RESUMEN
Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in patients with cystic fibrosis (CF). CFRD has been correlated with important clinical outcomes, including poor nutrition, reduced pulmonary function, and earlier mortality. However, clinical decline due to abnormalities of blood glucose (dysglycemia) begins early in CF, before the diagnosis of CFRD by the gold-standard oral glucose tolerance test (OGTT). Continuous glucose monitoring (CGM) has been validated in patients with CF and has been recognized as a valuable tool in detecting early glucose abnormalities in patients with CF. Several CGM parameters have been used to predict CFRD in some but not all studies, and there is no consensus regarding CGM use for diagnostic purposes. Thus, it remains a complementary test to OGTT in CFRD diagnosis. The aim of this review is to provide an update on the pathophysiological mechanisms of CFRD, recent advances in the use of CGM for CFRD screening, and the association between CGM measures and CF-related clinical outcomes.
Asunto(s)
Fibrosis Quística , Diabetes Mellitus , Humanos , Glucemia , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Automonitorización de la Glucosa Sanguínea , Monitoreo Continuo de GlucosaRESUMEN
C-reactive protein (CRP) and leukocyte count are standard tools for recognising inflammation in COPD patients. This study aimed to find if there is a pattern in monocyte related haematological indices - monocyte to neutrophil ratio (MNR) and monocyte to lymphocyte ratio (MLR) - which could be helpful in differentiating COPD patients in need for hospitalization due to acute exacerbation of COPD or differentiating frequent COPD exacerbators from non-frequent COPD exacerbators. The study included 119 patients with COPD and 35 control subjects, recruited at the Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Croatia. Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. The COPD patients were divided into three groups - frequent exacerbators (FE), non-frequent exacerbators (NFE), patients hospitalized for acute COPD exacerbations (HAE) and the control group were healthy smokers (HS). A statistically significant difference was found in the values of MNR while comparing these groups of patients: FE vs HAE (p<0.000), NFE vs HAE (p<0.000) and HS vs HAE (p<0.001); and for the values of MLR: FE vs HAE (p<0.022), NFE vs HAE (p<0.000) and HS vs HAE (p<0.000). As MLR and MNR have shown the statistical difference comparing the group of HAE to NFE, FE and HS, MLR and MNR could be valuable and available markers of acute COPD exacerbations and need for hospitalization.
RESUMEN
The nutritional status of patients with chronic obstructive pulmonary disease (COPD) is a significant factor that influences the prognosis of the disease. This observational study aimed to analyse the nutritional status of COPD patients and assess the associations between nutritional status, disease severity, and exercise capacity in four different regions of Croatia. In this multicentre study, 534 COPD patients were recruited and evaluated concerning fat-free mass (FFM), fat-free mass index (FFMI), skeletal muscle mass index (SMMI), phase angle (PhA), pulmonary function tests, and the 6-minute walk test (6MWT). There were 325 (60.9%) male and 209 (39.1%) female patients with a mean age of 66.7±8.4 years. Most patients (73.2%) exhibited a moderate to severely abnormal obstructive pattern and had a reduced 6MWT distance (396.5±110.8 m). Among the participants, 32.8% were overweight and 22.3% were obese, and they had satisfactory values for nutritional status variables (FFM, FFMI, SMMI, PhA). There were no statistical differences between the centres in terms of nutritional status variables. There was a significantly positive correlation of FEV1 with BMI (r=0.148, p=0.001), PhA (r=0.256, p=0.00), FFM (r=0.365, p=0.00), and SMMI (r=0.238, p=0.00). However, there was no significant correlation of the 6MWT with BMI (r=-0.049, p=0.254), FFM (r=0.065, p=0.133), and SMMI (r=-0.007, p=0.867). The data analysis demonstrated that our patients were not underweight and that there was no significant difference between the centres in terms of BMI, FFM, FFMI, SMMI, and PhA. This lack of significant difference was observed even though one of the regions studied was Mediterranean.
