26例(PAH n=17;CTEPH n=9)进行增量症状受限周期运动试验。在运动过程中评估分钟通气(V'E)、呼吸模式、肺容积和呼吸困难强度。使用三项问卷(呼吸困难描述符)连续评估运动期间的呼吸困难质量。潮汐量的拐点(VT)相对于V'E为每个增量试验确定。运动时吸气量的变化分为两组患者:过度充气者(65%)和非过度充气者(35%)。运动后使用多维呼吸困难剖面对呼吸困难进行多维特征描述。在过度充气者中，吸气量在整个运动过程中逐渐下降0.36 L，而非过度充气者则保持稳定。在这两类患者中，“工作/努力”描述符在整个运动过程中最常被选择(占所有反应的65%)。 At the VT/V'E inflection, work/effort plateaued while "unsatisfied inspiration" descriptors became selected predominantly only in hyperinflators (77% of all responses). In the affective domain, the emotion most frequently associated with dyspnoea was anxiety.
In pulmonary hypertension patients who develop hyperinflation during exercise, dyspnoea descriptors referring to unsatisfied inspiration become predominant following the VT/V'E inflection. As these descriptors are generally associated with more negative emotional experiences, delaying or preventing the VT/V'E inflection may have important implications for symptom management in patients with pulmonary hypertension.
哮喘是一种异质性疾病，以气道慢性炎症为特征，通常用吸入支气管扩张剂和皮质类固醇治疗。在不受控制的哮喘情况下，经常处方口服皮质类固醇(OCSs)。良好的依从性和吸入技术与改善预后相关;然而，很难监测个别患者的适当药物摄入量和有效性。呼出的气含有成千上万的挥发性有机化合物(VOCs)，它们反映了人体化学物质的变化，可能对监测药物药代动力学/药效动力学有用。我们旨在研究U-BIOPRED队列中严重哮喘患者呼出的VOCs(通过气相色谱-飞行时间质谱联用)与尿液中沙丁胺醇和OCSs(通过液相色谱-高分辨率质谱联用)水平的关系。
在基线和随访12–18 月后采集样本。基于单变量和多变量建模进行统计分析，然后计算受试者工作特征曲线下面积(AUC)。结果通过纵向复制和独立验证进行验证。< / p > < /秒> Data were available for 78 patients (baseline n=48, replication n=30 and validation n=30). Baseline AUC values were 82.1% (95% CI 70.4–93.9%) for salbutamol and 78.8% (95% CI 65.8–91.8%) for OCS. These outcomes could be adequately replicated and validated. Additional regression analysis between qualified exhaled VOCs and urinary concentrations of salbutamol and prednisone showed statistically significant correlations (p<0.01). We have linked exhaled VOCs to urinary detection of salbutamol and OCSs. This merits further development of breathomics into a point-of-care tool for therapeutic drug monitoring.
哮喘和慢性阻塞性肺病(COPD)在世界范围内造成严重的发病率和死亡率。在疾病发病机制方面，哮喘和慢性阻塞性肺病都涉及肺部慢性炎症，其特征是炎症细胞因子的异常释放、免疫细胞活性失调和气道重塑。迄今为止，目前的治疗方法仍然只能治疗症状，不能逆转原发疾病的进程。在最近的工作中，白细胞介素(IL)-1& α;和IL-1β已被认为在哮喘和慢性阻塞性肺病中发挥重要作用。在这篇综述中，我们总结了il -1和α信号失调的压倒性临床前证据;和IL-1β并讨论IL-1在哮喘和COPD治疗研究中的悖论。考虑到最近完成的和正在进行的IL-1生物制剂的临床试验，这些试验作为哮喘和COPD疾病的治疗手段有不同程度的失败和成功，这一点尤为重要
We collected DNA from 14 patients with PAM and four relatives, and analysed the coding regions of SLC34A2 by direct DNA sequencing. To determine the phenotype characteristics, clinical data were collected and a severity score was created for each variant, based on type and localisation within the protein.
We identified eight novel allelic variants of SLC34A2 in 14 patients with PAM. Four of these were nonsense variants, three were missense and one was a splice site variant. One patient was heterozygous for two different variants and all other patients were homozygous. Four patients were asymptomatic and 10 patients were symptomatic. The severity of the disease was associated with the variant severity.
Our findings support a significant role for SLC34A2 in PAM and expand the variant spectrum of the disease. Thus, SLC34A2 variants were detected in all patients and eight novel allelic variants were discovered. An association between disease severity and the severity of the variants was found; however, this needs to be investigated in larger patient populations.
