Fractional Exhaled Nitric Oxide Nonsuppression Identifies Corticosteroid-Resistant Type 2 Signaling in Severe Asthma.
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ABSTRACT:
SUBMITTER: Couillard S
PROVIDER: S-EPMC8521703 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
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Fractional Exhaled Nitric Oxide Nonsuppression Identifies Corticosteroid-Resistant Type 2 Signaling in Severe Asthma.
Couillard Simon S Shrimanker Rahul R Chaudhuri Rekha R Mansur Adel H AH McGarvey Lorcan P LP Heaney Liam G LG Fowler Stephen J SJ Bradding Peter P Pavord Ian D ID Hinks Timothy S C TSC
American journal of respiratory and critical care medicine 20210901 6
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Project description:BackgroundBlood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO) concentration are established biomarkers in asthma, associated particularly with the risk of exacerbations. We evaluated the relationship of BEC and FeNO as complementary and independent biomarkers of severe asthma exacerbations.MethodsThis observational study included data from the Optimum Patient Care Research Database. Asthma patients (18-80 years) with valid continuous data for 1 year before FeNO reading, ≥ 1 inhaled corticosteroid prescription, and BEC recorded ≤ 5 years before FeNO reading were separated into cohorts. Categorisation 1 was based on the American Thoracic Society criteria for elevated FeNO concentration (high: ≥ 50 ppb; non-high: < 25 ppb) and BEC (high: ≥ 0.300 × 109 cells/L; non-high: < 0.300 × 109 cells/L). Categorisation 2 (FeNO concentration, high: ≥ 35 ppb; non-high: < 35 ppb) was based on prior research. Reference groups included patients with neither biomarker raised.ResultsIn categorisation 1, patients with either high FeNO or high BEC (n = 200) had a numerically greater exacerbation rate (unadjusted rate ratio, 1.31 [95% confidence interval: 0.97, 1.76]) compared with patients in the reference group. Combination of high FeNO and high BEC (n = 27) resulted in a significantly greater exacerbation rate (3.67 [1.49, 9.04]). Similarly, for categorisation 2, when both biomarkers were raised (n = 53), a significantly greater exacerbation rate was observed (1.72 [1.00, 2.93]).ConclusionThe combination of high FeNO and high BEC was associated with significantly increased severe exacerbation rates in the year preceding FeNO reading, suggesting that combining FeNO and BEC measurements in primary care may identify asthma patients at risk of exacerbations.
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Project description:ObjectiveFractional exhaled nitric oxide (FeNO) is a well-established measure of allergic airway inflammation and possible useful adjunct disease management tool. We investigated the association of baseline and follow-up FeNO measurements with disease burden in minority children with persistent asthma.MethodsA retrospective chart review was conducted on 352 African American and Hispanic children seen at an urban Asthma Center in Bronx, NY. Demographic, clinical characteristics, and pulmonary function tests (PFTs) were compared between children with low, intermediate, and high baseline FeNO levels. Among 95 children with subsequent follow up visits, associations of change in FeNO with demographics, clinical characteristics, and PFTs were examined using mixed effects linear regression models.ResultsA higher proportion of children with intermediate (54%) and high FeNO (58%) levels had lower airways obstruction compared to those with low FeNO levels (33%). Children with intermediate FeNO levels had more annual hospitalizations (2.8 ± 6.2) compared to those with low and high FeNO levels (1.3 ± 2.8 and 1.3 ± 2.5). These associations did not differ between ethnicities. An increase in FeNO over time was associated with higher BMI z-scores (β = 6.2, 95% CI: 1.0 to 11.4) and two or more hospitalizations in the past year (β = 16.1, 95% CI: 1.5 to 30.8).ConclusionsIntermediate and high FeNO levels are associated with lower airways obstruction and hospitalizations. Initial and serial FeNO measurements can be a useful adjunctive tool in identifying asthma-related morbidity in urban African American and Hispanic children.
