Molecular changes underlying pulmonary emphysema and chronic bronchitis in Chronic Obstructive Pulmonary Disease: An updated review.

The aim of this review is to update and synthesize the molecular mechanisms that lead to the heterogeneous effect on tissue remodeling observed in the two most important clinical phenotypes of chronic obstructive pulmonary disease (COPD), pulmonary emphysema (PE) and chronic bronchitis (CB). Clinical and experimental evidence suggests that this heterogeneous response to promote PE, CB, or both, is related to differentiated genetic, epigenetic, and molecular conditions. Specifically, a tendency toward PE could be related to a variant in the DSP gene, SIRT1 downregulation, macrophage polarization to M1, as well as the involvement of the noncanonical Wnt5A signaling pathway, among other alterations. Additionally, in advanced stages of COPD, PE development is potentiated by dysregulations in autophagy, which promotes senescence and subsequently cell apoptosis, through exacerbated inflammasome activation and release of caspases. On the other hand, CB or the pro-fibrotic phenotype could be potentiated by the downregulated activity of HDAC2, the activation of the TGF-ß/Smad or Wnt/ß-catenin signaling pathways, macrophage polarization to M2, upregulation of TIMP-1, and/or the presence of the epithelial-mesenchymal transition (EMT) mechanism. Interestingly, the upregulated activity of MMPs, especially MMP-9, is widely involved in the development of both phenotypes. Furthermore, MMP-9 and MMP-12 enhance the severity, perpetuation, and exacerbation of COPD, as well as the development of autoimmunity in this disease.

[Mesenchymal stem cells: Therapeutic option in ARDS, COPD, and COVID-19 patients]. / Células troncales mesenquimales: opción terapéutica en pacientes con SDRA, EPOC y COVID-19.

Acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and COVID-19 have as a common characteristic the inflammatory lesion of the lung epithelium. The therapeutic options are associated with opportunistic infections, a hyperglycemic state, and adrenal involvement. Therefore, the search for new treatment strategies that reduce inflammation, and promote re-epithelialization of damaged tissue is very important. This work describes the relevant pathophysiological characteristics of these diseases and evaluates recent findings on the immunomodulatory, anti-inflammatory and regenerative effect of mesenchymal stem cells (MSC) and their therapeutic use. In Pubmed we selected the most relevant studies on the subject, published between 2003 and 2022 following the PRISMA guide. We conclude that MSCs are an important therapeutic option for regenerative treatment in COPD, ARDS, and COVID-19, because of their ability to differentiate into type II pneumocytes and maintain the size and function of lung tissue by replacing dead or damaged cells.

El síndrome de dificultad respiratoria aguda (SDRA), la enfermedad pulmonar obstructiva crónica (EPOC) y la COVID-19 tienen tienen en común provocar lesión inflamatoria del epitelio pulmonar. El tratamiento actual suele asociarse con infecciones oportunistas, hiperglicemia y afectación suprarrenal, por lo que es importante proponer opciones relacionadas con la disminución de la inflamación y estimulación de la reepitelización del tejido dañado. En esta revisión se detallan las características fisiopatológicas relevantes de dichas enferme-dades y se evalúan los hallazgos recientes del efecto inmunomodulador, antiinflamatorio y regenerativo de las células troncales mesenquimales (MSC) y sus aplicaciones terapéuticas. Se seleccionaron los estudios sobresalientes del tema, publicados entre 2003 y 2022 en PubMed, siguiendo los criterios de la guía PRISMA. Las células troncales mesenquimales representan una opción importante de tratamiento regenerativo en pacientes con EPOC, SDRA y COVID-19, pues se diferencian a neumocitos tipo II, y mantienen el tamaño y la función del tejido pulmonar, supliendo a las células muertas o dañadas.

Relación entre la distancia recorrida en la prueba de caminata de 6 minutos y el sexo, la edad, comorbilidades y la disnea en pacientes con EPOC / Relationship between the Distance Traveled in the Test of 6- Minute Walk and Sex, Age, Comorbidities and Dyspnea in Patients with CORP

