Radiographic airway abnormalities in untreated early rheumatoid arthritis are associated with peripheral neutrophil activation.

BACKGROUND: The role of the lung for the initiation and progression of rheumatoid arthritis (RA) is still unclear. Up to 10% of RA patients develop interstitial lung disease which remains a clinical challenge. Understanding early disease mechanisms is of great importance. The objective of this study was to determine whether there is an association between peripheral neutrophil phenotypes and presence of pulmonary abnormalities (PA) on chest high-resolution computed tomography (HRCT) in untreated early RA (ueRA). METHODS: Clinical data and blood were collected, and HRCT performed at diagnosis on 30 consecutive anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) positive ueRA patients. HRCTs were evaluated for the presence of RA-associated parenchymal, airway and/or pleural abnormalities. Expression of phenotype markers on neutrophils were determined by flow cytometry. Levels of calprotectin, ACPA and RF were measured using immunoassays. RESULTS: The frequency of having any PA was 60%. Airway abnormalities were present in 50%, parenchymal nodules in 43% and interstitial lung abnormalities (ILA) in 10%. Unsupervised multivariate data analysis showed clustering of any PA with neutrophil activation, parameters of inflammation and RF titres. In univariate analysis, the patients with PA displayed significantly increased CD11b and decreased CD62L expression on neutrophils (1.2-fold, p = 0.014; 0.8-fold, p = 0.012) indicating activation and significantly increased RF IgM titre and CRP (5.7-fold, p = 0.0025; 2.3-fold, p = 0.0035) as compared to no PA. Titres of RF, but not ACPA, correlated with expression of the neutrophil activation marker CD11b. A stratified analysis demonstrated that airway involvement was the PA subtype with the strongest association with neutrophil activation. CONCLUSION: We report a strong association between radiographic airway findings and activation of circulating neutrophils in early RA supporting a role of innate immunity and the lung at disease onset. Our results also indicate different contributions of RF and ACPA in the RA pathogenesis.

Treatment effect of memantine on survival in dementia with Lewy bodies and Parkinson's disease with dementia: a prospective study.

OBJECTIVE: To investigate the effect on survival of treatment with memantine in patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). METHODS: 75 patients with DLB and PDD were included in a prospective double-blinded randomised placebo-controlled trial (RCT) of memantine, of whom long-term follow-up was available for 42. Treatment response was recorded 24 weeks from baseline and measured by Clinical Global Impression of Change (CGIC). The participants were grouped as responders (CGIC 1-3) or non-responders (CGIC 4-7). The 24-week RCT was followed by open-label treatment and survival was recorded at 36 months. RESULTS: After 36-month follow-up, patients in the memantine group had a longer length of survival compared with patients in the placebo group (log rank x²=4.02, p=0.045). Within the active treatment group, survival analysis 36 months from baseline showed that the memantine responders, based on CGIC, had higher rates of survival compared with the non-responders (log rank x²=6.595, p=0.010). Similar results were not seen in the placebo group. CONCLUSIONS: Early treatment with memantine and a positive clinical response to memantine predicted longer survival in patients with DLB and PDD. This suggests a possible disease-modifying effect and also has implications for health economic analysis. However, owing to the small study sample, our results should merely be considered as generating a hypothesis which needs to be evaluated in larger studies. TRIAL REGISTRATION NUMBER: ISRCTN89624516.

The impact of autonomic dysfunction on survival in patients with dementia with Lewy bodies and Parkinson's disease with dementia.

INTRODUCTION: Autonomic dysfunction is a well-known feature in neurodegenerative dementias, especially common in α-synucleinopathies like dementia with Lewy bodies and Parkinson's disease with dementia. The most common symptoms are orthostatic hypotension, incontinence and constipation, but its relevance in clinical practice is poorly understood. There are no earlier studies addressing the influence of autonomic dysfunction on clinical course and survival. The aim of this study was to investigate the frequency of the three most common features of autonomic dysfunction and analyze how it affects survival. METHODS: Thirty patients with dementia with Lewy bodies and Parkinson's disease with dementia were included in this prospective, longitudinal follow-up study. Presence of incontinence and constipation was recorded at baseline. Blood pressure was measured at baseline, after 3 months and after 6 months according to standardized procedures, with 5 measurements during 10 minutes after rising. Orthostatic hypotension was defined using consensus definitions and persistent orthostatic hypotension was defined as 5 or more measurements with orthostatic hypotension. Difference in survival was analyzed 36 months after baseline. RESULTS: There was a high frequency of persistent orthostatic blood pressure (50%), constipation (30%) and incontinence (30%). Patients with persistent orthostatic hypotension had a significantly shorter survival compared to those with no or non-persistent orthostatic hypotension (Log rank x(2) = 4.47, p = 0.034). Patients with constipation and/or urinary incontinence, in addition to persistent orthostatic hypotension, had a poorer prognosis compared to those with isolated persistent orthostatic hypotension or no orthostatic hypotension (Log rank x(2) = 6.370, p = 0.041). DISCUSSION: According to our findings, the identification of autonomic dysfunction seems to be of great importance in clinical practice, not only to avoid falls and other complications, but also as a possible predictor of survival.

Differences in survival between patients with dementia with Lewy bodies and patients with Alzheimer's disease--measured from a fixed cognitive level.

INTRODUCTION: The aim of this study was to compare survival in patients with Alzheimer's disease (AD) and patients with dementia with Lewy bodies (DLB). Since anamnestic and retrospective information about disease duration are unreliable variables, we measured survival from a fixed cognitive level. METHODS: Survival time was measured from the reported disease onset, from the time of diagnosis, from Mini-Mental State Examination (MMSE) 20 ± 1, and from MMSE 17 ± 1. RESULTS: Survival time was significantly shorter in the DLB group compared to the AD group both from the time of diagnosis and from the cognitive levels of 20 and 17 on the MMSE. There was no difference in survival when measured from the reported disease onset. DISCUSSION: Our findings indicate that DLB patients have a more malignant clinical course. Our method of investigating survival in a cognitively homogenous population may gain scientific power. Reliable methods to predict survival and the clinical course are of great value for patients, caregivers, doctors, and society.