Comparison of the sputum microbiome between patients with stable nontuberculous mycobacterial pulmonary disease and patients requiring treatment.

BACKGROUND: We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics. METHODS: We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups. RESULTS: In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013). CONCLUSIONS: Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.

Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

Novel Artificial Intelligence-Based Technology to Diagnose Asthma Using Methacholine Challenge Tests.

PURPOSE: The methacholine challenge test (MCT) has high sensitivity but relatively low specificity for asthma diagnosis. This study aimed to develop and validate machine learning (ML) models to improve the diagnostic performance of MCT for asthma. METHODS: Data from 1,501 patients with asthma symptoms who underwent MCT between 2015 and 2020 were analyzed. The patients were grouped as either the training (80%, n = 1,265) and test sets (20%, n = 236) depending on the time of referral. The conventional model (provocative concentration that causes a 20% decrease in forced expiratory volume in one second [FEV1]; PC20 ≤ 16 mg/mL) was compared with the prediction models derived from five ML methods: logistic regression, support vector machine, random forest, extreme gradient boosting, and artificial neural network. The area under the receiver operator characteristic curves (AUROC) and area under the precision-recall curves (AUPRC) of each model were compared. The prediction models were further analyzed using different input combinations of FEV1, forced vital capacity (FVC), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) values obtained during MCT. RESULTS: In total, 545 patients (36.3%) were diagnosed with asthma. The AUROC of the conventional model was 0.856 (95% confidence interval [CI], 0.852-0.861), and the AUPRC was 0.759 (95% CI, 0.751-0.766). All the five ML prediction models had higher AUROC and AUPRC values than those of the conventional model, and random forest showed both highest AUROC (0.950; 95% CI, 0.948-0.952) and AUROC (0.909; 95% CI, 0.905-0.914) when FEV1, FVC, and FEF25%-75% were included as inputs. CONCLUSIONS: Artificial intelligence-based models showed excellent performance in asthma prediction compared to using PC20 ≤ 16 mg/mL. The novel technology could be used to enhance the clinical diagnosis of asthma.

Baseline Cohort Profile of the Korean Chronic Cough Registry: A Multicenter, Prospective, Observational Study.

PURPOSE: The Korean Chronic Cough Registry study was initiated to characterize patients with chronic cough (CC) and investigate their outcomes in real-world clinical practice. This report aims to describe the baseline cohort profile and study protocols. METHODS: This multicenter, prospective observational cohort study included newly referred CC patients and those already being treated for refractory or unexplained chronic cough (RUCC). Cough status was assessed using a visual analog scale, the Leicester Cough Questionnaire (LCQ), and the Cough Hypersensitivity Questionnaire (CHQ). RESULTS: A total of 610 patients (66.9% women; median age 59.0 years) were recruited from 18 centers, with 176 being RUCC patients (28.9%). The median age at CC onset was 50.1 years, and 94.4% had adult-onset CC (≥ 19 years). The median cough duration was 4 years. Compared to newly referred CC patients, RUCC patients had a longer cough duration (6.0 years vs. 3.0 years) but had fewer symptoms and signs suggesting asthma, rhinosinusitis, or gastroesophageal acid reflux disease. Subjects with RUCC had lower LCQ scores (10.3 ± 3.3 vs. 11.6 ± 3.6; P < 0.001) and higher CHQ scores (9.1 ± 3.9 vs. 8.4 ± 4.1; P = 0.024). There were no marked differences in the characteristics of cough between refractory chronic cough and unexplained chronic cough. CONCLUSIONS: Chronic cough typically develops in adulthood, lasting for years. Cough severity and quality of life impairment indicate the presence of unmet clinical needs and insufficient cough control in real-world clinical practice. Longitudinal follow-up is warranted to investigate the natural history and treatment outcomes.

Clinical Relevance of Staphylococcus aureus Nasal Colonization and Staphylococcal Enterotoxin-Specific IgE Sensitization in Late-Onset Asthma.

