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1.
Pulmonology ; 30(1): 43-52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36797151

RESUMO

PURPOSE: A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. AIM: to investigate genotype and clinical profile of Greeks with AATD. METHODS: Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. RESULTS: Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). CONCLUSION: Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.


Assuntos
Deficiência de alfa 1-Antitripsina , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/epidemiologia , Deficiência de alfa 1-Antitripsina/genética , alfa 1-Antitripsina/genética , Grécia/epidemiologia , Genótipo
2.
Expert Opin Biol Ther ; 20(12): 1427-1434, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32779950

RESUMO

INTRODUCTION: Patients with severe asthma experience a significant burden of symptoms, disease exacerbations and medication side-effects. Severe asthma interferes with the patients' quality of life and has high health-care costs. New targeted biologic therapies have improved the management of severe asthma by significantly reducing exacerbations and maintenance corticosteroid use, and also improving lung function and patient quality of life. AREAS COVERED: Not all severe asthmatics are eligible for such therapies. Those with allergic and eosinophilic asthma, usually referred to as 'T2-high' asthma benefit from anti-IgE and anti-IL-5/5 R antibodies respectively, whereas some asthmatics are eligible for both: 'overlap' endotype. In this review, we present briefly the monoclonal antibodies that have been approved in the management of severe asthma and we focus on the 'overlap' endotype. EXPERT OPINION: Since these therapies are costly, it is extremely important to choose the right treatment for the right patient especially in the 'overlapping' one. The decision is mainly based on the judgment of the clinician and is often driven by the most easily obtainable biomarker, thus the blood eosinophil count. Comorbidities, patient's input and administration frequency may aid the decision of choosing one over another biologic.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/patologia , Produtos Biológicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Terapia Biológica/métodos , Progressão da Doença , Humanos , Fenótipo , Qualidade de Vida , Índice de Gravidade de Doença
3.
J Breath Res ; 14(3): 036007, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32392552

RESUMO

Asthma is a heterogeneous disease with diverse severity and represents a considerable socio-economic burden. Exhaled Breath Condensate (EBC) is a biofluid directly obtained from the airway lining fluid non-invasively. We attempted to discriminate severe from mild-to-moderate asthma using EBC metabolomics based on both NMR and UHPLC-MS techniques. 36 patients were included in this study (15 patients with severe and 21 with mild-to-moderate asthma). EBC was collected and analyzed using both NMR and UHPLC-MS techniques for possible metabolites. Using PLS and oPLS analysis for the UHPLC-MS data, no metabolite was found to be sufficient for the discrimination of asthma severity. However, when another PLS-regression model was applied five metabolites were found to discriminate severe from mild-to-moderate asthma. Amino-acid lysine was the only metabolite that discriminated the two study groups using NMR data (p= 0.04, t-test with Welch's correction, AUC 0.66). EBC is an easily available biofluid which directly represents the lower airways but difficult-to-use for metabolomic analysis. Our study presents some encouraging findings for the discrimination of asthma severity subgroups using EBC metabolomics but more well-designed studies with a higher number of patients need to be conducted.


Assuntos
Asma/diagnóstico , Asma/metabolismo , Testes Respiratórios/métodos , Expiração , Metabolômica , Índice de Gravidade de Doença , Biomarcadores/metabolismo , Análise Discriminante , Feminino , Humanos , Análise dos Mínimos Quadrados , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade
4.
Allergy ; 72(11): 1761-1767, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28407269

