Long-term treatment with human immunoglobulin for antisynthetase syndrome-associated interstitial lung disease.

BACKGROUND: Interstitial lung disease-associated antisynthetase syndrome (AS-ILD) carries significant morbidity and mortality. Corticosteroids and immunosuppressive drugs are the mainstay of treatment. Human immunoglobulin (IVIg), an immunomodulator without immunosuppressive properties, is effective in myositis but the evidence supporting its use in ILD is scarce. OBJECTIVE: To describe clinical outcomes of AS-ILD patients receiving IVIg. METHODS: Retrospective analysis of AS-ILD patients. Linear mixed models using restricted maximum likelihood estimation was used to estimate the change in lung function and corticosteroid dose over time. RESULTS: Data from 17 patients was analyzed. Median follow-up was 24.6 months. Fourteen patients had refractory disease. The mean percent-predicted forced vital capacity (FVC%) (p = 0.048) and percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (p = 0.0223) increased over time, while the mean prednisone dose (p < 0.001) decreased over time. Seven patients achieved a >10% increase in FVC%, including two who used IVIg as initial treatment. Five patients showed a >10% increase in DLCO% and TLC%. Nine (53%) patients experienced side effects. CONCLUSIONS: IVIg may be a useful complementary therapy in active progressive AS-ILD but is associated with potential side effects. Fssssurther investigation is required to determine the value of IVIg as an initial treatment in AS-ILD.

The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies.

RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.

Increased survival by feeding tetradecylthioacetic acid during a natural outbreak of heart and skeletal muscle inflammation in S0 Atlantic salmon, Salmo salar L.

We have previously documented increased survival by feeding tetradecylthioacetic acid (TTA) during a natural outbreak of infectious pancreatic necrosis in post-smolt S1 Atlantic salmon. The aim of the present study was to test the effects of dietary TTA in S0 smolt at a location where fish often experience natural outbreaks of heart and skeletal muscle inflammation (HSMI) during their first spring at sea. The experimental groups were fed a diet supplemented with 0.25% TTA for a 6-week period prior to a natural outbreak of HSMI in May 2007. Relative percent survival for the groups fed TTA was 45% compared with control diets, reducing mortality from 4.7% to 2.5%. Expression of genes related to lipid oxidation was higher in cardiac ventricles from salmon fed TTA compared with controls. In addition, salmon fed TTA had periodically reduced levels of plasma urea, and increased cardiosomatic index and growth. Reduced mortality and increased growth after administration of TTA may be related to a combination of anti-inflammatory effects, and an altered metabolic balance with better protein conservation because of increased lipid degradation.

Evaluation of penicillin and hyperbaric oxygen in the treatment of streptococcal myositis.

The purpose of this study was to evaluate effects of hyperbaric oxygen (HBO) and penicillin (PCN) therapy in a murine model of streptococcal myositis. The thighs of Swiss Webster mice were inoculated with Streptococcus pyogenes. Four groups were evaluated: (1) control (N = 10), (2) HBO treatment (N = 10), (3) PCN treatment (N = 8), and (4) PCN and HBO treatment (N = 6). Mortality (day of death) and the number of colony-forming units (cfu) were measured. PCN significantly lowered cfu from control (p < 0.05). Cfu in group 4 was significantly lower than PCN alone (p = 0.006). Survival was significantly longer in the PCN group compared with the control (p < 0.01). Survival in the combined treatment group was significantly longer than PCN alone (p < 0.01). These results suggest that (1) HBO treatment alone does not decrease mortality or bacterial proliferation in vivo significantly, (2) PCN therapy alone improves outcome significantly, and (3) the combined treatment of PCN and HBO exerts at least additive effects in both decreasing bacterial counts in vivo and increasing survival in this model.