RESUMEN
Sputum eosinophilia in Chronic Obstructive Pulmonary Disease (COPD) patients seems to be associated with a better response to inhaled corticosteroids (ICS). To verify if this feature could identify a specific subpopulation of COPD patients, we retrospectively compared functional and inflammatory parameters of 110 COPD patients according to the presence of sputum eosinophilia (>2%). Patient with eosinophilia were characterized by lower dyspnea score, lower functional impairment and lower ICS use, suggesting that airway eosinophilia may be associated to a lower COPD severity and some functional "asthma-like" characteristics, therefore explaining the better response to ICS in this subgroup of patients.
Asunto(s)
Eosinófilos/metabolismo , Recuento de Leucocitos , Enfermedad Pulmonar Obstructiva Crónica/patología , Esputo/citología , Anciano , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Glucocorticoides/administración & dosificación , Humanos , Masculino , Nebulizadores y Vaporizadores , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND AND AIMS: Severe asthma may require the prescription of one of the biologic drugs currently available, using surrogate markers of airway inflammation (serum IgE levels and allergic sensitization for anti-IgE, or blood eosinophils for anti-IL5/IL5R). Our objective: to assess upper and lower airway inflammation in severe asthmatics divided according to the eligibility criteria for one of the target biologic treatments. METHODS: We selected 91 severe asthmatics, uncontrolled despite high-dose ICS-LABA, and followed for >6 months with optimization of asthma treatment. Patients underwent clinical, functional and biological assessment, including induced sputum and nasal cytology. They were then clustered according to the eligibility criteria for omalizumab or mepolizumab/benralizumab. RESULTS: Four clusters were selected: A (eligible for omalizumab, n = 23), AB (both omalizumab and mepolizumab, n = 26), B (mepolizumab, n = 22) and C (non-eligible for both omalizumab and mepolizumab, n = 20). There was no difference among clusters for asthma control (Asthma Control Test and Asthma Control Questionnaire 7), pre-bronchodilator forced expiratory volume in 1 s, serum IgE and fractional exhaled nitric oxide levels. Sputum eosinophils were numerically higher in clusters AB and B, in agreement with the higher levels of blood eosinophils. Allergic rhinitis was more frequent in clusters A and AB, while chronic rhinosinusitis with nasal polyps prevalence increased progressively from A to C. Eosinophils in nasal cytology were higher in clusters AB, B and C. CONCLUSION: Eosinophilic upper and lower airway inflammation is present in the large majority of severe asthmatics, independently from the prescription criteria for the currently available biologics, and might suggest the use of anti-IL5/IL5R or anti IL4/13 also in patients without blood eosinophilia.The reviews of this paper are available via the supplemental material section.
Asunto(s)
Asma/tratamiento farmacológico , Eosinófilos/metabolismo , Mucosa Nasal/citología , Esputo/citología , Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/complicaciones , Omalizumab/uso terapéutico , Rinitis/complicaciones , Rinitis Alérgica/complicaciones , Sinusitis/complicacionesRESUMEN
Diabetic nephropathy (DN) is a microangiopathic complication of diabetes mellitus (DM) affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs), expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2), via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM), 11 with proteinuric nondiabetic nephropathy (NDN), and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN.
Asunto(s)
Albuminuria/diagnóstico , Acuaporina 2/orina , Acuaporina 5/orina , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/diagnóstico , Anciano , Albuminuria/orina , Biomarcadores/orina , Nefropatías Diabéticas/orina , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In difficult-to-treat asthmatics, uncontrolled despite a high level of therapy and followed for 3 years with a mean number of sputum samples/patient = 10, sputum eosinophilia (≥3%) was observed in 87% of all sputum samples. Persistent sputum eosinophilia is a characteristic of severe uncontrolled asthma.
