Respiratory Bronchiolitis-associated Interstitial Lung Disease with Unusual Histopathological Findings

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a mild inflammatory reaction commonly seen in asymptomatic young male cigarette smokers. This report describes unusual pathological findings in a 63-yearold Japanese female with RB-ILD. She had a 40 pack-year smoking history. Chest computed tomography showed multiple patchy shadows, especially in the right lower lobe. Diagnosis could not be established by bronchoalveolar lavage and transbronchial lung biopsy. Thoracoscopic lung biopsy was performed from right S5 and S9, which demonstrated the typical pathological findings of RB-ILD, including the presence of pigmented macrophages within respiratory bronchioles, thickening of alveolar septa by fibrosis, accumulation of intrapulmonary blue bodies and lack of granulomatous changes. Our patient had atypical RB-ILD based on old age at presentation (commonly -40 years of age), marked fibrosis and presence of numerous blue bodies

Associations of chemical composition and sources of PM2.5 with lung function of severe asthmatic adults in a low air pollution environment of urban Nagasaki, Japan

Previous studies have linked ambient PM2.5 to decreased pulmonary function, but the influence of specific chemical elements and emission sources on the severe asthmatic is not well understood. We examined the mass, chemical constituents, and sources of PM2.5 for short-term associations with the pulmonary function of adults with severe asthma in a low air pollution environment in urban Nagasaki, Japan. We recruited 35 asthmatic adults and obtained the daily record of morning peak expiratory flow (PEF) in spring 2014–2016. PM2.5 filters were extracted from an air quality monitoring station (178 days) and measured for 27 chemical elements. Source apportionment was performed using Positive Matrix Factorization (PMF). We fitted generalized linear model with generalized estimating equation (GEE) method to estimate changes in PEF (from personal monthly maximum) and odds of severe respiratory deterioration (first ≥ 15% PEF reduction within a 1-week interval) associated with mass, constituents, and sources of PM2.5, with adjustment for temperature and relative humidity. Constituent sulfate (SO42−) and PM2.5 from oil combustion and traffic were associated with reduced PEF. An interquartile range (IQR) increase in SO42− (3.7 μg/m3, average lags 0–1) was associated with a decrease of 0.38% (95% confidence interval = −0.75% to −0.001%). An IQR increase in oil combustion and traffic-sourced PM2.5 (2.64 μg/m3, lag 1) was associated with a decrease of 0.33% (−0.62% to −0.002%). We found a larger PEF decrease associated with PM2.5 from dust/soil on Asian Dust days. There was no evidence linking total mass and metals to reduced pulmonary function. The ventilatory capacity of adults with severe asthma is susceptible to specific constituents/sources of PM2.5 such as sulfate and oil combustion and traffic despite active self-management of asthma and low air pollution levels in the study location

One-year risk of stroke after transient ischemic attack or minor stroke in Hunter New England, Australia (INSIST study)

Background: One-year risk of stroke in transient ischemic attack and minor stroke (TIAMS) managed in secondary care settings has been reported as 5-8%. However, evidence for the outcomes of TIAMS in community care settings is limited. Methods: The INternational comparison of Systems of care and patient outcomes In minor Stroke and TIA (INSIST) study was a prospective inception cohort community-based study of patients of 16 general practices in the Hunter–Manning region (New South Wales, Australia). Possible-TIAMS patients were recruited from 2012 to 2016 and followed-up for 12 months post-index event. Adjudication as TIAMS or TIAMS-mimics was by an expert panel. We established 7-day, 90-day, and one-year risk of stroke, TIA, myocardial infarction (MI), coronary or carotid revascularization procedure and death; and medications use at 24 hours post-event. Results: Of 613 participants (mean age; 70 ± 12 years), 298 (49%) were adjudicated as TIAMS. TIAMS-group participants had ischemic strokes at 7-days, 90-days, and one-year, at Kaplan-Meier (KM) rates of 1% (95% confidence interval; 0.3, 3.1), 2.1% (0.9, 4.6), and 3.2% (1.7, 6.1), respectively, compared to 0.3%, 0.3% and 0.6% of TIAMS-mimic-group participants. At one year, TIAMS-group-participants had twenty-five TIA events (KM rate: 8.8%), two MI events (0.6%), four coronary revascularization (1.5%), eleven carotid revascularization (3.9%) and three death (1.1%), compared to 1.6%, 0.6%, 1.0%, 0.3% and 0.6% of TIAMS-mimic-group participants. Of 167 TIAMS-group participants who commenced or received enhanced therapies, 95 (57%) were treated within 24 hours post-index event. For TIAMS-group participants who commenced or received enhanced therapies, time from symptom onset to treatment was median 9.5 hours [IQR 1.8-89.9]). Conclusion: One-year risk of stroke in TIAMS participants was lower than reported in previous studies. Early implementation of antiplatelet/anticoagulant therapies may have contributed to the low stroke recurrence

Effect of Respiratory Syncytial Virus Infection on Plasmacytoid Dendritic Cell Regulation of Allergic Airway Inflammation.