Introducción: la enfermedad pulmonar obstructiva crónica (EPOC) es un trastorno res-piratorio caracterizado por síntomas clínicos y compromiso funcional que afecta la ca-pacidad aeróbica limitando las actividades cotidianas y la calidad de vida. La prueba de caminata de 6 minutos (C6M) es una prueba sencilla y de bajo costo que evalúa la capa-cidad de los pacientes para realizar sus actividades cotidianas. Objetivo: evaluar la re-lación entre la capacidad aeróbica medida por la distancia recorrida en la C6M y el se-xo, edad, disnea y comorbilidades cardiometabólicas en pacientes con EPOC. Material y métodos: estudio de corte transversal, descriptivo, basado en pruebas de caminatas de 6 minutos (C6M) realizadas en pacientes con EPOC. Resultados: se evaluaron 101 pacientes, hombres (63,4%), con una edad promedio de 74,1±8,7 años. Al correlacionar C6M con otras variables se encontraron diferencias estadísticamente significativas. La distancia media recorrida fue mayor en hombres que en mujeres (DM: 58,3 metros, IC 95%; 16 - 100,6, p=0,007). Los pacientes < 75 años, sin comorbilidades y disnea < 2 tu-vieron mejor desempeño en la C6M que los > 75 años (DM; 62,012 metros IC 95% 21,5 - 102,4, p=0,003), con comorbilidades (DM: 42,2 metros, IC 95%, 0.003 - 84,4; p=0,050) y disnea ≥ 2 (DM: 65,8 IC 95% 23,9 - 107,6, p=0,002). Conclusiones: el sexo femenino, la presencia de comorbilidad cardiovascular y metabólica, y la edad se asocian con dis-minución en la capacidad física aeróbica y funcional en los pacientes con EPOC. (AU)

Introduction: chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by clinical symptoms and functional impairment that affects aerobic capacity, limiting daily activities and quality of life. The 6-minute walk test (C6M) is a simple, low-cost test that assesses a patient's ability to perform their daily activities. Objective: to evaluate the relationship between aerobic capacity measured by the distance covered in the C6M and gender, age, dyspnea and cardiometabolic comorbidities in patients with COPD. Materials and methods: cross-sectional, descriptive study, based on 6-minute walk tests (C6M) performed in patients with COPD. Results: 101 male patients (63.4%), with a mean age of 74.1 ± 8.7 years, were evaluated. When correlating C6M with other variables, statistically significant differences were found. The mean distance traveled was greater in men than in women (MD: 58.3 meters, 95% CI: 16 - 100.6, p=0.007). Patients <75 years old, without comorbidities and dyspnea <2 had better performance in the C6M than those >75 years old (MD; 62 meters CI 95% 21.5 - 102.4, p=0.003), with comorbidities (MD: 42.2 meters, 95% CI, 0.003 - 84.4; p=0.050) and dyspnea ≥ 2 (MD: 65.8, 95% CI 23.9 - 107.6, p=0.002). Conclusions: female sex, the presence of cardiovascular and metabolic comorbidity, and age are associated with decreased aerobic and functional physical capacity in patients with COPD. (AU)

Effects of the intranasal application of gold nanoparticles on the pulmonary tissue after acute exposure to industrial cigarette smoke.

Inhalation of harmful particles appears as a primary factor for the onset and establishment of chronic obstructive pulmonary disease (COPD). Cigarette smoke acutely promotes an exacerbated inflammatory response with oxidative stress induction with DNA damage. Administration of Gold Nanoparticles (GNPs) with 20 nm in different concentrations can revert damages caused by external aggravations. The effects of GNPs in a COPD process have not been observed until now. The objective of this work was to evaluate the therapeutic effects of intranasal administration of different doses of GNPs after acute exposure to industrial cigarette smoke. Thirty male Swiss mice were randomly divided into five groups: Sham; cigarette smoke (CS); CS + GNPs 2.5 mg/L; CS + GNPs 7.5 mg/L and CS + GNPs 22.5 mg/L. The animals were exposed to the commercial cigarette with filter in an acrylic inhalation chamber and treated with intranasal GNPs for five consecutive days. The results demonstrate that exposure to CS causes an increase in inflammatory cytokines, histological changes, oxidative and nitrosive damage in the lung, as well as increased damage to the DNA of liver cells, blood plasma and lung. Among the three doses of GNPs (2.5, 7.5, and 22.5 mg/L) used, the highest dose had better anti-inflammatory effects. However, GNPs at a dose of 7.5 mg/L showed better efficacies in reducing ROS formation, alveolar diameter, and the number of inflammatory cells in histology, in addition to significantly reduced rate of DNA damage in lung cells without additional systemic genotoxicity already caused by cigarette smoke.

Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease.

