Colonización por Pneumocystis jirovecii en la enfermedad pulmonar obstructiva crónica / Colonization by Pneumocystis jirovecii in Chronic Obstructive Pulmonary Disease

La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad prevalente en la población colombiana, que característicamente tiene un deterioro progresivo y altera la calidad de vida de los pacientes. Solo del 15% al 20% de los pacientes con antecedente de tabaquismo desarrollan la enfermedad, por lo que factores ambientales y genéticos adicionales influyen en su progresión. De las causas infecciosas que han tomado importancia, el Pneumocystis jiroveái, un hongo ubicuo que entra en contacto con la vía aérea de los humanos desde la infancia, es causa de neumonía en pacientes inmunosuprimidos. Se han descrito tasas elevadas de colonización en pacientes con EPOC, que aumentan con la severidad de la enfermedad. EPOC e infección por P jiroveái parecen compartir una respuesta inmunológica similar; lo cual podría explicar el papel de la colonización por el hongo en su progresión y gravedad.

Chronic obstructive pulmonary disease (COPD) is a prevalent disease in our population, which characteristically has a Progressive deterioration and alters the quality of Iife of patients. Only 15-20% of patients with a history of smoking develop the disease, so there are additional environmental and genetic factors that influence the progression of the disease. Of the infectious causes that have taken importance is Pneumocystis jiroveái, this is a ubiquitous fungus that comes into contact with the airway of humans since childhood and is a cause of pneumonía in immunosuppressed patients. In addition, high rates of colonization have been reported in patients with COPD, which increase with the severity of the disease. COPD and P jiroveái infection appear to share a similar immune response, which may explain the role of fungal colonization in the progression and severity of the disease.

Inflammatory and immunological profiles in patients with COPD: relationship with FEV 1 reversibility / Perfil inflamatório e imunológico em pacientes com DPOC: relação com a reversibilidade do VEF 1

ABSTRACT Objective: To determine whether COPD severity correlates with sputum cell counts, atopy, and asthma. Methods: This was a cross-sectional study involving 37 patients with COPD and 22 healthy subjects with normal lung function (controls). Sputum cell counts were determined by microscopy after centrifugation of samples. Skin prick tests were performed, and serum cytokines were determined by ELISA. Results: Patients were stratified by bronchodilator response: a non-reversible airflow limitation (nonRAL) group comprised 24 patients showing no significant post-bronchodilator change in FEV1; and a partially reversible airflow limitation (partialRAL) group comprised 13 patients showing FEV1 reversibility (post-bronchodilator FEV1 increase ≥ 12%). The proportion of eosinophils in sputum was higher in the partialRAL group than in the nonRAL group (p < 0.01), and there was an inverse correlation between the proportion of eosinophils and FEV1 (p < 0.05). However, none of the patients had a history of asthma and skin prick test results did not differ between the two groups. In the patient sputum samples, neutrophils predominated. Serum levels of TNF, IL-6, IL-8, and RANTES (CCL5) were higher in patients than in controls (p < 0.001) but did not differ between the two patient groups. Conclusions: COPD patients with partial FEV1 reversibility appear to have higher sputum eosinophil counts and greater airway hyperresponsiveness than do those with no FEV1 reversibility. However, we found that COPD severity did not correlate with atopy or with the cytokine profile.

