Remodeling changes of the upper airway with chronic rhinosinusitis : Remodeling of upper airway in CRS

Chronic rhinosinusitis (CRS) clinically is a heterogeneous group of sinus diseases, which may cover different disease entities, or may represent a disease continuum. Studying inflammatory cells and mediators in clearly defined disease subgroups may lead to a better differentiation of chronic sinus diseases. Sinonasal mucosal tissue from 10 nasal polyp (NP) patients, 13 cystic fibrosis patients (CF-NP), eight CRS subjects without polyps, and nine control patients were stained for CD3, CD25, CD68, CD20, myeloperoxidase (MPO), CD138 and tissue homogenates were assayed for eotaxin, interleukin (IL)-1beta, IL-2sRalpha, IL-5, interferon (IFN)-gamma, IL-8, transforming growth factor (TGF)-beta1, tumor necrosis factor-alpha, and MPO by enzyme-linked immunosorbent assay or UNICAP system. Nasal polyp and CF-NP showed increased numbers and activation of T cells, while only NP displayed an increase in plasma cells. Nasal polyp had significantly higher levels of eosinophilic markers [eosinophils, eotaxin, and eosinophil cationic protein (ECP)] compared with CRS, controls and CF-NP. Chronic rhinosinusitis was characterized by a Th1 polarization with high levels of IFN-gamma and TGF-beta, while NP showed a Th2 polarization with high IL-5 and immunoglobulin (Ig) E concentrations. Nasal polyp and CF-NP were discriminated by edema from CRS and controls, with CF-NP displaying a very prominent neutrophilic inflammation. Based on cellular and mediator profiles, we suggest that CRS, NP, and CF-NP are distinct disease entities within the group of chronic sinus diseases.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common causes of adverse drug reactions. Majority of them are of the hypersensitivity type. The two frequent clinical presentations of aspirin hypersensitivity are: aspirin-induced bronchial asthma/rhinosinusitis (AIA/R) and aspirin-induced urticaria/angioedema (AIU). The decisive diagnosis is based on provocation tests with aspirin, as the in vitro test does not hold diagnostic value as yet. Detailed protocols of oral, bronchial and nasal aspirin provocation tests are presented. Indications, contraindications for the tests, the rules of drug withdrawal and equipment are reviewed. Patient supervision and interpretations of the tests are proposed.

Chronic rhinosinusitis is an inflammatory disease with distinct cytokine and remodeling patterns. The objective was to analyze the presence of TGF-beta isoforms, receptors, intracellular signaling, and collagen deposition in chronic rhinosinusitis. Sinonasal mucosal samples obtained from chronic rhinosinusitis with nasal polyps (CRSwNP; n = 13), chronic rhinosinusitis without nasal polyps (CRSsNP; n = 13), and controls (n = 10) were analyzed for TGF-beta isoforms 1 and 2 by means of ELISA and IHC, and for TGF-beta R1, 2, and 3 by RT-PCR and IHC. As downstream proteins, phospho-Smad 2 (pSmad 2) and collagen were analyzed by performing immunostaining and picrosirius red staining, respectively. TGF-beta 1 and 2 protein concentrations, TGF-beta receptor (R) I and TGF-beta RIII mRNA expression, the number of pSmad 2-positive cells, and total collagen amount were significantly higher in CRSsNP versus controls. In CRSwNP, TGF-beta 1 protein concentration, TGF-beta RII and TGF-beta RIII mRNA expression, the number of pSmad 2-positive cells, and total collagen amount were significantly lower versus controls. Only TGF-beta 2 protein was found higher in CRSwNP versus controls. A high TGF-beta 1 protein expression, increased TGF-beta RI expression, and a high number of pSmad 2-positive cells all indicate an enhanced TGF-beta signaling in CRSsNP, whereas a low TGF-beta 1 protein concentration, a decreased expression of TGF-beta RII, and a low number of pSmad 2-positive cells in CRSwNP indicate a low level of TGF-beta signaling in CRSwNP. These findings are compatible with the remodeling patterns observed, reflected by a lack of collagen in CRSwNP, and excessive collagen production with thickening of the collagen fibers in the extracellular matrix in CRSsNP.