Impairment of lung function, health status and functional capacity in patients with ANCA-associated vasculitis

Newall, C; Schinke, S.; Savage, Caroline O. S.; Hill, Susan L.; Harper, Lorraine

doi:10.1093/rheumatology/keh548

Cited by 25 publications

(24 citation statements)

References 20 publications

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“…The consequences of persistent neutrophilic inflammation and unopposed protease action are best understood in chronic obstructive airways disease and bronchiectasis [10], features of which have been reported in both IPF and GPA cohorts [7]. Elevated MPO activity has previously been reported in active GPA [39]; this study confirms these findings and goes on to show that MPO activity remains elevated during clinical remission.…”

Section: Discussionsupporting

confidence: 85%

“…Additionally, examining tissue samples would confirm whether these chemokines are also elevated in the interstitium. Finally, the median BVAS was lower in the acute patients than had been expected from other studies [7]. Our interpretation is that a number of patients had respiratory-limited GPA and that the BVAS, which is weighted towards renal disease, does not score single-organ pulmonary disease highly.…”

Section: Discussioncontrasting

confidence: 51%

“…GPA frequently involves the lungs [5,6], with one series suggesting up to 90% of patients suffer from lower respiratory tract involvement at some stage during the disease course [7]. Increased neutrophil levels have been previously reported in the bronchoalveolar lavage fluid (BALF) from GPA patients during active disease [8,9].…”

mentioning

confidence: 99%

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Neutrophil chemotaxis in granulomatosis with polyangiitis (Wegener's) and idiopathic pulmonary fibrosis

Richter¹,

Perkins²,

Chavda³

et al. 2011

European Respiratory Journal

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The presence of antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis (Wegener's) (GPA) implicates the neutrophil as a key effector cell. Previous studies have reported elevated neutrophil counts in the lung, although the determinants of neutrophil chemotaxis in the GPA lung are unknown.Bronchoalveolar lavage fluid (BALF) cell counts, myeloperoxidase (MPO) and chemokines were measured in 27 patients with GPA, 20 disease controls with idiopathic pulmonary fibrosis (IPF) and six healthy controls. CXC chemokine ligand (CXCL)8, interleukin (IL)-1b, epithelial neutrophilactivating protein 78, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor were measured by ELISA. The neutrophil chemotactic potential of BALF was investigated using the under-agarose method, and specific antibodies were used to examine the role of CXCL8 and IL-1b.GPA BALF had an increased neutrophil percentage, and elevated MPO, CXCL8 and G-CSF concentrations compared with healthy controls. Chemotaxis of control neutrophils towards BALF from patients with active (p50.006) and remission (p50.077) GPA, and IPF (p50.001) patients was increased compared with normal controls. BALF-induced chemotaxis correlated with BALF IL-1b (r50.761, p50.001) and CXCL8 (r50.640, p50.012) in GPA, and was inhibited by anti-CXCL8 (85%; p,0.001) and anti-IL-1b (69%; p,0.001).Our study confirms a neutrophilia and pro-inflammatory alveolar milieu that persists in clinical remission. CXCL8 and IL-1b appear to play important roles in the neutrophil chemotactic response to BALF.

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Section: Discussionsupporting

confidence: 85%

Section: Discussioncontrasting

confidence: 51%

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Neutrophil chemotaxis in granulomatosis with polyangiitis (Wegener's) and idiopathic pulmonary fibrosis

Richter¹,

Perkins²,

Chavda³

et al. 2011

European Respiratory Journal

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“…We believe that ours is the first study to demonstrate that lower airway bacterial infection, especially with S aureus , is also common in patients with WG. Chronic lung damage is a recognised feature of the WG lung 14. and this may contribute to pathogen growth in conjunction with immunosuppressant therapy.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary infection in Wegener granulomatosis and idiopathic pulmonary fibrosis

