Spirometry is a physiological test for assessing the functional aspect of the lungs using an objective indicator to measure the maximum amount of air that a patient can inhale and exhale. Acceptable spirometry testing needs to be conducted three times by an acceptable and reproducible method for determining forced vital capacity (FVC). Until the results of three tests meet the criteria of reproducibility, the test should be repeated up to eight times. Interpretation of spirometry should be clear, concise, and informative. Additionally, spirometry should guarantee optimal quality prior to the interpreting spirometry results. Our guideline adopts a fixed normal predictive value instead of the lower limit of normal as the reference value because fixed value is more convenient and also accepts FVC instead of vital capacity (VC) because measurement of VC using a spirometer is impossible. The bronchodilator test is a method for measuring the changes in lung capacity after inhaling a short-acting b-agonist that dilates the airway. When an obstructive ventilatory defect is observed, this test helps to diagnose and evaluate asthma and chronic obstructive pulmonary disease by measuring reversibility with the use of an inhaled bronchodilator. A positive response to a bronchodilator is generally defined as an increase of ≥12% and ≥200 mL as an absolute value compared with a baseline in either forced expiratory volume at 1 second or FVC.
Asthma is traditionally regarded as a chronic airway disease, and recent literature proves its heterogeneity, based on distinctive clusters or phenotypes of asthma. In defining such asthma clusters, the nature of comorbidity among patients with asthma is poorly understood, by assuming no causal relationship between asthma and other comorbid conditions, including both communicable and noncommunicable diseases. However, emerging evidence suggests that the status of asthma significantly affects the increased susceptibility of the patient to both communicable and noncommunicable diseases. Specifically, the impact of asthma on susceptibility to noncommunicable diseases such as chronic systemic inflammatory diseases (e.g., rheumatoid arthritis), may provide an important insight into asthma as a disease with systemic inflammatory features, a conceptual understanding between asthma and asthma-related comorbidity, and the potential implications on the therapeutic and preventive interventions for patients with asthma. This review discusses the currently under-recognized clinical and immunological phenotypes of asthma; specifically, a higher risk of developing a systemic inflammatory disease such as rheumatoid arthritis and their implications, on the conceptual understanding and management of asthma. Our discussion is divided into three parts: literature summary on the relationship between asthma and the risk of rheumatoid arthritis; potential mechanisms underlying the association; and implications on asthma management and research.
Assessing response to therapy allows for prospective end point evaluation in clinical trials and serves as a guide to clinicians for making decisions. Recent prospective and randomized trials suggest the development of imaging techniques and introduction of new anti-cancer drugs. However, the revision of methods, or proposal of new methods to evaluate chemotherapeutic response, is not enough. This paper discusses the characteristics of the Response Evaluation Criteria In Solid Tumor (RECIST) version 1.1 suggested in 2009 and used widely by experts. It also contains information about possible dilemmas arising from the application of response assessment by the latest version of the response evaluation method, or recently introduced chemotherapeutic agents. Further data reveals the problems and limitations caused by applying the existing RECIST criteria to anti-cancer immune therapy, and the application of a new technique, immune related response criteria, for the response assessment of immune therapy. Lastly, the paper includes a newly developing response evaluation method and suggests its developmental direction.
Background: Fluoroquinolones are considered important substitutes for the treatment of tuberculosis. This study investigates the current status of fluoroquinolone for the treatment of tuberculosis. Methods: In 2009, a retrospective analysis was performed at one tertiary referral center for 953 patients diagnosed with tuberculosis. Results: A total of 226 patients (23.6%), who received fluoroquinolone at any time during treatment for tuberculosis, were enrolled in this study. The most common reasons for fluoroquinolone use were adverse events due to other antituberculosis drugs (52.7%), drug resistance (23.5%), and underlying diseases (16.8%). Moxifloxacin (54.0%, 122/226) was the most commonly administered fluoroquinolone, followed by levofloxacin (36.3%, 82/226) and ofloxacin (9.7%, 22/226). The frequency of total adverse events from fluoroquinolone-containing anti-tuberculosis medication was 22.6%, whereas fluoroquinolone-related adverse events were estimated to be 2.2% (5/226). The most common fluoroquinolonerelated adverse events were gastrointestinal problems (3.5%, 8/226). There were no significant differences in the treatment success rate between the fluoroquinolone and fluoroquinolone-naïve groups (78.3% vs. 78.4%, respectively). Conclusion: At our institution, fluoroquinolones are commonly used for the treatment of both multidrug-resistant tuberculosis and susceptible tuberculosis, especially as a substitute for adverse event-related drugs. Considering the low adverse event rates and the comparable treatment success rates, fluoroquinolones seem to be an invaluable drug for the treatment of tuberculosis.