RESUMEN
Coronavirus disease 2019 (COVID-19) is presented with a wide range of symptoms, from asymptomatic disease to severe and progressive interstitial pneumonia. As part of interstitial pneumonia, respiratory failure is typically presented as hypoxia and is the most common cause of hospitalization. When oxygen therapy fails, continuous positive airway pressure (CPAP) or noninvasive mechanical ventilation (NIV) are used as respiratory support measures of first choice. Noninvasive respiratory support (NIRS) is applied in order to save intensive care unit resources and to avoid complications related to invasive mechanical ventilation. Emerging evidence has shown that the use of CPAP or NIV in the management of acute hypoxemic respiratory failure in COVID-19 reduces the need for intubation and mortality. The advantage of NIRS is the feasibility of its application on wards. NIV could be administered via a face mask or helmet interface. Helmet adheres better than mask and therefore leakage is reduced, a delivery of positive end-expiratory pressure is more accurate, and the risk of nosocomial transmission of infections is lowered. Patients on NIRS must be carefully monitored so that further respiratory deterioration is not overlooked and additional measures of care including timely intubation and invasive mechanical ventilation could be performed if needed.
Asunto(s)
COVID-19 , Ventilación no Invasiva , Insuficiencia Respiratoria , Humanos , Presión de las Vías Aéreas Positiva Contínua/métodos , COVID-19/complicaciones , COVID-19/terapia , Ventilación no Invasiva/métodos , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/etiología , SARS-CoV-2RESUMEN
AIM: To determine the frequency of common symptoms in long COVID and their effect on the quality of life, and to determine the factors contributing to a more severe long COVID. METHODS: The study enrolled 266 patients who were either referred to long-COVID outpatient clinic or were inpatients undergoing rehabilitation. The data were collected between December 2020 and May 2021. We evaluated the symptoms experienced during acute and long COVID and comorbidities. Functional status was assessed with Post Covid Functional Status (PCFS). RESULTS: The final sample consisted of 261 patients. After acute COVID-19 period (>4 weeks), almost 80% of patients had impaired functional status. Only 21.5% reported no functional impairment (0 on PCFS scale). A higher PCFS score was associated with female sex (P<0.001) and oxygen therapy requirement during acute disease (P=0.001). However, it was not associated with having a pre-existing lung disease (P=0.749). Disease severity did not pose a risk for developing a more severe long COVID. CONCLUSION: Women were at greater risk for developing greater functional impairment in long COVID, although we have no explanation why. Malignant disease and hypertension also presented a risk factor for greater functional impairment. More studies are warranted to determine if patients with certain lung disease are more susceptible to long COVID.
Asunto(s)
COVID-19 , COVID-19/complicaciones , COVID-19/epidemiología , Croacia/epidemiología , Femenino , Humanos , Calidad de Vida , Factores de Riesgo , SARS-CoV-2 , Síndrome Post Agudo de COVID-19RESUMEN
BACKGROUND AND AIMS: Limited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy. METHODS AND RESULTS: The study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI-I, CRI-II), and monocyte to HDL ratio (MHR) were calculated. HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C-reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742-0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases. CONCLUSION: Lipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia.
Asunto(s)
Aterosclerosis/sangre , Dislipidemias/sangre , Lípidos/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Biomarcadores/sangre , Broncodilatadores/uso terapéutico , Comorbilidad , Dislipidemias/diagnóstico , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiología , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Fumar/efectos adversos , Fumar/sangreRESUMEN
BACKGROUND: To determine the effect of lockdown measures on lung transplant patients during the COVID-19 pandemic. SUBJECTS AND METHODS: We collected data from Croatian lung transplant patients before and after the lockdown and analyzed changes in weight, BMI, lung function and blood lipid status. RESULTS: An average increase of 3.74 kg (+4.92%) body weight during the 4 month lockdown period was observed. Lung function values and blood lipid status remained stable. CONCLUSION: Such weight gain could have detrimental effects on the morbidity and mortality of lung transplant patients. Further follow up is needed to determine the long term impacts of this observation.
Asunto(s)
COVID-19 , Trasplante de Pulmón , Índice de Masa Corporal , Control de Enfermedades Transmisibles , Croacia/epidemiología , Humanos , Pandemias , SARS-CoV-2 , Aumento de PesoRESUMEN
Interstitial lung diseases (ILD) are a heterogeneous group of diseases and one of the differential diagnosis which have to be excluded during diagnostic procedures are malignancies. We will present four patients who were referred to our Department because of suspicion of interstitial lung diseases according to radiology finding. In one case only, one of the radiologist's differential diagnosis was pulmonary lymphangitic carcinomatosis. All four patients had exertional dyspnea and dry cough which are nonspecific and can be first manifestation of ILD or obstructive lung diseases. After diagnostic evaluation in three cases, diagnosis was pulmonary lymphangitic carcinomatosis due to metastatic lung adenocarcinoma and in one due to metastatic adenocarcinoma of unknown primary origin. Patients with lymphangitic carcinomatosis have poor prognosis without treatment and usually die because of respiratory failure. With these four cases we want to highlight importance of thinking about malignancies when we have patients with suspicion of interstitial lung disease especially when reticular pattern is present on chest X ray. We also wanted to show how important is radiology finding and multidisciplinary approach, and how radiologist's differential diagnosis can be very helpful in making decisions in further investigations and way of clinicians thinking.
