Neuromuscular blocking agent re-exposure in a retrospective cohort with neuromuscular blocking agent-associated anaphylaxis.

BACKGROUND: Neuromuscular blocking agents (NMBAs) are one of the most common causes of perioperative anaphylaxis. Although skin test positivity may help identify reactive NMBAs, it is unclear whether skin test negativity can guarantee the safety of systemically administered NMBAs. OBJECTIVE: This study aimed to evaluate the real-world safety of alternative NMBAs screened using skin tests in patients with suspected NMBA-induced anaphylaxis. METHODS: A retrospective cohort of suspected NMBA-induced anaphylaxis were recruited among patients at Seoul National University Hospital from June 2009 to May 2021, and their characteristics and outcomes were assessed. RESULTS: A total of 47 cases (0.017%) of suspected anaphylaxis occurred in 282,707 patients who received NMBAs. Cardiovascular manifestations were observed in 95.7%, whereas cutaneous findings were observed in 59.6%. Whereas 83% had a history of undergoing general anesthesia, 17% had no history of NMBA use. In skin tests, the overall positivity to any NMBA was 94.6% (81.1% to culprit NMBAs) and the cross-reactivity was 75.7%, which is related to the chemical structural similarity among NMBAs; the cross-reactivity and chemical structure similarity of rocuronium were 85.3% and 0.814, respectively, with vecuronium; this is in contrast to 50% and 0.015 with cisatracurium and 12.5% and 0.208 with succinylcholine. There were 15 patients who underwent subsequent surgery with a skin test-negative NMBA; whereas 80.0% (12/15) safely completed surgery, 20.0% (3/15) experienced hypotension. CONCLUSION: Similarities in chemical structure may contribute to the cross-reactivity of NMBAs in skin tests. Despite the high negative predictability of skin tests for suspected NMBA-induced anaphylaxis, the potential risk of recurrent anaphylaxis has not been eliminated.

Rapamycin Restores Different Patterns of Cytokine Expression to Dexamethasone Treatment on CD14++CD16+ Monocytes from Steroid-Resistant Asthma Patients.

OBJECTIVE: We aimed to investigate the differences in interleukin (IL)-10, IL-1ß, IL-6, and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated CD14++CD16+ monocytes obtained from asthmatics after dexamethasone or dexamethasone plus rapamycin treatments between clinical steroid responders (R) and non-responders (NR). METHODS: Cytokine expressions in LPS-stimulated CD14++CD16+ p-mammalian target of rapamycin (mTOR) monocytes from R and NR were determined using flow cytometry. RESULTS: IL-10high CD14++CD16+ p-mTOR population following LPS stimulation increased in the R group although decreased in the NR group with dexamethasone treatment. IL-1ßhigh population decreased in the R group although increased in the NR group. Rapamycin treatment after LPS and dexamethasone resulted in a significant increase in the IL-10high population and a significant decrease in the IL-1ßhigh population in the NR group. CONCLUSION: Dexamethasone treatment resulted in different patterns of change in cytokine expressions in LPS-stimulated CD14++CD16+ p-mTOR monocytes between the R and NR. mTOR inhibition can restore steroid responsiveness involving IL-10 and IL-1ß in CD14++CD16+ p-mTOR monocytes.

A Critical Systematic Review for Inhaled Corticosteroids on Lung Cancer Incidence: Not Yet Concluded Story.

