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BACKGROUND: Although asthma is often seen as an eosinophilic disease associated with atopy, patients with noneosinophilic asthma represent a substantial part of the population with asthma. OBJECTIVE: To apply an unsupervised clustering method in a cohort of 588 patients with noneosinophilic asthma (sputum eosinophils < 3%) recruited from an asthma clinic of a secondary care center. METHODS: Our cluster analysis of the whole cohort identified 2 subgroups as cluster 1 (n = 417) and cluster 2 (n = 171). RESULTS: Cluster 1 comprised a predominantly female group with late disease onset, a low proportion of atopy (24%), and a substantial smoking history (53%). In this cluster, treatment burden was low (<50% of inhaled corticosteroid users); asthma control and quality of life were poor, with median Asthma Control Test, Asthma Control Questionnaire, and Asthma Quality of Life scores of 16, 1.7, and 4.5, respectively, whereas lung function was preserved with a median postbronchodilation forced expiratory volume in 1 second of 93% predicted. Cluster 2 was a predominantly male group, almost exclusively comprising patients with atopy (99%) with early disease onset and a moderate treatment burden (median inhaled corticosteroids dose 800 µg/d equivalent beclomethasone). In cluster 2, asthma was partially controlled, with median Asthma Control Test and Asthma Control Questionnaire scores reaching 18 and 1.3, respectively, and lung function well preserved with a median postbronchodilation of 95% predicted. Although systemic and airway neutrophilic inflammation was the dominant pattern in cluster 1, cluster 2 essentially comprised paucigranulocytic asthma with moderately elevated fraction exhaled nitric oxide. CONCLUSION: Noneosinophilic asthma splits into 2 clusters distinguishing by disease onset, atopic status, smoking history, systemic and airway inflammation, and disease control and quality of life.
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Asma , Calidad de Vida , Humanos , Asma/tratamiento farmacológico , Asma/epidemiología , Asma/inmunología , Asma/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Análisis por Conglomerados , Eosinófilos/inmunología , Corticoesteroides/uso terapéutico , Anciano , Estudios de Cohortes , Encuestas y CuestionariosRESUMEN
Several clinical trials have demonstrated that anti-IL-5(R) biologics were able to improve lung function, asthma control and chronic oral corticosteroid exposure and reduce exacerbations among eosinophilic asthmatic patients. However, a certain variability in clinical responses to anti-IL-5(R) biologics was brought to light. Our study aimed at evaluating the role of baseline sputum eosinophils in identifying super-responders to mepolizumab and benralizumab. Our study reinforces the importance to examine sputum eosinophils in patients suffering from severe asthma before starting a biologic as it is associated with the intensity of response to mepolizumab and benralizumab.
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Antiasmáticos , Asma , Productos Biológicos , Eosinofilia , Humanos , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Eosinófilos , Esputo , Interleucina-5/antagonistas & inhibidores , Interleucina-5/inmunología , Receptores de Interleucina-5/antagonistas & inhibidores , Receptores de Interleucina-5/inmunologíaRESUMEN
PURPOSE: Asthma negatively impacts health-related quality of life (HRQL). The objective is to investigate the longitudinal relationship between HRQL in asthma and disease control, demographic and clinical objective parameters in an adult population in real-life settings. METHODS: We conducted a longitudinal study on adult asthmatics recruited from Liege University Hospital Asthma Clinic (Belgium) between 2011 and 2019. We selected those who had two visits and completed two patient-reported outcome measures (PROMs), the asthma control test (ACT) and the mini asthma quality of life questionnaire (AQLQ) (n = 290). AQLQ was the dependent variable. Demographic, functional and inflammatory characteristics, asthma control, and exacerbations were the independent variables. We applied generalized linear mixed models to identify the factors associated with change in AQLQ and its dimensions. RESULTS: Median (IQR) time interval between the two visits was 7 (5-19) months. Overall, median (IQR) global AQLQ increased from 4.1 (3-5.1) to 4.6 (3.4-5.9) (p < 0.0001). All AQLQ dimensions significantly improved, apart the environmental one. AQLQ improved in patients who had both step-up and step-down pharmacological treatment as well as in patients reporting no change between the two visits. The fitted models indicated that change in ACT was the main predictor of change in AQLQ (p < 0.0001). A rise in 3 units in ACT predicted an improvement of 0.5 AQLQ (AUC-ROC = 0.85; p < 0.0001). Change in BMI inversely impacted global AQLQ (p < 0.01) and its activity dimension (p < 0.0001). CONCLUSION: Asthma control and BMI are key predictors of asthma quality of life acting in an opposite direction. AQLQ may improve without step-up in the pharmacological treatment.
