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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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| 5. |
- 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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| 6. |
- Perez-Bogerd, Silvia, et al.
(författare)
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COPD patients with peripheral airway obstruction reversibility identified by exhaled nitric oxide
- 2019
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Ingår i: Journal of Breath Research. - : IOP Publishing. - 1752-7155 .- 1752-7163. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Rationale:Besides its role as an inflammatory marker in asthma, fractional exhaled nitric oxide (FENO) provides information on the extent of the airway obstruction process through evaluating its change after bronchodilation.Objective:To investigate whether FENO change after bronchodilation can identify different sites of airway obstruction in COPD patients.Methods:FENO, FEV(1 )and the slopes (S) of the alveolar plateau of the single breath washout test (SBWT) were measured in 61 stable COPD patients (FEV1 34.5% predicted) before and after the inhalation of 400 mu g salbutamol. SBWT used Helium (He), and sulfur-hexafluoride (SF6). Obstruction relief occurring in pre-acinar and intra-acinar small airways is expected to decrease S-He and S-F6 , respectively. Indices changes (Delta) after bronchodilation were expressed as a percentage of pre-bronchodilation values.Results:FENO stability (vertical bar Delta FENO vertical bar <= 11%) was observed in 19 patients [-2.7(6.7)%] [mean (SD)] (NO = group); Delta FENO > 11% [+37.4(27.7)%] in 20 patients (NO+group) and Delta FENO < -11% in 22 patients [-31.2(9.8)%] (NO- group). A similar Delta FEV1 (p = 0.583; [+9.4(9.6)%]) was found in the three groups. In NO = and NO+ groups, neither S-He nor S-SF6 changed; in NO- both S-He [-12.4(27.5)%, p = 0.007] and S-SF6 [ -20.2(20.4)%, p < 0.001] significantly decreased.Conclusion:Different patterns of FENO response to beta(2) -agonists were observed in COPD most likely depending on the extent of the dilation process. A profile of airway obstruction with an extensive beta(2) -agonist response down to lung periphery is identified by FENO reduction after acute bronchodilation in 30% of COPD patients. The clinical relevance of this profile requires further investigation.
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| 7. |
- Perez-Bogerd, Silvia, et al.
(författare)
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LAMA improve tissue oxygenation more than LABA in patients with COPD
- 2024
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 137:1, s. 154-165
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Tidskriftsartikel (refereegranskat)abstract
- Background The effect of bronchodilators is mainly assessed with forced expiratory volume in 1s (FEV1) in COPD. Their impact on oxygenation and lung periphery is less known. Objectives To compare the action of long-acting ß2-agonists (LABA-olodaterol) and muscarinic antagonists (LAMA-tiotropium) on tissue oxygenation in COPD, considering their impact on proximal and peripheral ventilation as well as lung perfusion. Methods FEV1, Helium slope (SHe) from a single-breath washout test (SHe decrease reflecting a peripheral ventilation improvement), frequency dependence of resistance (R5-R19), area under reactance (AX), lung capillary blood volume (Vc) from double diffusion (DLNO/DLCO) and transcutaneous oxygenation (TcO2) were measured before and 2 hours post-LABA (day 1) and LAMA (day 3) in 30 COPD patients (FEV1 54±18% pred; GOLD A 31%/B 48%/E 21%) after 5-7 days of washout, respectively. Results TcO2 increased more (p=0.03) after LAMA (11±12%from baseline, p<0001) compared to LABA (4±11%, p=0.06) despite a lower FEV1 increase (p=0.03) and similar SHe (p=0.98), AX (p=0.63) and R5-R19 decreases (p=0.37). TcO2 and SHe changes were negatively correlated (r=-0.47, p=0.01) after LABA, not after LAMA (r=0.10, p=0.65). DLNO/DLCO decreased and Vc increased after LAMA (p=0.04; p=0.01, respectively) but not after LABA (p=0.53; p=0.24). Conclusion LAMA significantly improved tissue oxygenation in COPD patients, while only a trend was observed with LABA. The mechanisms involved may differ between both drugs: LABA increased peripheral ventilation while LAMA increased lung capillary blood volume. Should oxygenation differences persist over time, LAMA could arguably become the first therapeutic choice in COPD.
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