Steroid-independent upregulation of matrix metalloproteinase 9 in chronic rhinosinusitis patients with radiographic evidence of osteitis.

BACKGROUND: Chronic sinonasal inflammation is associated with tissue remodeling, such as osteitis, which may be a marker of refractory disease; however, the pathophysiology of osteitis in chronic rhinosinusitis (CRS) is insufficiently understood. METHODS: Ethmoid mucosa and bone samples were obtained from 35 medically refractory CRS patients and 9 control subjects. Quantitative real-time polymerase chain reaction (RT-PCR) was performed separately on bone and mucosa for matrix metalloproteinase 2 and 9 (MMP2, MMP9) and tissue inhibitor of matrix metalloproteinase 1 (TIMP1). Osteitis was classified as mild, moderate, or severe by measuring bone thickness of the maxillary, sphenoid, and ethmoid sinuses on multiplanar computed tomography (CT). Patients were classified based on severity of osteitis and compared to controls. RESULTS: Nine patients demonstrated radiographic evidence of osteitis (mild = 3, moderate/severe = 6). Bone PCR revealed biologically significant upregulation of MMP9 in all patients with CRS, but the magnitude of the upregulation decreased with severity of osteitis. Mucosa PCR showed upregulation of MMP9 in moderate/severe osteitis only. No significant changes were seen in MMP2 or TIMP1 regulation. CONCLUSION: This is the first study to evaluate the role of MMP in the bone and mucosa of patients with sinonasal osteitis. The pattern of expression suggests there may be a time- and tissue-dependent role for MMP9 in the pathophysiology of osteitis. In addition, MMP9 overexpression is seen despite preoperative oral and intranasal steroid use, suggesting that if MMP9 is an important factor in the development of osteitis then steroids may not be the best treatment in prevention of osteitis.

Chitin stimulates expression of acidic mammalian chitinase and eotaxin-3 by human sinonasal epithelial cells in vitro.

BACKGROUND: Sinonasal epithelial cells participate in host defense by initiating innate immune mechanisms against potential pathogens. Antimicrobial innate mechanisms have been shown to involve Th1-like inflammatory responses. Although epithelial cells can also be induced by Th2 cytokines to express proeosinophilic mediators, no environmental agents have been identified that promote this effect. METHODS: Human sinonasal epithelial cells from patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls were harvested and grown in primary culture. Cell cultures were exposed to a range of concentrations of chitin for 24 hours, and mRNA for acidic mammalian chitinase (AMCase), eotaxin-3, and thymic stromal-derived lymphopoietin (TSLP) were assessed. Other cultures were exposed to interleukin 4 (IL- 4) alone and in combination with dust-mite antigen (DMA) for 36 hours. Extracted mRNA and cell culture supernatant were analyzed for expression of AMCase and eotaxin-3. RESULTS: Chitin induced a dose-dependent expression of AMCase and eotaxin-3 mRNA but not TSLP. Patients with recalcitrant CRSwNPs showed lower baseline expression of AMCase when compared with treatment-responsive CRSwNP and less induction of AMCase expression by chitin. DMA did not directly induce expression of AMCase or eotaxin-3. Expression of eotaxin-3 was stimulated by IL-4 and further enhanced with the addition of DMA. Levels of AMCase were not significantly affected by either IL-4 or DMA exposure. In some cases, the combination of IL-4 and DMA was able to induce AMCase expression in cell cultures not producing AMCase at baseline. CONCLUSION: The abundant biopolymer chitin appears to be recognized by a yet uncharacterized receptor on sinonasal epithelial cells. Chitin stimulates production of AMCase and eotaxin-3, two pro-Th2 effector proteins. This finding suggests the existence of a novel innate immune pathway for local defense against chitin-containing organisms in the sinonasal tract. Dysregulation of this function could precipitate or exacerbate Th2 inflammation, potentially acting as an underlying factor in recalcitrant CRSwNP.

Olfactory dysfunction in sinusitis with infiltration of numerous activated eosinophils.

OBJECTIVES: To compare the number of activated eosinophils in the ethmoidal sinus mucosa with the computed tomographic findings and degree of olfactory dysfunction, and study the clinical characteristics of this disease. MATERIAL AND METHODS: Ethmoidal sinus mucosal specimens were obtained from 84 patients with bilateral sinusitis accompanied by endoscopic sinus surgery (ESS). The percentage of activated eosinophils identified by staining with EG2 antibody was compared with the nasal symptoms (nasal obstruction, nasal discharge, headache, problems of smell and overall), the CT images and the olfactory dysfunction assessed using the T&T olfactometry kit and the Alinamin test. In addition, comparison was made of the endoscopic findings obtained after the ESS and the results of the T&T olfactometry assessment. RESULTS: Specimens from 42 patients were classified in the group showing a high percentage of EG2-positive cells, while specimens from 40 patients were classified in the group showing a low percentage of EG2-positive cells. Comparison of the subjective symptoms in these two groups found a statistically significant difference only in relation to "problems of smell", while comparison of the two groups in terms of the CT scan findings found significant differences only in relation to the anterior and posterior ethmoidal sinuses. In addition, it was found that there was a possibility of manifestation of olfactory dysfunction in the group with a high percentage of EG2-positive cells even when the overall CT score was low. Comparison of the postoperative ethmoidal sinus endoscopic findings and the results using the T&T Olfactometry kit revealed that olfactory dysfunction occurs together with aggravation of the lesions. CONCLUSIONS: For the diagnosis of sinusitis accompanied by severe infiltration of activated eosinophils, attention should be paid not only to the eosinophil counts in the blood and the tissues, but also to the clinical findings, such as the status of lesions in the ethmoidal sinus as seen in CT scans and the manifestation of olfactory dysfunction.

