Familial spontaneous pneumothorax: importance of screening for Birt-Hogg-Dubé syndrome.

家族性自发性气胸: 筛查 Birt-Hogg-dub é 综合征的重要性。

  • 影响因子:2.26
  • DOI:10.1093/ejcts/ezz171
  • 作者列表:"Liu Y","Xing H","Huang Y","Meng S","Wang J
  • 发表时间:2020-01-01

OBJECTIVES:The goal of this study was to investigate the prevalence of Birt-Hogg-Dubé (BHD) syndrome in patients with familial spontaneous pneumothorax (FSP) and the clinical characteristics of pneumothorax related to BHD syndrome compared with those of primary spontaneous pneumothorax. METHODS:A total of 37 families diagnosed with FSP from 2007 to 2017 were enrolled in this study. The FLCN gene, which is responsible for BHD syndrome, was sequenced using the Sanger method in 25 probands. For the patients with confirmed BHD syndrome-related pneumothorax, clinical characteristics including the median onset age of pneumothorax, the male-to-female ratio, the mean height and body mass index (BMI) and the recurrence rate after different treatment modalities were obtained and compared with those of patients with primary spontaneous pneumothorax. RESULTS:Of the 25 probands with FSP, 16 [64.0%, 95% confidence interval (CI) 43.8-84.2%] harboured FLCN germline mutations. In the patients with BHD syndrome-related pneumothorax, the median onset age of pneumothorax was 34 years; the male-to-female ratio was 1.3:1; and the mean height and BMI were 167.0 ± 8.6 cm and 23.6 ± 3.4 kg/m2, respectively. These characteristics were significantly different from those in patients with primary spontaneous pneumothorax from the same centre. The recurrence rate of BHD syndrome-related pneumothorax after conservative therapy was 53.1% (95% CI 38.6-67.5%) compared with 9.1% (95% CI 0-19.4%) after surgical treatment. CONCLUSIONS:BHD syndrome is one of the most common causes of FSP. Patients with FSP should be recommended for mutation screening for the FLCN gene to facilitate early diagnosis and proper intervention.


目的: 本研究的目的是调查家族性自发性气胸 (FSP) 患者中 Birt-Hogg-dub é (BHD) 综合征的患病率。并与原发性自发性气胸的临床特征进行比较。 方法: 共 37 个被诊断为 FSP 的家庭 (2007年至 2017年) 入组本研究。使用 Sanger 方法对 25 例先证者进行了负责 BHD 综合征的 FLCN 基因测序。对于确诊的 BHD 综合征相关性气胸患者,临床特征包括气胸的中位发病年龄、男女比例、平均身高和体重指数 (BMI) 获得不同治疗方式后的复发率,并与原发性自发性气胸患者进行比较。 结果: 25 例 FSP 先证者中,16 例 [64.0%,95% 置信区间 (CI) 43.8-84.2%] 存在 FLCN 种系突变。在 BHD 综合征相关性气胸患者中,气胸的中位发病年龄为 34 岁,男女之比为 1.3: 1; 平均身高和 BMI 分别为 167.0 ± 8.6 cm 和 23.6 ± 3.4 kg/m2。这些特征与来自同一中心的原发性自发性气胸患者明显不同。经保守治疗后 BHD 综合征相关性气胸的复发率为 53.1% (95% CI 38.6-67.5%),而手术治疗后为 9.1% (95% CI 0-19.4%)。 结论: BHD 综合征是 FSP 最常见的病因之一。应推荐 FSP 患者进行 FLCN 基因突变筛查,以利于早期诊断和正确干预。



作者列表:["De Cunto G","Brancaleone V","Riemma MA","Cerqua I","Vellecco V","Spaziano G","Cavarra E","Bartalesi B","D'Agostino B","Lungarella G","Cirino G","Lucattelli M","Roviezzo F"]

METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.

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作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

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作者列表:["Zaragosi LE","Deprez M","Barbry P"]

METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.

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