Clinical characteristics of the BREATHE cohort - a real-life study on patients with asthma and COPD.
ABSTRACT: Background: The BREATHE study is a cross-sectional study of real-life patients with asthma and/or COPD in Denmark and Sweden aiming to increase the knowledge across severities and combinations of obstructive airway disease. Design: Patients with suspicion of asthma and/or COPD and healthy controls were invited to participate in the study and had a standard evaluation performed consisting of questionnaires, physical examination, FeNO and lung function, mannitol provocation test, allergy test, and collection of sputum and blood samples. A subgroup of patients and healthy controls had a bronchoscopy performed with a collection of airway samples. Results: The study population consisted of 1403 patients with obstructive airway disease (859 with asthma, 271 with COPD, 126 with concurrent asthma and COPD, 147 with other), and 89 healthy controls (smokers and non-smokers). Of patients with asthma, 54% had moderate-to-severe disease and 46% had mild disease. In patients with COPD, 82% had groups A and B, whereas 18% had groups C and D classified disease. Patients with asthma more frequently had childhood asthma, atopic dermatitis, and allergic rhinitis, compared to patients with COPD, asthma + COPD and Other, whereas FeNO levels were higher in patients with asthma and asthma + COPD compared to COPD and Other (18 ppb and 16 ppb vs 12.5 ppb and 14 ppb, p < 0.001). Patients with asthma, asthma + COPD and Other had higher sputum eosinophilia (1.5%, 1.5%, 1.2% vs 0.75%, respectively, p < 0.001) but lower sputum neutrophilia (39.3, 43.5%, 40.8% vs 66.8%, p < 0.001) compared to patients with COPD. Conclusions: The BREATHE study provides a unique database and biobank with clinical information and samples from 1403 real-life patients with asthma, COPD, and overlap representing different severities of the diseases. This research platform is highly relevant for disease phenotype- and biomarker studies aiming to describe a broad spectrum of obstructive airway diseases.
Project description:Allergic rhinitis (AR) is a risk factor for asthma development. The value of fractional exhaled nitric oxide (FeNO) in detecting lower airway involvement in the progress of AR-asthma march has not been evaluated. The aim of the present study was to investigate the value of FeNO in assessing lower airway inflammation and predicting bronchial hyperresponsiveness (BHR) in AR with or without asthma. FeNO and eosinophil count in induced sputum, and a methacholine bronchial provocation test were performed in 93 subjects, including: 45 AR patients (AR group); 20 patients with AR and asthma (AR with asthma group); and 28 normal controls (control group). The AR group was divided into two sub-groups: AR with asymptomatic BHR group and AR without BHR group. Correlation between FeNO and eosinophil count was assessed. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive and diagnostic value of FeNO in detecting BHR. The values of FeNO in the AR and AR with asthma groups were higher [29.5 (22.0) ppb and 61.5 (33.0) ppb] compared with the normal control group (16.0 (10.0) ppb), where the values in brackets indicate the interquartile range of the values. The percentages of eosinophils in induced sputum were 2.43±3.56, 7.36±4.98 and 18.58±11.26% in the control, AR and AR with asthma groups, respectively. For the diagnosis of BHR, the area under the curve (AUC) was 0.910 (95%CI 0.836, 0.984), with the sensitivity and specificity 0.846 and 0.817 when the cut-off value takes 31.5 ppb. For diagnosis of asthma, the AUC was 0.873 (95%CI 0.753, 0.992) with sensitivity 0.857 and specificity 0.847 when taking the cut-off value to be 38.0 ppb. The value of FeNO was well correlated with eosinophil count in the sputum. The measurement of FeNO is an effective method in detecting lower airway involvement in AR developing to asthma.
