Legionnaire's disease presenting as bilateral central scotomata: a case report.

BACKGROUND: Legionnaire's disease is one of the major causes of community-acquired pneumonia and is occasionally complicated by neurological symptoms. However, reports of ocular lesions due to Legionnaire's disease are limited. CASE PRESENTATION: We report the case of a patient with Legionnaire's disease presenting as bilateral central scotomata due to retinal lesions. The patient consulted due to fever and bilateral central scotomata, as well as other extrapulmonary symptoms. Optical coherence tomography (OCT) showed bilateral accumulations of fluid under the retina, and the patient was diagnosed with bilateral exudative retinal detachment. Later, Legionnaire's disease was confirmed by pulmonary infiltrates on chest imaging and positive urinary antigen for Legionella pneumophila. After administration of antibiotics, the bilateral central scotomata and bilateral subretinal fluid accumulations completely resolved, as did the other extrapulmonary symptoms and the pulmonary infiltrates. Thus, the bilateral central scotomata due to exudative retinal detachment were thought to be caused by Legionnaire's disease. CONCLUSIONS: This case demonstrates that Legionnaire's disease can present as bilateral central scotomata. We may consider the possibility of extrapulmonary involvement complicating Legionnaire's disease when we encounter bilateral ocular lesions in patients with fever and pneumonia.

Recombinant thrombomodulin for acute exacerbation in idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) or other idiopathic interstitial pneumonias (IIP) is a poor prognostic event despite conventional therapy with corticosteroids and/or immunosuppressants. We aimed to evaluate the efficacy and safety of recombinant human soluble thrombomodulin (rhTM) for AE-IIP. METHODS: For this prospective single-arm open-label multicentre cohort study, we retrospectively registered 61 cases of AE-IIP treated with conventional therapy between 2011 and 2013 (control arm), and prospectively enrolled 39 cases of AE-IIP treated with conventional therapy and rhTM (380 U/kg/day for 6 days) between 2014 and 2016 (rhTM arm). To reduce potential confounding in treatment comparisons, an adjusted mortality analysis for 90-day survival was conducted with weighted Cox proportional hazards regression models using inverse probability of treatment weighting. Weights were derived from propensity scores estimated using a multivariable logistic regression analysis including potential confounders. RESULTS: The 90-day survival rates of AE-IIP patients treated with/without rhTM were 66.7% (26/39) and 47.5% (29/61), respectively. After adjusting for imbalances, rhTM therapy was significantly associated with reduced mortality (adjusted hazard ratio (HR): 0.453; 95% CI: 0.237-0.864; P = 0.0163). The frequencies of adverse events with/without rhTM were 17.9% (7/39) and 19.7% (12/61), which were similar in both arms (P = 1.0). Two bleeding-related adverse events occurred in the rhTM arm. CONCLUSION: Safety and efficacy were observed for rhTM treatment of AE-IIP. A future randomized controlled trial is required to draw final conclusions.

Development and validation of a prognostic scoring model for Mycobacterium avium complex lung disease: an observational cohort study.

BACKGROUND: Patients with Mycobacterium avium complex (MAC) lung disease (LD) have a heterogeneous prognosis. This study aimed to develop and validate a prognostic scoring model for these patients using independent risk factors for survival. METHODS: We retrospectively analyzed the data of patients with MAC-LD from two hospitals (cohort 1, n = 368; cohort 2, n = 118). Cohort 1 was evaluated using a multivariate Cox proportional hazards model to identify independent risk factors for overall survival (OS). A prognostic scoring model composed of these factors was developed, and cohort 1 was stratified into three groups according to risk using the log-rank test. Finally, the prognostic scoring model was validated using the data of cohort 2. RESULTS: Seven independent risk factors for OS were selected from cohort 1, including the male sex, age ≥ 70 years, the presence of a malignancy, body mass index <18.5 kg/m2, lymphocyte count <1000 cells/µL, serum albumin levels <3.5 g/dL, and fibrocavitary disease. The areas under the receiver operating characteristic curves for the prognostic scoring model were 0.84 [95% confidence interval (CI), 0.80 - 0.89] for cohort 1 and 0.84 (95% CI, 0.75 - 0.92) for cohort 2. The 5-year OS rates of patients stratified into low-risk, intermediate-risk, and high-risk groups were 97.6, 76.6, and 30.8%, respectively (P < 0.001), in cohort 1, and 97.2, 82.3, and 45.4%, respectively (P < 0.001), in cohort 2. CONCLUSIONS: This study is the first to develop and validate a prognostic scoring model for patients with MAC-LD. This model may prove useful in clinical settings and practical in estimating the prognosis.