RESUMO Objetivo: Determinar se a gravidade da DPOC se correlaciona com a contagem de células no escarro, atopia e asma. Métodos: Estudo transversal com 37 pacientes com DPOC e 22 indivíduos saudáveis com função pulmonar normal (controles). As contagens de células no escarro foram determinadas por microscopia após a centrifugação das amostras. Foram realizados testes cutâneos de puntura, e as citocinas séricas foram determinadas por ELISA. Resultados: Os pacientes foram estratificados pela resposta ao broncodilatador: o grupo de limitação ao fluxo aéreo não reversível (LFAnr) envolveu 24 pacientes sem alteração significativa do VEF1 pós-broncodilatador, e o grupo de limitação ao fluxo aéreo parcialmente reversível (LFApr) envolveu 13 pacientes com reversibilidade do VEF1 (aumento do VEF1 pós-broncodilatador ≥ 12%). A proporção de eosinófilos no escarro foi maior no grupo LFApr do que no LFAnr (p < 0,01), e houve uma correlação inversa entre a proporção de eosinófilos e VEF1 (p < 0,05). Entretanto, nenhum dos pacientes apresentou histórico de asma e os resultados dos testes cutâneos não diferiram entre os dois grupos. Nas amostras de escarro dos pacientes, os neutrófilos predominaram. Os níveis séricos de TNF, IL-6, IL-8 e RANTES (CCL5) foram maiores nos pacientes que nos controles (p < 0,001), mas não diferiram entre os dois grupos de pacientes. Conclusões: Pacientes com DPOC e reversibilidade parcial do VEF1 parecem apresentar maiores contagens de eosinófilos no escarro e maior hiper-responsividade das vias aéreas que aqueles sem reversibilidade do VEF1. Entretanto, a gravidade da DPOC não se correlacionou com atopia ou perfil das citocinas.

Las células T reguladoras en la enfermedad pulmonar obstructiva crónica / Regulatory T cells in chronic obstructive pulmonary disease

La exposición al humo del tabaco induce inflamación de las vías aéreas y es el principal factor de riesgo para desarrollar la enfermedad pulmonar obstructiva crónica (EPOC). En este proceso inflamatorio participan varias poblaciones celulares. Algunas fallas en la modulación de la respuesta inflamatoria han sido aceptadas como un factor para el desarrollo de esta enfermedad. Las células T reguladoras (Treg) son un tipo de linfocitos T CD4+ que modulan la respuesta inmune mediante contacto directo con las células efectoras, así como por la secreción de citocinas inmunorreguladoras. El papel de las células Treg en la EPOC no se encuentra completamente comprendido, por lo cual es importante evaluar su participación en la inmunopatogénesis de la enfermedad. Con el objetivo de elaborar una revisión sistemática de artículos originales que nos permitiera describir las células Treg (su origen, características y mecanismos de acción) y su participación en la EPOC, realizamos una búsqueda intencionada en las siguientes bases electrónicas: MEDLINE, AMED, PubMed y Scielo; para ello usamos la combinación de las siguientes palabras clave: <

Exposition to tobacco smoke has been established as the main risk factor to develop chronic obstructive pulmonary disease (COPD), by inducing inflammation of the airways. Several cell populations participate in this inflammatory process. It has been accepted that a maladaptive modulation of inflammatory responses plays a critical role in the development of the disease. Regulatory T cells (Treg) are a subset of T CD4+ lymphocytes that modulate the immune response through secretion of cytokines. The role of the Treg cells in chronic obstructive pulmonary disease is not clearly known, that is why it is important to focus in understanding their participation in the pathogenesis of the disease. To elaborate a systematic review of original articles in which we could describe Treg cells (their ontogeny, mechanisms of action) and their role in COPD, we made a systematic literature search in some data bases (MEDLINE, AMED, PubMed and Scielo) looking through the next keywords: ''COPD and Regulatory T cells/EPOC y células T reguladoras'', <

Manifestações sistêmicas na doença pulmonar obstrutiva crônica / Systemic manifestations in chronic obstructive pulmonary disease