Asunto(s)
Asma/inmunología , Eosinofilia/inmunología , Esputo/inmunología , Anciano , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate the potential determinants of forced expiratory volume in 1â s (FEV1) decline in workers with occupational asthma (OA) still exposed to the causative agent. We hypothesised that sputum eosinophilia might be a predictor of poor asthma outcome after diagnosis. SETTING, DESIGN AND PARTICIPANTS: In a specialistic clinical centre of the University Hospital of Pisa, we studied 39 participants (28 M, 11 F) diagnosed as having OA, routinely followed up between 1990 and 2009. They were a subgroup of 94 participants diagnosed as affected by OA in that period: 9 had been removed from work at the diagnosis, 21 were excluded for having ceased occupational exposure after few months from diagnosis, and 25 were lost at the follow-up or had no acceptable sputum measurements at the diagnosis. Estimates of the decline in FEV1 were obtained by means of simple regression analysis during the period of occupational exposure after diagnosis. Logistic regression was used to analyse the effects of factors (baseline FEV1 and sputum inflammatory cells, duration and type of exposure) that may potentially influence FEV1 decline. RESULTS: At follow-up (5.7+3.7â years), most participants were still symptomatic despite inhaled corticosteroids (ICS) treatment and had their occupational exposure reduced. Participants with higher sputum eosinophils (>3%) at baseline had a significantly greater decline of FEV1 (-52.5 vs -18.6â mL/year, p=0.012). Logistic regression showed that persistent exposure and sputum eosinophilia were significantly associated with a greater decline in FEV1 (OR 11.5, 95% CI 1.8 to 71.4, p=0.009 and OR 6.7, 95% CI 1.1 to 41.7, p= 0.042, respectively). CONCLUSIONS: Sputum eosinophilia at diagnosis, together with the persistence of occupational exposure during follow-up, may contribute to a greater decline in FEV1 in patients with OA still at work. Further long-term studies are required as to whether intensive ICS treatment may be beneficial for patients with OA and increase ad eosinophilic inflammation.
Asunto(s)
Asma Ocupacional/inmunología , Eosinofilia/inmunología , Esputo/inmunología , Corticoesteroides/uso terapéutico , Adulto , Asma Ocupacional/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/inmunología , Humanos , Estudios Longitudinales , Masculino , Exposición ProfesionalAsunto(s)
Obstrucción de las Vías Aéreas/diagnóstico , Asma/diagnóstico , Inflamación/diagnóstico , Obstrucción de las Vías Aéreas/inmunología , Asma/inmunología , Biomarcadores/análisis , Dióxido de Carbono/sangre , Eosinófilos , Espiración , Volumen Espiratorio Forzado , Humanos , Inflamación/inmunología , Óxido Nítrico , Oxígeno/sangre , Proyectos Piloto , Sistema Respiratorio/inmunología , Esputo/citologíaRESUMEN
BACKGROUND AND OBJECTIVE: Symptomatic, steroid-naïve asthmatic patients may have low sputum eosinophil numbers. The aim of the study was to determine whether low sputum eosinophil numbers persisted over time, during treatment with salmeterol monotherapy. METHODS: Forty steroid-naïve, symptomatic asthmatic patients, with sputum eosinophils <3%, were randomized to receive open-label salmeterol (50 µg twice a day, n = 30) or fluticasone (125 µg twice a day, n = 10) and were then assessed at 1, 3 and 6 months. All patients underwent spirometry, a methacholine challenge test and sputum induction at each visit. Symptom scores and peak expiratory flow were recorded throughout the study. Patients were permitted to withdraw from the study at any time, if they experienced exacerbations or deterioration of symptoms. RESULTS: The average sputum eosinophil percentage remained normal (≤1.9%) in both groups over the study period. The eosinophil percentages were ≤1.9% in 65 of the 80 samples obtained from salmeterol-treated patients throughout the study period. Eight patients had an asthma exacerbation or deterioration, during which one developed sputum eosinophilia. Twelve patients, 11 of whom were randomized to salmeterol and one to fluticasone, developed transient sputum eosinophilia at least once during the study. This was not associated with asthma exacerbation (except for one patient). Sputum neutrophil percentage did not change in either group. CONCLUSIONS: Low sputum eosinophil numbers persisted over 6 months in a majority of patients with non-eosinophilic asthma who received salmeterol monotherapy. However, transient sputum eosinophilia occurred in 40% indicating that non-eosinophilic asthma may not be a stable phenotype.
