Risk adjustment model for tuberculosis compared to non-tuberculosis mycobacterium or latent tuberculosis infection: Center for Personalized Precision Medicine of Tuberculosis (cPMTb) cohort database.

BACKGROUND: The Center for Personalized Precision Medicine of Tuberculosis (cPMTb) was constructed to develop personalized pharmacotherapeutic systems for tuberculosis (TB). This study aimed to introduce the cPMTb cohort and compare the distinct characteristics of patients with TB, non-tuberculosis mycobacterium (NTM) infection, or latent TB infection (LTBI). We also determined the prevalence and specific traits of polymorphisms in N-acetyltransferase-2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) phenotypes using this prospective multinational cohort. METHODS: Until August 2021, 964, 167, and 95 patients with TB, NTM infection, and LTBI, respectively, were included. Clinical, laboratory, and radiographic data were collected. NAT2 and SLCO1B1 phenotypes were classified by genomic DNA analysis. RESULTS: Patients with TB were older, had lower body mass index (BMI), higher diabetes rate, and higher male proportion than patients with LTBI. Patients with NTM infection were older, had lower BMI, lower diabetes rate, higher previous TB history, and higher female proportion than patients with TB. Patients with TB had the lowest albumin levels, and the prevalence of the rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 39.2%, 48.1%, and 12.7%, respectively. The prevalence of rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 42.0%, 44.6%, and 13.3% for NTM infection, and 42.5%, 48.3%, and 9.1% for LTBI, respectively, which did not differ significantly from TB. The prevalence of the normal, intermediate, and lower transporter SLCO1B1 phenotypes in TB, NTM, and LTBI did not differ significantly; 74.9%, 22.7%, and 2.4% in TB; 72.0%, 26.1%, and 1.9% in NTM; and 80.7%, 19.3%, and 0% in LTBI, respectively. CONCLUSIONS: Understanding disease characteristics and identifying pharmacokinetic traits are fundamental steps in optimizing treatment. Further longitudinal data are required for personalized precision medicine. TRIAL REGISTRATION: This study registered ClinicalTrials.gov NO. NCT05280886.

Association of Underlying Comorbidities and Sites of tuberculosis: an analysis using surveillance data.

BACKGROUND: Tuberculosis (TB) is a highly heterogeneous disease that can affect any organ. Extrapulmonary TB (EPTB) is more difficult to diagnose due to various clinical presentations. Depending on the characteristics of the patient, the involved site of TB may vary. However, data on clinical characteristics of EPTB are inconsistent and insufficient. This study aimed to identify the characteristics of patients with pulmonary TB (PTB) and EPTB and describe characteristic differences for each involved site. METHODS: We systemically collected data of TB patients included in the national surveillance system in South Korea from July 2018 to June 2019 and compared the characteristics of patients with EPTB with that of PTB. RESULTS: A total of 7674 patients with a mean age of 60.9 years were included. Among them, 6038 (78.7%) patients were diagnosed with PTB and 1636 (21.3%) with EPTB. In PTB group, the mean age (61.7 ± 18.7 vs. 57.8 ± 19.9) and proportion of male sex (63.3% vs. 50.1%) were higher, but the body mass index was lower (21.2 ± 3.4 vs. 22.7 ± 3.5) than that of the EPTB group. Prevalence of diabetes (20.5% vs. 16.9%) and chronic lung disease (5.1% vs. 2.9%) were higher in PTB group, meanwhile, those of chronic kidney disease (CKD) (2.7% vs. 5.4%) and long-term steroid use (0.4% vs. 1.0%) were higher in EPTB group. Abdominal TB was more prevalent in patients with chronic liver disease (odds ratio [OR]: 2.69, 95% CI: 1.52-4.74), and urogenital TB was more prevalent in patients with CKD (OR: 2.75, 95% CI: 1.08-6.99). CONCLUSIONS: We found that underlying comorbidities were closely associated with the location of TB development, and therefore, the possibility of EPTB should be carefully evaluated while monitoring for underlying disease in TB-endemic areas.

