The association of blood eosinophil counts and FEV1 decline: a cohort study.

BACKGROUND: Accelerated lung function decline is characteristic of COPD. However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood. METHODS: This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used a linear mixed-effects model to estimate the annual change in forced expiratory volume in 1 s (FEV1) (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. In addition, we performed a stratified analysis by baseline and time-varying smoking status. RESULTS: During a mean follow-up of 6.5 years (maximum 17.8 years), the annual change in FEV1 (95% CI) in participants with eosinophil counts <100, 100-199, 200-299, 300-499 and ≥500 cells·µL-1 in the fully adjusted model were -23.3 (-23.9--22.7) mL, -24.3 (-24.9--23.7) mL, -24.8 (-25.5--24.2) mL, -25.5 (-26.2--24.8) mL and -26.8 (-27.7--25.9) mL, respectively. When stratified by smoking status, participants with higher eosinophil count had a faster decline in FEV1 than those with lower eosinophil count in both never- and ever-smokers, which persisted when time-varying smoking status was used. CONCLUSIONS: Higher blood eosinophil counts were associated with a faster lung function decline among healthy individuals without lung disease, independent of smoking status. The findings suggest that higher blood eosinophil counts contribute to the risk of faster lung function decline, particularly among younger adults without a history of lung disease.

Risk of incident chronic obstructive pulmonary disease during longitudinal follow-up in patients with nontuberculous mycobacterial pulmonary disease.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease 2023 revision proposed that chronic obstructive pulmonary disease (COPD) has various etiologies including infections (COPD-I), such as tuberculosis and human immunodeficiency virus. While nontuberculous mycobacterial pulmonary disease (NTM-PD) and pulmonary tuberculosis share similar clinical manifestations, research on COPD development during longitudinal follow-up in patients with NTM-PD is limited. In this study, we aimed to evaluate the incidence and risk of COPD development in patients with NTM-PD. METHODS: We retrospectively enrolled patients with NTM-PD with normal lung function and 1:4 age-, sex-, body mass index-, and smoking status-matched controls between November 1994 and January 2022. We compared the risks of spirometry-defined COPD between the NTM-PD and control groups (study 1). A nationwide cohort study using the health insurance claims database was conducted to validate the findings (study 2). RESULTS: In study 1, during a mean follow-up of 3.3 years, COPD occurred in 14.0% (241/1,715) and 4.3% (293/6,860) of individuals in the NTM-PD and matched control cohorts, respectively. The NTM-PD cohort exhibited a higher risk of incident COPD (adjusted hazard ratio [aHR], 2.57; 95% CI, 2.15-3.09) compared to matched controls. In study 2, COPD occurred in 6.2% (24/386) and 2.5% (28/1,133) of individuals with and without NTM-PD, respectively. The NTM-PD cohort had a higher risk of incident COPD (aHR, 2.04; 95% CI, 1.21-3.42) compared to matched controls. CONCLUSION: These findings suggest that NTM-PD could be considered a new etiotype of COPD-I and emphasize the importance of monitoring lung function in individuals with NTM-PD.

Impact of smoking reduction on lung cancer risk in patients with COPD who smoked fewer than 30 pack-years: a nationwide population-based cohort study.

BACKGROUND: The effects of smoking reduction on the incidence of lung cancer in patients with chronic obstructive pulmonary disease (COPD) are not well known. This study aimed to investigate the effects of changes in smoking habits after COPD diagnosis on lung cancer development in patients who smoked less than 30 pack-years. METHODS: This nationwide retrospective cohort study included 16,832 patients with COPD who smoked less than 30 pack-years at the time of COPD diagnosis. Based on changes in smoking habits in the health screening examination data, smokers were categorized into three groups: quitters, reducers, and sustainers. The primary outcome was the risk of lung cancer development, which was estimated using the Cox proportional hazards model. We also modelled the amount of smoking reduction as a continuous variable. RESULTS: During a median follow-up of 4 years, the cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters. Compared with sustainers, reducers (adjusted HR 0.74, 95% CI:0.56-0.98) and quitters (adjusted HR 0.78, 95% CI:0.64-0.96) had a significantly lower risk of lung cancer. Incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity < 0.01). CONCLUSIONS: In patients with COPD who smoked less than 30 pack-years, smoking reduction and cessation lowered the risk of lung cancer.

Features which discriminate between tuberculosis and haematologic malignancy as the cause of pleural effusions with high adenosine deaminase.

