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.

Persistently high exhaled nitric oxide and loss of lung function in controlled asthma.

BACKGROUNDS: It remains unclear whether a persistently high exhaled nitric oxide fraction (FeNO) in patients with controlled asthma is associated with the progressive loss of lung function. METHODS: This was a 3-year prospective study. We examined the changes in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1) and FeNO in 140 patients with controlled asthma. We initially determined the FeNO cut-off point for identifying patients with a rapid decline in FEV1 (>40 mL/yr). Next, a total of 122 patients who maintained high or non-high FeNO were selected, and the associations between the FeNO trend and changes in FEV1 and bronchodilator response (BDR) were investigated. RESULTS: A FeNO level >40.3 ppb yielded 43% sensitivity and 86% specificity for identifying patients with a rapid decline in FEV1. Patients with persistently high FeNO had higher rates of decline in FEV1 (42.7 ± 37.5 mL/yr) than patients with non-high FeNO (16.7 ± 31.5 mL/yr) (p < 0.0005). The changes in BDR from baseline to the end of the study, in patients who had high or non-high levels of FeNO were -0.8% and 0.1%, respectively (p < 0.01). In a multivariate analysis adjusted by age, body mass index, asthma control, blood eosinophil numbers, and FEV1% of predicted, a FeNO level of ≥40 ppb was independently associated with an accelerated decline in FEV1 (p < 0.05). CONCLUSIONS: This study suggests that FeNO is potentially valuable tool for identifying individuals who are at risk of a progressive loss of lung function among patients with controlled asthma.

Interleukin-18 expression, CD8(+) T cells, and eosinophils in lungs of nonsmokers with fatal asthma.

BACKGROUND: The process of airway inflammation in the lungs of nonsmokers who die of asthma (fatal asthma) has not been reported in detail. OBJECTIVE: To examine nonsmokers who had died of asthma to exclude chronic obstructive pulmonary disease and investigate pulmonary inflammatory cells and the expression of interleukin-18 (IL-18) and its receptor in lung tissues compared with those in patients with well-controlled mild asthma and nonsmokers. METHODS: Lung tissues were obtained at autopsy examination from 12 nonsmokers with fatal asthma, excluding cases of chronic obstructive pulmonary disease, and from 5 nonsmokers with well-controlled mild asthma and 10 nonsmokers who had undergone surgical resection for lung cancer. Pulmonary inflammatory cells were examined and the expression of the proinflammatory cytokine IL-18 and its receptor in the lungs was evaluated. RESULTS: The numbers of eosinophils and lymphocytes, but not basophils or macrophages, were significantly increased in the lungs of patients with fatal asthma compared with the other 2 groups. The lung neutrophil count did not differ significantly between the fatal and mild asthma groups but was significantly higher in the fatal asthma group than in nonsmokers. CD8(+) T cells, but not CD4(+) T cells, were significantly increased in the lungs of the fatal asthma group compared with the other 2 groups. IL-18 protein and IL-18 receptor were strongly expressed in the lungs in the fatal asthma group. CONCLUSION: Caspase-1 inhibitors, anti-IL-18 antibodies, anti-IL-18 receptor antibodies, IL-18 binding protein, or inhibitors of genes downstream of the IL-18 signal transduction pathway may be of clinical benefit for the treatment of patients with severe asthma.

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.

Diagnostic Utility of Specific Frailty Questionnaire: The Kihon Checklist for Hippocampal Atrophy in COPD.

