Occupational exposure and idiopathic pulmonary fibrosis: a multicentre case-control study in Korea.

SETTING: Multicentred hospital-based cases and control subjects in Korea. OBJECTIVE: To evaluate the association between idiopathic pulmonary fibrosis (IPF) and hazardous materials to which people are occupationally exposed. DESIGN: A multicentre, hospital-based, matched case-control study was performed. The ratio of IPF cases to controls was 1:1 (n = 78 in each group). IPF cases and controls were matched in terms of age group, sex and place of residence. Conditional logistic regression analysis was performed. RESULTS: In simple logistic regression analysis, exposure to metal dust and any exposure for >1 year in an occupational setting were significantly associated with IPF (metal dust OR 4.00, 95%CI 1.34-11.97; any exposure OR 3.67, 95%CI 1.02-13.14). After adjustment for environmental and military exposures and smoking history, the OR for metal dust exposure was 4.97 (95%CI 1.36-18.17) in multiple logistic regression analysis. CONCLUSIONS: Metal dust was associated with incident IPF in Seoul and Gyeonggi Provinces in Korea. This information will be used to support a tailored preventive strategy in specific industries or occupations.

Incidence and prevalence of idiopathic interstitial pneumonia and idiopathic pulmonary fibrosis in Korea.

SETTING: Although the incidence and prevalence of idiopathic interstitial pneumonia (IIP) and idiopathic pulmonary fibrosis (IPF) have been assessed in Western countries, their epidemiology has not been analysed in Asian countries, including the Republic of Korea. OBJECTIVE: To estimate the prevalence and incidence of IIP, including IPF, in Korea, using a large, nationwide database. DESIGN: The Health Insurance Review and Assessment Services claims database, which includes information on every patient with diagnostic codes for IPF and IIP from 2010 to 2013, was reviewed. Age- and sex-specific IPF and IIP prevalence and incidence rates were estimated. RESULTS: Among Korean males and females, IPF prevalence from 2010 to 2013 was estimated at respectively 39.7 and 24.3 per 100 000 population, while IIP prevalence was estimated at respectively 97.1 and 66.5/100 000. The annual incidence rates among Korean males and females during 2011 and 2012 were respectively 16.4 and 9.7/100 000, for IPF, and respectively 42.3 and 27.5/100 000 for IIP. CONCLUSIONS: IPF is more prevalent in Korea than previously reported; its prevalence may be similar to or higher than in the United States and in European countries.

Risk factors for lung function impairment among the general non-smoking Korean population.

SETTING: Nationwide general population in South Korea. OBJECTIVE: Except for tobacco smoking, risk factors for the impairment of lung function have not been widely evaluated. We evaluated the risk factors for lung function impairment among the general non-smoking Korean population. DESIGN: A total of 8164 non-smokers from the spirometry data set of the Korean National Health and Nutrition Examination Surveys IV and V (2008-2010) were included in the study. After sex stratification, multiple survey logistic regression analyses were performed to estimate the association between potential risk factors and impaired lung function in this nationwide cross-sectional study. RESULTS: The proportion of non-smokers among the general Korean population with forced expiratory volume in 1 s (FEV1) < 80% of predicted, forced vital capacity (FVC) < 80% of predicted and FEV1/FVC ratio < 0.7 were respectively 46.2%, 50.3% and 30.2%. In multiple survey logistic regression analyses, lung function impairment was associated with tuberculosis (TB) and asthma in female non-smokers and asthma in male non-smokers. CONCLUSIONS: TB and asthma are risk factors for lung function impairment among Korean non-smokers. To prevent further lung function impairment, a careful control system for these factors should be considered when setting health policy priorities.

Effect of fudosteine on mucin production.