A doença pulmonar obstrutiva crônica é progressiva e está relacionada a uma resposta inflamatória anormal dos pulmões à inalação de partículas e/ou gases tóxicos, sobretudo a fumaça de cigarro. Embora acometa primariamente os pulmões, diversas manifestações extrapulmonares relacionadas a esta enfermidade têm sido descritas. O aumento do número de células inflamatórias, que resulta em produção anormal de citocinas pró-inflamatórias, e o desequilíbrio entre a formação de radicais livres e a capacidade antioxidante, resultando em sobrecarga oxidativa, provavelmente são mecanismos envolvidos na inflamação local e sistêmica. Além disso, a diminuição do condicionamento físico secundária às limitações ventilatórias pode estar envolvida no desenvolvimento de alterações musculares. A doença pulmonar obstrutiva crônica apresenta diversas manifestações sistêmicas que incluem a depleção nutricional, a disfunção dos músculos esqueléticos, que contribui para a intolerância ao exercício, e as manifestações relacionadas a co-morbidades comumente observadas nestes pacientes. Essas manifestações têm sido relacionadas à sobrevida e ao estado geral de saúde dos pacientes. Nesse sentido, esta revisão tem como objetivo discutir os achados da literatura relacionados às manifestações sistêmicas da doença pulmonar obstrutiva crônica, ressaltando o papel da inflação sistêmica, e algumas perspectivas de tratamento.

Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation

Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory illnesses characterized by chronic inflammation of the airways. The characterization of induced or spontaneously produced sputum is a useful technique to assess airway inflammation. In the present study, we compared the concentrations of CCL2, CCL11, CXCL8, and tumor necrosis factor-alpha (TNF-alpha) in plasma and induced sputum of patients with severe asthma or COPD and correlated the levels of these mediators with inflammatory cells in sputum. Asthmatic patients had elevated levels of eosinophils (40.1 ± 6.24 percent) in sputum whereas neutrophils (63.3 ± 4.66 percent) predominated in COPD patients. The levels of the chemokine CCL11 were markedly increased in sputum (708.7 ± 330.7 pg/ml) and plasma (716.6 ± 162.2 pg/ml) of asthmatic patients and correlated with the percentage of eosinophils in induced sputum. The concentrations of CXCL8 (817.0 ± 105.2 pg/ml) and TNF-alpha (308.8 ± 96.1 pg/ml) were higher in sputum of COPD patients and correlated with the percentage of neutrophils in induced sputum. There was also an increase in the concentrations of CXCL8 (43.2 ± 6.8 pg/ml) in sputum of asthmatic patients. These results validate that sputum is a suitable method to assess chemokines and cytokines associated with asthma and COPD. Moreover, the mechanisms involved in the synthesis of CCL11 and CXCL8/TNF-alpha would be helpful to better understand the inflammatory profile associated with asthma and COPD, respectively.

Assessment of Il-8 and TNF-alpha in serum and BAL of patients with COPD and lung cancer

There is an increasing evidence for the role of cytokines, especially interlukin-8 [IL-8] and tumor necrosis factor-alpha [TNF-alpha] in the pathogenesis of many chest diseases especially chronic obstructive pulmonary disease [COPD] and to some extent lung cancer. Tins study was conducted on three groups comprising 70 smoker subjects; 25 patients [21 males and 4 female] with mild to moderate degree of COPD, 25 patients [21 males and 4 females] with lung cancer and 20 asymptomatic control subject [17 males and 3 females], All subjects were subjected to full history taking, clinical examination, radiological assessment, pulmonary function testing, tissue diagnosis of lung cancer, blood sampling and bronchoscopic bronchoalveolar lavage [BAL] for assessment of TNF-alpha and IL-8 levels both in scrum and BAL fluid using the enzyme linked immunosorbant assay [ELISA] method. There was a highly significant [P < 0.05] elevation in both serum and BAL levels of IL-8 in COPD and lung cancer patients compared to the healthy control subjects but the difference between the COPD and lung cancer patients was insignificant [P > 0.05], Also, there was a highly significant elevation in both serum and BAL levels of TNF-alpha in COPD and lung cancer patients compared to the control group and the serum as well as the BAL levels of TNF-alpha were significantly higher in lung cancer patients compared to the COPD ones. The BAL levels of IL-8 and TNF-alpha were always significantly higher than the serum levels of the same cytokine in the same group of patients or control subjects. This study concludes that IL-8 and TNF-a levels are increased both in BAL and serum of COPD and lung cancer patients and their assessment may add to the understanding of the ongoing pathogenic inflammatory processes occurring in the smoker's airways till the development of COPD or lung cancer