Predictive Role of White Blood Cell Differential Count for the Development of Acute Exacerbation in Korean Chronic Obstructive Pulmonary Disease.

Purpose: Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic inflammation. Acute exacerbation of COPD (AECOPD) manifests as acute worsening of respiratory symptoms and is associated with high morbidity and mortality. The aim of the present study was to evaluate the predictive value of white blood count (WBC) and its derived inflammatory biomarkers for AECOPD. Methods: From the Korean COPD Subgroup Study cohort, a prospective and multicenter observational study, 826 patients who had baseline complete blood count (CBC) and 3-year AECOPD data were included. Follow-up CBC data at 1 (n = 385), 2 (n = 294), and 3 (n = 231) years were collected for available patients. The primary outcome was the occurrence of AECOPD at 3 years. The risk of AECOPD was evaluated using a binary logistic analysis. Results: The cumulative incidences of 12-, 24-, and 36-month AECOPD were 47.6%, 60.5%, and 67.6%, respectively. Patients with AECOPD at 3 years had higher baseline WBC counts, neutrophil counts, neutrophil/lymphocyte ratio (NLR), and neutrophil/monocyte ratio than those without AECOPD. Higher WBC count, neutrophil count, and NLR were associated with the 3-year occurrence of AECOPD in the univariate analysis, but only the higher neutrophil count was a significant risk factor (odds ratio [OR] = 1.468; 95% confidence interval [CI]: 1.024-2.104) in the covariates-adjusted analysis. In the analysis of changes in inflammatory parameters, a decrease in the platelet count (OR = 0.502; 95% CI: 0.280-0.902) and NLR (OR = 0.535; 95% CI: 0.294-0.974) at 2 years and an increase in the eosinophil count (OR = 2.130; 95% CI: 1.027-4.416) at 3 years were significantly associated with AECOPD in the adjusted analysis. Conclusion: Our data suggest that a high baseline WBC count, particularly neutrophil count, was associated with a higher incidence of long-term AECOPD.

Glucocorticoid pulse therapy in an elderly patient with post-COVID-19 organizing pneumonia: A case report.

BACKGROUND: Pulmonary fibrosis often occurs as a sequel of coronavirus disease 2019 (COVID-19); however, in some cases, it can rapidly progress, similar to the acute exacerbation of interstitial lung disease. Glucocorticoids are the standard treatment for severe COVID-19 pneumonia requiring oxygen supply; however, the post-COVID-19 efficacy of high-dose steroid therapy remains unclear. Here, we presented a case of an 81-year-old man who developed acute respiratory failure after COVID-19 and was treated with glucocorticoid pulse therapy. CASE SUMMARY: An 81-year-old man with no respiratory symptoms was admitted due to a diabetic foot. He had been previously treated for COVID-19 pneumonia six weeks prior. However, upon admission, he suddenly complained of dyspnea and required a high-flow oxygen supply. Initial simple chest radiography and computed tomography (CT) revealed diffuse ground-glass opacities and consolidation in both lungs. However, repeated sputum tests did not identify any infectious pathogens, and initial broad-spectrum antibiotic therapy did not result in any clinical improvement with the patient having an increasing oxygen demand. The patient was diagnosed with post-COVID-19 organizing pneumonia. Thus, we initiated glucocorticoid pulse therapy of 500 mg for three days followed by a tapered dose on hospital day (HD) 9. After three days of pulse treatment, the patient's oxygen demand decreased. The patient was subsequently discharged on HD 41, and chest radiography and CT scans have almost normalized nine months after discharge. CONCLUSION: Glucocorticoid pulse therapy may be considered when the usual glucocorticoid dose is ineffective for patients with COVID-19 sequelae.

Clinical Experiences of High-Risk Pulmonary Thromboembolism Receiving Extracorporeal Membrane Oxygenation in Single Institution.