我们分析了三种不同的哮喘小鼠模型，并根据炎症表型分层评估了人类哮喘患者痰中的细胞因子谱。此外，我们评估了各种细胞因子阻断在中性粒细胞性哮喘小鼠模型中的治疗效果。在CSF中，气道粒细胞CSF (G-CSF)通过促进骨髓中中性粒细胞的发育而促进气道中性粒细胞的形成，从而在哮喘小鼠模型中区分嗜中性粒细胞炎症与嗜酸性粒细胞炎症。G-CSF是由白细胞介素(IL)-17A和肿瘤坏死因子(TNF)-& α同时刺激肺上皮细胞产生的;因此，使用单克隆抗体对上游刺激进行双重阻断或IL-17A中细胞因子的遗传缺陷xTNF-& α;双敲除小鼠降低了G-CSF的血清水平，从而缓解了气道中的中性粒细胞炎症。 In humans, the sputum level of G-CSF can be used to stratify patients with asthma with neutrophil-dominated inflammation.
Our results indicated that myelopoiesis-promoting G-CSF and cytokines as the upstream inducing factors are potential diagnostic and therapeutic targets in patients with neutrophilic asthma.
1286例T-CHEQ参与者从出生到预后(2016年3月31日)或失去随访，平均随访17年。利用地面观测、化学/气象模型、遥感和土地利用回归模型，将1999年1月1日至2012年12月31日期间的二氧化氮(NO2)、臭氧(O )和50%截止气动直径为2.5 µm的颗粒物(PM2.5)的浓度分配给参与者，根据他们出生时的邮政编码。研究结果包括医生诊断的哮喘、过敏性鼻炎和湿疹的发生率。Cox比例风险回归模型用于估计每四分位暴露范围和结果的风险比，并对潜在混杂因素进行了调整。< / p > < /秒> Hazard ratios of 1.17 (95% CI 1.05–1.31) for asthma and 1.07 (95% CI 0.99–1.15) for eczema were observed for total oxidants (O3 and NO2) at birth. No significant increase in risk was found for PM2.5. Exposures to oxidant air pollutants (O3 and NO2) but not PM2.5 were associated with an increased risk of incident asthma and eczema in children. This suggests that improving air quality may contribute to the prevention of asthma and other allergic disease in childhood and adolescence.
中度至重度OSA患者为1.6次(95% CI为1.18–2.15次;经心血管危险因素调整后，p=0.002)比无OSA的患者更容易发生升胸主动脉钙化(≥100 单位)。此外，中重度OSA与升主动脉钙化之间的相关性，较高心外膜脂肪量的患者略强于无OSA患者和最低心外膜脂肪量的患者(OR 2.11, 95% CI 1.30–3.43)。
一般人群中OSA的严重程度与亚临床系统性动脉粥样硬化独立相关。这些发现强调了严重OSA的潜在重要性，尤其是在心外膜脂肪含量较高的受试者中，它可能是全身性动脉粥样硬化和心血管疾病的预测因素
TAC的信息来自8年的食物频率调查问卷。8岁和16岁时采用肺活量测定法、脉冲振荡测定法(IOS)和16岁时呼出一氧化氮分数(FeNO)测量肺功能。低肺功能定义为用力呼气量1 s (FEV1) z-score低于25百分位。TAC与肺功能之间的纵向关联通过混合效应模型进行分析，以调整潜在的混杂因素。在8年按哮喘进行分层，以检查效果的改变。中位TAC摄入量为10 067 μmol Trolox当量(TE)·g–1，男性的平均值低于女性(9963 vs 10 819 μmol TE·g–1)。在对8 - 16年肺功能变化的分析中，对于整个研究人群，TAC与肺活量测定结果之间没有统计学意义上的相关性。在8岁哮喘儿童中(患病率为7%)，较高的TAC与较高的平均FEV1 (0.46
High dietary antioxidant intake in school age may be associated with improved lung function development from school age to adolescence among children with asthma.
