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1.
Lung ; 202(4): 441-448, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39007944

RESUMEN

BACKGROUND: Nasal polyposis (NP) is a comorbidity of type 2 severe asthma (SA) which could influence response to SA biologics. METHODS: We evaluated (super-) response in SA patients with (NP +) and without NP (NP-) enrolled in the Belgian Severe Asthma Registry (BSAR). RESULTS: 914 patients, of whom 31% NP + , were included. At enrollment, NP + patients had higher annual exacerbation rates, higher number of emergency room visits and more elevated type 2 biomarkers. In the longitudinal subanalysis of 104 patients, both groups had significant and similar asthma responses to asthma biologics, except for a greater increase in FEV1 in the NP + group. Super-response was achieved in 33 patients (32%), irrespective of NP status or type of biologic. CONCLUSION: In conclusion, both NP + and NP - patients had positive treatment responses, with some able to achieve super-response. In SA patients with NP, a greater FEV1 improvement as compared to SA patients without NP was observed.


Asunto(s)
Asma , Productos Biológicos , Pólipos Nasales , Sistema de Registros , Humanos , Asma/tratamiento farmacológico , Asma/fisiopatología , Asma/epidemiología , Masculino , Femenino , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/complicaciones , Pólipos Nasales/epidemiología , Persona de Mediana Edad , Bélgica/epidemiología , Adulto , Productos Biológicos/uso terapéutico , Volumen Espiratorio Forzado , Índice de Severidad de la Enfermedad , Antiasmáticos/uso terapéutico , Anciano , Resultado del Tratamiento , Omalizumab/uso terapéutico , Anticuerpos Monoclonales Humanizados
2.
J Asthma ; 58(4): 448-458, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-31928102

RESUMEN

OBJECTIVE: Patients with severe asthma require high-dose inhaled corticosteroids, with or without add-on treatments, to maintain asthma control. Because symptom control remains unsatisfactory in some patients despite these therapies, maintenance therapy with oral corticosteroids (OCS) remains considered a treatment option by physicians. Besides physician-diagnosed exacerbations, many patients intermittently self-medicate with OCS during episodes of worsening symptoms or as a prevention of such episodes. However, long-term OCS use is associated with several comorbidities that may decrease health-related quality of life, worsen prognosis, and should ideally require monitoring and management. In this review, we discuss the adverse effects of OCS use, the OCS-sparing effect of biologics in severe asthma, and the need for optimal referral pathways to ensure the best outcomes for those at-risk asthma patients. DATA SOURCES: PubMed. STUDY SELECTION: Studies with results on the OCS-sparing effect of biologics in adult severe asthma were selected. RESULTS: Chronic and intermittent OCS use in asthma is associated with considerable adverse effects in asthma. Omalizumab, mepolizumab, benralizumab, and dupilumab reduce the need for OCS in severe asthma, while also reducing the exacerbation rate and improving several patient-related outcomes. CONCLUSION: Targeted biologic therapies have revolutionized the treatment of uncontrolled severe asthma by reducing or even eliminating the need for OCS and improving other major outcomes. Novel agents are now rapidly increasing the therapeutic armamentarium, but additional efforts are needed to optimize referral pathways in order to ensure sustainable access to these therapies.


Asunto(s)
Corticoesteroides/uso terapéutico , Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Antiasmáticos/administración & dosificación , Antiasmáticos/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Preparaciones de Acción Retardada , Humanos , Derivación y Consulta , Índice de Severidad de la Enfermedad
4.
Eur Respir J ; 51(2)2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29467201

RESUMEN

Abnormal airway reactivity and overproduction of nitric oxide (NO) occurring in small airways have been found in asthma. If the "one airway, one disease" concept is consistent, such dysfunctions should also be detected in the peripheral airways of patients suffering from allergic rhinitis.We investigated whether peripheral airway reactivity and NO overproduction could be documented in distal airways in patients with allergic rhinitis. Exhaled NO fraction (FeNO) and the slope (S) of phase III of the single-breath washout test (SBWT) of helium (He) and sulfur hexafluoride (SF6) were measured in 31 patients with allergic asthma, 23 allergic rhinitis patients and 24 controls, before and after sputum induction. SBWT is sensitive to airway calibre change occurring in the lung periphery.The FeNO decrease 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). SSF6 and SHe increased in all groups. Change in SHe (ΔSHe) > ΔSSF6 was observed in rhinitis (p=0.004) and asthma (p<0.001), whereas ΔSSF6 = ΔSHe in controls (p=0.431).This study provides evidence of peripheral airway dysfunction in patients with allergic rhinitis quite similar to that described in asthma. Furthermore, a large proportion of the increased NO production reported in allergic rhinitis appears to originate in the peripheral airways.