BACKGROUND: The main cause of death in pulmonary embolism (PE) is right-heart failure due to acute pressure overload. In this sense, extracorporeal membrane oxygenation (ECMO) might be useful in maintaining hemodynamic stability and improving organ perfusion. Some previous studies have reported ECMO as a bridge to reperfusion therapy of PE. However, little is known about the patients that benefit from ECMO. METHODS: Patients who underwent ECMO due to pulmonary thromboembolism at a single university-affiliated hospital between January 2010 and December 2018 were retrospectively reviewed. RESULTS: During the study period, nine patients received ECMO in high-risk PE. The median age of the patients was 60 years (range, 22-76 years), and six (66.7%) were male. All nine patients had cardiac arrests, of which three occurred outside the hospital. All the patients received mechanical support with veno-arterial ECMO, and the median ECMO duration was 1.1 days (range, 0.2-14.0 days). ECMO with anticoagulation alone was performed in six (66.7%), and ECMO with reperfusion therapy was done in three (33.3%). The 30-day mortality rate was 77.8%. The median time taken from the first cardiac arrest to initiation of ECMO was 31 minutes (range, 30-32 minutes) in survivors (n=2) and 65 minutes (range, 33-482 minutes) in non-survivors (n=7). CONCLUSION: High-risk PE with cardiac arrest has a high mortality rate despite aggressive management with ECMO and reperfusion therapy. Early decision to start ECMO and its rapid initiation might help save those with cardiac arrest in high-risk PE.

Therapy-related myeloid leukemia during erlotinib treatment in a non-small cell lung cancer patient: A case report.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are tolerable drugs used for patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). Serious adverse reactions are uncommon compared with cytotoxic drugs. CASE SUMMARY: A 52-year-old man presented with general weakness and cytopenia. He had been taking erlotinib for 11 mo to treat NSCLC. The pathological diagnosis from the right upper lobe mass was adenocarcinoma with an EGFR mutation in exon 21 (L858R). He had previously received paclitaxel/carboplatin, gemcitabin/ vinorelbine chemotherapy, stereotactic radiosurgery for brain metastasis, and whole-brain radiotherapy as treatment for NSCLC. We diagnosed the patient with acute myeloid leukemia (AML). During the induction and consolidation chemotherapy for AML, the erlotinib was discontinued. When complete remission of the AML was achieved, since the lung masses were increased, pemetrexed/ cisplatin for the NSCLC was initiated. After two cycles of chemotherapy, the cytopenia was prolonged. AML relapse occurred with the same karyotype. CONCLUSION: Therapy-related acute myeloid neoplasm (t-MN) is a rare but fatal late complication. Although a patient may be taking EGFR-TKIs, the possibility of t-MN should be considered. Further studies are needed to determine whether EGFR-TKI usage is a predisposing factor for t-MN.

Prognosis After Weaning from Respiratory Extracorporeal Membrane Oxygenation.

Successful weaning from extracorporeal membrane oxygenation (ECMO) does not necessarily imply patient survival. We retrospectively analyzed 441 patients with acute respiratory failure from 16 hospitals in South Korea who underwent ECMO from January 2012 to December 2015. We evaluated the clinical factors associated with mortality after successful weaning from ECMO. Of all 441 patients, 245 (55.6%) were successfully weaned from ECMO. The majority of patients were initially supported with veno-venous ECMO (86.9%). Among those, 182 patients (41.3%) were discharged from hospital. Only 165 (37.4%) were alive after 6 months. Most cases of death occurred within the first month after weaning from ECMO (65%), and the most frequent reason for death was sepsis (76.2%). In the multivariate Cox regression analysis, patient age (per 10 years) (hazard ratio [HR] = 1.34, 95% CI = 1.12-1.61; p = 0.001), sequential organ failure assessment score (HR = 1.07, 95% CI = 1.02-1.13; p = 0.010), steroid (HR = 2.38, 95% CI = 1.27-4.45; p = 0.007), interstitial lung disease (HR = 1.20, 95% CI = 1.05-1.36; p = 0.006), and ECMO duration (per day) (HR = 1.02, 95% CI = 1.01-1.04; p < 0.001) were associated with the in-hospital mortality after weaning from ECMO. Furthermore, age (per 10 years) (HR = 1.45, 95% CI = 1.24-1.71; p < 0.001), steroid (HR = 2.19, 95% CI = 1.27-3.78; p = 0.005), and interstitial lung disease (HR = 1.16, 95% CI = 1.02-1.31; p = 0.021) were significantly associated with 6 month mortality. The prognosis after weaning from respiratory ECMO might be related to baseline conditions affecting the reversibility of the primary lung disease and to acquired infections.

Clinical outcomes of immunocompromised patients on extracorporeal membrane oxygenation support for severe acute respiratory failure.

