Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Does Low FEV1 in Addition to Fixed Ratio and/or Lower Limit of Normal of FEV1/FVC Improve Prediction of Mortality in COPD? The NHANES-III-linked-mortality Cohort

Purpose

There is presently an ongoing debate on the relative merits of suggested criteria for spirometric airway obstruction. This study tests the null hypothesis that no superiority exists with the use of fixed ratio (FR) of forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) < 0.7 versus less than lower limit predicted (LLN) criteria with or without FEV1 <80% predicted in regards to future mortality.

Time course of the increase in airway responsiveness associated with late asthmatic reactions to toluene diisocyanate in sensitized subjects

To understand better the mechanism of the increase in airway responsiveness associated with late asthmatic reactions, we determined the time course of toluene diisocyanate (TDI) effect on airway responsiveness in six sensitized subjects who exhibited a late asthmatic response after TDI exposure (0.018 +/- 0.005 ppm, 30 min) in the laboratory. Airway responsiveness was assessed before TDI exposure and then at 8 hr, 1 day, 1 wk, and 1 mo after TDI exposure. To assess responsiveness we determined the provocative dose of methacholine causing a decrease in FEV1 of 20% (PD20FEV1). The methacholine PD20 decreased from 0.50 mg geometric standard error of the mean (GSEM = 1.54) to 0.06 mg (GSEM = 1.55) (p less than 0.001) at 8 hr after exposure to TDI, was still decreased to 0.15 mg (GSEM = 1.93) (p less than 0.05) at 1 day, returned to 0.26 mg (GSEM = 1.91) (p greater than 0.05) at 1 wk, and returned to 0.43 mg (GSEM = 1.71) at 1 mo, indicating that full recovery occurred within 1 to 4 wk. These results demonstrate that TDI-induced late asthmatic response is associated with a reversible increase in airway responsiveness to methacholine and suggest that the TDI effect is linked to an acute inflammatory response in the airways.     

Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline

Background

Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre-BD) forced expiratory volume in 1 second (FEV₁) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate-to-severe (phase 3) asthma.

Methods

In patients on high-dose inhaled corticosteroids (ICS) with type 2-high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre-BD FEV₁ and asthma control (5-item asthma control questionnaire [ACQ-5]) were analyzed.

Results

In high-dose ICS type 2-high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%-69%/57%-60% (all P<.05) and 53%-69%/48%-66% (all P < .001), respectively, except in patients with ≥ 300 eosinophils/µL in phase 2b study (24%/50% (P = .52/0.15). Across subgroups, pre-BD FEV₁ improved by 0.18-0.22 L/0.19-0.24 L (all P < .05) and 0.23-0.36 L/0.15-0.25 L (all P < .01) and ACQ-5 scores were reduced by 0.46-0.55/0.47-0.85 (all P < .05) and 0.38-0.50/0.24-0.30 (all P < .05), respectively, except dupilumab 200 mg q2w in phase 2b in patients with FeNO ≥ 25 ppb (0.41; P = .09). Dupilumab was also effective in patients taking medium-dose ICS.

Conclusion

Dupilumab significantly reduced severe exacerbations and improved lung function and asthma control in patients with type 2-high asthma on high-dose ICS at baseline.

     

清咳平喘颗粒治疗痰热郁肺型咳嗽的临床疗效观察

目的 观察清咳平喘颗粒治疗痰热郁肺型咳嗽的临床有效性。方法 选取2020年1月—2021年6月上海中医药大学附属龙华医院呼吸科门诊就诊的痰热郁肺型咳嗽患者100例,按随机数字表法分为对照组和治疗组各50例,对照组为西医常规治疗,治疗组在西医常规治疗基础上联合清咳平喘颗粒治疗。两组均连续治疗2周。观察两组患者治疗前后的中医证候、咳嗽症状、气道反应（血清免疫球蛋白E、外周血嗜酸性粒细胞）、肺功能［最大呼气流量、第1秒用力呼气容积（forced expiratory volume for 1 second,FEV1）与用力肺活量（forced vital capacity,FVC）的比值］、生活质量及不良反应情况。结果 治疗后,对照组和治疗组的总有效率分别是90%、94%,两组比较差异无统计学意义（P>0.05）。治疗后,两组患者中医证候评分、日间及夜间咳嗽积分较治疗前降低,且治疗组明显低于对照组（P<0.05）。治疗后,两组血清免疫球蛋白E、外周血嗜酸性粒细胞较治疗前明显下降,且治疗组气道反应指标改善好于对照组（P<0.05）。治疗后,两组最大呼气流量、FEV1/FVC较治疗前明显上升（P<0.05）,但两组比较差异无统计学意义（P>0.05）。随访时两组患者的生活质量评分较治疗前均显著升高,治疗组评分改善优于对照组,两组比较差异具有统计学意义（P<0.05）。治疗期间两组均未发生不良反应。结论 清咳平喘颗粒在治疗痰热郁肺型咳嗽安全性良好,有助于改善咳嗽症状,改善肺通气,提高患者生活质量。     

中西医结合治疗支气管哮喘的临床观察

为了探讨支气管哮喘的治疗方法,将本病患者87例随机分为中西医结合治疗组46例和西药对照组41例,治疗组用中西医结合方法治疗,对照组单纯用西医方法治疗;观察两组症状、体征治疗前后的变化.治疗组总有效率86.96%,对照组总有效率73.81%,两组疗效有显著性差异(P＜0.05);肺功能改善治疗组明显优于对照组.应用中西医结合方法治疗支气管哮喘的疗效明显优于单用西医治疗.     

