Circulating fibrocytes as biomarkers of impaired lung function in adults with sickle cell disease

Mehrad, Borna; Burdick, Marie D.; Wandersee, Nancy J.; Shahir, Kaushik; Zhang, Liyun; Simpson, Pippa; Strieter, Robert M.; Field, Joshua J.

doi:10.1182/bloodadvances.2017010777

Cited by 10 publications

(12 citation statements)

References 38 publications

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“…Importantly, the predictive value of fibrocytes was cumulative and continuous, conferring a 5% increased risk per 10 5 increase in fibrocyte concentration, and was independent of the gender–age–physiology score and UIP pattern, each of which have previously been linked to worse outcomes in autoimmune ILD [ 28 , 29 , 37 , 38 ]. The threshold value of fibrocyte concentration identified in this study is similar to the values we identified in patients with Hermansky–Pudlak syndrome, chronic sickle cell lung disease and post-acute respiratory distress syndrome (ARDS) pulmonary fibrosis [ 13 , 27 , 39 ].…”

Section: Discussionsupporting

confidence: 84%

Circulating fibrocytes as prognostic biomarkers of autoimmune interstitial lung disease

Odackal

Gomez-Manjerres

et al. 2020

ERJ Open Res

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BackgroundAutoimmunity is a common cause of pulmonary fibrosis and can present either as a manifestation of an established connective tissue disease or as the recently described entity of interstitial pneumonia with autoimmune features. The rate of progression and responsiveness to immunosuppression in these illnesses are difficult to predict. Circulating fibrocytes are bone marrow-derived progenitor cells that home to injured tissues and contribute to lung fibrogenesis. We sought to test the hypothesis that the blood fibrocyte concentration predicts outcome and treatment responsiveness in autoimmune interstitial lung diseases.MethodsWe compared the concentration of circulating fibrocytes in 50 subjects with autoimmune interstitial lung disease and 26 matched healthy controls and assessed the relationship between serial peripheral blood fibrocyte concentrations and clinical outcomes over a median of 6.25 years.ResultsAs compared to controls, subjects with autoimmune interstitial lung disease had higher circulating concentrations of total fibrocytes, the subset of activated fibrocytes, and fibrocytes with activation of PI3K/AKT/mTOR, TGF-beta receptor, and IL4/IL13 receptor signalling pathways. Over the follow-up period, there were episodes of marked elevation in the concentration of circulating fibrocytes in subjects with autoimmune interstitial lung disease but not controls. Initiation of immunosuppressive therapy was associated with a decline in the concentration of circulating fibrocytes. For each 100 000 cell·mL−1 increase in peak concentration of circulating fibrocytes, we found a 5% increase in odds of death or lung function decline.ConclusionIn patients with autoimmune interstitial lung disease, circulating fibrocytes may represent a biomarker of outcome and treatment response.

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Section: Discussionsupporting

confidence: 84%

Circulating fibrocytes as prognostic biomarkers of autoimmune interstitial lung disease

Odackal

Gomez-Manjerres

et al. 2020

ERJ Open Res

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“…Fibrosis is initiated by stimulated fibroblasts, and circulating fibrocytes also contribute minimally [4]. Transforming growth factor (TGF)-β is the most well established pro-fibrotic signal [5], and is mainly secreted by macrophages responding to inflammation in injured tissues [6].…”

Section: Introductionmentioning

confidence: 99%

HDAC Inhibitors: Therapeutic Potential in Fibrosis-Associated Human Diseases

Yoon

Kang

Eom

2019

IJMS

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Fibrosis is characterized by excessive deposition of the extracellular matrix and develops because of fibroblast differentiation during the process of inflammation. Various cytokines stimulate resident fibroblasts, which differentiate into myofibroblasts. Myofibroblasts actively synthesize an excessive amount of extracellular matrix, which indicates pathologic fibrosis. Although initial fibrosis is a physiologic response, the accumulated fibrous material causes failure of normal organ function. Cardiac fibrosis interferes with proper diastole, whereas pulmonary fibrosis results in chronic hypoxia; liver cirrhosis induces portal hypertension, and overgrowth of fibroblasts in the conjunctiva is a major cause of glaucoma surgical failure. Recently, several reports have clearly demonstrated the functional relevance of certain types of histone deacetylases (HDACs) in various kinds of fibrosis and the successful alleviation of the condition in animal models using HDAC inhibitors. In this review, we discuss the therapeutic potential of HDAC inhibitors in fibrosis-associated human diseases using results obtained from animal models.

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“…On the other hand, in adult SCD patients with a restrictive lung function pattern (figure 1), reduced spirometry indices and TLC correlated with lobar volume loss on high-resolution computed tomography [19], which is common in fibrotic lung disease. FIELD et al [20] demonstrated higher levels of circulating activated fibrocytes in SCD patients with impaired FEV 1 and FVC, which could contribute to the pathogenesis of lung fibrosis [21]. However, interstitial pulmonary fibrosis does not seem to be the only mechanism responsible for loss of lung volume in this group [22].…”

Section: Lung Function Abnormalitiesmentioning

confidence: 85%

Management of chronic respiratory complications in children and adolescents with sickle cell disease

Arigliani

Gupta

2020

Eur Respir Rev

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Sickle cell disease (SCD) is a life-threatening hereditary blood disorder that affects millions of people worldwide, especially in sub-Saharan Africa. This condition has a multi-organ involvement and highly vascularised organs, such as the lungs, are particularly affected. Chronic respiratory complications of SCD involve pulmonary vascular, parenchymal and airways alterations. A progressive decline of lung function often begins in childhood. Asthma, sleep-disordered breathing and chronic hypoxaemia are common and associated with increased morbidity. Pulmonary hypertension is a serious complication, more common in adults than in children. Although there is a growing attention towards respiratory care of patients with SCD, evidence regarding the prognostic meaning and optimal management of pulmonary issues in children with this condition is limited.This narrative review presents state-of-the-art evidence regarding the epidemiology, pathophysiology and therapeutic options for chronic respiratory complications commonly seen in paediatric patients with SCD. Furthermore, it highlights the gaps in the current knowledge and indicates future directions for studies that aim to improve our understanding of chronic respiratory complications in children with SCD.

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Circulating fibrocytes as biomarkers of impaired lung function in adults with sickle cell disease

Abstract: Key Points Fibrocytes are progenitor cells that home to injured organs and contribute to fibrosis. Levels of circulating fibrocytes are associated with pulmonary dysfunction in adults with SCD.

Cited by 10 publications

References 38 publications

Circulating fibrocytes as prognostic biomarkers of autoimmune interstitial lung disease

Circulating fibrocytes as prognostic biomarkers of autoimmune interstitial lung disease

HDAC Inhibitors: Therapeutic Potential in Fibrosis-Associated Human Diseases

Management of chronic respiratory complications in children and adolescents with sickle cell disease

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