/ethnicity. A significant proportion of individuals with normal FeNO given by the equations were classified as having intermediate levels by the current recommendations. Further lower predicted FeNO compared with previous linear models was seen. In conclusion, we suggest a novel model for the prediction of reference FeNO values that can contribute to the interpretation of FeNO in clinical practice. This approach should be further validated in large samples with an objective measurement of atopy and a medical diagnosis of asthma and rhinitis. NEW & NOTEWORTHY Novel reference equations and fraction of exhaled nitric oxide (FeNO)-predicted values to improve interpretation of FeNO in clinical practice are presented. These may increase the accuracy of ruling out airway inflammation in patients with asthma or suspected asthma.
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| 8. |
- Jacinto, Tiago, et al.
(författare)
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Setting reference values for exhaled nitric oxide : a systematic review
- 2013
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Ingår i: Clinical Respiratory Journal. - 1752-6981 .- 1752-699X. ; 7:2, s. 113-120
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Forskningsöversikt (refereegranskat)abstract
- 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 individual-specific 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. R2 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.
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| 9. |
- Malinovschi, Andrei, et al.
(författare)
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Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects
- 2013
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 132:4, s. 821-
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Tidskriftsartikel (refereegranskat)abstract
- 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 reportedwheeze 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. Methods: FENO and B-Eos values were measured in 12,408 subjects aged 6 to 80 years from the National Health and Nutrition Examination Survey 2007-2008 and 2009-2010. Current wheeze and asthma diagnosis, as well as asthma attacks and asthma-related emergency department (ED) visits within the last 12 months, were assessed by means of questionnaires. Results: Intermediate or high FENO values and intermediate or high B-Eos values were independently associated with having asthma, wheeze, and asthma attacks. However, only intermediate and high B-Eos values were independently associated with asthma-related ED visits. High FENO (>= 50 ppb) and B-Eos (>= 500 cells/ mm(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(3)) values. Conclusions: Exhaled nitric oxide and B-Eos values offered independent information in relation to the prevalence of wheeze, asthma diagnosis, and asthma events in this random population sample. The clinical importance of these findings in asthmatic patients with regard to phenotyping and individualized treatment, considering both local and systemic eosinophilic inflammation, needs to be determined.
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| 10. |
- Mogensen, Ida, et al.
(författare)
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Inflammatory patterns in fixed airflow obstruction are dependent on the presence of asthma
- 2020
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Fixed airflow obstruction (FAO) can complicate asthma. Inflammation is a proposed underlying mechanism.Objective: Our aim in this cross-sectional investigation was to evaluate the blood leucocyte pattern and level of exhaled nitric oxide in asthmatics and non-asthmatics with or without FAO.Methods: A total of 11,579 individuals aged >= 20 years from the US National Health and Nutrition Examination Survey were included. They were grouped as: controls without asthma and FAO (n = 9,935), asthmatics without FAO (n = 674), asthmatics with FAO (n = 180) and non-asthmatics with FAO (n = 790). FAO was defined as post-bronchodilator FEV1/FVC < lower limit of normal. Exhaled nitric oxide >= 25ppb, blood eosinophil levels >= 300 cells/mu L, and blood neutrophil levels >= 5100 cells/mu L were defined as elevated. Stratified analyses for smoking and smoking history were performed.Results: Elevated blood eosinophil levels were more common in all groups compared to the controls, with the highest prevalence in the group with asthma and fixed airflow obstruction (p<0.01). In a multiple logistic regression model adjusted for potential confounders including smoking, the asthma groups had significantly higher odds ratios for elevated B-Eos levels compared to the control group (odds ratio 1.4, (confidence interval: 1.1-1.7) for the asthma group without fixed airflow obstruction and 2.5 (1.4-4.2) for the asthma group with fixed airflow obstruction). The group with fixed airflow obstruction without asthma had higher odds ratio for elevated blood neutrophil levels compared to the controls: 1.4 (1.1-1.8). Smoking and a history of smoking were associated to elevated B-Neu levels.Conclusion: Fixed airflow obstruction in asthma was associated with elevated blood eosinophil levels, whereas fixed airflow obstruction without asthma was associated with elevated blood neutrophil levels.
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