This prospective observational study examined whether Staphylococcus aureus (SA) nasal colonization and staphylococcal enterotoxin (SE)-specific IgE sensitization synergistically affect clinical outcomes of adults with late-onset asthma (onset age ≥ 40 years). Nasal swabs were taken to evaluate SA colonization. Serum SE-IgE level was measured. Subjects were classified into 4 groups according to SA colonization and SE-IgE sensitization positivity. Among 181 patients with late-onset asthma recruited, the proportions of SA/SE (‒/‒), SA/SE (+ /‒), SA/SE (‒/ +), and SA/SE (+ / +) were 33.7%, 15.5%, 28.2%, and 22.6%, respectively. Severe asthma was more frequent in the SA/SE (+ / +) group than in the SA/SE (‒/‒) group (41.5% vs. 13.1%). The relationship of SA/SE (+ / +) with severe asthma was significant in multivariate logistic regression (vs. SA/SE (‒/‒); adjusted odds ratio: 4.36; 95% confidence intervals: 1.50‒12.73; p = 0.007), whereas SA/SE (+ /‒) or SA/SE (‒/ +) was not. In conclusion, SA nasal colonization and SE-IgE sensitization may synergistically affect disease severity in late-onset asthmatics.

The lung microbiota in nontuberculous mycobacterial pulmonary disease.

BACKGROUND: The role of bacterial microbiota in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is unclear. We aimed to compare the bacterial microbiome of disease-invaded lesions and non-invaded lung tissue from NTM-PD patients. METHODS: We analyzed lung tissues from 23 NTM-PD patients who underwent surgical lung resection. Lung tissues were collected in pairs from each patient, with one sample from a disease-involved site and the other from a non-involved site. Lung tissue microbiome libraries were constructed using 16S rRNA gene sequences (V3-V4 regions). RESULTS: Sixteen (70%) patients had Mycobacterium avium complex (MAC)-PD, and the remaining seven (30%) had Mycobacterium abscessus-PD. Compared to non-involved sites, involved sites showed greater species richness (ACE, Chao1, and Jackknife analyses, all p = 0.001); greater diversity on the Shannon index (p = 0.007); and genus-level differences (Jensen-Shannon, PERMANOVA p = 0.001). Analysis of taxonomic biomarkers using linear discriminant analysis (LDA) effect sizes (LEfSe) demonstrated that several genera, including Limnohabitans, Rahnella, Lachnospira, Flavobacterium, Megamonas, Gaiella, Subdoligranulum, Rheinheimera, Dorea, Collinsella, and Phascolarctobacterium, had significantly greater abundance in involved sites (LDA >3.00, p <0.05, and q <0.05). In contrast, Acinetobacter had significantly greater abundance at non-involved sites (LDA = 4.27, p<0.001, and q = 0.002). Several genera were differentially distributed between lung tissues from MAC-PD (n = 16) and M. abscessus-PD (n = 7), and between nodular bronchiectatic form (n = 12) and fibrocavitary form (n = 11) patients. However, there was no genus with a significant q-value. CONCLUSIONS: We identified differential microbial distributions between disease-invaded and normal lung tissues from NTM-PD patients, and microbial diversity was significantly higher in disease-invaded tissues. TRIAL REGISTRATION: Clinical Trial registration number: NCT00970801.

Health-Related Quality of Life and Its Determinants in Chronic Cough: The Korean Chronic Cough Registry Study.

PURPOSE: Chronic cough (CC) is associated with health-related quality of life (HRQoL) impairment. However, the determinants of HRQoL are under-investigated. METHODS: Patients aged 19-80 years with CC were prospectively recruited from 10 referral clinics. Comparisons were made with age- and sex-matched controls (1:4 ratio) selected from a Korean general population survey database; 1) a group without current cough (non-cough controls) and 2) another group without major chronic illnesses (healthy controls). HRQoL was assessed using the EuroQoL 5-dimension (EQ-5D) index. In CC patients, cough-specific patient-reported outcomes (PROs) were additionally measured. Cross-sectional analyses were performed to evaluate demographic and clinical parameters associated with the EQ-5D index of CC patients. RESULTS: A total of 200 CC patients (137 newly referred with CC and 63 refractory or unexplained CC [RUCC] patients), 800 non-cough controls, and 799 healthy controls were analyzed. The EQ-5D index of CC patients was significantly lower than that of non-cough controls or healthy controls (0.82 ± 0.14 vs 0.92 ± 0.14/0.96 ± 0.08; P < 0.001, respectively). The index was also associated with older age (≥ 60 years), female sex, and comorbidities such as asthma or depression. Among the patients with CC, the index was significantly lower in patients with RUCC than in those with newly referred CC, being treated with codeine or cough neuromodulators, or with cough-related fatigue. In Spearman analyses, the EQ-5D index correlated with cough-specific quality of life and cough severity scores, not with throat sensation or cough trigger scores. CONCLUSIONS: The HRQoL impairment of CC patients was associated with older age, female sex, and comorbidities but it was also affected by cough severity, complications, treatments, and treatment responses. Longitudinal studies are warranted to further understand and improve the HRQoL of CC patients.