Project description:The fractional exhaled nitric oxide measured at an expiratory flow of 50mL/s (FENO50) is a marker of airway inflammation, and high levels are associated with greater response to steroid treatment. In asthma, FENO50 increases with bronchodilation and decreases with bronchoconstriction, the latter potentially causing an underestimate of the degree of airway inflammation when asthma worsens. It is unknown whether the same effect occurs in chronic obstructive lung disease (COPD). Likewise, it is not known whether changes in airway calibre in COPD patients alter flow-independent parameters describing pulmonary nitric oxide exchange, such as the maximal flux of nitric oxide (NO) from the proximal airway compartment (J'awNO) and the distal airway/alveolar concentration of NO (CANO). We recruited 24 patients with COPD and performed FENO analysis at multiple expiratory flows before and after treatment with inhaled ?2-agonist bronchodilator therapy. For the 21 patients analysed, FENO50 rose from 17.1 (1.4) ppb (geometric mean (geometric SD)) at baseline, to 19.3 (1.3) ppb after bronchodilator therapy, an increase of 2.2 ppb (95% CI, 0.7-3.6; P = 0.005). There were non-significant changes in flow-independent NO parameters. The change in FENO50 correlated positively with the change in J'awNO (rs = 0.67, P < 0.001; rs = 0.62, P = 0.002 before and after correction for axial back-diffusion respectively) following bronchodilation. Inhaled bronchodilator therapy can increase exhaled nitric oxide measurements in COPD. The standardisation of inhaled bronchodilator therapy before FENO analysis in COPD patients should therefore be considered in both research and clinical settings.
Project description:Some patients with chronic obstructive pulmonary disease (COPD) have eosinophilic inflammation which may be evaluated via the measurement of fractional exhaled nitric oxide (FeNO) like asthma. The aim of this prospective study was to assess whether FeNO levels can be used to identify patients with COPD with eosinophilic inflammation who may respond to inhaled corticosteroid (ICS) therapy.This study included patients (N = 112) with COPD (age >18 years) who were divided into 4 groups depending upon whether they had high (≥25 parts per billion [ppb]) or low (<25 ppb) pretreatment (baseline) FeNO and if they were treated with either ICS plus long-acting β-agonist (ICS + LABA) or a long-acting muscarinic antagonist (LAMA). The 4 groups were: high FeNO/ICS + LABA, high FeNO/LAMA, low FeNO/ICS + LABA, and low FeNO/LAMA. Outcomes assessed included FeNO, COPD assessment test (CAT), and pulmonary function.The high FeNO/ICS + LABA group had the greatest reduction from baseline in FeNO levels (-25.80 ppb ± 27.14) compared with the high FeNO/LAMA, low FeNO/ICS + LABA, and low FeNO/LAMA groups (range, -4.45 to 1.31 ppb; P < .001). The high FeNO/ICS + LABA group also showed the greatest improvement in CAT (-7.20), which was statistically larger than the low FeNO/ICS + LABA and low FeNO/LAMA groups (-1.72 and -2.03, respectively). No difference in pulmonary function following treatment was observed across the 4 groups.This study found that patients with high FeNO showed the greatest reduction in FeNO and improvement in CAT with ICS + LABA therapy, supporting the use of FeNO to identify patients who would benefit from ICS use.
Project description:BACKGROUND:Fractional exhaled nitric oxide (FeNO) is regarded as a potential biomarker for identifying eosinophilic inflammation. We aimed to evaluate the clinical implication of FeNO and its influence on inhaled corticosteroids (ICS) prescription rate in Korean chronic obstructive pulmonary disease (COPD) patients. METHODS:FeNO level and its association with clinical features were analyzed. Changes in the prescription rate of ICS before and after FeNO measurement were identified. RESULTS:A total of 160 COPD patients were divided into increased (?25 parts per billion [ppb], n=74) and normal (<25 ppb, n=86) FeNO groups according to the recommendations from the American Thoracic Society. Compared with the normal FeNO group, the adjusted odds ratio for having history of asthma without wheezing and with wheezing in the increased FeNO group were 2.96 (95% confidence interval [CI], 1.40-6.29) and 4.24 (95% CI, 1.37-13.08), respectively. Only 21 out of 74 patients (28.4%) with increased FeNO prescribed ICS-containing inhaler and 18 of 86 patients (20.9%) with normal FeNO were given ICS-containing inhaler. Previous exacerbation, asthma, and wheezing were the major factors to maintain ICS at normal FeNO level and not to initiate ICS at increased FeNO level. CONCLUSION:Increased FeNO was associated with the history of asthma irrespective of wheezing. However, FeNO seemed to play a subsidiary role in the use of ICS-containing inhalers in real-world clinics, which was determined with prior exacerbation and clinical features suggesting Th2 inflammation.
