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-1β) 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-1β 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-1β and enhanced gene expression of IL1B, NLRP3 and CASP1 compared to controls. There was no difference in IL-1β 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-1β 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-1β concentration suggest the activation of NLRP3 inflammasome in the systemic compartment of patients with stable COPD.
Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, with oxidative stress and inflammation implicated in its development. Uric acid (UA) could exert anti-oxidative, ...pro-oxidative or pro-inflammatory effects, depending on the specific context. It was recently shown that soluble UA, and not just its crystals, could activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to interleukin (IL)-1beta secretion. We aimed to assess the differences in blood levels of UA and its ratio with creatinine (UCR) between COPD patients and healthy subjects, as well as their association with disease severity, smoking status, common COPD comorbidities and therapy regimes. The diagnostic characteristics of UA and UCR were also explored. This study included 109 stable COPD patients and 95 controls and measured white blood cells (WBC), C-reactive protein (CRP), fibrinogen (Fbg), IL-1beta, creatinine (CREAT) and UA. All of the parameters were increased in COPD patients, except for CREAT. UA and UCR were positively associated with WBC, CRP and IL-1beta. COPD smokers had lower UA and UCR values. Common COPD therapy did not affect UA or UCR, while patients with cardiovascular diseases (CVD) had higher UA, but not UCR, levels. Patients with higher UCR values showed worse disease-related outcomes (lung function, symptoms, quality of life, history of exacerbations, BODCAT and BODEx). Also, UCR differentiated patients with different severity of airflow limitation as well as symptoms and exacerbations. The great individual predictive potential of UCR and IL-1beta was observed with their odds ratios (OR) being 2.09 and 5.53, respectively. Multiparameter models of UA and UCR that included IL-1beta were able to correctly classify 86% and 90% of cases, respectively. We suggest that UA might be a useful biomarker when combined with IL-1beta, while UCR might be even more informative and useful in overall COPD assessments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims Biologics have been proven efficacious for patients with severe asthma (SA). It is essential to diagnose such individuals correctly. This study was designed to survey pulmonologists to identify ...barriers to early diagnosis and subsequent appropriate use of biologics for SA in Croatia. Methods A pulmonologist group with expertise in SA developed the initial list of questions, with the final questionnaire created according to a 2-round Delphi method. The resulting survey consisted of 23 items consequently divided into 4 domains: 1) Pulmonologists' demographics and professional experiences; 2) Concerns about asthma management; 3) Attitudes toward SA diagnosis; and 4) Beliefs and attitudes regarding the use of biologics in managing SA. The given answers represented the respondents' estimates. Results Eighty-four surveys were analyzed, with pulmonologists observing that general practitioners often inaccurately diagnose asthma and treat acute exacerbations. Although specialist centers are capably and correctly equipped, the time to diagnose patients with SA is approximately 3.5 months, with initial use of biologics delayed an additional 2 months. The primary indications for prescribing biologics are conventional therapy with oral glucocorticoids (91.7%) and frequent acute exacerbations (82.1%). In addition to improper diagnosis (64.3%), many patients with SA do not receive the indicated biologics owing to strict administrative directives for reimbursement (70.2%) or limited hospital resources (57.1%). Limitations The limitations of this survey include the subjective nature of the collected data, the relatively small sample size, and the lack of the biologic efficacy evaluation. Conclusions Croatian pulmonologists observed that a significant number of patients with SA who are eligible for biologics are not prescribed them, largely because of an inaccurate and/or delayed diagnosis, a delayed referral to a specialist center, highly restrictive criteria for reimbursement, and/or institutional budgetary limitations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the ...long-term effectiveness of VIT.
1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms.
285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% n = 207 of 610 with Ring-Messmer grade 3-4 vs. 11% n = 78 of 709 with Grade 1-2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% n = 207 in Grade 3-4 vs. 0.001% n = 78 in Grade 1-2; p < .0001), and the majority had normal baseline serum tryptase levels (69% n = 196 of 285). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01).
By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.
Blood cells are involved in systemic inflammation in chronic obstructive pulmonary disease (COPD). We aimed to assess differences in leukocyte subsets and their ratios between COPD patients and ...healthy individuals as well as their association with disease severity, smoking status and therapy in COPD.
One hundred and nine patients in the stable phase of COPD and 95 controls participated in the study. After blood sampling, white blood cells (WBC), neutrophils (NEUTRO), monocytes (MO), lymphocytes (LY) and basophils (BA) were determined on a Sysmex XN-1000 analyser, and ratios were calculated afterwards.