RESUMO

BACKGROUND: According to induced sputum cell count, four different asthma phenotypes have been recognized (eosinophilic, neutrophilic, mixed and paucigranulocytic). The aim of this study was to detect functional and inflammatory characteristics of patients with paucigranulocytic asthma. METHODS: A total of 240 asthmatic patients were categorized into the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of fraction of exhaled nitric oxide (FeNO). The levels of IL-8, IL-13 and eosinophilic cationic protein (ECP) were also measured in sputum supernatant. Treatment, asthma control and the presence of severe refractory asthma (SRA) were also recorded. RESULTS: Patients were categorized into the four phenotypes as follows: eosinophilic (40%), mixed (6.7%), neutrophilic (5.4%) and paucigranulocytic (47.9%). Although asthma control test did not differ between groups (P=.288), patients with paucigranulocytic asthma had better lung function (FEV1 % pred) [median (IQR): 71.5 (59.0-88.75) vs 69.0 (59.0-77.6) vs 68.0 (60.0-85.5) vs 80.5 (69.7-95.0), P=.009] for eosinophilic, mixed, neutrophilic and paucigranulocytic asthma, respectively, P=.009). SRA occurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7%, respectively) and less frequently in the neutrophilic and paucigranulocytic phenotype (25% and 21.7%, respectively, P=.01). FeNO, ECP and IL-8 were all low in the paucigranulocytic, whereas as expected FeNO and ECP were higher in eosinophilic and mixed asthma, while IL-8 was higher in patients with neutrophilic and mixed asthma (P<.001 for all comparisons). Interestingly, 14.8% of patients with paucigranulocytic asthma had poor asthma control. CONCLUSION: Paucigranulocytic asthma most likely represents a "benign" asthma phenotype, related to a good response to treatment, rather than a "true" phenotype of asthma. However, paucigranulocytic patients that remain not well controlled despite optimal treatment represent an asthmatic population that requires further study for potential novel targeted interventions.


Assuntos
Asma/diagnóstico , Escarro/química , Adulto , Idoso , Asma/classificação , Asma/patologia , Eosinófilos , Feminino , Granulócitos , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Neutrófilos , Fenótipo , Testes de Função Respiratória
6.
Clin Exp Allergy ; 46(7): 923-31, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26990030

RESUMO

BACKGROUND: Asthma control refers to the extent to which the manifestations of asthma have been reduced or eradicated by treatment. Interleukin-13 (IL-13) has a central role in Th2 response and serves as a possible therapeutic target in uncontrolled asthma. Fraction of exhaled nitric oxide (FeNO) and sputum eosinophils have modest performance in the evaluation of asthma control. OBJECTIVE: To assess the diagnostic performance of sputum IL-13 for the evaluation of asthma control and furthermore to investigate the performance of sputum eosinophils and FeNO. METHODS: One hundred and seventy patients with asthma were studied. All subjects underwent assessment of asthma control by asthma control test (ACT), lung function tests, FeNO measurement and sputum induction for cell count identification and IL-13 measurement in supernatants. RESULTS: IL-13 (pg/mL) levels in sputum supernatant differed significantly among patients with well-controlled asthma and those with not well-controlled asthma [median IQR 78 (66-102) vs. 213 (180-265), P < 0.001]. Receiver operating characteristic (ROC) analysis showed that, for the whole study population, the diagnostic performance of IL-13 was superior to both sputum eosinophils and FeNO levels [area under the curve (AUC) 0.92, 95% CI 0.87 to 0.95 vs. AUC 0.65, 95% CI 0.58 to 0.72 vs. AUC 0.65, 95% CI 0.55 to 0.72, respectively]. CONCLUSION: The diagnostic performance of sputum IL-13 was superior to both sputum eosinophils and FeNO levels for the identification of well-controlled asthma. Sputum IL-13 levels could serve as a useful biomarker for asthma control assessment.


Assuntos
Asma/diagnóstico , Asma/metabolismo , Interleucina-13/metabolismo , Escarro/metabolismo , Adulto , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Biomarcadores , Eosinófilos/imunologia , Eosinófilos/metabolismo , Eosinófilos/patologia , Expiração , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico , Prognóstico , Curva ROC , Testes de Função Respiratória , Fatores de Risco , Índice de Gravidade de Doença , Escarro/citologia , Resultado do Tratamento
7.
Allergy ; 70(6): 711-4, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25728058