Project description:Background:FeNO has been used as a marker for Th2-mediated airway inflammation in asthma. There is evidence which recommends the use of this biomarker in asthma management. Little is known about whether the FeNO test alone or in combination with the ACT score can reflect asthma control in Vietnamese patients. Materials and Methods:A cross-sectional study was conducted in asthmatic patients (?18 years old) recruited at the University Medical Center, Ho Chi Minh City, Vietnam from March 2016 to March 2017. Asthma control levels were assessed following the GINA 2017 guidelines, and FeNO was measured by a Niox Mino device. FeNO cut-offs predicting asthma control status were determined using the ROC curve analysis. The combination of FeNO and ACT was investigated in detecting well-controlled and uncontrolled asthma. The results of the study are as follows: 278 patients with 68% females, mean age of 44 years, and mean asthma duration of 10 years were analyzed. All patients were treated following step 2 to 4 of GINA guidelines. Mean (SD) FeNO was 30.6 (24) ppb. Patients with uncontrolled (16%), partly controlled (29%), and well-controlled asthma (55%) had a median (IQR) FeNO of 50.0 (74), 25.0 (23), and 21.0 (22.3) ppb, respectively, and the mean of FeNO in the uncontrolled group was significantly higher than that in other groups (p < 0.001). The area under the ROC curve (AUC) for FeNO detecting uncontrolled asthma was 0.730 with an optimal cut-off point of FeNO?>?50?ppb, and this AUC increased to 0.89 when combining FeNO and ACT. The AUC for FeNO detecting well-controlled asthma was 0.601 with an optimal cut-off point of FeNO <25?ppb and this AUC increased to 0.78 if combining FeNO and ACT. Conclusions:FeNO can predict asthma control status with an estimated cut-off point of <25?ppb for well-controlled and >50?ppb for uncontrolled asthma. The combination of FeNO and ACT provides better information regarding asthma control than FeNO alone, and this combination is useful to predict asthma control statuses in asthmatic patients in Viet Nam.
Project description:PURPOSE:To evaluate whether exhaled nitric oxide measurement can facilitate in the assessment of chronic cough patients based on their airway inflammatory phenotype. METHODS:We have studied consecutive patients attending a specialist cough clinic. 30 patients with high FeNO (> 30 ppb) and 20 patients with low FeNO (< 20 ppb) were recruited. RESULTS:There was a significant correlation between FeNO, B-Eos and sputum eosinophil count (p < 0.001). The number of recorded coughs in 24 h and HARQ scores were significantly (p < 0.05) higher in patients with a low FeNO. In contrast to the high FeNO group (48%), the greater proportion of these patients were women (90%). LCQ scores were worse in the low FeNO group but it was not significant. CONCLUSION:A strong relationship between FeNO, blood eosinophils and sputum eosinophils confirming phenotypic identity was observed. Whether the observed gender disparity accounts for the different cough frequency characteristics is unknown.
Project description:BACKGROUND: The fractional concentration of nitric oxide in exhaled air (FENO) is used as a biomarker of eosinophilic airway inflammation. FENO is increased in patients with asthma. The relationship between subjective asthma symptoms and airway inflammation is an important issue. We expected that the subjective asthma symptoms in women might be different from those in men. Therefore, we investigated the gender differences of asthma symptoms and FENO in a survey of asthma prevalence in university students. METHODS: The information about asthma symptoms was obtained from answers to the European Community Respiratory Health Survey (ECRHS) questionnaire, and FENO was measured by an offline method in 640 students who were informed of this study and consented to participate. RESULTS: The prevalence of asthma symptoms on the basis of data obtained from 584 students (266 men and 318 women), ranging in age from 18 to 24 years, was analyzed. Wheeze, chest tightness, an attack of shortness of breath, or an attack of cough within the last year was observed in 13.2% of 584 students. When 38.0 ppb was used as the cut-off value of FENO to make the diagnosis of asthma, the sensitivity was 86.8% and the specificity was 74.0%. FENO was ? 38.0 ppb in 32.7% of students. FENO was higher in men than in women. The prevalence of asthma symptoms estimated by considering FENO was 7.2%; the prevalence was greater in men (9.4%) than women (5.3%). A FENO ? 38.0 ppb was common in students who reported wheeze, but not in students, especially women, who reported cough attacks. CONCLUSIONS: The prevalence of asthma symptoms in university students age 18 to 24 years in Japan was estimated to be 7.2% on the basis of FENO levels as well as subjective symptoms. Gender differences were observed in both FENO levels and asthma symptoms reflecting the presence of eosinophilic airway inflammation. TRIAL REGISTRATION NUMBER: UMIN000003244.