纤维化间质性肺疾病(ILDs)是一种慢性且经常进展的疾病，对发病率、与健康相关的生活质量(HRQoL)和卫生系统费用有重大影响。在日常活动中使用流动氧(AO)可改善运动表现，减轻症状，改善日常生活中的活动能力。英国一项前瞻性、多中心、混合方法、随机对照交叉试验(AmbOx试验:NCT02286063)对纤维化性ILD患者的日常生活影响进行了首次研究，报告称，与没有干预相比，AO治疗2周后HRQoL改善，通过King’s Brief ILD (K-BILD)问卷测量[1–3]。虽然AO用于ILD，但缺乏支持其健康-经济影响的证据。在这里，我们利用AmbOx试验收集的数据，评估了AO在ILD患者中的成本效益
MAPK通路改变(BRAFV600E突变:36%，BRAFN486_P490缺失:28%，MAP2K1突变:15%，分离NRASQ61突变:4%)，而KRAS突变在PLCH病变中几乎不存在。在PLCH患者中，BRAFV600E突变与诊断时的LCH表现(包括吸烟状况和肺功能)无关。BRAFV600E状态不影响LCH进展的风险。因此，MAPK改变存在于成人LCH患者的大多数病变中，尤其是PLCH。 Unlike reports in paediatric LCH, BRAFV600E genotyping did not provide additional information on disease outcome. The search for alterations involved in the MAPK pathway, including BRAF deletions, is useful for guiding targeted treatment in selected patients with refractory progressive LCH.
持续哮喘和缓解哮喘之间有4个cpg位点和42个区域甲基化差异。 I n cis位点的DNA甲基化与ACKR2和DGKQ位点的基因表达相关。在缓解受试者和健康对照组之间，有1163个cpg位点和328个区域甲基化差异。DNA甲基化与一组在纤毛上皮中表达的基因的表达相关。
缓解期和持续性哮喘之间差异甲基化的CpGs确定了与炎症和气道反应性缓解相关的遗传位点。 Despite the absence of symptoms, remission subjects have a DNA methylation profile that is distinct from that of healthy controls, partly due to changes in cellular composition, with a higher gene expression signal related to ciliated epithelium in remission versus healthy controls.
Hs-TnI在2020例患者中检测到(96.9%)。中位hs-TnI浓度为3.8 ng·L–1(四分位范围2.5–6.6 ng·L–1)， 1.8%的患者的水平高于99百分位参考限值27 ng·L–1。在Cox回归分析中，包括调整气流限制、呼吸困难等级、运动能力和严重加重史，以及传统心血管危险因素、估计的肾小球滤过率、踝臂指数、n端脑钠肽前体和流行的心血管疾病，hs-TnI是全因死亡率的显著预测因子，两者都是连续变量(危险比(HR)为log hs-TnI 1.28，95% CI 1.01–1.62)，并根据6 ng·L–1 (HR 1.63, 95% CI 1.10–2.42)的截止值进行分类。
在稳定期COPD患者中，hs-TnI是超过既定COPD死亡率预测指标的全因死亡率的强有力预测指标，并且独立于广泛的心血管危险因素和流行的心血管疾病。Hs-TnI浓度远低于上参考限值，添加到已建立的风险评估时，为所有COPD患者提供进一步的预后价值
妊娠期哮喘加重与不良母婴健康结果之间的关系尚未得到适当的调查。我们的目的是确定哮喘孕妇哮喘加重的短期和长期代际影响。
使用安大略哮喘监测系统和人口级卫生管理数据进行了一项人口队列研究。患有哮喘的孕妇哮喘加重的定义为以下标准中的至少一项:至少五次医生就诊，或一次急诊或一次妊娠期间哮喘住院。妊娠并发症、不良围产期结局和儿童早期呼吸障碍采用国际疾病分类代码(第9版和第10版)进行识别。
该队列由103 424名患有哮喘的单胎妊娠妇女组成。伴有哮喘的孕妇哮喘加重与先兆子痫(OR 1.30, 95% CI 1.12–1.51)和妊娠高血压(OR 1.17, 95% CI 1.02–1.33)的较高几率相关;低出生体重(OR 1.14, 95% CI 1.00–1.31)、早产(OR 1.14, 95% CI 1.01–1.29)和先天性畸形(OR 1.21, 95% CI 1.05–1.39)的几率较高。妊娠期间哮喘加重的妇女所生的孩子在出生后5年内患哮喘(OR 1.23, 95% CI 1.13–1.33)和肺炎(OR 1.12, 95% CI 1.03–1.22)的风险较高。
患有哮喘的妇女妊娠期间哮喘加重显示妊娠并发症、不良围产期结局和儿童早期呼吸障碍的风险增加，表明适当的哮喘管理可能降低不良健康结局的风险
肺腺癌(LUADs)在放射学上表现为亚实性结节(ssn)，比实性LUADs表现出更多的惰性生物学行为。SSNs通常包括浸润前和浸润性早期腺癌，可分为纯磨玻璃状结节和部分实性结节。ssr的基因组特征仍然知之甚少。< / p > < /秒> We subjected 154 SSN samples from 120 treatment-naïve Chinese patients to whole-exome sequencing. Clinical parameters and radiological features of these SSNs were collected. The genomic landscape of SSNs and differences from that of advanced-stage LUADs were defined. In addition, we investigated the intratumour heterogeneity and clonal relationship of multifocal SSNs and conducted radiogenomic analysis to link imaging and molecular characteristics of SSNs. Fisher's exact and Wilcoxon rank sum tests were used in the statistical analysis. The median somatic mutation rate across the SSN cohort was 1.12 mutations per Mb. Mutations in EGFR were the most prominent and significant variation, followed by those in RBM10, TP53, STK11 and KRAS. The differences between SSNs and advanced-stage LUADs at a genomic level were unravelled. Branched evolution and remarkable genomic heterogeneity were demonstrated in SSNs. Although multicentric origin was predominant, we also detected early metastatic events among multifocal SSNs. Using radiogenomic analysis, we found that higher ratios of solid components in SSNs were accompanied by significantly higher mutation frequencies in EGFR, TP53, RBM10 and ARID1B, suggesting that these genes play roles in the progression of LUADs. Our study provides the first comprehensive description of the mutational landscape and radiogenomic mapping of SSNs.
