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.
Arthritis, Rheumatoid ; Asian Continental Ancestry Group ; Autoantibodies ; Connective Tissue Diseases ; Connective Tissue ; Diagnosis ; Disease Management ; Guidelines as Topic ; Humans ; Idiopathic Interstitial Pneumonias ; Incidence ; Lung ; Lung Diseases, Interstitial ; Myositis ; Prognosis ; Scleroderma, Systemic ; Thorax

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.
Autoimmune Diseases ; Collagen ; Connective Tissue Diseases ; Connective Tissue* ; Fibrosis ; Humans ; Idiopathic Pulmonary Fibrosis ; Immunosuppressive Agents ; Inflammation ; Lung Diseases, Interstitial* ; Mortality ; Respiratory Insufficiency ; Scleroderma, Systemic ; Vascular Diseases

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.
Comorbidity ; Herpesvirus 1, Cercopithecine ; Hospitalization ; Humans ; Incidence* ; Influenza, Human* ; Leukocyte Count ; Multivariate Analysis ; Odds Ratio ; Platelet Count ; Pneumonia* ; Polymerase Chain Reaction ; Retrospective Studies ; Risk Factors* ; Seasons* ; Sputum

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.
Anticoagulants ; Atrial Fibrillation ; Enoxaparin* ; Hemorrhage ; Hemostasis ; Heparin, Low-Molecular-Weight ; Humans ; Incidence ; Injections, Subcutaneous ; Korea ; Male ; Minor Surgical Procedures ; Mortality ; Retrospective Studies ; Thromboembolism ; Venous Thromboembolism ; Warfarin

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-1β (IL-1β), 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-1β 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-1β in lung tissues from both the normal and elastase-induced emphysema groups. The secretion of IL-1β 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-1β 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.
Antioxidants ; Blotting, Western ; Emphysema* ; Humans ; Immunohistochemistry ; Lung* ; Models, Animal ; Pancreatic Elastase ; Pulmonary Disease, Chronic Obstructive ; RAW 264.7 Cells* ; Reactive Oxygen Species ; Smoking ; Vehicle Emissions*

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.
Air Pollutants ; Animals ; Antioxidants ; Asthma ; Blotting, Western ; Bronchoalveolar Lavage ; Eosinophils ; Glutathione ; Humans ; Immunohistochemistry ; Lung ; Methacholine Chloride ; Mice ; Ovalbumin ; Oxidants ; Oxygen ; Ozone ; Proliferating Cell Nuclear Antigen ; Respiratory Hypersensitivity

Smoking-related interstitial fibrosis (SRIF) is characterized by marked alveolar septal fibrosis seen as distinct thick collagen bundles, along with emphysema and respiratory bronchiolitis. In 2010, SRIF was deemed a new entity that differed from idiopathic pulmonary fibrosis (IPF) clinically, pathologically, and radiologically. No case of SRIF has been reported in Korea and it is rare worldwide. Here, we report the 1-year follow-up of three cases of SRIF.
Bronchiolitis ; Collagen ; Emphysema ; Fibrosis* ; Follow-Up Studies* ; Idiopathic Pulmonary Fibrosis ; Korea ; Smoking

BACKGROUND/AIMS: Acute exacerbations in chronic obstructive pulmonary disease may be related to air pollution, of which ozone is an important constituent. In this study, we investigated the protein profiles associated with ozone-induced exacerbations in a smoking-induced emphysema model. METHODS: Mice were divided into the following groups: group I, no smoking and no ozone (NS + NO); group II, no smoking and ozone (NS + O); group III, smoking and no ozone (S + NO); and group IV, smoking and ozone (S + O). Bronchoalveolar lavage, the mean linear intercept (MLI) on hematoxylin and eosin staining, nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS), and Western blotting analyses were performed. RESULTS: The MLIs of groups III (S + NO) and IV (S + O) (45 +/- 2 and 44 +/- 3 microm, respectively) were significantly higher than those of groups I (NS + NO) and II (NS + O) (26 +/- 2 and 23 +/- 2 microm, respectively; p < 0.05). Fourteen spots that showed significantly different intensities on image analyses of two-dimensional (2D) protein electrophoresis in group I (NS + NO) were identified by LC-MS/MS. The levels of six proteins were higher in group IV (S + O). The levels of vimentin, lactate dehydrogenase A, and triose phosphate isomerase were decreased by both smoking and ozone treatment in Western blotting and proteomic analyses. In contrast, TBC1 domain family 5 (TBC1D5) and lamin A were increased by both smoking and ozone treatment. CONCLUSIONS: TBC1D5 could be a biomarker of ozone-induced lung injury in emphysema.
Animals ; Biological Markers/metabolism ; Blotting, Western ; Bronchoalveolar Lavage Fluid/chemistry/cytology ; Chromatography, Liquid ; Disease Models, Animal ; Electrophoresis, Gel, Two-Dimensional ; Lung/*metabolism/pathology ; Male ; Mice, Inbred C57BL ; *Ozone ; Proteins/*metabolism ; *Proteomics/methods ; Pulmonary Disease, Chronic Obstructive/etiology/*metabolism/pathology ; Pulmonary Emphysema/etiology/*metabolism/pathology ; Smoking/*adverse effects ; Tandem Mass Spectrometry

Coccidioidomycosis is a fungal infection caused by Coccidioides immitis. The endemic area is mostly south-western United States. As increasing in overseas travel to endemic areas, the incidence rate has been recently increased in non-endemic areas. The diagnosis may be delayed in non-endemic area. It is important to elicit traveling histories and to differentiate lung consolidation with eosinophilia, for timely diagnosis of coccidioidomycosis. Recently, we experienced a case with pulmonary coccidioidomycosis in a Korean American who visited Korea showed consolidation in right lower lobe on chest X-ray and prolonged eosinophilia. In the case, a confirmatory diagnostic method was percutaneous transthoracic needle biopsy of lung. We report acute pulomonary coccidioidomycosis case and review previous published reports with pulmonary manifestation in Korea.
Asian Americans ; Biopsy, Needle ; Coccidioides ; Coccidioidomycosis* ; Diagnosis ; Endemic Diseases ; Eosinophilia ; Humans ; Incidence ; Korea* ; Lung Diseases, Fungal ; Lung* ; Thorax ; United States

Cryptogenic organizing pneumonia (COP) is an idiopathic interstitial pneumonia characterized by a subacute course and favorable prognosis with corticosteroids. However, some patients show resistance to steroids. Macrolides have been used with success in those patients showing resistance to steroids. A few reports showed treatment failure with macrolides in patients with COP who were resistant to steroids. In this report, we described two cases of COP who showed different responses to clarithromycin. One recovered completely, but the other gradually showed lung fibrosis with clarithromycin.
Adrenal Cortex Hormones ; Clarithromycin* ; Cryptogenic Organizing Pneumonia* ; Fibrosis ; Humans ; Idiopathic Interstitial Pneumonias ; Lung ; Macrolides ; Prognosis ; Steroids ; Treatment Failure