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BACKGROUND: Interleukin(IL)-33 is an epithelial alarmin important for eosinophil maturation, activation and survival. The aim of this study was to examine the association between IL-33, its receptor expression and airway eosinophilic inflammation in non-atopic COPD. METHODS: IL-33 concentrations were measured in exhaled breath condensate (EBC) collected from healthy non-smokers, asthmatics and non-atopic COPD subjects using ELISA. Serum and sputum samples were collected from healthy non-smokers, healthy smokers and non-atopic COPD patients. Based on sputum eosinophil count, COPD subjects were divided into subgroups with airway eosinophilic inflammation (sputum eosinophils > 3%) or without (sputum eosinophils ≤3%). IL-33 and soluble form of IL-33 receptor (sST2) protein concentrations were measured in serum and sputum supernatants using ELISA. ST2 mRNA expression was measured in peripheral mononuclear cells and sputum cells by qPCR. Hemopoietic progenitor cells (HPC) expressing ST2 and intracellular IL-5 were enumerated in blood and induced sputum by means of flow cytometry. RESULTS: IL-33 levels in EBC were increased in COPD patients to a similar extent as in asthma and correlated with blood eosinophil count. Furthermore, serum and sputum IL-33 levels were higher in COPD subjects with sputum eosinophilia than in those with a sputum eosinophil count ≤3% (p < 0.001 for both). ST2 mRNA was overexpressed in sputum cells obtained from COPD patients with airway eosinophilic inflammation compared to those without sputum eosinophilia (p < 0.01). Similarly, ST2 + IL-5+ HPC numbers were increased in the sputum of COPD patients with airway eosinophilia (p < 0.001). CONCLUSIONS: Our results indicate that IL-33 is involved in the development of eosinophilic airway inflammation in non-atopic COPD patients.
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Interleucina-33/biosíntesis , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Eosinofilia Pulmonar/inmunología , Eosinofilia Pulmonar/metabolismo , Anciano , Eosinófilos/inmunología , Eosinófilos/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esputo/inmunología , Esputo/metabolismoRESUMEN
BACKGROUND: Previous murine models have demonstrated interleukin (IL)-33 to be an important mediator of type-2 inflammation and to promote airway hyperresponsiveness in allergic asthma. A number of inflammatory cells produce IL-33 and eosinophils express ST2 mRNA. The relationship between IL-33 and eosinophils in allergic asthma, however, remains unclear. OBJECTIVE: The aim of this work was to evaluate in vitro the effect of allergen inhalation on IL-33 levels and expression of its receptor (ST2L) on eosinophils in allergic asthmatics, and the effect of IL-33 stimulation on eosinophil activity. METHODS: Plasma and sputum IL-33, soluble ST2 (sST2) levels, and ST2L expression on eosinophils were measured in 10 healthy controls and 10 allergic asthmatics. Asthmatics underwent allergen and diluent inhalation challenges. Blood and sputum samples were collected to measure IL-33, sST2, and ST2L eosinophil expression before and 24 h after allergen inhalation. Purified blood eosinophils from allergic asthmatics were incubated overnight with IL-33 to assess ST2 and intracellular IL-5 expression. RESULTS: Baseline levels of IL-33 in sputum and sST2 in plasma and sputum were similar in allergic asthmatics compared to healthy controls. In addition, there was no difference in blood or sputum eosinophil ST2L expression in healthy controls versus allergic asthmatics. Eosinophil ST2L expression was significantly increased 24 h postallergen inhalation in allergic asthmatics. In vitro stimulation of human eosinophils with IL-33 and LPS significantly increased eosinophil ST2L expression and IL-33 stimulation increased intracellular IL-5 expression, which was attenuated by treatment with sST2 and ST2 blockade. CONCLUSION AND CLINICAL RELEVANCE: In mild asthmatics, there was a significant upregulation of ST2 surface expression on eosinophils from blood and sputum following allergen inhalation challenge. In vitro, IL-33 stimulation of eosinophils increases both ST2 membrane expression and IL-5 production. These results support a role for IL-33 in causing allergen-induced eosinophilia. Blockade of IL-33 and ST2 signaling may present a novel therapeutic avenue for asthma treatment.