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.

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.

Quantitative Assessment of Chest CT Patterns in COVID-19 and Bacterial Pneumonia Patients: a Deep Learning Perspective.

BACKGROUND: It is difficult to distinguish subtle differences shown in computed tomography (CT) images of coronavirus disease 2019 (COVID-19) and bacterial pneumonia patients, which often leads to an inaccurate diagnosis. It is desirable to design and evaluate interpretable feature extraction techniques to describe the patient's condition. METHODS: This is a retrospective cohort study of 170 confirmed patients with COVID-19 or bacterial pneumonia acquired at Yeungnam University Hospital in Daegu, Korea. The Lung and lesion regions were segmented to crop the lesion into 2D patches to train a classifier model that could differentiate between COVID-19 and bacterial pneumonia. The K-means algorithm was used to cluster deep features extracted by the trained model into 20 groups. Each lesion patch cluster was described by a characteristic imaging term for comparison. For each CT image containing multiple lesions, a histogram of lesion types was constructed using the cluster information. Finally, a Support Vector Machine classifier was trained with the histogram and radiomics features to distinguish diseases and severity. RESULTS: The 20 clusters constructed from 170 patients were reviewed based on common radiographic appearance types. Two clusters showed typical findings of COVID-19, with two other clusters showing typical findings related to bacterial pneumonia. Notably, there is one cluster that showed bilateral diffuse ground-glass opacities (GGOs) in the central and peripheral lungs and was considered to be a key factor for severity classification. The proposed method achieved an accuracy of 91.2% for classifying COVID-19 and bacterial pneumonia patients with 95% reported for severity classification. The CT quantitative parameters represented by the values of cluster 8 were correlated with existing laboratory data and clinical parameters. CONCLUSION: Deep chest CT analysis with constructed lesion clusters revealed well-known COVID-19 CT manifestations comparable to manual CT analysis. The constructed histogram features improved accuracy for both diseases and severity classification, and showed correlations with laboratory data and clinical parameters. The constructed histogram features can provide guidance for improved analysis and treatment of COVID-19.

Clinical Role of the Chronic Obstructive Pulmonary Disease Assessment Test in Prediction of the Response to Treatment for Exacerbations.

BACKGROUND: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a validated, eight-item questionnaire used to quantify the health status of patients. The aim of this study was to evaluate the usefulness of the CAT questionnaire as a tool to assess the response to treatment in acute exacerbations of COPD in an outpatient setting. METHODS: A multicenter, phase 3 randomized controlled trial was conducted previously to examine the efficacy and safety of oral zabofloxacin for the treatment of COPD exacerbations. In the present post hoc analysis of the original study, patients with COPD exacerbation were categorized as responders or non-responders according to the respiratory symptoms persisting on day 10 (visit 3) of treatment. The CAT questionnaire was completed daily by patients at home from the initial visit to the second visit on day 5. Subsequently, the questionnaire was completed in the presence of a physician on days 10 (visit 3) and 36 (visit 4). Multivariate regression analysis was performed to determine the association between CAT scores and the therapeutic response. RESULTS: The CAT scores decreased more rapidly in responders compared to non-responders during the first 5 days (23.3-20.4 vs. 23.5-22). Among responders, patients with higher severity of illness also revealed higher CAT scores on the first day of an exacerbation (mild, 19.8; moderate, 21.4; severe, 23.8; very severe, 28.6). Multivariate analysis revealed that a change in the CAT score during the first 3 days influenced the therapeutic response. A significant decrease in scores in the domains of sputum production, chest tightness, and activities of daily living was seen among responders. CONCLUSION: Early improvement in CAT scores may be associated with a more favorable response to the treatment of COPD exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01658020. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0000532.

Clinical profiles of early and tuberculosis-related mortality in South Korea between 2015 and 2017: a cross-sectional study.