BACKGROUND: Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood. METHODS: We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes. RESULTS: We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed. CONCLUSION: These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.

Protective Role of Genetic Variants in HSP90 Genes-Complex in COPD Secondary to Biomass-Burning Smoke Exposure and Non-Severe COPD Forms in Tobacco Smoking Subjects.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory disease characterized by airflow obstruction, commonly present in smokers and subjects exposed to noxious particles product of biomass-burning smoke (BBS). Several association studies have identified single-nucleotide polymorphisms (SNP) in coding genes related to the heat shock proteins family-genes that codify the heat shock proteins (Hsp). Hsp accomplishes critical roles in regulating immune response, antigen-processing, eliminating protein aggregates and co-activating receptors. The presence of SNPs in these genes can lead to alterations in immune responses. We aimed to evaluate the association of SNPs in the HSP90 gene complex and COPD. METHODS: We enrolled 1549 participants, divided into two comparison groups; 919 tobacco-smoking subjects (cases COPD-TS n = 294 and, controls SWOC n = 625) and 630 chronic exposed to BBS (cases COPD-BBS n = 186 and controls BBES n = 444). We genotyped 2 SNPs: the rs13296 in HSP90AB1 and rs2070908 in HSP90B1. RESULTS: Through the dominant model (GC + CC), the rs2070908 is associated with decreased risk (p < 0.01, OR = 0.6) to suffer COPD among chronic exposed BBS subjects. We found an association between rs13296 GG genotype and lower risk (p = 0.01, OR = 0.22) to suffer severe COPD-TS forms in the severity analysis. CONCLUSIONS: single-nucleotide variants in the HSP90AB1 and HSP90B1 genes are associated with decreased COPD risk in subjects exposed to BBS and the most severe forms of COPD in tobacco-smoking subjects.

Decreased Bone Type I Collagen in the Early Stages of Chronic Obstructive Pulmonary Disease (COPD).

Smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD) and is known to have deleterious effects on bone metabolism. However, the effects on bone collagen matrix during the development of COPD are unclear. The aim of this study was to evaluate the temporal effect of cigarette smoke exposure on bone type I collagen during COPD development in a cigarette smoke-induced model. C57BL/6 mice were allocated to three groups: control (C), animals exposed to filtered air for 1, 3 and 6 months; cigarette smoke (S), animals exposed to cigarette smoke for 1, 3 and 6 months; provisional smoking (PS), animals exposed to cigarette smoke for 3 months, followed by another 3 months of filtered air exposure. Evaluation of the respiratory mechanics and alveolar enlargement were performed. Femoral and tibial extraction was also performed to evaluate the type I collagen by immunofluorescence and COL1A1 gene expression. Exposure to cigarette smoke led to an alveolar enlargement and progressive reduction in lung tissue resistance and elastance, progressive reduction of type I collagen and reduction in COL1A1 gene expression. Although we did not observe any improvement in the functional and histological parameters in the provisional smoking group, we detected an increase in COL1A1 gene expression. A worsening in bone collagen matrix is part of the initial physiopathological events during COPD development and the smoking cessation induced an evident recovery of COL1A1 expression, possibly to attempt at tissue repair.

Mitochondrial Dysfunction in Skeletal Muscle Pathologies.

Several molecular mechanisms are involved in the regulation of skeletal muscle function. Among them, mitochondrial activity can be identified. The mitochondria is an important and essential organelle in the skeletal muscle that is involved in metabolic regulation and ATP production, which are two key elements of muscle contractibility and plasticity. Thus, in this review, we present the critical and recent antecedents regarding the mechanisms through which mitochondrial dysfunction can be involved in the generation and development of skeletal muscle pathologies, its contribution to detrimental functioning in skeletal muscle and its crosstalk with other typical signaling pathways related to muscle diseases. In addition, an update on the development of new strategies with therapeutic potential to inhibit the deleterious impact of mitochondrial dysfunction in skeletal muscle is discussed.

The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association.

We proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 ± 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 µl) or lipopolysaccharide (LPS) (1 mg/kg in 50 µl of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4+ and CD8+ T cells, Treg cells, and IL-10+ and IL-17+ cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-γ, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4+ and CD8+ T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17+ cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5+ cells corroborated the increased numbers of IL-17+ and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL-10+ cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model.

Common and Rare Variants Genetic Association Analysis of Cigarettes per Day Among Ever-Smokers in Chronic Obstructive Pulmonary Disease Cases and Controls.