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Alérgenos/inmunología , Asma/inmunología , Proteína 1 Similar al Receptor de Interleucina-1/análisis , Interleucina-33/análisis , Adulto , Eosinófilos/inmunología , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana EdadRESUMEN
RATIONALE: IL-25 is an epithelial-derived cytokine, whose effects are mediated by the IL-25 receptor (IL-17RB), and that has been implicated in the pathogenesis of allergic disease and airway viral responses. Airway myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells. pDCs may play a protective role in asthma and are key players in the innate immune response through recognition of microbial products via Toll-like receptors (TLRs). The effects of inhaled allergens on the expression of IL-17RB by mDCs and pDCs, and the effects of IL-25 on pDCs, are unknown. OBJECTIVES: To evaluate allergen-induced changes in IL-17RB expression by mDCs and pDCs and to investigate the effects of IL-25 on pDCs. METHODS: Patients with mild atopic asthma (n = 13) were challenged with inhaled allergen. Blood and sputum DCs were enumerated and IL-17RB expression was determined by flow cytometry before and 7 and 24 hours after allergen challenge. The effects of IL-25 on pDCs in vitro were also assessed. MEASUREMENTS AND MAIN RESULTS: Inhaled allergen significantly increased mDC and pDC numbers in sputum but not in blood. The percentage of IL-17RB(+) mDCs and pDCs was significantly increased in blood and sputum 24 hours after challenge. IL-25 up-regulated TLR9 expression by pDCs and orchestrated the responses to TLR9 ligation. CONCLUSIONS: IL-17RB is up-regulated on blood and sputum mDCs and pDCs after allergen inhalation. IL-25 modulates pDC function through an effect on TLR9 expression.
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Asma/inmunología , Pruebas de Provocación Bronquial/métodos , Células Dendríticas/inmunología , Receptores de Interleucina/inmunología , Administración por Inhalación , Adolescente , Adulto , Anciano , Alérgenos/administración & dosificación , Alérgenos/inmunología , Alérgenos/metabolismo , Asma/metabolismo , Células Dendríticas/metabolismo , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Receptores de Interleucina/metabolismo , Esputo/inmunología , Adulto JovenRESUMEN
BACKGROUND: The alarmin cytokines IL-25 and IL-33 are key promoters of type 2 inflammation. Basophils respond to alarmin cytokines, however the relationship of these cytokines with basophil activation and recruitment in human studies of allergic asthma has not been well characterized. This study investigated the effect of IL-25 and IL-33 on basophils in a model of allergic asthma. METHODS: 10 mild allergic asthmatics underwent allergen and diluent inhalation challenges. Bone marrow aspirates were collected at pre-challenge and 24 h (h) post challenge. Peripheral blood and sputum samples were collected at pre-challenge, 7 h, and 24 h post-challenge to measure basophil expression of IL-17RB, ST2, and intracellular IL-25. Freshly isolated peripheral blood basophils from allergic donors were incubated overnight with IL-25 and IL-33, or sputum supernatant collected post-allergen to assess pro-inflammatory effects of mediators released in the airways. RESULTS: There were increased percentage of basophils expressing IL-17RB, ST2, and intracellular IL-25 collected from bone marrow, peripheral blood, and sputum after allergen inhalation challenge. In vitro stimulation with IL-25 and IL-33 increased the percentage of basophils expressing intracellular type 2 cytokines and surface activation markers, and primed eotaxin-induced migratory potential of basophils, which was mediated directly through IL-17RB and ST2, respectively. Stimulation of basophils with sputum supernatants collected post-allergen challenge up-regulated the percentage of basophils expressing markers of activation and intracellular type 2 cytokines, which was reversed following blockade of the common ß chain (ßc). CONCLUSIONS: Our findings indicate that the alarmin cytokines IL-33 and IL-25 increase basophil activation and migratory potential, and may pose as a novel therapeutic targets for the treatment of allergic asthma.