Background: Respiratory syncytial virus (RSV) can infect myeloid dendritic cells (mDCs) and regulate their function in the development of allergy. It has been widely reported that plasmacytoid DCs (pDCs) play a critical role in antiviral innate immunity. In contrast, not much is known about the role of pDCs in the interaction between allergy and viral infection. The purpose of the present study was to investigate the effect of RSV infection on pDC function in the regulation of allergic airway inflammation in a murine model of Dermatophagoides farinae-sensitized allergic asthma. Methods: Splenic pDCs isolated from D. farinae-sensitized donor mice were infected with live RSV ex vivo. Subsequently, these pDCs were inoculated into the airways of D. farinae-sensitized recipient mice. Lung pathology, lung tissue cytokine profiles, the number of regulatory T cells (T(reg)) and mDCs as well as the effects of IL-10 neutralization in the lung tissue of recipient mice were determined. Results: Intranasal inoculation of D. farinae-sensitized pDCs significantly inhibited the development of allergic airway inflammation and both Th1 and Th2 immunity. Live RSV infection of these pDCs prior to inoculation interfered with their inhibitory effects through decreasing T(reg) and IL-10 and increasing mDCs. Conclusions: In asthmatic airways, pDCs mediate tolerance to inhaled allergens through the regulation of T(reg), IL-10 and mDCs. RSV infection of pDCs potentially inhibits their immunotolerogenic effects and thus exacerbates allergic airway inflammation

Observational study of the additive effects of pranlukast on inflammatory markers of clinically stable asthma with inhaled corticosteroids and long-acting beta 2 agonists.

BACKGROUND: Little is understood about the additive effects of leukotriene receptor antagonists (LTRA) on asthmatics currently medicated with inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA). OBJECTIVES: The present study examines the anti-inflammatory effects of the LTRA pranlukast in addition to ICS and LABA, among asthmatic patients with normal pulmonary function and unremarkable clinical symptoms. METHODS: Fifteen adult asthmatics participated in a 2-month, open-label, uncontrolled, prospective, multicenter, observational trial. Patients stabilized (predicted forced expiratory volume in 1 s >80%) by medication with ICS and LABA were also given pranlukast (450 mg daily). Asthma-related symptoms, pulmonary function, blood eosinophil counts and several inflammatory markers in sputum were monitored at week 0, as well as at 4 and 8 weeks after starting therapy with pranlukast. RESULTS: Adding pranlukast did not further improve blood eosinophil counts, pulmonary function and symptoms, but significantly attenuated sputum cysteinyl leukotrienes, tumor necrosis factor-alpha and interleukin-5 concentrations. CONCLUSIONS: Although the clinical relevance remains obscure, adding an LTRA attenuates allergic airway inflammation in some asthmatics undergoing treatment with ICS and LABA

Whole blood viscosity is associated with baseline cerebral perfusion in acute ischemic stroke

Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk factor for stroke. Poor microcirculation due to elevated WBV can prevent adequate perfusion of the brain and might act as an important secondary factor for hypoperfusion in acute ischaemic stroke. In the present study, we examined the association of WBV with basal cerebral perfusion assessed by CT perfusion in acute ischaemic stroke. Confirmed acute ischemic stroke patients (n = 82) presenting in hours were recruited from the single centre. Patients underwent baseline multimodal CT (non-contrast CT, CT angiography and CT perfusion). Where clinically warranted, patients also underwent follow-up DWI. WBV was measured in duplicate within 2 h after sampling from 5-mL EDTA blood sample. WBV was significantly correlated with CT perfusion parameters such as perfusion lesion volume, ischemic core volume and mismatch ratio; DWI volume and baseline NIHSS. In a multivariate linear regression model, WBV significantly predicted acute perfusion lesion volume, core volume and mismatch ratio after adjusting for the effect of occlusion site and collateral status. Association of WBV with hypoperfusion (increased perfusion lesion volume, ischaemic core volume and mismatch ratio) suggest the role of erythrocyte rheology in cerebral haemodynamic of acute ischemic stroke. The present findings open new possibilities for therapeutic strategies targeting erythrocyte rheology to improve cerebral microcirculation in stroke