Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

Association between obesity and lung function changes by sex and age in adults with asthma.

OBJECTIVE: The lung function changes presenting before and after asthma treatment in obese people remain largely unknown. This study aimed to investigate the association between obesity and lung function changes before and after treatment in adults with asthma. METHODS: We enrolled 937 newly diagnosed asthma patients from Cohort for Reality and Evolution of Adult Asthma in Korea cohort in 2015-2017, who performed follow-up spirometry after three months of asthma treatment. The percentage changes (Δ) between the spirometry results before and after treatment were calculated. Patients were categorized into four body mass index (BMI) groups; underweight (<18.5), normal (18.5-22.9), overweight (23.0-24.9), and obese (≥25.0). Association between percent change of pulmonary function and BMI was analyzed according to sex and/or age (< 45 yrs, 45-65 yrs, ≥ 65 yrs), which were statistically corrected for age, sex, smoking status, and medication history. RESULTS: There was no consistent correlation between BMI and each lung function parameter. However, there were significant differences between BMI and ΔFEV1/FVC before and after 3 months of controller treatment. The obese asthmatics showed significantly lower ΔFEV1/FVC (6.0 ± 13.5%) than the underweight (12.6 ± 21.4%, P = 0.044) or normal weight (9.1 ± 14.6%, P = 0.031). Middle-aged women had higher BMI (24.11 ± 3.60 vs. 22.39 ± 3.52) and lower ΔFEV1/FVC (5.7 ± 11.9% vs. 8.9 ± 14.3%, P = 0.012) than young women. CONCLUSIONS: Obesity is negatively correlated with the ΔFEV1/FVC before and after controller treatment. Sex and age differentially contribute to lung function changes in response to asthma medications in adult asthmatics, showing a significant decrease in the ΔFEV1/FVC in middle-aged women.

Assessment of Inhaler Satisfaction and Determinants of High Satisfaction Among Korean COPD Patients.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD) recommend considering patient preference when choosing an inhaler device. However, few studies have assessed both inhaler satisfaction and factors associated with high inhaler satisfaction. Therefore, we assessed inhaler satisfaction and determinants of high satisfaction in Korean COPD patients. METHODS: COPD patients were prospectively enrolled from January 2018 to November 2019. The 308 inhalers used by the 261 participants in this study included dry powder inhalers (Turbuhaler, Breezhaler, Ellipta, Diskus, and Genuair), a soft mist inhaler (Respimat), and pressurized metered dose inhalers (pMDIs). Inhaler satisfaction was assessed by the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire. High inhaler satisfaction was defined as an FSI-10 ≥ 43. RESULTS: Among 261 COPD patients, 163 (62.5%) were highly satisfied with their inhaler device. The rates of high inhaler satisfaction for Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair, Respimat, and pMDI usage were 40.0%, 67.2%, 66.7%, 50.0%, 55.6%, 63.4%, and 45.0%, respectively (P = 0.215). In univariate analyses, higher body mass index, non-current smoker, GOLD grades I and II, a modified Medical Research Council (mMRC) score < 2, lower inhaler puff burden, once daily usage of inhaler, and good inhaler adherence were associated with high inhaler satisfaction. In multivariate analyses, an mMRC score < 2, and good inhaler adherence were independently associated with high inhaler satisfaction. CONCLUSION: High inhaler satisfaction was associated with dyspnea symptom and good inhaler adherence in COPD patients. Effective strategies are needed including appropriate inhaler device selection, consideration of patient preference, and repeated inhaler education to improve patient satisfaction of inhalers.

Association Between Clinical Burden and Blood Eosinophil Counts in Asthma: Findings From a Korean Adult Asthma Cohort.

BACKGROUND: Some reports have suggested that the clinical and economic burdens of asthma are associated with blood eosinophil levels. The association between clinical burden and blood eosinophil counts were evaluated in a Korean adult asthma cohort. METHODS: Clinical information including blood eosinophil counts that were not affected by systemic corticosteroids were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea database. Clinical burden was defined as 1) asthma control status, 2) medication demand and 3) acute exacerbation (AE) events during 1 consecutive year after enrollment. All patients were divided into atopic and non-atopic asthmatics. The associations between asthma outcomes and the blood eosinophil count were evaluated. RESULTS: In total, 302 patients (124 atopic and 178 non-atopic asthmatics) were enrolled. In all asthmatics, the risk of severe AE was higher in patients with blood eosinophil levels < 100 cells/µL than in patients with levels ≥ 100 cells/µL (odds ratio [OR], 5.406; 95% confidence interval [CI], 1.266-23.078; adjusted P = 0.023). Among atopic asthmatics, the risk of moderate AE was higher in patients with blood eosinophil levels ≥ 300 cells/µL than in patients with levels < 300 cells/µL (OR, 3.558; 95% CI, 1.083-11.686; adjusted P = 0.036). Among non-atopic asthmatics, the risk of medication of Global Initiative for Asthma (GINA) steps 4 or 5 was higher in patients with high blood eosinophil levels than in patients with low blood eosinophil levels at cutoffs of 100, 200, 300, 400, and 500 cells/µL. CONCLUSION: The baseline blood eosinophil count may predict the future clinical burden of asthma.