RESUMO

Clara cell secretory protein (CC16) is associated with Th2 modulation. Surfactant protein D (SPD) plays an important role in surfactant homeostasis and eosinophil chemotaxis. We measured CC16 and SPD in sputum supernatants of 84 asthmatic patients and 12 healthy controls. In 22 asthmatics, we additionally measured CC16 and SPD levels in BAL and assessed smooth muscle area (SMA), reticular basement membrane (RBM) thickness, and epithelial detachment (ED) in bronchial biopsies. Induced sputum CC16 and SPD were significantly higher in patients with severe asthma (SRA) compared to mild-moderate and healthy controls. BAL CC16 and SPD levels were also higher in SRA compared to mild-moderate asthma. CC16 BAL levels correlated with ED, while SPD BAL levels correlated with SMA and RBM. Severity represented a significant covariate for these associations. CC16 and SPD levels are upregulated in SRA and correlate with remodeling indices, suggesting a possible role of these biomarkers in the remodeling process.


Assuntos
Asma/patologia , Brônquios/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Proteína D Associada a Surfactante Pulmonar/imunologia , Escarro/imunologia , Uteroglobina/imunologia , Asma/imunologia , Membrana Basal/patologia , Biópsia , Estudos de Casos e Controles , Humanos , Músculo Liso/patologia , Mucosa Respiratória/patologia , Índice de Gravidade de Doença
8.
Int Arch Allergy Immunol ; 162(1): 58-64, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23816757

RESUMO

BACKGROUND: As fractional exhaled nitric oxide (FeNO) has been evaluated only in certain settings for asthma diagnosis, we investigated whether FeNO values could predict positive methacholine challenge testing (expressed as PD20) in subjects with suspected asthma but without spirometric reversibility. METHODS: Subjects with asthma-like symptoms and negative bronchodilation test were initially evaluated to undergo FeNO measurement and methacholine bronchial challenge. Diagnostic performance of FeNO to predict PD20 to methacholine <800 µg was examined by constructing receiver-operating characteristic curves. RESULTS: A total of 112 subjects met the inclusion criteria. In all subjects, FeNO >32 ppb was associated with a sensitivity of 0.47 and a specificity of 0.85 for the identification of the PD20 <800 µg (AUC = 0.691, 95% CI = 0.6-0.775, p = 0.00002). In smokers, FeNO >11 ppb was associated with a sensitivity of 0.85 and a specificity of 0.5 for the identification of PD20 <800 µg (AUC = 0.625, 95% CI = 0.45-0.772, p = 0.18), while in atopics a FeNO level >26 ppb was associated with a sensitivity of 0.55 and a specificity of 0.85 (AUC = 0.677, 95% CI = 0.53-0.8, p = 0.02). CONCLUSIONS: In subjects with symptoms compatible with asthma but without spirometric reversibility, specific cutoff levels for FeNO levels significantly predict the positive methacholine challenge, with significant confounding factors being atopy and current smoking.


Assuntos
Asma/diagnóstico , Óxido Nítrico , Adulto , Testes Respiratórios , Broncodilatadores , Expiração , Feminino , Humanos , Masculino , Cloreto de Metacolina , Curva ROC , Espirometria
9.
Clin Exp Allergy ; 43(6): 616-24, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23711123

RESUMO

BACKGROUND: Smoking is associated with worse asthma outcomes and may modify airway inflammation. Such modification may be mediated through an effect on prostaglandin E(2) (PGE(2)) and cysteinyl leukotrienes (Cyst-LTs). OBJECTIVE: We aimed to determine the levels of both PGE(2) and Cyst-LTs in sputum supernatants of patients with asthma and to investigate the effect of smoking habit as well as their associations with inflammatory cells, bronchial hyperresponsiveness (BHR) and lung function. METHODS: Ninety-eight patients to asthma (47 smokers) and 40 healthy subjects (20 smokers) were studied. All subjects underwent sputum induction for cell count identification, PGE(2) and Cyst-LTs levels measurement in supernatants, pulmonary function tests and BHR to methacholine. RESULTS: Patients with asthma had significantly higher levels of both Cyst-LTs and PGE(2) in sputum supernatants compared to healthy subjects [median (interquartile ranges) 432 (287, 575) vs. 91.5 (73.5, 111) pg/mL and 654 (456,789) vs. 117.5 (92,157) pg/mL, respectively, P < 0.001 for both comparisons]. Smoking asthmatics had significantly higher Cyst-LTs and PGE(2) levels compared to non-smoking asthmatics. Cyst-LTs levels in sputum supernatant of smoking asthmatics presented a significant positive association with sputum eosinophils, while PGE(2) levels were positively associated with sputum neutrophils. CONCLUSIONS: The increased concentrations of PGE(2) and Cyst-LTs in sputum supernatants of smoking asthma are consistent with an up-regulation of these two mediators in this specific phenotype of asthma. Furthermore, Cyst-LTs are associated with eosinophilic inflammation, while PGE(2) is associated with the presence of neutrophilic inflammation in smoking asthma.