Asunto(s)
Albuterol/análogos & derivados , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Eosinofilia/inducido químicamente , Esputo/citología , Adulto , Albuterol/efectos adversos , Albuterol/uso terapéutico , Androstadienos/efectos adversos , Androstadienos/uso terapéutico , Asma/diagnóstico , Broncodilatadores/efectos adversos , Femenino , Fluticasona , Humanos , Masculino , Cloruro de Metacolina , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Xinafoato de Salmeterol , Adulto JovenRESUMEN
BACKGROUND: Asthma Control Test (ACT) is a simple tool for assessing the level of asthma control in clinical practice, and it has been validated in comparison with a general clinical assessment of asthma control, including forced expiratory volume in the first second (FEV(1)). OBJECTIVE: To evaluate the relationship between ACT score and clinical and functional findings of asthma control and biomarkers of airway inflammation. METHODS: A total of 68 asthmatic patients observed in our asthma clinic (33 regularly treated with inhaled corticosteroids (ICS) and 35 ICS-naïve) filled ACT questionnaire and underwent the following measurements: (a) FEV(1) before and after salbutamol; (b) exhaled nitric oxide; (c) bronchial hyperresponsiveness to methacholine; (d) sputum eosinophil count; and (e) daytime and nighttime symptoms, rescue salbutamol, and twice-daily peak expiratory flow (PEF) recording on a 4-week diary card. RESULTS: ACT score significantly correlated with symptom score, rescue medication use, and PEF variability, but not with FEV(1), FEV(1) reversibility, and markers of airway inflammation, which could not distinguish controlled from uncontrolled patients according to ACT, regardless of ICS treatment. CONCLUSION: ACT score is a valid tool to simply assess the current level of asthma control in terms of symptoms, rescue medication use, and PEF variability. Pulmonary function and biomarkers of airway inflammation are not related to the clinical asthma control as assessed by ACT and may represent additional measurements potentially useful in asthma management.
Asunto(s)
Asma/diagnóstico , Asma/tratamiento farmacológico , Biomarcadores/metabolismo , Encuestas y Cuestionarios , Corticoesteroides/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Adulto , Albuterol/farmacología , Albuterol/uso terapéutico , Asma/metabolismo , Asma/fisiopatología , Pruebas Respiratorias , Pruebas de Provocación Bronquial , Eosinófilos/patología , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Cloruro de Metacolina/farmacología , Persona de Mediana Edad , Neutrófilos/patología , Óxido Nítrico/metabolismo , Ápice del Flujo Espiratorio/fisiología , Esputo/citologíaRESUMEN
BACKGROUND: Severe asthma occurs in a heterogeneous group of patients in whom symptoms and airway inflammation persist despite maximal antiasthma treatment. OBJECTIVE: To verify whether a short-term course of oral steroids would modify sputum inflammatory cytokine and sputum eosinophil concentrations and whether this effect is related to the presence of sputum eosinophilia. METHODS: In 59 patients with severe refractory asthma, we measured pulmonary function and inflammatory markers in hypertonic saline-induced sputum before and after 2 weeks of treatment with 0.5 mg/kg of oral prednisone (n = 39) or placebo (n = 20) daily. Selected sputum portions were assayed for total and differential cell counts and supernatant interleukin (IL) 5 and IL-8 concentrations. RESULTS: At baseline, no statistical differences were found among placebo- and prednisone-treated patients in terms of sputum inflammatory cell percentages and IL-5 and IL-8 concentrations. After treatment, forced expiratory volume in 1 second significantly increased and sputum eosinophil percentages and IL-5 and IL-8 concentrations significantly decreased in the prednisone group, whereas no changes were observed in the placebo group. The positive effect of prednisone treatment was observed only in patients with baseline sputum eosinophilia, whereas in noneosinophilic patients with severe asthma prednisone induced only a significant decrease of sputum IL-8. CONCLUSIONS: Additional high-dose oral corticosteroids improve pulmonary function and reduce not only sputum eosinophil but also sputum proinflammatory cytokine concentrations in patients with severe refractory asthma.