Nontuberculous Mycobacteria Infection and Prognosis after Surgery of Lung Cancer: A Retrospective Study.

To investigate the association between pulmonary nontuberculous mycobacteria infection (PNTMI) and prognosis after pulmonary resection for non small cell lung cancer (NSCLC), we retrospectively analyzed 391 consecutive patients with NSCLC who underwent surgery. Subjects were grouped based on with/without PNTMI defined by two criteria (12 and 23 PNTMI subjects). Kaplan-Meier analysis showed no significant difference between the two groups regarding overall survival (p = 0.800 and p = 0.912 by two criteria). PNTMI was not identified as a significant factor associated with prognosis by either univariate or multivariate analysis (hazard ratio [HR] = 0.950 and HR = 0.948, respectively).

Development and validation of a preoperative prognostic index independent of TNM stage in resected non-small cell lung cancer.

BACKGROUND: Previously reported prognostic tools for patients with resected non-small cell lung cancer (NSCLC) include factors found postoperatively, but not preoperatively. However, it would be important to predict patient prognosis before NSCLC resection. To suggest a novel preoperative prognostic tool, we evaluated the relationship of preoperative prognostic factors with the survival of patients with resected NSCLC. METHODS: We retrospectively reviewed the data of two independent cohorts of patients with completely resected NSCLC. To develop the prognostic index in one cohort, the overall survival (OS) was evaluated using the Cox proportional hazards model. We assessed the disease-free survival (DFS) and OS of three risk groups defined according to the prognostic index. Then, the prognostic index was validated in the other cohort. RESULTS: Seven independent risk factors for OS were selected: age ≥ 70 years, ever-smokers, vital capacity <80%, neutrophil-to-lymphocyte ratio ≥ 2.1, cytokeratin 19 fragment >normal limit, non-usual interstitial pneumonia (UIP) pattern, and UIP pattern. Three risk groups were defined: low-risk (36.9%), intermediate-risk (54.0%), and high-risk (9.1%). In the derivation cohort, the 5-year DFS rate was 77.8%, 58.8%, and 22.6% (P < 0.001), and the 5-year OS rate was 95.2%, 70.4%, and 28.9% (P < 0.001), respectively. Multivariate analyses showed that the prognostic index predicted DFS and OS, independent of pathological stage and tumor histology, in both derivation and validation cohorts. CONCLUSIONS: We developed and validated a simple preoperative prognostic index composed of seven variables, which may help clinicians predict prognosis before surgery in patients with NSCLC.

Longitudinal shape irregularity of airway lumen assessed by CT in patients with bronchial asthma and COPD.