BACKGROUND: Adenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE). This study aimed to investigate the features that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L. METHODS: This was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the features associated with TBP and hMPE, respectively. RESULTS: Among 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 70 and 150 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95-4.95; P < 0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14-0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67-30.79; P < 0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD. A combination of lymphocytes ≥ 35%, LD/ADA < 18, and ADA < 150 IU/L demonstrated a sensitivity of 0.824 and specificity of 0.937 for predicting TBP. CONCLUSION: In patients with very high levels of pleural effusion ADA, hMPE should be considered. Several features in pleural effusion and serum may help to more effectively differentiate TBP from hMPE.

Longitudinal BMI change and outcomes in Chronic Obstructive Pulmonary Disease: a nationwide population-based cohort study.

BACKGROUND: The association between longitudinal body mass index (BMI) change and clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) has not fully investigated. METHODS: This retrospective cohort study included 116,463 COPD patients aged ≥ 40, with at least two health examinations, one within 2 years before and another within 3 years after COPD diagnosis (January 1, 2014, to December 31, 2019). Associations between BMI percentage change with all-cause mortality, primary endpoint, and initial severe exacerbation were assessed. RESULTS: BMI decreased > 5% in 14,728 (12.6%), while maintained in 80,689 (69.2%), and increased > 5% in 21,046 (18.1%) after COPD diagnosis. Compared to maintenance group, adjusted hazard ratio (aHR) for all-cause mortality was 1.70 in BMI decrease group (95% CI:1.61, 1.79) and 1.13 in BMI increase group (95% CI:1.07, 1.20). In subgroup analysis, decrease in BMI showed a stronger effect on mortality as baseline BMI was lower, while an increase in BMI was related to an increase in mortality only in obese COPD patients with aHRs of 1.18 (95% CI: 1.03, 1.36). The aHRs for the risk of severe exacerbation (BMI decrease group and increase group vs. maintenance group) were 1.30 (95% CI:1.24, 1.35) and 1.12 (95% CI:1.07, 1.16), respectively. CONCLUSIONS: A decrease in BMI was associated with an increased risk of all-cause mortality in a dose-dependent manner in patients with COPD. This was most significant in underweight patients. Regular monitoring for weight loss might be an important component for COPD management.

Clinical Course of Patients With Mediastinal Lymph Node Tuberculosis and Risk Factors for Paradoxical Responses.

BACKGROUND: Paradoxical responses (PR) occur more frequently in lymph node tuberculosis (LNTB) than in pulmonary tuberculosis and present difficulties in differential diagnosis of drug resistance, new infection, poor patient compliance, and adverse drug reactions. Although diagnosis of mediastinal LNTB has become much easier with the development of endosonography, limited information is available. The aim of this study was to investigate the clinical course of mediastinal LNTB and the risk factors associated with PR. METHODS: Patients diagnosed with mediastinal LNTB via endosonography were evaluated retrospectively between October 2009 and December 2019. Multivariable logistic regression was applied to evaluate the risk factors associated with PR. RESULTS: Of 9,052 patients who underwent endosonography during the study period, 158 were diagnosed with mediastinal LNTB. Of these, 55 (35%) and 41 (26%) concurrently had pulmonary tuberculosis and extrapulmonary tuberculosis other than mediastinal LNTB, respectively. Of 125 patients who completed anti-tuberculosis treatment, 21 (17%) developed PR at a median of 4.4 months after initiation of anti-tuberculosis treatment. The median duration of anti-tuberculosis treatment was 6.3 and 10.4 months in patients without and with PR, respectively. Development of PR was independently associated with age < 55 years (adjusted odds ratio [aOR], 5.72; 95% confidence interval [CI], 1.81-18.14; P = 0.003), lymphocyte count < 800/µL (aOR, 8.59; 95% CI, 1.60-46.20; P = 0.012), and short axis diameter of the largest lymph node (LN) ≥ 16 mm (aOR, 5.22; 95% CI, 1.70-16.00; P = 0.004) at the time of diagnosis of mediastinal LNTB. CONCLUSION: As PR occurred in one of six patients with mediastinal LNTB during anti-tuberculosis treatment, physicians should pay attention to patients with risk factors (younger age, lymphocytopenia, and larger LN) at the time of diagnosis.

The use of epidermal growth factor in dermatological practice.

