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- Demey, Lucas, et al.
(författare)
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Exploring the sites and kinetics of bronchodilator response to ß-2 agonists in asthma
- 2021
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 130:4, s. 1106-1113
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Tidskriftsartikel (refereegranskat)abstract
- We previously documented, in patients with asthma, three different profiles of bronchodilation induced by short-acting beta-2 mimetics (SABA), characterized by dilation up to central, preacinar, and intra-acinar airways assessed by ventilation distribution tests and associated with no change, increase, and decrease of fractional exhaled nitric oxide concentration (FENO), respectively. To investigate the dynamics of these profiles over the entire SABA action period, assuming that bronchodilation of proximal and peripheral airways could exhibit varying kinetics due to differences in the distribution of beta-2 receptors in both the central and peripheral human airways. FENO, forced expired volume in one second (FEV1), and the slope (S) of He and SF6 phase III (single-breath test) were measured in asthma patients before, and up to 6 h after SABA inhalation (salbutamol 400 mu g). S-He and S-SF6 decrease reflects pre- and intra-acinar obstruction relief, respectively. Thirty patients with asthma (12F/18M, aged 45 +/- 18 yr) were divided into groups with positive (NO +, n = 9), negative (NO-, n = 11), and no (NO=, n = 10) FENO acute change. In the NO- group, FEV1 increased for up to 4 h, whereas FENO, S-He, and S-F6 decreased in the early phase only. In stark contrast, in the NO - group, FEV1 increased in the early phase only whereas the FENO increase and the S-He decrease lasted for up to 4 h. This study documents various profiles of SABA-induced bronchodilation in patients with asthma, differing both by sites and dynamics of the bronchodilator process. So, detailed understanding of the bronchodilator effect of beta 2-agonists in asthma should not solely be limited to studying their impact on FEV1. NEW & NOTEWORTHY FEV1 increase usually observed after the inhalation of short-acting beta 2-agonists in asthma patients tends to involve peripheral airways. This study shows that the heterogeneity of responses to short-acting beta 2-agonists in asthma not only involves distinct sites of bronchodilation, but also distinct sequences between these sites. This indicates that a detailed understanding of the bronchodilator effect of beta 2-agonists in asthma should not be limited to studying its early impact on FEV1.
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| 3. |
- Haccuria, Amaryllis, et al.
(författare)
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Small airways dysfunction : the link between allergic rhinitis and allergic asthma
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 51:2
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal airway reactivity and overproduction of nitric oxide (NO) occurring in smallairways have been found in asthma. If the“one airway, one disease”concept is consistent, suchdysfunctions should also be detected in the peripheral airways of patients suffering from allergicrhinitis.We investigated whether peripheral airway reactivity and NO overproduction could bedocumented in distal airways in patients with allergic rhinitis. Exhaled NO fraction (FeNO)andtheslope (S) of phase III of the single-breath washout test (SBWT) of helium (He) and sulfurhexafluoride (SF6)weremeasuredin31patientswithallergicasthma,23allergicrhinitispatientsand 24 controls, before and after sputum induction. SBWT is sensitive to airway calibre changeoccurring in the lung periphery.TheFeNOdecrease was more significant in asthma and rhinitis than in controls (−55.1% and−50.0%,respectively,versus−40.8%) (p=0.007 and p=0.029, respectively). SSF6and SHeincreased in all groups.Change in SHe(ΔSHe)>ΔSSF6was observed in rhinitis (p=0.004) and asthma (p<0.001), whereasΔSSF6=ΔSHein controls (p=0.431).This study provides evidence of peripheral airway dysfunction in patients with allergic rhinitis quitesimilar to that described in asthma. Furthermore, a large proportion of the increased NO productionreported in allergic rhinitis appears to originate in the peripheral airways.
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| 4. |
- Malinovschi, Andrei, et al.
(författare)
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FeNO as a predictor of asthma control improvement after starting inhaled steroid treatment
- 2014
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Ingår i: Nitric oxide. - : Elsevier BV. - 1089-8603 .- 1089-8611. ; 40, s. 110-116
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The fraction of NO in exhaled air (FeNO) is a marker of inflammation in asthma. The aim of the present study was to assess, in a real-world setting, whether only high ( >= 50 ppb) FeNO levels predict improvement in asthma control when being treated with inhaled corticosteroids (ICS), as suggested by current guidelines on the clinical use of FeNO. Methods: FeNO and asthma control were assessed in a retrospective observational study in 153 non-smoking, steroid-nave, adult subjects with asthma with a mean age of 40 years both before and after 6 weeks (median follow-up time) of treatment with 500 mu g beclomethasone (median). Results: Having at the initial visit intermediate FeNO ( >= 25 and <50 ppb) and high FeNO ( >= 50 ppb), compared to normal FeNO (<25 ppb), were associated with a larger proportion of subjects achieving an improvement of Asthma Control Questionnaire (ACQ) score with >= 1 (78% and 67% vs 43%, p <0.05) or both >= 1 improvement and asthma control at follow-up (31% and 37% vs 4%, p < 0.05). These associations were consistent in multiple logistic regression models after adjustments for confounders. Conclusions: It is not only high but also intermediate FeNO levels that are associated with a significant improvement in asthma control after starting ICS treatment. This challenges current clinical guidelines stating that only high FeNO levels predict response to ICS treatment.
