Management Reality of Female Patients with COPD: A Multicenter Cross-Sectional CAP Study in Japan.

Background: Reports from Europe and North America suggest that female chronic obstructive pulmonary disease (COPD) patients have a higher symptom burden and mortality than male patients. However, little is known about the management reality of female patients with COPD in Japan. Patients and Methods: We compared the clinical characteristics of female COPD patients with those of male using the cohort of the COPD Assessment in Practice study, which is a cross-sectional multicenter observational study. Results: Of the 1168 patients, 133 (11.4%) were female. A history of never smoking was higher in females than males (p<0.01). Although there was no difference in age or forced expiratory volume in one second (FEV1) % predicted between the groups, modified medical research council dyspnea scale (mMRC) and number of frequent exacerbators were higher in females (mMRC≥2: p<0.01; number of exacerbations≥2: p=0.011). The mean forced vital capacity and FEV1 values in females were lower than those in males (p<0.0001 and p<0.0001, respectively). Females were more likely to use long-term oxygen therapy and inhaled corticosteroids than males (p=0.016 and p<0.01, respectively). The prevalence of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, D (ABCD GOLD 2017 classification), and E (ABE GOLD 2023 classification) was higher in females than in males. Conclusion: The disease burden of female patients with COPD is higher than that of male patients in Japan, suggesting the importance of interventions considering female-dominant features such as lower absolute FVC and FEV1, respiratory failure, and asthma-like conditions.

Correlation between frailty and reduction in cortical thickness in patients with chronic obstructive pulmonary disease.

Physical inactivity and cognitive impairment in patients with chronic obstructive pulmonary disease (COPD) can lead to frailty and poor prognoses. However, little is known regarding the association between frailty and the human brain. We hypothesized that the brain structure could change according to frailty in patients with COPD and focused on cortical thickness. Cortical thickness measured by magnetic resonance imaging and frailty scores using the Kihon Checklist (KCL) were assessed in 40 patients with stable COPD and 20 healthy controls. Among the 34 regions assessed, multiple regions were thinner in patients with COPD than in healthy individuals (p < 0.05). We found significant negative correlations between the eight regions and the KCL scores only in patients with COPD. After adjusting for age and cognitive impairment, the association between the left and six right regions remained statistically significant. The correlation coefficient was the strongest in the bilateral superior frontal gyrus (left: ρ = - 0.5319, p = 0.0006) (right: ρ = - 0.5361, p = 0.0005). Interestingly, among the KCL scores, the daily activity domain showed the strongest correlation (sensitivity, 90%; specificity, 73%) with the bottom quartile of the reduction in the superior frontal gyrus. Frailty in patients with COPD is associated with a thickness reduction in the cortical regions, reflecting social vulnerability.

Gender Difference in the Relationship between Extrapulmonary Factors and Reduced Lung Function in Early Adulthood.

(1) Background: Reduced lung function in early adulthood is associated with future risks to health outcomes that have not been fully explored by gender. We investigated gender-specific relationships between lung function and extrapulmonary variables, assessing their potential as screening markers for respiratory dysfunction in young adults. (2) Methods: The participants were 151 medical students. Clinical data, handgrip strength (HS); body composition parameters such as skeletal muscle mass index (SMI), whole-body phase angle (WBPhA), and bone mineral content (BMC); and pulmonary function variables, vital capacity (VC), forced VC (FVC), and forced expiratory volume in one second (FEV1), were measured. (3) Results: FEV1 was significantly correlated with BMI, SMI, WBPhA, BMC, and both left and right HS (p < 0.0001, respectively) across all participants. According to gender, FEV1 had the strongest positive association with left HS in males (p < 0.0001) and BMC in females (p < 0.0001). The area under the curve for detecting the bottom quartile of FEV1 was 0.705 (cut-off 41.0 kg, sensitivity 91%) for left HS in males and 0.742 (cut-off 2.11 kg, sensitivity 81%) for BMC in females. (4) Conclusions: Gender-specific relationships between intrapulmonary and extrapulmonary factors such as left HS and BMC could be useful for screening suspected respiratory dysfunction in early adulthood.

Relief of Airflow Limitation and Airway Inflammation by Endoscopic Sinus Surgery in a Patient with Severe Asthma with Eosinophilic Chronic Rhinosinusitis.

