Treatment Outcomes for Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Real-World, Multisite Study of the Impact of Immunosuppression on Pulmonary Function Trajectory

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice. RESEARCH QUESTION: How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD? STUDY DESIGN AND METHODS: Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers. Change in lung function before and after treatment was analyzed using a linear spline mixed-effect model with random intercept. Prespecified secondary analyses examined the impact of radiologic pattern of ILD (ie, usual interstitial pneumonia [UIP] vs non-UIP) on treatment trajectory. RESULTS: Two hundred twelve patients were included in the analysis: 92 patients (43.4%) were treated with azathioprine, 77 patients (36.3%) were treated with mycophenolate mofetil, and 43 patients (20.3%) were treated with rituximab. In the combined analysis of all three agents, an improvement in FVC % predicted was found after 12 months of treatment compared with the potential 12-month response without treatment (+3.90%; P ≤ .001; 95% CI, 1.95-5.84). Diffusing capacity of the lungs for carbon monoxide (Dlco) % predicted also improved at 12 months (+4.53%; P ≤ .001; 95% CI, 2.12-6.94). Neither the UIP pattern of ILD nor choice of immunosuppressive agent significantly impacted the pulmonary function trajectory on immunosuppression. INTERPRETATION: Immunosuppression was associated with an improved trajectory in FVC and Dlco compared with the pretreatment pulmonary function trajectory. Prospective, randomized trials are required to validate these findings

International laboratory comparison of influenza microneutralization assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) influenza viruses by CONSISE

The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HAMNassay protocols to enable better correlation of these assays in the future

Treatment outcomes for rheumatoid arthritis associated interstitial lung disease; a real-world, multisite study of the impact of immunosuppression on pulmonary function trajectory

Background Rheumatoid arthritis (RA) associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. There are no randomized, placebo-controlled data to support the role of immunosuppression to treat RA-ILD despite being widely used in clinical practice. Research Question How does immunosuppression impact pulmonary function trajectory in a multi-site retrospective cohort of RA-ILD patients? Study Design and Methods Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were retrospectively identified from five ILD centers. Change in lung function before and after treatment was analyzed using a linear spline mixed effect model with random intercept. Prespecified secondary analyses examined the impact of radiologic pattern of ILD (i.e., usual interstitial pneumonia [UIP] vs non-UIP) on treatment trajectory. Results 212 patients were included in the analysis: 92 (43.4%) were treated with azathioprine, 77 (36.3%) with mycophenolate mofetil and 43 (20.3%) with rituximab. In the combined analysis of all three agents, there was an improvement in forced vital capacity (FVC) % predicted after 12 months of treatment compared to the potential 12-month response without treatment [+3.90%, p=< 0.001; 95% CI, (1.95, 5.84)]. Diffusing capacity for carbon monoxide (DLCO) % predicted also improved at 12 months [+4.53%, p=<0.001; (2.12, 6.94)]. Neither the UIP pattern of ILD or choice of immunosuppressive agent significantly impacted the pulmonary function trajectory on immunosuppression. Interpretation Immunosuppression was associated with an improved trajectory in FVC and DLCO compared to the pre-treatment pulmonary function trajectory. Prospective, randomized trials are required to validate these findings

Free-electron laser data for multiple-particle fluctuation scattering analysis.

Fluctuation X-ray scattering (FXS) is an emerging experimental technique in which solution scattering data are collected using X-ray exposures below rotational diffusion times, resulting in angularly anisotropic X-ray snapshots that provide several orders of magnitude more information than traditional solution scattering data. Such experiments can be performed using the ultrashort X-ray pulses provided by a free-electron laser source, allowing one to collect a large number of diffraction patterns in a relatively short time. Here, we describe a test data set for FXS, obtained at the Linac Coherent Light Source, consisting of close to 100 000 multi-particle diffraction patterns originating from approximately 50 to 200 Paramecium Bursaria Chlorella virus particles per snapshot. In addition to the raw data, a selection of high-quality pre-processed diffraction patterns and a reference SAXS profile are provided

Free-electron laser data for multiple-particle fluctuation scattering analysis.

Fluctuation X-ray scattering (FXS) is an emerging experimental technique in which solution scattering data are collected using X-ray exposures below rotational diffusion times, resulting in angularly anisotropic X-ray snapshots that provide several orders of magnitude more information than traditional solution scattering data. Such experiments can be performed using the ultrashort X-ray pulses provided by a free-electron laser source, allowing one to collect a large number of diffraction patterns in a relatively short time. Here, we describe a test data set for FXS, obtained at the Linac Coherent Light Source, consisting of close to 100 000 multi-particle diffraction patterns originating from approximately 50 to 200 Paramecium Bursaria Chlorella virus particles per snapshot. In addition to the raw data, a selection of high-quality pre-processed diffraction patterns and a reference SAXS profile are provided

25 Signatures

175 Issue 251985 Issue 11986 Issue 21987 Issue 31988 Issue 41989 Issue 51990 Issue 61991 Issue 71992 Issue 81993 Issue 91994 Issue 101995 Issue 111997 Issue 121998 Issue 131999 Issue 142000 Issue 152001 Issue 162002 Issue 172003 Issue 182004 Issue 192005 Issue 202006 Issue 212007 Issue 222008 Issue 232009 Issue 2