结果表明，至少部分观察到的RDW与多环芳烃的相关性是继发于疾病进展的。铁治疗PAH的试验结果应谨慎解释，因为观察到的任何改善可能与PAH的发展没有机械联系
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运动中肺动脉压升高的识别具有重要的诊断、预后和治疗意义。在运动测试中，压力超声心动图常用于估计肺动脉压力，但支持这种做法的数据有限。本研究检验了多普勒超声心动图在休息和运动时估计肺动脉压力的准确性。< / p > < /秒> Simultaneous cardiac catheterisation-echocardiographic studies were performed at rest and during exercise in 97 subjects with dyspnoea. Echocardiography-estimated pulmonary artery systolic pressure (ePASP) was calculated from the right ventricular (RV) to right atrial (RA) pressure gradient and estimated RA pressure (eRAP), and then compared with directly measured PASP and RAP. Estimated PASP was obtainable in 57% of subjects at rest, but feasibility decreased to 15–16% during exercise, due mainly to an inability to obtain eRAP during stress. Estimated PASP correlated well with direct PASP at rest (r=0.76, p<0.0001; bias –1 mmHg) and during exercise (r=0.76, p=0.001; bias +3 mmHg). When assuming eRAP of 10 mmHg, ePASP correlated with direct PASP (r=0.70, p<0.0001), but substantially underestimated true values (bias +9 mmHg), with the greatest underestimation among patients with severe exercise-induced pulmonary hypertension (EIPH). Estimation of eRAP during exercise from resting eRAP improved discrimination of patients with or without EIPH (area under the curve 0.81), with minimal bias (5 mmHg), but wide limits of agreement (–14–25 mmHg). The RV–RA pressure gradient can be estimated with reasonable accuracy during exercise when measurable. However, RA hypertension frequently develops in patients with EIPH, and the inability to noninvasively account for this leads to substantial underestimation of exercise pulmonary artery pressures.
在纤维化间质性肺病(ILD)患者中，运动时低氧血症频繁发生，可导致运动不耐受、运动性呼吸困难和生活质量降低[1–3]。临床上显著的运动性低氧血症通常定义为经皮动脉氧饱和度(SpO2)在6分钟行走试验(6MWT)[4]中下降至le88%，与ILD患者[5].
生存率降低相关在癌症患者中，目前的指南建议对偶发和症状性静脉血栓栓塞(VTE)进行类似的治疗，主要基于回顾性数据。我们旨在评估抗凝治疗在偶发和症状性静脉血栓栓塞的癌症患者。< / p > < /秒> The Hokusai VTE Cancer Study was a randomised controlled trial comparing edoxaban with dalteparin for cancer-associated VTE. The primary outcome was the composite of first recurrent VTE or major bleeding. Secondary outcomes included major bleeding, recurrent VTE and mortality. Outcomes in patients with incidental and symptomatic VTE were evaluated during the 12-month study period. 331 patients with incidental VTE and 679 patients with symptomatic VTE were enrolled, of whom the index event was confirmed by an independent radiologist. Median durations of anticoagulant treatment were 195 and 189 days, respectively. In patients with incidental VTE, the primary outcome occurred in 12.7% of patients, major bleeding in 6.6% of patients and recurrent VTE in 7.9% of patients. Out of the 26 VTE recurrences in patients with incidental VTE, five (31%) were incidental, seven (44%) were symptomatic and four (25%) were deaths for which pulmonary embolism could not be ruled out. In patients with symptomatic VTE, the primary outcome occurred in 13.8% of patients, major bleeding in 4.9% of patients and recurrent VTE in 10.9% of patients. All-cause mortality was similar in both groups. Clinical adverse outcomes are substantial in both cancer patients with incidental and symptomatic VTE, supporting current guideline recommendations that suggest treating incidental VTE in the same manner as symptomatic VTE.