Assuntos
Asma/metabolismo , Cisteína/metabolismo , Dinoprostona/metabolismo , Leucotrienos/metabolismo , Escarro/metabolismo , Adulto , Asma/imunologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/fisiopatologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Fatores de Risco , Fumar/efeitos adversos , Escarro/citologia , Escarro/imunologia
10.
PLoS One ; 7(6): e39172, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22761732

RESUMO

PURPOSE: The aim of this study was to evaluate markers of systemic oxidative stress and antioxidant capacity in subjects with and without OSAS in order to investigate the most important factors that determine the oxidant-antioxidant status. METHODS: A total of 66 subjects referred to our Sleep laboratory were examined by full polysomnography. Oxidative stress and antioxidant activity were assessed by measurement of the derivatives of reactive oxygen metabolites (d-ROMs) and the biological antioxidant capacity (BAP) in blood samples taken in the morning after the sleep study. Known risk factors for oxidative stress, such as age, sex, obesity, smoking, hypelipidemia, and hypertension, were investigated as possible confounding factors. RESULTS: 42 patients with OSAS (Apnea-Hypopnea index >15 events/hour) were compared with 24 controls (AHI<5). The levels of d-ROMS were significantly higher (p = 0.005) in the control group but the levels of antioxidant capacity were significantly lower (p = 0.004) in OSAS patients. The most important factors predicting the variance of oxidative stress were obesity, smoking habit, and sex. Parameters of sleep apnea severity were not associated with oxidative stress. Minimal oxygen desaturation and smoking habit were the most important predicting factors of BAP levels. CONCLUSION: Obesity, smoking, and sex are the most important determinants of oxidative stress in OSAS subjects. Sleep apnea might enhance oxidative stress by the reduction of antioxidant capacity of blood due to nocturnal hypoxia.


Assuntos
Biomarcadores/análise , Obesidade/complicações , Estresse Oxidativo , Apneia Obstrutiva do Sono/fisiopatologia , Fumar/efeitos adversos , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Oxirredução , Polissonografia , Prognóstico , Fatores de Risco , Fatores Sexuais
11.
Allergy ; 67(3): 396-402, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22229541

RESUMO

BACKGROUND: Airway and vascular remodeling may play a prominent role in the clinical severity of severe refractory asthma (SRA). Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. OBJECTIVE: We aimed to determine the levels of angiopoietins in sputum supernatants of patients with SRA and to investigate the possible associations with mediators and cells involved in both the inflammatory and the vascular remodeling processes. METHODS: Thirty-eight patients with SRA, 35 patients with moderate asthma, and 20 healthy subjects were studied. All participants underwent lung function tests, bronchial hyperresponsiveness assessment and sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-ß1, Cys-LTs, MMP-2, IL-13, ECP, and IL-8 measurement in supernatants. Airway vascular permeability (AVP) index was also assessed. RESULTS: Ang-1 (ng/ml) and Ang-2 (pg/ml) levels were significantly elevated in patients with SRA compared with patients with moderate asthma and control subjects [median, interquartile ranges: 30 (17-39) vs 7.5 (5-11) vs 4.7 (3.8-5.9) respectively, P < 0.001; and 506 (400-700) vs 190 (146-236) vs 96 (89-120) respectively, P < 0.001]. Regression analysis showed a significant positive association between Ang-2 and AVP index, MMP-2, Ang-1, and VEGF in SRA. A weak association was also observed between Ang-1 and sputum eosinophils% in SRA. CONCLUSION: Our results indicate that both angiopoietins levels are higher in SRA compared with moderate asthma and healthy subjects. In SRA, Ang-2 is associated with mediators involved in both the inflammatory and the vascular remodeling processes.