Project description:INTRODUCTION:During the last decade, many articles have been published, including reviews on fractional exhaled nitric oxide (FeNO) use and utility in clinical practice and for monitoring and identifying eosinophilic airway inflammation, especially in asthma, and evaluating corticosteroid responsiveness. However, the exact role of FeNO in patients with chronic obstructive pulmonary disease (COPD) and its ability to distinguish patients with COPD and those having concomitant asthma, that is, asthma-COPD overlap (ACO) is still unclear and needs to be defined. Due to the broad topics of FeNO in chronic airway disease, we undertook a scoping review. The present article describes the protocol of a scoping review of peer-reviewed published literature specific to FeNO in COPD/ACO over the last decade. METHODS AND ANALYSIS:We used Joanna Briggs Institute Reviewers' Manual scoping review methodology as well as Levac et al's and Arksey et al's framework as guides. We searched a variety of databases, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science, and BioSciences Information Service (BIOSIS) on 29 June 2016. Additional studies will be recognised by exploring the reference list of identified eligible studies. Screening of eligible studies will be independently performed by two reviewers and any disagreement will be solved by the third reviewer. We will analyse the gathered data from article bibliographies and abstracts. ETHICS AND DISSEMINATION:To investigate the body of published studies regarding the role of FeNO in patients with COPD and its usefulness in the clinical setting, a scoping review can be used as a modern and pioneer model, which does not need ethics approval. By this review, new insights for conducting new research specific to FeNO in COPD/ACO population will emerge. The results of this study will be reported in the scientific meetings and conferences, which aim to provide information to the clinicians, primary care providers and basic science researchers.
Project description:<h4>Background</h4>Fractional exhaled nitric oxide (FENO) is a useful and noninvasive biomarker for eosinophilic airway inflammation, particularly in asthma. However, its utility in chronic obstructive pulmonary disease (COPD) remains controversial. In this study, we performed a systematic review and meta-analysis to evaluate FENO levels in COPD.<h4>Methods</h4>A search of PubMed, Embase, Cochrane Library, and clinical trial registry was conducted from inception to January 2018. Studies were included if they reported FENO levels in patients with COPD and healthy controls. We then extracted relevant information and analyzed data. Standard mean difference (SMD) with 95% confidence interval (CI) was applied in this meta-analysis.<h4>Results</h4>A total of 2,073 studies were reviewed for eligibility, with 24 studies pooled for analysis. The FENO levels in patients with COPD were elevated mildly compared with healthy controls (SMD 1.28, 95% CI 0.60-1.96). A similar result was also observed in stable COPD, with an SMD of 1.21 (95% CI 0.47-1.96). On the other hand, we found no association between FENO levels and exacerbated COPD. Additionally, for patients with COPD, ex-smokers had higher levels of FENO than current smokers (SMD 2.05, 95% CI 1.13-2.97).<h4>Conclusion</h4>Our studies demonstrated a mild elevation of FENO in COPD, and the association between exacerbated COPD and FENO levels needs to be further explored. The potential mechanism is still unknown and conflicting.
Project description:Studies on airway inflammation, measured as fraction of exhaled nitric oxide (FENO), have focused on its relation to control of asthma, but the contribution of allergen exposure to the increase in FENO levels is unknown.We evaluated (1) whether FENO levels were increased in children with allergic sensitization or asthma; (2) whether specific allergen exposure increased FENO levels in sensitized, but not unsensitized, children; and (3) whether sedentary behavior increased FENO levels independent of allergen exposures.At age 12 years, in a birth cohort of children with a parental history of allergy or asthma, we measured bed dust allergen (dust mite, cat, and cockroach) by means of ELISA, specific allergic sensitization primarily based on specific IgE levels, and respiratory disease (current asthma, rhinitis, and wheeze) and hours of television viewing/video game playing by means of questionnaire. Children performed spirometric maneuvers before and after bronchodilator responses and had FENO levels measured by using electrochemical detection methods (NIOX MINO).FENO levels were increased in children with current asthma (32.2 ppb), wheeze (27.0 ppb), or rhinitis (23.2 ppb) compared with subjects without these respective symptoms/diagnoses (16.4-16.6 ppb, P < .005 for all comparisons). Allergic sensitization to indoor allergens (cat, dog, and dust mite) predicted higher FENO levels and explained one third of the variability in FENO levels. FENO levels were highest in children both sensitized and exposed to dust mite. Greater than 10 hours of weekday television viewing was associated with a 0.64-log increase in FENO levels after controlling for indoor allergen exposure, body mass index, and allergic sensitization.Allergen exposures and sedentary behavior (television viewing/video game playing) might increase airway inflammation, which was measured as the FENO.