Do-Jin Kim

Interleukin-13 and Its Receptors in Idiopathic Interstitial Pneumonia: Clinical Implications for Lung Function

Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-γ has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-γ were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Rα1/α2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-γ levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Rα1, rather than IL-13Rα2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease.

A promoter SNP rs4073T>A in the common allele of the interleukin 8 gene is associated with the development of idiopathic pulmonary fibrosis via the IL-8 protein enhancing mode

BackgroundInterleukin-8 (IL-8) is a potent chemo-attractant cytokine responsible for neutrophil infiltration in lungs with idiopathic pulmonary fibrosis (IPF). The IL-8 protein and mRNA expression are increased in the lung with IPF. We evaluated the effect of single nucleotide polymorphisms (SNPs) of the IL-8 gene on the risk of IPF.MethodsOne promoter (rs4073T>A) and two intronic SNPs (rs2227307T>G and rs2227306C>T) of the IL-8 genes were genotyped in 237 subjects with IPF and 456 normal controls. Logistic regression analysis was applied to evaluate the association of these SNPs with IPF. IL-8 in BAL fluids was measured using a quantitative sandwich enzyme immunoassay, and promoter activity was assessed using the luciferase reporter assay.ResultsThe minor allele frequencies of rs4073T>A and rs2227307T>G were significantly lower in the 162 subjects with surgical biopsy-proven IPF and 75 subjects with clinical IPF compared with normal controls in the recessive model (OR = 0.46 and 0.48, p = 0.006 and 0.007, respectively). The IL-8 protein concentration in BAL fluids significantly increased in 24 subjects with IPF compared with 14 controls (p = 0.009). Nine IPF subjects homozygous for the rs4073 T>A common allele exhibited higher levels of the IL-8 protein compared with six subjects homozygous for the minor allele (p = 0.024). The luciferase activity of the rs4073T>A common allele was significantly higher than that of the rs4073T>A minor allele (p = 0.002).ConclusionThe common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.

Differences in radiological/HRCT findings in eosinophilic bronchitis and asthma: implication for bronchial responsiveness

Background: Airway hyperresponsiveness in asthmatics is considered to be one of the major consequences of airway inflammation and remodelling. Airway responsiveness is normal in patients with eosinophilic bronchitis (EB), despite eosinophilic inflammation of the airways comparable to that which occurs in asthmatics. Comparisons between asthma and EB should clarify the changes in airway morphology that are related specifically to AHR in asthmatics. Methods: Eighteen asthmatic patients, 15 patients with EB, and 11 healthy subjects were recruited. Airway wall area percentage (WA%), centrilobular prominence, and air trapping were compared using thin slice section computed tomography. Results: WA% was significantly greater in asthmatics than in patients with EB (72 (3.1)% v 54 (2.1)%, pu200a=u200a0.032) and was similar in EB patients and controls (54 (2.1)% v 57 (1.8)%, p>0.05). Centrilobular prominence and air trapping were similar in EB patients and asthmatics and were significantly greater than in controls. Conclusion: WA% rather than air trapping or centrilobular prominence may be associated with the airway hyperresponsiveness that occurs in asthmatics but not in patients with EB.

Risk factors related to fixed airway obstruction in patients with asthma after antiasthma treatment

BACKGROUNDnThere are many unanswered questions about the role of airway remodeling in asthma.nnnOBJECTIVEnTo evaluate the physiologic factors related to airway remodeling after antiasthma drug treatment for 1 year.nnnMETHODSnWe gave 582 patients with asthma long-term control medication for 1 year according to the severity of their asthma. Airway remodeling was defined using forced expiratory volume in 1 second/forced vital capacity and a predicted forced expiratory volume in 1 second of less than 75% after antiasthma treatment.nnnRESULTSnOf the 582 patients, 49 (8.4%) had airway remodeling. Severe asthma resulted in more airway remodeling than mild-to-moderate asthma. Asthmatic patients with airway remodeling were significantly older and had a longer duration of asthma. Asthmatic patients with airway remodeling had more emphysema on high-resolution computed tomography, a higher rate of near-fatal asthma attacks, a lower percentage of sputum eosinophils, a lower atopy frequency, a greater response to short-acting bronchodilators, and a lower body mass index (BMI) than those without airway remodeling. Age, asthma duration, and BMI were important discriminators of airway remodeling.nnnCONCLUSIONnNonatopy, asthma duration, emphysema on high-resolution computed tomography, sputum eosinophils, age, and BMI before antiasthma treatment are important factors related to airway remodeling in patients with asthma.

Effects of smoking cessation on airflow obstruction and quality of life in asthmatic smokers.

Purpose Smoking elicits airway inflammation and airflow obstruction in patients with asthma, even after smoking cessation. The aim of this study was to examine the effects of smoking cessation on lung function and quality of life (QOL) in asthmatic patients. Methods Thirty-two patients with asthma who were active smokers were recruited. After education on the effects of smoking on asthma, 22 patients continued to smoke, and 10 quit smoking. All patients were treated with inhaled fluticasone propionate (1 mg/day) for 3 months. We compared forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow between 25 and 75% FVC (FEF25-75%), and scores on a QOL questionnaire at baseline, 1, 2, and 3 months. Results Quitters showed a greater percent change in FEV1 (19.1±6.3 vs. 7.9±2.4%, P=0.024) and FEV1/FVC (6.5±4.14 vs. 3.5±1.5%, P=0.05) than smokers. Both quitters and smokers showed improved QOL scores after 1, 2, and 3 months of fluticasone treatment. Conclusions Patients with asthma who quit smoking showed less airway obstruction, suggesting that smoking cessation is crucial in the management of asthma.

Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients

BACKGROUNDnBiological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue.nnnPATIENTS AND METHODSnExpression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients.nnnRESULTSnLow expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients.nnnCONCLUSIONSnThe proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.BACKGROUNDnBiological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue.nnnPATIENTS AND METHODSnExpression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients.nnnRESULTSnLow expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients.nnnCONCLUSIONSnThe proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.

Autologous Serum Skin Test for Autoantibodies Is Associated with Airway Hyperresponsiveness in Patients with Asthma

Background: Autoimmune diseases have been implicated as a cause of intrinsic asthma; however, there is little data on the role of autoimmunity in the pathogenesis of asthma. Objective: The purpose of this study was to investigate circulating functional autoantibodies against the high-affinity IgE receptor FcΕRI or IgE in patients with asthma. Methods: Twenty-eight patients with asthma and 19 control subjects were included. All subjects were skin tested with autologous serum to assess for the potential presence of receptor FcΕRI or IgE autoantibodies. If the serum-induced wheal diameter was 1.5 mm larger than the histamine-induced wheal diameter and that was 3 mm larger than the saline-induced wheal diameter at 30 min, the reaction was defined positive. Results: Of the 47 total subjects (both asthma patients and control subjects), 13 (27.7%) had a positive autologous serum skin test (ASST). Of the 28 asthma patients, 8 (28.6%) were regarded as having autoimmune origin. Autoantibodies against FcΕRI or IgE were found in asthma patients, irrespective of atopic status (atopy+ 3/13 vs. atopy– 5/15). The wheal diameter related to ASST was not related to atopy. Asthma patients with ASST-positive results as compared with patients with ASST-negative results exhibited a significant increased airway hyperresponsiveness (PC20 methacholine, 2.70 ± 1.27 vs. 9.08 ± 2.35; p < 0.026). Conclusion: Our data demonstrate that aberrant autoantibodies against the high-affinity IgE receptor FcΕRI or IgE are related to airway hyperresponsiveness in patients with asthma.

The Impact of Smoking on Clinical and Therapeutic Effects in Asthmatics

Smoking is associated with poor symptom control and impaired therapeutic responses in asthma. A total of 843 patients with asthma were recruited. The patients received treatment for 1 yr according to the severity of their asthma. We compared the forced expiratory volume in 1 sec (FEV1), the ratio of FEV1 to forced vital capaity (FVC), atopy, total IgE, emphysema on high-resolution computed tomography (HRCT), the number of near-fatal asthma attacks, and physiological fixed airway obstruction between the smoking and nonsmoking groups. The study population consisted of 159 (18.8%) current smokers, 157 (18.7%) ex-smokers, and 525 (62.5%) nonsmokers. Although the prevalence of atopy was not different between the smoking and nonsmoking groups, the total IgE was higher among the smokers than the nonsmokers. Compared with the nonsmoking group, the smokers had a lower FEV1 % predicted and forced expiratory flow between 25 and 75% of FVC. A greater prevalence of emphysema and a significantly higher number of asthmatic patients with fixed airway obstruction were detected in the smoking versus nonsmoking group. The 37.5% of asthmatic patients who were former or current smokers showed decreased pulmonary function and increased IgE, emphysema on HRCT, and fixed airway obstruction, indicating that smoking can modulate the clinical and therapeutic responses in asthma.

The Effect of Passive Smoking on Asthma Symptoms, Atopy, and Airway Hyperresponsiveness in Schoolchildren

Passive smoking is a major cause of respiratory morbidity, and is associated with increased bronchial responsiveness in children. To evaluate the effect of smoking by a parent on asthma symptoms, atopy, and airway hyperresponsiveness (AHR), we conducted a cross-sectional survey of 503 schoolchildren that involved questionnaires, spirometry, allergy testing, and a bronchial challenge test. If the PC20 methacholine was less than 16 mg/mL, the subject was considered to have AHR. The prevalence of a parent who smoked was 68.7%. The prevalence of AHR was 45.0%. The sensitization rate to common inhalant allergens was 32.6%. Nasal symptoms such as rhinorrhea, sneezing, nasal itching, and nasal obstruction were present in 42.7%. Asthma symptoms such as cough and wheezing were present in 55.4%. The asthma symptoms were significantly more prevalent in children who had a parent who smoked than in those whose parents did not. The nasal symptoms, atopy, and AHR did not differ according to whether a parent smoked. In a multiple logistic regression model, the asthma symptoms and atopy were independently associated with AHR, when adjusted for confounding variables. Passive smoking contributed to asthma symptoms in schoolchildren and was not an independent risk factor of airway hyperresponsiveness in an epidemiological survey.

A Case of Propofol-Induced Oropharyngeal Angioedema and Bronchospasm

Propofol (2,6-diisopropylphenol) is an ultrashort-acting sedative agent with sedative and amnestic effects that is used not only for anesthesia but also for sedation during minor outpatient procedures and endoscopic examinations. Rare cases of anaphylaxis following propofol administration have been reported in the medical literature. Documentation of anaphylaxis is often lacking because the cause and effect relationship is often hard to prove. Only a minority of patients get referred for allergy testing to confirm the offending drug. Here we report a 74-year-old woman who had an anaphylactic reaction with severe oropharyngeal edema and bronchospasm for a few minutes after receiving propofol during endoscopic examination. An allergy skin test was positive for both propofol and soybean. Soybean in the intralipid is one component of propofol, and we concluded that this anaphylaxis was caused by soybean.