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Asma , Calidad de Vida , Humanos , Adulto , Calidad de Vida/psicología , Estudios Longitudinales , Encuestas y Cuestionarios , Asma/tratamiento farmacológico , BélgicaRESUMEN
BACKGROUND: Chlamydia pneumoniae and Mycoplasma pneumoniae have been implicated in the pathogenesis of asthma and are responsible for chronic inflammation when host immune system fails to eradicate the bacteria. METHOD: We performed a prospective study on 410 patients who underwent a visit at the asthma clinic of CHU of Liege between June 2016 and June 2018 with serology testing for C. pneumoniae and M. pneumoniae. RESULTS: 65% of our asthmatic population had serum IgA and/or IgG towards C. pneumoniae, while only 12.6% had IgM and/or IgG against M. pneumoniae. Compared to seronegative asthmatics, asthmatics with IgA+ and IgG+ against C. pneumoniae were more often male and older with a higher proportion of patients with smoking history. They received higher doses of inhaled corticosteroids (ICS) and displayed lower FEV1/FVC ratio, higher RV/TLC ratio and lower conductance. They had higher levels of fibrinogen, though in the normal range and had lower sputum eosinophil counts. Patients with IgA- and IgG+ against C. pneumoniae were older and had higher blood monocyte counts and alpha-1-antitrypsin levels as compared to seronegative patients. Patients with IgM and/or IgG towards M. pneumoniae were more often males than seronegative asthmatics. In a subpopulation of 14 neutrophilic asthmatics with Chlamydia pneumoniae IgA + /IgG + treated with macrolides, we found a significant decrease in blood neutrophils and normalization of sputum neutrophil count but no effect on asthma quality of life and exacerbations. CONCLUSION: Positive Chlamydia serologic test is more common than positive Mycoplasma serology. Asthmatics with IgA and IgG against C. pneumoniae have more severe disease with increased airway obstruction, higher doses of ICS, more signs of air trapping and less type-2 inflammation.
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Asma/epidemiología , Infecciones por Chlamydophila/epidemiología , Chlamydophila pneumoniae , Mycoplasma pneumoniae , Neumonía Bacteriana/epidemiología , Neumonía por Mycoplasma/epidemiología , Adulto , Anciano , Asma/sangre , Asma/diagnóstico , Infecciones por Chlamydophila/sangre , Infecciones por Chlamydophila/diagnóstico , Chlamydophila pneumoniae/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycoplasma pneumoniae/metabolismo , Fenotipo , Neumonía Bacteriana/sangre , Neumonía Bacteriana/diagnóstico , Neumonía por Mycoplasma/sangre , Neumonía por Mycoplasma/diagnóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Randomized control trials performed in selected populations of severe eosinophilic asthmatics have shown that mepolizumab, an anti-IL5 therapy, was able to reduce exacerbations and OCS maintenance dose and in some studies, to improve asthma control and lung function. OBJECTIVE: The aim of this study was to confirm the results of the RCTs in real-life in a population of 116 severe eosinophilic asthmatics treated with mepolizumab and who were followed up at the asthma clinic every month for at least 18 months. Severe asthmatics underwent FENO, lung function, asthma control and quality of life questionnaires, sputum induction and gave a blood sample at baseline, after 6 months and then every year. RESULTS: We found a significant reduction in exacerbations by 85% after 6 months (P < .0001), which was maintained over time. We also found a significant and maintained reduction by 50% in the dose of oral corticosteroids (P < .001). Patients improved their ACT (+5.31pts, p<0.0001) ACQ (-1.13pts, P < .0001) and their AQLQ score (+1.24, P < .0001) at 6 months and this was maintained during follow-up. Only 37% reached asthma control (ACQ <1.5, ACT> 20). We observed a progressive increase in post-BD FEV1 that reached significance after 18 months (190ml or 11%, P < .01). Patients improving their FEV1had higher baseline sputum eosinophils than those not improving airway caliber. We found a significant reduction in sputum eosinophil counts by 60% after 6 months (P < .01) and a maintained reduction in blood eosinophil counts by 98% (P < .0001). CONCLUSION: In our real-life study, we confirm the results published in the RCTs showing a sharp reduction in exacerbation and oral corticosteroids dose and an improvement in asthma control and quality of life. CLINICAL RELEVANCE: Mepolizumab is efficient in severe eosinophilic asthma in real life.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Asma , Pulmón/fisiopatología , Calidad de Vida , Adulto , Anciano , Asma/tratamiento farmacológico , Asma/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pruebas de Función RespiratoriaRESUMEN
