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 NLRP 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 NLRP 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 (FEV₁% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1β compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220; OR = 0.55, p = 0.03) and NLRP4 (rs12462372; OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 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.

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 TLR5^N592S was associated with increased chemosensitivity in the H1299 cell line. Finally, genome-wide transcriptomic analysis on WI-38 and H1299 cells overexpressing TLR5^WT or TLR5^N592S, 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.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide. Although it is well known that comorbidities are highly prevalent in patients with COPD, they are not considered for treatment effect analysis. Aims and objectives: To observe frequency of comorbidities in patients with COPD and compare its distribution in 4 GOLD groups. Methods: Observational cross sectional study was designed to identify comorbidities related with categorized disease groups. Patients with COPD treated at University Hospital Centre were included. Severity of COPD was estimated and number of comorbidities was counted. Comorbidity was defined as the presence of disorder in addition to COPD irrespective of their relation to COPD. Results: We enrolled 460 COPD patients (68,5% males; average age at diagnosis 61,3 years. Majority of patients were in GOLD group A (41%) and B (29%), followed by group D (25%) and C (5%). Comorbidities were present in 90% of patients, with 31% of patients with 1 comorbidity, 31% with 2 comorbidities and 28% with 3 or more (mean of 1.9).There was no significant difference in number of comorbidities among GOLD groups (P=0.81). Most common comorbidities were arterial hypertension (47%), lung neoplasm (40%) and cardiovascular diseases (23%). Conclusions: We showed that COPD is rarely diagnosed as an isolated condition, since different comorbidities were present in 90% of patients. Hypertension, lung neoplasms and cardiovascular diseases were revealed as the most common ones. High proportion of lung cancer can be attributed to searching for COPD in lung cancer patients. A multidimensional COPD diagnosis approach should be taken into account when classifying COPD patients into GOLD groups.

We report a rare case of perforation of the intermediate bronchus by a loosened osteosynthetic implant, 8 years after the patient had undergone surgery for right thoracic scoliosis with the VDS instrumentation. Due to chronic lung inflammatory alteration caused by bronchial obstruction, lower bi-lobectomy was performed. We believe that spinal growth and progression of idiopathic scoliosis can lead to implant failure, while the variance in intrathoracic topographic relations and respiratory excursion facilitate it's penetration into the bronchus. In order to impede foreign body perforation of mediastinal structures and to reduce its complications, preventive methods, along with timely diagnostics, are required. Atelectatic and chronic inflammatory alterations that compromise adequate lung ventilation could require a resection procedure.