BACKGROUND: Airway remodelling in bronchial asthma (BA) and COPD has been quantitatively assessed by analysing the airway wall area and the luminal area on cross-sectional CT images. To date, there have been no reports on assessment of the longitudinal structure of the airway lumen. METHODS: Quantitative airway analysis using CT was performed on three groups consisting of 29 patients with BA, 58 patients with COPD and 59 healthy controls. To assess the longitudinal shape irregularity of the airway lumen, new quantitative CT parameters, validated by a phantom study, were established. The internal radii of imaginary inscribed spheres in the airway lumen were measured as a function of distance from the level of the carina to the fifth-order branches of the right posterior basal bronchus. The gaps of these radii from the regression line were calculated as parameters to reflect the longitudinal airway lumen shape irregularity. These new parameters were compared among the study groups as well as with the conventional parameters of airway wall thickening and luminal area. RESULTS: Longitudinal airway lumen shape irregularity was significantly greater in patients with COPD than in those with BA and healthy controls. Wall thickening was significantly greater, and luminal area smaller, in patients with BA than in those with COPD and healthy controls. These results were consistent even among the BA and COPD subgroups with similar airflow limitation. CONCLUSIONS: The combination of cross-sectional and longitudinal airway structure analyses using CT images may suggest differences in the characteristics of airway remodelling between COPD and asthma.

Effectiveness of azithromycin in aspiration pneumonia: a prospective observational study.

BACKGROUND: Aspiration pneumonia is an urgent health concern with high mortality and long hospitalization in industrialized and aging countries. However, there is no information about the effectiveness of azithromycin (AZM) for the treatment of aspiration pneumonia. This study investigated if AZM is effective for the treatment of aspiration pneumonia. METHODS: Patients with aspiration pneumonia with no risk of multidrug-resistant pathogens were included in this prospective study at Kishiwada City Hospital from December 2011 to June 2013. Patients were divided into the ampicillin/sulbactam (ABPC/SBT) and AZM (intravenous injection) groups. The success rates of 1(st)-line antibiotic therapy, mortality, length of hospital stay, and total antibiotic costs were compared. RESULTS: There were 81 and 36 patients in the ABPC/SBT and AZM groups, respectively. There was no significant difference in the success rate of 1(st)-line antibiotics between the groups (74.1% vs. 75.0%, respectively, P = 1.000). Mortality and hospitalization periods did not differ between the 2 groups (11.1% vs. 8.3%, P = 0.753, and 22.3 ± 7.3 days vs. 20.5 ± 8.1 days, P = 0.654, respectively). However, the total antibiotic costs were significantly lower in the AZM group than the ABPC/SBT group (2.19 ± 1.65 × 10,000 yen vs. 2.94 ± 1.67 × 10,000 yen, respectively, P = 0.034). The febrile period of the ABPC/SBT group was significantly shorter than that of the AZM group (P = 0.025). CONCLUSIONS: In this small prospective non-randomized observational study, we found no statistically significant differences in mortality or antibiotic failure in patients receiving AZM compared to ABPC/SBT for the treatment of patients with aspiration pneumonia who require hospital admission and have no risk of drug-resistant pathogens. Therefore, AZM may be another first choice of antibiotic treatment for patients with aspiration pneumonia when they have no risk of multidrug-resistant pathogens.

p38 mitogen-activated protein kinase determines the susceptibility to cigarette smoke-induced emphysema in mice.

BACKGROUND: There is a need for agents that suppress inflammation and progression of chronic obstructive pulmonary disease. p38 mitogen-activated protein kinase (p38 MAPK) has been associated with this disorder, and several inhibitors of this cascade are in clinical trials for its treatment, but their efficacy and utility are unknown. This study evaluated the relationship between p38 MAPK activation and susceptibility to cigarette smoke (CS)-induced emphysema, and whether its inhibition ameliorated the lung inflammation and injury in murine models of cigarette smoke exposure. METHODS: In acute and chronic CS exposure, the activation and expression of p38 MAPK in the lungs, as well as lung inflammation and injury (proteinase production, apoptosis, and oxidative DNA damage), were compared between two mouse strains: C57BL/6 (emphysema-susceptible) and NZW (emphysema-resistant). The selective p38 MAPK inhibitor SB203580 (45 mg/kg) was administrated intra-peritoneally to C57BL/6 mice, to examine whether it ameliorated cigarette smoke-induced lung inflammation and injury. RESULTS: Acute CS-induced lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2), proteinase expression (MMP-12 mRNA), apoptosis, and oxidative DNA damage were significantly lower in NZW than C57BL/6 mice. p38 MAPK was significantly activated and up-regulated by both acute and chronic CS exposure in C57BL/6 but not NZW mice. mRNA expression of p38 MAPK was also upregulated in C57BL/6 by chronic CS exposure and tended to be constitutively suppressed in NZW mice. SB203580 significantly attenuated lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2, protein levels of KC, MIP-1α, IL-1ß, and IL-6), proteinase expression (MMP-12 mRNA), oxidative DNA damage, and apoptosis caused by acute CS exposure. CONCLUSIONS: Cigarette smoke activated p38 MAPK only in mice that were susceptible to cigarette smoke-induced emphysema. Its selective inhibition ameliorated lung inflammation and injury in a murine model of cigarette smoke exposure. p38 MAPK pathways are a possible molecular target for the treatment of chronic obstructive pulmonary disease.