Asunto(s)
Adenocarcinoma del Pulmón/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , Neoplasias Pulmonares/diagnóstico , Anciano , Tos/etiología , Diagnóstico Diferencial , Disnea/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Lung cancer incidence in heart transplant patients is higher than in general population and correlates with smoking history. EGFR-mutations are more frequent in adenocarcinoma and among non-smoking women but incidence in solid organ transplanted patients is still not known. We present case of a 65-year-old ex-smoker male with history of heart transplantation and EGFR positive metastatic lung adenocarcinoma. At admission he was in a severe clinical condition and treatment with erlotinib was started. Initially he had good clinical and radiologic response to treatment with only grade 1 side effects. Data about drug interactions between cyclosporine and erlotinib are insufficient but we have to take this interaction into consideration during treatment because both drugs are substrates and inhibitors of CYP34A. In our case erlotinib was safe and well tolerated drug, there were no relevant toxicity, but close monitoring and dose reduction of cyclosporine was needed.
Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Trasplante de Corazón/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Ciclosporina/administración & dosificación , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Receptores ErbB/genética , Clorhidrato de Erlotinib/administración & dosificación , Clorhidrato de Erlotinib/efectos adversos , Humanos , Inmunosupresores/administración & dosificación , Neoplasias Pulmonares/genética , Masculino , MutaciónRESUMEN
Pulmonary hypertension (PH) is a chronic disease which severely impairs quality of life (QoL). The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific tool to assess patient-reported symptoms, functioning and QoL in PH patients. The aim of this study was to adapt and validate the CAMPHOR for use in Croatia. The adaptation process involved three stages: translation (bilingual and lay panel), cognitive debriefing interviews with patients and psychometric validation. For the latter stage, a postal survey was conducted with 50 patients to examine the reliability and validity of the adapted scale. All three scales of the Croatian CAMPHOR demonstrated excellent internal consistency (Symptoms = 0.93; Activity limitations = 0.94; QoL = 0.92) and test-retest reliability correlations (Symptoms = 0.90; Activity limitations = 0.95; QoL = 0.90). Predicted correlations with the SF-36 scales provided evidence for construct validity of the CAMPHOR scales. Evidence for known group validity was shown by the ability of the scales to distinguish between participants based on patient-perceived general health and disease severity. The Croatian version of the CAMPHOR is a valid and reliable tool for use in clinical routine and clinical research.
Asunto(s)
Hipertensión Pulmonar/psicología , Calidad de Vida/psicología , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios/normas , Actividades Cotidianas/psicología , Adaptación Fisiológica , Adulto , Anciano , Croacia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Reproducibilidad de los Resultados , TraducciónRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex condition, whose diagnosis requires spirometric assessment. However, considering its heterogeneity, subjects with similar spirometric parameters do not necessarily have the same functional status. To overcome this limitation novel biomarkers for COPD have been investigated. Therefore, we aimed to explore the potential value of N-glycans as COPD biomarkers and to examine the individual variation of plasma protein and immunoglobulin G (IgG) glycosylation profiles in subjects with COPD and healthy controls. METHODS: Both the total plasma protein and IgG N-glycome have been profiled in the total of 137 patients with COPD and 95 matching controls from Croatia. Replication cohort consisted of 61 subjects with COPD and 148 controls recruited at another Croatian medical centre. RESULTS: Plasma protein N-glycome in COPD subjects exhibited significant decrease in low branched and conversely, an increase in more complex glycan structures (tetragalactosylated, trisialylated, tetrasialylated and antennary fucosylated glycoforms). We also observed a significant decline in plasma monogalactosylated species, and the same change replicated in IgG glycome. N-glycans also showed value in distinguishing subjects in different COPD GOLD stages, where the relative abundance of more complex glycan structures increased as the disease progressed. Glycans also showed statistically significant associations with the frequency of exacerbations and demonstrated to be affected by smoking, which is the major risk factor for COPD development. CONCLUSIONS: This study showed that complexity of glycans associates with COPD, mirroring also the disease severity. Moreover, changes in N-glycome associate with exacerbation frequency and are affected by smoking. In general, this study provided new insights into plasma protein and IgG N-glycome changes occurring in COPD and pointed out potential novel markers of the disease progression and severity.