Epidermal growth factor (EGF) is a growth factor that plays a pivotal role in wound healing and maintaining tissue homeostasis by regulating cell survival, proliferation, migration, and differentiation. Exogenous administration of bioidentical human recombinant epidermal growth factor (rhEGF) has been known to promote skin wound healing, although rhEGF is increasingly being used in drug delivery systems and nanotechnology. However, despite considerable attention being focused on the potential clinical applications of rhEGF in several dermatological conditions beyond wound healing, the number of studies still remains relatively low. Herein, we conducted a literature search of PubMed/Medline and Google Scholar databases to retrieve published literature related to rhEGF and summarised the effects of rhEGF in the treatment of various wound types, radiotherapy or chemotherapy-related skin reactions, atopic dermatitis, skin aging, and post-inflammatory hyperpigmentation.

Association of body mass index and COPD exacerbation among patients with chronic bronchitis.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) patients with a body mass index (BMI) < 25 kg/m2 are prone to develop adverse event of pharmacological treatment for frequent exacerbation. As chronic bronchitis (CB) is one of the strong risk factors of exacerbation, we investigated the associations between BMI and COPD exacerbations in patients with CB. METHODS: Patients with COPD were included from the Korean COPD Subgroup Study (KOCOSS), a multicenter observational cohort study. CB was defined using the St. George's Respiratory Questionnaire and the participants were categorized according to BMI cut-off of 25 kg/m2. Exacerbations during a 1-year follow-up were compared among four groups: non-CB with BMI ≥ 25 kg/m2, non-CB with BMI < 25 kg/m2, CB with BMI ≥ 25 kg/m2, and CB with BMI < 25 kg/m2. RESULTS: Among the 1264 patients with COPD, 451 (35.7%) had CB and 353 (27.9%) had both CB and BMI < 25 kg/m2. The COPD exacerbation risk increased across the non-CB with BMI < 25 kg/m2, CB with BMI ≥ 25 kg/m2, and CB with BMI < 25 kg/m2 groups (adjusted incidence rate ratio [95% confidence interval] 1.21 [0.89-1.62], 1.20 [0.77-1.88], and 1.41 [1.02-1.91], respectively, compared to the non-CB with BMI ≥ 25 kg/m2 group). CONCLUSIONS: COPD patients having both CB and a BMI < 25 kg/m2 are at higher risk of exacerbations. Considering that a BMI < 25 kg/m2 often limits treatment options preventing exacerbations, modified guidelines might be needed for non-obese CB patients in Asia.

Rheological properties and preclinical data of novel hyaluronic acid filler containing epidermal growth factor.

Recently, a novel hyaluronic acid (HA) filler containing the epidermal growth factor (EGF) was developed. The objective of this study was to evaluate the rheological properties, preclinical efficacy and biocompatibility of the EGF-containing HA filler (HA-EGF filler) using a photoaged mouse model. The rheological properties of the new HA-EGF filler were assessed. Twenty-four female hairless mice (SKH1) underwent photoaging induction with 8 weeks of ultraviolet-B irradiation. The mice were randomly divided into four groups and intradermally injected 100 µl of phosphate-buffered saline, HA-EGF filler, HA filler or polynucleotide (PN) into the dorsal region. We examined the effect of fillers on photoaged skin by dermoscopic examination. Furthermore, histological evaluation with immunohistochemical staining was performed to determine the biocompatibility and collagen formation at the 10th week. A real-time quantitative polymerase chain reaction analysis and western blot test assessed the expression of collagen I/III, matrix metalloproteinases (MMPs) and transforming growth factor. The viscosity and elasticity of the HA-EGF filler were lower than those of the HA filler. Histological evaluation revealed no significant differences in the collagen synthesis between the HA-EGF, HA and PN filler groups. No inflammation was observed during the experimental period. The HA-EGF filler induced type I/III collagen production and downregulated the expression of MMP-1, 3 and 9. Our results suggest that the novel HA-EGF filler may be an additional therapeutic option for photoaged skin, which works by inducing collagen synthesis. Based on these preclinical results, further well-controlled clinical studies are required.

Exosomes as novel player in dermatologic field.