Th1 and Th2 cell population in chronic ethmoidal rhinosinusitis: a chemokine receptor assay.

BACKGROUND: It is necessary for the immune system in the nasal and paranasal sinus mucosa to possess appropriate responses to infective agents as well as allergic responses. Recently, the T helper (Th)1/Th2 paradigm has been proposed as a new concept to explain various immunologic phenomena. OBJECTIVE: Toward the goal of better understanding chronic rhinosinusitis, we have tried to define the predominating helper T-cell subsets among patients with chronic rhinosinusitis through characterizing the expressed chemokine receptors by these cells to find out the relation between these chemokine receptors' expression and the underlying pathogenesis of chronic rhinosinusitis. METHODS: Thirty patients with ethmoidal chronic rhinosinusitis were used in our study. Patients were divided into atopic and nonatopic groups according to their serum immunoglobulin (Ig)E levels. Samples from ethmoidal sinus mucosa were processed as follows: frozen sections were examined immunohistochemically for detection of CCR4, CCR5, and EG2 positive cells and the mRNA of CCR4, and CCR5 transcripts were then examined by real-time quantitative polymerase chain reaction (PCR). RESULTS: By immunohistochemistry, atopic patients showed high expression of CCR4 and EG2 positive cells, whereas nonatopic patients showed high expression of CCR5 positive cells. The expression of CCR4 and CCR5 mRNA, detected by real-time quantitative PCR, supported the data obtained by immunohistochemistry. CONCLUSION: The present study suggests that eosinophil recruitment associated with Th2 cell infiltration is the main factor responsible for the pathology of atopic rhinosinusitis.

Eosinophilic apoptosis in sinus mucosa: relationship to tissue eosinophilia and its resolution in allergic sinusitis.

BACKGROUND: Apoptosis, which is regulated by both cell survival and death signals, is important for the swift clearance of unwanted cells. OBJECTIVE: We sought to elucidate whether eosinophilic apoptosis is associated with tissue eosinophilia and to determine its resolution in allergic sinusitis (AS). METHODS: Numbers of eosinophils, numbers of IL-5(+) cells, and the apoptosis index of eosinophils were calculated in the submucosa (both superficial and deep layers) of patients with AS by using histochemical methods before and after prednisolone treatment. Patients without AS were used for control groups. Anti-EG2 antibody was used to identify eosinophils. IL-5, Fas, or Bax expression of eosinophils was evaluated to elucidate the role of the factors affecting eosinophilic apoptosis. RESULTS: EG2 and IL-5(+) cells were abundant in the submucosa of patients with AS, especially in the superficial layer. About 50% to 60% of the IL-5-producing cells were eosinophils. Apoptotic eosinophils were less numerous in the superficial layer than the deep layer in these diseases. After prednisolone treatment, an induction of eosinophilic apoptosis was accompanied by a significant decrease in the number of EG2(+) and IL-5(+) cells. No remarkable difference was observed in the Fas or Bax expression of eosinophils after prednisolone treatment. CONCLUSION: Autocrine secretion of IL-5 from eosinophils may be one reason why eosinophilic disease is difficult to manage. Induction of eosinophilic apoptosis is critical for reversing tissue eosinophilia in patients with AS.

[Immunological features of patients with polypous ethmoiditis]. / Nekotorye osobennosti immunologicheskikh pokazatelei pri polipoznom étmoidite.

34 patients with nasal polyps (NP) and 12 normal individuals were studied immunologically to investigate association of nasal polyp formation with disorders of general and local immunity. In NP patients there were decreased preoperative and early postoperative levels of peripheral blood T- and B-lymphocytes, functional activity of lymphocytes and neutrophils. In contrast to normal individuals, nasal secretion of NP patients contained degenerative epithelial cells and neutrophils, activated lymphocytes, monocytes and eosinophils. Nasal polyp tissues obtained after polypectomy contained more B-lymphocytes than T-lymphocytes. Lymphocytes and neutrophils in nasal polyps had elevated functional activity in tissue culture. We conclude that local hyperactivation of T- and B-lymphocytes as well as neutrophils contribute much to nasal polyp formation.

Report of the first case of invasive fungal sinusitis caused by Scopulariopsis acremonium: review of scopulariopsis infections.