Rationale: Analysis of exhaled breath for asthma phenotyping using endogenously generated volatile organic compounds (VOCs) offers the possibility of noninvasive diagnosis and therapeutic monitoring. Induced sputum is indeed not widely available and markers of neutrophilic asthma are still lacking.Objectives: To determine whether analysis of exhaled breath using endogenously generated VOCs can be a surrogate marker for recognition of sputum inflammatory phenotypes.Methods: We conducted a prospective study on 521 patients with asthma recruited from the University Asthma Clinic of Liege. Patients underwent VOC measurement, fraction of exhaled nitric oxide (FeNO) spirometry, sputum induction, and gave a blood sample. Subjects with asthma were classified in three inflammatory phenotypes according to their sputum granulocytic cell count.Measurements and Main Results: In the discovery study, seven potential biomarkers were highlighted by gas chromatography-mass spectrometry in a training cohort of 276 patients with asthma. In the replication study (n = 245), we confirmed four VOCs of interest to discriminate among asthma inflammatory phenotypes using comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry. Hexane and 2-hexanone were identified as compounds with the highest classification performance in eosinophilic asthma with accuracy comparable to that of blood eosinophils and FeNO. Moreover, the combination of FeNO, blood eosinophils, and VOCs gave a very good prediction of eosinophilic asthma (area under the receiver operating characteristic curve, 0.9). For neutrophilic asthma, the combination of nonanal, 1-propanol, and hexane had a classification performance similar to FeNO or blood eosinophils in eosinophilic asthma. Those compounds were found in higher levels in neutrophilic asthma.Conclusions: Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of patients with asthma and provide surrogate markers for neutrophilic asthma.
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Asma/inmunología , Eosinofilia/inmunología , Eosinófilos , Neutrófilos , Esputo/citología , Adulto , Anciano , Asma/clasificación , Asma/diagnóstico , Asma/metabolismo , Pruebas Respiratorias , Eosinofilia/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Estudios Prospectivos , Espirometría , Compuestos Orgánicos VolátilesRESUMEN
Chronic obstructive pulmonary disease (COPD) is a complex, multidimensional and heterogeneous disease. The main purpose of the present study was to identify clinical phenotypes through cluster analysis in adults suffering from COPD. A retrospective study was conducted on 178 COPD patients in stable state recruited from ambulatory care at University hospital of Liege. All patients were above 40 years, had a smoking history of more than 20 pack years, post bronchodilator FEV1/FVC <70% and denied any history of asthma before 40 years. In this study, the patients were described by a total of 84 mixed sets of variables with some missing values. Hierarchical clustering on principal components (HCPC) was applied on multiple imputation. In the final step, patients were classified into homogeneous distinct groups by consensus clustering. Three different clusters, which shared similar smoking history were found. Cluster 1 included men with moderate airway obstruction (n = 67) while cluster 2 comprised men who were exacerbation-prone, with severe airflow limitation and intense granulocytic airway and neutrophilic systemic inflammation (n = 56). Cluster 3 essentially included women with moderate airway obstruction (n = 55). All clusters had a low rate of bacterial colonization (5%), a low median FeNO value (<20 ppb) and a very low sensitization rate toward common aeroallergens (0-5%). CAT score did not differ between clusters. Including markers of systemic airway inflammation and atopy and applying a comprehensive cluster analysis we provide here evidence for 3 clusters markedly shaped by sex, airway obstruction and neutrophilic inflammation but not by symptoms and T2 biomarkers.