OBJECTIVES: There are limited data regarding extracorporeal membrane oxygenation (ECMO) support in immunocompromised patients, despite an increase in ECMO use in patients with respiratory failure. The aim of this study was to investigate the clinical characteristics and outcomes of immunocompromised patients requiring ECMO support for severe acute respiratory failure. METHODS: Between January 2012 and December 2015, all consecutive adult patients with severe acute respiratory failure who underwent ECMO for respiratory support at 16 tertiary or university-affiliated hospitals in South Korea were enrolled retrospectively. The patients were divided into 2 groups based on the immunocompromised status at the time of ECMO initiation. In-hospital and 6-month mortalities were compared between the 2 groups. In addition, association of immunocompromised status with 6-month mortality was evaluated with logistic regression analysis. RESULTS: Among 461 patients, 118 (25.6%) were immunocompromised. Immunocompromised patients were younger and had lower haemoglobin and platelet counts than immunocompetent patients. Ventilatory parameters and the use of adjunctive/rescue therapies were similar between the 2 groups, but prone positioning was more commonly used in immunocompetent patients. Successful weaning rates from ECMO (46.6% vs 58.9%; P = 0.021) was lower and hospital mortality (66.1% vs 59.8%; P = 0.22) was higher in immunocompromised patients. In addition, immunocompromised status was associated with higher 6-month mortality (74.6% vs 64.7%, adjusted odds ratio 2.10, 95% confidence interval 1.02-4.35; P = 0.045). CONCLUSIONS: Immunocompromised patients treated with ECMO support for severe acute respiratory failure had poorer short- and long-term prognoses than did immunocompetent patients.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 5. Connective Tissue Disease Associated Interstitial Lung Disease.

Connective tissue disease (CTD) is a collection of disorders characterized by various signs and symptoms such as circulation of autoantibodies in the entire system causing damage to internal organs. Interstitial lung disease (ILD) which is associated with CTD is referred to as CTD-ILD. Patients diagnosed with ILD should be thoroughly examined for the co-occurrence of CTD, since the treatment procedures and prognosis of CTD-ILD are vary from those of idiopathic interstitial pneumonia. The representative types of CTD which may accompany ILD include rheumatoid arthritis, systemic sclerosis (SSc), Sjögren's syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematous. Of these, ILD most frequently co-exists with SSc. If an ILD is observed in the chest, high resolution computed tomography and specific diagnostic criteria for any type of CTD are met, then a diagnosis of CTD-ILD is made. It is challenging to conduct a properly designed randomized study on CTD-ILD, due to low incidence. Therefore, CTD-ILD treatment approach is yet to been established in absence of randomized controlled clinical trials, with the exception of SSc-ILD. When a patient is presented with acute CTD-ILD or if symptoms occur due to progression of the disease, steroid and immunosuppressive therapy are generally considered.

Clinical outcomes of patients receiving prolonged extracorporeal membrane oxygenation for respiratory support.

BACKGROUND: There are limited data regarding prolonged extracorporeal membrane oxygenation (ECMO) support, despite increase in ECMO use and duration in patients with respiratory failure. The objective of this study was to investigate the outcomes of severe acute respiratory failure patients supported with prolonged ECMO for more than 28 days. METHODS: Between January 2012 and December 2015, all consecutive adult patients with severe acute respiratory failure who underwent ECMO for respiratory support at 16 tertiary or university-affiliated hospitals in South Korea were enrolled retrospectively. The patients were divided into two groups: short-term group defined as ECMO for ⩽28 days and long-term group defined as ECMO for more than 28 days. In-hospital and 6-month mortalities were compared between the two groups. RESULTS: A total of 487 patients received ECMO support for acute respiratory failure during the study period, and the median support duration was 8 days (4-20 days). Of these patients, 411 (84.4%) received ECMO support for ⩽28 days (short-term group), and 76 (15.6%) received support for more than 28 days (long-term group). The proportion of acute exacerbation of interstitial lung disease as a cause of respiratory failure was higher in the long-term group than in the short-term group (22.4% versus 7.5%, p < 0.001), and the duration of mechanical ventilation before ECMO was longer (4 days versus 1 day, p < 0.001). The hospital mortality rate (60.8% versus 69.7%, p = 0.141) and the 6-month mortality rate (66.2% versus 74.0%, p = 0.196) were not different between the two groups. ECMO support longer than 28 days was not associated with hospital mortality in univariable and multivariable analyses. CONCLUSIONS: Short- and long-term survival rates among patients receiving ECMO support for more than 28 days for severe acute respiratory failure were not worse than those among patients receiving ECMO for 28 days or less.