Exosomes are nano-sized extracellular vesicles released by the majority of the cell types. Exosomes play a major role in intercellular communication via transferring cargoes between cells and altering specific functions of the target cells. The interest in the biological activities of exosomes has been increasing and their therapeutic role has already been demonstrated in various diseases. Recently, there is growing evidence that stem cell-derived exosomes (including mesenchymal stem cell, umbilical cord-derived mesenchymal cell, adipose-derived stem cell, and pluripotent stem cell) can also be used in a variety of skin conditions due to their regenerative and anti-inflammatory capacity. In this paper, we will provide a brief overview of recent studies on practical applications of exosomes in several dermatologic conditions and their potential mechanisms. By elucidating the different mechanisms and therapeutic roles of exosomes in various disease conditions, we hope dermatologists and other clinicians to establish better strategies for disease treatment with further research.

Evaluation of the efficacy and safety of the 1064 nm picosecond Nd:YAG laser with a topically applied gold and diamond suspension for facial skin rejuvenation: A pilot study.

To investigate the efficacy and safety of combined treatment with a serum comprising a micro-diamond suspension and micro-gold cage with a 1064 nm picosecond neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for facial skin rejuvenation. Topical serum was applied to the entire face and allowed to penetrate the skin and hair follicles for 20 min. Each participant was then treated with a 1064 nm picosecond Nd:YAG laser on the face. Photographs of each participant were taken at baseline, immediately after treatment, and 2 weeks after treatment using an imaging tool (Mark-Vu®; PSI PLUS, Suwon, Republic of Korea). Global improvement scores by two blinded investigators and participants' satisfaction scores were also assessed. The melanin index (MI), transepidermal water loss (TEWL), and skin hydration were evaluated using a device. Parameters associated with skin rejuvenation were assessed using Mark-Vu®. Adverse events were observed and reported by participants and physicians during the treatment and follow-up visit. At week 2, 40% (4/10) of the participants showed more than moderate clinical improvement in the investigator's global improvement assessment. No significant differences were observed in the MI, TEWL, skin hydration level, or skin parameters of Mark-Vu®. At week 2, 40% of the participants reported a high satisfaction score and minimal side effects. The novel topical facial serum comprising micro-diamond suspension and micro-gold cage is safe and effective when combined with laser treatment for facial rejuvenation.

A randomized, double-blind, multi-center, placebo-controlled, Phase 2 clinical trial to evaluate the efficacy and safety of DWJ211 in the treatment of moderate to severe submental fat.

Excessive accumulation of submental fat (SMF) causes a lower face cosmetic problem. A lipolytic injectable has recently been developed as a solution. The objective of this study is to investigate the effects and safety of DWJ211 (a newly developed lipolytic injectable) in the reduction of SMF and to identify the optimum dose. In this multi-center, double-blind, placebo-controlled study, subjects with moderate to severe SMF were randomized to injections of DWJ211 0.5%, DWJ211 1%, DWJ211 2% or placebo in the submental area, every 4 weeks, up to Week 12. Efficacy was determined by improvements in physician-assisted SMF rating scales (PA-SMFRS) and subject-assisted SMF rating scales (SA-SMFRS) 4 weeks after the last treatment (Week 16). Safety was assessed by inquiries, subject diary entries of adverse events, laboratory tests, and vital sign checks. Of 140 enrolled subjects, 136 were included in the analysis. The proportions of subjects, who achieved ≥1-grade improvement on the PA-SMFRS were 41.7%, 65.7%, 84.4%, and 72.7%, and the proportions of subjects, who achieved ≥1-grade improvement on the SA-SMFRS were 50.0%, 71.4%, 93.8%, and 81.8% for the placebo, DWJ211 0.5%, DWJ211 1%, and DWJ211 2% group, respectively. Adverse drug reactions (ADRs) were more common in each of the treatment groups compared with placebo, with the most common ADR being injection site pain. No subjects experienced any serious adverse events. In conclusion, the 1% DWJ211 dose was beneficial for SMF reduction and had a tolerable safety profile. Thus, we selected 1% as the dose to be tested in a Phase 3 clinical trial.

Low-intensity cold atmospheric plasma reduces wrinkles on photoaged skin through hormetic induction of extracellular matrix protein expression in dermal fibroblasts.