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Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Adulto , Factores de Edad , Anciano , Bélgica , Biomarcadores/metabolismo , Recuento de Células Sanguíneas , Análisis por Conglomerados , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Fumar , Esputo/citología , Esputo/metabolismoRESUMEN
The concept of asthma inflammatory phenotypes has proved to be important in predicting response to inhaled corticosteroids. Induced sputum, which has been pivotal in the development of the concept of inflammatory phenotypes, is however not widely available. Several studies have proposed to use surrogate exhaled or blood biomarkers, like fractional exhaled nitric oxide (FENO), blood eosinophils and total serum immunoglobulin E (IgE). However, taken alone, each of these biomarkers has moderate accuracy to identify sputum eosinophilia. Here, we propose a new approach based on the likelihood ratio to study which thresholds of these biomarkers, taken alone or in combination, were able to rule in or rule out sputum eosinophils ≥3%. We showed in a large population of 869 asthmatics that combining FENO, blood eosinophils and total serum IgE could accurately predict sputum eosinophils ≥ or <3% in 58% of our population.
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Asma/diagnóstico , Asma/metabolismo , Eosinófilos/metabolismo , Esputo/metabolismo , Adulto , Asma/sangre , Biomarcadores/sangre , Biomarcadores/metabolismo , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: The technique of induced sputum has allowed to subdivide asthma patients into inflammatory phenotypes according to their level of granulocyte airway infiltration. There are very few studies which looked at detailed sputum and blood cell counts in a large cohort of asthmatics divided into inflammatory phenotypes. The purpose of this study was to analyze sputum cell counts, blood leukocytes and systemic inflammatory markers in these phenotypes, and investigate how those groups compared with healthy subjects. METHODS: We conducted a retrospective cross-sectional study on 833 asthmatics recruited from the University Asthma Clinic of Liege and compared them with 194 healthy subjects. Asthmatics were classified into inflammatory phenotypes. RESULTS: The total non-squamous cell count per gram of sputum was greater in mixed granulocytic and neutrophilic phenotypes as compared to eosinophilic, paucigranulocytic asthma and healthy subjects (p < 0.005). Sputum eosinophils (in absolute values and percentages) were increased in all asthma phenotypes including paucigranulocytic asthma, compared to healthy subjects (p < 0.005). Eosinophilic asthma showed higher absolute sputum neutrophil and lymphocyte counts than healthy subjects (p < 0.005), while neutrophilic asthmatics had a particularly low number of sputum macrophages and epithelial cells. All asthma phenotypes showed an increased blood leukocyte count compared to healthy subjects (p < 0.005), with paucigranulocytic asthmatics having also increased absolute blood eosinophils compared to healthy subjects (p < 0.005). Neutrophilic asthma had raised CRP and fibrinogen while eosinophilic asthma only showed raised fibrinogen compared to healthy subjects (p < 0.005). CONCLUSIONS: This study demonstrates that a significant eosinophilic inflammation is present across all categories of asthma, and that paucigranulocytic asthma may be seen as a low grade inflammatory disease.
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Asma/inmunología , Proteína C-Reactiva/inmunología , Eosinófilos/inmunología , Fibrinógeno/inmunología , Macrófagos/inmunología , Neutrófilos/inmunología , Esputo/citología , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Eosinófilos/citología , Femenino , Granulocitos/citología , Granulocitos/inmunología , Humanos , Inflamación , Recuento de Leucocitos , Recuento de Linfocitos , Macrófagos/citología , Masculino , Persona de Mediana Edad , Neutrófilos/citología , Fenotipo , Estudios RetrospectivosRESUMEN
Systemic and airway eosinophilia are recognised features of asthma. There are, however, patients who exhibit discordance between local and systemic eosinophilia. In this study, we sought to determine the prevalence and characteristics of patients with concordant and discordant systemic and bronchial eosinophilia. We conducted a retrospective study on 508 asthmatics with successful sputum induction. We assessed the relationship between blood and sputum eosinophils by breaking down the population into four groups according to blood (≥400 cells per mm3) and sputum (≥3%) eosinophils. Then, we prospectively reassessed the link between eosinophils and asthma control (Asthma Control Questionnaire (ACQ)) and exacerbation rate in a new cohort of 250 matched asthmatics. In our retrospective cohort, asthmatics without eosinophilic inflammation were the largest group (49%). The group with isolated sputum eosinophilia (25%) was, compared with noneosinophilic asthma, associated with lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity ratio and higher bronchial hyperresponsiveness and exhaled nitric oxide fraction (FeNO). Asthmatics exhibiting isolated systemic eosinophilia (7%) had similar characteristics as noneosinophilic asthmatics. The group with concordant systemic and airway eosinophilia (19%) showed remarkable male predominance, and had the lowest airway calibre, asthma control and quality of life, and the highest bronchial hyperresponsiveness, FeNO and exacerbation rate. The prospective cohort confirmed the different subgroup proportions and the higher ACQ and exacerbation rates in cases of diffuse eosinophilia compared with noneosinophilic asthmatics. Concomitant systemic and bronchial eosinophilic inflammation contribute to poor asthma control.