Utility of Radial Probe Endobronchial Ultrasound Guided Transbronchial Lung Biopsy in Bronchus Sign Negative Peripheral Pulmonary Lesions.

BACKGROUND: The presence of the bronchus sign on chest computed tomography is associated with an increased diagnostic yield of radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB). However, the utility of RP-EBUS-TBLB for bronchus sign negative peripheral pulmonary lesions (PPLs) remains unknown. We investigated the utility of RP-EBUS-TBLB in bronchus sign negative PPLs. METHODS: We retrospectively reviewed data from 109 patients who underwent RP-EBUS for bronchus sign negative PPLs from January 2019 to August 2020. TBLB was performed using RP-EBUS with a guide sheath and without fluoroscopy. The EBUS visualization and TBLB diagnostic yields were assessed. Multivariable logistic regression analyses were used to identify factors affecting the EBUS visualization and diagnostic yields. RESULTS: The EBUS visualization yield was 74.1% (68/109). Of the 109 lung lesions, 92 were definitively diagnosed. The overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 50.5% (55/109), 34.9% (29/83), 100% (26/26), 100% (29/29), and 32.5% (26/80), respectively. In multivariable analyses, the size of the lesion (≥ 20 mm; odds ratio [OR], 2.62; 95% confidence interval [CI], 1.16-5.93; P = 0.021) and the distance from the pleura (> 10 mm; OR, 2.37; 95% CI, 1.02-5.52; P = 0.045) were associated with EBUS visualization. Regarding diagnostic yield, having the probe within the lesion (OR, 28.50; 95% CI, 6.26-129.85; P < 0.001) and a solid lesion (OR, 14.58; 95% CI, 2.64-80.38; P = 0.002) were associated with diagnostic success. Pneumothorax and hemoptysis occurred in 3.7% (4/109) and 0.9% (1/109), respectively, of the patients. CONCLUSION: RP-EBUS-TBLB using a GS can be considered a diagnostic method in bronchus sign negative solid PPLs. Having the probe within the lesion and a solid lesion were important for diagnostic success. Complication rates were acceptable.

Diagnostic properties of the methacholine and mannitol bronchial challenge tests: a comparison study.

BACKGROUND AND OBJECTIVE: Airway hyperresponsiveness is a common feature of asthma. Methacholine and mannitol are two representative agonists for bronchial challenge. They have theoretically different mechanisms of action, and may have different diagnostic properties. However, their difference has not been directly evaluated among Korean adults. In this study, we compare the diagnostic properties of methacholine and mannitol bronchial provocation tests. METHODS: Asthmatic patients and non-asthmatic controls were recruited prospectively from four referral hospitals in Korea. Participants were challenged with each of methacholine and mannitol inhalation on different days. Their diagnostic utility was evaluated by calculating their sensitivity and specificity for asthma diagnosis. Response-dose ratio was also compared. RESULTS: A total of 50 asthmatic adults and 54 controls were enrolled (mean age 43.8 years). The sensitivity and specificity of mannitol challenge (defined by a PD15 of <635 mg) were 48.0% and 92.6%, respectively, whereas those of methacholine (defined by a PC20 of <16 mg/mL) were 42.0% and 98.1%, respectively. Twenty asthmatic participants (24%) showed positive response to a single agonist only. In the receiver operating curve analyses using response-dose ratio values, area under the curve was 0.77 (95% confidence interval (CI): 0.68-0.86) for mannitol, and 0.89 (95% CI: 0.83-0.95) for methacholine. The correlations between log- transformed mannitol and methacholine response-dose ratios were significant but moderate (r = 0.683, P < 0.001). CONCLUSIONS: The present study demonstrated overall similar diagnostic properties of two diagnostic tests, but also suggested their intercomplementary roles for asthma. The clinical trial registration number at ClinicalTrial.gov is NCT02104284.