Fudosteine is a novel mucoactive agent, although little is known about how fudosteine decreases mucin production. The present study examined the effects of fudosteine on MUC5AC mucin synthesis and cellular signalling. An animal model of lipopolysaccharide (LPS)-induced inflammation and a bronchial epithelial cell line model of tumour necrosis factor (TNF)-alpha-induced inflammation were used. Fudosteine was administered before stimulation with LPS or TNF-alpha. The MUC5AC mucin levels were assayed and the expression of the MUC5AC gene was measured. Western blotting was carried out for the detection of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and phosphorylated extracellular signal-related kinase (p-ERK). MUC5AC mucin synthesis and the expression of the MUC5AC gene were increased by LPS in rats or TNF-alpha in NCI-H292 cells; these effects were inhibited by fudosteine treatment. After stimulation with LPS or TNF-alpha, the expression of p-EGFR, p-p38 MAPK and p-ERK were detected. Fudosteine treatment reduced the expression levels of p-p38 MAPK and p-ERK in vivo and of p-ERK in vitro. The present results suggest fudosteine inhibits MUC5AC mucin hypersecretion by reducing MUC5AC gene expression and the effects of fudosteine are associated with the inhibition of extracellular signal-related kinase and p38 mitogen-activated protein kinase in vivo and extracellular signal-related kinase in vitro.

Arachidonic acid metabolites in antrochoanal polyp and nasal polyp associated with chronic paranasal sinusitis.

The aim of this study was to investigate the role of arachidonic acid metabolites (AAMs) in the pathogenesis of antrochoanal polyp (ACP). Using high-performance liquid chromatography (HPLC), we assayed the tissue concentrations of 6-keto-PGF1alpha, leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETE). Concentrations of AAMs in ACP were compared with the level in the control turbinate tissues and nasal polyps associated with chronic paranasal sinusitis (NPS). The concentrations of 6-keto-PGF1alpha were not significantly different in the control turbinate, ACP and NPS groups. In ACP, concentrations of LTC4, 15-HETE and 12-HETE were significantly lower than in the control turbinate. The striking differences in the profile of AAMs between ACP and NPS included a lack of production of LTD4 and LTE4 in ACP, also detectable in NPS, and markedly lower concentrations of 15-HETE and 12-HETE in ACP. The results of this study indicate that decreased lipoxygenase pathway products in arachidonic acid metabolism may be involved in the pathogenesis of ACP. However, in the pathogenesis of NPS, increased production of LTD4 and LTE4 may have an important role. Taken together, our results demonstrate a difference in pathogenesis between ACP and NPS, particularly in terms of arachidonic acid metabolism.

Intratumoral hypericin and KTP laser therapy for transplanted squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: To test intratumoral photodynamic therapy (IPDT) as a new treatment for squamous cell carcinoma in a preclinical tumor model. STUDY DESIGN AND METHODS: Human P3 squamous carcinoma cells were transplanted subcutaneously in athymic nude mice and allowed to grow into 300- to 500-mm3 tumors. Hypericin dye at 1 microg/gm of body weight was injected intratumorally (IT) or intravenously (IV). After 4 hours hypericin biodistribution was assessed in ethanol extracts from tissues by fluorescence spectroscopy. IPDT also was tested by KTP laser fiberoptic insertion in tumors 4 hours after IT dye injection compared to KTP532 laser therapy alone (532 nm, 1W, 40-60 J, 0.6-mm fiber). RESULTS: Hypericin concentration in tissues was as follows: (IT vs. IV) for tumors (3660 vs. 135 ng dye/gm tissue), lung (760 vs. 6345), liver (75 vs. 935), blood (65 vs. 480) compared to skin (465 vs. 110) or muscle (335 vs. 80) adjacent to the squamous cell tumors. Four hours after dye injection, the tumor exhibited bright orange fluorescence when excited by KTP 532-nm green laser light. The IPDT-treated tumors had a 3.32+/-0.32-mm radius of cell destruction when H&E-stained sections were examined compared with 2.5+/-0.38 mm for the laser only control group (n = 10, P = .003). CONCLUSIONS: This pilot study indicates laser IPDT with hypericin induces a significant increase in tumor necrosis compared with laser alone and may be useful as a less invasive adjuvant treatment for recurrent or inoperable human squamous cell cancers of the head and neck.