Squamous Cell Carcinoma of the Lung Presenting Unilateral Thoracic Hyperhidrosis: A Case Report and Review of Literature.

Unilateral hyperhidrosis is an uncommon manifestation, and the majority of cases have been attributed to neurological diseases. There are few cases of unilateral hyperhidrosis associated with thoracic malignant tumors. We herein report a 74-year-old Japanese man with squamous cell carcinoma of the lung who presented with unilateral hyperhidrosis in the right thoracic area as one of the first clinical manifestations. We should consider the possibility of pleural diseases, including metastatic lung cancer, when encountering patients presenting with unilateral thoracic hyperhidrosis.

Diagnosis of pulmonary leiomyosarcoma extending into the main bronchus using repeated transbronchial cryobiopsy.

The diagnosis of pulmonary leiomyosarcoma using bronchoscopy is difficult, and surgical resection is often performed for definitive diagnosis and curative therapy. We report a case of pulmonary leiomyosarcoma, successfully diagnosed using repeated transbronchial cryobiopsy (TBCB). A 69-year-old-woman was found to have an oval mass in the left hilar region extending into the left main bronchus on computed tomography (CT). All transbronchial biopsy specimens were necrotic, but repeated TBCB removed the necrotic tissue from the tumour and finally led to the diagnosis of pulmonary leiomyosarcoma. Proton therapy was administered, which caused shrinkage of the tumour. Thus, TBCB is useful for definitive diagnosis of leiomyosarcoma without surgical biopsy. Repeated TBCB can reduce tumour volume, eliminate atelectasis, and reduce the extent of radiotherapy exposure.

Successful treatment of tuberculous meningitis in an Indian female under hemodialysis therapy.

Hemodialysis is a well-known risk factor for severe infection by putting patients under an immunocompromised state. Such patients are prone to opportunistic pathogen and present with atypical manifestations during infection. Tuberculous meningitis is a central nervous system infection of Mycobacterium tuberculosis, accounting for the highest mortality of all forms of tuberculosis. In fact, the mortality rate of tuberculous meningitis in hemodialysis patients is extremely poor because early clinical diagnosis is difficult. Here, we report a case of tuberculous meningitis in a 61-year-old Indian hemodialysis patient, who presented with fever of unknown origin and was successfully treated with empiric treatment with standard four-drug regimen against tuberculosis. Comprehensive screening of the origin of fever revealed only the positive results of interferon-gamma release assay, which led us to initiate an empiric therapy for tuberculosis, before making a definitive diagnosis by cerebrospinal fluid nested PCR. Soon after the initiation of the treatment, the fever immediately abated. Although the patient experienced a single episode of paradoxical worsening and severe liver injury, she recovered well without any complications. This report provides a clinical course of the disease in a hemodialysis patient, highlighting the importance of early clinical diagnosis and rapid initiation of empirical tuberculosis treatment.