White blood cells, NEUTRO, MO and BA were higher in COPD patients than in controls. Also, COPD patients had increased neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), monocyte to lymphocyte ratio (MLR), basophil to lymphocyte ratio (BLR), basophil to monocyte ratio (BMR) and monocyte/granulocyte to lymphocyte ratio (M/GLR). Smoking has an impact on leukocyte counts, with BA, BLR and BMR being higher in COPD smokers vs. ex-smokers. Patients with very severe COPD were distinguished from moderate COPD by NLR, dNLR and M/GLR. In addition, those parameters were associated with lung function and dyspnoea, and NLR and dNLR also with multicomponent COPD indices BODCAT and DOSE. Great potential of dNLR, NLR and M/GLR in identifying COPD patients was observed regarding their odds ratios (OR) of 5.07, 2.86, 2.60, respectively (
< 0.001). Common COPD therapy did not affect any of the parameters investigated.
Leukocyte subsets and their ratios could be implemented in COPD assessment, especially in evaluating disease severity and prediction.
Objective: Studies show high comorbidity of mood disorders in asthma. As asthma is a highly heterogeneous disease with different phenotypes it can be expected that there is a difference in this ...association with different asthma phenotypes. The aim of our cross-sectional study was to assess the association of specific asthma phenotypes with anxiety and/or depression and their impact on asthma control. Methods: A cross-sectional study in 201 consecutive adult outpatients with asthma (≥18 years of age) was conducted. Each patient underwent physical examination, detailed medical history, Hospital Anxiety and Depression Scale, Asthma Control Questionnaire, Asthma Control Test, together with measurements of lung function and fraction of exhaled nitric oxide. Phenotypes were assessed using cluster analysis, and a multivariate analysis was used to identify associations of mood disorders with different phenotypes. Results: Five asthma phenotypes were identified: allergic (AA, 43.8%), aspirin-exacerbated respiratory disease (AERD, 21.9%), late-onset (LOA, 18.9%), obesity-associated (OAA, 10.0%), and respiratory infections associated asthma (RIAA, 5.5%). A multivariate analysis showed a significant association of anxiety with LOA and comorbid hypertension (LOA, odds ratio (OR) = 2.12; hypertension, OR = 2.37, p = 0.012), and depression with AA, RIAA, hypertension, and ACQ score (AA, OR = 6.07; RIAA, OR = 4.73; hypertension, OR = 5.67; ACQ, OR = 1.87; p < 0.001). Comorbid anxiety/depression was associated with AA, LOA, RIAA, hypertension, and ACQ score (AA, OR = 10.15; LOA, OR = 2.98; RIAA, OR = 6.29; hypertension, OR = 5.15; ACQ, OR = 1.90; p < 0.001. Conclusion: Mood disorders were significantly associated with AA, LOA, and infection-associated asthma, together with comorbid hypertension and the level of asthma control.
Dyspnea or breathlessness is a term primarily used in respiratory medicine. Nevertheless, in the last fifteen years, studies from other fields focus on the affective component of this complex ...phenomenon due to the frequent observation that psychological states can cause or be caused by dyspnea. Research so far shows that besides the biological component, dyspnea has a strong emotional and psychosocial determinant. This means that apart from its biological factors, dyspnea and its intensity are affected by emotions, personality, anxiety and depression, etc. Individuals with psychiatric disorders, in the same conditions, will evaluate their dyspnea as more intense and disturbing compared to individuals without psychiatric comorbidity. Emotional states in healthy individuals can amplify the sense of dyspnea which is of extreme importance for clinical practice in order to consider the whole person and not just the symptom which is being presented. Also, dyspnea seems to be frequent complaint in some groups of patients with psychiatric disorders (e.g.panic disorder), where the fear of suffocation is presented as clinical symptom. Futher research of dyspnea as a complex, multicomponent phenomenon, can contribute to better treatment options and better differential diagnosis concerning possible psychiatric background of physical symptoms.
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.
Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1β-induced inflammation. We ...have hypothesized that single nucleotide polymorphisms (SNPs) in
genes, coding for key regulators of IL-1β, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different
genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients' overall survival was analyzed with the Kaplan-Meier method with the log-rank test. Serum IL-1β concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV
% predicted), was significantly associated with the minor allele genotypes (AT + TT) of
rs12150220 (
= 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1β compared to the AA genotype (
= 0.027) in COPD patients.
rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (
= 0.0083). Polymorphisms in
(rs12150220; OR = 0.55,
= 0.03) and
(rs12462372; OR = 0.36,
= 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in
rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.
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