Giant Coronary Artery Aneurysm with Thrombosis Complicated in a Patient with Idiopathic Hypereosinophilic Syndrome.

Idiopathic hypereosinophilic syndrome (iHES) is a rare systemic disease that is characterized by persistent peripheral eosinophilia (absolute eosinophil count ≥1500/uL) for more than 6 months, with end-organ damage and absence of a primary cause for eosinophilia. Coronary artery aneurysm (CAA) is a rare but life-threatening complication. Here, we report a case of CAA with thrombosis in a patient with iHES in whom the disease activity was well-controlled (eosinophil count <500/uL) for several years. Despite modest control of the disease activity, giant CAA can be associated with iHES; and therefore, close surveillance and monitoring for the development of complications is warranted.

Deep learning analysis to predict EGFR mutation status in lung adenocarcinoma manifesting as pure ground-glass opacity nodules on CT.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) showed potency as a non-invasive therapeutic approach in pure ground-glass opacity nodule (pGGN) lung adenocarcinoma. However, optimal methods of extracting information about EGFR mutation from pGGN lung adenocarcinoma images remain uncertain. We aimed to develop, validate, and evaluate the clinical utility of a deep learning model for predicting EGFR mutation status in lung adenocarcinoma manifesting as pGGN on computed tomography (CT). Methods: We included 185 resected pGGN lung adenocarcinomas in the primary cohort. The patients were divided into training (n = 125), validation (n = 23), and test sets (n = 37). A preoperative CT-based deep learning model with clinical factors as well as clinical and radiomics models was constructed and applied to the test set. We evaluated the clinical utility of the deep learning model by applying it to 83 GGNs that received EGFR-TKI from an independent cohort (clinical validation set), and treatment response was regarded as the reference standard. Results: The prediction efficiencies of each model were compared in terms of area under the curve (AUC). Among the 185 pGGN lung adenocarcinomas, 122 (65.9%) were EGFR-mutant and 63 (34.1%) were EGFR-wild type. The AUC of the clinical, radiomics, and deep learning with clinical models to predict EGFR mutations were 0.50, 0.64, and 0.85, respectively, for the test set. The AUC of deep learning with the clinical model in the validation set was 0.72. Conclusions: Deep learning approach of CT images combined with clinical factors can predict EGFR mutations in patients with lung adenocarcinomas manifesting as pGGN, and its clinical utility was demonstrated in a real-world sample.

Intractable middle ear effusion in EGPA patients might cause permanent hearing loss: a case-control study.

