Methacholine bronchial provocation test in patients with asthma: serial measurements and clinical significance

BACKGROUND/AIMS: The methacholine bronchial provocation test (MBPT) is used to detect and quantify airway hyper-responsiveness (AHR). Since improvements in the severity of asthma are associated with improvements in AHR, clinical studies of asthma therapies routinely use the change of airway responsiveness as an objective outcome. The aim of this study was to assess the relationship between serial MBPT and clinical profiles in patients with asthma. METHODS: A total of 323 asthma patients were included in this study. The MBPT was performed on all patients beginning at their initial diagnosis until asthma was considered controlled based on the Global Initiative for Asthma guidelines. A responder was defined by a decrease in AHR while all other patients were considered non-responders. RESULTS: A total of 213 patients (66%) were responders, while 110 patients (34%) were non-responders. The responder group had a lower initial PC20 (provocative concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20%) and longer duration compared to the non-responder group. Members of the responder group also had superior qualities of life, compared to members of the non-responder group. Whole blood cell counts were not related to differences in PC20; however, eosinophil concentration was. No differences in sex, age, body mass index, smoking history, serum immunoglobulin E, or frequency of acute exacerbation were observed between responders and non-responders. CONCLUSIONS: The initial PC20, the duration of asthma, eosinophil concentrations, and quality-of-life may be useful variables to identify improvements in AHR in asthma patients.

Apolipoprotein A1 Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-β1-induced EMT in experimental lung fibrosis and clarify its mechanism of action. METHODS: The A549 alveolar epithelial cell line was treated with TGF-β1 with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and α-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-β1 receptor type 1 (TβRI) and type 2 (TβRII) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. RESULTS: TGF-β1-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-β1-induced change of the EMT phenotype. ApoA1 inhibited the TGF-β1-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-β1-induced increase in TβRI and TβRII expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. CONCLUSION: Our data demonstrate that ApoA1 inhibits TGF-β1-induced EMT in experimental lung fibrosis.

Serum sickness reaction with skin involvement induced by bee venom injection therapy

Bee venom injection therapy is an alternative treatment sometimes used for chronic inflammatory diseases, including rheumatoid arthritis and multiple sclerosis, to reduce pain. Several chemical components of bee venom have anti-inflammatory effects, and apitoxin, one of the mixed components, has been used for pain prevention therapy. However, there have been no large-scale investigations regarding the efficacy or side effects or apitoxin. In this study, a case of serum sickness reaction that developed after receiving bee venom injection therapy is reported.

MYH9 nephropathy

MYH9-related disorder is an autosomal dominant disease caused by a mutation in the MYH9 gene, which encodes nonmuscle myosin heavy chain IIA (NMMHC-IIA). This disease is characterized by giant platelets, thrombocytopenia, granulocyte inclusion bodies, proteinuria, and high-pitch sensorineural deafness. Nephropathy has been observed in 30% of patients with MYH9-related disorder. The characteristic features are early onset proteinuria and rapidly progressing renal disorder. However, the prognosis of MYH9 nephropathy remains unclear. Herein, we describe a 36-year-old woman who presented with proteinuria and was diagnosed with MYH9 nephropathy via renal biopsy and gene analysis. Her proteinuria improved after administration of an angiotensin II receptor blocker, but was aggravated after changing to a calcium channel blocker.

The differences of clinical profiles by house dust mite sensitization in patients with asthmatics in Soonchunhyang University Hospital cohort

PURPOSE: The majority of patients with allergic disease are highly sensitized to house dust mites (HDM). There is few data to observe sensitization rate to HDM in asthmatics in Korea. The aim of this study was to observe the differences of clinical profiles by HDM sensitization in patients with asthmatics in Soonchunhyang University Hospital (SCH) cohort. METHODS: We recruited 2,345 asthmatic patients in SCH cohort. Lung function, body mass index and sputum and blood eosinophils, and PC20, and clinical profiles were compared by HDM sensitization. RESULTS: Dermatophagoides farinae (Derf) and/or Dermatophagoides pteronyssinus (Derp) (+) sensitization rate was higher prevalence in male than in female. Compared with nonatopy asthmatics, Derf and/or Derp (+) asthmatics had early onset of age [Derf and/or Derp (+) vs. Derf and Derp (-) vs. atopy (-); 32.5+/-0.51 vs. 36.1+/-0.88 vs. 43.1+/-0.54, P<0.05]. Derf and/or Derp (+) asthmatics had shorter duration of asthma symptom than that of nonatopy asthmatics. Derf and/or Derp (+) asthmatics had lower forced expiratory volume in one second and forced vital capacity than those of Derf and Derp (-) asthmatics. PC20 in Derf and/or Derp (+) asthmatics had lower than those of Derf and Derp (-) and nonatopy asthmatics [Derf and/or Derp (+) vs. Derf and Derp (-) vs. atopy (-); 5.4+/-0.24 mg/mL vs. 6.59+/-0.52 mg/mL vs. 7.19+/-0.33 mg/mL, P<0.05]. Blood eosinophils number in Derf and/or Derp (+) asthmatics had higher than that of nonatopy asthmatics (414.7+/-131.1 vs. 350.6+/-14.0, P<0.05). Total immunoglobulin E (IgE) in Derf and/or Derp positive asthmatics had higher than that of Derf and Derp negative and nonatopy asthmatics. There was no difference of body mass index among three groups. CONCLUSIONS: Our data indicate that atopy asthmatics sensitized to Derf and/or Derp had early onset of age, high total IgE and airway responsiveness, and eosinophilic inflammation.