Background: Cough hypersensitivity is a major factor mediating chronic persistent cough. Capsaicin inhalation cough challenge is a representative tool for assessing cough sensitivity. However, the normal ranges and determinants have not been investigated in healthy Korean adults. Methods: Healthy adult volunteers were recruited by public postings at a single tertiary medical institution. For every volunteer, four age-gender-matched patients with chronic cough (lasting more than 8 weeks) were included. Capsaicin cough challenge tests were performed by dose-response, tidal-breathing method (15 seconds) in 1 minute intervals and the concentration causing five or more coughs (C5) was determined. Results: A total of 65 volunteers (52 females and 13 males) with mean age of 35.5 ± 11.4 (SEM) were recruited. Age, gender, atopy, sputum eosinophilia did not influence capsaicin cough sensitivity. In healthy females, BMI showed moderate negative correlation to C5 (r= -0.353, p= 0.001). Healthy volunteers had significantly higher C5 values compared to the patients (median C5 (IQR): 32 (112) vs 16 (24) respectively; p-value= 0.000). However, in ROC curve analysis, C5 showed poor discriminating value (AUC= 0.329) in identifying clinical cough. Conclusions: Capsaicin cough reflex was examined in Korean adults. Chronic cough patients had significantly more sensitive capsaicin reflex; however, its wide overlap between volunteers and patients may limit its application in the diagnosis of cough patients. The significant relationship between capsaicin sensitivity and BMI in healthy females warrants further consideration in the interpretation of the results.
Hypersensitivity reaction to progesterone is a rare pathologic condition which consists of autoimmune response to endogenous progesterone, known as autoimmune progesterone dermatitis, and hypersensitivity reaction to exogenous progestogen. We report the case of a 31-year-old woman with a history of whole body urticaria during exogenous progesterone supplementation for in vi-tro fertilization (IVF). She was admitted to the hospital for the diagnosis and management of progestogen hypersensitivity. An intra-dermal test with progesterone revealed positivity to 5 mg/mL of progesterone. For her next IVF, progesterone desensitization was performed in a method combining oral and intramuscular progesterone administration. After successfully achieving a target dose of 100 mg per day, the route of progesterone administration was converted to intravaginal tablet (90 mg twice a day) without any hypersensitivity reactions. (Allergy Asthma Respir Dis 2017;5:294-297)
TGF-β1 is a multifunctional molecule that is expressed in an exaggerated fashion during injury, inflammation and repair. Its expression is dysregulated in lung tissues from patients with pulmonary fibrosis and chronic obstructive pulmonary disease. In animal models, introduction of TGF-β1 expression in the lung causes prominent tissue fibrosis and alveolar destruction. On the other hand, the exaggerated production of TGF-β1, an inability to activate TGF-β1 or a block in TGF-β1 signaling have all been associated with the development of emphysematous pulmonary lesions. A number of studies have demonstrated that TGF-β1 is a major player in the pathogenesis of pulmonary fibrosis and emphysema. In this review, we discuss how TGF-β1 expression is regulated and mechanistically related to the development of tissue fibrosis and emphysema in experimental animal models and humans. We further highlight potential therapeutic options that control TGF-β1-associated genes or signals to restore extracellular matrix homeostasis in which TGF-β1 plays a central role.
가려움은 임상의가 빈번하게 마주하는 흔하고 비특이적인 증상으로 삶의 질 저하와 밀접하게 연관되어 있다. 가려움은 말초에서 염증반응, 물리적 자극, 항원 노출 등에 의해 시작되며, 다양한 매개물질과 감각신호전달 경로를 통해 시상과 대뇌피질로 전달되어 가려움이라는 자극을 느끼게 된다.