INTRODUCTION: Cigarette smoking is a major environmental risk factor for many diseases, including chronic obstructive pulmonary disease (COPD). There are shared genetic influences on cigarette smoking and COPD. Genetic risk factors for cigarette smoking in cohorts enriched for COPD are largely unknown. METHODS: We performed genome-wide association analyses for average cigarettes per day (CPD) across the Genetic Epidemiology of COPD (COPDGene) non-Hispanic white (NHW) (n = 6659) and African American (AA) (n = 3260), GenKOLS (the Genetics of Chronic Obstructive Lung Disease) (n = 1671), and ECLIPSE (the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) (n = 1942) cohorts. In addition, we performed exome array association analyses across the COPDGene NHW and AA cohorts. We considered analyses across the entire cohort and stratified by COPD case-control status. RESULTS: We identified genome-wide significant associations for CPD on chromosome 15q25 across all cohorts (lowest p = 1.78 × 10-15), except in the COPDGene AA cohort alone. Previously reported associations on chromosome 19 had suggestive and directionally consistent associations (RAB4, p = 1.95 × 10-6; CYP2A7, p = 7.50 × 10-5; CYP2B6, p = 4.04 × 10-4). When we stratified by COPD case-control status, single nucleotide polymorphisms on chromosome 15q25 were nominally associated with both NHW COPD cases (ß = 0.11, p = 5.58 × 10-4) and controls (ß = 0.12, p = 3.86 × 10-5) For the gene-based exome array association analysis of rare variants, there were no exome-wide significant associations. For these previously replicated associations, the most significant results were among COPDGene NHW subjects for CYP2A7 (p = 5.2 × 10-4). CONCLUSIONS: In a large genome-wide association study of both common variants and a gene-based association of rare coding variants in ever-smokers, we found genome-wide significant associations on chromosome 15q25 with CPD for common variants, but not for rare coding variants. These results were directionally consistent among COPD cases and controls. IMPLICATIONS: We examined both common and rare coding variants associated with CPD in a large population of heavy smokers with and without COPD of NHW and AA descent. We replicated genome-wide significant associations on chromosome 15q25 with CPD for common variants among NHW subjects, but not for rare variants. We demonstrated for the first time that common variants on chromosome 15q25 associated with CPD are similar among COPD cases and controls. Previously reported associations on chromosome 19 showed suggestive and directionally consistent associations among common variants (RAB4, CYP2A7, and CYP2B6) and for rare variants (CYP2A7) among COPDGene NHW subjects. Although the genetic effect sizes for these single nucleotide polymorphisms on chromosome 15q25 are modest, we show that this creates a substantial smoking burden over the lifetime of a smoker.

Estudio comparativo de la estadificación de pacientes con EPOC según GOLD 2007, 2011 y 2019 / Comparative study of the categorization of COPD patients based on GOLD 2007, 2011 and 2019

INTRODUCCIÓN: La Enfermedad Pulmonar Obstructiva Crónica afecta a 260 millones de personas a nivel mundial y representará la tercera causa de muerte para el año 2020. MATERIALES Y MÉTODOS: Se realizó un estudio observacional descriptivo transversal con la finalidad de comparar la estadificación de un grupo de pacientes venezolanos con EPOC según la Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2007, 2011 y 2019. RESULTADOS: La muestra estuvo constituida por ochenta y nueve (89) pacientes con una edad promedio de 66,7 ± 0,9 años, siendo el 60,7% de los pacientes del sexo masculino y 82% fumadores. El 14,6% de los pacientes presentaban EPOC leve, 36% EPOC moderado, 41,6% EPOC severo y 7,9% EPOC muy severo. El valor del test Kappa de Cohen entre las escalas mMRC y CAT (COPD Assessment Test) fue de 0,529 (GOLD 2011) y 0,555 (GOLD 2019). CONCLUSIONES: 1) la poca concordancia entre el VEF1, grado de disnea e historial de exacerbaciones impacta la clasificación de la severidad de la EPOC al utilizar GOLD 2011; 2) la concordancia moderada entre las escalas mMRC y CAT sugiere que el tipo de cuestionario utilizado afecta la categorización de la severidad de la enfermedad; 3) los pacientes del grupo B mostraron una importante afectación en el intercambio gaseoso dado por valores más bajos de DLCO y oximetría arterial y 4) una proporción significativa de pacientes fueron clasificados en los grupos de alto riesgo (B y D) en GOLD 2011 y 2019.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) affects 260 million people worldwide and it is thought to become the third leading cause of mortality by the year 2020. MATERIAL AND METHODS: A transversal descriptive observational study was conducted to compare the categorization of a group of Venezuelan COPD patients according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2007, 2011 and 2019. RESULTS: Eighty-nine (89) patients with a mean age of 66.7 ± 0.9 years were included, 60.7% were male and 82% smokers. 14.6% of the patients had mild COPD, 36% moderate COPD, 41.6% severe COPD and 7.9% very severe COPD. Cohen's Kappa coefficient value between mMRC and COPD Assessment test (CAT) was 0,529 (GOLD 2011) and 0,555 (GOLD 2019). CONCLUSIONS: 1) the lack of concordance between FEV1 values, degree of dyspnea and history of exacerbations impacts COPD severity classification when using GOLD 2011; 2) moderate agreement between mMRC and CAT scales suggests that the type of questionnaire used to evaluate perception of dyspnea can affect disease severity categorization; 3) group B patients showed a significant gas exchange impairment due to lower values of DLCO and arterial oxymetry and 4) a significant proportion of patients were categorized in the high-risk groups (B and D) both in GOLD 2011 and 2019. Optimization of the evaluation of COPD severity is important to allow a better standardization of care and pharmacological management of patients with this disease.