Paradoxical increase of IgE binding components during allergen-specific immunotherapy in pollinosis patients.

Allergen-specific immunotherapy (SIT) reduces allergen specific IgE (sIgE) levels and achieves clinical and immunological tolerance by modulating innate and adaptive immunological responses. Increased temperature and CO2 concentrations caused by climate changes contribute to an increase of pollen count and allergenicity that influences clinical SIT outcomes. In this study, we investigated the changes of IgE binding components to tree and weed pollens in pollinosis patients who showed a paradoxical increase of serum sIgE level during pollen-SIT. We enrolled nine patients who showed an increasing pattern of serum sIgE level to alder, birch, ragweed and mugwort pollens by enzyme-linked immunosorbant assay. IgE immunoblot analysis confirmed the intensification or new generation of major IgE binding components that could be induced by climate change. The findings suggest that the regular monitoring of sIgE levels and symptom changes is required to improve the clinical outcomes of SIT in patients undergoing SIT for tree and weed pollens.

Co-existence of chronic urticaria and metabolic syndrome: clinical implications.

A systemic pro-inflammatory and pro-coagulating state occurs in subjects who have both chronic urticaria and metabolic syndrome. To investigate the prevalence and clinical impact of metabolic syndrome in Korean patients with chronic urticaria, a hospital-based cross-sectional study of 131 patients was performed. Metabolic syndrome was assessed by the criteria of the National Cholesterol Education Program's Adult Treatment Panel III. Urticaria disease activity was assessed by total urticaria activity score (range 0-15). Thirty-nine patients (29.8%) had metabolic syndrome compared to 17.8% in a matched control group (p=0.001). Patients with chronic urticaria and metabolic syndrome were older, had a higher mean urticaria activity score and serum levels of eosinophil cationic protein, tumour necrosis factor-α, and complements, and showed a higher rate of negative autologous serum skin tests compared with those with-out metabolic syndrome. Logistic regression analysis indicated that an urticaria activity score of ≥ 13 (p=0.025) and the presence of metabolic syndrome (p=0.036) were independent predictors of uncontrolled chronic urticaria. We conclude that patients with severe and uncontrolled chronic urticaria should be evaluated for metabolic syndrome in order to reduce cardiovascular risk and improve chronic urticaria outcomes.

Comparison of specific IgE antibodies to wheat component allergens in two phenotypes of wheat allergy.

Specific IgE to gliadin was proposed as a marker for wheat dependent exercise induced anaphylaxis, while Tri a 14 was found to induce IgE response in baker's asthma. We evaluated whether these components could be used for discriminating phenotypes of wheat allergy. Twenty-nine patients who were wheat-induced anaphylaxis and/or urticaria (n=21, group I) and baker's asthma (n=8, group II) were enrolled. The prevalence of serum specific IgE to Tri a 14 was higher in group II (25%) than in group I (4.8%), while the serum specific IgE to gliadin was significantly higher in group I (70%) than in group II (12.5%). The cutoff value for predicting the baker's asthma using the ratio of serum specific IgE to Tri a 14 to gliadin was 742.8 optical density×1,000/(kU/L) with high sensitivity and specificity. These findings suggest that Tri a 14/gliadin may be a potential marker for predicting baker's asthma.

Effect of genetic polymorphism of ALOX15 on aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome associated with chronic inflammation in the airways coincident with chronic rhinitis, sinusitis, recurrent polyposis and asthma. Eosinophils are the key inflammatory cells in the development of AERD. AERD has been attributed to abnormalities of the arachidonic acid metabolism, but the pathogenesis of AERD is not fully understood. Our aim was to investigate the genetic contribution of the arachidonate 15-lipoxygenase gene (ALOX15) to the development of AERD. METHODS: We enrolled 171 patients with AERD, 229 patients with aspirin-tolerant asthma, and 195 normal healthy controls in a Korean population. Three polymorphisms (-427G/A, -272C/A, -217G/C) in the promoter region of ALOX15 were genotyped. The functional variability of the promoter polymorphisms were analyzed by luciferase reporter activity assay. RESULT: No significant difference in the genotype frequency of the ALOX15 genetic polymorphism was found. Peripheral total eosinophil count was significantly higher in the patients carrying the GG genotype of the -427G/A polymorphism (p = 0.016). Similarly, the patients carrying haplotype 1 (ht1) (GCG) of -427G/A, -272C/A and -217G/C showed a significantly higher total eosinophil count compared to the other haplotypes (p = 0.008) in the AERD group. The promoter activity of the ht1 (GCG) construct was significantly higher compared to that of the ht3 (AGG) construct in A549 and U937 cells (both p < 0.001). CONCLUSION: These results suggest that the promoter polymorphisms of the ALOX15 gene affect ALOX15 activity leading to increased eosinophil infiltration in AERD patients.