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Project description:Asthma is the most prevalent pediatric chronic disease. Bronchodilator drug response (BDR) and fractional exhaled nitric oxide (FeNO) are clinical biomarkers of asthma. Although DNA methylation (DNAm) contributes to asthma pathogenesis, the influence of DNAm on BDR and FeNO is scarcely investigated. This study aims to identify DNAm markers in whole blood associated either with BDR or FeNO in pediatric asthma. We analyzed 121 samples from children with moderate-to-severe asthma. The association of genome-wide DNAm with BDR and FeNO has been assessed using regression models, adjusting for age, sex, ancestry, and tissue heterogeneity. Cross-tissue validation was assessed in 50 nasal samples. Differentially methylated regions (DMRs) and enrichment in traits and biological pathways were assessed. A false discovery rate (FDR) < 0.1 and a genome-wide significance threshold of p < 9 × 10-8 were used to control for false-positive results. The CpG cg12835256 (PLA2G12A) was genome-wide associated with FeNO in blood samples (coefficient= -0.015, p = 2.53 × 10-9) and nominally associated in nasal samples (coefficient = -0.015, p = 0.045). Additionally, three CpGs were suggestively associated with BDR (FDR < 0.1). We identified 12 and four DMRs associated with FeNO and BDR (FDR < 0.05), respectively. An enrichment in allergic and inflammatory processes, smoking, and aging was observed. We reported novel associations of DNAm markers associated with BDR and FeNO enriched in asthma-related processes.
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Project description:Current methods to assess asthma and guide inhaled corticosteroid (ICS) dose titration mainly centre on patient-reported symptoms and lung function assessments. However, these methods correlate only weakly with airway inflammation making them unreliable predictors of future exacerbations and ICS requirement. Fractional Exhaled Nitric Oxide (FeNO) is a simple non-invasive objective measure of airways inflammation used predominantly in specialist clinics. Previous qualitative studies have mainly focused on the acceptability of FeNO in secondary care and there is limited insight to support clinicians and patients using FeNO in primary care asthma reviews. This study aimed to explore adult patient with asthma and primary care health care professional (HCP) views on introducing FeNO as part of routine asthma reviews. Twenty-three health care professionals and 22 patients were interviewed over the phone or online. Both groups reported that current asthma reviews are often seen as tick-box exercises and that introducing the FeNO test would make reviews more tailored to the individual patient, rather than relying on subjective patient reports of asthma control. Adults with asthma also highlighted support more open communication and their understanding of asthma, as they desired to feel more engaged in decisions and conversations about their asthma. HCPs reported valuing patient education and empowerment over a paternalistic approach, when time and resources allow. They also recognised FeNO to provide an objective measure of inflammation that could support them in the education and empowerment of patients. FeNO was seen by both groups as a potentially valuable addition to current asthma reviews mainly led by nurses, both for increasing their understanding of current risk of exacerbation and also to provide more tailored and personalised asthma management to patients. Our findings highlighted the need for open and clear communication about how to interpret FeNO results.
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Project description:BackgroundAsthma and lipid metabolism are associated with systemic inflammation. However, the studies about the relationship between lipid profile, fractional exhaled nitric acid (FeNO) and pulmonary function test (PFT) results are currently lacking.MethodsWe enrolled asthma patients who had serum lipid profiles including apolipoprotein levels from March 1, 2019 to December 31, 2019. We classified the asthma patients into two groups according to the diagnosis method: (I) patients who were diagnosed based on clinical symptoms/signs and PFT results and (II) patients diagnosed with clinical symptoms/signs. Clinical characteristics including age, underlying diseases, smoking status, allergy test results and treatment agents were compared between the two groups. The associations between blood cholesterol levels including apolipoprotein and pulmonary functions were analyzed. Moreover, patients were divided into two groups according to the median value of apolipoprotein B (Apo B), and lung function test results were compared between the patients who had high and low Apo B levels.ResultsAmong the 167 patients, 93 (55.7%) were PFT-proven asthma patients. In PFT-proven asthma patients, the levels of total cholesterol (TC) (r =0.37, P=0.03), low-density lipoprotein (LDL) (r =0.46, P=0.01) and Apo B (r =0.38, P=0.02) showed a significant correlation with FeNO, which had no statistical significance in physician-diagnosed asthma group. In multivariate regression analysis, log (FeNO) showed a significant correlation with Apo B (P<0.01) after adjustment for presence of PFT-proven asthma (P=0.01) and current smoking (P=0.01). Patients with high Apo B levels had a lower post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio (69.8 vs. 74.9, P=0.02) and lower post-BD FEV1 (%) (77.5 vs. 85.0, P=0.04) compared with those showing low Apo B levels.ConclusionsThe levels of Apo B and FeNO had positive correlations and high Apo B levels were associated with severe airflow obstruction and low FEV1 (%). Apo B could reflect the uncontrolled status of bronchial asthma and poor lung function.