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| 8. |
- Michils, Alain, et al.
(författare)
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Different patterns of exhaled nitric oxide response to β2-agonists in asthmatic patients according to the site of bronchodilation
- 2016
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 137:3, s. 806-812
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In asthmatic patients undergoing airway challenge, fraction of exhaled nitric oxide (Feno) levels decrease after bronchoconstriction. In contrast, model simulations have predicted both decreased and increased Feno levels after bronchodilation, depending on the site of airway obstruction relief.OBJECTIVE: We sought to investigate whether β2-agonists might induce divergent effects on Feno values in asthmatic patients as a result of airway obstruction relief occurring at different lung depths.METHODS: Feno, FEV1, and the slope of phase III of the single-breath washout test (S) of He (SHe) and sulfur hexafluoride (SSF6) were measured in 68 asthmatic patients before and after salbutamol inhalation. SHe and SSF6 decreases reflected preacinar and intra-acinar obstruction relief, respectively. Changes (Δ) were expressed as a percentage from the baseline.RESULTS: No Feno change (|ΔFeno| ≤ 10%) was found in 16 patients (mean [SD]: 2.5% [5.2%]; ie, Feno= group); a ΔFeno value of greater than 10% was found in 23 patients (31.7% [20.3%]; ie, the Feno+ group); and a ΔFeno value of less than -10% was found in 29 patients (-31.5% [17.3%]; ie, the Feno- group). All groups had similar ΔFEV1 values. In the Feno= group neither SHe nor SSF6 changed, in the Feno+ group only SHe decreased significantly (-21.8% [SD 28.5%], P = .03), and in the Feno- group both SHe (-29.8% [24.0%], P < .001) and SSF6 (-27.2% [23.3%], P < .001) decreased.DISCUSSION: Three Feno behaviors were observed in response to β2-agonists: a decrease likely caused by relief of an intra-acinar airway obstruction that we propose reflects amplification of nitric oxide back-diffusion, an increase likely associated with a predominant dilation up to the preacinar airways, and Feno stability when obstruction relief involved predominantly the central airways. In combination, these results suggest a new role for Feno in identifying the site of airway obstruction in asthmatic patients.
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| 10. |
- Michils, Alain, et al.
(författare)
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The Impact of Airway Obstruction on Feno Values in Asthma Patients.
- 2024
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 2213-2198 .- 2213-2201. ; 12:1, s. 111-117
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exhaled nitric oxide (Feno) is used as a marker of type-2 airway inflammation in asthma management. Studies with airway challenges demonstrated that a reduction in airway caliber decreases Feno levels.OBJECTIVE: To evaluate the impact of airway caliber reduction occurring spontaneously in patients with asthma on Feno values in daily clinical practice.METHODS: In this post hoc analysis, Feno, FEV1, and asthma control questionnaire scores were recorded on each visit for 120 (1073 visits) adult patients with asthma. Blood eosinophils were measured intermittently. The intraindividual relationship between Feno and FEV1 was evaluated via a linear mixed model. The determinants of the individual mean Feno were measured by a stepwise multivariate linear model including individual mean FEV1, inhaled corticosteroid dose, asthma control questionnaire score, and blood eosinophils.RESULTS: Variations in the negative Feno-FEV1 relationship within individuals at different times were significantly determined by the individual's mean FEV1. This relationship did not hold for individuals above the 75th and below the 25th quartiles. The best explanatory variables for individual mean Feno were FEV1 (+4.3 parts per billion/10%pred) and blood eosinophil count (+1 part per billion per 100 cells/mm3).DISCUSSION: In the presence of variable degrees of heterogeneous patterns of airway inflammation, airway caliber is shown to be an independent and significant determinant of Feno when measured in patients with asthma. We would propose a +4-parts-per-billion correction factor to the measured Feno value for each 10% reduction below 100% predicted FEV1. Doing this should improve the rigor of interpretation of Feno as an indicator of type-2 inflammation in patients with low FEV1.
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