Improvement in the survival rates of extracorporeal membrane oxygenation-supported respiratory failure patients: a multicenter retrospective study in Korean patients.

BACKGROUND: Although the utilization of extracorporeal membrane oxygenation (ECMO) is increasing and its technology is evolving, only a few epidemiologic reports have described the uses and outcomes of ECMO. The aim of this study was to investigate the changes in utilization and survival rate in patients supported with ECMO for severe respiratory failure in Korea. METHODS: This was a multicenter study on consecutive patients who underwent ECMO across 16 hospitals in Korea. The records of all patients who required ECMO for acute respiratory failure between 2012 and 2015 were retrospectively reviewed, and the utilization of ECMO was analyzed over time. RESULTS: During the study period, 5552 patients received ECMO in Korea as a whole, and a total of 2472 patients received ECMO at the participating 16 hospitals. We analyzed 487 (19.7%) patients who received ECMO for respiratory failure. The number of ECMO procedures provided for respiratory failure increased from 104 to 153 during the study period. The in-hospital survival rate increased from 30.8% to 35.9%. The use of prone positioning increased from 6.8% to 49.0% (p < 0.001), and the use of neuromuscular blockers also increased from 28.2% to 58.2% (p < 0.001). Multiple regression analysis showed that old age (OR 1.038 (95% CI 1.022, 1.054)), use of corticosteroid (OR 2.251 (95% CI 1.153, 4.397)), continuous renal replacement therapy (OR 2.196 (95% CI 1.135, 4.247)), driving pressure (OR 1.072 (95% CI 1.031, 1.114)), and prolonged ECMO duration (OR 1.020 (95% CI 1.003, 1.038)) were associated with increased odds of mortality. CONCLUSIONS: Utilization of ECMO and survival rates of patients who received ECMO for respiratory failure increased over time in Korea. The use of pre-ECMO prone positioning and neuromuscular blockers also increased during the same period.

Association of Genetic Variants of NLRP4 with Exacerbation of Asthma: The Effect of Smoking.

Asthma exacerbation is induced by the interaction of genes and environmental factors such as cigarette smoke. NLRP4 counteracts the activity of the inflammasome, which is responsible for asthma exacerbation. In this study, we analyzed the association of single-nucleotide polymorphisms of NLRP4 with the annual rate of exacerbation and evaluated the additive effect of smoking in 1454 asthmatics. Asthmatics possessing the minor allele of rs1696718G > A had more frequent exacerbation episodes than those homozygous for the common allele (0.59 vs. 0.36/year) and the association was present only in current and ex-smokers. There was a significant interaction between the amount smoked and rs16986718 genotypes (p = 0.014) and a positive correlation between the number of annual exacerbation episodes and amount smoked only in rs16986718G > A AA homozygotes. The prevalence of frequent exacerbators (≥2 exacerbation episodes/year) was 2.5 times higher in rs16986718G > A minor allele homozygotes than in common allele homozygotes (12.0% vs. 5.9%). Furthermore, the prevalence was 6 times higher in rs16986718G > A minor allele homozygotes who were current and ex-smokers than in nonsmokers (25.6% vs. 4.1%). The minor allele of rs16986718G > A in NLRP4 may be a genetic marker that predicts asthma exacerbation in adult asthmatics who smoke.

Genome-wide assessment of gene-by-smoking interactions in COPD.

Cigarette smoke exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) and its interactions with genetic variants could affect lung function. However, few gene-smoking interactions have been reported. In this report, we evaluated the effects of gene-smoking interactions on lung function using Korea Associated Resource (KARE) data with the spirometric variables-forced expiratory volume in 1 s (FEV1). We found that variations in FEV1 were different among smoking status. Thus, we considered a linear mixed model for association analysis under heteroscedasticity according to smoking status. We found a previously identified locus near SOX9 on chromosome 17 to be the most significant based on a joint test of the main and interaction effects of smoking. Smoking interactions were replicated with Gene-Environment of Interaction and phenotype (GENIE), Multi-Ethnic Study of Atherosclerosis-Lung (MESA-Lung), and COPDGene studies. We found that individuals with minor alleles, rs17765644, rs17178251, rs11870732, and rs4793541, tended to have lower FEV1 values, and lung function decreased much faster with age for smokers. There have been very few reports to replicate a common variant gene-smoking interaction, and our results revealed that statistical models for gene-smoking interaction analyses should be carefully selected.