BACKGROUND: Ear, nose, and throat involvement are common in eosinophilic granulomatosis with polyangiitis (EGPA). Among otologic manifestation, middle ear effusion (MEE) is less recognized but a problematic condition as it may progress to hearing impairment when left untreated. This study aimed to evaluate the characteristics, risk factors and clinical outcomes of MEE in EGPA patients. METHODS: This is a case-control study of patients who were diagnosed and treated for EGPA from January 1995 to November 2018. Patients with ear symptoms (ear fullness, ear discharge, tinnitus or hearing loss) were assessed by otologists and were included in the case group (n = 23) if clinically relevant. The other patients without MEE were included in the control group (n = 52). Risk of MEE was calculated using the Cox proportional-hazard model. RESULTS: During median follow-up of 9.9 years, 23 (30.7%) out of 75 patients had MEE. In MEE group, 12 (52.2%) patients had hearing loss; conductive type in 10 (10/12, 83.3%) and mixed type in two (2/12, 16.7%). In multivariable regression analysis, major organ involvement at diagnosis (adjusted hazard ratio [aHR] 65.4; 95% confidence interval [CI], 1.50-2838.39; P = 0.030] , early onset of ear symptom after systemic therapy (< 6 months) (aHR 40.0; 95% CI, 1.35-1183.43; P = 0.033) and continuing the maintenance steroid without cessation (aHR 8.59; 95% CI, 1.13-65.42; P = 0.038) were independently associated with a risk of MEE. To control MEE, 16 (69.6%) patients had to increase maintenance steroid dose and 9 (39.1%) patients experienced recurrent MEE whenever maintenance dose was tapered. CONCLUSIONS: MEE is a common but frequently neglected condition in EGPA which is often intractable. The maintenance steroid dose should be adequately adjusted to control MEE and to prevent from progressive hearing loss. Novel biologic agents possibly have a role in controlling MEE in EGPA.

Cut-off value for exercise-induced bronchoconstriction based on the features of the airway obstruction.

The current cut-off value for diagnosing exercise-induced bronchoconstriction (EIB) in adults-percent fall in FEV1 (ΔFEV1) ≥ 10% after exercise challenge test (ECT)-has low specificity and weak evidences. Therefore, this study aimed to identify the cut-off value for EIB that provides the highest diagnostic sensitivity and specificity. Participants who underwent the ECT between 2007 and 2018 were categorized according to ΔFEV1: definite EIB (ΔFEV1 ≥ 15%), borderline (10% ≤ ΔFEV1 < 15%), and normal (ΔFEV1 < 10%). Distinct characteristics of the definite EIB group were identified and explored in the borderline EIB group. A receiver operating characteristic curve was plotted to determine the optimal cut-off value. Of 128 patients, 60 were grouped as the definite EIB group, 23 as the borderline group, and 45 as the normal group. All participants were men, with a median age of 20 years (interquartile range [IQR:] 19-23 years). The definite EIB group exhibited wheezing on auscultation (P < 0.001), ΔFEV1/FVC ≥ 10% (P < 0.001), and ΔFEF25-75% ≥ 25% (P < 0.001) compared to other groups. Eight (8/23, 34.8%) patients in the borderline group had at least one of these features, but the trend was more similar to that of the normal group than the definite EIB group. A cut-off value of ΔFEV1 ≥ 13.5% had a sensitivity of 98.5% and specificity of 93.5% for EIB. Wheezing on auscultation, ΔFEV1/FVC ≥ 10%, and ΔFEF25-75% ≥ 25% after ECT may be useful for the diagnosis of EIB, particularly in individuals with a ΔFEV1 of 10-15%. For EIB, a higher cut-off value, possibly ΔFEV1 ≥ 13.5%, should be considered as the diagnostic criterion.

On-Site Deployment of an Air-Liquid-Interphase Device to Assess Health Hazard Potency of Airborne Workplace Contaminants: The Case of 3-D Printers.