Asunto(s)
Asma/tratamiento farmacológico , Eosinófilos/efectos de los fármacos , Interleucina-5/análisis , Interleucina-8/análisis , Prednisona/farmacología , Esputo/inmunología , Administración Oral , Adulto , Anciano , Asma/inmunología , Asma/patología , Método Doble Ciego , Eosinófilos/fisiología , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Esputo/citologíaRESUMEN
BACKGROUND: The inhibitory effect of corticosteroids (CS) on the secretions of cysteinyl-leukotrienes (Cys-LTs) in asthma is controversial. The aim of this study was to evaluate the effect of CS on allergen-induced increase in urinary leukotriene E4 (uLTE4) during early (EAR) and late (LAR) asthmatic responses in mild untreated asthmatics. MATERIAL AND METHODS: Nine subjects with mild untreated allergic asthma performed two allergen challenges, after 1-week treatment with beclomethasone dipropionate (BDP, 500 microg b.i.d) or placebo. Forced Expiratory Volume in one second 1 (FEV1) was monitored to assess EAR and LAR, and uLTE4 was measured before and during EAR and LAR. RESULTS: After placebo, uLTE4 increased significantly during EAR, but not during and after LAR, in comparison with baseline values. Beclomethasone dipropionate induced a significant attenuation of the uLTE4 increase during EAR, in comparison with placebo, in association with a good protection of LAR (P = 0.002) and a mild protection of EAR (P = 0.07). CONCLUSIONS: Beclomethasone dipropionate blunts the early increase in uLTE4 excretion due to allergen challenge, in association with a significant effect on the severity of LAR. These data support the hypothesis that inhaled CS may inhibit the allergen-induced release of cys-LTs in asthma.
Asunto(s)
Asma/tratamiento farmacológico , Beclometasona/farmacología , Glucocorticoides/farmacología , Leucotrieno E4/orina , Administración por Inhalación , Adulto , Alérgenos/administración & dosificación , Asma/fisiopatología , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Espirometría , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: The discrepancy between functional and inflammatory airway response to ozone has been reported in normal subjects, but few data are available for stable asthmatics regularly treated with inhaled corticosteroids. METHODS: Twenty-three well controlled, regularly treated, mild-to-moderate asthmatic patients underwent two sequential randomised exposures to either filtered air or ozone (0.3 ppm for 2 hours) in a challenge chamber. Pulmonary function (PF) was monitored, and patients with FEV1 decrease greater than 10% from pre-challenge value were considered as responders. Immediately after each exposure, exhaled breath condensate (EBC) was collected to measure malondialdehyde (MDA). Six hours after each exposure, PF and EBC collection were repeated, and sputum was induced to measure inflammatory cell counts and soluble mediators (IL-8 and neutrophil elastase). The response to ozone was also evaluated according to the presence of polymorphism in oxidative stress related NQO1 and GSTM1 genes. RESULTS: After ozone exposure, sputum neutrophils significantly increased in responders (n = 8), but not in nonresponders (n = 15). Other markers of neutrophil activation in sputum supernatant and MDA in EBC significantly increased in all patients, but only in nonresponders the increase was significant. In nonresponders, sputum eosinophils also significantly increased after ozone. There was a positive correlation between ozone-induced FEV1 fall and increase in sputum neutrophils. No difference in functional or inflammatory response to ozone was observed between subjects with or without the combination of NQO1wt- GSTM1null genotypes. CONCLUSIONS: Markers of neutrophilic inflammation and oxidative stress increase also in asthmatic subjects not responding to ozone. A greater functional response to ozone is associated with greater neutrophil airway recruitment in asthmatic subjects.
Asunto(s)
Asma/metabolismo , Citocinas/metabolismo , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Activación Neutrófila/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ozono/toxicidad , Adulto , Asma/terapia , Biomarcadores/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by a combination of 3 different disorders, namely chronic asthma, chronic bronchitis and pulmonary emphysema, sometimes simultaneously present in the same subject. OBJECTIVES: The aim of our study was to compare sputum inflammatory markers in patients with different phenotypes of chronic airway obstruction. METHODS: Forty-five subjects (forced expiratory volume in 1 s/vital capacity, FEV(1)/VC: 58.8 +/- 12.2%; FEV(1): 49.8 +/- 11.5% of predicted) were classified as chronic asthma (n = 10) or COPD patients (n = 35); the latter were further divided into patients with prevalent chronic bronchitis (n = 24) or prevalent pulmonary emphysema (n = 11) according to clinical history and functional evaluation, and underwent sputum induction and analysis of inflammatory cell and soluble mediators. RESULTS: Patients with chronic asthma showed higher sputum eosinophil percentages and eosinophilic cationic protein levels, and lower neutrophil percentages and neutrophil elastase levels than COPD patients. Neutrophil chemotactic activity in sputum supernatant was higher than the pool of normal subjects both in chronic asthma and COPD patients. No difference in sputum cell composition and levels of soluble mediators was observed between patients with chronic bronchitis and patients with pulmonary emphysema. CONCLUSIONS: The pattern of airway inflammation in induced sputum of patients with chronic asthma is different from that of COPD patients with a similar FEV(1). Among COPD patients, however, the pattern of airway inflammation shows no difference between chronic bronchitis and patients with pulmonary emphysema, suggesting that these two clinically and functionally distinct phenotypes share a common inflammatory pattern as detected by induced sputum.