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Asma/complicaciones , Eosinofilia/complicaciones , Esputo/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asma/sangre , Asma/metabolismo , Estudios de Casos y Controles , Eosinofilia/sangre , Eosinofilia/metabolismo , Eosinófilos/citología , Volumen Espiratorio Forzado , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
Introduction: Although asthma is a common disease, its diagnosis remains a challenge in clinical practice with both over- and underdiagnosis. Here, we performed a prospective observational study investigating the value of symptom intensity scales alone or combined with spirometry and exhaled nitric oxide fraction (F ENO) to aid in asthma diagnosis. Methods: Over a 38-month period we recruited 303 untreated patients complaining of symptoms suggestive of asthma (wheezing, dyspnoea, cough, sputum production and chest tightness). The whole cohort was split into a training cohort (n=166) for patients recruited during odd months and a validation cohort (n=137) for patients recruited during even months. Asthma was diagnosed either by a positive reversibility test (≥12% and ≥200â mL in forced expiratory volume in 1â s (FEV1)) and/or a positive bronchial challenge test (provocative concentration of methacholine causing a 20% fall in FEV1 ≤8â mg·mL-1). In order to assess the diagnostic performance of symptoms, spirometric indices and F ENO, we performed receiver operating characteristic curve analysis and multivariable logistic regression to identify the independent factors associated with asthma in the training cohort. Then, the derived predictive models were applied to the validation cohort. Results: 63% of patients in the derivation cohort and 58% of patients in the validation cohort were diagnosed as being asthmatic. After logistic regression, wheezing was the only symptom to be significantly associated with asthma. Similarly, FEV1 (% pred), FEV1/forced vital capacity (%) and F ENO were significantly associated with asthma. A predictive model combining these four parameters yielded an area under the curve of 0.76 (95% CI 0.66-0.84) in the training cohort and 0.73 (95% CI 0.65-0.82) when applied to the validation cohort. Conclusion: Combining a wheezing intensity scale with spirometry and F ENO may help in improving asthma diagnosis accuracy in clinical practice.
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BACKGROUND: Staphylococcus aureus enterotoxins (SE) may act as superantigens and induce an intense T-cell activation, causing local production of polyclonal IgE and resultant eosinophil activation. OBJECTIVE: To assess whether asthma with sensitization to SE but not to common aeroallergens (AAs) displays different inflammatory characteristics. METHODS: We conducted a prospective study on a series of 110 consecutive patients with asthma recruited from the University Asthma Clinic of Liège. We compared clinical, functional, and inflammatory characteristics of this general population of patients with asthma categorized into 4 groups according to sensitization to AAs and/or SE. We also compared sputum supernatant cytokines in patients sensitized to SE or not. RESULTS: Patients with asthma sensitized only to AAs represented 30%, while 29% were sensitized to both AAs and SE. One-fifth of the population had no specific IgE. Sensitization to SE but not to AA (21%) was associated with later onset of disease, higher rate of exacerbations, nasal polyps, and more severe airway obstruction. As for airway type 2 biomarkers, patients presenting with specific IgE against SE displayed higher fractional exhaled nitric oxide, sputum IgE, and sputum IL-5 levels but not IL-4. We confirm that the presence of specific IgE against SE is associated with elevated serum IgE to levels well above those observed in patients sensitized only to AAs. CONCLUSIONS: Our study suggests that asthma specialists should measure specific IgE against SE during the phenotyping process because it may allow the identification of a subgroup of patients with more asthma exacerbations, more nasal polyposis and chronic sinusitis, lower lung function, and more intense type 2 inflammation.