Assuntos
Angiopoietina-1/análise , Angiopoietina-2/análise , Asma/metabolismo , Asma/fisiopatologia , Índice de Gravidade de Doença , Escarro/química , Idoso , Remodelação das Vias Aéreas/fisiologia , Asma/imunologia , Hiper-Reatividade Brônquica , Permeabilidade Capilar/fisiologia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória
12.
Curr Med Chem ; 18(10): 1432-43, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21428897

RESUMO

The need for non-invasive assessment of airway inflammation is imperative, since inflammatory airway diseases, such as asthma and COPD, are characterized by variation in their clinical presentation throughout their course. Exhaled breath condensate (EBC) collection represents a rather appealing method that can be used to conveniently and noninvasively collect a wide range of volatile and non-volatile molecules from the respiratory tract, without affecting airway function or inflammation. Although promising, EBC is currently used only as a research tool, due to the lack of appropriate standardization and the absence of reference values. A large number of mediators of inflammation, oxidative and nitrosative stress, including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, prostanoids, nitrogen oxides, peptides and cytokines, have been studied in EBC. This review focuses mainly on the presentation of the above biomarkers in asthma as well as on the effect of various factors on their concentrations. Concentrations of such mediators have been shown to be related to the underlying asthma and its severity and to be modulated by therapeutic interventions. Despite the encouraging positive results up-to-date, the introduction of EBC in everyday clinical practice requires the work-out of some methodological pitfalls, the standardization of EBC collection, and finally the identification of a reliable biomarker which is reproducible, has normal values and provides information for the underlying inflammatory process and the response to treatment. So far none of the parameters studied in EBC fulfils the aforementioned requirements.


Assuntos
Asma/diagnóstico , Asma/metabolismo , Biomarcadores/análise , Testes Respiratórios/métodos , Dinoprosta/análogos & derivados , Dinoprosta/análise , Dinoprosta/metabolismo , Eicosanoides/análise , Eicosanoides/metabolismo , Humanos , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/metabolismo , Leucotrienos/análise , Leucotrienos/metabolismo , Óxidos de Nitrogênio/análise , Óxidos de Nitrogênio/metabolismo , Estresse Oxidativo/fisiologia
13.
Clin Exp Allergy ; 38(4): 557-65, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18352973

RESUMO

Exhaled breath condensate (EBC) analysis, a rather appealing and promising method, can be used to evaluate conveniently and non-invasively a wide range of molecules from the respiratory tract, and to understand better the pathways propagating airway inflammation. A large number of mediators of inflammation, including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, prostanoids, nitrogen oxides, peptides and cytokines, have been studied in EBC. Concentrations of such mediators have been shown to be related to the underlying asthma and its severity and to be modulated by therapeutic interventions. Despite the encouraging positive results to date, the introduction of EBC in everyday clinical practice requires the resolution of some methodological pitfalls, the standardization of EBC collection and finally the identification of a reliable biomarker that is reproducible has normal values and provides information regarding the underlying inflammatory process and the response to treatment. So far, none of the parameters studied in EBC fulfils the aforementioned requirements with one possible exception: pH. EBC pH is reproducible, has normal values, reflects a significant part of asthma pathophysiology and is measurable on-site with standardized methodology although some methodological aspects of measurement of pH in EBC (e.g. the effect of ambient CO(2), sample de-aeration, time for pH measurement) require further research. However, EBC pH has not been evaluated prospectively as a guide for treatment, in a manner similar to exhaled NO and sputum eosinophils. EBC represents a simple and totally non-invasive procedure that may contribute towards our understanding of asthma pathophysiology. Besides the evaluation of new biomarkers, the standardization of the already existing procedures is warranted for the introduction of EBC in clinical practice.