Richter

Stockley

Harper

et al. 2009

Thorax

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Rationale: Wegener granulomatosis (WG) has previously been associated with increased nasal carriage of Staphylococcus aureus, but no studies have investigated the occurrence of pathogen growth in the lower airways. Objectives: To culture bronchoalveolar lavage fluid (BALF) from patients with WG, patients with idiopathic pulmonary fibrosis (IPF) and normal controls. Methods: 33 patients with WG, 22 with IPF and 8 normal controls underwent bronchoscopy and bronchoalveolar lavage. Quantitative culture established bacterial levels in the lower airways. Culture experiments were designed to investigate whether BALF is a supportive environment for S aureus growth. BALF cytokines were measured by ELISA. Results: Pathogens were commonly grown from BALF of patients with WG and those with IPF. S aureus was particularly associated with patients with WG both in relapse and in remission. BALF levels of interleukin 1 receptor antagonist (IL1ra) were statistically significantly elevated in those patients who grew a pathogen from lavage fluid. BALF from patients with WG and IPF stimulated S aureus growth compared with normal lavage fluid. Conclusions: Pathogens are more commonly isolated from BALF from patients with WG than from that of patients with IPF or normal controls, and with a different culture profile. IL1ra was associated with pathogen growth in WG and IPF. WG BALF is a trophic environment for S aureus growth. Pulmonologists treating patients with acute or relapsing WG should consider bronchoscopic microbiological sampling and consider antibiotics with antistaphylococcal activity.

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“…Until recently, the performance of the SF-36 had not been formally evaluated as an outcome measure in AAV. Both clinical practice and trial data consistently demonstrate that HRQOL is impaired among patients with AAV 24,25,31,32,33,34 .…”

Section: Core Set Domain: Patient-reported Outcomes: Health-related Qmentioning

confidence: 87%

The OMERACT Core Set of Outcome Measures for Use in Clinical Trials of ANCA-associated Vasculitis

Merkel¹,

Aydın²,

Boers

et al. 2011

J Rheumatol

108

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There has been a marked increase in the past 15 years in the number and quality of clinical trials in the idiopathic inflammatory vasculitides, especially the small-vessel vasculitides known as antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis [AAV; granulomatosis, with polyangiitis (Wegener's)]. These trials have been conducted by multicenter, international groups in Europe and the United States with financial support provided by government agencies and biopharmaceutical companies. This increased clinical trial activity in vasculitis has been accompanied by the development and validation of new outcome measures — a challenging process for these complex, multiorgan system diseases. The international OMERACT Vasculitis Working Group has developed and implemented an iterative research agenda that has utilized accumulated experience and datasets from several multicenter clinical trials and large cohort studies. This work has led to the development, evaluation, validation, and endorsement, through the OMERACT consensus and validation processes, of a “core set” of outcome measurements for use in clinical trials of AAV. The core set includes domains of disease activity, damage assessment, patient-reported outcomes, and mortality; there is at least one validated outcome measurement instrument available for each domain. This report reviews the domains of illness in AAV included in the OMERACT core set, describes the instruments validated to measure these domains, and presents the approved core set.

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Impairment of lung function, health status and functional capacity in patients with ANCA-associated vasculitis

Abstract: Patients with ANCA-associated disease may have significant lung function impairment irrespective of lung involvement at the time of diagnosis. Patients showed reduced respiratory muscle strength, health status and exercise capacity, which correlated with reduced transfer factor.

Cited by 25 publications

References 20 publications

Neutrophil chemotaxis in granulomatosis with polyangiitis (Wegener's) and idiopathic pulmonary fibrosis

Neutrophil chemotaxis in granulomatosis with polyangiitis (Wegener's) and idiopathic pulmonary fibrosis

Pulmonary infection in Wegener granulomatosis and idiopathic pulmonary fibrosis

The OMERACT Core Set of Outcome Measures for Use in Clinical Trials of ANCA-associated Vasculitis

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