吸入性皮质类固醇(ICS)被认为是肺癌潜在的化学预防手段。几项针对慢性阻塞性肺疾病(COPD)患者的观察性研究报告了不一致的结果，使用ICS后肺癌发病率显著降低或没有效果。我们评估了这种关联，使用了一种避免影响某些研究的偏见的方法。< / p > < /秒> A cohort of patients with COPD, new users of long-acting bronchodilators over 2000–2014, was formed using the Quebec healthcare databases, and followed until 2015 for a first diagnosis of lung cancer. A 1-year delay after cohort entry was used to avoid protopathic bias and a 1-year latency period was included after the initiation of ICS use. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) of lung cancer associated with ICS exposure, adjusted for covariates. The cohort involved 63 276 subjects, including 63% receiving ICS, with 3743 lung cancers occurring during a mean follow-up of 5 years. The adjusted HR of lung cancer associated with any ICS exposure was 1.01 (95% CI 0.94–1.08), relative to no ICS use. The HR with longer time (>4 years) since ICS initiation was 0.92 (95% CI 0.83–1.03), while with higher mean daily ICS dose (>1000 μg fluticasone equivalents) was 1.36 (95% CI 1.03–1.81). Inhaled corticosteroid use is not associated with a reduction in lung cancer incidence in patients with COPD. Observational studies reporting such reduction may have been affected by time-related biases and the inclusion of patients with asthma. The proposition of a randomised trial warrants some caution.
全球巨大负担的肺外结核(EPTB)病例中有很大一部分是凭经验治疗的，没有准确定义疾病部位和多器官疾病累及的程度。正电子发射断层扫描(PET)在结核病中使用2-脱氧-2-(氟-18)氟- We conducted a study of HIV-negative adult patients with a new clinical diagnosis of EPTB across eight centres located in six countries: India, Pakistan, Thailand, South Africa, Serbia and Bangladesh, to assess the extent of disease and common sites involved at first presentation. 18F-FDG PET/computed tomography (CT) scans were performed within 2 weeks of presentation. 358 patients with EPTB (189 females; 169 males) were recruited over 45 months, with an age range of 18–83 years (females median 30 years; males median 38 years). 350 (98%) out of 358 patients (183 female, 167 male) had positive scans. 118 (33.7%) out of 350 had a single extrapulmonary site and 232 (66.3%) out of 350 had more than one site (organ) affected. Lymph nodes, skeleton, pleura and brain were common sites. 100 (28%) out of 358 EPTB patients had 18F-FDG PET/CT-positive sites in the lung. 110 patients were 18F-FDG PET/CT-positive in more body sites than were noted clinically at first presentation and 160 patients had the same number of positive body sites. 18F-FDG PET/CT scan has potential for further elucidating the spectrum of disease, pathogenesis of EPTB and monitoring the effects of treatment on active lesions over time, and requires longitudinal cohort studies, twinned with biopsy and molecular studies.
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肺动脉高压(PH)描述了一组与发病率和死亡率增加相关的异质性疾病，无论病因如何[1–4]。诊断和表型PH值的金标准仍然是侵入性测量通过右心导管[5]。肺血流动力学的无创评估是一种有吸引力的替代方法，以降低手术风险，并更广泛地研究患者亚群谁没有统一进行右心导管评估PH值(，例如。多为左心PH患者)[5–7]。然而，有创测量和无创测量之间的不完全相关性限制了无创策略在PH评估中的广泛采用[8–13]
作为全球公民，我们有责任减少环境退化和气候变化对地球福祉和人口健康构成的严重威胁。现在对我们未来的这些毫无疑问的威胁是由于人口增长和人类的资源消耗模式造成的。同时，作为医疗专业人员，我们应该为患者寻求最好的治疗结果，我们需要考虑不同患者群体之间的公平。在呼吸医学专业，目前关于如何处理压力计量吸入器(pmis)中使用的推进剂在全球变暖中的作用的争论是一个非常紧迫的例子，说明这些有时相互冲突的命令如何在我们的日常实践中面对我们