Mimetic peptide AC2-26 of annexin A1 as a potential therapeutic agent to treat COPD.

Chronic obstructive pulmonary disease (COPD) is related to inflammatory process caused by smoking habit. In this scenario, the anti-inflammatory protein Annexin A1 (AnxA1) may represent a therapeutic alternative. We performed experiments to evaluate the effects of the AnxA1 mimetic peptide Ac2-26 in an initial COPD model by physiological, histopathological, biochemical and immunohistochemical analyses. Weight loss, increased blood pressure, reductions in the pulmonary frequency and ventilation, loss of tracheal cilia, enlargement of the pulmonary intra-alveolar spaces and lymphoid tissue found in untreated smoke-exposed group were attenuated by AnxA1 peptide treatment. The Ac2-26 administration also protected against leukocytes influx in bronchoalveolar lavage (BAL), lung and trachea, and it also led to decreased hemoglobin, glucose, cholesterol, gamma glutamyl transferase and aspartato aminotransferase levels. Similarly, reduction of proinflammatory mediators and higher concentration of anti-inflammatory cytokine were found in macerated lung supernatant, blood plasma and BAL in the treated animals. Besides Ac2-26 group showed reduced tissue expressions of AnxA1, cyclooxygenase-2 and metalloproteinase-9, but formylated peptide receptor 2 (FPR2) overexpression. Our results all together highlighted the protective role of the Ac2-26 mimetic peptide in COPD with promising perspectives.

Enfermedad pulmonar crónica en pacientes VIH positivos con inmunidad conservada / Chronic lung disease in HIV-positive patients with preserved immunity

Introducción: La infección por VIH puede asociarse a EPOC, sobre todo en estadios avanzados de enfermedad. La inflamación asociada al virus puede facilitar las alteraciones de la función respiratoria. Objetivos: Investigar la presencia de alteraciones de la función respiratoria en pacientes VIH positivos sin inmunocompromisoni hábito tabáquico. Comparar la función respiratoria de pacientes VIH con la población general(grupo control). Establecer la relación entre función pulmonar, sexo, edad del paciente, valor de CD4, uso de TARV,presencia de síntomas, enfermedad respiratoria y antecedentes de las mismas.Material y Métodos: Se realizó un estudio prospectivo, transversal, de tipo observacional y descriptivo. Luego deun análisis de la historia clínica y una entrevista en búsqueda de síntomas respiratorios, se estudiaron 68 pacientes,no fumadores, a los que se les realizó una espirometría. 46 (67%) eran VIH positivos (casos) y 22 (32,4%) VIH negativos (controles)...

Introduction: HIV infection can be associated with COPD, especially in advanced stages. Objectives: To investigate the presence of respiratory function alterations in HIV-positive patients without immunocompromiseor tobacco habit. Compare the respiratory function of HIV patients with the general population (control group).To establish the relationship between lung function and sex, age of the patient, CD4 value, use of ART, presence of symptoms, respiratory disease and history of symptoms. Material and Methods: A prospective, cross-sectional, observational and descriptive study was conducted. After a medical history analysis and an interview in search of respiratory symptoms, 68 patients, non-smokers, were studied and spirometry was performed. 46 (67%) were HIV positive (cases) and 22 (32.4%) were HIV negative (controls)...