BACKGROUND: To systematically review studies on inhaled corticosteroids (ICS) and lung cancer incidence in chronic airway disease patients. METHODS: We conducted electronic bibliographic searches on OVID-MEDLINE, EM- BASE, and the Cochrane Database before May 2020 to identify relevant studies. Detailed data on the study population, exposure, and outcome domains were reviewed. RESULTS: Of 4,058 screened publications, 13 eligible studies in adults with chronic obstructive pulmonary disease (COPD) or asthma evaluated lung cancer incidence after ICS exposure. Pooled hazard ratio and odds ratio for developing lung cancer in ICS exposure were 0.81 (95% confidence interval, 0.64 to 1.02; I2=95.7%) from 10 studies and 1.02 (95% confidence interval 0.50 to 2.07; I2=94.7%) from three studies. Meta-regression failed to explain the substantial heterogeneity of pooled estimates. COPD and asthma were variously defined without spirometry in 11 studies. Regarding exposure assessment, three and 10 studies regarded ICS exposure as a time-dependent and fixed variable, respectively. Some studies assessed ICS use for the entire study period, whereas others assessed ICS use for 6 months to 2 years within or before study entry. Smoking was adjusted in four studies, and only four studies introduced 1 to 2 latency years in their main or subgroup analysis. CONCLUSION: Studies published to date on ICS and lung cancer incidence had heterogeneous study populations, exposures, and outcome assessments, limiting the generation of a pooled conclusion. The beneficial effect of ICS on lung cancer incidence has not yet been established, and understanding the heterogeneities will help future researchers to establish robust evidence on ICS and lung cancer incidence.

Chronic viral hepatitis accelerates lung function decline in smokers.

Although hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotrophic viruses, they may affect pulmonary diseases. The purpose of this study was to assess whether chronic viral hepatitis (CVH) infection was associated with a rapid decline in lung function. Repeated measurements of lung function were obtained from a well-curated health check-up database. A case was defined as an individual positive for HBsAg or anti-HCV antibody. A control was randomly selected (from the same dataset) after 1:1 matching in terms of age, sex, height, the body mass index, and smoking status. Separate analyses of non-smokers and smokers were performed. A total of 701 cases were enrolled (586 with HBV and 115 with HCV). In cross-sectional analysis, both forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) decreased significantly only in smokers (smoking cases vs. smoking controls) (adjusted p = 6.6 × 10-5 and adjusted p = 2.2 × 10-3, respectively). In longitudinal analysis, smoking cases showed significantly greater FEV1 and FVC decline rates than did smoking controls (adjusted p = 8.5 × 10-3 and adjusted p = 1.2 × 10-5, respectively). Such associations were particularly high in smoking cases at intermediate-to-high risk of hepatic fibrosis, as evaluated by the non-invasive Fibrosis-4 index. In summary, CVH was associated with both decreased lung function and accelerated lung function decline in smokers. A non-invasive measurement of hepatic fibrosis may be useful in predicting rapid lung function decline in smokers with CVH.

Analysis of Breakthrough Reactions in 1,143 Desensitization Procedures in a Single Tertiary Hospital Using a One-Bag Desensitization Protocol.

Background: Drug desensitization is helpful for patients who have experienced significant hypersensitivity reactions (HSRs) to antineoplastic agents. One-bag desensitization protocols, attracting attention in recent years, need to be validated on their safety and efficacy in a large number. Methods: One-bag desensitization procedures conducted from 2018 to 2020 were analyzed; their outcomes and the risk factors for breakthrough reactions (BTRs) were assessed in desensitization procedures to major drug types (platins, taxanes, and monoclonal antibodies). Results: A total of 1,143 procedures of one-bag desensitization were performed in 228 patients with 99% completion rate. BTRs occurred in 26% of the total desensitization procedures-34% in platins, 12% in taxanes, and 18% in mAbs. BTR occurrence rate decreased along the desensitization process with 80% of BTRs occurring within the 6th desensitization attempts. Severe BTR occurred more frequently with severe initial HSRs (1% in mild to moderate initial HSRs vs. 16% in severe). Severe initial HSR was also a significant risk factor for moderate to severe BTR in platins (odds ratio 1.56, 95% confidence interval [CI] 1.06-2.29, p = 0.025). The use of steroid was also associated with lower occurrence of moderate to severe BTR (odds ratio 0.50, 95% CI 0.35-0.72, p < 0.001). Conclusion: Most patients with HSRs to antineoplastic agents can safely receive chemotherapy through a one-bag desensitization protocol. Further studies on each drug with larger sample size can help verify the risk factors of BTRs and evaluate the efficacy of steroid premedication in improving the safety of desensitization in high-risk patients.

Relationships between lung function decline and skeletal muscle and fat mass changes: a longitudinal study in healthy individuals.

