Inflammasome signalling pathway in the regulation of inflammation - its involvement in the development and exacerbation of asthma and chronic obstructive pulmonary disease.

Inflammasomes are multiprotein oligomers, whose main function is the recruitment and activation of caspase-1, which cleaves the precursor forms of interleukin (IL)-1ß and IL-18, generating biologically active cytokines. Activation of inflammasome is an essential component of the innate immune response, and according to recent reports it is involved in epithelial homeostasis and type 2 T helper cell (Th2) differentiation. In recent years, the contribution of inflammasome dependent signalling pathways to the development of inflammatory diseases became a topic of multiple research studies. Asthma and chronic obstructive pulmonary disease (COPD) are the most prevalent obstructive lung diseases. Recent studies have focused on inflammatory aspects of asthma and COPD development, demonstrating the key role of inflammasome-dependent processes. Factors responsible for activation of inflammasome complex are similar in both asthma and COPD and include bacteria, viruses, cigarette smoke, and particulate matter. Some recent studies have revealed that NLRP3 inflammasome plays a crucial role, particularly in the development of acute exacerbations of COPD (AECOPD). Activation of NLRP3 inflammasome has been linked with neutrophilic severe steroid-resistant asthma. Although most of the studies on inflammasomes in asthma and COPD focused on the NLRP3 inflammasome, there are scarce scientific reports linking other inflammasomes such as AIM2 and NLRP1 with obstructive lung diseases. In this mini review we focus on the role of molecular pathways associated with inflammasome in the most prevalent lung diseases such as asthma and COPD. Furthermore, we will try to answer the question of whether inhibition of inflammasome can occur as a modern therapy in these diseases.

COEXISTENCE OF PULMONARY FIBROSIS AND PROLIFERATION OF PULMONARY NEUROENDOCRINE CELLS FORMING TUMORLET.

Tumorlet is a disease rarely diagnosed in clinical practice. It is characterized by pulmonary neuroendocrine cell (PNEC) proliferation which invades the bronchiolar basement membrane and forms nodules with a diameter smaller than 5 mm. Case report: 72-year-old female patient was suffered for many years from progressive dyspnea and coughing with evidence of pulmonary fibrosis on high resolution computed tomography (HRCT). As a result of a lung biopsy, based on immunohistochemical tests, a 2 mm cluster of neuroendocrine cells (NEC) was found and it was diagnosed as tumorlet. Due to a long-term, insidious progress of the disease, as well as sex and age of the patient, the case emphasizes that differential diagnosis should include tumorlet as well as diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) as a more extensive manifestation of neuroendocrine cell proliferation in the respiratory tract.

Non-necrotizing inflammatory granulomas (n-ngs) in the course of inflammatory bowel disease - immunology and clinical manifestation of intestinal and respiratory N-NGS.

OBJECTIVE: The aim:The article describes and summarizes the immunological pathomechanisms controlling the development of non-necrotizing granulomas in the course of non-specific inflammatory bowel diseases (IBD) in lungs and intestines; it also reviews the possible clinical correlations between the processes in the gastrointestinal and respiratory tracts based on the example of Crohn's disease (CD) and non-specific inflammatory bowel disease (IBC). While the dominant cell subpopulation in ulcerative colitis (UC) is Th2, which produces interleukins IL-4, IL-5, IL-6, IL-10 and IL-13 and Th17 cells; CD characterized by the Th1 cell subpopulation and macrophages predominate, producing IL-23. These are considered to be the key factors crucial for the occurrence of chronic inflammation. Another important causative factor of non-specific inflammatory bowel diseases and granulation is the expression of CD40/CD40L proteins on activated T-cells, i.e. type 2 transmembrane proteins similar to TNF-alpha. However, the interactions between gastrointestinal neuroendocrine peptides/amines (NEPA) and the immune system are believed to have a significant influence on the pathophysiology of non-specific inflammatory bowel diseases and non-necrotizing granulation. The key functions of the immune response of the gastrointestinal tract are managed by the neuroendocrine regulatory system (NES) whose activities govern the production of various hormones including chromogranin/secretogranin, serotonin, vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), substance P, somatostatin or ghrelin.

[Pulmonary manifestations of crohn's disease or chronic pharmacotherapy complications? - case report].

Pareneteral manifestations of Crohn's disease (ChLC), apart from the most common skin and joint symptoms include also complications from the respiratory system. In addition chronic pharmacotherapy of ChLC, especially 5-aminosalicylic acid or anti-TNF- α drugs, is associated with possible pulmonologic side effects, sometimes difficult to differentiate. In this study, we describe a patient with ChLC, with a history of pneumocystic pneumonia, who was diagnosed with exfoliative institial pneumonitis as a result of chronic use of mesalazine. This disease is characterized by accumulation of alveolar macrophages in the lumen of the alveoli and intrabepticular septum. The most common etiologic factor is exposure to tobacco smoke. Our patient, non-smoker, was finally diagnosed after lung biopsy and histopathological evaluation. The gradual clinical improvement after mesalazine was an additional factor confirming the etiology of the disease. This side effect of mesalazine is not common but it should be considered in all patient treated with 5-aminosalicylic acid.