Asunto(s)
Asma/fisiopatología , Hipersensibilidad/fisiopatología , Rinitis Alérgica/fisiopatología , Adulto , Asma/complicaciones , Pruebas Respiratorias , Estudios de Casos y Controles , Femenino , Volumen Espiratorio Forzado , Helio/química , Humanos , Hipersensibilidad/complicaciones , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Estudios Prospectivos , Rinitis Alérgica/complicaciones , Espirometría , Esputo , Hexafluoruro de Azufre/química , Adulto Joven
5.
Eur Respir J ; 50(2)2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28818874

RESUMEN

Changes in airway calibre have the potential to modify exhaled nitric oxide fraction (FENO) values and could hamper how FENO captures changes in asthma control. Here, our objective was to assess whether forced expiratory volume in 1 s (FEV1) variations alter the ability of FENO to reflect asthma control.FENO, asthma control (Asthma Control Questionnaire (ACQ)) and FEV1 were measured at least two times in 527 patients during 1819 pairs of visits. Determinants of FENO-ACQ discordance probability were evaluated through a logistic regression analysis. The effectiveness of FENO at capturing either asthma control worsening or improvement between two visits was then assessed by undertaking a stratified receiver operating characteristic curves analysis.When FEV1 and FENO change in the same direction, the odds of FENO-ACQ being discordant are multiplied by 3 (p<0.001). The area under the curve values were 0.765 (95% CI 0.713-0.805) (improvement; p<0.001) and 0.769 (95% 0.706-0.810) (worsening; p<0.001) or 0.590 (95% 0.531-0.653) (improvement; p=0.001) and 0.498 (95% 0.416-0.567) (worsening; p=0.482) when FEV1 and FENO changed in the opposite or same direction, respectively.The manner in which FENO and FEV1 vary concomitantly when asthma control changes determines the ability of FENO to capture this change: parallel or opposite changes in FEV1 and FENO either decrease or increase this ability to capture asthma control changes.


Asunto(s)
Manejo de la Vía Aérea/métodos , Asma , Óxido Nítrico/análisis , Sistema Respiratorio , Adulto , Asma/diagnóstico , Asma/fisiopatología , Asma/terapia , Bélgica , Bronquios/patología , Bronquios/fisiopatología , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Pruebas de Función Respiratoria/métodos , Sistema Respiratorio/patología , Sistema Respiratorio/fisiopatología , Encuestas y Cuestionarios
6.
J Allergy Clin Immunol ; 137(3): 806-12, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26688519

RESUMEN

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 ß2-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 (S(He)) and sulfur hexafluoride (S(SF6)) were measured in 68 asthmatic patients before and after salbutamol inhalation. S(He) and S(SF6) 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 S(He) nor S(SF6) changed, in the FENO+ group only S(He) decreased significantly (-21.8% [SD 28.5%], P = .03), and in the FENO- group both S(He) (-29.8% [24.0%], P < .001) and S(SF6) (-27.2% [23.3%], P < .001) decreased. DISCUSSION: Three FENO behaviors were observed in response to ß2-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.


Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Asma/metabolismo , Espiración , Óxido Nítrico/metabolismo , Agonistas de Receptores Adrenérgicos beta 2/farmacología , Adulto , Anciano , Antiasmáticos/farmacología , Asma/fisiopatología , Biomarcadores , Broncodilatadores/farmacología , Broncodilatadores/uso terapéutico , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Pruebas de Función Respiratoria , Sensibilidad y Especificidad , Capacidad Vital
9.
J Allergy Clin Immunol ; 134(3): 554-9, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24522091