BACKGROUND: The associations between long-term changes in body mass composition and decline in lung function in healthy adults are unknown. METHODS: Using a well-defined health check-up database, we first assessed individual longitudinal changes in muscle mass (MM) and fat mass (FM) measured via bioelectrical impedance analyses. Then we classified the enrolled individuals into five body composition groups according to their MM index (MMI) [MM (kg)/height (m)2 ] or FM index (FMI) [FM (kg)/height (m)2 ] change rate quartiles. Linear mixed models adjusted for age, smoking status, height, and body mass index were used to analyse the rate of forced expiratory volume in 1 s (FEV1) decline and body composition groups. RESULTS: A total of 15 476 middle-aged individuals (6088 women [mean age ± standard deviation: 50.74 ± 7.44] and 9388 men [mean age ± standard deviation: 49.36 ± 6.99]) were enrolled. The mean number of measurements was 6.96 (interquartile range [IQR]: 5-9) over an average follow-up period of 8.95 years (IQR: 6.73-11.10). Decrease in MMI was significantly associated with accelerated FEV1 decline in men only (P = 1.7 × 10-9 ), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10-10 and P < 2.0 × 10-16 respectively). Linear mixed model analyses indicated that annual increase of 0.1 kg/m2 in MMI was related to accelerated FEV1 decline by 30.79 mL/year (95% confidence interval [CI]: 26.10 to 35.48 mL/year) in men. Annual increase of 0.1 kg/m2 in FMI was related to accelerated FEV1 decline by 59.65 mL/year in men (95% CI: 56.84 to 62.28 mL/year) and by 22.84 mL/year in women (95% CI: 18.95 to 26.74 mL/year). In body composition analysis, we found increase in MMI was significantly associated with attenuated FEV1 decline in men only (P = 1.7 × 10-9 ), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10-10 and P < 2.0 × 10-16 respectively). Individuals characterized with gain MM combined with loss of FM were associated with the most favourable outcome (i.e. the smallest rate of decline in FEV1) in both women and men. In men, loss of FM over time is more closely related with attenuated FEV1 decline than change in MM (gain or loss). CONCLUSIONS: Change in body composition over time can be used to identify healthy middle-aged individuals at high risk for rapid FEV1 decline.

Lung function decline is associated with serum uric acid in Korean health screening individuals.

We performed a retrospective cohort study of 19,237 individuals who underwent at least three health screenings with follow-up periods of over 5 years to find a routinely checked serum marker that predicts lung function decline. Using linear regression models to analyze associations between the rate of decline in the forced expiratory volume in 1 s (FEV1) and the level of 10 serum markers (calcium, phosphorus, uric acid, total cholesterol, total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, creatinine, and C-reactive protein) measured at two different times (at the first and third health screenings), we found that an increased uric acid level was significantly associated with an accelerated FEV1 decline (P = 0.0014 and P = 0.037, respectively) and reduced FEV1 predicted % (P = 0.0074 and P = 8.64 × 10-7, respectively) at both visits only in non-smoking individuals. In addition, we confirmed that accelerated forced vital capacity (FVC) and FEV1/FVC ratio declines were observed in non-smoking individuals with increased serum uric acid levels using linear mixed models. The serum uric acid level thus potentially predicts an acceleration in lung function decline in a non-smoking general population.

Vitamin D deficiency and lung function decline in healthy individuals: A large longitudinal observation study.

AIM: A reliable evidence from a comprehensive large-scale study supporting associations between serum vitamin D (25-hydroxyvitamin D) level (SVDL) and lung function decline (LFD) in healthy individuals has been unavailable. Using a well-established health screening database, we assessed the associations between SVDL and LFDs, measured as the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio. METHODS: Serial SVDL and lung function data were analyzed using linear mixed models, which were performed in smokers and non-smokers, separately. Vitamin D-deficient individuals (VDDs) were defined when their SVDLs were consistently lower than 20 ng/mL at all measurements. RESULTS: A total of 1371 individuals were analyzed. The mean FEV1 decline rates of VDDs and vitamin D-normal individuals (VDNs) in smokers were -33.35 mL/year (95% CI: 39.44 to -27.26 mL/year) and -15.61 mL/year (95% CI: 27.29 to -4.21 mL/year) respectively, over a mean of 6.29 years of observation with statistical significance (P < 0.001). However, there was no significant differences observed between decline rates of FEV1 in non-smokers. Similarly, FVC decline rates of VDDs were significantly greater than those of VDNs only in smokers (P < 0.001). However, FEV1/FVC ratio decline rates showed no significant difference between VDDs and VDNs regardless of their smoking status. CONCLUSIONS: Consistently low SVDLs predicted more rapid FEV1 and FVC declines in smokers. However, FEV1/FVC decline rate was not associated with SVDL. SVDL may be used to identify healthy smoking individuals at high risk for accelerated LFD.