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Asma/inmunología , Basófilos/inmunología , Interleucina-17/inmunología , Interleucina-33/inmunología , Hipersensibilidad Respiratoria/inmunología , Adulto , Asma/clasificación , Asma/patología , Basófilos/patología , Movimiento Celular/inmunología , Proliferación Celular , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hipersensibilidad Respiratoria/clasificación , Hipersensibilidad Respiratoria/patología , Adulto JovenRESUMEN
INTRODUCTION: Lysine aspirin (l-ASA) bronchial challenge can be used in the diagnostics of aspirin exacerbated respiratory disease. It is safer than oral challenge, however it is characterized by a lower sensitivity. AIM: We sought to investigate whether additional indicators of the positive result of l-ASA bronchial challenge, i.e. late phase reaction (LPR) and extrabronchial symptoms (EBS), may enhance its diagnostic value. MATERIAL AND METHODS: Sixty-seven patients with a positive history of asthma exacerbated by aspirin and/or other non-steroidal inflammatory drugs underwent l-ASA bronchial challenge. The control groups comprised 15 aspirin tolerant asthmatics and 15 healthy subjects. Forced expiratory volume in 1 s (FEV1) and 24-hour peak expiratory flow (PEF) measurements were performed in all subjects in order to recognize early and late response to l-ASA. All subjects underwent oral ASA challenge 2 weeks after l-ASA bronchial challenge. RESULTS: Basing on FEV1 and PEF results, early reaction was present in 50.7% of patients, early and LPR in 29.9% and LPR in only 10.4% of aspirin exacerbated respiratory disease patients. The EBS were noted in 31.3% of subjects. Inclusion of LPR and EBS as positive criteria of the challenge increased sensitivity to 94.0%. CONCLUSIONS: These results indicate that both LPR and EBS should be considered as positive criteria of aspirin bronchial challenge as they enhance its diagnostic value.
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Omalizumab is a monoclonal antibody against IgE, nowadays approved for the treatment of persistent severe (EU) or moderate-to severe (USA) IgE-mediated asthma but there is also some evidence (case reports and four published clinical trials) on the effectiveness of this medication in urticaria and angioedema. The case of a 42-year-old woman suffering from severe allergic asthma and severe chronic urticaria with concomitant angioedema is presented in the article. She had a life-threatening episode of bronchospasm and larynx edema after exposure to house dust recorded in her medical history. The patient did not respond to standard therapy. The improvement in asthma control and remission of chronic urticaria and angioedema was achieved after introducing the therapy with omalizumab.
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The article presents case reports of 2 women who became pregnant during therapy with omalizumab. Both subjects suffered from very severe asthma and were treated chronically with all available medications including systemic steroids (first - 20 mg prednisolone/day, second - 40 mg prednisolone/day). Both were enrolled into treatment with omalizumab and started regular therapy in 2007. The course of asthma significantly improved in both cases (withdrawal of oral steroids or significant reduction of their dose, better asthma control). The first woman, 32-year-old, became pregnant in 2010 and gave birth in Oct 2010 - it was her 3(rd) pregnancy, and 3(rd) labor. The second woman, 31-year-old, also became pregnant in 2010 and gave birth in Jan 2011 - it was her 5(th) pregnancy and 2(nd) labor. Both had severe asthma exacerbations during previous pregnancies and labors, and decided to continue therapy with omalizumab. The first woman, besides omalizumab, was treated with high doses of inhaled corticosteroids (ICS) and long-acting ß agonists (LABA) while the second one was treated with high doses of ICS, LABA and 2.5 mg to 5 mg prednisone/day. The pregnancies proceeded without asthma exacerbations. The first woman delivered a healthy girl (Apgar 9, weight 3200 g, length 56 cm) in the 40(th) week of pregnancy by caesarean section due to the narrow pelvis. The second one delivered a healthy boy (Apgar 9, weight 3800 g, length 56 cm) in week 40 by caesarean section due to the aggravating obstetrical history. In both cases, treatment with omalizumab did not affect pregnancies and newborns.