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Asma , Staphylococcus aureus , Humanos , Alérgenos , Asma/diagnóstico , Asma/epidemiología , Enterotoxinas , Inmunoglobulina E , Interleucina-5 , Pulmón , Estudios Prospectivos , Esputo/química , Esputo/metabolismoRESUMEN
BACKGROUND: Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments. Even if high blood eosinophil counts seem to be associated with a reduction in exacerbations with treatment targeting IL-5, we lack biomarkers for the prediction of remission after these very expensive treatments. RESEARCH QUESTION: Are there biomarkers of remission after therapy targeting IL-5 in the sputum of patients with severe eosinophilic asthma? STUDY DESIGN AND METHODS: This observational study included 52 patients with severe asthma initiated with anti-IL-5 therapy and recruited from the asthma clinic of the Centre Hospitalier Universitaire of Liege, Belgium. Remission was defined as patients who combined the following at 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire score < 1.5, asthma control test score > 19, or both; FEV1 of ≥ 80% predicted, improvement of FEV1 of ≥ 10%, or both; and a blood eosinophil count < 300 cells/µL. Eosinophil peroxidase (EPX), IgE, IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor, thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels were measured in the sputum of these patients before anti-IL-5 treatment. RESULTS: Among the 52 patients, 11 were classified as being in remission. These patients were characterized by higher sputum eosinophil, macrophage, and lymphocyte counts, whereas the sputum neutrophil percentage was lower than in the nonremission group. In addition, the sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein levels were higher at baseline in the remission group compared with the nonremission group. Univariate regression analysis revealed that male vs female sex, sputum neutrophil percentage, eotaxin-1, IL-5, and EPX were potential predictors of remission. INTERPRETATION: Sputum type 2 markers seemed to be potentially predictive of remission after anti-IL-5 therapy in a cohort of patients with severe eosinophilic asthma. These results need validation on a larger cohort.
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Asma , Eosinofilia Pulmonar , Humanos , Masculino , Femenino , Quimiocina CCL11 , Esputo/metabolismo , Asma/tratamiento farmacológico , Eosinófilos , Citocinas , Biomarcadores/metabolismo , Linfopoyetina del Estroma Tímico , Inmunoglobulina ERESUMEN
Background: Randomised controlled trials have shown that benralizumab, an anti-interleukin-5 receptor monoclonal antibody, reduces exacerbations and oral corticosteroid dose and improves asthma control and lung function in severe eosinophilic asthma. The aim of this study was to confirm results of randomised controlled trials in real life in a population of 73 patients with severe eosinophilic asthma treated with benralizumab for at least 12â months. Methods: Patients underwent careful monitoring of asthma exacerbations, exhaled nitric oxide fraction, lung function, asthma control and quality of life questionnaire responses and sputum induction, and gave a blood sample at baseline, after 6â months and then every year. Results: We found significant reductions in exacerbations (by 92%, p<0.0001) and oral corticosteroid dose (by 83%, p<0.001) after 6â months that were maintained over time, with 78% of patients able to stop oral corticosteroid therapy. Patients improved their Asthma Control Test (ACT) score (from 11.7±5.1 to 16.9±5.35, p<0.0001), Asthma Control Questionnaire (ACQ) score (from 2.88±1.26 to 1.77±1.32, p<0.0001) and Asthma Quality of Life Questionnaire score (+1.04, p<0.0001) at 6â months and this was maintained during follow-up. Only 35% and 43% of patients reached asthma control according to an ACT score ≥20 and ACQ score <1.5, respectively. We observed stable post-bronchodilation lung function over time and a significant reduction in sputum eosinophil count, with 85% of patients exhibiting sputum eosinophil counts <3% after 6â months (p<0.01) with no effect on exhaled nitric oxide fraction. Conclusion: In our real-life study, we confirm the results published in randomised controlled trials showing a sharp reduction in exacerbations and oral corticosteroid therapy, an improvement in asthma control and quality of life, and a dramatic reduction in sputum eosinophil count.
