Biomarkers from bronchoalveolar lavage fluid in systemic sclerosis patients with interstitial lung disease relate to severity of lung fibrosis

Hesselstrand, Roger; Wildt, Marie; Božović, Gracijela; Andersson-Sjöland, Annika; Andréasson, Kristofer; Scheja, Agneta; Westergren‐Thorsson, Gunilla; Bjermer, Leif; Wuttge, Dirk M.

doi:10.1016/j.rmed.2013.03.015

Cited by 56 publications

(46 citation statements)

References 33 publications

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“…The invers correlation of CD48 expression with vital capacity may suggest, however, that peripheral eosinophil activation could be related to pulmonary pathology. We have shown previously, that increased cell counts of eosinophils in bronchoalveolar lavage fluid are related to increased fibrosis on high resolution computer tomography scans [2]. Importantly, Goh et al identified an increased mortality in SSc associated ILD in patients with increased eosinophil counts in bronchoalveolar lavage [21].…”

Section: Discussionmentioning

confidence: 92%

“…Inflammation may precede and contribute to development of pulmonary fibrosis and can be detected as increase in alveolar nitric oxide concentration (CANO) [1]. Increased eosinophil counts in bronchoalveolar lavage have been associated with extent of pulmonary fibrosis [2] and with outgrowth of fibroblasts with altered phenotype from bronchoalveolar lavage fluid that may contribute to development of pulmonary fibrosis [3]. Also, increased eosinophil counts in bronchoalveolar lavage have been associated with increased mortality in SSc related ILD [4].…”

Section: Introductionmentioning

confidence: 99%

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CD81 and CD48 show different expression on blood eosinophils in systemic sclerosis: new markers for disease and pulmonary inflammation?

Wuttge

Andreasson

Tufvesson

et al. 2015

Scandinavian Journal of Rheumatology

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Objective: In systemic sclerosis (SSc) related interstitial lung disease, elevated eosinophil counts in bronchoalveolar lavage are associated with worse outcome. We hypothesize that eosinophils are activated in the peripheral circulation, thereby increasing their recruitment to affected tissues and contributing to inflammation and fibrosis. The aim of this study was to characterize the blood eosinophils in SSc patients. Methods:Expressions of surface markers CD11b, CD44, CD48, CD54, CD69, CD81 and HLA-DR on CD16 low CD9 high expressing eosinophils were measured by flow cytometry in whole blood from SSc patients (n = 32) and controls (n = 11).Results: Expression of CD54, CD69 and HLA-DR were undetectable in all groups. CD44and CD11b expression levels were similar between groups. CD81 expression was lower in patients compared to controls independent of disease duration (p = 0.001). CD48 expression was increased in patients with a short disease duration (< 2 years) compared to both controls (p = 0.042) and patients with longer disease duration (p = 0.027). In patients with short disease duration, increased CD48 expression was associated with alveolar inflammation as measured by an increased concentration of alveolar nitric oxide (r = 0.76, p = 0.003). Conclusion:Blood eosinophils change phenotype during disease evolution in SSc, and CD48 expression may be used as a biomarker for pulmonary inflammation.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

CD81 and CD48 show different expression on blood eosinophils in systemic sclerosis: new markers for disease and pulmonary inflammation?

Wuttge

Andreasson

Tufvesson

et al. 2015

Scandinavian Journal of Rheumatology

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“…A meta-analysis of 26 studies identified male sex, disease extent on HRCT, presence of honeycombing, elevated Krebs von den Lungen (KL-6) values and increased alveolar epithelial permeability as predictors of both mortality and ILD progression in unadjusted analysis, while disease extent on the HRCT scan was the only variable that independently predicted both mortality and ILD progression [39]. Recently, a loss of density on capillaroscopy was shown to be associated with worse FVC and DLCO [40] and biomarkers that correlate with the severity of fibrosis have been proposed: elevated levels of chitinase [41], tenascin C [42], growth differentiation protein 15 [43], cartilage oligomeric matrix protein, alveolar epithelial cell antigen, KL-6 [44] and the chemokine CXCL4 [45]. Serum IL-6 predicted early disease progression and IL-6 values >767 pg·mL −1 were predictive of risk of death within the first 30 months in patients with mild SSc-ILD [46].…”