BACKGROUND: Although the incidence of tuberculosis (TB) has decreased in South Korea, the mortality rate remains high. TB mortality is a key indicator for TB control interventions. The purpose of this study was to assess early and TB-related mortality during anti-TB treatment and describe the associated clinical characteristics. METHODS: A multicenter cross-sectional study was performed across South Korea. Patients with pulmonary TB who died during anti-TB treatment and whose records were submitted to the national TB surveillance system between 2015 and 2017 were enrolled. All TB deaths were categorized based on cause (TB-related or non-TB-related) and timing (early or late). We identified statistical associations using the frequency table, chi-square test, and binary logistic regression. RESULTS: Of 5595 notifiable mortality cases, 3735 patients with pulmonary TB were included in the analysis. There were 2541 (68.0%) male patients, and 2935 (78.6%) mortality cases were observed in patients older than 65 years. There were 944 (25.3%) cases of TB-related death and 2545 (68.1%) cases of early death. Of all cases, 187 (5.0%) patients were diagnosed post-mortem and 38 (1.0%) patients died on the first day of treatment. Low body mass index (adjusted odds ratio (aOR) = 1.26; 95% confidence interval (CI) = 1.08-1.48), no reported illness (aOR = 1.36; 95% CI = 1.10-1.68), bilateral disease on chest X-ray (aOR = 1.30; 95% CI = 1.11-1.52), and positive acid-fast bacilli smear result (aOR = 1.30; 95% CI = 1.11-1.52) were significantly associated with early death, as well as TB-related death. Acute respiratory failure was the most common mode of non-TB-related death. Malignancy was associated with both late (aOR = 0.71; 95% CI = 0.59-0.89) and non-TB-related (aOR = 0.35; 95% CI = 0.26-0.46) death. CONCLUSIONS: A high proportion of TB death was observed in elderly patients and attributed to non-TB-related causes. Many TB-related deaths occurred during the intensive phase, particularly within the first month. Further studies identifying risk factors for different causes of TB death at different phases of anti-TB treatment are warranted for early targeted intervention in order to reduce TB mortality.

Validation of Previous Spirometric Reference Equations and New Equations.

BACKGROUND: Pulmonary functions are interpreted using predicted values from reference equations that vary with ethnicity, gender, age, height, and weight. The universally used Choi's reference equations are not validated for Korean populations, and the purpose of this study was to validate them and develop new reference equations. METHODS: Subjects with normal spirometry and chest radiographs, no co-morbidities, and non-smokers, from the Korean National Health and National Examination Survey (KNHANES)-VI were enrolled (n = 117). Intraclass correlation coefficient (ICC) was assessed for reliability of reference equations. New reference equations were developed using linear regression analysis. Differences between observed and predicted values were assessed to compare the reference equations from Choi's, Global Lung Function Initiative 2012, KNHANES-IV, and newly developed equations. RESULTS: The ICC of Choi's reference equations was 0.854 (P < 0.001). The new reference equations for men were: forced vital capacity (FVC) (L) = - 4.38775 - 0.01184 × age + 0.05547 × height, forced expiratory volume - 1 second (FEV1) (L) = - 2.40147 - 0.02134 × age + 0.04103 × height; and for women: FVC (L) = - 3.09063 + 0.003904 × age + 0.038694 × height; FEV1 (L) = - 1.32933 - 0.00872 × age + 0.02762 × height. The differences between the predicted and observed means were largest in Choi's equations, but lowest in the new equations with highest goodness of fit. CONCLUSION: Because Choi's reference equations presented larger differences from the observed values, despite reliability, and the new reference equations showed better goodness of fit, we suggest the latter for Korean populations.

Association of physical and psychological health status between chronic obstructive pulmonary disease patients and their family caregivers.

We performed this cross-sectional study with 72 chronic obstructive pulmonary disease (COPD) patients and their family caregivers to analyze relationship of physical and psychological health status between COPD patients and caregivers. Most caregivers were female (100%). Caregiver depression and burden were significantly associated with caregiving hours. In path analysis, the higher the patient's social support, the higher the patient's self-efficacy. The higher the patient's self-efficacy, the lower the care burden of the caregiver. Based on our results, there was a significant correlation of physical and psychological factors between patients and family caregivers.