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Background: Atopic asthma is one of the most common asthma phenotypes and is generally opposed to the non-atopic counterpart. There have been very few large-scale studies comparing atopic and non-atopic asthmatics in terms of systemic and airway inflammation across the age spectrum. Methods: Here, we have undertaken a retrospective study investigating 1626 patients (924 atopic and 702 non-atopic asthmatics) recruited from our university asthma clinic who underwent extensive clinical investigations including induced sputum. Atopy was defined by any positive specific IgE to common aeroallergens (>0,35 kU/L). We performed direct comparisons between the groups and sought to appreciate the influence of age on the airway and systemic inflammatory components. The study was approved by the ethics committee of the University Hospital of Liege (Ref. 2016/276). Informed consents were obtained from healthy subjects. Results: Atopic asthmatics were younger (P < .001), had a higher male/female ratio (P < .001), an earlier disease onset (P < .001) and a greater proportion of treated rhinitis (P < .001) while non-atopic asthmatics had greater smoke exposure (P < .001), lower FEV1/FVC ratio (P = .01) and diffusing capacity (P < .001). There was no difference between the 2 groups regarding FEV1 (% predicted), asthma control, asthma quality of life and exacerbations in the previous 12 months. Regarding inflammation, atopic patients had higher FeNO levels (median = 28 ppb, P < .001), were more eosinophilic both in blood (median = 2.8%, P < .001) and in sputum (median = 2.2%, P < .001) while non-atopic patients displayed greater blood (median = 57%, P = .01) and sputum (median = 58.8%, P = .01) neutrophilic inflammation. However, stratifying patients by age showed that non-atopic asthmatics above 50 years old became equally eosinophilic in the sputum (P = .07), but not in the blood, as compared to atopic patients. Likewise, FeNO rose in non-atopic patients after 50 years old but remained, however, lower than in atopic patients. Conclusions: We conclude that, while sharing many features, atopic group still differentiates from non-atopic asthmatics by demographics, functional and inflammatory profiles. When atopic asthmatics showed a constant eosinophilic pattern across the age spectrum, non-atopic asthmatics were found to be neutrophilic before the age of 50 but eosinophilic above 50 years old.
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BACKGROUND: In recent decades, asthma-related quality of life questionnaires have joined objective clinical indicators as important outcome measures. In this study, we sought to investigate the predictors of asthma-related quality of life in a large cohort of patients recruited from a secondary care center. METHODS: We conducted a cross-sectional study on asthmatics (N = 1301) recruited from the Liège University Hospital asthma clinic (Belgium). After performing a descriptive analysis highlighting the distribution of scores from the Mini Asthma Quality of Life Questionnaire (Mini AQLQ) and its four dimensions (symptoms, activity limitation, emotional function, and environmental stimuli), we did multiple regression analysis to identify the independent predictors of AQLQ. RESULTS: Multiple regression beta analysis showed that AQLQ and its four dimensions were primarily associated with asthma control (p < 0.0001 in all instances). Female gender was associated with a lower score for the AQLQ's activity and environmental dimensions (p < 0.05 for both), while current smokers had a higher score on the AQLQ's environmental dimension (p < 0.0001). The burden of asthma treatment was associated with a lower score for the AQLQ's emotional (p < 0.05) and environmental (p < 0.05) dimensions. BMI was associated with a lower score in the AQLQ's activity dimension (p < 0.0001), while the opposite was true for the FeNO test (p < 0.0001). Sputum neutrophils were inversely related to the score for the AQLQ's symptom dimension (p < 0.05), whereas post-bronchodilator FEV1 showed a positive relationship for that same dimension (p < 0.05). CONCLUSION: Asthma control is the main predictor of AQLQ score and impacts all its dimensions, but demographic, functional, and airway inflammatory parameters may also influence some dimensions of the AQLQ.
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BACKGROUND: Asthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease. OBJECTIVE: To evaluate if obstructive diseases are risk factors for intensive care unit (ICU) stay and death due to coronavirus disease 2019 (COVID19). METHODS: We collected data from the electronic medical record from 596 adult patients hospitalized in University Hospital of Liege between March 18 and April 17, 2020, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We classified patients into 3 groups according to the underlying respiratory disease, present before the COVID19 pandemic. RESULTS: Among patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7%, respectively. The proportions of asthmatics, patients with COPD, and patients without obstructive airway disease hospitalized in the ICU were 17.5%, 19.6%, and 14%, respectively. One-third of patients with COPD died during hospitalization, whereas only 7.0% of asthmatics and 13.6% of patients without airway obstruction died due to SARS-CoV2. The multivariate analysis showed that asthma, COPD, inhaled corticosteroid treatment, and oral corticosteroid treatment were not independent risk factors for ICU admission or death. Male gender (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.1-3.2) and obesity (OR: 8.5; 95% CI: 5.1-14.1) were predictors of ICU admission, whereas male gender (OR 1.9; 95% CI: 1.1-3.2), older age (OR: 1.9; 95% CI: 1.6-2.3), cardiopathy (OR: 1.8; 95% CI: 1.1-3.1), and immunosuppressive diseases (OR: 3.6; 95% CI: 1.5-8.4) were independent predictors of death. CONCLUSION: Asthma and COPD are not risk factors for ICU admission and death related to SARS-CoV2 infection.