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INTRODUCTION: Inhaled fluticasone is used in the treatment of chronic bronchial asthma. Its high efficacy and good safety profile have been proven by clinical trials and observations. Its unique pharmacokinetic properties make it distinguishable from other drugs from this group. In vitro tests run on an artificial model of the airways and pharmacokinetic studies conducted on healthy volunteers have shown that the new formulation of this drug is outstanding due a twofold better lung deposition, compared to the reference medicine. The aim of this study was to evaluate the efficacy and safety of the new formulation of fluticasone propionate administered through new generation cyclohaler (CNG), compared to original fluticasone administered through dry powder inhaler (DPI) in patients with chronic moderate asthma. MATERIAL END METHODS: The study included 457 patients. 376 subjects were randomized to one out of the three groups: 127 subjects--to the group treated with the new formulation of fluticasone at a dose of 125 µg BID, 125 subjects--to the group treated with new formulation of fluticasone at a dose of 250 µg BID, and 124 subjects--to the group treated with the reference drug--fluticasone DPI 500 µg BID. At the beginning of the study, the groups did not differ in demographical or clinical aspects. Active therapy lasted 12 weeks. The primary endpoint was a mean change in morning PEF during a 12-week course of therapy (ΔmPEF of 15 L/min was considered as statistically significant). Additionally, other functional parameters of the respiratory system--clinical symptoms and the use of rescue drugs were studied. During the whole study the safety of patients was monitored by recording adverse events; in addition, a systemic exposure to fluticasone was evaluated by testing the changes of cortisol in serum and in a 24-hour collection of urine in a subgroup consisting of 45 patients. Statistical analysis was conducted on both groups: intention-to-treat (ITT) and per protocol (PP). RESULTS: In PP as well as in ITT analysis, a mean change in morning PEF at the end of the therapy in comparison with the initial period was statistically significant in all therapeutic groups. The efficacy of the treatment with fluticasone at doses of 125 µg BID and 250 µg and the reference medicines did not differ statistically significantly after a 12-week course of therapy or during the whole period of treatment. During the study, significant improvement in the range of other functional parameters such as evening PEF, FEV1, clinical symptoms and the use of rescue drugs was observed in all therapeutic groups, without significant differences in efficacy between the study groups. The comparison of efficacy of fluticasone at a dose of 125 µg BID with the generic product at a dose of 250 µg BID showed a weak dose-response relationship concerning the change in morning PEF, which arises from the almost flat dose-response curve in the range of medium and high doses for this drug. No significant quantitative or qualitative differences were shown between the groups in the recorded adverse events, qualified as related to treatment with fluticasone. There were no significant changes revealed in cortisol concentration in serum or in a 24-hour collection of urine between the initial level and the final visit in any of the groups. CONCLUSIONS: Fluticasone administered through the new generation cyclohaler, compared to original fluticasone DPI, allows a twofold reduction in drug dose, retaining in new formulation clinical efficacy that corresponds to the reference drug at twice the dose. New formulation of fluticasone administered through the new generation cyclohaler has a safety profile clinically comparable to the reference drug.