Which bronchodilator reversibility criteria can predict severe acute exacerbation in chronic obstructive pulmonary disease patients?

BACKGROUND: It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD). The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients. METHODS: Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study. The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS). The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models. RESULTS: Among a total of 854 patients, the BDR-positive cases varied according to the criteria used. There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria. Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15-0.93). This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants. CONCLUSIONS: Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients. Increase use of ICS/LABA may have affected this relationship.

Comparison of Korean COPD guideline and GOLD initiative report in term of acute exacerbation: a validation study for Korean COPD guideline.

The purpose of this study was to compare the Korean COPD guideline to GOLD consensus report in terms of acute exacerbation. A total of 361 patients were enrolled in this study, and 16.9% of them experienced acute exacerbation during the follow-up. A total of 6.3% of patients in GOLD A, 9.5% in GOLD B, 7.7% in GOLD C and 17.0% of GOLD D experienced exacerbation during the first year of follow-up, respectively (P=0.09). There was no one who experienced exacerbation during the first year of follow-up in the Korean group 'ga'. The 12-month exacerbation rates of Korean group 'na' and 'da' were 4.5% and 16.0%, respectively (P<0.001). We explore the experience of exacerbation in patients with change of their risk group after applying Korean COPD guideline. A total of 16.0% of the patients who were reclassified from GOLD A to Korean group 'da' experienced acute exacerbation,and 15.3% from GOLD B to Korean group 'da' experienced acute exacerbation. In summary, the Korean COPD guideline is useful to differentiate the high risk from low risk for exacerbation in terms of spirometry. This indicates that application of Korean COPD guideline is appropriate to treat Korean COPD patients.

Epidemiological aspects of pertussis among adults and adolescents in a Korean outpatient setting: a multicenter, PCR-based study.

Epidemiological data of Bordetella pertussis infection among adolescents and adults are limited in Korea. Patients (≥ 11 yr of age) with a bothersome cough for less than 30 days were enrolled during a 1-yr period at 22 hospitals in Korea. Nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and for bacteriologic culture. In total, 490 patients were finally enrolled, and 34 (6.9%) patients tested positive for B. pertussis; cough duration (14.0 days [7.0-21.0 days]) and age distribution were diverse. The incidence was the highest in secondary referral hospitals, compared to primary care clinics or tertiary referral hospitals (24/226 [10.6%] vs. 3/88 [3.4%] vs. 7/176 [4.0%], P = 0.012), and the peak incidence was observed in February and August (15.8% and 15.9%), with no confirmed cases between March and June. In the multivariate analysis, post-tussive vomiting was significantly associated with pertussis (odds ratio, 2.508; 95% confidence interval, 1.146-5.486) and secondary referral hospital showed a borderline significance. In conclusion, using a PCR-based method, 6.9% of adolescent and adult patients with an acute cough illness had pertussis infection in an outpatient setting. However, hospital levels and seasonal trends must be taken into account to develop a better strategy for controlling pertussis.

Durvalumab Consolidation After Chemoradiotherapy in Elderly Patients With Unresectable Stage III NSCLC: A Real-World Multicenter Study.