Genetic polymorphisms and their involvement in the regulation of the inflammatory response in asthma and COPD.

Asthma and chronic obstructive pulmonary disease (COPD) are widely documented diseases with an inflammatory component. Asthma is a heterogeneous disorder of the airways that involves chronic inflammation, decline of the airway function and tissue remodeling. Chronic obstructive pulmonary disease is a preventable and treatable disease, which is characterized by persistent limited airflow, and is usually progressive with an increased inflammatory response in the airways. The inflammatory response is evoked by the stimulus of noxious particles and gases. Inflammation is a natural process in response to injury, but in asthma and COPD patients it occurs as an abnormal immune response to pathogenic stimuli which induce chronic inflammation, a key process in the pathogenesis of both diseases. However, the inflammatory process is different in both diseases, and is involved in several release patterns of inflammation mediators. It is not entirely clear whether these proteins are simply markers of the inflammatory process that accompanies a chronic disease or if they play a major role in the pathogenesis of the disease. The main proteins which have been described in these illnesses are: IL-4, IL-6, IL-8, and TNF-α. In addition, polymorphisms have been described in genes encoding these proteins that alter the transcription and susceptibility associated with these diseases. In this review, we will focus on asthma and COPD, and the involvement of these proteins and their genetic polymorphisms.

[Immunopathology of chronic obstructive pulmonary disease]. / Inmunopatología de la enfermedad pulmonar obstructiva crónica.

Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable condition that has a complex pathophysiology and an even more complex immunopathological process. The purpose of this review was to analyze COPD immunopathological aspects, which was addressed by undertaking a literature search for the most relevant documents indexed in the PubMed database over the last 10 years. Different conclusions could be drawn: in COPD immunopathology there are immune and non-immune inflammatory changes with oxidative stress imbalance, there are alterations in the protease/anti-protease ratio caused by direct and indirect genetic and epigenetic-environmental defects; COPD produces irreversible tissue damage and chronic inflammation with tissue repair alteration, which induces chronic obstruction of the airway, bronchitis and systemic damage. Most common resulting comorbidities include cardiovascular disease, metabolic syndrome, osteoporosis, depression, musculoskeletal dysfunction, increased biological age, lung cancer and other types of malignancies. In the conception of COPD, recognizing that it is a non-transmittable and preventable disease is indispensable.

La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad común, prevenible y tratable que presenta una fisiopatología compleja y un proceso inmunopatológico aún más complicado. El objetivo de esta revisión fue analizar los aspectos inmunopatológicos de la EPOC, para lo cual se llevó a una cabo una pesquisa bibliográfica de los documentos más relevantes indexados en la base de datos PubMed durante los últimos 10 años. Diversos aspectos pudieron concluirse: en la inmunopatología de la EPOC existen cambios inflamatorios, inmunológicos y no inmunológicos con un desequilibrio en el estrés oxidativo, así como alteraciones en la relación proteasas/antiproteasas debidas a efectos genéticos, epigenéticos, ambientales directos e indirectos. La EPOC produce daño tisular irreversible e inflamación crónica con alteración de la reparación tisular que induce obstrucción crónica de la vía aérea, bronquitis, enfisema y daño sistémico. Las comorbilidades resultantes más comunes son enfermedad cardiovascular, síndrome metabólico, osteoporosis, depresión, disfunción músculo esquelética, incremento de la edad biológica, cáncer pulmonar y otros tipos de neoplasias. En la concepción de la EPOC es indispensable reconocer que es una enfermedad no transmisible y prevenible.

Existe diferença entre o estado nutricional de pacientes com doença pulmonar obstrutiva crônica e outras doenças pulmonares? / Is there a difference between the nutritional status of patients with chronic obstructive pulmonary disease and other lung diseases?