Diagnostic value of the serum-specific IgE ratio of ω-5 gliadin to wheat in adult patients with wheat-induced anaphylaxis.

BACKGROUND: Wheat is an important food allergen associated with severe allergic reactions, including wheat-dependent exercise-induced anaphylaxis (WDEIA) and wheat-induced anaphylaxis (WIA). To diagnose WDEIA, an exercise challenge test following wheat ingestion is performed, which is time-consuming and unsafe. The compound ω-5 gliadin has been identified as a major allergen for WDEIA and WIA. We evaluated the diagnostic value of serum immunoglobulin E (IgE) ratios of ω-5 gliadin to wheat in adult patients with WDEIA or WIA. METHODS: In total, 27 patients were enrolled and classified into 2 groups according to the severity of their allergic reactions to wheat. Serum IgE, specific to wheat and ω-5 gliadin, was measured using the ImmunoCAP system. To evaluate the diagnostic value, receiver operator characteristic curves were produced. RESULTS: Group 1 included 17 patients with a history of anaphylaxis and group 2 included 10 patients having urticaria or atopic dermatitis. Serum IgE specific to wheat was increased in 47% of group 1 and 100% of group 2. However, all patients in group 1 had high serum IgE specific to ω-5 gliadin, whereas only 20% of group 2 showed increased levels. To identify a better diagnostic value, the log-transformed IgE ratio of ω-5 gliadin to wheat was calculated, with the cutoff value at 0.3. Based on these criteria, we found 100% sensitivity and specificity. CONCLUSIONS: This study confirms that the serum IgE ratio of ω-5 gliadin to wheat may be a useful marker for the diagnosis of WDEIA and WIA.

Effect of interleukin-18 gene polymorphisms on sensitization to wheat flour in bakery workers.

Lower respiratory symptoms in bakery workers may be induced by wheat flour and endotoxins. We hypothesized that endotoxins from wheat flour may stimulate innate immunity and that interleukin-18 (IL-18) gene polymorphisms may affect their regulatory role in innate immune responses to endotoxins. To investigate the genetic contribution of IL-18 to sensitization to wheat flour, we performed a genetic association study of IL-18 in Korean bakery workers. A total of 373 bakery workers undertook a questionnaire regarding work-related symptoms. Skin prick tests with common and occupational allergens were performed and specific antibodies to wheat flour were measured by ELISA. Three polymorphisms of the IL-18 gene (-607A/C, -137G/C, 8674C/G) were genotyped, and the functional effects of the polymorphisms were analyzed using the luciferase reporter assay. Genotypes of -137G/C (GC or CC) and haplotype ht3 [ACC] showed a significant association with the rate of sensitization to wheat flour. Luciferase activity assay indicated ht3 [AC] as a low transcript haplotype. In conclusion, the regulatory role of IL-18 in lipopolysaccharide-induced responses in bakery workers may be affected by this polymorphism, thus contributing to the development of sensitization to wheat flour and work-related respiratory symptoms.

Successful treatment of chronic eosinophilic pneumonia with anti-IgE therapy.

Anti-IgE therapy, using recombinant humanized anti-IgE antibodies, is clinically effective in patients with eosinophil-related disorders such as allergic asthma, allergic rhinitis, and chronic urticaria. Chronic eosinophilic pneumonia tends to respond promptly to systemic corticosteroid therapy, however; relapses are common following corticosteroid tapering. We treated two patients (17- and 19-yr-old males) of chronic eosinophilic pneumonia whose symptoms were cough and dyspnea on exertion. The symptoms were recurrent while tapering off corticosteroid. They were treated with anti-IgE antibody without recurrence for 2 yr and 15 months. Here, we first describe clinical experience of the 2 cases of chronic eosinophilic pneumonia.

Identifying genetic susceptibility to sensitization to cephalosporins in health care workers.