A Nationwide Study of Severe Cutaneous Adverse Reactions Based on the Multicenter Registry in Korea.

BACKGROUND: Because severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) rarely occur, clinical data based on large-scale studies are still lacking. OBJECTIVE: To provide information on culprit drugs and clinical characteristics, including morbidity and mortality of SCARs based on a nationwide registry. METHODS: SCAR cases that occurred from 2010 to 2015 were recruited to the Korean SCAR registry from 34 tertiary referral hospitals. Demographics, causative drugs, causality, and clinical outcomes were collected by reviewing the medical record. RESULTS: A total of 745 SCAR cases (384 SJS/TEN cases and 361 DRESS cases) due to 149 drugs were registered. The main causative drugs were allopurinol (14.0%), carbamazepine (9.5%), vancomycin (4.7%), and antituberculous agents (6.3%). A strong preference for SJS/TEN was observed in carbonic anhydrase inhibitors (100%), nonsteroidal anti-inflammatory drugs (84%), and acetaminophen (83%), whereas dapsone (100%), antituberculous agents (81%), and glycopeptide antibacterials (78%) were more likely to cause DRESS. The mortality rate was 6.6% (SJS/TEN 8.9% and DRESS 4.2%). The median time to death was 19 days and 29 days in SJS/TEN and DRESS respectively, and 89.8% of deaths occurred within 60 days after the onset of the skin symptoms. CONCLUSION: Allopurinol, carbamazepine, vancomycin, and antituberculous agents were the leading causes of SCARs in Korea. Some drugs preferentially caused a specific phenotype. The mortality rate of SCARs was 6.6%, and most of the deaths occurred within 2 months.

Blood Eosinophil Count as a Predictor of Lung Function Decline in Healthy Individuals.

BACKGROUND: Little is known about the effect of blood eosinophil count (BEC) on a decline in lung function in healthy individuals. OBJECTIVE: Using a well-established health screening database, we assessed the associations between BEC and a decline in lung function, measured as the forced expiratory volume in 1 second (FEV1). METHODS: Serial BEC and FEV1 data were analyzed using linear mixed models adjusted for gender, height, and smoking status. The association between BEC consistency and a decline in FEV1 was evaluated in subpopulation analyses. RESULTS: A total of 4634 individuals were enrolled. The mean number of health screenings was 7.49 over an average of 11.74 years of observation. A higher log2-transformed BEC was significantly associated with a greater decline in FEV1 that was stronger in nonsmokers (P = 8.56 × 10-8) than in smokers (P = 1.52 × 10-3). In subpopulation analyses of 2018 individuals with consistent BECs, those with BECs consistently ≥100/µL (P = 4.58 × 10-6), ≥200/µL (P = 3.53 × 10-7), and ≥300/µL (P = 1.12 × 10-3) had a significantly higher dose-dependent FEV1 decline than those with BECs consistently <100/µL. A BEC threshold of 100/µL in nonsmokers and 200/µL in smokers may predict an accelerated decline in FEV1. CONCLUSIONS: BEC is associated with a decline in FEV1, and a consistently high BEC is an independent risk factor for an accelerated decline in FEV1. These results suggest the use of the BEC to identify healthy individuals at high risk for developing chronic lung disease, which in turn may enable a tailored preventive strategy.

A One-Bag Rapid Desensitization Protocol for Paclitaxel Hypersensitivity: A Noninferior Alternative to a Multi-Bag Rapid Desensitization Protocol.