Oxidative stress induced interleukin-32 mRNA expression in human bronchial epithelial cells.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and persistent inflammation in the airways and lung parenchyma. Oxidative stress contributes to the pathogenesis of COPD. Interleukin (IL)-32 expression has been reported to increase in the lung tissue of patients with COPD. Here, we show that IFNγ upregulated IL-32 expression and that oxidative stress augmented IFNγ-induced-IL-32 expression in airway epithelial cells. We further investigated transcriptional regulation responsible for IFNγ induced IL-32 expression in human airway epithelial cells. METHODS: Human bronchial epithelial (HBE) cells were stimulated with H2O2 and IFNγ, and IL-32 expression was evaluated. The cell viability was confirmed by MTT assay. The intracellular signaling pathways regulating IL-32 expression were investigated by examining the regulatory effects of MAPK inhibitors and JAK inhibitor after treatment with H2O2 and IFNγ, and by using a ChIP assay to identify transcription factors (i.e. c-Jun, CREB) binding to the IL-32 promoter. Promoter activity assays were conducted after mutations were introduced into binding sites of c-Jun and CREB in the IL-32 promoter. IL-32 expression was also examined in HBE cells in which the expression of either c-Jun or CREB was knocked out by siRNA of indicated transcription factors. RESULTS: There were no significant differences of cell viability among groups. After stimulation with H2O2 or IFNγ for 48 hours, IL-32 expression in HBE cells was increased by IFNγ and synergistically upregulated by the addition of H2O2. The H2O2 augmented IFNγ induced IL-32 mRNA expression was suppressed by a JNK inhibitor, but not by MEK inhibitor, p38 inhibitor, and JAK inhibitor I. Significant binding of c-Jun and CREB to the IL-32 promoter was observed in the IFNγ + H2O2 stimulated HBE cells. Introducing mutations into the c-Jun/CREB binding sites in the IL-32 promoter prominently suppressed its transcriptional activity. Further, knocking down CREB expression by siRNA resulted in significant suppression of IL-32 induction by IFNγ and H2O2 in HBE cells. CONCLUSION: IL-32 expression in airway epithelium may be augmented by inflammation and oxidative stress, which may occur in COPD acute exacerbation. c-Jun and CREB are key transcriptional factors in IFNγ and H2O2 induced IL-32 expression.

A NOD2 gene polymorphism is associated with the prevalence and severity of chronic obstructive pulmonary disease in a Japanese population.

BACKGROUND AND OBJECTIVE: Genetic background is thought to be one of the risk factors for development of COPD. Recently, it has been proposed that the innate immune system is involved in the pathophysiology of COPD. We hypothesized that polymorphisms in the nucleotide-binding and oligomerization domain (NOD)1 and NOD2 genes would be associated with the pathogenesis of COPD. In addition, the associations between these single nucleotide polymorphisms (SNPs) and phenotypes of COPD were analysed. METHODS: Japanese COPD patients (n = 228) and non-COPD smokers (n = 101) were recruited from the outpatient clinic at Kyoto University Hospital, Kyoto, Japan. At entry into the study, a blood sample was taken and a pulmonary function test was performed. Genotyping was performed for 6 selected tag SNPs of NOD1 and 5 tag SNPs of NOD2. Further investigations were performed for SNP that were associated with COPD, including baseline gene expression, the relative proportions of splicing variants in whole blood, responses to ligand and enhancement of gene expression in peripheral blood neutrophils stimulated with pro-inflammatory cytokines. RESULTS: The distribution of NOD2 rs1077861 genotypes differed between Japanese COPD patients and non-COPD smokers (P = 0.036). This SNP was also associated with a lower FEV(1) % predicted (57.2 ± 1.8 for TT vs 50.8 ± 2.3 for TA/AA, P = 0.03) and DL(CO) /V(A) (2.89 ± 0.1 in TT vs 2.53 ± 0.14 in TA/AA, P = 0.036) in COPD patients. NOD2 gene expression after stimulation with 10 ng/mL of tumour necrosis factor-α for 4 h, was increased to a greater extent in TA/AA genotype than in TT genotype peripheral blood neutrophils (P = 0.015). CONCLUSIONS: The NOD2 rs1077861 SNP may influence the development and progression of COPD in Japanese subjects.