Biomonitoring of workers is an approach of evaluating workers' exposure to chemicals and particulate matter by measuring biomarkers of parent chemicals, their metabolites, and reaction products in workers' biospecimens. Prerequisites for biological monitoring in the workplace include permission to enter the workplace, approval of the study plan from the IRB (Institutional Review Board), and obtaining consent from workers. Because of the complex legal process involved in biomonitoring, few studies have been conducted so far on biomonitoring of workers' exposures to nanoparticles and other hazards from emerging materials and advanced nanotechnologies. We have developed a cell-based biomonitoring device that can evaluate acute cytotoxicity and various other effect biomakers, such as inflammation, at realistic workplace exposure. This device is based on air-liquid interphase (ALI) and can be used to evaluate cell toxicity and early effect biomarkers along adverse outcome pathways. Following exposure of A549 lung epithelial cells in ALI to workplace air for 1-2 h, the cells were processed to assess the induction of inflammatory and cell damage biomarkers. Initially, we estimated the deposition rate of nanoparticles in the transwell by exposing the cell-free ALI device to silver nanoparticle aerosols (AgNP 20-30 nm) for 2 h in the laboratory. Then A549 lung epithelial cells cultured on the transwell in the ALI device were exposed to AgNP nanoaerosols for 2 h and evaluated for cytotoxicity and induction of mRNAs of pro-inflammatory cytokines IL-1b, IL-6, and TNF-α. Then the cells in the ALI device were exposed to 3-D printer emissions at the workplace and evaluated for the same matched endpoints. The mRNA levels for IL-1b, IL-6, and TNF-α increased significantly at the end of 2-h exposure of A549 cells to the positive control AgNP aerosols. These mRNAs, as well as LDH and microprotein concentrations, increased even more after 24-h post-exposure incubation (p < 0.05). Cytotoxicity evaluation of 3-D printer emissions at 810 and 957 µg/m3, which was more than 80 times higher than the airborne total suspended particulate concentrations in the workplace air (9-12.5 µg/m3), suggested no significant acute cytotoxicity at the end of 2-h exposure to 3-D-printing emission, as well as at 24-h post-exposure incubation. Hyperspectral microscopic observation showed that 3-D printers emitted particles to be attached to A549 cells after 2-h exposure, and many particles were internalized by A549 cells after 24 h of post-exposure incubation. The mRNA expression of pro-inflammatory cytokine IL-1b and IL-6 increased significantly after 2-h exposure to 3-D printer emissions and after 24-h incubation (only IL-6). In contrast, the expression of TNF-α mRNA decreased significantly after 2 h of exposure to 3-D printers and decreased even more after 24-h post-exposure incubation. These results support the use of cell-based ALI devices for direct assessment of airborne hazards in the workplace, for probing toxicological properties of airborne contaminants using adverse molecular pathways, and for guiding study design for workplace biomonitoring. ALI devices can bridge conventional exposure assessment with cellular toxicity testing platforms for hazard and risk assessment.

The Impact of EGFR Tyrosine Kinase Inhibitor on the Natural Course of Concurrent Subsolid Nodules in Patients with Non-Small Cell Lung Cancer.

PURPOSE: The role of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the management of persistent subsolid nodules (SSNs) is unclear. This study aimed to investigate the impact of EGFR-TKIs on concurrent SSNs in patients with stage IV non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients who received an EGFR-TKI for at least 1 month for stage IV NSCLC and had concurrent SSN(s) that had existed for at least 3 months on chest computed tomography were included in this retrospective study. Size change of each nodule before and after EGFR-TKI therapies were evaluated using a cutoff value of 2 mm; increase (≥ 2 mm), decrease (≤ -2 mm), and no change (-2 mm < size change < +2 mm). RESULTS: A total of 77 SSNs, 51 pure ground-glass (66.2%) and 26 part-solid nodules (33.8%), were identified in 59 patients who received gefitinib (n=45) and erlotinib (n=14). Among 58 EGFR mutation analysis performed for primary lung cancer, 45 (77.6%) were EGFR mutant. The proportions of decrease group were 19.5% (15/77) on per-nodule basis and 25.4% (15/59) on per-patient basis. Four SSNs (5.2%) disappeared completely. On per-patient based multivariable analysis, EGFR exon 19 deletion positivity for primary lung cancer was associated with a decrease after initial EGFR-TKI therapy (adjusted odds ratio, 4.29; 95% confidence interval, 1.21 to 15.29; p=0.025). CONCLUSION: Approximately 20% of the concurrent SSNs decreased after the initial EGFR-TKI therapy. EGFR exon 19 deletion positivity for primary lung cancer was significantly associated with the size change of concurrent SSNs.

Infectious complications of EBUS-TBNA: A nested case-control study using 10-year registry data.

OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become a standard procedure, but little is known about its infectious complications. The aim of this study is to evaluate the incidence and risk factors of infectious complications of EBUS-TBNA and its clinical course, including effects on anti-cancer treatment. METHODS: This is a nested case-control study of patients who received EBUS-TBNA and were followed for at least 2 months at Samsung Medical Center from August 2009 to April 2019. Patients with clinical symptoms of infection and correlating chest images were defined as the infection group (n = 33). The controls were randomly selected from patients without infectious complication. Multivariate logistic regression with backward selection was used to identify the risk factors of infectious complications. RESULTS: Of the 6826 patients, 33 (0.48%) infectious complications were identified, comprising pneumonia (n = 20) and mediastinal infections (n = 13). Target lesions with necrotic features on chest computed tomography (CT) scan (adjusted odds ratio [aOR], 3.08; 95% confidence interval [CI], 1.49-6.40; P = 0.002) and procedures that were performed via the esophagus (aOR, 3.19; 95% CI, 1.47-6.88; P = 0.003) were independently associated with infectious complications. Among patients ultimately diagnosed with cancer, the infection group tended to refuse anti-cancer treatment compared to controls (32/459, 7.0% vs. 5/30, 16.7%; P = 0.066). However, among the patients who received anti-cancer treatment, there was no delay in onset of treatment. CONCLUSIONS: Infectious complications of EBUS-TBNA are rare; however, attention should be paid if the target lesion appears necrotic on chest CT or if the procedure is performed via the esophagus. Although it was not conclusive due to its rarity, patients with infectious complications tended not to receive anti-cancer treatment.

Clinical Characteristics of COPD Patients According to COPD Assessment Test (CAT) Score Level: Cross-Sectional Study.

PURPOSE: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is widely used to assess the impact of COPD symptoms on health status. Whilst the CAT consists of eight different items, details on the distribution of each item are limited. This study aimed to investigate the distribution and clinical implication of each CAT item, stratified by CAT severity group, in stable COPD patients. PATIENTS AND METHODS: This was a cross-sectional study at a single referral hospital in South Korea. Spirometry confirmed COPD patients with CAT measured at the first clinical visit were retrospectively identified. Patients were categorized into three groups: low (0 ≤ CAT < 10), medium (10 ≤ CAT < 20), and high (20 ≤ CAT ≤ 40) impact group. For the purpose of this analysis, the first four items (cough, sputum, chest tightness, and dyspnea) and the remaining four items (activities, confidence, sleep and energy) were also grouped as "pulmonary" and "extra-pulmonary", respectively. RESULTS: A total of 815 patients were included, and mean (SD) forced expiratory volume in 1 s (FEV1) was 62.8 (17.4) % pred. Among them, 300 patients (36.8%) were in the high impact group and had a greater exacerbation history and lower lung function. The proportion of "extra-pulmonary" items score was greater in patients with higher total CAT scores, with the activity and confidence items showing higher scores. CONCLUSION: In our study, in addition to dyspnea, activity limitation is a particular problem in individual patients with higher CAT total scores, for which physicians need to pay more attention. Our study suggests that whilst CAT total score captures the overall impact of COPD, each item of the CAT contains potentially useful information in understanding the patient's symptom burden.

Favorable Response to Long-Term Azithromycin Therapy in Bronchiectasis Patients with Chronic Airflow Obstruction Compared to Chronic Obstructive Pulmonary Disease Patients without Bronchiectasis.

PURPOSE: Long-term macrolide treatment is recommended for patients with chronic obstructive pulmonary disease (COPD) with frequent exacerbations. Bronchiectasis is a common comorbid condition in patients with COPD, for which long-term azithromycin is effective in preventing exacerbation. This study aimed to compare the effect of long-term azithromycin between bronchiectasis patients with chronic airflow obstruction (CAO) and COPD patients without bronchiectasis. PATIENTS AND METHODS: Patients with CAO who received azithromycin for more than 12 weeks were retrospectively identified at a single referral hospital. CAO was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7, and bronchiectasis was determined using computed tomography. The development of exacerbation and symptom improvement were compared between bronchiectasis patients with CAO and COPD patients without bronchiectasis. RESULTS: A total of 59 patients (43 in bronchiectasis with CAO group vs 16 in COPD without bronchiectasis group) were included in this study. Compared to COPD patients without bronchiectasis, those in bronchiectasis with CAO group were younger, more likely to be female, and never smokers. There was no difference in the previous exacerbation history or FEV1 between the two groups. The median duration of azithromycin treatment was 15 months (interquartile range, 8-25 months). At the 12-month follow-up, the development of ≥2 moderate or ≥1 severe exacerbations was significantly lower in bronchiectasis with CAO group than in COPD without bronchiectasis group (46.5% vs 87.5%, P = 0.005). The proportion of patients with symptom improvement determined by the COPD assessment test score was also significantly higher in bronchiectasis with CAO group than COPD without bronchiectasis group at the 12-month follow-up (68.2% vs 16.7%, P = 0.004). CONCLUSION: Bronchiectasis patients with CAO could benefit more from long-term azithromycin treatment than COPD patients without bronchiectasis.