BACKGROUND: Desensitization is used to safely continue treatment with a culprit drug in patients with drug hypersensitivity. Currently, a multi-bag protocol is widely used for rapid desensitization, but performing the desensitization procedure is labor intensive as pharmacists and nurses need to prepare and administer diluted solutions. However, it has not been investigated whether dilution is essential for successful desensitization. OBJECTIVE: To investigate the efficacy and safety of a nondilution, 1-bag protocol in comparison with a conventional multi-bag protocol for desensitization of patients with paclitaxel hypersensitivity. METHODS: Patients who underwent paclitaxel desensitization between 2011 and 2018 were analyzed in this retrospective cohort study. The completion rate, time to completion, and occurrence and severity of breakthrough reaction (BTR) between a 1-bag protocol and a multi-bag protocol were compared. RESULTS: A total of 211 desensitization procedures were performed, of which 207 procedures (98.1%) were completed successfully. The administration time was significantly shorter in the 1-bag protocol group compared with the conventional multi-bag protocol group (266.0 ± 149.3 minutes vs 484.2 ± 178.6 minutes, P < .05) without differences in the completion rate (97.6% vs 98.9%, P = .645), the incidence of BTR (16.1% vs 27.6%, P = .778), and the proportion of severe BTR (2.6% vs 5.7%, P = .134). CONCLUSIONS: A nondilution, 1-bag protocol is noninferior to a multi-bag rapid desensitization protocol and can be a safe and effective option for paclitaxel desensitization.

Favorable longitudinal change of lung function in patients with asthma-COPD overlap from a COPD cohort.

BACKGROUND: The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased. Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD. METHODS: COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort. ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1, or 3) peripheral blood eosinophils ≥300 cells/µL. Lung function decline was compared using a linear mixed effects model for longitudinal data with random intercept and random slope. RESULTS: Among 239 patients, 47 were diagnosed with ACO (19.7%). During the follow-up period, change in smoking status, use of inhaled corticosteroids (ICS) and long-acting ß2-agonists or ICS and at least 2 exacerbations per year were similar between patients with non-ACO COPD and ACO. Over a median follow-up duration of 5.8 years, patients with non-ACO COPD experienced a faster annual decline in pre-bronchodilator FEV1 than patients with ACO (- 29.3 ml/year vs. -13.9 ml/year, P = 0.042), which was persistent after adjustment for confounders affecting lung function decline. CONCLUSION: Patients with ACO showed favorable longitudinal changes in lung function compared to COPD patients over a median follow-up of 5.8 years.

Incidence and Risk of Oxaliplatin-Induced Hypersensitivity in Patients with Asymptomatic Prior Exposure: A Prospective Observational Study.

BACKGROUND: Oxaliplatin-related hypersensitivity reactions (HSRs), which can be life threatening, have introduced a dilemma regarding the use of chemotherapeutic agents. Because repeated exposure to oxaliplatin may increase the risk of sensitization, patients with a history of prior asymptomatic exposure require risk-stratified care. OBJECTIVE: This study aimed to elucidate the incidence and risk of oxaliplatin HSRs in patients with a history of asymptomatic prior exposure. METHODS: We performed a prospective observational study of patients who completed oxaliplatin-based chemotherapy between March 2013 and January 2015. Prior exposure to oxaliplatin, the oxaliplatin-free interval, reaction severity, eosinophil counts, and premedication were reviewed to assess the risk factors. RESULTS: A total of 793 patients were enrolled, among whom 148 (18.7%) experienced an HSR. The HSR incidence was 15.2% among oxaliplatin-naive patients but increased to 31.9% among those with a history of asymptomatic exposure and 75.0% among those with a history of oxaliplatin HSRs during the previous exposure, despite prophylaxis. The mean HSR onset cycle was earliest in the previous HSR group, followed by the previous asymptomatic exposure and nonexposure groups. The HSR severity also differed according to the previous exposure history and HSRs. In the multivariate analysis, prior exposure to oxaliplatin (odds ratio [OR], 3.78; 95% confidence interval [CI], 2.46-5.79) and a longer oxaliplatin-free interval (≥36 months; OR, 4.85; 95% CI, 1.60-14.37) were independent risk factors for HSRs. CONCLUSIONS: Previous exposure to oxaliplatin is a risk factor for earlier HSR onset and more severe and frequent HSR episodes, even if prior therapy was well tolerated.