Assuntos
Asma/diagnóstico , Biomarcadores/análise , Testes Respiratórios/métodos , Ensaios Clínicos como Assunto , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Respir Med ; 101(4): 826-32, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16965907

RESUMO

Leukotriene E(4) (LTE(4)) is implicated in asthma pathophysiology and possibly in chronic obstructive pulmonary disease (COPD) as one of the causes of persistent bronchoconstriction and mucus hypersecretion. Cigarette smoking stimulates cysteinyl leukotrienes (CysLTs) production. We investigated whether LTE(4) is equally increased in asthma and COPD and whether smoking significantly affects LTE(4) levels. Secondary outcomes involved correlations with inflammatory and functional parameters. We studied 40 patients with COPD [20 smokers], 40 asthmatics [20 smokers] and 30 healthy subjects [15 smokers]. Spirometry (FEV(1)% pred., FEV(1)/FVC) was performed, urine was collected for measurement of LTE(4) and creatinine, induced sputum was collected for differential cell counts and serum for ECP. LTE(4)/creatinine levels (pg/mg) [mean (sd)] were increased in asthmatic patients compared to COPD and controls, [125.6(54.5) vs. 54.5(19) vs. 55.9(18.9)pg/mg, respectively, P<0.0001 for asthma]. Smoking significantly affects LTE(4) levels only in asthmatic patients [164 (48) vs. 87 (26.3), P<0.0001 for smokers]. The only significant correlation was between eosinophils in induced sputum and LTE(4)/creatinine levels in asthmatics. In conclusion, patients with asthma presented higher LTE(4) values compared to normals and patients with COPD. Smoking significantly affects LTE(4) values only in asthmatics indicating a different underlying CysLTs inflammatory process in this condition.


Assuntos
Asma/urina , Leucotrieno E4/urina , Doença Pulmonar Obstrutiva Crônica/urina , Fumar/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatinina/urina , Eosinofilia/urina , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Risco , Fumar/efeitos adversos , Escarro/citologia
16.
Eur J Clin Invest ; 36(5): 362-7, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16634841

RESUMO

BACKGROUND: Expired breath condensate (EBC) has never been used to explore the level of oxidative stress in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to measure the levels of H2O2 and 8-isoprostane, as biomarkers of oxidative stress, in the EBC of patients with IPF. MATERIALS AND METHODS: We investigated 16 patients with IPF and 15 healthy subjects as the control group. The levels of H2O2 and 8-isoprostane were measured in the EBC of all subjects and were compared between the IPF and control groups. In patients with IPF, H2O2 and 8-isoprostane were further correlated with pulmonary function tests (PFTs), the resting pO2 and the differential cell count from the bronchoalveolar lavage fluid (BALF). RESULTS: The mean (95%CI) concentration of H2O2 was increased in the patients with IPF compared with the normal subjects (0.36, 0.24-0.47 microM vs. 0.16, 0.10-0.23 microM, P=0.003). The mean (95%CI) concentration of 8-isoprostane was also increased in the patients with IPF compared with the controls (74, 38-110 pg mL-1 vs. 33, 28-39 pg mL-1, P=0.02). In the patients with IPF, the diffusing capacity of the lung for carbon monoxide was negatively correlated with the levels of H2O2 in EBC (P=0.03, r=-0.58). No other correlation was found between the oxidative stress markers in the EBC and PFT values, pO2 or BALF cell count. CONCLUSIONS: Our data suggest that H2O2 and 8-isoprostane are increased in the EBC of patients with IPF. H2O2 may be correlated with the severity of the disease in IPF.


Assuntos
Estresse Oxidativo , Fibrose Pulmonar/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Testes Respiratórios/métodos , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Dinoprosta/análogos & derivados , Dinoprosta/análise , Expiração , Feminino , Volume Expiratório Forçado , Humanos , Peróxido de Hidrogênio/análise , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/metabolismo , Testes de Função Respiratória , Capacidade Pulmonar Total
17.
Eur Respir J ; 26(3): 523-48, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16135737

RESUMO

Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.