BACKGROUND: The PACIFIC trial demonstrated survival benefit of durvalumab after concurrent chemoradiotherapy (CCRT) in unresectable stage III non-small-cell lung cancer. Data on the effectiveness and safety of durvalumab in elderly patients is lacking. METHODS: This retrospective study was conducted between September 2017 and September 2022. Progression-free survival (PFS), overall survival (OS), recurrence patterns, first subsequent treatment after recurrence, factors associated with survival outcomes, and adverse events (AEs) were compared. RESULTS: Of the 286 patients, 120 (42.0%) were ≥ 70 years and 166 (58.0%) were < 70 years. The median PFS (17.7 vs. 19.4 months; P = .43) and median OS (35.7 months vs. not reached; P = .13) were similar between 2 groups. Proportion of patients who completed durvalumab was lower in elderly patients (27.5% vs. 39.2%; P = .040). In elderly patients, ECOG PS 0 or 1 was associated with better PFS, and being male and having received a cisplatin-based regimen during CCRT were factors associated with better and worse OS, respectively. In patients aged < 70 years, a PD-L1 ≥ 50% was associated with improved PFS and OS. Elderly patients experienced more treatment-related AEs, grade 3/4 AEs, permanent discontinuation of durvalumab, and treatment-related deaths. Among the AEs leading to permanent discontinuation or death, pulmonary AE was significantly more common in elderly patients. CONCLUSION: Durvalumab demonstrated similar outcomes in elderly compared to younger patients. However, AEs were more common in elderly patients. Thus, judicious selection of patients and chemotherapy regimens, coupled with careful AE monitoring, are important factors for ensuring optimal durvalumab treatment.

Efficacy and safety of mixture of ivy leaf extract and coptidis rhizome in the treatment of acute bronchitis: multicenter, randomized, double-blinded, active-controlled, parallel, therapeutic confirmatory clinical trial.

BACKGROUND: Acute bronchitis is the most common respiratory disease. Mixture of Ivy Leaf Extract and Coptidis rhizome syrup has shown good treatment efficacy against chronic bronchitis and acute respiratory infections. This study aimed to evaluate the efficacy and safety of Mixture of Ivy Leaf Extract and Coptidis rhizome compared with those of Pelargonium sidoides extract, for the treatment of acute bronchitis. METHODS: We performed a multicenter, randomized, double-blind, active-controlled, parallel phase III study in 220 patients with acute bronchitis. The participants were offered either Mixture of Ivy Leaf Extract and Coptidis rhizome syrup (AGS) and placebo of P. sidoides tablet or placebo syrup and active tablet of P. sidoides (AGU) for 7 days. The primary endpoint was the change in the Bronchitis Severity Score (BSS) from the baseline visit (visit 2) to day 7 (visit 3). RESULTS: For the primary outcome, there was no significant difference in the change of total BSS between visits 2 and 3 (-4.10 ± 1.93 vs. -4.24 ± 1.85, p = 0.5125), and since the upper limit of the confidence interval (1.00) was smaller than the predetermined non-inferiority margin (1.17), it was confirmed that the AGS group was non-inferior to the AGU group. The changes in each symptom in the BSS between visits 2 and 3 also showed no significant differences. The overall improvement rate measured by the investigator (91.7 vs. 89.7%; p = 0.3506) and the satisfaction rate of the participants at visit 3 also showed no significant differences (97.2 vs. 94.4%; p = 0.4388). Regarding safety issues, adverse reactions were noted in both groups similarly, with no serious adverse events (4.55 vs. 3.64%, p > 0.999). CONCLUSION: Mixture of Ivy Leaf Extract and Coptidis rhizome syrup is as effective and safe as P. sidoides in controlling symptoms of acute bronchitis.

Pulmonary Rehabilitation Is Associated With Decreased Exacerbation and Mortality in Patients With COPD: A Nationwide Korean Study.