BACKGROUND: Recent evidence indicates that cold atmospheric plasma (CAP) can upregulate the production of extracellular matrix (ECM) proteins in dermal fibroblasts and enhance transdermal drug delivery when applied at a low intensity. OBJECTIVES: The aim of this study was to evaluate the effect of low-intensity CAP (LICAP) on photoaging-induced wrinkles in an animal model and the expression profiles of ECM proteins in human dermal fibroblasts. METHODS: Each group was subjected to photoaging induction and allocated to therapy (LICAP, topical polylactic acid (PLA), or both). The wrinkles were evaluated via visual inspection, quantitative analysis, and histology. The expression of collagen I/III and fibronectin was assessed using reverse transcription-quantitative polymerase chain reaction, western blot analysis, and immunofluorescence. The amount of aqueous reactive species produced by LICAP using helium and argon gas was also measured. RESULTS: Wrinkles significantly decreased in all treatment groups compared to those in the untreated control. The differences remained significant for at least 4 weeks. Dermal collagen density increased following LICAP and PLA application. LICAP demonstrated a hormetic effect on ECM protein expression in human dermal fibroblasts. The production of reactive species increased, showing a biphasic pattern, with an initial linear phase and a slow saturation phase. The initial linearity was sustained for a longer time in the helium plasma (~60 s) than in the argon plasma (~15 s). CONCLUSION: LICAP appears to be a novel treatment option for wrinkles on the photodamaged skin. This treatment effect seems to be related to its hormetic effect on dermal ECM production.

Mortality and lung function decline in patients who develop chronic pulmonary aspergillosis after lung cancer surgery.

BACKGROUND: Lung cancer surgery is reported as a risk factor for chronic pulmonary aspergillosis (CPA). However, limited data are available on its clinical impact. We aimed to determine the effect of developed CPA after lung cancer surgery on mortality and lung function decline. METHODS: We retrospectively identified the development of CPA after lung cancer surgery between 2010 and 2016. The effect of CPA on mortality was evaluated using multivariable Cox proportional hazard analyses. The effect of CPA on lung function decline was evaluated using multiple linear regression analyses. RESULTS: During a median follow-up duration of 5.01 (IQR, 3.41-6.70) years in 6777 patients, 93 developed CPA at a median of 3.01 (IQR, 1.60-4.64) years. The development of CPA did not affect mortality in multivariable analysis. However, the decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were greater in patients with CPA than in those without (FVC, - 71.0 [- 272.9 to - 19.4] vs. - 10.9 [- 82.6 to 57.9] mL/year, p < 0.001; FEV1, - 52.9 [- 192.2 to 3.9] vs. - 20.0 [- 72.6 to 28.6] mL/year, p = 0.010). After adjusting for confounding factors, patients with CPA had greater FVC decline (ß coefficient, - 103.6; 95% CI - 179.2 to - 27.9; p = 0.007) than those without CPA. However, the FEV1 decline (ß coefficient, - 14.4; 95% CI - 72.1 to 43.4; p = 0.626) was not significantly different. CONCLUSION: Although the development of CPA after lung cancer surgery did not increase mortality, the impact on restrictive lung function deterioration was profound.

The Higher Incidence of COVID-19 in Patients With Non-Tuberculous Mycobacterial Pulmonary Disease: A Single Center Experience in Korea.

The aim of our study was to investigate the incidence of and risk factors for coronavirus disease 2019 (COVID-19) in patients with non-tuberculous mycobacterial-pulmonary disease (NTM-PD). A total of 3,866 patients with NTM-PD were retrospectively identified from a single center. Compared to the general population of Korea, patients with NTM-PD had a substantially increased age-standardized incidence of COVID-19 from January 2020 to February 2021 (2.1% vs. 0.2%). The odds of being infected with COVID-19 was particularly higher in patients who received treatment for NTM-PD than in those who did not receive treatment for NTM-PD (adjusted odd ratio = 1.99, 95% confidence interval = 1.09-3.64, P = 0.026). Patients with NTM-PD might be regarded as a high-risk group for COVID-19 and may need a more proactive preventive strategy for COVID-19 and other pandemics in the future.

Blood eosinophil counts and the development of obstructive lung disease: the Kangbuk Samsung Health Study.

AIM: The impact of blood eosinophil counts on the development of chronic obstructive lung disease (COPD) is unknown. We investigated whether a higher blood eosinophil count was associated with the risk of developing obstructive lung disease (OLD) in a large cohort of men and women free from lung disease at baseline. METHODS: This was a cohort study of 359 456 Korean adults without a history of asthma and without OLD at baseline who participated in health screening examinations including spirometry. OLD was defined as pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and FEV1 <80% predicted. RESULTS: After a median (interquartile range) follow-up of 5.6 (2.9-9.2) years, 5008 participants developed incident OLD (incidence rate 2.1 (95% CI 2.1-2.2) per 1000 person-years). In the fully adjusted model, the hazard ratios for incident OLD comparing eosinophil counts of 100- <200, 200- <300, 300- <500 and ≥500 versus <100 cells·µL-1 were 1.07 (95% CI 1.00-1.15), 1.30 (95% CI 1.20-1.42), 1.46 (95% CI 1.33-1.60) and 1.72 (95% CI 1.51-1.95), respectively (ptrend<0.001). These associations were consistent in clinically relevant subgroups, including never-, ex- and current smokers. CONCLUSION: In this large longitudinal cohort study, blood eosinophil counts were positively associated with the risk of developing of OLD. Our findings indicate a potential role of the eosinophil count as an independent risk factor for developing COPD.