RESUMEN

BACKGROUND: The increased fraction of exhaled nitric oxide (Feno) values observed in asthmatic patients are thought to reflect increased airway inflammation. However, Feno values can be affected by airway caliber reduction, representing a bias when using Feno values to assess asthma control. OBJECTIVE: We sought to determine the effect of changes in both airway caliber and inflammation on Feno values using the allergen challenge model. METHODS: FEV1 and Feno values were measured during early airway responses (EARs) and late airway responses after challenge with house dust mite allergens in 15 patients with mild allergic asthma. Helium and sulfur hexafluoride (SF6) phase III expired concentration slopes (SHe and SSF6, respectively) from single-breath washout tests were measured to identify sites of airway constriction. RESULTS: In EARs, FEV1 and Feno value decreases reached 36.8% and 22%, respectively (P < .001). ΔSHe was greater than ΔSSF6 (+189.4% vs +82.2%, P = .001). In late airway responses FEV1 and Feno value decreases reached 31.7% and 28.7%, respectively (P < .001), with the same ΔSHe and ΔSSF6 pattern (+155.8% vs +76%, P = .001). Eight hours after the EAR, FEV1 was still decreased (P < .001), whereas Feno values had returned to baseline. At 24 hours, FEV1 had returned to baseline, with Feno values increased by 38.7% (P = .04). CONCLUSION: In patients with mild allergic asthma, airway caliber changes modulate changes in Feno values resulting from airway inflammation. Therefore Feno should no longer be considered solely an inflammation biomarker but rather a biomarker that integrates both airway inflammation and lung function changes. Furthermore, early and late phases resulting from allergen exposure were shown to involve similar lung regions.


Asunto(s)
Asma/diagnóstico , Biomarcadores/metabolismo , Pruebas Respiratorias/métodos , Óxido Nítrico/metabolismo , Sistema Respiratorio/inmunología , Adulto , Remodelación de las Vías Aéreas (Respiratorias) , Animales , Antígenos Dermatofagoides/inmunología , Asma/inmunología , Progresión de la Enfermedad , Espiración , Femenino , Humanos , Masculino , Neumonía/inmunología , Estudios Prospectivos , Pyroglyphidae , Pruebas de Función Respiratoria
10.
Nitric Oxide ; 40: 110-6, 2014 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-25014062

RESUMEN

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-naïve, 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 µg 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.


Asunto(s)
Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Óxido Nítrico/análisis , Administración por Inhalación , Corticoesteroides/administración & dosificación , Adulto , Asma/diagnóstico , Biomarcadores/análisis , Femenino , Humanos , Masculino , Óxido Nítrico/administración & dosificación , Curva ROC , Estudios Retrospectivos
11.
J Allergy Clin Immunol Pract ; 12(1): 111-117, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37634805

RESUMEN

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.


Asunto(s)
Obstrucción de las Vías Aéreas , Asma , Adulto , Humanos , Asma/diagnóstico , Asma/tratamiento farmacológico , Sistema Respiratorio , Eosinófilos , Inflamación , Óxido Nítrico , Pruebas Respiratorias
12.
J Appl Physiol (1985) ; 137(1): 154-165, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38722752

RESUMEN

The effect of bronchodilators is mainly assessed with forced expiratory volume in 1 s (FEV1) in chronic obstructive pulmonary disease (COPD). Their impact on oxygenation and lung periphery is less known. Our objective was 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. FEV1, Helium slope (SHe) from a single-breath washout test (SHe decreases 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 h post-LABA (day 1) and LAMA (day 3) in 30 patients with COPD (FEV1 54 ± 18% pred; GOLD A 31%/B 48%/E 21%) after 5-7 days of washout, respectively. We found that TcO2 increased more (P = 0.03) after LAMA (11 ± 12% from baseline, P < 001) compared with 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). In conclusion, LAMA significantly improved tissue oxygenation in patients with COPD, while only a trend was observed with LABA. The mechanisms involved may differ between both drugs: LABA increased peripheral ventilation, whereas LAMA increased lung capillary blood volume. Should oxygenation differences persist over time, LAMA could arguably become the first therapeutic choice in COPD.NEW & NOTEWORTHY Long-acting muscarinic antagonists (LAMAs) significantly improved tissue oxygenation in patients with COPD, while only a trend was observed with ß2-agonists (LABAs). The mechanisms involved may differ between drugs: increased peripheral ventilation for LABA and likely lung capillary blood volume for LAMA. This could argue for LAMA as the first therapeutic choice in COPD.


Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2 , Pulmón , Antagonistas Muscarínicos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Antagonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/administración & dosificación , Masculino , Femenino , Agonistas de Receptores Adrenérgicos beta 2/farmacología , Anciano , Persona de Mediana Edad , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Oxígeno/metabolismo , Volumen Espiratorio Forzado/efectos de los fármacos , Broncodilatadores/farmacología , Broncodilatadores/administración & dosificación , Bromuro de Tiotropio , Combinación de Medicamentos , Benzoxazinas
13.
J Allergy Clin Immunol Pract ; 10(2): 467-477, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34563736

RESUMEN

BACKGROUND: Asthmatics have accelerated lung function decline over time compared with healthy individuals. OBJECTIVE: To evaluate risk factors for accelerated lung function decline. METHODS: In a longitudinal analysis on severe asthmatics enrolled in the Belgian Severe Asthma Registry with at least 2 visits a minimum of 12 months apart, we compared characteristics of patients with and without decline (loss of post-bronchodilation forced expiratory volume in 1 s [FEV1] (% predicted)/y greater than zero) over time. Multiple linear regression was applied to study the factors independently associated with FEV1 decline. RESULTS: In the overall population (n = 318), median annual FEV1 decline was 0.27 (-4.22 to 3.80) % predicted/y over a period of 23 months (12-41 months). Asthma was less controlled at baseline in nondecliners than in decliners (53%). Lung function and residual volume at baseline were higher in the declining group. Decliners presented with increased bronchial reactivity (ie, a lower provocative concentration of methacholine causing a 20% fall in FEV1) at baseline. Twenty-five percent of nondecliners were started on anti-interleukin-5 (anti-IL-5) for severe eosinophilic asthma during the study compared with 10% of decliners. The multivariable model suggested that Asthma Control Questionnaire score at baseline, late-onset asthma, and addition of anti-IL-5 during follow-up were associated with lower FEV1 decline, independently from other variables such as evolution in exacerbations, smoking status, inhaled corticosteroids or oral corticosteroids dose, or add-on anti-immunoglobulin E over time, whereas reversibility to salbutamol and higher FEV1 were associated with accelerated FEV1 decline. CONCLUSIONS: Add-on therapy with anti-IL-5 in severe eosinophilic asthma was associated with an attenuated FEV1 decline. The causality of this observation should, however, be confirmed in future prospective controlled studies.


Asunto(s)
Asma , Asma/tratamiento farmacológico , Asma/epidemiología , Bélgica/epidemiología , Bronquios , Volumen Espiratorio Forzado , Humanos , Sistema de Registros
14.
J Allergy Clin Immunol ; 126(4): 730-735.e2, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20709384

RESUMEN

BACKGROUND: The effects of inhaled corticosteroids (ICSs) on distal lung inflammation, as assessed by alveolar nitric oxide concentration (C(A)NO), are a matter of debate. Recently, a theoretic study suggested that acinar airway obstruction that is relieved by ICS treatment and associated with a decrease in fraction of exhaled nitric oxide (FeNO) concentration might, paradoxically, increase C(A)NO. This increase could be a hallmark effect of ICSs at the acinar level. OBJECTIVE: In the light of this new hypothesis, we studied changes in C(A)NO and FeNO after administration of ICSs. METHODS: C(A)NO and FeNO were measured before and after ICS treatment of 38 steroid-naive patients with uncontrolled asthma who showed clinical improvement after ICS therapy. RESULTS: The average FeNO decreased from 78.3 to 28.9 ppb (P < .001); C(A)NO decreased from 7.7 to 4.3 ppb (P = .009). In 14 subjects (low-slope group), slope (= ΔC(A)NO/ΔFeNO) values (Δ = post-ICS - pre-ICS value) were less than the 95% normal CI (average ΔFeNO = -32.7 ppb and average ΔC(A)NO= +2.9 ppb). In this group, baseline C(A)NO was abnormally low when FeNO was taken into account. In 11 subjects (the high-slope group), the slope was above the normal interval (average ΔFeNO = -42.5 ppb and average ΔC(A)NO = -14.7 ppb). CONCLUSION: Opposite patterns (one that was predicted) can indicate peripheral actions of ICSs; this difference might account for conflicting data reported from studies using C(A)NO to determine the peripheral action of ICSs. We show that a low C(A)NO does not preclude distal inflammation.