Impact of exacerbations on emphysema progression in chronic obstructive pulmonary disease.

RATIONALE: Low-attenuation areas assessed by computed tomography reflect the extent of pathological emphysema and correlate with airflow limitation and mortality in patients with chronic obstructive pulmonary disease. The cumulative size distribution of low-attenuation area clusters follows a power law characterized by an exponent, D. The values of D reflect the complexity of the terminal airspace geometry and sensitively detect alveolar structural changes. Exacerbations of chronic obstructive pulmonary disease have a negative impact on lung function and prognosis. However, the impact on emphysema progression remains unclear. OBJECTIVES: We investigated the relationship between exacerbation and emphysema progression assessed by computed tomography in patients with chronic obstructive pulmonary disease. METHODS: Exacerbations were prospectively recorded for 2 years. Annual changes in computed tomography parameters of emphysema were compared between patients with and without a history of exacerbations. MEASUREMENTS AND MAIN RESULTS: In patients with exacerbations, increases in the percentage of low-attenuation areas and decreases in D were greater than in patients without exacerbations. To interpret these results, we established a novel simulation model and found that not only enlargement of preexisting low-attenuation areas but also coalescence of adjoining low-attenuation areas due to alveolar wall destruction caused emphysema progression in patients with exacerbations. CONCLUSIONS: This is the first longitudinal study to demonstrate that exacerbations are involved in emphysema progression in patients with chronic obstructive pulmonary disease. Emphysema progression should be evaluated as part of the outcomes of exacerbations in the management of chronic obstructive pulmonary disease.

Adult T Cell Leukemia/Lymphoma Becoming Apparent during Treatment of Pulmonary Abscess and Empyema Caused by Nocardia asiatica: A Case Report and Review of the Literature.

Nocardia is a Gram-positive bacterium that causes opportunistic infections. Nocardia asiatica was newly isolated in 2004, and there have been no case reports describing the empyema caused by N. asiatica. Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). We herein report a case in which immunosuppression attributable to ATL may have led to pulmonary abscess and empyema caused by N. asiatica. Our case demonstrates the need to investigate causes of immunosuppression, including ATL, in patients showing nocardiosis.

Durvalumab-associated Late-onset Myocarditis Successfully Treated with Corticosteroid Therapy.

We herein report a 66-year-old man with locally advanced non-small-cell lung cancer (NSCLC) who developed durvalumab-associated myocarditis. The patient underwent durvalumab administration every two weeks following concurrent chemoradiotherapy, without any adverse events or apparent disease progression. He presented with fatigue and dyspnea on exertion seven months after the first administration. Myocarditis was suspected based on laboratory data, an electrocardiogram, echocardiography, and magnetic resonance imaging findings. The definitive diagnosis was confirmed by a myocardial biopsy. Myocarditis was alleviated by cessation of durvalumab and corticosteroid therapy. This is a noteworthy case to describe late-onset myocarditis following the administration of durvalumab for NSCLC.

Antimelanoma Differentiation-Associated Gene 5 Antibody-Positive Interstitial Lung Disease After Vaccination With COVID-19 mRNA Vaccines.