Incidence and Risk Factors of Pneumonia in Hospitalized Patients with Seasonal Influenza A or B.

BACKGROUND: Most patients with influenza recover spontaneously or following treatment with an anti-viral agent, but some patients experience pneumonia requiring hospitalization. We conducted a retrospective review to determine the incidence and risk factors of pneumonia in hospitalized patients with influenza A or B. METHODS: A total of 213 patients aged 18 years or older and hospitalized with influenza between January 2012 and January 2015 were included in this study. A reverse-transcriptase polymerase chain reaction assay was used to detect the influenza A or B virus in the patients' sputum samples. We collected demographic and laboratory data, combined coexisting diseases, and radiologic findings. RESULTS: The incidence of pneumonia was higher in patients in the influenza A group compared to those in the influenza B group (68.6% vs. 56.9%), but this difference was not statistically significant. The presence of underlying respiratory disease was significantly associated with pneumonia in the influenza A group (adjusted odds ratio [OR], 3.975; 95% confidence interval [CI], 1.312-12.043; p=0.015). In the influenza B group, the white blood cell count (adjusted OR, 1.413; 95% CI, 1.053-1.896; p=0.021), platelet count (adjusted OR, 0.988; 95% CI, 0.978-0.999; p=0.027), and existence of an underlying medical disease (adjusted OR, 15.858; 95% CI, 1.757-143.088; p=0.014) were all significantly associated with pneumonia in multivariate analyses. CONCLUSION: The incidence of pneumonia was 65.7% in hospitalized patients with influenza A or B. The risk factors of pneumonia differed in hospitalized patients with influenza A or B.

The activation of NLRP3-inflammsome by stimulation of diesel exhaust particles in lung tissues from emphysema model and RAW 264.7 cell line.

BACKGROUND/AIMS: Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inf lammasome. In this study, we elucidated whether NLRP3 -inf lammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation. METHODS: RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of interleukin-1ß (IL-1ß), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry. RESULTS: NAC and caspase-1 inhibitor suppressed CSE- and DEP-induced secretion of IL-1ß in RAW 264.7 cells. The expression levels of the NLRP3-inflammasome and caspase-1 were upregulated in RAW 264.7 cells by stimulation with CSE and DEPs and were inhibited by NAC. CSE and DEPs increased the secretion of IL-1ß in lung tissues from both the normal and elastase-induced emphysema groups. The secretion of IL-1ß by CSE and DEPs was increased in the elastin-induced emphysema group more than that in the normal group (CSE: 309 ± 19 pg/mL vs. 151 ± 13 pg/mL, respectively, p < 0.05; DEP: 350 ± 24 pg/mL vs. 281 ± 15 pg/mL, respectively, p < 0.05). NAC inhibited CSE- and DEP-induced IL-1ß secretion in both the normal and elastase-induced emphysema groups. NLRP3-inflammasome expression as determined by immunohistochemistry was increased by CSE and DEPs in both the normal and elastin-induced emphysema groups, and was suppressed by NAC. CONCLUSIONS: The NLRP3-inf lammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC.

Increased antioxidant activity after exposure of ozone in murine asthma model.

BACKGROUND: Ozone is well known as an important component of ambient air pollutants. Ozone can aggravate respiratory symptoms in patients with bronchial asthma, but, not in healthy person. We hypothesized asthma itself may show different response to ozone compared to nonasthma. OBJECTIVE: This study was performed to evaluate the differences of response to ozone between normal and asthmatic mice model in terms of status of oxidant injury and antioxidant activity. METHODS: Three parts per million of ozone was exposed to ovalbumin (OVA)-induced murine asthma model for 3 hours at 3, 7, 14, 21 days after completion of asthma model. Airway responsiveness to methacholine was measured after completion of asthma model. Bronchoalveolar lavage (BAL), protein extraction from lung for Western blot and immunohistochemistry of 4-hydroxy-2-nonenal (4-HNE), proliferating cell nuclear antigen (PCNA), NF-E2 related factor 2 (Nrf-2), and activity of glutathione were performed at before and each ozone exposure day. RESULTS: Airway hyper-responsiveness and increased eosinophils in BAL fluid were observed in asthma model. In asthma model, the expression of 4-HNE already more increased at baseline (without ozone) compared to those in sham model. This increased expression is more enhanced at 3 days after ozone exposure. The expression of PCNA was significantly increased in OVA-model compared to those in sham model. The expression of Nrf-2 was observed at baseline, and 3 and 7 days after exposure ozone in asthma model, but not in sham model. The activity of glutathione increased significantly after exposure of ozone, but not in sham model. CONCLUSION: Murine asthma model has enhanced oxygen toxicity and antioxidant activity response to ozone.