Outcomes of Inhaled Amikacin-Containing Multidrug Regimens for Mycobacterium abscessus Pulmonary Disease.

BACKGROUND: Mycobacterium abscessus pulmonary disease (M abscessus-PD) is challenging to treat because of its resistance to antibiotics. RESEARCH QUESTION: What are the outcomes of treatment-naive patients with M abscessus-PD treated with inhaled amikacin-containing multidrug regimens? STUDY DESIGN AND METHODS: We identified 82 treatment-naive patients with M abscessus-PD from a prospective observational cohort treated with regimens containing inhaled amikacin with or without clofazimine between March 2015 and June 2018 (ClinicalTrials.gov identifier: NCT00970801). During the initial phase, all patients received IV amikacin, imipenem (or cefoxitin), and oral azithromycin. Oral clofazimine was added in cases of (1) M abscessus subspecies abscessus (here M abscessus) or (2) M abscessus subspecies massiliense (here M massiliense) with cavitary lesions. During the continuation phase, amikacin was changed from an injectional to inhalational form. RESULTS: Of 82 patients, 46 (56%) had M massiliense-PD and 36 (44%) had M abscessus-PD. Among 59 patients with nodular bronchiectatic disease (72%), 23 of 59 had a concurrent cavitary lesion. The remaining 23 patients (28%) had fibrocavitary disease. Twelve months after treatment initiation, cure was achieved in 53 patients (65%): 42 of 46 patients (91%) with M massiliense-PD and 11 of 36 patients (31%) with M abscessus-PD (P < .001). Symptomatic and radiologic improvements were observed in 72 patients (88%) and 64 patients (78%), respectively, with significantly greater improvement in patients with M massiliense-PD (symptom improvement, 96% vs 78% [P = .047]; improvement on CT scanning, 93% vs 61% [P = .002]). INTERPRETATION: Inhaled amikacin with or without clofazimine in the regimen provides favorable treatment outcomes in M massiliense-PD. However, more effective treatments are needed for M abscessus-PD.

Assessment and Mitigation of Exposure of 3-D Printer Emissions.

This study monitored particulates, and volatile organic compounds (VOCs) emitted from 3-D printers using acrylonitrile-butadiene-styrene copolymer (ABS) filaments at a workplace to assess exposure before and after introducing exposure mitigation measures. Air samples were collected in the printing room and adjacent corridor, and real-time measurements of ultrafine and fine particle were also conducted. Extensive physicochemical characterizations of 3-D printer emissions were performed, including real-time (size distribution, number concentration) nanoparticle characterization, size-fractionated mass distribution and concentration, as well as chemical composition for metals by ICP-MS and VOCs by GC-FID, real-time VOC monitors, and proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS). Air sampling showed low levels of total suspended particulates (TSP, 9-12.5/m3), minimal levels (1.93-4 ppm) of total volatile organic chemicals (TVOC), and formaldehyde (2.5-21.7 ppb). Various harmful gases, such as formaldehyde, acrolein, acetone, hexane, styrene, toluene, and trimethylamine, were detected at concentrations in the 1-100 ppb by PTR-TOF-MS when air sample was collected into the Tedlar bag from the front of the 3-D printer. Ultrafine particles having an average particle size (30 nm count median diameter and 71 nm mass median diameter) increased during the 3-D printing operation. They decreased to the background level after the 3-D printing operation, while fine particles continually increased after the termination of 3-D printing to the next day morning. The exposure to 3-D printer emissions was greatly reduced after isolating 3-D printers in the enclosed space. Particle number concentration measured by real-time particle counters (DMAS and OPC) were greatly reduced after isolating 3-D printers to the isolated place.