Background: Recently, increased levels of high-mobility group box 1 protein (HMGB1) have been identified in various inflammatory conditions and infections. However, no studies have evaluated the HMGB1 level in nontuberculous mycobacterial (NTM) lung disease, and compared it to mycobacterial lung disease. Methods: A total of 60 patients newly diagnosed with NTM lung disease, 44 culture-positive pulmonary tuberculosis (TB) patients, and 34 healthy controls, were included in this study. The serum HMGB1 concentrations were quantified using HMGB1 enzyme-linked immunosorbent assay kits. Results: Serum HMGB1 level in patients with pulmonary TB or NTM lung disease, was significantly lower than that of the healthy controls. In addition, the serum HMGB1 level in TB patients was significantly lower than patients with NTM lung disease. However, the levels in NTM patient subgroups did not differ according to the causative species, disease progression, and disease phenotype. Conclusion: Although low levels of serum HMGB1 has the potential to be a marker of mycobacterial lung disease, these levels were unable to differentiate disease progression and disease phenotype in NTM lung diseases.
Background: Streptomycin (SM) is recommended by the World Health Organization (WHO) as a part of standard regimens for retreating multidrug-resistant tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19% in Thailand. To date, information on SM resistance (SMR) gene mutations correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In this study, the mutations in rpsL , rrs , gidB, and whiB7 were investigated and their association to SMR and the lineage of M. tuberculosis were explored. Methods: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were identified by spoligotyping. Drug susceptibility profiles were evaluated by the absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55 SM-susceptible isolates were examined by DNA sequencing. Results: Three rpsL (Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations were present exclusively in the SM resistant M. tuberculosis . Lys43Arg rpsL was the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates (p<0.001). No SMR-related mutation in was found rrs . The combination of rpsL and gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C, 615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored. This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1. Conclusion: Our study suggested that the majority of SMR in M. tuberculosis Thai isolates were responsible by rpsL and gidB polymorphisms constantly providing the novel lineage specific makers.
Background: The purpose of this study was to assess the effect of our new video-assisted asthma education program on patients’ knowledge regarding asthma and asthma control. Methods: Adult asthmatics who were diagnosed by primary care physicians and followed for at least 1 year were educated via smart devices and pamphlets. The education sessions were carried out three times at 2-week intervals. Each education period lasted at most 5 minutes. The effectiveness was then evaluated using questionnaires and an asthma control test (ACT). Results: The study enrolled 144 patients (mean age, 56.7±16.7 years). Half of the patients had not been taught how to use their inhalers. After participating in the education program, the participants’ understanding of asthma improved significantly across all six items of a questionnaire assessing their general knowledge of asthma. The proportion of patients who made errors while manipulating their inhalers was reduced to less than 10%. The ACT score increased from 16.6±4.6 to 20.0±3.9 (p<0.001). The number of asthmatics whose ACT score was at least 20 increased from 45 (33.3%) to 93 (65.3%) (p<0.001). The magnitude of improvement in the ACT score did not differ between patients who received an education session at least three times within 1 year and those who had not. The majority of patients agreed to the need for an education program (95.8%) and showed a willingness to pay an additional cost for the education (81.9%). Conclusion: This study indicated that our newly developed education program would become an effective component of asthma management in primary care clinics.
Background: Although the World Health Organization (WHO) classification of lung squamous cell carcinoma (SCC) was revised in 2015, its clinical implications for lung SCC subsets remain unclear. We investigated whether the morphologic characteristics of lung SCC, including keratinization, were associated with clinical parameters and clinical outcome of patients. Methods: A total of 81 patients who underwent curative surgical resection of diagnosed lung SCC, were enrolled in this study. Attributes such as keratinization, tumor budding, single cell invasion, and nuclear size within the tumor, as well as immunohistochemistry of Bcl-xL and pS6 expressions, were evaluated. Results: The keratinizing and nonkeratinizing subtypes did not differ with respect to age, sex, TNM stage, and morphologic parameters such as nuclear diameter, tumor budding, and single cell invasion at the tumor edge. Most patients with the keratinizing subtype (98.0%) had a history of smoking, whereas the nonkeratinizing group had a relatively higher proportion of never-smokers relative to the keratinizing group (24.0% vs. 2.0%; p=0.008, chi-square test). Expression of pS6 (a surrogate marker of mammalian target of rapamycin complex 1 [mTORC1] signaling that regulates keratinocyte differentiation), and Bcl-xL (a key anti-apoptotic molecule that may inhibit keratinization), did not correlate significantly with the presence of keratinization. Patients with the keratinizing subtype had a significantly shorter overall survival (85.2 months vs. 135.7 months, p=0.010, log-rank test), and a multivariate analysis showed that keratinization was an independent, poor prognostic factor (hazard ratio, 2.389; 95% confidence interval, 1.090–5.233; p=0.030). Conclusion: In lung SCC, keratinization is associated with a poor prognosis, and might be associated with smoking.