Effect of Pregnancy on Quantitative Medication Use and Relation to Exacerbations in Asthma.

BACKGROUND: The quantification of asthma medication reduction and its relation to an aggravation of asthma during pregnancy at an individual level are unclear. METHODS: We conducted a nationwide retrospective cohort study of asthmatic pregnant women in South Korea. All of the asthma medications were ranked from 1 to 4 according to the guideline-based stepwise approach. We assessed the daily sums of the ranks of the asthma medications and their association with exacerbations during three phases based on the individual's delivery date: before, during, and after pregnancy. RESULTS: The study cohort included 115,169 asthmatic pregnant women who gave birth between 2011 and 2013. The subjects were clustered into four groups according to the daily rank sums of their asthma medication. Asthma medications were rapidly reduced at the beginning of the pregnancy and then slowly increased after delivery. Exacerbations were more frequent in the group with higher rank-sum values than in the group with lower values. Overall exacerbations were reduced during pregnancy compared to before or after delivery. CONCLUSIONS: Asthmatic pregnant women tended to reduce their asthma medication use during pregnancy. This led to a greater number of exacerbations in a small part of the study population.

Treatment of connective tissue disease-associated interstitial lung disease: the pulmonologist's point of view.

Interstitial lung disease (ILD) occurs in 15% of patients with collagen vascular disease (CVD), referred to as connective tissue disease (CTD). Despite advances in management strategies, ILD continues to be a significant cause of mortality in patients with CVD-associated ILD (CTD-ILD). There is a lack of randomized, clinical trials assessing pharmacological agents for CTD-ILD, except in cases of ILD-associated systemic sclerosis (SSc). This may be due to the lack of CTD cases available, the difficulty of histological confirmation of ILD, and the various types of CTD and ILD. As a result, evidence-based pharmacological treatment of CTD-ILD is not yet well established. CTD-ILD presents with varying degrees of histology, from inflammation to fibrosis, and a wide spectrum of clinical manifestations, from minimal symptoms to respiratory failure. This renders it difficult for clinicians to make decisions regarding treatment options, observational strategies, optimal timing for interventions, and the appropriateness of pharmacological agents for treatment. There is no specific treatment for reversing fibrosis-like idiopathic pulmonary fibrosis in a clinical setting. This review describes pharmacological interventions for SSc-ILD described in randomized control trials, and presents an overview of recent advances of CTD-ILD-dependent treatments based on the types of CTD.

The Perioperative Management of Antithrombotic Therapies Using Enoxaparin.

Oral anticoagulant therapy is frequently and increasingly prescribed for patients at risk of arterial or venous thromboembolism (VTE). Although elective surgical or invasive procedures have necessitated temporary interruption of anticoagulants, managing these patients has been performed empirically and been poorly investigated. This study was designed to evaluate the adequacy of perioperative anticoagulation using enoxaparin. This was a retrospective, single-center study that evaluated the efficacy and safety of therapeutic-dose enoxaparin for bridging therapy in patients on long-term warfarin at Soonchunhyang University Hospital in Korea between August 2009 and July 2011. Warfarin was discontinued 5 days before surgery, and enoxaparin was administered twice daily by subcutaneous injection at a dose of 1 mg per kg from 3 days before the procedure to the last dose 24 hours before the procedure. Anticoagulation was restarted if proper hemostasis had been confirmed. There were 49 patients, of whom 25 (51%) were men, and the mean age was 63 years. Thirty-four (69%) received warfarin therapy for VTE, and 9 (18%) for atrial fibrillation. Twenty-nine patients (59%) underwent major surgery and 20 (41%) minor surgery. The mean postoperative duration of enoxaparin was 4 days. No patients had thromboembolic complications through 30 days after the procedure. The overall 30-day mortality rate was 0%. In conclusion, our findings demonstrate that bridging therapy with therapeutic-dose enoxaparin is feasible and associated with a low incidence of major bleeding and no thromboembolic complications. However, the optimal approach to managing patients perioperatively is uncertain and requires further evaluation.