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Androstadienos/administración & dosificación , Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Administración por Inhalación , Adolescente , Adulto , Anciano , Androstadienos/química , Broncodilatadores/administración & dosificación , Química Farmacéutica , Esquema de Medicación , Inhaladores de Polvo Seco , Femenino , Fluticasona , Humanos , Masculino , Persona de Mediana Edad , Nebulizadores y Vaporizadores , Adulto JovenRESUMEN
Bcl I in the promoter polymorphism observed within h-GR/NR3C1 gene may play an important role in the development of bronchial asthma and resistance to GCs in the severe bronchial asthma. The aim of the investigation was to study the correlation between this h-GR/NR3C1 gene polymorphism and occurrence of asthma in the population of Polish asthmatics. Peripheral blood was obtained from 70 healthy volunteers and 59 asthma patients. Structuralized anamnesis, spirometry and allergy skin prick tests were performed in all participants. Genotyping was carried out with PCR-RFLP method. In healthy, non-atopic population variants of Bcl I: GG, GC, CC were found with frequency 0.129/0.471/0.400, respectively. In asthma patients Bcl I: GG, GC, CC occurred with respective frequencies of 0.410/0.462/0.128. Chi-square analysis revealed a significantly different (P<0.05) distribution between cases and controls for the Bcl I polymorphism. The Bcl I polymorphism of h-GR/NR3C1 gene is significantly associated with bronchial asthma, susceptibility to the development of severe form and resistance to GCs in Polish population.
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Asma/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas , Receptores de Glucocorticoides/genética , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Programas InformáticosAsunto(s)
Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Inmunoglobulina E/inmunología , Omalizumab/administración & dosificación , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/inmunología , Esquema de Medicación , Humanos , Omalizumab/uso terapéuticoRESUMEN
INTRODUCTION: The procedure of lung parenchyma resection may result in impairment of physical capacity and quality of life. In patients with operable non-small cell lung cancer (NSCLC), lobectomy is an elective procedure. Chronic obstructive pulmonary disease (COPD) is a common coexisting condition in patients with NSCLC. Effectiveness of post-operative pulmonary rehabilitation (PR) in patients who underwent lobectomy due to NSCLC and suffering from COPD as compared to individuals without COPD has not been determined yet. The aim of the study was to compare effectiveness of post-operative PR in patients with COPD after lobectomy due to NSCLC (COPD[+] L [+]) with individuals with COPD without lung parenchyma resection (COPD(+) L(-)) and those who underwent lobectomy due to NSCLC and not suffering from COPD (COPD[-] L[+]). MATERIAL AND METHODS: Thirty-seven patients with non-small cell lung cancer (21 patients with and 16 patients without COPD) who underwent lobectomy and 29 subjects with COPD referred to the Lung Diseases Treatment and Rehabilitation Centre in Lodz in 2018-2019 were included in this retrospective analysis. The patients participated in a 3-week inpatient pulmonary rehabilitation (PR) program which included breathing exercises, physical workout, relaxation exercises, education, psychological support and nutrition consulting. The evaluation included lung function measurements, six-minute walking test (6MWT) and the St. George's Respiratory Questionnaire (SGRQ) score. The results obtained before the rehabilitation were compared to those achieved after the 3-week PR program and compared between the study groups. RESULTS: A significant increase in the distance covered during 6MWT was observed in all the three groups studied: COPD(+) L(+) (Δ = 62.52 ± 14.58 m); COPD(-) L(+) (Δ = 73.67 ± 11.58 m); and COPD(+) L(-) (Δ = 59.93 ± 10.02 m) (p < 0.001 for all). Similarly, a statistically and clinically significant improvement in the total SGRQ score was recorded: COPD(+) L(+) ∆ = -12.05 ± 3.96 points; p < 0.05 and COPD(-) L(+) ∆ = -12.30 ± 4.85 points; p < 0.01 and COPD(+) (L-) ∆= -14.07 ± 3.36 points (p < 0.001). No significant differences in the outcome improvement between the study groups were identified. CONCLUSIONS: The results of the study show that COPD(+) L(+) patients gained benefits from post-operative PR comparable to COPD(+) L(-) and COPD(-) L(+) subjects by improving their physical capacity and quality of life.