Synthesis and biological studies of catechol ether type derivatives as potential phosphodiesterase (PDE) IV inhibitors.

New series of catechol ether type derivatives 5, 6 have been synthesized and applied to biological tests. Even though it is a preliminary data, some of our target molecules show the promising result against PDE IV inhibition. SAR and biological studies with synthetic compounds will be discussed in detail.

Effects of leukotrienes and prostaglandins on cochlear blood flow in the chinchilla.

Prostaglandins (PGs) such as PGE2 and PGI2 are vasodilators, and leukotrienes (LTs) such as LTB4 and LTC4 are vasoconstrictors. Our previous studies have shown that salicylate ototoxicity is associated with decreased levels of PGs and increased levels of LTs. We hypothesized that vasodilating PGs increase cochlear blood flow and vasoconstricting LTs decrease cochlear blood flow. PGE2, Iloprost (a PGI2 analog), LTB4, and LTC4 were applied to the round window membranes of chinchillas and cochlear blood flow was measured with a laser Doppler flowmeter. PGE2 increased cochlear blood flow, while LTC4 decreased cochlear blood flow. This findings show that vasodilating PGs may have therapeutic implications for sensorineural hearing loss and/or vertigo by increasing cochlear blood flow. Vasoconstricting LTs may cause hearing loss by decreasing cochlear blood flow.

Correlation between anthropometric measurements of the oropharyngeal area and severity of apnea in patients with snoring and obstructive sleep apnea.

The aim of this study was to investigate the relationship between severity of apnea and anthropometric oropharyngeal measurements in patients with snoring and obstructive sleep apnea. A total of 22 patients complaining of snoring and apneic spell during sleep were evaluated by polysomnographic and anthropometric measurements of the oropharyngeal area. The horizontal width of the uvula at the mid-point and the length of the uvula were measured using a T-shaped ruler. The distance between the anterior pillars, posterior pillars and retromolar raphes were also measured. The correlation between these anthropometric measurements and polysomnographic parameters including the respiratory disturbance index (RDI) and the lowest arterial O2 saturation level (lowest SaO2) of the patients were analyzed. Of the anthropometric measurements, the horizontal width of the uvula showed a significant correlation with RDI and lowest SaO2. The results of the present study indicate that patients with broader uvula may have severer sleep apnea and that anthropometric oropharyngeal measurements may give additional information to polysomnographic findings for selecting surgical candidates.

The superiorly based flap long-term tracheostomy in pediatric patients.

PURPOSE: Tracheostomy is commonly used to provide control of the upper airway in pediatric patients. The traditional approach, which uses a midline vertical incision in the anterior tracheal wall, is associated with relatively high rates of complications when it is used on a long-term basis. Alternative approaches, such as removing tracheal window or creating tracheal flaps, have been avoided in the pediatric patient because of the risk of tracheal stenosis and the potential for the subsequent effect on tracheal growth. The superiorly based flap tracheostomy (SBFT) has greatly reduced these risks in adults and offers better stomal maintenance, safety, and patient acceptance, but it has not been widely evaluated in pediatric patients. METHODS: We reviewed 21 superiorly based flap tracheostomies performed in children at our institution between 1986 and 1993. Routine follow-up assessments included fixed and flexible laryngotracheoscopy. Average follow-up was 17 months. RESULTS: The most common indication for performing the SBFT was bilateral vocal cord paralysis. Short-term complications included wound infection and granuloma in 2 patients. Long-term complications were not observed. One patient died from lower respiratory tract causes. Five of the patients were eventually decannulated, and the stoma closed without laryngotracheal stenosis. Morbidity rates were less and mortality was comparable to those of traditional tracheostomy. CONCLUSION: We conclude that the SBFT is promising a technique for establishing long-term control of the airway in pediatric patients.

Adenomatous lesions of the temporal bone immunohistochemical analysis and theories of histogenesis.