Genetic variants of the gasdermin B gene associated with the development of aspirin-exacerbated respiratory diseases.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by a severe and sudden asthma attack after aspirin ingestion in patients with asthma. We studied associations with six common single nucleotide polymorphisms (SNP) of the gasdermin B gene (GSDMB). OBJECTIVE: DNA obtained from 572 patients with asthma (with AERD, n = 165; and with aspirin-tolerant asthma, n = 407) and 391 normal controls was subjected to genotyping of six SNPs of GSDMB. METHODS: An association analysis between GSDMB variants and AERD, with a fall rate of the forced expiratory volume in the first second of expiration (FEV1), was performed by using logistic and regression models. RESULTS: Two SNPs in the intron (rs870830, rs7216389) showed significant associations with AERD (minimum p = 7.00 × 10-4 in the dominant model), even after Bonferroni correction (pcorr = 0.01 for the rs870830). Regression analysis of the genetic variants with FEV1 revealed significant associations with rs870830 and the haplotype 2 (pcorr = 4.71 × 10-4 for rs870830 and pcorr = 1.14 × 10-3 for haplotype 2, respectively). CONCLUSION: We found strong associations among GSDMB polymorphisms and the presence of AERD and FEV1 in Korean patients with asthma. Our findings indicated that genetic variations of GSDMB may be associated with the development of AERD and aspirin-induced bronchospasm.

Neutrophilic inflammation in asthma: mechanisms and therapeutic considerations.

INTRODUCTION: Neutrophilic airway inflammation represents a pathologically distinct form of asthma and frequently appears in symptomatic adulthood asthmatics. However, clinical impacts and mechanisms of the neutrophilic inflammation have not been thoroughly evaluated up to date. Areas covered: Currently, distinct clinical manifestations, triggers, and molecular mechanisms of the neutrophilic inflammation (namely Toll-like receptor, Th1, Th17, inflammasome) are under investigation in asthma. Furthermore, possible role of the neutrophilic inflammation is being investigated in respect to the airway remodeling. We searched the related literatures published during the past 10 years on the website of Pub Med under the title of asthma and neutrophilic inflammation in human. Expert commentary: Epidemiologic and experimental studies have revealed that the neutrophilic airway inflammation is induced by a wide variety of stimuli including ozone, particulate matters, cigarette smoke, occupational irritants, endotoxins, microbial infection and colonization, and aeroallergens. These triggers provoke diverse immune and inflammatory responses leading to progressive and sometimes irreversible airway obstruction. Clinically, neutrophilic airway inflammation is frequently associated with severe asthma and poor response to glucocorticoid therapy, indicating the need for other treatment strategies. Accordingly, therapeutics will be targeted against the main mediators behind the underlying molecular mechanisms of the neutrophilic inflammation.

Relationship between survival and age in patients with idiopathic pulmonary fibrosis.

BACKGROUND: There is a debate that older patients with idiopathic pulmonary fibrosis (IPF) have a worse prognosis. We evaluated whether age affects the survival of patients with IPF. METHODS: The Korean Interstitial Lung Disease (ILD) Research Group conducted a national survey to evaluate the clinical, physiological, radiological, and survival characteristics of patients with IPF. A total of 1,663 patients with IPF were stratified into three groups according to age: (I) <60 years (n=309); (II) 60-69 years (n=613); and (III) ≥70 years (n=741). RESULTS: The 1-, 3- and 5-year observed survival rates were 83.0%, 62.6%, and 49.2% in the total population, respectively. The 1-, 3-, and 5-year relative survival rates were 85.7%, 69.1%, and 58.0% in all patients, respectively. The observed survival rate of the group ≥70 years of age was significantly lower than those of the other groups (P<0.001). In contrast, no significant difference in relative survival rate was detected among the three age groups. Compared with patients less than 60 years of age, patients with above 70 years of age had not increased risk of worse relative survival [P=0.252; hazard ratio (HR), 1.11; 95% confidence interval (CI), 0.76-1.64]. CONCLUSIONS: The prognosis of patients above 70 years of age with IPF was not different to that of patients less than 60 years of age, using relative survival rate. Age may not affect survival in patients with IPF.