Although endoscopic sinus surgery (ESS) is beneficial in improving asthma symptoms, its impact on the lung function in patients with asthma and chronic rhinosinusitis remains unclear. We herein report a case of severe asthma with eosinophilic chronic rhinosinusitis, in which ESS substantially improved airflow limitation and concomitantly reduced fractional exhaled nitric oxide and blood eosinophil counts. ESS likely relieved airflow limitation by suppressing type 2 inflammatory pathways. This case highlights ESS as a promising strategy for achieving clinical remission in patients with severe asthma and chronic rhinosinusitis.

A case of pulmonary edema due to guanfacine intoxication with measurement of serum guanfacine concentrations.

Guanfacine hydrochloride extended-release (GXR) is used to treat attention deficit hyperactivity disorder. It is a selective α2A-adrenorecepor agonist that was reported to cause QT prolongation and hypotension in the event of overdosing. We report the case of a 17-year-old man who took 226 tablets of GXR 3 mg for attempted suicide. He was found complaining of dyspnea, and emergency medical services were called. When the patient was transferred to our hospital, his Glasgow coma scale was 12 (E4V3M5). He was agitated and hypoxemic. He was intubated for invasive mechanical ventilation under sedation. His chest X-ray and computed tomography scan showed pulmonary edema. Transthoracic echocardiography showed markedly reduced cardiac function. His serum guanfacine concentration peaked on day 3 after admission. His pulmonary edema improved quickly after a decrease in serum guanfacine concentration, but cardiac decompensation persisted for about 1 month. This case reveals that the decline in cardiac function after guanfacine intoxication is prolonged even after its serum concentration has decreased.

Utility of the Shortness of Breath in Daily Activities Questionnaire (SOBDA-Q) to Detect Sedentary Behavior in Patients with Chronic Obstructive Pulmonary Disease (COPD).

Sedentary behavior has been shown to be an independent predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). However, physicians have difficulty ascertaining patients' activity levels because they tend to avoid shortness of breath. The reformed shortness of breath (SOB) in the daily activities questionnaire (SOBDA-Q) specifies the degree of SOB by measuring low-intensity activity behavior in everyday living. Therefore, we aimed to explore the utility of the SOBDA-Q in detecting sedentary COPD. We compared the modified Medical Research Council dyspnea scale (mMRC), COPD assessment test (CAT), and SOBDA-Q with physical activity levels (PAL) in 17 healthy patients, 32 non-sedentary COPD patients (PAL ≥ 1.5 METs·h), and 15 sedentary COPD patients (PAL < 1.5 METs·h) in this cross-sectional study. CAT and all domains of the SOBDA-Q in all patients are significantly correlated with PAL, even after adjusting for age. The dietary domain has the highest specificity, and the outdoor activity domain has the highest sensitivity for detecting sedentary COPD. Combining these domains helped determine patients with sedentary COPD (AUC = 0.829, sensitivity = 1.00, specificity = 0.55). The SOBDA-Q is associated with PAL and could be a useful tool for determining patients with sedentary COPD. Moreover, eating and outing inactivity claims reflect sedentary behavior in patients with COPD.

A case of development of autoimmune pulmonary alveolar proteinosis during the treatment of hypersensitivity pneumonitis.

Herein, we report the case of a 73-year-old woman with an occupational history of plaster grinding who developed autoimmune pulmonary alveolar proteinosis (PAP) during the treatment of fibrotic hypersensitivity pneumonitis with steroids and immunosuppressive drugs. Based on the changes in computed tomography imaging findings, poor response to steroid therapy, and markedly elevated KL-6 levels, PAP was suspected and diagnosed by bronchoscopy. Repeated segmental bronchoalveolar lavage under high-flow nasal cannula oxygen therapy resulted in slight improvement. Steroids and immunosuppressive treatments for other interstitial lung diseases may cause PAP or exacerbate latent PAP.

A Real-World Study of Achievement Rate and Predictive Factors of Clinical and Deep Remission to Biologics in Patients with Severe Asthma.

BACKGROUND: Recent advances in biologics have provided new insights into the clinical course of asthma, including disease modification, clinical remission (CR), and deep remission (DR). However, the extent to which biologics achieve CR and DR in severe asthma patients is poorly understood. METHODS: To assess the achievement rate and predictors of CR and DR using long-term biologics, we retrospectively evaluated 54 severe asthma patients recently started on biologics. "CR" denotes the achievement of all three criteria: (1) absence of asthma symptoms, (2) no asthma exacerbations, and (3) no use of oral corticosteroids. DR denoted CR plus (4) normalized pulmonary function and (5) suppressed type 2 inflammation. RESULTS: CR and DR achievement rates were 68.5% and 31.5%, respectively. Compared with the non-deep remission group, the DR group had higher adult-onset asthma rates (94.1% vs. 70.3%, p = 0.078), shorter asthma duration (5 vs. 19 years, p = 0.006), and higher FEV1 (91.5% vs. 71.5%, p < 0.001). There were no significant differences in the Asthma Control Questionnaire scores, exacerbation frequency, or type 2 inflammation at baseline between groups. Asthma duration combined with FEV1 can stratify the achievement rates of CR and DR. CONCLUSIONS: the early introduction of biologics in severe asthma patients may help achieve CR and DR.