Asunto(s)
Proteínas Sanguíneas/metabolismo , Inmunoglobulina G/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/sangre , Anciano , Femenino , Glicosilación , Humanos , Masculino , Persona de Mediana Edad , Polisacáridos/metabolismo , Factores de Riesgo , FumarRESUMEN
Hemoptysis is a life-threatening emergency and a possible first sign of pulmonary tuberculosis. Minor hemoptysis, as a possible clinical aspect of adult tuberculosis, usually has limited course and in most cases, is resolved with antitubercular therapy. However, massive hemoptysis is a life-threatening condition associated with a mortality rate of >50% in the absence of well-timed and proper handling. Hence, prompt diagnosis and early interventions are essential. In this study, we present a rare case of pseudoaneurysm causing massive hemoptysis in a patient with pulmonary tuberculosis.
RESUMEN
Introduction: Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) lead to poor outcomes and increased burden for patients and healthcare systems. The Global Initiative for COPD (GOLD) includes specific recommendations for AECOPD interventions, discharge criteria, and follow-up. Aligning the AECOPD discharge letters (DL) with GOLD guidelines could facilitate dissemination of recommendations among general practitioners (GPs). Purpose: This study was conducted to assess the compliance of DL with the GOLD recommendations in Croatia. Methods: Pre-pandemic DL of patients presenting for AECOPD to emergency room (ER) were analyzed and stratified by clinical decision to hospitalize (HDL) or discharge patients for outpatient treatment (ERDL). Experienced pulmonologists checked the information from DL against guidelines by using online study-specific questionnaires. Results: In total, 225 HDL and 368 ERDL were analyzed. In most cases, the GOLD ABCD categories (85% HDL, 92% ERDL) or the spirometry-based degree of severity (90% HDL, 91% ERDL) were not included. The number of AEs in the previous year was recorded, but the specific frequent exacerbator phenotype not explicitly stated. The AE phenotype was included in two thirds of HDL and one third of ERDL. The blood eosinophil count was frequently available, but not considered decision-relevant information. Adjustments of previous maintenance therapy, mostly escalation, were recommended in 58.4% HDL and 27.9% ERDL, respectively. Education on proper use of inhalers was recommended only in 15.6% of HDL. Smoking cessation measures were advised in 23.1% HDL and 7.9% ERDL; pulmonary rehabilitation in 35.6% HDL and 0.8% ERDL. Early follow-up was frequently advised (>50%), but rarely appointed. Conclusion: Significant deficiencies in compliance with the GOLD guidelines were identified, translating into a missed opportunity for GPs to become acquainted with GOLD recommendations. These findings emphasize the necessity to increase compliance with guidelines first at specialist level and consequent standardization of DL.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Cese del Hábito de Fumar , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Alta del Paciente , Espirometría , Cooperación del Paciente , Progresión de la EnfermedadRESUMEN
Acute coronary syndrome (ACS) presents today the leading group of post-operative cardiovascular complications, while endothelial dysfunction (ED) is one of the key elements in its development. The chronic ED represents thus the basis for the gradual development of atherosclerotic changes, while its sudden aggravation leads to ACS. The persistent ED occurs due to the effects of chronic cardiovascular risk factors, while according to the available studies it can also develop or aggravate under the impact of different acute events. We have directed this study to the investigation of the dynamic of endothelial function before and after a major orthopaedic surgical intervention. This randomised prospective study included 19 patients that underwent the intervention of total knee replacement and 20 healthy examinees of the adequate age and gender High-resolution ultrasound test based on the flow mediated dilatation of the brachial artery is what at we carried out at the beginning of the research, respectively 12, 24, 48 and 72 hours, as well as 7 days after the surgical intervention. The starting values of the FMD test were within the normal range in both groups, although the ability of dilatation upon stimulus was significantly lower in the investigated group. The FMD percentage change in the total sample was negatively connected with the body weight, not having shown additional connections with other cardiovascular risk factors. During the early post-operative period, a significant transitory lowering of the FMD percentage change was recorded, having reached the lowest value 24 hours after the surgery. During the seven-day prospective surveillance, no significant cardiovascular complications were recorded. Further research is necessary in order to confirm these results as well as the testing of the possible connection of the described post-operative transitory endothelial dysfunction with the development of cardiovascular complications and the adverse event.
