Patients with psoriatic arthritis have higher levels of FeNO than those with only psoriasis, which may reflect a higher prevalence of a subclinical respiratory involvement.
银屑病关节炎患者的 FeNO 水平高于单纯银屑病患者，这可能反映了亚临床呼吸系统受累的患病率较高。
- 作者列表："Damiani G","Pacifico A","Rizzi M","Santus P","Bridgewood C","Bragazzi NL","Adawi M","Watad A
BACKGROUND:Psoriatic arthritis (PsA) patients are often affected by numerous comorbidities. However, contrasting results have been reported with regard to the respiratory involvement in PsA patients. The aim of this study was to evaluate the presence of subclinical airway inflammation in non-smoking PsA patients compared to patients with only psoriasis using the fraction of exhaled nitric oxide (FeNO) as an indirect marker of airway inflammation. METHODS:The study included 164 non-smoking psoriatic patients (Psoriasis Area of Severity Index or PASI score > 10): 82 with and 82 without PsA, who underwent FeNO tests at different flow rates (30, 50, 100, 200 mL/s). PsA patients were evaluated with Disease Activity in PSoriatic Arthritis Score (DAPSA). Both study groups were compared in terms of FeNO values and its association with the PASI score. The correlations between the variables were evaluated by means of Pearson's coefficient. RESULTS:Patient with PsA had higher levels of FeNO than those with psoriasis but without arthritis (at 30 mL/s, 71.09 ± 18.40 ppb vs 66.88 ± 19.12 ppb (NS); at 50 mL/s, 36.61 ± 9.30 ppb vs 30.88 ± 9.73 ppb (p < 0.001); at 100 mL/s, 19.09 ± 4.66 ppb vs 16.63 ± 4.90 ppb (p < 0.001); and at 200 mL/s, 10.88 ± 2.53 ppb vs 9.43 ± 2.55 ppb (p < 0.001), respectively). PASI score correlated to FeNO only in psoriatic patients without arthritis. However, CASPAR index correlated with FeNO (FeNO30: r = 0.81, p < 0.001; FeNO50: r = 0.84, p < 0.001; FeNO100: r = 0.71, p < 0.001; FeNO200: r = 0.58, p < 0.001). DAPSA was also correlated with FeNO to all flows (FeNO30: r = 0.43, p < 0.001; FeNO50: r = 0.33, p < 0.001; FeNO100: r = 0.34, p < 0.001; FeNO200: r = 0.25, p < 0.001). CONCLUSIONS:PsA patients seem to have more commonly subclinical airway inflammation than those with only psoriasis. Further studies are needed to replicate these findings.Key Points• Fraction of exhaled nitric oxide (FeNO) is a useful device to detect and monitor airway inflammation not only in asthma but also in systemic inflammatory diseases such as psoriatic arthritis and psoriasis.• Clinicians should be aware to check respiratory diseases in patients with psoriatic arthritis.
背景: 银屑病关节炎 (PsA) 患者常受到多种合并症的影响。然而，关于 PsA 患者呼吸受累的对比结果已有报道。本研究的目的是使用呼出气一氧化氮 (FeNO) 分数评估非吸烟 PsA 患者与仅银屑病患者相比存在亚临床气道炎症的情况作为气道炎症的间接标志物。 方法: 研究纳入 164 例非吸烟银屑病患者 (银屑病严重程度面积指数或 PASI 评分> 10 分): 82 例伴和 82 例不伴 PsA,在不同流速 (30 、 50 、 100 、 200 mL/s) 下进行 FeNO 试验。对 PsA 患者进行银屑病关节炎疾病活动度评分 (DAPSA) 评估。比较两个研究组的 FeNO 值及其与 PASI 评分的相关性。通过 Pearson 系数评价变量之间的相关性。 结果: PsA 患者的 FeNO 水平高于银屑病但无关节炎的患者 (30 mL/s, 71.09 ± 18.40 ppb vs 66.88 ± 19.12 ppb (NS); 50 mL/s, 36.61 ± 9.30 ppb vs 30.88 ± 9.73 ppb (p <0.001); 100 mL/s 时,19.09 ± 4.66 ppb vs 16.63 ± 4.90 ppb (p <0.001); 和 200 mL/s,10.88 ± 2.53 ppb vs 9.43 ± 2.55 ppb (分别为 p <0.001)。PASI 评分仅在无关节炎的银屑病患者中与 FeNO 相关。然而，CASPAR 指数与 FeNO 相关 (FeNO30: r = 0.81，p <0.001; FeNO50: r = 0.84，p <0.001; FeNO100: r = 0.71,P <0.001; FeNO200: r = 0.58，p <0.001)。DAPSA 也与所有流量的 FeNO 相关 (FeNO30: r = 0.43，p <0.001; FeNO50: r = 0.33，p <0.001; FeNO100: R = 0.34，p <0.001; FeNO200: r = 0.25，p <0.001)。 结论: PsA 患者似乎比单纯银屑病患者有更常见的亚临床气道炎症。需要进一步的研究来复制这些发现。要点 • 呼出气一氧化氮 (FeNO) 分数是检测和监测气道炎症的有用设备，不仅在哮喘中，而且在系统性炎症性疾病如银屑病关节炎和银屑病中。• 临床医生应注意检查银屑病关节炎患者的呼吸系统疾病。
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.
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.
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.