Asunto(s)
Asma/diagnóstico , Biomarcadores/metabolismo , Bronquitis Crónica/diagnóstico , Enfisema Pulmonar/diagnóstico , Esputo/metabolismo , Anciano , Asma/inmunología , Asma/metabolismo , Bronquitis Crónica/inmunología , Bronquitis Crónica/metabolismo , Proteína Catiónica del Eosinófilo/metabolismo , Femenino , Granulocitos/citología , Humanos , Interleucina-8/metabolismo , Elastasa de Leucocito/metabolismo , Masculino , Persona de Mediana Edad , Fenotipo , Enfisema Pulmonar/inmunología , Enfisema Pulmonar/metabolismo , Esputo/citología , Esputo/inmunologíaRESUMEN
BACKGROUND: Late asthmatic response (LAR) to allergen challenge is a validated method for studying the pathogenesis of and new treatments for asthma in the laboratory. OBJECTIVE: To evaluate the relationship between the magnitude of allergen-induced LAR and clinical and biological determinants, including sputum and blood eosinophil percentages and eosinophil cationic protein concentrations. METHODS: Thirty-eight untreated mild asthmatic patients (mean age, 21.2 years) were selected for the presence of allergen-induced early asthmatic response (EAR) and LAR. Each patient measured methacholine responsiveness (provocation dose that caused a decrease in forced expiratory volume in 1 second of 20% [PD20FEV1]) at baseline, differential blood cell counts and eosinophil cationic protein levels in blood and induced sputum, and serum neutrophil chemotactic activity at baseline and 24 hours after allergen challenge. RESULTS: A correlation was found between LAR (as area under the curve [AUC]) and sputum eosinophil percentages at baseline (r = 0.51; P = .001) and 24 hours after allergen challenge (r = 0.44; P < .007). Furthermore, we found significant correlations between AUC LAR and AUC EAR, baseline methacholine PD20FEV1, baseline blood eosinophil percentages, and baseline serum neutrophil chemotactic activity. A stepwise multiple regression analysis showed that the stronger determinants of AUC LAR were baseline sputum eosinophilia and AUC EAR. CONCLUSION: Baseline sputum eosinophilia and functional findings are determinants of the magnitude of allergen-induced LAR.
Asunto(s)
Asma/inmunología , Pruebas de Provocación Bronquial/métodos , Eosinofilia/inmunología , Esputo/citología , Adolescente , Adulto , Alérgenos/administración & dosificación , Alérgenos/inmunología , Asma/sangre , Asma/fisiopatología , Recuento de Células , Quimiotaxis de Leucocito/inmunología , Proteína Catiónica del Eosinófilo/sangre , Proteína Catiónica del Eosinófilo/metabolismo , Eosinofilia/sangre , Eosinófilos/citología , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Volumen Espiratorio Forzado/fisiología , Humanos , Recuento de Leucocitos , Macrófagos Alveolares/citología , Masculino , Cloruro de Metacolina/farmacología , Neutrófilos/citología , Esputo/inmunología , Esputo/metabolismoRESUMEN
BACKGROUND: The effect of corticosteroids on the ozone (O3)-induced airway inflammation is still debated. OBJECTIVE: The aim of the study was to confirm the effect of a short-term treatment with oral glucocorticosteroids on O3-induced airway inflammation, detected by induced sputum analysis, and on functional response in glucocorticosteroid-naive subjects. METHODS: A randomized, placebo-controlled study using oral prednisone (25 mg o.d. for 4 days) was carried out. Nine mild persistent asthmatics were exposed for 2 h, on separatedays, to 0.27 ppm O3 and to air in random order, after 4 days of treatment with prednisone (25 mg o.d.) and after 4 days of placebo.Before and after exposure, pulmonary function test was measured; 6 h afterexposure, sputum induction was done. RESULTS: Oral glucorticosteroids did not prevent pulmonary function decrement due to O3. After placebo, the percentage of neutrophils in induced sputum was significantly higher after O3 than after air [52.1 (15.7-77.3) vs. 17.8 (1.7-58.4), p=0.02, O3 vs. air]. This difference was lost after 4 days of treatment with prednisone [35.2% (10-96.2) vs. 30.9% (6.1-75.6), n.s., O3 vs. air]. Neutrophil elastase in sputum supernatant increased after O3 exposure in the sample obtained after placebo, but not after prednisone treatment. CONCLUSIONS: This study confirms that glucocorticosteroids reduce inflammatory airway response, but do not prevent the airway functional impairment after O3 exposure.