Background: Third-generation tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have proved efficacious in treating non-small cell lung cancer (NSCLC) patients with acquired resistance resulting from the T790M mutation. However, since almost 50% patients with the acquired resistance do not harbor the T790M mutation, retreatment with first- or second-generation EGFR-TKIs may be a more viable therapeutic option. Here, we identified positive response predictors to retreatment, in patients who switched to a different EGFR-TKI, following initial treatment failure. Methods: This study retrospectively reviewed the medical records of 42 NSCLC patients with EGFR mutations, whose cancers had progressed following initial treatment with gefitinib or erlotinib, and who had switched to a different firstgeneration EGFR-TKI during subsequent retreatment. To identify high response rate predictors in the changed EGFR-TKI retreatment, we analyzed the relationship between clinical and demographic parameters, and positive clinical outcomes, following retreatment with EGFR-TKI. Results: Overall, 30 (71.4%) patients received gefitinib and 12 (28.6%) patients received erlotinib as their first EGFR-TKI treatment. Following retreatment with a different EGFR-TKI, the overall response and disease control rates were 21.4% and 64.3%, respectively. There was no significant association between their overall responses. The median progressionfree survival (PFS) after retreatment was 2.0 months. However, PFS was significantly longer in patients whose time to progression was ≥10 months following initial EGFR-TKI treatment, who had a mutation of exon 19, or whose treatment interval was <90 days. Conclusion: In patients with acquired resistance to initial EGFR-TKI therapy, switched EGFR-TKI retreatment may be a salvage therapy for individuals possessing positive retreatment response predictors.
Background: Medical thoracoscopy (MT) is a minimally invasive, endoscopic procedure for exploration of the pleural cavity under conscious sedation and local anesthesia. MT has been performed at the Seoul National University Hospital since February 2014. This paper summarizes the findings and outcomes of MT cases at this hospital. Methods: Patients who had undergone MT were enrolled in the study. MT was performed by pulmonologists, using both rigid and semi-rigid thoracoscopes. During the procedure, patients were under conscious sedation with fentanyl and midazolam. Medical records were reviewed for clinical data. Results: From February 2014 to January 2016, 50 procedures (47 cases) were performed (diagnostic MT, 26 cases; therapeutic MT, 24 cases). The median age of patients was 66 years (59–73 years), and 38 patients (80.9%) were male. The median procedure duration from initial incision to insertion of the chest tube was 37 minutes. The median doses of fentanyl and midazolam were 50 μg and 5 mg, respectively. All procedures were performed without unexpected events. Of the 26 cases of pleural disease with an unknown cause, 19 were successfully diagnosed using MT. Additionally, diagnostic MT provided clinically useful information in the other six patients. Therapeutic MT was very effective for treatment of malignant pleural effusion or empyema. The median number of days with chest tube drainage was 6 (3 days for diagnostic MT and 8 days for therapeutic MT). Conclusion: MT is a useful and necessary procedure for both diagnosis and treatment of pleural diseases.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) infection is a severe and life-threatening disease in patients with community-onset (CO) pneumonia. However, the current guidelines lack specificity for a screening test for MRSA infection. Methods: This study was retrospectively conducted in elderly patients aged ≥65 years, who had contracted COpneumonia during hospitalization at the Jeju National University Hospital, between January 2012 and December 2014. We analyzed the risk factors of MRSA in these patients and developed a scoring system to predict MRSA infection. Results: A total of 762 patients were enrolled in this study, including 19 (2.4%) with MRSA infection. Healthcareassociated pneumonia (HCAP) showed more frequent MRSA infection compared to community-acquired pneumonia (4.4% vs. 1.5%, respectively; p=0.016). In a multivariate logistic regression analysis, admissions during the influenza season (odds ratio [OR], 2.896; 95% confidence interval [CI], 1.022–8.202; p=0.045), chronic kidney disease (OR, 3.555; 95% CI, 1.157–10.926; p=0.027), and intensive care unit admission (OR, 3.385; 95% CI, 1.035–11.075; p=0.044) were identified as predictive factors for MRSA infection. However, the presence of HCAP was not significantly associated with MRSA infection (OR, 1.991; 95% CI, 0.720–5.505; p=0.185). The scoring system consisted of three variables based on the multivariate analysis, and showed moderately accurate diagnostic prediction (area under curve, 0.790; 95% CI, 0.680– 0.899; p<0.001). Conclusion: MRSA infection would be considered in elderly CO-pneumonia patients, with three risk factors identified herein. When managing elderly patients with pneumonia, clinicians might keep in mind that these risk factors are associated with MRSA infection, which may help in selecting appropriate antibiotics.