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Carcinoma de Pulmón de Células no Pequeñas/rehabilitación , Neoplasias Pulmonares/rehabilitación , Neoplasias Pulmonares/cirugía , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Insuficiencia Respiratoria/rehabilitación , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Terapia por Ejercicio/métodos , Humanos , Neoplasias Pulmonares/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/etiología , Insuficiencia Respiratoria/etiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Prueba de PasoRESUMEN
INTRODUCTION: Interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP) are epithelial alarmins involved in innate immune responses and have been shown to play an important role in chronic lung diseases. No data are available regarding their levels in exhaled breath condensate (EBC) in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To examine IL-25, IL-33 and TSLP levels in the EBC obtained from patients with IPF and compare them to those in healthy controls, patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS: Twenty-three patients with asthma, 25 patients with COPD, 15 patients with IPF and 16 healthy controls were studied. Concentrations of alarmins in the EBC were evaluated by means of ELISA. RESULTS: IL-25 EBC levels were numerically lowest in IPF (25.33 ± 8.84 pg/ml). However, they did not differ significantly from healthy subjects (43.18 ± 5.53 pg/ml), but were significantly lower compared to asthma (72.07 ± 6.03 pg/ml; P < .001). IL-33 EBC levels were significantly increased in IPF (3.41 ± 0.55 pg/ml) compared to healthy controls (1.20 ± 0.60 pg/ml; P < .01) but did not differ from asthma (3.68 pg/ml) and COPD levels (2.47 ± 0.34 pg/ml). There were significant correlations between IL-33 EBC levels and lung diffusion capacity of carbon monoxide (DLco ) absolute (r = .63; P < .05) and % of predicted values (r = .67; P < .01) as well as with time since diagnosis (r = -.59; P < .05) in IPF subjects. TSLP was undetectable in examined samples. CONCLUSION: IL-25 and IL-33 are detectable in the EBC obtained from IPF subjects. Increased levels of IL-33 compared to healthy controls indicate its possible role in the pathobiology of IPF.
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Alarminas/metabolismo , Pruebas Respiratorias/métodos , Espiración/inmunología , Fibrosis Pulmonar Idiopática/metabolismo , Anciano , Asma/metabolismo , Citocinas/metabolismo , Epitelio/metabolismo , Femenino , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/fisiopatología , Interleucina-17/inmunología , Interleucina-33/inmunología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Linfopoyetina del Estroma TímicoRESUMEN
Background: Despite the absence of endogenous chitin in humans, chitinases are present in the serum of healthy subjects and their levels are increased in a variety of chronic inflammatory conditions. It has been shown that chitotriosidase and structurally related chitinase-like protein-YKL-40 contribute to the pathogenesis of COPD. However, details regarding the relation of their systemic and local airways levels remain unknown. Objectives: To examine peripheral blood and sputum chitotriosidase and YKL-40 expression in smokers and patients with COPD. Methods: Forty patients with COPD, 20 healthy smokers and 10 healthy never-smokers were studied. Serum and induced sputum chitotriosidase protein and activity levels, YKL-40 concentrations, and their gene expression in sputum cells and peripheral blood mononuclear cells (PBMC) were evaluated. Results: Both chitotriosidase protein levels and activity were higher in sputum obtained from COPD subjects compared to healthy never-smokers (P<0.05 and P<0.01, respectively). A similar pattern was observed for PBMC chitotriosidase mRNA expression (P<0.001). YKL-40 serum concentrations were elevated in healthy smokers and COPD subjects compared to healthy never-smokers (P<0.001 and P<0.01, respectively). In sputum, YKL-40 levels were increased in COPD compared to healthy never-smokers (P<0.01). PBMC YKL-40 mRNA expression was increased in COPD and healthy smokers compared to healthy never-smokers (P<0.0001). No associations were found between chitotriosidase or YKL-40 peripheral blood levels and sputum levels. Conclusions: Our results demonstrate that chitotriosidase and YKL-40 are overexpressed in peripheral blood and airways in both healthy smokers and COPD subjects which may indicate smoking-related activation of macrophages, neutrophils, and epithelial cells.