Asunto(s)
Asma/tratamiento farmacológico , Bronquitis/patología , Glucocorticoides/uso terapéutico , Neutrófilos/efectos de los fármacos , Oxidantes Fotoquímicos/efectos adversos , Ozono/efectos adversos , Prednisona/uso terapéutico , Administración por Inhalación , Administración Oral , Adulto , Asma/patología , Bronquitis/inducido químicamente , Bronquitis/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Humanos , Elastasa de Leucocito/metabolismo , Masculino , Neutrófilos/enzimología , Neutrófilos/patología , Oxidantes Fotoquímicos/administración & dosificación , Ozono/administración & dosificación , Prednisona/administración & dosificación , Método Simple Ciego , Esputo/citología , Esputo/enzimología , Resultado del TratamientoRESUMEN
BACKGROUND: Severe asthma represents a heterogeneous group of patients whose characteristics of airway inflammation are poorly known. OBJECTIVE: To evaluate the sputum cytokine profiles of different phenotypes of severe asthma. METHODS: Severe asthmatic patients (n = 45) were divided into 3 groups: frequent exacerbations, persistent bronchoconstriction, and both features. Two other groups (9 patients with untreated mild asthma and 10 control subjects) were also studied. Selected sputum portions were assayed for differential cell count, supernatant interleukin 5 (IL-5), granulocyte-macrophage colony-stimulating factor, IL-8, and eosinophil cationic protein. RESULTS: There were no statistically significant differences among the 3 severe asthma groups in terms of sputum inflammatory cell percentages, IL-8 levels, and eosinophil cationic protein levels, although IL-8 levels tended to be higher in patients with persistent bronchoconstriction. Sputum concentrations of granulocyte-macrophage colony-stimulating factor and IL-5 were significantly higher in patients with frequent exacerbations compared with the other 2 groups. Levels of IL-5 and IL-8 were higher in severe asthmatic patients compared with mild asthmatic patients and controls, whereas sputum eosinophil percentages were intermediate between those of mild asthmatic patients and controls. CONCLUSIONS: Proeosinophilic cytokine levels are increased in severe asthmatic patients with frequent exacerbations but not in severe asthmatic patients with persistent bronchoconstriction, suggesting that different cytokine profiles could be associated with different phenotypes of severe asthma.
Asunto(s)
Asma/inmunología , Biomarcadores/análisis , Citocinas/inmunología , Esputo/inmunología , Adulto , Anciano , Eosinófilos/inmunología , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/análisis , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Humanos , Inflamación/inmunología , Interleucina-5/análisis , Interleucina-5/metabolismo , Interleucina-8/análisis , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Esputo/química , Esputo/citologíaRESUMEN
BACKGROUND: The prognostic role of low sputum eosinophils in steroid-naïve, symptomatic asthmatic patients is controversial. AIM: To verify whether low sputum eosinophils predict poor response to treatment with inhaled corticosteroids. METHODS: Sixty-seven symptomatic asthmatic patients with moderate asthma were examined before and after 2 weeks and 4 weeks of treatment with beclomethasone dipropionate, 500 microg bid. None received corticosteroids in the 3 months preceding the study. At each visit, all patients underwent spirometry, methacholine challenge, and sputum induction. The patients recorded symptom scores and peak expiratory flow (PEF) throughout the study. RESULTS: Seventeen patients had low sputum eosinophils despite being symptomatic. Patients with high (> 3%) sputum eosinophils at baseline showed significant improvement in symptoms, pulmonary function, and bronchial hyperresponsiveness after treatment, whereas patients with low sputum eosinophils showed no significant improvement in most clinical and functional outcomes. Among the baseline indexes examined, sputum eosinophils had the highest negative predictive value but low positive predictive value for the response to treatment. Multiple stepwise regression showed that only baseline FEV(1) and sputum eosinophil percentages significantly correlated with changes in FEV(1) after treatment. CONCLUSIONS: We suggest that, among the indexes examined, low sputum eosinophils are the best predictor for poor corticosteroid effects in asthma.