Asunto(s)
Síndrome Coronario Agudo/epidemiología , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Endotelio Vascular/fisiopatología , Complicaciones Posoperatorias/epidemiología , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/fisiopatología , Anciano , Endotelio Vascular/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Factores de Riesgo , UltrasonografíaRESUMEN
Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation plays an important role in chronic obstructive pulmonary disease (COPD) pathogenesis and might be involved in ongoing chronic inflammation. This study aimed to determine interleukin-1beta (IL-1ß) plasma concentration as well as IL1B, NLRP3 and caspase-1 (CASP1) gene expression in the Croatian COPD patients. 109 patients with stable COPD and age- and sex-matched 95 controls were included in the study. Plasma IL-1ß concentration was measured by Luminex technology, and gene expression analysis was performed using TaqMan assays. It was shown that COPD patients had increased concentration of IL-1ß and enhanced gene expression of IL1B, NLRP3 and CASP1 compared to controls. There was no difference in IL-1ß or IL1B, NLRP3 and CASP1 in patients with COPD regarding airflow obstruction severity and smoking history. Finally, the diagnostic potential of the determined parameters was evaluated, and it was found that IL-1ß correctly classified 89% of cases in the combination with common inflammatory biomarkers, white blood cell count and fibrinogen, showing a potential in COPD prediction. In conclusion, up-regulation of IL1B, NLRP3, CASP1 and increased IL-1ß concentration suggest the activation of NLRP3 inflammasome in the systemic compartment of patients with stable COPD.
Asunto(s)
Inflamasomas , Enfermedad Pulmonar Obstructiva Crónica , Caspasa 1 , Humanos , Inflamasomas/metabolismo , Inflamación/patología , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
Chronic obstructive pulmonary disease (COPD) is considered as the strongest independent risk factor for lung cancer (LC) development, suggesting an overlapping genetic background in both diseases. A common feature of both diseases is aberrant immunity in respiratory epithelia that is mainly regulated by Toll-like receptors (TLRs), key regulators of innate immunity. The function of the flagellin-sensing TLR5 in airway epithelia and pathophysiology of COPD and LC has remained elusive. We performed case−control genetic association and functional studies on the importance of TLR5 in COPD and LC development, comparing Caucasian COPD/LC patients (n = 974) and healthy donors (n = 1283). Association analysis of three single nucleotide polymorphisms (SNPs) (rs725084, rs2072493_N592S, and rs5744174_F616L) indicated the minor allele of rs2072493_N592S to be associated with increased risk for COPD (OR = 4.41, p < 0.0001) and NSCLC (OR = 5.17, p < 0.0001) development and non-small cell LC risk in the presence of COPD (OR = 1.75, p = 0.0031). The presence of minor alleles (rs5744174 and rs725084) in a co-dominant model was associated with overall survival in squamous cell LC patients. Functional analysis indicated that overexpression of the rs2072493_N592S allele affected the activation of NF-κB and AP-1, which could be attributed to impaired phosphorylation of p38 and ERK. Overexpression of TLR5N592S was associated with increased chemosensitivity in the H1299 cell line. Finally, genome-wide transcriptomic analysis on WI-38 and H1299 cells overexpressing TLR5WT or TLR5N592S, respectively, indicated the existence of different transcription profiles affecting several cellular pathways potentially associated with a dysregulated immune response. Our results suggest that TLR5 could be recognized as a potential biomarker for COPD and LC development with functional relevance.