Exposure to cephalosporins could cause occupational allergic diseases in health care workers (HCWs). We evaluated the prevalence of serum specific IgE and IgG antibodies to cephalosporin-human serum albumin (HSA) conjugate and to identify potential genetic risk factors associated with sensitization to cephalosporins in exposed HCWs. The study population consisted of 153 HCWs who had been exposed to antibiotics in a single university hospital and 86 unexposed healthy controls. A questionnaire survey of work-related symptoms (WRS) was administered. A skin-prick test (SPT) was performed, and serum-specific IgE and IgG antibodies to 3 commonly prescribed cephalosporins were measured by ELISA. Four single-nucleotide polymorphisms of the candidate genes related to IgE sensitization were genotyped. The prevalence of WRS to cephalosporins was 2.6%. The prevalence rates of serum-specific IgE and IgG antibodies to cephalosporins were 20.3% and 14.7%, respectively. The FcεR1ß-109T > C polymorphism was significantly associated with IgE sensitization to cephalosporins in HCWs (P = 0.036, OR = 3.553; CI, 1.324-9.532). The in vitro functional assay demonstrated that the T allele of FcεR1ß-109T had greater promoter activity than did the C allele (P < 0.001). The FcεR1ß-109T > C polymorphism may be a potential genetic risk factor for increased IgE sensitization to cephalosporins.

Frozen section utilization to omit systematic biopsy in diagnosing high risk prostate cancer.

The current guidelines for targeted prostate biopsy recommend an additional systematic biopsy regardless of clinical risk assessment. To evaluate frozen section biopsy utilization in targeted prostate biopsy to omit systematic biopsies in cases of positive frozen section results of patients with clinical features suggestive of high-risk prostate cancer. In this prospective, single-center study, we enrolled patients with a Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesion on magnetic resonance imaging (MRI) with clinical evidence suggestive of high-risk prostate cancer (either an extracapsular extension or prostate-specific antigen level > 20 ng/ml). All patients underwent 2-4 core targeted biopsies utilizing frozen section biopsy with immediate results, allowing patients with a positive result to omit a systematic biopsy. In case of a negative result, additional systematic biopsies were performed. The primary endpoint was the detection rate of targeted biopsy. Patient demographics, clinical variables were analyzed using SPSS version 20. Sixty-six patients were enrolled in this study. Among them, 63 patients were diagnosed with cancer without the need for an additional systematic biopsy. Three patients were non-diagnostic with target biopsy alone. Hence an additional systematic biopsy was performed. Two of these patients were diagnosed with prostate cancer and one tested negative for cancer. In this report we looked into the necessity of taking a routine systematic biopsy in patients with high risk features of prostate cancer. We found that utilizing frozen section biopsy for targeted biopsy reduces unneccessary systematic biopsy in 97% of cases and still provides a means for systematic biopsy when targeted biopsy alone fails to make the diagnosis.

Gender-related outcomes in robot-assisted radical cystectomy: A multi-institutional study.

PURPOSE: Robot-assisted radical cystectomy (RARC) optimizes patient recovery and has outcomes comparable with those of open surgery. This study aimed to compare the perioperative and oncologic outcomes of RARC in female and male patients. MATERIALS AND METHODS: A retrospective cohort study of the Korean Robot-Assisted Radical Cystectomy Study Group database from 2007 to 2019 identified 749 patients (111 females and 638 males). Female were matched 1:1 to male by propensity score matching using a logistic regression. We compared perioperative outcomes, oncologic outcomes, and complications between the two groups. RESULTS: The female group had comparable perioperative outcomes to the male group in terms of operation time, lymph node yield, positive surgical margin, blood transfusion rate, and hospitalization days. Complication rate and grade were not significantly different between the two groups. The most common complication was infection in female and gastrointestinal complications in male. We compared the 5-year overall, disease-specific, and recurrence-free survival of female and male: 58.2% vs. 68.0% (p=0.495), 75.7% vs. 79.3% (p=0.645), and 40.8% vs. 53.5% (p=0.913), respectively. On multivariable analysis, T stage (>T2), postoperative complications, and positive surgical margin were prognostic factors of poor outcome. Sex was not an independent predictor of the three survivals. CONCLUSIONS: The current study suggests that RARC in female has comparable perioperative and oncologic outcomes to those in male. The complication rate of RARC in female was comparable to that in male, but the type of complications differed by sex.

Clinical predictors of treatment response to tiotropium add-on therapy in adult asthmatic patients: From multicenter real-world cohort data in Korea.

