Performance of GAP and ILD-GAP models in predicting lung transplant or death in interstitial pneumonia with autoimmune features.

OBJECTIVES: To assess the ability of two risk prediction models in interstitial lung disease (ILD) to predict death or lung transplantation in a cohort of patients with interstitial pneumonia with autoimmune features (IPAF). METHODS: We performed a retrospective cohort study of adults with IPAF at an academic medical center. The primary outcome was a composite of lung transplantation or death. We applied the patient data to the previously described GAP and ILD-GAP models to determine the ability of these models to predict the composite outcome. Model discrimination was assessed using the c-index, and model calibration was determined by comparing the incidence ratios of observed versus expected deaths. RESULTS: Ninety-four patients with IPAF were included. Mean (standard deviation) age was 58 (13.5) years and the majority were female (62%). The majority met serologic and morphologic criteria for IPAF (94% and 91%, respectively). The GAP model had a c-index of 0.664 (95% confidence interval [CI] 0.547-0.781), while the ILD-GAP model had a c-index of 0.569 (95% CI 0.440-0.697). In those with GAP stage 1 or GAP stage 2 disease, calibration of the GAP model was satisfactory at 2 and 3 years for the cumulative end point of lung transplantation or death. CONCLUSION: In patients with IPAF, the GAP model performed well as a predictor of lung transplantation or death at 2 years and 3 years from ILD diagnosis in patients with GAP stage 1 and GAP stage 2 disease.

Assessing predictors of rheumatoid arthritis-associated interstitial lung disease using quantitative lung densitometry.

OBJECTIVE: To assess predictors of subclinical RA-associated interstitial lung disease (RA-ILD) using quantitative lung densitometry (qLD). METHODS: RA patients underwent multi-detector row CT scanning at baseline and after an average of 39 months. Scans were analysed with qLD for the percentage of lung parenchyma with high attenuation areas (%HAA: the percentage of voxels of -600 to -250 Hounsfield units). Additionally, a pulmonary radiologist calculated an expert radiologist scoring (ERS) for RA-ILD features. Generalized linear models were used to identify indicators of baseline %HAA and predictors of %HAA change. RESULTS: Baseline %HAA was assessed in 193 RA patients and 106 had repeat qLD assessment. %HAA was correlated with ERS (Spearman's rho = 0.261; P < 0.001). Significant indicators of high baseline %HAA (>10% of lung parenchyma with high attenuation) included female sex, higher pack-years of smoking, higher BMI and anti-CCP ≥200 units, collectively contributing an area under the receiver operator curve of 0.88 (95% CI 0.81, 0.95). Predictors of %HAA increase, occurring in 49% with repeat qLD, included higher baseline %HAA, presence of mucin 5B (MUC5B) minor allele and absence of HLA-DRB1 shared epitope (area under the receiver operator curve = 0.69; 95% CI 0.58, 0.79). The association of the MUC5B minor allele with %HAA change was higher among men and those with higher cumulative smoking. Within the group with increased %HAA, anti-CCP level was significantly associated with a greater increase in %HAA. CONCLUSIONS: %HAA, assessed with qLD, was linked to several known risk factors for RA-ILD and may represent a more quantitative method to identify RA-ILD and track progression than expert radiologist interpretation.

Risk of progression of interstitial pneumonia with autoimmune features to a systemic autoimmune rheumatic disease.

OBJECTIVE: The aim of this study was to determine the risk of developing a systemic autoimmune rheumatic disease (ARD) after an initial diagnosis of interstitial pneumonia with autoimmune features (IPAF). METHODS: We performed a retrospective cohort study of patients with interstitial lung disease (ILD) who were evaluated at Columbia University Irving Medical Center from 2009 to 2017. We divided patients with idiopathic ILD into two groups: those who met IPAF criteria and those who did not meet IPAF criteria at initial ILD diagnosis. We examined the association between IPAF and diagnosis of ARD during the follow-up period using a multivariable-adjusted logistic regression model. RESULTS: Of the 697 patients with ILD who were screened, 174 met inclusion criteria (50 met IPAF criteria and 124 did not). During a median follow-up period of 5.2 years, 16% (8/50) of subjects with IPAF were diagnosed with an ARD compared with 1.6% (2/124) of subjects without IPAF (P = 0.001). Adjusting for age, sex, smoking status and use of immunosuppressive therapy, the odds of progressing to an ARD were 14 times higher in subjects with IPAF than in those without IPAF (odds ratio 14.18, 95% CI 1.44-138.95, P = 0.02). CONCLUSION: The presence of IPAF confers an increased risk of developing an ARD. Patients with IPAF should therefore be followed closely for the development of an ARD.

Stress triggers coronary mast cells leading to cardiac events.