Detection of impaired gas exchange using the 1-minute sit-to-stand test in patients with interstitial lung disease.

BACKGROUND: Although pulmonary function tests (PFTs) are important in patients with interstitial lung disease (ILD), they cannot be easily performed in a primary healthcare setting. This study aimed to examine the usefulness of the difference between pulse oxygen saturation (SpO2) at rest and the lowest SpO2 during the 1-min sit-to-stand test (delta SpO2-1STST) for predicting pulmonary function impairment. METHODS: We retrospectively reviewed 116 patients with ILD who underwent 1STST and PFTs. RESULTS: The delta SpO2-1STST and diffusing capacity for carbon monoxide (DLco) strongly correlated (ρ = 0.70). The delta SpO2-1STST was effective in predicting impaired gas exchange (cut-off value, -4%; AUC, 0.86; sensitivity, 74%; specificity, 87%). CONCLUSIONS: The Delta SpO2-1STST may be a reasonable tool for predicting abnormalities in PFTs.

Platypnea-orthodeoxia syndrome in a patient with ongoing COVID-19.

SARS-CoV-2 infection of the vascular endothelium causes excessive vasodilation. It is important in the rehabilitation of patients with COVID-19 to recognize that increased blood flow in lung lesions at the base of the lung due to vasodilation may cause V/Q mismatch and result in platypnea-orthodeoxia syndrome.

Invasive thymoma extending to the right atrium with superior vena cava syndrome presenting massive intracardiac thrombosis immediately after the start of chemotherapy: an autopsy case report.

Invasive thymomas with intraluminal tumor thrombi are rare. Removal of the thymoma and infiltration of the superior vena cava (SVC) is a curative alternative. We report an autopsy case of invasive thymoma with intraluminal growth into the intracardiac right atrium extension. Furthermore, the patient died of massive intracardiac thrombosis 5 days after the start of chemotherapy. A 66-year-old man with SVC syndrome was referred to our hospital. He had been aware of swelling of the face for 6 months. The patient was diagnosed with invasive thymoma by a CT-guided needle biopsy of the anterior mediastinal mass. Contrast-enhanced chest computed tomography showed a mass in the anterior mediastinum extending to the SVC and right atrium. As a result of discussion with surgeons and radiotherapists, we planned a multidisciplinary treatment in which neoadjuvant chemotherapy would reduce the tumor size, and surgery and postoperative radiotherapy were followed by chemotherapy. He was administered neo-adjuvant chemotherapy with CBDCA + PTX (carboplatin, area under the curve = 6, and paclitaxel, 200 mg/m2). On the 4th day of chemotherapy, he suddenly developed obstructive shock due to intracardiac thrombosis in the right ventricle. We believe that chemotherapy may trigger rapid thrombus formation. If an invasive thymoma spreads into a large vessel or the right atrium, surgical treatment should be considered if possible. However, if surgery is impossible, administration of anticoagulants should be considered to prevent thrombus formation before chemotherapy.

False-positive Elevation of Beta-D-glucan and Aspergillus Galactomannan Levels Due to Mendelson's Syndrome after Rice Aspiration.

Both 1,3-beta-D-glucan (BDG) and galactomannan (GM) are polysaccharide components of the fungal cell wall. Although elevated levels of serum BDG and Aspergillus GM suggest invasive fungal infection or Pneumocystis pneumonia and aspergillosis, respectively, it is also necessary to consider the possibility of false-positives. We herein report a 68-year-old man with marked elevation in serum BDG and GM levels accompanied by Mendelson's syndrome after rice aspiration. With the improvement of Mendelson's syndrome, his serum BDG and GM levels decreased. The false-positive serum BDG and GM findings may have been due to his aspiration of food containing them. It is important to take a detailed history of aspiration in addition to making a conventional differential diagnosis in patients with pneumonia with elevated serum BDG and GM levels.

Antineutrophil cytoplasmic antibody-negative granulomatosis with polyangiitis localized to the lungs.