Asunto(s)
Asma/tratamiento farmacológico , Beclometasona/uso terapéutico , Eosinófilos , Glucocorticoides/uso terapéutico , Esputo/citología , Adulto , Asma/fisiopatología , Pruebas de Provocación Bronquial , Proteína Catiónica del Eosinófilo/análisis , Femenino , Volumen Espiratorio Forzado , Humanos , Recuento de Leucocitos , Linfocitos , Masculino , Neutrófilos , Pronóstico , Curva ROC , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
The aim of this study was to evaluate whether fluticasone propionate (FP) is effective as well as prednisone (P) in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbations not requiring hospitalization. We measured, in a parallel-group, double-blind double-dummy, randomized study, sputum and blood inflammatory cell counts and soluble mediators in 37 asthmatic subjects during a spontaneous exacerbation of asthma (Visit 1) and after a 2 week (Visit 2) treatment with inhaled FP (1000microg bid) (Group A, n=18) or a reducing course of oral P (Group B, n=19). Asthma exacerbation was accompanied by sputum eosinophilia (eosinophils >2%) in almost all patients (95%). FP improved FEV(1) (from 53.9%+/-16.8 at Visit 1 to 76.4%+/-21.2 at Visit 2, p=0.0001) and reduced the percentage of sputum eosinophils (from 38%[0-78] to 3%[1-31, p=0.0008) as well as oral P (FEV(1): from 51.5%+/-14.4 to 83.6%+/-21.1, p=0.0001; sputum eosinophils: from 52%[1-96] to 11%[0-64], p=0.0003). At Visit 2, sputum eosinophils were significantly lower in Group A than in Group B. P but not FP induced significant decrease in blood and sputum ECP. Oxygen saturation, PEF variability, symptom score and use of rescue medication similarly improved in both groups. We conclude that FP is effective at least as well as P in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbation. However, the cost/effectiveness ratio of this option should be further evaluated.
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Androstadienos/uso terapéutico , Asma/tratamiento farmacológico , Prednisona/uso terapéutico , Esputo/citología , Enfermedad Aguda , Administración por Inhalación , Administración Oral , Androstadienos/administración & dosificación , Asma/patología , Asma/fisiopatología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Proteína Catiónica del Eosinófilo/sangre , Eosinofilia/tratamiento farmacológico , Eosinofilia/patología , Eosinófilos/química , Eosinófilos/citología , Eosinófilos/efectos de los fármacos , Femenino , Fluticasona , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Oximetría , Prednisona/administración & dosificación , Prednisona/efectos adversos , Recurrencia , Índice de Severidad de la Enfermedad , Esputo/química , Esputo/efectos de los fármacos , Resultado del TratamientoRESUMEN
The aim of this study was to assess the distribution of the occurrence of tolerance to the protective effect of salmeterol on allergen challenge in a large sample of asthmatic subjects. We investigated 53 subjects (45 male and eight female), mean age 24+/-8.2 years, with mild intermittent asthma, in stable phase of the disease, never previously treated with regular beta2-agonists. All subjects with a previous positive early airway response (EAR) to a screening allergen challenge underwent, in double blind randomized, cross-over manner, three further allergen challenges: after placebo (T0), after a single dose (50 microg) of inhaled salmeterol (T1), and after regular treatment with inhaled salmeterol (50 microg bid) for 1 week (T2). All subjects showed an EAR after placebo treatment (T0), and were completely protected against EAR by the single dose of salmeterol (T1). After 1-week regular treatment with salmeterol (T2). 24 out of 53 subjects (45%) were still protected, whereas 29 subjects (55%) showed a significant EAR. The distribution of the response to allergen challenge, which was quite homogeneous at T0 and T1, showed considerable heterogeneity at T2. Tolerance to the protective effect of salmeterol on allergen challenge can be observed in a large group of previously untreated mild asthmatic subjects. This phenomenon is heterogeneously distributed, with some subjects still showing a complete protection similar to that obtained after a single dose of salmeterol and others showing a response similar to that obtained after placebo. The reason of this heterogeneity needs to be elucidated.