RESUMEN
Chronic inflammatory lung diseases are characterized by uncontrolled immune response in the airways as their main pathophysiological manifestation. The lack of specific diagnostic and therapeutic biomarkers for many pulmonary diseases represents a major challenge for pulmonologists. The majority of the currently approved therapeutic approaches are focused on achieving disease remission, although there is no guarantee of complete recovery. It is known that angiotensin-converting enzyme 2 (ACE2), an important counter-regulatory component of the renin-angiotensin-aldosterone system (RAAS), is expressed in the airways. It has been shown that ACE2 plays a role in systemic regulation of the cardiovascular and renal systems, lungs and liver by acting on blood pressure, electrolyte balance control mechanisms and inflammation. Its protective role in the lungs has also been presented, but the exact pathophysiological mechanism of action is still elusive. The aim of this study is to review and discuss recent findings about ACE2, including its potential role in the pathophysiology of chronic inflammatory lung diseases:, i.e., chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. Additionally, in the light of the coronavirus 2019 disease (COVID-19), we will discuss the role of ACE2 in the pathophysiology of this disease, mainly represented by different grades of pulmonary problems. We believe that these insights will open up new perspectives for the future use of ACE2 as a potential biomarker for early diagnosis and monitoring of chronic inflammatory lung diseases.
Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , Asma/diagnóstico , Prueba de COVID-19 , COVID-19/enzimología , Hipertensión Pulmonar/diagnóstico , Pulmón/enzimología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , SARS-CoV-2/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Asma/enzimología , Asma/genética , COVID-19/genética , Humanos , Hipertensión Pulmonar/enzimología , Hipertensión Pulmonar/genética , Inflamación/diagnóstico , Inflamación/enzimología , Inflamación/genética , Pulmón/patología , Enfermedad Pulmonar Obstructiva Crónica/enzimología , Enfermedad Pulmonar Obstructiva Crónica/genética , Sistema Renina-AngiotensinaRESUMEN
Interleukin (IL)-1α, IL-1ß, IL-6, IL-8 and tumor necrosis factor (TNF)α contribute to inflammation in chronic obstructive pulmonary disease (COPD). We wanted to investigate their interrelations and association with disease severity, as well as to combine them with other inflammation-associated biomarkers and evaluate their predictive value and potential in identifying various patterns of systemic inflammation. One hundred and nine patients with stable COPD and 95 age- and sex-matched controls were enrolled in the study. Cytokines' concentrations were determined in plasma samples by antibody-based multiplex immunosorbent assay kits. Investigated cytokines were increased in COPD patients but were not associated with disease or symptoms severity. IL-1ß, IL-6 and TNFα showed the best discriminative values regarding ongoing inflammation in COPD. Inflammatory patterns were observed in COPD patients when cytokines, C-reactive protein (CRP), fibrinogen (Fbg), extracellular adenosine triphosphate (eATP), extracellular heat shock protein 70 (eHsp70) and clinical data were included in cluster analysis. IL-1ß, eATP and eHsp70 combined correctly classified 91% of cases. Therefore, due to the heterogeneity of COPD, its assessment could be improved by combination of biomarkers. Models including IL-1ß, eATP and eHsp70 might identify COPD patients, while IL-1ß, IL-6 and TNFα combined with CRP, Fbg, eATP and eHsp70 might be informative regarding various COPD clinical subgroups.
RESUMEN
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a complex inflammatory condition that can affect haemostasis. This study aimed to determine differences in platelet-related parameters between controls and COPD subjects. The hypothesis was that platelet indices are disturbed in COPD patients, and this would be accompanied by increased C-reactive protein (CRP), fibrinogen (Fbg) and white blood cells (WBC). Therefore, platelet count (Plt), platelet-related parameters - mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (Pct), their ratios (MPV/Plt, MPV/Pct, PDW/Plt, PDW/Pct), platelet to lymphocyte ratio (PLR), Plt index as well as CRP, Fbg and WBC were assessed. MATERIALS AND METHODS: Study included 109 patients with stable COPD and 95 control subjects, recruited at Clinical Department for Lung Diseases Jordanovac, University Hospital Centre Zagreb (Zagreb, Croatia). Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. RESULTS: Platelet (P = 0.007) and PLR (P = 0.006) were increased, while other platelet indices were decreased in COPD patients compared to controls. Combined model that included PLR, PDW and WBC showed great diagnostic performances, and correctly classified 75% of cases with an AUC of 0.845 (0.788 - 0.892), P < 0.001. Comorbidities (cardiovascular or metabolic diseases) had no effect on investigated parameters, while inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) therapy increased MPV and PDW values in COPD patients. CONCLUSION: Platelet indices were altered in COPD patients and they could be valuable as diagnostic markers of COPD development, especially if combined with already known inflammatory markers.