Background: Tiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on. Methods: We performed a multicenter, retrospective, cohort study using data from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). We enrolled asthmatic participants who took ICS-LABA with at least 2 consecutive lung function tests at 3-month intervals. We compared tiotropium users and non-users, as well as tiotropium responders and non-responders to predict positive responses to tiotropium, defined as 1) increase in forced expiratory volume in 1 s (FEV1) ≥ 10% or 100 mL; and 2) increase in asthma control test (ACT) score ≥3 after 3 months of treatment. Results: The study included 413 tiotropium users and 1756 tiotropium non-users. Tiotropium users had low baseline lung function and high exacerbation rate, suggesting more severe asthma. Clinical predictors for positive response to tiotropium add-on were 1) positive bronchodilator response (BDR) [odds ratio (OR) = 6.8, 95% confidence interval (CI): 1.6-47.4, P = 0.021] for FEV1 responders; 2) doctor-diagnosed asthma-chronic obstructive pulmonary disease overlap (ACO) [OR = 12.6, 95% CI: 1.8-161.5, P = 0.024], and 3) initial ACT score <20 [OR = 24.1, 95% CI: 5.45-158.8, P < 0.001] for ACT responders. FEV1 responders also showed a longer exacerbation-free period than those with no FEV1 increase (P = 0.014), yielding a hazard ratio for the first asthma exacerbation of 0.5 (95% CI: 0.3-0.9, P = 0.016). Conclusions: The results of this study suggest that tiotropium add-on for uncontrolled asthma with ICS-LABA would be more effective in patients with positive BDR or ACO. Additionally, an increase in FEV1 following tiotropium may predict a lower risk of asthma exacerbation.

A case of piperacillin-induced occupational anaphylaxis: detection of serum IgE to piperacillin-HSA conjugate.

This is the first reported detection of serum IgE antibody to piperacillin-human serum albumin (HSA) conjugate in a patient presenting with anaphylaxis that developed after occupational exposure. A 24-yr-old nurse, who had worked at a University Hospital for 2 yr, experienced chest tightness, dizziness, generalized urticaria, abdominal pain, and diarrhea 10 min after administering a piperacillin injection. She had previously suffered from atopic dermatitis. A skin prick test for common inhalant allergens was entirely negative; in contrast, her serum total IgE was elevated (283 IU/mL). A high level of piperacillin-specific serum IgE was detected by ELISA using piperacillin-HSA conjugate. Significant inhibition upon addition of both free piperacillin and piperacillin-HSA conjugate was detected by inhibition ELISA. These data suggest that piperacillin exposure in the workplace can induce occupational anaphylaxis and urticaria mediated by an interaction of IgE with the hapten of piperacillin.

Incidence and Prognostic Factors of Respiratory Viral Infections in Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: Severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) that require hospitalization and emergency department visits are associated with considerable morbidity and mortality. Respiratory viral infection is an important cause of severe AECOPD. We evaluated the incidence and prognostic factors of viral infection in severe AECOPD. Patients and Methods: We performed a retrospective study of 262 cases of severe AECOPD in 192 patients who required hospitalization and emergency department visits at a tertiary teaching hospital in Daegu, Korea. A multiplex polymerase chain reaction panel using a nasopharyngeal swab sample was performed to detect viral infection. Results: Viral infection was detected in 108 events (41.2%) from 96 patients. The most common virus was rhinovirus/enterovirus (27.5%), followed by influenza virus (22.5%), respiratory syncytial virus (13.3%), parainfluenza virus (12.5%), coronavirus (12.5%), metapneumovirus (7.5%), and adenovirus (4.2%). Virus-positive exacerbations, compared to virus-negative exacerbations, had a higher frequency of symptoms of rhinopharyngitis, higher neutrophil count and C-reactive protein (CRP) level, and lower eosinophil count. Multivariate analysis demonstrated that elevated CRP levels (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.24-6.15), symptoms of rhinopharyngitis (OR, 1.98; 95% CI, 1.03-3.78), low eosinophil count (OR, 1.74; 95% CI, 1.03-2.92), and inhaled corticosteroid (ICS) use (OR, 1.70; 95% CI 1.04-2.80) were associated with viral infection in severe AECOPD. Conclusion: The incidence of viral infection in severe AECOPD was 41.2%, and the most commonly detected virus was rhinovirus/enterovirus. Increased CRP level, symptoms of rhinopharyngitis, low eosinophil count, and use of ICS were associated with viral infection in severe AECOPD.