Introdução: A doença pulmonar obstrutiva crônica (DPOC) é caracterizada pela lenta e progressiva obstrução crônica do fluxo aéreo, pouco reversível, associada a uma resposta inflamatória anormal dos pulmões e inalação de partículas ou gases tóxicos. Objetivo: Comparar o estado nutricional de pacientes hospitalizados com diagnóstico clínico de DPOC com outras doenças pulmonares. Método: Foram utilizados prontuários com dados referentes às características antropométricas, clínicas e alimentares de pacientes com diagnóstico clínico de DPOC e de outras doenças pulmonares. Para associar os dois grupos de pacientes, foram aplicados os testes T de Student, exato de Fisher e Mann-Whitney conforme a distribuição de normalidade. Resultados: Participaram do estudo 76 pacientes, não havendo diferença estatística entre ambos os grupos quanto à ingestão alimentar (p>0,05). Os pacientes com DPOC apresentaram mais desnutrição, porém sem significância (p>0,05) e a prega cutânea tricipital foi menor entre os pacientes com DPOC (p<0,05). Conclusões: Não há diferença entre o estado nutricional e dietético de pacientes com DPOC e demais doenças pulmonares.(AU)

Introduction: Chronic obstructive pulmonary disease (COPD) are characterized by slow and progressive chronic airflow obstruction, not easy reversible, associated with an abnormal inflammatory response of the lungs and inhalation of toxic particles or gases. Objective: To compare the nutritional status of hospitalized patients with clinical diagnosis of COPD with other pulmonary diseases. Methods: Documents of data regarding the anthropometric, clinical and dietary characteristics of patients with clinical diagnosis of COPD and other pulmonary diseases was used. In order to associate the two groups of patients, T Student, Fisher's exact and Mann-Whitney tests was applied according to the distribution of normality. Results: 76 patients participated, and there was no statistical difference between the two groups regarding food intake (p>0.05), patients with COPD have shown more malnutrition, but without significance (p>0.05) and triceps tick up was lower among the patients with COPD (p<0.05). Conclusions: There is no difference between the nutritional status of patients with COPD and other pulmonary diseases.(AU)

Regulatory T-Cell Distribution within Lung Compartments in COPD.

The importance of the adaptive immune response, specifically the role of regulatory T (Treg) cells in controlling the obstruction progression in smokers, has been highlighted. To quantify the adaptive immune cells in different lung compartments, we used lung tissues from 21 never-smokers without lung disease, 22 current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex-smokers with chronic obstructive pulmonary disease (COPD) for histological analysis. We observed increased T, B, IL-17 and BAFF+ cells in small and large airways of COPD individuals; however, in the NOS, we only observed increase in T and IL-17+ cells only in small airways. A decrease in the density of Treg+, TGF-ß+ and IL-10+ in small and large airways was observed only in COPD individuals. In the lymphoid tissues, Treg, T,B-cells and BAFF+ cells were also increased in COPD; however, changes in Treg inhibitory associated cytokines were not observed in this compartment. Therefore, our results suggest that difference in Treg+ cell distributions in lung compartments and the decrease in TGF-ß+ and IL-10+ cells in the airways may lead to the obstruction in smokers.

Severe pulmonary hypertension due to combined pulmonary fibrosis and emphysema: another cause of death among smokers

In 2005, the combined pulmonary fibrosis and emphysema (CPFE) was first defined as a distinct entity, which comprised centrilobular or paraseptal emphysema in the upper pulmonary lobes, and fibrosis in the lower lobes accompanied by reduced diffused capacity of the lungs for carbon monoxide (DLCO). Recently, the fibrosis associated with the connective tissue disease was also included in the diagnosis of CPFE, although the exposure to tobacco, coal, welding, agrochemical compounds, and tire manufacturing are the most frequent causative agents. This entity characteristically presents reduced DLCO with preserved lung volumes and severe pulmonary hypertension, which is not observed in emphysema and fibrosis alone. We present the case of a 63-year-old woman with a history of heavy tobacco smoking abuse, who developed progressive dyspnea, severe pulmonary hypertension, and cor pulmonale over a 2-year period. She attended the emergency facility several times complaining of worsening dyspnea that was treated as decompensate chronic obstructive pulmonary disease (COPD). The imaging examination showed paraseptal emphysema in the upper pulmonary lobes and fibrosis in the middle and lower lobes. The echo Doppler cardiogram revealed the dilation of the right cardiac chambers and pulmonary hypertension, which was confirmed by pulmonary trunk artery pressure measurement by catheterization. During this period, she was progressively restricted to the minimal activities of daily life and dependent on caregivers. She was brought to the hospital neurologically obtunded, presenting anasarca, and respiratory failure, which led her to death. The autopsy showed signs of pulmonary hypertension and findings of fibrosis and emphysema in the histological examination of the lungs. The authors highlight the importance of the recognition of this entity in case of COPD associated with severe pulmonary hypertension of unknown cause.