OBJECTIVE: Melanoma differentiation-associated gene 5 (MDA5) is a viral RNA sensor induced by SARS-CoV-2. Similarities have been reported between the clinical presentations of coronavirus disease 2019 (COVID-19) pneumonia and anti-MDA5 antibody-positive interstitial lung disease (anti-MDA5-ILD). However, it is unknown whether COVID-19 mRNA vaccines are associated with anti-MDA5-ILD. METHODS: We retrospectively reviewed consecutive patients with anti-MDA5-ILD admitted to our hospital between April 2017 and March 2022. In addition, we investigated the clinical presentations of patients who developed anti-MDA5-ILD after vaccination with COVID-19 mRNA vaccines. We also examined the annual number of anti-MDA5-ILD cases before and after the COVID-19 vaccination campaign. RESULTS: Nine patients with anti-MDA5-ILD were seen during the study period, of whom 4 developed anti-MDA5-ILD between August and October 2021, approximately 6 to 12 weeks after vaccination with a COVID-19 mRNA vaccine and a few months after the rapid mRNA COVID-19 vaccination campaign in Japan. None of the 4 patients had evidence of SARS-CoV-2 infection. The difference in the annual number of anti-MDA5-ILD cases before vs after the COVID-19 vaccination campaign (1.25 ± 0.96 cases/yr vs 4.0 cases/yr) was not statistically significant (P = 0.08). CONCLUSION: We encountered 4 cases of anti-MDA5-ILD after COVID-19 vaccination. Further large population studies are needed to clarify the relationship between anti-MDA5-ILD and vaccination with COVID-19 mRNA vaccines.

Relationship Between Episodic Nocturnal Hypercapnia and History of Exacerbations in Patients with Advanced Chronic Obstructive Pulmonary Disease.

Purpose: An episodic increase in transcutaneous carbon dioxide pressure (PtcCO2) is often recognized in patients with advanced chronic obstructive pulmonary disease (COPD) by overnight PtcCO2 monitoring. This phenomenon, called episodic nocturnal hypercapnia (eNH), mainly corresponds to rapid eye movement (REM) sleep-related hypoventilation. However, it is unclear whether eNH is associated with the frequency of COPD exacerbation. We aimed to investigate whether a relationship exists between COPD exacerbation and eNH. Patients and Methods: We enrolled consecutive patients with stable, severe, or very severe COPD with a daytime arterial carbon dioxide pressure (PaCO2) <55.0 mmHg who underwent overnight PtcCO2 monitoring from April 2013 to January 2017. We retrospectively analyzed the prevalence of eNH and sleep-associated hypoventilation (SH) as defined by the American Academy of Sleep Medicine. Moreover, we compared the relationship between the frequency of COPD exacerbations in the previous year and eNH or SH. Results: Twenty-four patients were included in this study. The study patients had a mean daytime PaCO2 and nocturnal PtcCO2 of 43.3 ± 6.8 mmHg and 42.9 ± 9.6 mmHg, respectively. Six (25.0%) and 11 (45.9%) of the 24 patients met the SH and eNH criteria, respectively. The odds ratios of SH and eNH for at least one annual exacerbation were 1.0 [95% confidence interval (CI): 0.16-6.00] and 11.1 [95% CI: 1.39-87.7], respectively. The odds ratios of SH and eNH for at least two annual exacerbations were 0.3 [95% CI: 0.04-2.64] and 6.6 [95% CI: 1.06-39.4], respectively. Conclusion: In patients with advanced COPD and a daytime PaCO2 <55.0 mmHg, eNH may be associated with a history of more frequent exacerbations than SH. Further studies are required to validate these findings.

SARS-CoV-2-related Progressive Brain White Matter Lesion Associated with an Increased Cerebrospinal Fluid Level of IL-6.

We herein report a 49-year-old man with a fever, diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After two weeks of hospitalization, he suddenly mentioned visual field impairment. Computed tomography and magnetic resonance imaging revealed white matter damage and vasogenic edema. Cerebrospinal fluid showed increased levels of interleukin (IL)-6. His symptoms and white matter lesion deteriorated. After treatment with intravenous methylprednisolone therapy and plasmapheresis, his symptoms and white matter lesion improved gradually. We suspect that our patient was affected by a secondary hyperinflammatory syndrome related to cytokines, alone or in combination with direct viral injury through endothelial cell damage. The IL-6 levels were elevated only in the cerebrospinal fluid, suggesting focal central nervous system inflammation.