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Proteína 1 Similar a Quitinasa-3 , Hexosaminidasas , Enfermedad Pulmonar Obstructiva Crónica , Fumar , Esputo/metabolismo , Proteína 1 Similar a Quitinasa-3/sangre , Proteína 1 Similar a Quitinasa-3/metabolismo , Femenino , Perfilación de la Expresión Génica/métodos , Hexosaminidasas/sangre , Hexosaminidasas/metabolismo , Humanos , Leucocitos Mononucleares/inmunología , Activación de Macrófagos , Masculino , Persona de Mediana Edad , Activación Neutrófila , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Fumar/sangre , Fumar/metabolismo , Fumar/patologíaRESUMEN
Chronic Obstructive Pulmonary Disease (COPD) has been traditionally associated with neutrophilic inflammation of the bronchi. Studies from the early 1990s demonstrated that eosinophils may also get into the lower airways of patients with COPD and their increased numbers can be noticed during exacerbations as well as stable disease. Eosinophilic phenotype of COPD is characterized by several unique features, i.e. a specific pattern of airway inflammation and distinct clinical course or susceptibility to corticosteroid treatment. In this paper, we present an up-to-date review of the literature on clinical characteristics of eosinophilic COPD, as well as the role of eosinophils as a biomarker-guided therapy in COPD.
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Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Eosinofilia Pulmonar/metabolismo , Corticoesteroides/uso terapéutico , Biomarcadores/metabolismo , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Eosinofilia Pulmonar/tratamiento farmacológico , Eosinofilia Pulmonar/fisiopatologíaRESUMEN
BACKGROUND: The systemic (extrapulmonary) effects and comorbidities of chronic obstructive pulmonary disease (COPD) contribute substantially to its burden. The supposed link between COPD and its systemic effects on distal organs could be due to the low-grade systemic inflammation. The aim of this study was to investigate whether the systemic inflammation may influence the skin condition in COPD patients. MATERIALS AND METHODS: Forty patients with confirmed diagnosis of COPD and a control group consisting of 30 healthy smokers and 20 healthy never-smokers were studied. Transepidermal water loss, stratum corneum hydration, skin sebum content, melanin index, erythema index, and skin temperature were measured with worldwide-acknowledged biophysical measuring methods at the volar forearm of all participants using a multifunctional skin physiology monitor. Biomarkers of systemic inflammation, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), were measured in serum using commercially available enzyme-linked immunosorbent assays. RESULTS: There were significant differences between COPD patients and healthy never-smokers in skin temperature, melanin index, sebum content, and hydration level (P<0.05), but not for transepidermal water loss and erythema index. No significant difference was noted between COPD patients and smokers in any of the biophysical properties of the skin measured. The mean levels of hsCRP and IL-6 in serum were significantly higher in COPD patients and healthy smokers in comparison with healthy never-smokers. There were significant correlations between skin temperature and serum hsCRP (R=0.40; P=0.02) as well as skin temperature and serum IL-6 (R=0.49; P=0.005) in smokers. Stratum corneum hydration correlated significantly with serum TNF-α (R=0.37; P=0.01) in COPD patients. CONCLUSION: Differences noted in several skin biophysical properties and biomarkers of systemic inflammation between COPD patients, smokers, and healthy never-smokers may suggest a possible link between smoking-driven, low-grade systemic inflammation, and the overall skin condition.
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Inflamación/fisiopatología , Piel/fisiopatología , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Eritema/patología , Femenino , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Inflamación/etiología , Mediadores de Inflamación/sangre , Interleucina-6/sangre , Pulmón/fisiopatología , Masculino , Melaninas/metabolismo , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Factores de Riesgo , Sebo/metabolismo , Piel/metabolismo , Piel/patología , Temperatura Cutánea , Fumar/efectos adversos , Fumar/sangre , Fumar/fisiopatología , Factor de Necrosis Tumoral alfa/sangre , Pérdida Insensible de AguaRESUMEN
UNLABELLED: The measurements of exhaled nitric oxide (eNO) are simple and useful method of assessment of inflammation in asthmatics' airways. One of the causes of its limited application in clinical practice is a number of factors influencing the results of measurements. The aim of the study was to determine the usefulness of eNO measurements in assessing the inflammation in a heterogeneous, in relation to atopic and smoking status, group of patients. MATERIALS AND METHODS: 120 subjects suspected of having asthma participated in this study. During 2 weeks the patients noted daily asthma symptoms and daily use of rescue medication. After 14 days health related quality of life (HRQL) was determined by means of Asthma Quality of Life Questionnaire (AQLQ), eNO levels were measured and airways reversibility test was performed. RESULTS: Preliminary diagnosis of asthma was confirmed in 84 patients on the basis of positive result of airways reversibility test. Among them, 21 subjects (25%) were smokers and 60 (71.4%) were atopic. No correlation was found between eNO and daily asthma symptom score, daily use of rescue medication, percent of airway reversibility after beta2-agonist and HRQL. CONCLUSION: eNO measurements in a heterogeneous, in relation to atopic and smoking status, group of patients are of limited value in clinical assessment of asthma activity.