Clinical features of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a study of 25 patients in Korea.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare adverse drug reaction. This study aimed to evaluate the incidence of association with individual drugs, clinical manifestations, disease course, and outcomes of DRESS. METHODS: Using the criteria of the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR), the medical records of 25 patients diagnosed with DRESS between 2006 and 2015 were retrospectively reviewed. Demographic data, culprit drugs, latency periods, clinical and laboratory findings, and outcomes were investigated. RESULTS: The study group comprised 11 men (44%) and 14 women (56%) with an age range of 13-93 years (mean, 58 ± 19.86 years). The drugs most commonly implicated were carbamazepine (28%), allopurinol (16%), and antituberculosis drugs (12%). Individual latency periods ranged from 4 to 40 days (mean, 17.6 ± 9.95 days). Latency periods for anticonvulsants were significantly longer than those for other drugs (P < 0.05). However, no statistical differences were found between the RegiSCAR scores for anticonvulsants and those for other drugs. Disease severity, based on RegiSCAR score, was correlated with blood count abnormalities (P < 0.05). CONCLUSIONS: The results of our study revealed that anticonvulsants were the leading culprit drugs for DRESS, and carbamazepine was the individual drug most commonly associated with DRESS in Korea. Further studies of the mechanisms of action of these drugs are required in order to facilitate prompt diagnosis and effective management, which can affect prognosis and clinical outcome, of DRESS.

Sorafenib induces delayed-onset cutaneous hypersensitivity: a case series.

Sorafenib is an oral multikinase inhibitor with clinical activity against hepatocellular carcinoma (HCC) and renal cell carcinoma. Administration of sorafenib carries a variety of adverse cutaneous reactions. Common adverse effects induced by sorafenib include hand-foot skin reactions, facial erythema, splinter subungual hemorrhage, and alopecia. Although erythema multiforme (EM) related to sorafenib has been reported, delayed-type cutaneous hypersensitivity reactions are rare in patients treated with sorafenib and there has been no case of Stevens-Johnson syndrome (SJS) reported so far. We recently experienced 3 cases of delayed-type cutaneous hypersensitivity related to administration of sorafenib. The first case was a 47-year female had targetoid erythematous rashes on her arms 12 days after starting sorafenib for HCC. The rashes spread from the arms to the trunk rapidly except for the hands and feet, and erosive lesions developed in the oral mucosa and lips. She was diagnosed as SJS. The second case was an 81-year-old male had maculopapular eruptions with multiple targetoid lesions on the trunk, arms, and legs 10 days after starting sorafenib for his HCC. There was no evidence of mucosal involvement. He was diagnosed with EM. The last one was a 20-year-old female developed generalized maculopapular eruptions in the whole body 10 days after starting sorafenib for the treatment of HCC. All 3 patients completely recovered after discontinuation of sorafenib.

Reference ranges for induced sputum eosinophil counts in Korean adult population.

BACKGROUND: Induced sputum analyses are widely utilized to evaluate airway inflammation in asthmatics. However, the values have not been examined in Korean adults. OBJECTIVE: The purpose of this study is to determine reference ranges for induced sputum eosinophils and their influencing factors in Korean adults. METHODS: A total of 208 healthy nonasthmatic adults were recruited. Sputum induction and processing followed the international standard protocols. RESULTS: Adequate sputum samples were successfully collected from 81 subjects (38.9%). The upper 90 percentile for sputum eosinophil was calculated as 3.5%. The median value of eosinophil count percentage was significantly higher in subjects with atopy than those without atopy (median, 1.6%; range, 0-11.0% vs. median, 0%; range 0-3.6%, p=0.030). However, no significant correlations were found with age, gender, body mass index, smoking status, blood eosinophil, or fractional exhaled nitric oxide levels. CONCLUSION: Current study was the first attempt to determine the reference ranges of induced sputum eosinophils in Korean adults. The cutoff value for sputum eosinophilia was 3.5%, and was significantly associated with atopy.

