Exhaled nitric oxide, but not serum nitrite and nitrate, is a marker of interstitial lung disease in systemic sclerosis

Tiev, Kiet; Le-Dong, Nhât-Nam; Duong‐Quy, Sy; Hua-Huy, T.; Cabané, J.; Dinh-Xuan, Anh Tuan

doi:10.1016/j.niox.2008.11.004

Cited by 35 publications

(49 citation statements)

References 35 publications

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“…Immune activation leads to increased expression of inducible NO synthase (iNOS) in a variety of cell types, 23,24 and circulating NO metabolites are consistently elevated in SSc, 25,26 even among subjects with pulmonary hypertension. 27,28 Thus, inflammatory mechanisms may overshadow reduced NO production by the constitutive endothelial and neuronal NOS isoforms. 24,29 Our finding of a modestly lower J′aw NO in patients with SSc without pulmonary involvement relative to healthy controls mirrors earlier results of a study involving subjects with SSc-ILD.…”

Section: Discussionmentioning

confidence: 99%

Exhaled Nitric Oxide in Pulmonary Arterial Hypertension Associated with Systemic Sclerosis

et al. 2016

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Abstract:The fractional exhaled concentration of nitric oxide (FE NO ) has been shown to be reduced in idiopathic pulmonary arterial hypertension (PAH) but has not been adequately studied in PAH associated with systemic sclerosis (SSc). We measured FE NO at an expiratory flow rate of 50 mL/s in 21 treatment-naive patients with SSc-associated PAH (SSc-PAH), 94 subjects with SSc without pulmonary involvement, and 84 healthy volunteers. Measurements of FE NO at additional flow rates of 100, 150, and 250 mL/s were obtained to derive the flow-independent nitric oxide exchange parameters of maximal airway flux (J′aw NO ) and steady-state alveolar concentration (CA NO ). FE NO at 50 mL/s was similar (P = 0.22) in the SSc-PAH group (19 ± 12 parts per billion [ppb]) compared with the SSc group (17 ± 12 ppb) and healthy control group (21 ± 11 ppb). No change was observed after 4 months of targeted PAH therapy in 14 SSc-PAH group patients (P = 0.9). J′aw NO was modestly reduced in SSc group subjects without lung disease (1.2 ± 0.5 nl/s) compared with healthy controls (1.64 ± 0.9; P < 0.05) but was similar to that in the SSc-PAH group. CA NO was elevated in individuals with SSc-PAH (4.8 ± 2.6 ppb) compared with controls with SSc (3.3 ± 1.4 ppb) and healthy subjects (2.6 ± 1.5 ppb; P < 0.001 for both). However, after adjustment for the diffusing capacity of CO, there was no significant difference in CA NO between individuals with SSc-PAH and controls with SSc. We conclude that FE NO is not useful for the diagnosis of PAH in SSc. Increased alveolar nitric oxide in SSc-PAH likely represents impaired diffusion into pulmonary capillary blood.

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Section: Discussionmentioning

confidence: 99%

Exhaled Nitric Oxide in Pulmonary Arterial Hypertension Associated with Systemic Sclerosis

et al. 2016

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“…Currently, several biological markers, such as neutrophilic alveolitis surfactant A and D [14], or cytokines, such as tumour necrosis factor-a [15], and chemokines, such as interleukin-8 [16] and CCL2 [16][17][18], and alveolar concentration of nitric oxide [19,20], have been shown to be associated with the severity of ILD in SSc. Nevertheless, for each biomarker, long-term follow-up studies showing relevant prognostic value for progression are lacking.…”

Section: Discussionmentioning

confidence: 99%

Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis

Tiev¹,

Hua-Huy²,

Kettaneh³

et al. 2011

Eur Respir J

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Elevated serum CC chemokine ligand (CCL)18 reflects lung fibrosis activity in systemic sclerosis (SSc) and could be an early marker of lung function worsening. Therefore, we sought to evaluate whether serum CCL18 levels at baseline could predict worsening of lung disease in SSc.In this prospective study, 83 SSc patients were analysed longitudinally over a 4-yr observation period for the risk of occurrence of combined deleterious events, defined as a 10% decrease from baseline of total lung capacity or forced vital capacity % predicted, or death, according to serum CCL18 at inclusion. Receiver operating characteristic (ROC) curve analysis was performed for prediction of events during the first year after inclusion. The best cut-off level of serum CCL18 for prediction of a combined event within the follow-up period was 187 ng?mL -1 , with 53% sensitivity and 96% specificity (area under the ROC curve 0.86; p,0.001). After a mean¡SD follow-up of 33.7¡10.8 months, a higher rate of disease progression occurred in the group with serum CCL18 levels .187 ng?mL -1 . The adjusted hazard ratio was 5.36 (95% CI 2.44-11.75; p,0.001). In summary, serum CCL18 is an accurate predictive biomarker for the identification of patients with a higher risk of subsequent scleroderma lung disease worsening.

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“…Therefore, treatments should target disease when a reversible component is present. Defining this reversible component can be difficult but new methodogies such as exhaled nitric oxide [39] and CT scan computer-aided diagnostic tools [40] and composite scoring systems [32] are being developed. In general, appropriate candidates for therapy are those who have early stage lung disease, have ground glass opacities on CT scan or who are demonstrating progression of disease.…”

Section: Treatment Of Ild In Sscmentioning

confidence: 99%

Interstitial Lung Disease in Systemic Sclerosis: Diagnosis and Management

Schol

Carr²,

Frech³

et al. 2012

Rheumatology

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Exhaled nitric oxide, but not serum nitrite and nitrate, is a marker of interstitial lung disease in systemic sclerosis

Cited by 35 publications

References 35 publications

Exhaled Nitric Oxide in Pulmonary Arterial Hypertension Associated with Systemic Sclerosis

Exhaled Nitric Oxide in Pulmonary Arterial Hypertension Associated with Systemic Sclerosis

Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis

Interstitial Lung Disease in Systemic Sclerosis: Diagnosis and Management

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