Evaluating the Health Risk from Secondary Sulfates in Eastern North American Regional Ambient Air Particulate Matter

Epidemiological studies of particulate matter (PM) using central area monitors have associated total PM mass, as well as certain individual components of PM, including sulfate, with adverse human health effects. However, some recent studies that used concentrated ambient particles (CAPs) or analyzed the effects of air pollution from different sources or geographic areas suggest that while some particles may be harmful, other particulate species including secondary sulfates may have negligible health effects. Toxicology studies to date also suggest that secondary sulfates pose little health risk. While studies using central-area monitors implicitly assume that all residents of the area are exposed to the same levels of pollution, newer studies find substantial health effects for those in close proximity to major roads. These latter studies recognize that although population exposure to widespread pollutants, such as total PM mass and sulfates, may be relatively uniform over a wide area, exposure to pollutants from local sources is not. While there is an emerging literature associating several adverse health effects with proximity to local pollution sources, the current database provides limited information that allows identification of specific particulate species that may cause little to no harm. In this article, we suggest that ambient secondary sulfates, and eastern North American regional air masses generally, appear to have little adverse impact on public health. This suggestion is based on evidence gleaned from eight avenues of investigation: (1) recent non-central-area monitor studies, including exposure gradient or proximity studies; (2) CAPs studies; (3) studies that examine effects related to different geographic areas or sources; (4) toxicology studies; (5) the limited number of studies that analyze existing central-area monitor data to explicitly examine the health impacts of sulfate and acidity versus PM mass; (6) “modern” area monitor studies with additional capabilities to distinguish among sources of pollution; (7) partial reinterpretation of two pivotal cohort studies; and (8) studies separating effects of secondary sulfates from those of primary metal sulfates. However, uncertainties remain regarding the role that secondary sulfates may play in ambient PM chemistry pathways leading to potentially harmful products, such as the possible effects of secondary organic aerosols that may be the product of acid catalysis of sulfur dioxide. Thus, more targeted study is needed, and some research suggestions are made in this regard.     

Asbestos exposure and tuberculous pleurisy as developmental causes of progressive unilateral upper-lung field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis

BackgroundUnilateral upper-lung field pulmonary fibrosis (upper-PF), which is radiologically consistent with pleuroparenchymal fibroelastosis, develops after thoracic surgery. In most patients with unilateral upper-PF, aberrant intra-/extra thoracic air commonly emerges and an autopsy shows chronic pleuritis, which indicates that pleural involvement is associated with upper-PF development. If so, there may be patients with unilateral upper-PF who have a history of pleural involvement, including tuberculous pleurisy (TP) or asbestos exposure (AE). This study aimed to examine this supposition.MethodsWe examined the radiological reports of all consecutive patients from 2012 to 2018 to investigate whether there were patients having unilateral upper-PF and a history of TP or AE.ResultsEight patients were included in the study. Five patients had a history of TP, and the remaining three had that of AE. All patients were men and had respiratory symptoms, and seven patients presented with restrictive ventilatory impairment. The interval between TP or last AE and upper-PF development was long, with a median of over 20 years. The upper-PF lesion was commonly located in the right lung, and aberrant intrathoracic air was observed in five patients during their clinical course. Additionally, the upper-PF lesion transformed into a cystic lesion in six patients, which resulted in Aspergillus infection in two patients. The prognosis was poor, with a median overall survival of 38 months.ConclusionsUnilateral upper-PF developed even in patients with a history of pleural involvement. Our results indicate that pleural involvement plays an important role in the development of unilateral upper-PF.     

Combined Reduced Forced Expiratory Volume in 1 Second (FEV1) and Peripheral Artery Disease in Sedentary Elders With Functional Limitations

ObjectivesBecause they are potentially modifiable and may coexist, we evaluated the combined occurrence of a reduced forced expiratory volume in 1 second (FEV1) and peripheral artery disease (PAD), including its association with exertional symptoms, physical inactivity, and impaired mobility, in sedentary elders with functional limitations.DesignCross sectional.SettingLifestyle Interventions and Independence in Elder (LIFE) Study.ParticipantsA total of 1307 sedentary community-dwelling persons, mean age 78.9, with functional limitations (Short Physical Performance Battery [SPPB] <10).MeasurementsA reduced FEV1 was defined by a z-score less than −1.64 (<lower limit of normal), whereas PAD was defined by an ankle-brachial index less than 1.00. Exertional dyspnea was defined as moderate to severe (modified Borg index) immediately after a 400-meter walk test (400MWT). Exertional leg symptoms were established by the San Diego Claudication Questionnaire. Physical inactivity was evaluated by percent of accelerometry wear-time with activity less than 100 counts per minute (top quartile established high sedentary time). Mobility was evaluated by the 400MWT (gait speed <0.8 m/s defined as slow) and SPPB (≤7 defined moderate-to-severe mobility impairment).ResultsA combined reduced FEV1 and PAD was established in 6.0% (78/1307) of participants. However, among those who had a reduced FEV1, 34.2% (78/228) also had PAD, whereas 20.8% (78/375) of those who had PAD also had a reduced FEV1. The 2 combined conditions were associated with exertional dyspnea (adjusted odds ratio [adjOR] 2.59 [1.20–5.60]) and slow gait speed (adjOR 3.15 [1.72–5.75]) but not with exertional leg symptoms, high sedentary time, and moderate-to-severe mobility impairment.ConclusionsIn sedentary community-dwelling elders with functional limitations, a reduced FEV1 and PAD frequently coexisted and, in combination, were strongly associated with exertional dyspnea and slow gait speed (a frailty indicator that increases the risk of deleterious outcomes).