Patients with granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, sometimes exhibit no clinical features. Here, we describe a case of antineutrophil cytoplasmic antibody (ANCA)-negative GPA presenting with only lung granuloma. A 55-year-old woman with a right upper lung mass underwent lobectomy for suspected lung cancer; however, only granuloma was detected, and the etiology was not identified. Serum ANCA results were negative. Four years postoperatively, another pulmonary nodule appeared in the left lung's apex. The kidneys and sinuses were not impaired, but re-examination of the resected specimen revealed necrotizing vasculitis and granulomas around the vessels. Thus, the patient was diagnosed with GPA localized to the lungs. Although this was a non-life-threatening disease, the patient was administered oral prednisolone (PSL) and intravenous cyclophosphamide (IVCY) to prevent fatal complications of GPA as she was non-elderly and had no comorbidities, leading to a decrease in the mass size. Detailed re-examination by expert pulmonary pathologists could aid in GPA diagnosis when clinical features are absent, as in our case. In patients with granulomas of unknown etiology, a careful multidisciplinary approach is pivotal in the diagnosis. If patients tolerate adverse effects, a PSL and IVCY combination may prevent fatal outcomes, even in patients with non-life-threatening disease.

The 1-minute sit-to-stand test to detect desaturation during 6-minute walk test in interstitial lung disease.

Although the 6 min walk test (6MWT) is well-established for assessing desaturation in patients with interstitial lung disease (ILD), it cannot be easily performed in primary healthcare settings. This retrospective observational study aimed to evaluate the usefulness of the 1 min sit-to-stand test (1STST) for assessing desaturation during 6MWT in ILD patients with normal resting blood oxygen levels. We included 116 patients, and the pulse oxygen saturation (SpO2) for both methods was analyzed. The SpO2 nadir during the 1STST and 6MWT correlated strongly (ρ = 0.82). The frequency of patients with nadir SpO2 < 90% was consistent for both tests (κ = 0.82). 1STST was superior to diffusing capacity for carbon monoxide in detecting desaturation during the 6MWT. These findings were similarly stratified according to performance status or dyspnea scale. The 1STST can easily measure exertional desaturation in ILD patients with normal resting blood oxygen levels and is an alternative to the 6MWT.

Improved Prognostic Prediction by Combination of Early Initiation of Polymyxin B Hemoperfusion with Modified Gender-Age-Physiology Index in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

INTRODUCTION: Respiratory failure from acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. Direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP) has been reported to have beneficial effects on patients with AE-IPF. Whether patient characteristics influence the extent of this benefit remains unclear. METHODS: We retrospectively examined the records of 30 patients with AE-IPF who underwent PMX-DHP. The favorable factors of survival were determined using Cox proportional hazards analyses. RESULTS: The 1- and 12-month survival rates after PMX-DHP were 70.0% and 50.0%, respectively. The multivariate analysis revealed that low modified Gender-Age-Physiology (GAP) index (≤8 points) (hazard ratio [HR] 0.317, p = 0.015) and PMX-DHP received within 48 h of steroid pulse (HR 0.289, p = 0.012) were favorable factors. Notably, even in the patients with high modified GAP index (>8 points), that is, more advanced IPF, those who received PMX-DHP within 48 h of steroid pulse had a better prognosis than those who did after 48 h of the steroid pulse (p = 0.032). CONCLUSIONS: Early PMX-DHP initiation in patients with AE-IPF, specifically within 48 h after the steroid pulse therapy, may improve prognosis regardless of the severity of chronic phase of IPF before AE-IPF.

Impact of Frailty on Hippocampal Volume in Patients with Chronic Obstructive Pulmonary Disease.

Brain frailty may be related to the pathophysiology of poor clinical outcomes in chronic obstructive pulmonary disease (COPD). This study examines the relationship between hippocampal subfield volumes and frailty and depressive symptoms, and their combined association with quality of life (QOL) in patients with COPD. The study involved 40 patients with COPD. Frailty, depressive symptoms and QOL were assessed using Kihon Checklist (KCL), Hospital Anxiety and Depression Scale (HADS), and World Health Organization Quality of Life Assessment (WHO/QOL-26). Anatomical MRI data were acquired, and volumes of the hippocampal subfields were obtained using FreeSurfer (version 6.0). Statistically, HADS score had significant association with WHO/QOL-26 and KCL scores. KCL scores were significantly associated with volumes of left and right whole hippocampi, presubiculum and subiculum, but HADS score had no significant association with whole hippocampi or hippocampal subfield volumes. Meanwhile, WHO/QOL-26 score was significantly associated with volume of the left CA1. There was a significant association between frailty, depression, and QOL. Hippocampal pathology was related to frailty and, to some extent, with QOL in patients with COPD. Our results suggest the impact of frailty on hippocampal volume and their combined associations with poor QOL in COPD.