Asunto(s)
Corticoesteroides/administración & dosificación , Antiasmáticos/administración & dosificación , Antiinflamatorios/administración & dosificación , Asma/tratamiento farmacológico , Óxido Nítrico/metabolismo , Alveolos Pulmonares/metabolismo , Administración por Inhalación , Corticoesteroides/uso terapéutico , Antiasmáticos/uso terapéutico , Antiinflamatorios/uso terapéutico , Asma/metabolismo , Pruebas Respiratorias , Espiración , Volumen Espiratorio Forzado , Humanos , Espirometría , Resultado del Tratamiento
15.
J Appl Physiol (1985) ; 130(4): 1106-1113, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33444118

RESUMEN

We previously documented, in patients with asthma, three different profiles of bronchodilation induced by short-acting ß-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 ß-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 µg). SHe and SSF6 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, SHe, and SF6 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 SHe 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 ß2-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 ß2-agonists in asthma patients tends to involve peripheral airways. This study shows that the heterogeneity of responses to short-acting ß2-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 ß2-agonists in asthma should not be limited to studying its early impact on FEV1.


Asunto(s)
Asma , Broncodilatadores , Adulto , Albuterol/uso terapéutico , Asma/tratamiento farmacológico , Broncodilatadores/farmacología , Espiración , Femenino , Volumen Espiratorio Forzado , Humanos , Cinética , Masculino , Persona de Mediana Edad , Óxido Nítrico/farmacología
16.
J Appl Physiol (1985) ; 130(4): 903-913, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33475458

RESUMEN

Closing volume (CV) is commonly measured by single-breath nitrogen washout (CVSBW). A method based on the forced oscillation technique was recently introduced to detect a surrogate CV (CVFOT). As the two approaches are based on different physiological mechanisms, we aim to investigate CVFOT and CVSBW relationship at different degrees and patterns of airway obstruction. A mathematical model was developed to evaluate the CVSBW and CVFOT sensitivity to different patterns of airway obstruction, either located in a specific lung region or equally distributed throughout the lung. The two CVs were also assessed during slow vital capacity (VC) maneuvers in triplicate in 13 healthy subjects and pre- and postmethacholine challenge (Mch) in 12 subjects with mild-moderate asthma. Model simulations suggest that CVSBW is more sensitive than CVFOT to the presence of few flow-limited or closed airways that modify the contribution of tracer-poor and tracer-rich lung regions to the overall exhaled gas. Conversely, CVFOT occurs only when at least ∼65% of lung units are flow limited or closed, regardless of their regional distribution. CVSBW did not differ between healthy subjects and those with asthma (17 ± 9% VC vs. 22 ± 10% VC), whereas CVFOT did (16 ± 5% VC vs. 23 ± 6% VC, P < 0.01). In patients with asthma, both CVSBW and CVFOT increased post-Mch (33 ± 7% VC P < 0.001 and 43 ± 12% VC P < 0.001, respectively). CVSBW weakly correlated with CVFOT (r = 0.45, P < 0.01). The closing capacities (CV + residual volume) were correlated (r = 0.74, P < 0.001), but the changes with Mch in both CVs and closing capacities did not correlate. CVFOT is easy to measure and provides a reproducible parameter useful for describing airway impairment in obstructive respiratory diseases.NEW & NOTEWORTHY The forced oscillation technique can identify a surrogate of closing volume (CVFOT). We investigated its relationship with the one measured by single-breath washout (CVSBW). CVFOT weakly correlates with CVSBW. The respective closing capacities were correlated, but their increases after methacholine challenge in asthmatics did not. Our results suggest that CVFOT is less sensitive than CVSBW to few flow-limited/closed airways but more specific in detecting increases in flow-limited/closed airways involving the majority of the lung.


Asunto(s)
Asma , Volumen de Cierre , Pruebas de Provocación Bronquial , Volumen Espiratorio Forzado , Humanos , Pulmón , Mediciones del Volumen Pulmonar
17.
Thorax ; 65(12): 1039-44, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20671307