Asunto(s)
Asma/diagnóstico , Dermatitis Atópica/diagnóstico , Óxido Nítrico/análisis , Calidad de Vida , Adolescente , Adulto , Obstrucción de las Vías Aéreas/tratamiento farmacológico , Obstrucción de las Vías Aéreas/epidemiología , Antiasmáticos/uso terapéutico , Asma/epidemiología , Pruebas Respiratorias , Estudios de Casos y Controles , Comorbilidad , Dermatitis Atópica/epidemiología , Diagnóstico Diferencial , Errores Diagnósticos/prevención & control , Espiración , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Valores de Referencia , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Fumar/epidemiología , Estadística como AsuntoRESUMEN
UNLABELLED: Immunotherapy is the only effective method of treatment of allergy to Hymenoptera venom. Pretreatment with antihistamines diminishes the incidence of adverse reactions (AR) such as large local and mild systemic reactions but it is suggested that it may mask a development of serious allergic reactions. The aim of the study was a retrospective evaluation of the incidence and nature of AR during venom immunotherapy in patients receiving pretreatment with antihistamines in the Department of Pneumonology and Allergy of the Medical University of Lodz. RESULTS: 50 patients started "ultra-rush" immunotherapy in our center, 8 were taken in our care after the initiation phase had been conducted elsewhere. During the dose increase phase 10 systemic adverse reactions were observed. 50% of them were only subjective and the rest mild objective reactions. During the maintenance phase 10 systemic reactions were noted, among them 2 cases of the anaphylactic shock. The incidence of systemic adverse reactions was 1 per 86 injections. Late as well as unusual reactions appeared twice. CONCLUSIONS: Venom immunotherapy combined with pretreatment with antihistamines is safe. A vast majority of systemic adverse reactions is of subjective and mild objective nature and appropriate treatment leads to containment of severe reactions.
Asunto(s)
Venenos de Abeja/efectos adversos , Desensibilización Inmunológica/efectos adversos , Antagonistas de los Receptores Histamínicos/uso terapéutico , Hipersensibilidad Inmediata/inmunología , Hipersensibilidad Inmediata/terapia , Premedicación , Venenos de Avispas/efectos adversos , Adolescente , Adulto , Anciano , Anafilaxia/inducido químicamente , Anafilaxia/prevención & control , Animales , Venenos de Abeja/inmunología , Desensibilización Inmunológica/métodos , Eritema/inducido químicamente , Eritema/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prurito/inducido químicamente , Prurito/prevención & control , Ranitidina/uso terapéutico , Estudios Retrospectivos , Terfenadina/uso terapéutico , Resultado del Tratamiento , Venenos de Avispas/inmunologíaRESUMEN
Interleukin 10 (IL-10) is a pleiotropic cytokine which shows, under special conditions, some antiinflammatory properties. Among other things it inhibits the synthesis and release of proinflammatory cytokines, preventing persistence of the inflammation. Simultaneously it possesses several proinflammatory properties because of its influence on the B lymphocytes and cytotoxic T cells. It plays crucial role in induction and maintenance of T cells anergy. It was also noticed that some medicines can accomplish their antiinflammatory effects by increasing the production of IL-10.