Adenomatous lesions of the temporal bone represent a diverse group of neoplasms. At least three histopathologic patterns have been described: glandular; ribbon-like, or "festooning;" and aggressive papillary. Combinations of glandular and ribbon-like histologies in the same lesion are not uncommon. The glandular and ribbon-like histologies have been associated with carcinoid tumors, and the aggressive papillary tumor has been considered a separate entity. Recently, the endolymphatic sac has been proposed as the site of origin of the aggressive papillary lesions. Previous reports have described neuroendocrine properties with characteristics embracing the three histologic types. The authors postulate that the neural crest is the site of origin of this unusual group of neoplasms. Immunohistochemical analysis on the pathologic specimens of patients with adenomatous lesions of the temporal bone was performed to test this hypothesis. From 1975 to 1992 seven patients were treated at the Cleveland Clinic Foundation with a diagnosis of middle ear adenoma. A panel of special stains for neuroectodermal markers, including synaptophysin, chromogranin, neuron specific enolase, calcitonin, and serotonin was used on the paraffin-embedded formalin-fixed specimens. Three lesions were also evaluated by electron microscopy, all demonstrating dense core, intracytoplasmic granules. Three ribbon-like tumors were positive for synaptophysin and chromogranin, and two of these were positive for serotonin. One glandular tumor was positive for synaptophysin, and an aggressive papillary tumor was positive for synaptophysin and neuron specific enolase. An additional papillary tumor was referred following a third recurrence without accompanying immunohistochemical data. Cholesteatoma-like material was identified with a few glandular cells interspersed, all negative by immunohistochemical evaluation. The seventh specimen, initially diagnosed as papillary adenoma on light microscopy, was not studied by the aforementioned stains, and was later identified as a papilloma of sinonasal origin. The neural crest gives rise to pluripotential stem cells with widespread anatomic distribution, including the temporal bone. Because immunomarkers used in this study are specific for neuroectodermal differentiation, results suggest that temporal bone adenomas have neuroendocrine characteristics and could be derived from the specialized neuroectoderm of the neural crest.

Hypericin uptake in rabbits and nude mice transplanted with human squamous cell carcinomas: study of a new sensitizer for laser phototherapy.

Tissue uptake and biodistribution of hypericin was measured in rabbits and in nu/nu mice xenografted with P3 human squamous cell carcinoma to assess the value of this dye as an in vivo sensitizer for laser photoinactivation of solid tumors. Hypericin has absorption maxima at 545 and 590 nm with a fluorescence emission peak at 640 nm in ethanol. Dye uptake after intravenous injection was tested at 4 and 24 hours in rabbit tissues by ethanol extraction and quantitative fluorescence spectrophotometry. Maximum dye levels were seen at 4 hours in most vascular organs with lung having fivefold higher uptake than spleen followed by liver, blood, and kidney. Mice were examined after 2, 4, 6, 8, and 24 hours and after 3 and 7 days for dye uptake. The peak concentration of hypericin in murine organs was reached at 4 hours with uptake per gram of tissue as follows: lung > spleen > liver > blood > kidney > heart > gut > tumor > stomach > skin > muscle > brain. Elimination of hypericin was rapid in most murine organs with residual dye under 10% of maximum by 7 days compared to 25% to 30% retention for the squamous cell tumors and several normal tissues. These results suggest that hypericin may be a useful photosensitizer for KTP/532 laser interstitial therapy of human cancer.

Otolaryngologic approach to the diagnosis and management of otitis media.

Otitis media is a common childhood disease caused by multiple factors. Understanding the pathogenesis of otitis media is important in the diagnosis and management of it. The mode of therapy should be chosen depending on the type and stage of the disease. Treatment options available to an otolaryngologist include antibiotics, tympanocentesis, myringotomy and tympanostomy tube insertions, adenoidectomy with or without tonsillectomy, exploratory tympanotomy, atympanoplasty, and mastoidectomy.