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Agonistas Adrenérgicos beta/farmacología , Albuterol/análogos & derivados , Albuterol/farmacología , Asma/tratamiento farmacológico , Tolerancia a Medicamentos , Administración por Inhalación , Agonistas Adrenérgicos beta/administración & dosificación , Adulto , Resistencia de las Vías Respiratorias , Albuterol/administración & dosificación , Pruebas de Provocación Bronquial , Estudios Cruzados , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Xinafoato de SalmeterolRESUMEN
BACKGROUND: Acute airway inflammation is considered to characterize asthma exacerbations, but its specific cellular pattern has not yet been completely evaluated. AIM: To evaluate the prevalence of sputum eosinophilia during acute asthma exacerbations of moderate severity, compared with a stable phase of the disease, and to assess the concordance between changes in pulmonary function and sputum eosinophilia in the period between exacerbation and post exacerbation. METHODS: We compared sputum and blood inflammatory cell counts in 29 asthmatic subjects during a spontaneous moderate exacerbation of asthma (visit 1) with sputum and blood cell counts measured 4 weeks after the resolution of asthma exacerbation (visit 2). At visit 1, all subjects required an appropriate 1 week treatment with oral corticosteroids. RESULTS: At visit 1, all subjects were able to collect spontaneous sputum, whereas at visit 2 sputum was induced by inhalation of hypertonic saline (NaCl 3, 4, and 5%, 10 minutes each) with beta2-agonist pretreatment. Asthma exacerbation was accompanied by a significant increase in sputum eosinophil percentages compared with levels after exacerbation [25% (1-78) versus 4% (0-23), p<0.05). Only four subjects showed low sputum eosinophil percentages during exacerbation, and these showed no differences in main clinical findings with respect to subjects with sputum eosinophilia. At visit 2, the stability of asthma was assessed on the basis of PEF, FEV1, symptoms, and use of rescue beta2-agonist. Asthma was defined as stable in 21 out of 29 subjects. Sputum eosinophil percentages fell significantly between visit 1 and visit 2 in both stable and unstable patients, but at visit 2 sputum eosinophil percentages were still high in subjects with unstable asthma. In patients who proved to be stable at visit 2, there was a significant correlation between the changes recorded in sputum eosinophil percentages and in FEV1 between the two visits (rho: 0.723, p<0.001). CONCLUSION: Sputum cosinophil but not neutrophil percentages increase in most asthmatic subjects during moderate exacerbation of asthma. Changes in the degree of airway eosinophilic inflammation are related to changes in the severity of airway obstruction during asthma exacerbation.
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Asma/patología , Eosinofilia/patología , Esputo/citología , Estudios de Casos y Controles , Recuento de Células , Eosinófilos/patología , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Solución Salina HipertónicaRESUMEN
To evaluate the reproducibility of induced sputum analysis, and to estimate the sample size required to obtained reliable results, sputum was induced by hypertonic saline inhalation in 29 asthmatic subjects on two different days. The whole sample method was used for analysis, and inflammatory cells were counted on cytospin slides. Reproducibility, expressed by intra-class correlation coefficients, was good for macrophages (+0.80), neutrophils (+0.85), and eosinophils (+0.87), but not for lymphocytes (+0.15). Detectable differences were 5.5% for macrophages, 0.6% for lymphocytes, 5.2% for neutrophils, and 3.0% for eosinophils. We conclude that analysis of induced sputum is a reproducible method to study airway inflammation in asthma. Sample sizes greater than ours give little improvement in the detectable difference of eosinophil percentages.