BACKGROUND: Poor uptake to pulmonary rehabilitation (PR) is still challenging around the world. There have been few nationwide studies investigating whether PR impacts patient outcomes in COPD. We investigated the change of annual PR implementation rate, medical costs, and COPD outcomes including exacerbation rates and mortality between 2015 and 2019. RESEARCH QUESTION: Does PR implementation improve outcomes in patients with COPD in terms of direct cost, exacerbation, and mortality? STUDY DESIGN AND METHODS: Data of patients with COPD extracted from a large Korean Health Insurance Review and Assessment service database (2015-2019) were analyzed to determine the trends of annual PR implementation rate and direct medical costs of PR. Comparison of COPD exacerbation rates between pre-PR and post-PR, and the time to first exacerbation and mortality rate according to PR implementation, were also assessed. RESULTS: Among all patients with COPD in South Korea, only 1.43% received PR. However, the annual PR implementation rate gradually increased from 0.03% to 1.4% during 4 years, especially after health insurance coverage commencement. The direct medical cost was significantly higher in the PR group than the non-PR group, but the costs in these groups showed decreasing and increasing trends, respectively. Both the incidence rate and frequency of moderate-to-severe and severe exacerbations were lower during the post-PR period compared with the pre-PR period. The time to the first moderate-to-severe and severe exacerbations was longer in the PR group than the non-PR group. Finally, PR implementation was associated with a significant decrease in mortality. INTERPRETATION: We concluded that health insurance coverage increases PR implementation rates. Moreover, PR contributes toward improving outcomes including reducing exacerbation and mortality in patients with COPD. However, despite the well-established benefits of PR, its implementation rate remains suboptimal.

Pulmonary actinomycosis during the first decade of 21st century: cases of 94 patients.

BACKGROUND: Pulmonary actinomycosis is a chronic pulmonary infection caused by Actinomyces. Both improving oral hygiene and early application of antibiotics to the case of suspicious pulmonary infections result in changes in incidences and presentations of pulmonary actinomycosis. However, there are little reports dealt with the recent clinical characteristics of pulmonary actinomycosis. This study aimed to review the characteristics of pulmonary actinomycosis occurred during the first decade of 21st century. METHODS: This retrospective study was performed on 94 subjects with pulmonary actinomycosis diagnosed pathologically from January 2000 to December 2010 in 13 hospitals in Korea. RESULTS: The data of the study showed that pulmonary actinomycosis occurs frequently in middle to old-aged males (mean age; 57.7 years old) and that the most common symptoms are cough, hemoptysis, and sputum production. Various radiologic features such as the consolidation with central low attenuation (74.5%) and no regional predominance were also observed. Most of patients recovered completely with medical and/or surgical treatment, reaching approximately 98% cure rate. CONCLUSIONS: The results demonstrate that pulmonary actinomycosis is one of the cautious pulmonary diseases. More importantly, in cases of persistent hemoptysis or for differential diagnosis from lung malignancy, our data have revealed that surgical resection appears to be a useful intervention and that radiologic diagnosis may not provide decisive information. These findings indicate that it is important for the clinicians to include pulmonary actinomycosis as one of differential diagnoses for refractory pulmonary abnormal lesions to the current usual management.

Best immunohistochemical panel in distinguishing adenocarcinoma from squamous cell carcinoma of lung: tissue microarray assay in resected lung cancer specimens.

The emergence of the targeted therapies for non-small cell lung carcinoma (NSCLC) has generated a need for accurate histologic subtyping of NSCLC. In this study, we assessed the utility of immunohistochemical markers that could be helpful in distinction between adenocarcinoma (ADC) and squamous cell carcinoma (SCC). We performed a battery of immunohistochemistry using tissue microarray for napsin-A, Thyroid transcription factor 1 (TTF-1), p63, cytokeratin (CK) 5/6, thrombomodulin (CD141), Epithelial-related antigen (MOC-31), carcinoembryonic antigen (CEA), Cyclooxygenase 2 (COX-2), high-molecular-weight CK (HMWCK), p27kip1 (p27), and Rb protein in 129 resected primary NSCLC with 81 ADCs and 48 SCCs and 10 metastatic ADC to the lung (primary in colon, 7 cases; stomach, 2 cases; vagina, 1 case). Cases of ADC and SCC were morphologically unequivocal and solid tumors with no definite squamous or glandular differentiation were excluded for this analysis. Napsin-A and TTF-1 were positive in 81% and 70% of ADC and in 0% and 2% of SCC, respectively, whereas P63 and CK5/6 were positive in 91% and 90% of SCC and in 9% and 4% of ADC, respectively (P < .001). CD141 stained significantly higher in SCC over ADC (positive in 2% of ADC and 46% of SCC. MOC-31, CEA, COX-2, HMWCK, p27, and Rb appeared to be not useful markers in distinction between ADC and SCC because of their low specificity. None of metastatic ADC to the lung showed positive for napsin-A and TTF-1. It was evident that combination of napsin-A, TTF-1, CK5/6, and p63 was the best immunohistochemical panel in differentiating ADC from SCC of the lung in this study. CD141 appeared to be a potential new marker for SCC with high specificity. Cyclooxygenase 2, MOC-31, CEA, HMWCK, p27, and Rb showed less specificity for differentiation ADC from SCC.