Scopulariopsis acremonium is a species of saprophytic fungus not previously reported to cause invasive disease in humans, although invasive infections from other species of Scopulariopsis have been reported and are reviewed. Deep infection with this fungus is associated with a high mortality rate. Invasive fungal sinusitis, in general, is a potentially fatal disease that typically affects immunocompromised patients, such as those receiving intensive chemotherapy or undergoing bone marrow transplantation. We report a case of invasive fungal sinusitis caused by Scopulariopsis acremonium in a patient with leukemia, who was successfully treated with amphotericin B, itraconazole, endoscopic sinus surgery, and granulocyte colony-stimulating factor.

[Low-frequency vibrations in the treatment of patients with acute maxillary sinusitis and ethmoiditis. Non-specific resistance and immunity]. / Nizkochastotnye vibratsii v lechenii bol'nykh ostrym gaimoritom i gaimoroétmoiditom. Sostoianie nespetsificheskoi rezistentnosti i immuniteta.

The authors present clinicoroentgenological and immunological evaluation of low-frequency mechanical intermittent biovibromassage used in the treatment of acute maxillary sinusitis alone and in its combination with ethmoiditis. The massage provides simple-in-use and effective impact on inflammation in the cells of the ethmoidal labyrinth. It can be practiced both in hospital and outpatiently.

Comparison of inflammatory cell profile and Th2 cytokine expression in the ethmoid sinuses, maxillary sinuses, and turbinates of atopic subjects with chronic sinusitis.

Chronic sinusitis is a common disease characterized by persistent inflammation of the sinus mucosa. This study was undertaken to investigate immunopathologic findings in biopsy specimens from the ethmoid sinuses, maxillary sinuses, and inferior nasal turbinates of 14 allergic subjects with chronic sinusitis. The composition of the inflammatory infiltrate in the three tissue sites was examined by immunocytochemistry with anti-CD3 (total T cells), anti-CD4 (helper T cells), anti-CD8 (suppressor T cells), anti-MBP (eosinophils), antitryptase (mast cells), and antichymase (mast cells) antibodies. These revealed a significant increase in the T-cell helper/suppressor ratio and eosinophils in the ethmoid sinus mucosa compared with those in the maxillary sinus mucosa and the inferior turbinate. Eosinophil numbers were also higher in the maxillary sinus than in the inferior turbinate. Mast cells were present in significantly higher numbers in the ethmoid sinus and inferior turbinate biopsy sections than in the maxillary sinus. With antisense, radiolabeled riboprobes, we used in situ hybridization to examine the expression of interleukin-4 and interleukin-5 transcripts. The density of cells expressing interleukin-4 transcripts was significantly higher in the inferior turbinate biopsy sections than in those from the ethmoid and maxillary sinuses. In addition, the number of interleukin-4 mRNA-positive cells was higher in the ethmoid than in the maxillary sinus mucosa. The density of interleukin-5 mRNA-positive cells was significantly higher in the ethmoid and maxillary sinuses than in the inferior turbinate. The results of this study indicate (1) a more intense inflammatory response in the ethmoid sinus than in the maxillary sinus and inferior turbinate in allergic chronic sinusitis and (2) different inflammatory responses in the upper airways that are dependent on the anatomic site. These findings have potential implications in the design of new therapeutic interventions for allergic chronic sinusitis.

Allergic fungal sinusitis in the southeastern USA: involvement of a new agent Epicoccum nigrum Ehrenb. ex Schlecht. 1824.

Alternaria alternata, Aspergillus spp., Bipolaris spicifera, Curvularia lunata, Epicoccum nigrum and Fusarium solani were isolated repeatedly from groups of patients among 96 diagnosed with allergic fungal sinusitis (AFS). Epicoccum nigrum was obtained consistently from four patients, one of whom yielded mycelial masses consistent in morphology with E. nigrum. Fifteen of the predominant fungi recovered from air samples from selected patients' residences included the same species isolated from the mucin of its inhabitants. Air samples from other buildings, whose occupants (non-AFS individuals) complained of poor indoor air quality or of symptoms of the sick building syndrome (SBS), yielded some of the same species involved in AFS. An association of SBS with AFS was not established. Eight of the species implicated in AFS were found to colonize the surfaces of indoor construction and finishing materials at sites other than the residence of the patient. To our knowledge, this is the first report that E. nigrum can colonize nasal sinuses and cause AFS.

[The functional status of the thyroid gland and adrenal cortex in newborn babies and infants with acute ethmoiditis]. / Funktsional'noe sostoianie shchitovidnoi zhelezy i kory nadpochechnikov u novorozh-dennykh i grudnlykh detei s ostrymi étmoiditami.

Using the RIA method, thyroxine (T4), triiodothyroxine (T3), and cortisol (C) were measured in 10 patients with acute ethmoiditis, aged from 13 days to 6 months. At the peak of the disease, i. e. when infection toxicosis was very manifest, T3 was significantly lower and T4 tended to decrease. During the convalescence period T3 increased distinctly and T4 continued to decline. It can be concluded that the thyroid function was inhibited during the toxic period; however, this inhibition was transient and required no intervention. Nevertheless, in the case of complications, especially sepsis, transient hypothyrosis may develop which requires substitution therapy. Variations in cortisol serum concentrations were insignificant.