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Project description:PurposeFractional exhaled nitric oxide (FeNO) has emerged as an important biomarker in asthma. Increasing evidence points to atopy as a confounding factor in the interpretation of elevated FeNO. We conducted a longitudinal study to understand the clinical significance of FeNO as an inflammatory biomarker.MethodsWe identified 19 children aged 13-15 years at baseline with a significant elevation in FeNO ≥ 80 parts per billion (ppb) and randomly selected a group of children of similar age with a moderate elevation (40-79 ppb) and normal-to-low FeNO (<40 ppb). Between November 2010 and July 2011, three additional study visits were conducted.ResultsNinety-three children participated in the study. There were 16, 24, and 53 participants in the high, mid, and low FeNO groups. During 1.5 years of follow-up, mean FeNO levels were 82.6 ppb (standard deviation [SD] = 65.9) for atopic asthmatics, 50.6 ppb (SD = 42.6) for nonasthmatic atopics, 17.0 ppb (SD = 10.8) for nonatopic asthmatics, and 17.8 ppb (SD = 13.9) for nonatopic nonasthmatics (p < 0.001). FeNO levels remained stable: 63 % of the high FeNO group had a FeNO ≥ 80 across all 4 measurements and 87 % of the normal-to-low FeNO group had a FeNO of <40 across all 4 measurements. The high FeNO group also was found to have an elevation in IL-5 (p = 0.04), IL-6 (p = 0.003), IL-10 (p = 0.002), and total serum IgE (p < 0.001), after adjustment by age, sex, height, body mass index, and atopy and asthma status.ConclusionsAn elevation of FeNO appears to indicate an atopic phenotype regardless of an asthma diagnosis, clinical symptoms, or corticosteroid use. An elevation of FeNO also is associated with a systemic elevation in inflammatory cytokines.
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Project description:BackgroundAlthough the efficacy of corticosteroid treatment in controlling asthma is widely accepted, its effectiveness is undermined by poor adherence. However, the optimal method for measuring adherence to asthma therapy remains unclear.ObjectiveTo perform a review of the literature reporting biological, objective methods for assessing adherence to inhaled or oral corticosteroids in asthma; we included studies reporting direct measurement of exogenous corticosteroids in blood, or the effect of adherence on exhaled nitric oxide.DesignWe searched three databases MEDLINE (using both PubMed and Ovid), the Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Web of Science for articles published between January 1975 and July 2020. Quality of the studies was assessed using the National Institute of Health checklist.ResultsFrom 2850 screened articles, 26 fulfilled the inclusion criteria. Measurement of blood prednisolone with or without cortisol was used in eight studies as a measure of oral corticosteroid adherence, and fractional exhaled nitric oxide (FeNO) in 17 studies for inhaled corticosteroid adherence. Inhaled corticosteroids were measured directly in the blood in one study. By direct measurement of drug levels in the blood, adherence rates to oral corticosteroids ranged from 47% to 92%, although the performance and timing of the test were often not known, making interpretation of findings and serum prednisolone concentrations difficult. FeNO is generally lower in adherent than non-adherent patients, but no absolute cut-off can be proposed based on the available data. However, a fall in FeNO following supervised inhaled corticosteroid dosing could indicate previous poor adherence.Conclusions and clinical relevanceDespite prednisolone and cortisol levels commonly being used as adherence markers in clinical practice, further work is required to assess the influence of the dose and timing on blood levels. The promising findings of FeNO suppression testing should be explored in further prospective studies.
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Project description:BackgroundThe current study aimed to explore the value of fractional exhaled nitric oxide (FeNO), exhaled carbon monoxide (eCO), and pulmonary function in the management of asthmatic children.MethodsOne hundred children diagnosed with asthma were selected as research subjects. Patients were divided into a 3-5-year-old group and a group with children 6 years and older. They were also grouped depending on whether they had asthma alone (A0 group) or whether their asthma was complicated with allergic rhinitis (A+AR group). The FeNO, eCO levels, and pulmonary function in the acute attack period were analyzed 1 month after treatment and clinical remission period.ResultsAsthmatic children demonstrated greater pulmonary dysfunction and significantly higher FeNO and eCO during the acute attack phase compared to both one month after treatment and clinical remission. The remission phase was characterized by decreased levels of FeNO and eCO and improvement of pulmonary function. The eCO levels in children aged 3-5 years old, and both FeNO and eCO levels in children 6 years and older were statistically lower during remission regardless of whether the patients had asthma alone or asthma complicated with rhinitis. However, 10% of the 100 children in the clinical remission period still demonstrated mid to high levels of FeNO. The critical value of FeNO levels during the acute period in children 6 years and older with asthma and rhinitis was 34.5 ppb (AUROC 0.814, 95% CI: 0.684-0.944) with a sensitivity of 69.2% and specificity of 93.7%.ConclusionsDynamic monitoring of FeNO and eCO is an effective indicator of airway inflammation and thus represents an important clinical tool in assessing the severity of asthma in children.
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