Assuntos
Testes Respiratórios/métodos , Pneumopatias/metabolismo , Biomarcadores/metabolismo , Humanos , Pneumopatias/diagnóstico , Estresse Oxidativo/fisiologia , Reprodutibilidade dos Testes
18.
Monaldi Arch Chest Dis ; 61(2): 120-3, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15510713

RESUMO

A case of a 30-year-old male with a fever, dry cough and associated abnormal findings in imaging modalities (bilateral hilar lymphadenopathy and nodular parenchymal opacities) is described. After a further and scrutinized work-up, the diagnosis of GLUS syndrome was made. Clinical, etiological, pathological and therapeutical aspects of the disease are discussed, demonstrating the paramount importance of the use of the immunohistochemical methods in the diagnosis of this disorder.


Assuntos
Granuloma/diagnóstico , Pneumopatias/diagnóstico , Doenças Linfáticas/diagnóstico , Adulto , Granuloma/diagnóstico por imagem , Humanos , Pneumopatias/diagnóstico por imagem , Doenças Linfáticas/diagnóstico por imagem , Masculino , Tomografia Computadorizada por Raios X
19.
Monaldi Arch Chest Dis ; 61(1): 28-34, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15366333

RESUMO

BACKGROUND: Congenital bronchial atresia is a rare anomaly, which usually occurs in adulthood as an incidental finding on routine chest radiograph. METHODS: The purpose of the study was to retrospectively evaluate the cases that were diagnosed in our hospital, from January 1995 to March 2003, to estimate the prevalence of this disorder and to determine the diagnostic studies of choice, according to the existing literature. Since the main portion of the male population of our country is referred to our hospital for screening soon after their enrollment in the army, epidemiological data can be easily estimated for many congenital anomalies occuring in adulthood, such as bronchial atresia. RESULTS: We found seven patients with Congenital Bronchial Atresia and the prevalence of this disorder was estimated at 1.2 cases per 100,000 in males. The chosen diagnostic procedure is computed tomography of the chest with high-resolution scans. Bronchoscopy would only exclude serious alternative diagnosis and prevent unnecessary surgical interventions. CONCLUSIONS: Congenital bronchial atresia is a rare anomaly, with a mild clinical course. The diagnosis is made radiologically, the HRCT of the chest being the procedure of choice. Bronchoscopy should be performed to exclude any endobronchial lesion due to a different disease entity and to prevent unnecessary surgical intervention in an otherwise asymptomatic individual.


Assuntos
Brônquios/anormalidades , Adulto , Broncoscópios , Hospitais Militares , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Testes de Função Respiratória , Anormalidades do Sistema Respiratório/diagnóstico , Anormalidades do Sistema Respiratório/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
Ann Oncol ; 15(7): 1048-55, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15205198

RESUMO

PURPOSE: This randomized phase III trial of advanced or metastatic non-small-cell lung cancer (NSCLC) was designed to compare a standard treatment such as carboplatin (CRP)-paclitaxel (PCT) with a new combination, vinorelbine (VRL)-PCT-two agents acting in microtubules. PATIENTS AND METHODS: Three hundred and sixty patients (stage IIIa, IIIb and IV) were included and evaluated for response rate, survival and toxicity. Arm A patients were treated with the control combination of CRP 6 AUC and PCT 175 mg/m(2) repeated every 3 weeks for six cycles, and arm B with the investigational combination of VRL 25 mg/m(2) and PCT 135 mg/m(2) repeated every 2 weeks for nine cycles. The patients were well balanced with respect to gender, disease stage and performance status. Arm A received 849 cycles (mean 4.59 per patient) and arm B 951 cycles (mean 5.39 per patient). RESULTS: Complete and partial response rates were 45.95% and 42.86% for arms A and B, respectively. Median survival was 11 and 10 months, 1-year survival 42.7% and 37.85% and 2-year survival 10.12% and 19% for arms A and B, respectively. Toxicity was similar in all patients, except for neutropenia, which was significantly greater in arm B. CONCLUSIONS: PCT combined with VRL produces similar (non-significant) response rates, survival and toxicity (except for neutropenia, as noted above) to standard CRP-PCT treatment in untreated advanced-stage NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Qualidade de Vida , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina
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