Thrombin, an effector enzyme of coagulation system, has important biological functions not only in thrombosis and hemostasis but also in inflammation. Thrombin's precise role in sinonasal inflammation remains unknown but indirect evidence suggests it may play a fundamental role. We found that thrombin aided tissue remodeling by stimulating platelet-derived growth factor (PDGF) secretion and fibroblast or smooth muscle cell prolifration. The natural anticoagulant-activated protein C decreased PDGF expression and suppressed fibrosis in a lung fibrosis mouse model.
Elevated procoagulant and suppressed fibrinolytic activity is regularly encountered in different forms of clinical and experimental tissue remodeling of airways. We discuss evidence for impaired regulation of coagulation and fibrinolysis factors in clinical and experimental airway diseases and the role of protease-activated receptors (PARs) induced cellular events, especially in airway epithelial cells. Given experiments in clinical data and animal models of lung fibrosis, asthma, nasal allergy, and chronic rhinosinusitis, we also discuss therapeutic potential for treating of upper airway disease resistant to current therapeutics.

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Surgery in allergic rhinitis (AR) is viewed as a last resort. Surgical procedures and instruments depend on the depth of the target organ, and on the approach from outside or inside the inferior turbinate.
Among the most effective types of surgery are submucosal turbinectomy and posterior nasal neurectomy. The inferior turbinate bone has 3 or 4 canal-like structures including a cord-like structure with vessels and the most peripheral palatine nerve. Selective excision of cord-like structure of the inferior turbinate with submucosal turbinectomy provides better clinical results than submucosal turbinectomy alone, and comparable results with submucosal turbinectomy combined with posterior nasal neurectomy.

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Cedar pollinosis in Japan is more prevalent than perennial allergic rhinitis from mite allergens. Allergen-specific subcutaneous immunotherapy (SCIT), while clinically effective, involves problems, such as pain during injections, frequent medical visits, and side effects such as anaphylaxis. Sublingual immunotherapy (SLIT) was developed over-seas and clinical trials for Japanese cedar pollinosis were begun in Japan in 2005.
While a 2008 study showed SLIT symptom scores to be better than those of drug therapy, it was not as satisfactory as SCIT. SLIT was, however, safe and reduced the need for medication.
The immunotherapy mechanism is still unclear and biomarkers have yet to be found in both SCIT and SLIT. We previously showed antigen-induced histamine release from peripheral basophils down-regulated by SCIT, and rates related to their symptoms, so, we studied histamine release in SLIT in a double-blind placebo-controlled study. Changes in peak season/pre season histamine release rates were significantly lower in SLIT compared with placebo.
Regulatory T cells modify immunological response in allergy, but natural regulatory T cells in peripheral blood were not changed by SLIT in our study. Regulatory T cell subtypes were identified recently. We focused on the induced type 1 regulatory T cell (Tr1), which was positive for CD4 and CD25 with negative foxp3 and produces high IL-10. Our samples showed the Tr1 percentage in whole CD4 positive T cells up regulated by SLIT. Cell proliferation of T cells stimulated by the Japanese cedar antigen was suppressed in SLIT and recovered by adding anti-IL-10 antibody or anti-IL-10 receptor antibody. We hope IL-10 from Tr1 may prove to be a key to the immunotherapy mechanism.

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Antrochoanal polyps arise mostly from the maxillary sinus and are relatively common in children and young adults. The most important point during surgery for antrochoanal polyp is to remove it completely from its base. For this purpose, various techniques such as inferior meatal approach, endoscopic nasolacrimal duct inferior turbinate swing technique or canine fossa approach have been considered. The canine fossa approach is minimally invasive but risks trocar injury to infraorbital nerve branches. To avoid this, we use endoscopically guided canine fossa trephination. In some patients, nerve branches are clearly visible and a trephination site can be chosen that avoids these. Otherwise, anatomic landmarks least likely to risk injury to the nerve are the intersection of midpupillary line and a line through the nasal floor. In 10 subjects undergoing this approach, non experienced postoperative upper lip and/or tooth numbness or paresthesia. Endoscopically guided canine fossa trephination is thus useful in antrochoanal polyp removal due to fewer neurological complications than occur using a conventional approach.

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We evaluated efficacy in quality of life (QOL) in allergen-specific subcutaneous (SCIT) or sublingual (SLIT) immunotherapy for adult subjects with Japanese cedar pollinosis compared to drug therapy. Subjects involved 31 cases of SCIT, 40 of SLIT, 25 of in initial prescattering drug treatment, and 40 for whom medication was started after pollen scattering evaluated by the Japan rhinoconjunctivitis QOL questionnaire consisted of 6 symptoms and 17 items. Average scores are given for symptoms and QOL items numbered in the sequence of SCIT, SLIT, initial drug therapy, and postscattering therapy. SCIT was significantly better than SLIT for 3 items, but not significantly so for symptoms. SCIT was significantly better than initial drug therapy for rhinorrhea and eye symptoms and for 6 QOL items. SCIT was significantly better than postscattering therapy for all symptoms and for all QOL items except one. SLIT was superior to initial drug therapy in general, but not statistically significantly so for symptoms or QOL. SLIT was significantly better for all symptoms except sneezing and for 10 QOL items. These results suggest that immunotherapy had benefits for QOL and clinical efficacy.

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Fungal rhinosinusitis is classified into noninvasive rhinosinusitis including fungus balls, allergic fungal rhinosinusitis and invasive rhinosinusitis. We report two cases of fulminate fungal rhinosinusitis complicated by orbital and intracranial spread necessitating surgical debridement and medication. Those patients were successfully managed by combination with antifungal therapy and surgical debridement. Those with paranasal invasive mycosis were analyzed literally. Mortality remains unacceptably high, particularly in the subgroup with neurological symptoms, but surgery and effective drugs with different mechanisms of action improved results, over use of a single agent, needs in vitro, in vivo, and clinical validations. Early diagnosis and treatment are important in preventing unfavorable outcomes from such infection.

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Cases of hereditary hemorrhagic telangiectasia (HHT), an autosomal-dominant inherited disorder adversely affecting skin, mucous membrane, and visceral blood vessels, usually seen first by otolaryngologists because epistaxis is the most common manifestation. HHT varies greatly in epistaxis course and severity, requiring hospitalization and multiple transfusions in about one-third of all cases. None of the many available treatment strategies has proven entirely successful for all individuals. Since the early 1990s we have conducted 30 nasal dermoplasties (ND) treating those with moderate or severe HHT. To reduce epistaxis incidence by protecting fragile abnormal vessels in the superficial nasal mucosa from trauma by applying a split-thickness skin graft. We found ND to be effective in HHT subjects with moderate or severe nasal bleeding.
Saunders, who pioneered this technique, recommended anterior septal mucosal removal, but we have gone on to remove mucosa from the anterior septum, the nasal floor and the inferior turbinate, covering the denuded area with a split-skin graft. ND reduces bleeding frequency. Bleeding may, however, occur after ND, due to telangiectatic mucosal areas in the anterior superior septal mucosa, left uncovered at the suture margin. We have thus added further removal of the most anterosuperior septal mucosa, grafting the split-thickness skin circumferentially. This refinement has not produced nasal valve stenosis and has, in fact, improved postoperative intranasal findings. In the presence of septal perforation, the perforation should be repaired before or at least during skin grafting.

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