OBJECTIVE: Stress precipitates and worsens not only asthma and atopic dermatitis but also acute coronary syndromes (ACSs), which are associated with coronary inflammation. Evidence linking stress to ACS was reviewed and indicated that activation of coronary mast cells (MCs) by stress, through corticotropin-releasing hormone (CRH) and other neuropeptides, contributes to coronary inflammation and coronary artery disease. DATA SOURCES: PubMed was searched (2005-2013) for articles using the following keywords: allergies, anaphylaxis, anxiety, coronary arteries, coronary artery disease, C-reactive protein, cytokines, chymase, histamine, hypersensitivity, interleukin-6 (IL-6), inflammation, mast cells, myocardial ischemia, niacin, platelet-activating factor, rupture, spasm, statins, stress, treatment, tryptase, and uroctortin. STUDY SELECTIONS: Articles were selected based on their relevance to how stress affects ACS and how it activates coronary MCs, leading to coronary hypersensitivity, inflammation, and coronary artery disease. RESULTS: Stress can precipitate allergies and ACS. Stress stimulates MCs through the activation of high-affinity surface receptors for CRH, leading to a CRH-dependent increase in serum IL-6. Moreover, neurotensin secreted with CRH from peripheral nerves augments the effect of CRH and stimulates cardiac MCs to release IL-6, which is elevated in ACS and is an independent risk factor for myocardial ischemia. MCs also secrete CRH and uroctortin, which induces IL-6 release from cardiomyocytes. The presence of atherosclerosis increases the risk of cardiac MC activation owing to the stimulatory effect of lipoproteins and adipocytokines. Conditions such as Kounis syndrome, mastocytosis, and myalgic encephalopathy/chronic fatigue syndrome are particularly prone to coronary hypersensitivity reactions. CONCLUSION: Inhibition of cardiac MCs may be a novel treatment approach.

Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor.

BACKGROUND: Mast cells are involved in allergy and inflammation by the secretion of multiple mediators, including histamine, cytokines, and platelet-activating factor (PAF), in response to different triggers, including emotional stress. PAF has been associated with allergic inflammation, but there are no clinically available PAF inhibitors. OBJECTIVE: To investigate whether PAF could stimulate human mast cell mediator release and whether rupatadine (RUP), a dual histamine-1 and PAF receptor antagonist, could inhibit the effect of PAF on human mast cells. METHODS: Laboratory of allergic diseases 2 cultured mast cells were stimulated with PAF (0.001, 0.01, and 0.1 µmol/L) and substance P (1 µmol/L) with or without pretreatment with RUP (2.5 and 25 µmol/L), which was added 10 minutes before stimulation. Release of ß-hexosaminidase was measured in supernatant fluid by spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis factor were measured by enzyme-linked immunosorbent assay. RESULTS: PAF stimulated a statistically significant release of histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 µmol/L) that was comparable to that stimulated by substance P. Pretreatment with RUP (25 µmol/L) for 10 minutes inhibited this effect. In contrast, pretreatment of laboratory of allergic diseases 2 cells with diphenhydramine (25 µmol/L) did not inhibit mediator release, suggesting that the effect of RUP was not due to its antihistaminic effect. CONCLUSION: PAF stimulates human mast cell release of proinflammatory mediators that is inhibited by RUP. This action endows RUP with additional properties in treating allergic inflammation.

Implementing an Electronic Medical Record-Based Reminder for Cardiovascular Risk Screening in Rheumatoid Arthritis.

OBJECTIVE: Although cardiovascular disease (CVD) is the leading cause of death among individuals with rheumatoid arthritis (RA), CVD risks are not being assessed frequently and systematically in RA. We implemented an electronic medical record (EMR)-based reminder in a tertiary care center and assessed the effects of this intervention on CVD risk screening by rheumatologists and primary care providers. METHODS: The EMR reminder was implemented in December 2013 and included the most recent value and target ranges for body mass index, blood pressure (BP), and lipid profiles. It was displayed for every rheumatology and primary care visit for all patients with the International Classification of Diseases, Ninth Revision code for RA (714.0). Lipid screening rates, as well as changes in BP and obesity rates were compared pre- and postimplementation. Factors associated with lipid screening postimplementation were assessed using multivariate logistic regression. RESULTS: A total of 138 and 112 RA patients were seen in the outpatient clinics pre- and postimplementation, respectively. The demographic characteristics were similar in the pre- and postimplementation groups. Lipid screening rates were 50% preimplementation and 46% postimplementation (P = 0.58). There were no significant improvements in BP or obesity rates postimplementation. Factors associated with the higher odds of lipid screening included older age and history of diabetes mellitus. CONCLUSION: Implementing an EMR reminder did not improve CVD risk screening among RA patients. Future research is needed to identify and address barriers to CVD screening, and to educate patients and providers about RA-related risks.

Effect of stress on brain inflammation and multiple sclerosis.

Substantial evidence indicates that stress can precipitate or worsen symptoms of inflammation in general and more specifically in multiple sclerosis (MS), a demyelinating, autoimmune disease characterized by inflammation of the central nervous system (CNS). However, the mechanism of how stress affects MS is not well understood. We reviewed publications in PubMed since 1995 and propose that neuropeptides secreted under stress, such as corticotropin releasing hormone (CRH) and neurotensin (NT), activate microglia and mast cells to release inflammatory molecules. These lead to maturation and activation of T17 autoimmune cells, disruption of the blood-brain barrier (BBB) and T cell entry into the CNS, thus promoting brain inflammation and contributing to MS pathology. Reduction of stress and inhibition of these processes by select flavonoids could provide novel therapeutic approaches.