RESUMEN

BACKGROUND: It has been claimed that exhaled nitric oxide (FeNO) could be regarded as a surrogate marker for sputum eosinophil count in patients with asthma. However, the FeNO threshold value that identifies a sputum eosinophil count ≥3% in an unselected population of patients with asthma has been poorly studied. METHODS: This retrospective study was conducted in 295 patients with asthma aged 15­84 years recruited from the asthma clinic of University Hospital of Liege. Receiver-operating characteristic (ROC) curve and logistic regression analysis were used to assess the relationship between sputum eosinophil count and FeNO, taking into account covariates such as inhaled corticosteroids (ICS), smoking, atopy, age and sex. RESULTS: Derived from the ROC curve, FeNO ≥41 ppb gave 65% sensitivity and 79% specificity (AUC=0.777, p=0.0001) for identifying a sputum eosinophil count ≥3%. Using logistic regression analysis, a threshold of 42 ppb was found to discriminate between eosinophilic and non-eosinophilic asthma (p<0.0001). Patients receiving high doses of ICS (≥1000 µg beclometasone) had a significantly lower FeNO threshold (27 ppb) than the rest of the group (48 ppb, p<0.05). Atopy also significantly altered the threshold (49 ppb for atopic vs 30 ppb for non-atopic patients, p<0.05) and there was a trend for a lower threshold in smokers (27 ppb) compared with non-smokers (46 ppb, p=0.066). Age and sex did not affect the relationship between FeNO and sputum eosinophilia. When combining all variables into the logistic model, FeNO (p<0.0001), high-dose ICS (p<0.05) and smoking (p<0.05) were independent predictors of sputum eosinophilia, while there was a trend for atopy (p=0.086). CONCLUSION: FeNO is able to identify a sputum eosinophil count ≥3% with reasonable accuracy and thresholds which vary according to dose of ICS, smoking and atopy.


Asunto(s)
Asma/complicaciones , Eosinofilia/diagnóstico , Óxido Nítrico/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asma/tratamiento farmacológico , Asma/fisiopatología , Biomarcadores/análisis , Pruebas Respiratorias/métodos , Relación Dosis-Respuesta a Droga , Eosinofilia/etiología , Eosinófilos/patología , Métodos Epidemiológicos , Femenino , Volumen Espiratorio Forzado , Glucocorticoides/administración & dosificación , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Fumar/efectos adversos , Fumar/metabolismo , Esputo/citología , Adulto Joven
18.
Curr Med Chem ; 27(42): 7159-7167, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32660394

RESUMEN

Asthma is a heterogeneous disease with regard to the inflammatory pathways activated. In recent years, biologic drugs (monoclonal antibodies) directed towards specific components of type 2 inflammation have been approved for the treatment of severe asthma. Phenotyping of patients with severe asthma and evaluation of biomarkers have been recommended to help identify patients who are candidates for treatment with biologics and to monitor treatment responses. Fractional exhaled Nitric Oxide (FeNO) is a biomarker of type 2 inflammation in asthma, signaling activation of Interleukin (IL)-4/IL-13 pathway. FeNO could be useful to assess treatment response or identify candidates for a specific drug that acts on type 2 inflammation mechanisms linked to Nitric Oxide (NO) production, such as the IL-4/IL-13 pathway or upstream processes. The value of FeNO as a biomarker predictive of responses to the biologics available for treating severe asthma is discussed based on the published studies at the moment of the review.


Asunto(s)
Asma , Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Biomarcadores , Humanos , Interleucina-13/uso terapéutico , Óxido Nítrico , Índice de Severidad de la Enfermedad
19.
J Breath Res ; 13(3): 036002, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30802891

RESUMEN

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, FEV1 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 µg salbutamol. SBWT used Helium (He), and sulfur-hexafluoride (SF6). Obstruction relief occurring in pre-acinar and intra-acinar small airways is expected to decrease SHe and SSF6, respectively. Indices changes (Δ) after bronchodilation were expressed as a percentage of pre-bronchodilation values. RESULTS: FENO stability (∣ΔFENO∣ ≤ 11%) was observed in 19 patients [-2.7(6.7)%] [mean (SD)] (NO = group); ΔFENO > 11% [+37.4(27.7)%] in 20 patients (NO+ group) and ΔFENO < -11% in 22 patients [-31.2(9.8)%] (NO- group). A similar ΔFEV1 (p = 0.583; [+9.4(9.6)%]) was found in the three groups. In NO = and NO+ groups, neither SHe nor SSF6 changed; in NO- both SHe [-12.4(27.5)%, p = 0.007] and SSF6 [-20.2(20.4)%, p < 0.001] significantly decreased. CONCLUSION: Different patterns of FENO response to ß 2-agonists were observed in COPD most likely depending on the extent of the dilation process. A profile of airway obstruction with an extensive ß 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.


Asunto(s)
Obstrucción de las Vías Aéreas/diagnóstico , Obstrucción de las Vías Aéreas/etiología , Pruebas Respiratorias/métodos , Espiración/fisiología , Óxido Nítrico/química , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Obstrucción de las Vías Aéreas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
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