Non-pneumophila Legionella species pneumonia with orange-coloured sputum.

We herein report an immunocompromised patient familiar with gardening admitted to our hospital suffering from severe pneumonia caused by Legionella longbeachae. We suspected non-pneumophila Legionella species pneumonia because of gardening habits, the negative urine antigen test and the non-significant Gram staining results of orange-coloured sputum. The pathogen was identified using mass spectrometry analysis of bronchoalveolar lavage fluid. It is important to perform the medical interview carefully, noting the colour of sputum and gardening habits, for diagnosis and targeted therapy of non-pneumophila Legionella species pneumonia, even if the urine Legionella antigen test is negative.

Abundant TNF-LIGHT expression in the airways of patients with asthma with persistent airflow limitation: Association with nitrative and inflammatory profiles.

BACKGROUND: The role of the inflammatory secretory protein TNF-LIGHT (LIGHT) in the molecular mechanisms underlying persistent airflow limitation (PAL) in asthma remains unclear. We hypothesized that high airway LIGHT expression may be a feature of asthma with PAL associated with specific expression patterns of inflammatory molecules. METHODS: This hypothesis was tested in 16 patients with asthma on inhaled corticosteroid treatment. Induced sputum was collected, the expression of LIGHT and 3-nitrotyrosine (NT), which reflects the footprint of reactive nitrogen species content, was measured using immunohistochemical staining, and the inflammatory molecules in the sputum supernatant were analyzed using a magnetic bead array. RESULTS: LIGHT staining in the cells had a significantly higher intensity in participants with PAL than in participants without PAL (47.9 × 104/ml vs. 5.4 × 104/ml; p < 0.05). The array analysis indicated that IL-8, IL-19, matrix metalloproteinase 2, and osteopontin, were associated with high LIGHT immunoreactivity. The fractionation of 3-NT-positive cells was positively correlated with that of LIGHT-positive cells (r = 0.57, p < 0.05) and the TGF-ß1 level (r = 0.61, p < 0.05). LIGHT- and 3-NT-positive cells showed significant positive correlation with the differential cell counts of neutrophils, macrophages, and eosinophils in the induced sputum. Intense immunoreactivities of LIGHT (r = -0.54, p < 0.05) and 3-NT (r = -0.42, p = 0.1) were negatively associated with decreased forced expiratory volume in 1/forced vital capacity ratio. CONCLUSIONS: The findings suggest that LIGHT is a key component in the association between airway inflammation and airflow limitation in patients with asthma, and its expression may be persistently correlated with the abundance of inflammatory cells and inflammatory and profibrogenic radical/molecules.

Impact of sinus surgery on type 2 airway and systemic inflammation in asthma.

Objective: Asthma is frequently associated with chronic rhinosinusitis with nasal polyps (CRSwNP). Although endoscopic sinus surgery (ESS) improves asthma control in CRSwNP patients with asthma, the mechanism that underlies the response to surgical treatment is still unclear. We evaluated the relevance of changes in asthma control and changes in airway/systemic inflammation in eosinophilic CRSwNP patients with not well controlled asthma who underwent ESS.Methods: We prospectively assessed changes in the asthma control questionnaire (ACQ) score, blood eosinophil counts (B-Eos), forced expiratory volume in 1 s (FEV1), and fraction of exhaled nitric oxide (FeNO) levels at 1-week before and 8 and 52 weeks after ESS.Results: Twenty-five subjects were analyzed. The ACQ score, B-Eos, and FeNO decreased, and FEV1 increased significantly after ESS. In the period from baseline to 52 weeks after ESS, changes in ACQ were significantly correlated with the changes in blood eosinophil counts (r = 0.58, p<.01) and FeNO (r = 0.45, p<.05). Ten subjects (40%) showed consistently improved asthma control at 52-weeks after ESS. In the remaining subjects, although the ACQ score temporarily improved at 8-weeks after ESS, but eventually deteriorated at 52-weeks. Higher levels of total immunoglobulin E were associated with long-term improved asthma control after ESS.Conclusions: In eosinophilic CRSwNP patients with asthma, sinus surgery impacts asthma control through the suppression of airway/systemic type 2 inflammation. The present study reinforced the common pathophysiology of type 2 inflammation between the upper and lower airways.