Influence of chronic sinusitis and nasal polyp on the lower airway of subjects without lower airway diseases.

PURPOSE: Upper and lower respiratory tract pathologies are believed to be interrelated; however, the impact of upper airway inflammation on lung function in subjects without lung disease has not been evaluated. This study investigated the association of CT finding suggesting chronic sinusitis and lung function in healthy subjects without lung disease. METHODS: This was a retrospective study of prospectively collected data from 284 subjects who underwent a pulmonary function test, bronchial provocation test, rhinoscopy, and osteomeatal unit computed tomography offered as a private health check-up option. RESULTS: CT findings showed that the sinusitis group had a significantly lower FEV1/FVC ratio than subjects without sinusitis finding (78.62% vs 84.19%, P=0.019). Among the sinusitis group, subjects classified by CT findings as the extensive disease group had a slightly lower FEV1/FVC than those of the limited disease group (76.6% vs 79.5%, P=0.014) and the associations were independent of the presence of airway hyperresponsiveness. The subjects with nasal polyp had also lower FEV1 and FEV1/FVC than subjects without nasal polyp (FEV1: 100.0% vs 103.6%, P=0.045, FEV1/FVC: 77.4% vs 80.0%, P=0.005). CONCLUSIONS: CT findings suggesting chronic sinusitis and nasal polyp were associated with subclinical lower airway flow limitation even in the absence of underlying lung disease.

Overcoming oxaliplatin hypersensitivity: different strategies are needed according to the severity and previous exposure.

PURPOSE: This study investigated the characteristics of oxaliplatin-related hypersensitivity reactions (HSR) and evaluated the efficacy of premedication and desensitization administration for controlling HSR in patients with gastrointestinal malignancy. METHODS: This retrospective study includes oxaliplatin hypersensitivity cases reported to our in-hospital, adverse drug reaction monitoring system between May 2008 and April 2012. We analyzed administration histories of oxaliplatin and premedication treatments, chemotherapy cycle and severity of the initial HSR, and prophylactic measures and their outcomes in subsequent chemotherapy cycles. RESULTS: One hundred and seventy-three patients showed hypersensitivity to oxaliplatin-based chemotherapy. Oxaliplatin HSR developed after mean chemotherapy cycle 6.3 ± 0.3. Specifically, while HSR occurred at cycle 7.6 ± 0.3 in the case of patients previously unexposed to oxaliplatin-containing chemotherapy, it occurred at cycle 2.6 ± 0.3 in previously exposed patients. Of the 173 patients who exhibited HSR, premedication was administered in 134 patients and 71.6 % of them succeeded in preventing HSR. Desensitization was attempted in 38 patients, including 20 patients in whom premedication administration was unsuccessful, and 89 % of desensitized patients successfully underwent oxaliplatin chemotherapy without HSR. As severity of HSR increased, the success rate by premedication decreased and the percentage of patients that underwent desensitization increased. CONCLUSIONS: Attention should be paid to patients with any prior exposure to oxaliplatin, especially during early chemotherapy cycles. Given the high success rate of preventing HSR by desensitization administration and its apparent safety profile, we suggest that desensitization be considered as the first option for the treatment of grades 3 and 4 HSR cases.

Allergic diseases and air pollution.

The prevalence of allergic diseases has been increasing rapidly, especially in developing countries. Various adverse health outcomes such as allergic disease can be attributed to rapidly increasing air pollution levels. Rapid urbanization and increased energy consumption worldwide have exposed the human body to not only increased quantities of ambient air pollution, but also a greater variety of pollutants. Many studies clearly demonstrate that air pollutants potently trigger asthma exacerbation. Evidence that transportation-related pollutants contribute to the development of allergies is also emerging. Moreover, exposure to particulate matter, ozone, and nitrogen dioxide contributes to the increased susceptibility to respiratory infections. This article focuses on the current understanding of the detrimental effects of air pollutants on allergic disease including exacerbation to the development of asthma, allergic rhinitis, and eczema as well as epigenetic regulation.