Brain FDG PET for visualizing the relation between impaired lung function and cognitive decline in lung cancer: a preliminary study.

OBJECTIVE: Impaired lung function is associated with an increased risk for cognitive decline. F-18 fluorodeoxyglucose (FDG) PET is a well-known neurodegenerative biomarker for dementia. We investigated the association between lung and brain function using FDG PET in patients with lung cancer. METHODS: A random sub-sample of 102 patients with lung cancer and without a self-reported history of neuropsychiatric disorders were recruited and underwent both lung function tests and FDG PET scans before treatment. Lung function was analyzed as the percentage predicted value (% pred) of forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1). FDG uptake was measured as standardized uptake values (SUVs) in the frontal, parietal, temporal, and occipital cortices and cognition-related regions. Regional SUV ratios (SUVRs) were calculated by dividing the SUV in each region by the whole-brain SUV and were then evaluated against lung function indices and clinical variables. RESULTS: After excluding five patients with brain metastases, 97 patients were included in the final analysis (mean age, 67.7 ± 10.3 years). Mean FVC and mean FEV1 were 80.0% ± 15.4% and 77.6% ± 17.8%, respectively. Both FVC and FEV1 were positively correlated with SUVRs in all brain regions after adjusting the data for clinical variables. The degree of decrease in SUVRs related to lung function was not significantly different between cognition-related regions and other regions. CONCLUSION: Impaired lung function was associated with decreased glucose metabolism in all regions of the brain, indicating that cognitive decline related to decreased glucose metabolism may be due to reduced perfusion.

When is LABA/LAMA Better than LAMA in GOLD Group B or D Patients for Reducing Acute Exacerbations of COPD?

Long-acting ß2-agonist (LABA)/long-acting muscarinic-antagonist (LAMA) dual therapy has been found to be more effective than LAMA monotherapy in the treatment of chronic obstructive pulmonary disease (COPD). However, among patients with group B or D COPD, the characteristics of patients for whom LABA/LAMA dual therapy is superior to LAMA monotherapy in minimizing acute exacerbations remain unknown. With data from a prospective COPD cohort, subgroup analyses were conducted to determine whether LABA/LAMA dual therapy was superior to LAMA monotherapy in reducing the rate of acute exacerbations in group B and D COPD patients. Group B and D COPD patients taking LAMA or LABA/LAMA were enrolled according to the 2022 Global initiative for Chronic Obstructive Pulmonary Disease guidelines. A total of 737 patients were included in this study: 600 with group B COPD and 137 with group D COPD. Compared with patients taking LAMA monotherapy, those taking LABA/LAMA had a significantly lower incidence of acute exacerbations over 1 year. In the subgroup of patients ≥70 years old, there was a significantly lower risk of severe COPD exacerbations among group B patients taking LABA/LAMA than among those taking LAMA monotherapy (odds ratio [OR], 0.258; 95% confidence interval [CI], 0.095-0.703). In contrast, in the subgroup of group D patients with COPD Assessment Test scores ≥25, compared with LAMA monotherapy, LABA/LAMA treatment was associated with lower risk of severe COPD exacerbations (OR, 0.115; 95% CI, 0.018-0.749). The combination of LABA and LAMA was found to be superior to LAMA monotherapy, especially for treating older adults with group B COPD, as well as for group D patients with severe symptoms.