Efficacy and safety of botulinum toxin injection in reducing deltoid muscle hypertrophy.

With the increasing demand for body contouring, botulinum toxin (BTX) injection is being widely used off-label for muscular hypertrophy. However, to the best of our knowledge, no study has investigated the clinical efficacy of BTX type A (BTX-A) in deltoid muscle hypertrophy. This study was conducted to evaluate the efficacy and safety of intramuscular injection of BTX in reducing deltoid muscle hypertrophy. Overall, 10 patients with bilateral deltoid muscle hypertrophy were treated with an intramuscular injection of prabotulinum toxin A, with a total of 50 units [U] administered per patient. As measured by ultrasonography, the thickness of the deltoid muscles was significantly decreased at weeks 2 and 12. In addition, the clinical assessment score by blinded investigators was improved after the treatment; however, patients' satisfaction scores were relatively low. No major complications were reported. Therefore, intramuscular injection of BTX-A seems to be a candidate for novel treatment option for deltoid muscle hypertrophy. Further larger clinical studies are warranted to confirm the efficacy of BTX-A.

Changes in skin characteristics after using respiratory protective equipment (medical masks and respirators) in the COVID-19 pandemic among healthcare workers.

BACKGROUND: The coronavirus disease-2019 (COVID-19) outbreak has presented unique dermatologic challenges due to respiratory protective equipment (RPE)-related skin conditions. OBJECTIVE: To objectively evaluate the effects of RPE including medical masks and respirators on the skin barrier by measuring various physiological properties of the skin. METHODS: A cross-sectional study was designed. Twenty healthy healthcare workers were included in this study. Skin parameters including skin hydration, transepidermal water loss (TEWL), erythema, sebum secretion, pH, and skin temperature were measured in the RPE-covered and RPE-uncovered areas of the face 4 and 8 hours after wearing RPE and 14 hours after not wearing RPE. RESULTS: Skin hydration, TEWL, erythema, pH, and skin temperature increased in the RPE-covered areas after wearing RPE for 4 and 8 hours. By contrast, in the RPE-uncovered areas, skin hydration decreased and TEWL, erythema, and pH showed minimal changes over time. Based on the repeated-measure analysis, the changes in skin physiological properties over time were significantly different between RPE-covered and RPE-uncovered areas. CONCLUSION: We observed that skin physiological characteristics change with the prolonged use of RPE such as medical masks and respirators. These changes may lead to various adverse skin reactions after long-term use.

Ceramide Synthase 2 Null Mice Are Protected from Ovalbumin-Induced Asthma with Higher T Cell Receptor Signal Strength in CD4+ T Cells.

(1) Background: six mammalian ceramide synthases (CerS1-6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22-C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods: asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results: CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.

Chronic obstructive pulmonary disease and lung cancer incidence in never smokers: a cohort study.

There has been limited evidence for the association between chronic obstructive pulmonary disease (COPD) and the incidence of lung cancer among never smokers. We aimed to estimate the risk of lung cancer incidence in never smokers with COPD, and to compare it with the risk associated with smoking. This cohort study involved 338 548 subjects, 40 to 84 years of age with no history of lung cancer at baseline, enrolled in the National Health Insurance Service National Sample Cohort. During 2 355 005 person-years of follow-up (median follow-up 7.0 years), 1834 participants developed lung cancer. Compared with never smokers without COPD, the fully-adjusted hazard ratios (95% CI) for lung cancer in never smokers with COPD, ever smokers without COPD, and ever smokers with COPD were 2.67 (2.09 to 3.40), 1.97 (1.75 to 2.21), and 6.19 (5.04 to 7.61), respectively. In this large national cohort study, COPD was also a strong independent risk factor for lung cancer incidence in never smokers, implying that COPD patients are at high risk of lung cancer, irrespective of smoking status.