Background/Objectives: COPD patients who are frail have been reported to develop brain atrophy, but no non-invasive diagnostic tool has been developed to detect this condition. Our study aimed to explore the diagnostic utility of the Kihon Checklist (KCL), a frailty questionnaire, in assessing hippocampal volume loss in patients with COPD. Methods: We recruited 40 COPD patients and 20 healthy individuals using the KCL to assess frailty across seven structural domains. Hippocampal volumes were obtained from T1-weighted MRI images, and ROC analysis was performed to detect hippocampal atrophy. Results: Our results showed that patients with COPD had significantly greater atrophic left hippocampal volumes than healthy subjects (p < 0.05). The univariate correlation coefficient between the left hippocampal volume and KCL (1-20), which pertains to instrumental and social activities of daily living, was the largest (ρ = -0.54, p < 0.0005) among the KCL subdomains. Additionally, both KCL (1-25) and KCL (1-20) demonstrated useful diagnostic potential (93% specificity and 90% sensitivity, respectively) for identifying individuals in the lowest 25% of the left hippocampal volume (AUC = 0.82). Conclusions: Our study suggests that frailty questionnaires focusing on daily vulnerability, such as the KCL, can effectively detect hippocampal atrophy in COPD patients.

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.

Positive association between the plasma levels of 5-hydroxyindoleacetic acid and the severity of depression in patients with chronic obstructive pulmonary disease.

BACKGROUND: The role of plasma monoamines in patients with chronic obstructive pulmonary disease (COPD) with depression is unclear. To investigate monoamines in 20 depressed patients with COPD, the plasma concentrations of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured and compared with those in 50 non-depressed COPD patients, and also with 23 age- and gender-matched non-smokers and 13 smokers as non-depressed healthy controls. METHODS: Diagnosis of depression was assessed using the Centre for Epidemiologic Studies Depression Scale. Plasma concentrations of monoamines were measured by high-performance liquid chromatography. RESULTS: None of the depressed COPD patients had suicidal ideation. The plasma 5-HIAA level [median, (25% and 75% quartiles)] in depressed COPD patients [6.8 ng/mL, (4.9 and 13.1)] was significantly higher than in non-depressed COPD patients [5.4, (4.2 and 7.5)] (p=0.022) and non-smokers [5.1 (3.8 and 7.2)] (p=0.041), but not smokers [4.7, (4.0 and 6.7)] (p>0.05). The plasma 5-HIAA level (r=0.24, p=0.049) was significantly associated with the severity of depression in patients with COPD. The plasma MHPG level was significantly higher in depressed COPD patients (p=0.043) than in smokers, but was not higher than that in non-depressed COPD patients or non-smokers, although the level of MHPG was not associated with the severity of depression. CONCLUSION: The plasma 5-HIAA level is increased in depressed COPD patients. Plasma monoamines may be a good biomarker for detection of depression in patients with COPD.

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.

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.

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.

Depression, but not sleep disorder, is an independent factor affecting exacerbations and hospitalization in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) may experience depression and sleep disorders, which can adversely affect their health-related quality of life (HRQOL). The aim of this study was to investigate depression and sleep disorders among 85 COPD patients and 46 control subjects, aged 40 years and over. METHODS: Patients underwent spirometry and arterial blood gas analysis, self-completed St. George's respiratory questionnaire and were assessed on the center for epidemiologic studies depression (CES-D) and the Pittsburgh sleep quality index (PSQI). The frequency of exacerbations among COPD patients was prospectively monitored for 12 months. RESULTS: The prevalence of depression and sleep disorders was significantly higher among COPD patients than control subjects. The relative risks (95% confidence interval) of depression and sleep disorders were 7.58 (1.03 to 55.8) and 1.82 (1.03 to 3.22), respectively, in COPD patients compared with control subjects. Among COPD patients, there was a correlation between CES-D and PSQI. Lower body mass index, more severe dyspnoea, poorer HRQOL, lower partial pressure of arterial oxygen and higher partial pressure of arterial carbon dioxide were significantly associated with the incidence of depression and sleep disorders. Exacerbations and hospitalizations were more frequent among COPD patients with depression than those with sleep disorders alone or those without depression or sleep disorders. CONCLUSIONS: Depression and sleep disorders are very common co-morbidities among COPD patients and significantly reduce activities and HRQOL among these patients. Depression, but not sleep disorder, is an independent risk factor for exacerbations and hospitalization among COPD patients.

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.

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.

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.

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.