병적인 가려움을 일으키는 질환들은 크게 (1) 피부과적 질환, (2) 내과적 질환에 동반되는 가려움, (3) 신경병적 가려움, (4) 심인성 가려움의 4가지로 분류된다. 가려움을 호소하는 환자가 있다면 우선 정확한 병력청취와 피부병변 유무에 대한 검진이 필요하며, 동반된 내과적 질환 유무에 대한 평가를 위해 검사를 시행하여 감별 진단을 해야 한다. 가려움은 기간에 따라서 분류하기도 하는데, 6주 이상 지속될 때 만성 가려움으로 간주한다. 급성 가려움과 두드러기는 주로 히스타민 작용에 의해 발생하므로 항히스타민제 투여가 치료의 근간이 된다. 반면 만성 가려움을 일으키는 대부분의 질환의 경우 히스타민과 연관성이 없으며 원인 질환에 따른 맞춤 치료가 필요하다(Table 6, Fig. 2).
가려움의 치료에는 국소요법과 전신요법이 있으며, 가려움을 일으키는 기전에 대한 연구가 진행됨에 따라 치료법도 다양해지고 있다. 증상이 경한 경우에는 보습과 국소 도포제를 사용해 볼 수 있고, 증상이 심하거나 만성적으로 지속될 경우 전신치료법을 고려 할 수 있다. 흔히 가려움 치료제로 알려져 있는 항히스타민제 외 신경계 작용 약물, 면역조절제와 표적치료제가 임상에서 사용되고 있다. 향후 가려움의 발생기전에 대한 이해가 발전됨에 따라 “가렵다” 라는 비특이적인 증상에 대해 개별화된 치료법 개발을 기대해 본다.
Semaphorin (SEMA) 7A regulates neuronal and immune function. In these studies, we tested the hypothesis that SEMA 7A is also a critical regulator of tissue remodeling. These studies demonstrate that SEMA 7A and its receptors, plexin C1 and β1 integrins, are stimulated by transforming growth factor (TGF)-β1 in the murine lung. They also demonstrate that SEMA 7A plays a critical role in TGF-β1–induced fibrosis, myofibroblast hyperplasia, alveolar remodeling, and apoptosis. TGF-β1 stimulated SEMA 7A via a largely Smad 3–independent mechanism and stimulated SEMA 7A receptors, matrix proteins, CCN proteins, fibroblast growth factor 2, interleukin 13 receptor components, proteases, antiprotease, and apoptosis regulators via Smad 2/3–independent and SEMA 7A–dependent mechanisms. SEMA 7A also played an important role in the pathogenesis of bleomycin-induced pulmonary fibrosis. TGF-β1 and bleomycin also activated phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB)/AKT via SEMA 7A–dependent mechanisms, and PKB/AKT inhibition diminished TGF-β1–induced fibrosis. These observations demonstrate that SEMA 7A and its receptors are induced by TGF-β1 and that SEMA 7A plays a central role in a PI3K/PKB/AKT-dependent pathway that contributes to TGF-β1–induced fibrosis and remodeling. They also demonstrate that the effects of SEMA 7A are not specific for transgenic TGF-β1, highlighting the importance of these findings for other fibrotic stimuli.
Drug desensitization is a treatment strategy for patients with hypersensitivity to essential drugs without alternatives. The gradual increase in the drug dosage from low doses to therapeutic levels induces a transient immune tolerance to the culprit drug. Although desensitization has traditionally been recommended for IgE-mediated immediate hypersensitivity, this indication has recently been expanded to include non-IgE-mediated immediate responses, nonimmunological responses, and T-cell mediated delayed hypersensitivity reactions. Although the exact mechanism behind desensitization remains unclear, the process is thought to attenuate various intracellular signals in target cells through the high-affinity IgE receptor (FcɛRI) internalization, alteration in signaling pathways in mast cells and basophils, reduction in Ca2+ influx, and production of anti-drug IgG4 blocking antibody. Desensitization can be used for the safe administration of anti-neoplastic agents, antibiotics, aspirin, and nonsteroidal anti-inflammatory drugs. Various desensitization protocols have been proposed for each drug. The optimization of drug concentration, target dosage, administration interval, and route of administration is key to successful desensitization. In addition, the desensitization protocol should be individualized for each patient with consideration of the severity of the initial hypersensitivity response, the characteristics of the culprit drug, and the nature of the breakthrough reactions.
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