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Asma/epidemiología , COVID-19/mortalidad , Unidades de Cuidados Intensivos/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Bélgica/epidemiología , Comorbilidad , Enfermedad Crítica , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Factores de Riesgo , SARS-CoV-2RESUMEN
BACKGROUND: Methacholine bronchial challenge and bronchodilation to salbutamol are key tests in clinical practice to make asthma diagnosis. OBJECTIVE: To assess the concordance between the 2 tests and to see whether they actually identify the same population of asthmatics. METHOD: We conducted a retrospective study using our asthma clinic database to see how methacholine bronchial challenge compared to bronchodilation to salbutamol in untreated patients with recurrent or chronic symptoms suspicious of asthma. We identified 194 untreated patients with baseline forced expiratory volume in 1 second (FEV1) ≥70% predicted who had both a bronchodilation test with salbutamol and a methacholine bronchial challenge 7 to 14 days apart. A positive bronchial challenge was a provocative concentration of methacholine causing a 20% fall in FEV1 ≤16 mg/mL, whereas a positive bronchodilation test was a reversibility to 400 µg inhaled salbutamol ≥12% from baseline and 200 mL. RESULTS: Overall, asthma diagnosis was confirmed in 91% of cases leaving 9% of subjects with double negative tests. Isolated positive methacholine challenge was found in 71% of subjects, double positive tests in 17%, whereas isolated significant bronchodilation to salbutamol was rare (3%). There was no correlation between provocative concentration of methacholine causing a fall in FEV1 of 20% (PC20M) and the magnitude of salbutamol reversibility (P = .10). Baseline FEV1/forced vital capacity ratio inversely correlated with reversibility to salbutamol (P < .001) but not with PC20M (P = .1). No difference was found between the groups regarding demographic and immunoinflammatory features, including the proportion of eosinophilic asthma. CONCLUSION: We conclude that methacholine challenge outperforms reversibility to salbutamol to diagnose asthma without selecting patients with distinct inflammatory profile. Baseline airway obstruction predicts magnitude of reversibility but not hyperresponsiveness.
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Albuterol , Asma , Asma/diagnóstico , Asma/tratamiento farmacológico , Pruebas de Provocación Bronquial , Volumen Espiratorio Forzado , Humanos , Cloruro de Metacolina , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVE: Airway remodeling, as many other factors, may lead to lung function decline and irreversible airflow obstruction (IRAO) in asthma. This study was undertaken in order to highlight predictors of incomplete reversibility of airflow obstruction in adult asthmatics to identify patients with poorer prognosis and improve their care, and decrease morbidity. METHODS: A retrospective study was conducted in 973 asthmatics recruited from the University Asthma Clinic of Liege. Patients with IRAO (post-BD FEV1/FVC<0.7 & FEV1<80% predicted) were compared to patients with reversible airway obstruction (RAO) (post-BD FEV1/FVC≥0.7 & FEV1≥80% predicted). TGF-ß was measured in sputum supernatant of 85 patients. RESULTS: Seventeen percent of asthmatics presented with IRAO. These patients were significantly older, more smokers, with a lower proportion of female, a longer disease duration, were more poorly controlled with a lower quality of life. This sub-population of asthmatics also showed more often elevated blood and sputum eosinophils and neutrophils, and higher exacerbation and hospitalisation rates in the previous year. The multivariable analysis revealed male gender, longer disease duration, cigarette smoking, ACQ score, sputum eosinophils and neutrophils, ICS dose and OCS maintenance, BMI, and asthma onset as variables independently linked to IRAO. Total TGF-ß levels appeared higher in patients with IRAO (n = 38) compared to patients with RAO (n = 47). CONCLUSION: These data show that risk factors for IRAO are male gender, smoking, a longer disease duration, uncontrolled asthma, eosinophilic or neutrophilic airway inflammation, lower BMI, and later asthma onset. Moreover, TGF-ß levels are higher in IRAO.