Section: The Outcome and Its Predictorsmentioning

confidence: 99%

Interstitial lung disease in systemic sclerosis: where do we stand?

et al. 2015

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Interstitial lung disease (ILD) is common in systemic sclerosis (SSc) patients and despite recent advances in the treatment is, at present, the major cause of death. Today, an early diagnosis of ILD is possible, and is mandatory to improve the prognosis of the disease.Pulmonary function tests and high-resolution computed tomography remain the mainstay for the diagnosis of SSc-ILD, but there is a growing interest in lung ultrasound. Recently, the correlation between severity of fibrosis and some peripheral blood biomarkers has been described.Nonselective immunosuppressors are still the main treatment for ILD, with cyclophosphamide (CYC) most widely used to obtain remission. Novel therapies towards specific molecular and cellular targets have been suggested; in particular, rituximab (RTX) has shown promising results, but further research is needed. It is of paramount importance to define the severity of the disease and the risk of progression in order to define the need for treatment and the treatment intensity. We propose the division of the treatment strategies at our disposal to induce remission into three categories: high intensity (haematopoietic stem cell transplantation), medium intensity (CYC and RTX) and low intensity (azathioprine (AZA) and mycophenolate mofetil (MMF)). After obtaining remission, maintenance treatment with AZA or MMF should be started.In this review we explore new advances in the pathogenesis, diagnosis and treatment of SSc-ILD. @ERSpublications Early diagnosis of ILD is possible, and is mandatory to improve the prognosis of the disease http://ow.ly/P28JHThe relevance of interstitial lung disease in systemic sclerosisPulmonary disease in systemic sclerosis (SSc) mainly comprises interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). Over the past 40 years the SSc mortality rate has not changed significantly [1]. Nevertheless, while the frequency of deaths due to renal crisis has significantly decreased from 42% to 6%, the proportion of deaths due to ILD and PAH has increased [2]. In fact, ILD and PAH are the two main causes of death in SSc, accounting for 33% and 28% of deaths, respectively [2]. A European Scleroderma Trials and Research group (EUSTAR) analysis revealed, in a cohort of 3656 SSc patients, that ILD is present in 53% of cases with diffuse cutaneous SSc and in 35% of cases with limited

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“…Modest increases in BAL eosinophils (<25 %) may be observed in pulmonary Langerhans cell histiocytosis, IPF, connective tissue diseases, drug-induced pneumonitis and sarcoidosis [25]. One study showed that the eosinophilic pneumonia particularly presented with a significant increase in eosinophil counts and a cogent decrease in T cell proportions, compared to the sarcoidosis which showed a significant increase in CD4/CD8 ratio, as compared to the other ILDs [26•].…”

Section: Eosinophilic Cellular Pattern In Balmentioning

confidence: 99%

Role of broncho: alveolar lavage in approaching interstitial lung diseases

2015

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Biomarkers from bronchoalveolar lavage fluid in systemic sclerosis patients with interstitial lung disease relate to severity of lung fibrosis

Abstract: In SSc related ILD, biomarkers from BALF and serum correlate to findings on HRCT suggesting usefulness as markers of presence and extent of lung fibrosis.

Cited by 56 publications

References 33 publications

CD81 and CD48 show different expression on blood eosinophils in systemic sclerosis: new markers for disease and pulmonary inflammation?

CD81 and CD48 show different expression on blood eosinophils in systemic sclerosis: new markers for disease and pulmonary inflammation?

Interstitial lung disease in systemic sclerosis: where do we stand?

Role of broncho: alveolar lavage in approaching interstitial lung diseases

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