Associations of ω-3 Fatty Acids With Interstitial Lung Disease and Lung Imaging Abnormalities Among Adults.

Docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, attenuates interstitial lung disease (ILD) in experimental models, but human studies are lacking. We examined associations of circulating levels of DHA and other polyunsaturated fatty acids with hospitalization and death due to ILD over 12 years in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 6,573). We examined cross-sectional associations with CT lung abnormalities in MESA (2000-2012; n = 6,541), the Framingham Heart Study (2005-2011; n = 3,917), and the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik) (2002-2006; n = 1,106). Polyunsaturated fatty acid levels were determined from fasting blood samples and extracted from plasma phospholipids (MESA and AGES-Reykjavik) or red blood cell membranes (Framingham Heart Study). Higher DHA levels were associated with a lower risk of hospitalization due to ILD (per standard-deviation increment, adjusted rate ratio = 0.69, 95% confidence interval (CI): 0.48, 0.99) and a lower rate of death due to ILD (per standard-deviation increment, adjusted hazard ratio = 0.68, 95% CI: 0.47, 0.98). Higher DHA was associated with fewer interstitial lung abnormalities on computed tomography (per natural log increment, pooled adjusted odds ratio = 0.65, 95% CI: 0.46, 0.91). Higher DHA levels were associated with a lower risk of hospitalization and death due to ILD and fewer lung abnormalities on computed tomography in a meta-analysis of data from population-based cohort studies.

Mechanical Ventilation and Predictors of In-Hospital Mortality in Fibrotic Interstitial Lung Disease With Acute Respiratory Failure: A Cohort Analysis Through the Paradigm of Acute Respiratory Distress Syndrome.

OBJECTIVES: Prior studies report significant mortality in fibrotic interstitial lung disease patients undergoing mechanical ventilation. Little is known about baseline characteristics or ventilator strategies that might improve outcomes. We analyzed the ventilator characteristics of a large cohort of fibrotic interstitial lung disease patients from the perspective of an acute respiratory distress syndrome paradigm to see if any specific mechanical ventilation strategies might improve in-hospital mortality. DESIGN: Retrospective cohort study. SETTING: Single-center, multihospital medical ICUs. PATIENTS: Consecutive fibrotic interstitial lung disease patients who experienced mechanical ventilation for acute respiratory failure. INTERVENTIONS: Interstitial lung disease characteristics, demographics, and ventilator variables were analyzed for univariable and multivariable predictors of in-hospital mortality, adjusted for confounding with an a priori causation model. MEASUREMENTS AND MAIN RESULTS: A total of 111 patients accounted for 114 admissions. Idiopathic pulmonary fibrosis comprised 34% with idiopathic acute exacerbation (65%) being the most common admission type. Ninety-five percent were initiated on mandatory volume-control ventilation with only 50% achieving a low tidal volume strategy (plateau pressure ≤ 30 cm H2O) within 3 hours of intubation. Unadjusted clinical predictors of in-hospital mortality included age (unit odds ratio, 1.05; 1.01-1.10; p = 0.015), time from admission to intubation (hr) (unit odds ratio, 1.01; 1.01-1.03; p = 0.017), and use of paralytics (relative risk, 1.54; 1.26-1.90, p < 0.001). Adjusted mechanical ventilation-related predictors of in-hospital mortality included achieving early targeted plateau pressures (odds ratio, 0.23; 0.07-0.76; p = 0.016), PaO2/FIO2 ratio at 3 (unit odds ratio, 0.98; 0.96-0.99, p = 0.002) and 48 hours (unit odds ratio, 0.98; 0.97-0.99, p = 0.018), initial mean airway pressure (unit odds ratio, 1.13; 1.02-1.28, p = 0.019), and total net fluid status (mL) (unit odds ratio, 1.01; 1.001-1.02, p = 0.0001). CONCLUSIONS: Several factors predict in-hospital mortality in fibrotic interstitial lung disease-associated mechanical ventilation when viewed through an acute respiratory distress syndrome model. Further research is needed to refine strategies that may perhaps improve survival if mechanical ventilation is pursued in this set of patients.

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.

¹³¹I-labeled lipiodol-induced interstitial pneumonia: a series of 15 cases.

BACKGROUND: The drug (131)I-labeled lipiodol is used as internal radiotherapy for unresectable hepatocellular carcinoma. Although the drug was considered safe during preapproval studies, we observed several cases of interstitial pneumonia following its administration. METHODS: Cases were retrospectively identified through the drug safety unit database of Rennes University Hospital. RESULTS: From 1994 to 2009, interstitial pneumonia developed in 15 patients following (131)I-labeled lipiodol administration, with an estimated prevalence of 15.5 cases (95% CI, 7.7-23.2) per 1,000 treated patients. Mean age of the patients was 60 ± 8 years, and the male to female ratio was 6.5:1. All patients had cirrhosis, mainly related to long-term alcohol intoxication (n = 12). Most (n = 10) cases occurred after the second (131)I-labeled lipiodol injection. The median delay between last (131)I-labeled lipiodol administration and first respiratory symptoms was 30 days (interquartile range, 16.5-45 days). All patients presented with shortness of breath. Physical examination mostly revealed fever (n = 11) and bilateral crackles (n = 12). Chest CT scan showed bilateral ground-glass opacities (n = 8) with septal thickening, retraction, or both (n = 8). BAL (n = 7) was remarkable for increased neutrophils (n = 4) or CD8(+) T cell count (n = 3). Despite corticosteroids, 12 (80%) patients died, mostly of untractable respiratory failure (n = 9). Median delay between last (131)I-labeled lipiodol injection and death was 63 days (interquartile range, 34-129 days). CONCLUSIONS: Interstitial pneumonia may be a serious and not uncommon complication of (131)I-labeled lipiodol administration.

Acute interstitial pneumonia in feedlot cattle: effects of feeding feather meal or vitamin E.

We evaluated the effects of feeding 1.5% cysteine-rich feather meal or 550 IU of vitamin E for 40 d before slaughter on the rates of death and emergency slaughter due to acute interstitial pneumonia (AIP) in commercial feedlots. Blood and lung tissue were collected at slaughter from 83 animals clinically diagnosed with AIP, 40 asymptomatic penmates, and 40 heifers receiving either feather meal (20) or vitamin E (20); the left lung was subsampled for histologic examination. Blood and lung tissue were analyzed for thiol adducts of 3-methyleneindolenine (3ME) and reduced glutathione. Supplementation with feather meal or vitamin E had no effect on the rates of death and emergency slaughter attributable to AIP and did not influence the levels of 3ME or reduced glutathione in blood or lung tissue. Although supplementation with greater amounts of feather meal or vitamin E may have been necessary to significantly affect factors related to feedlot AIP, increased supplementation would be uneconomical for commercial feedlots, given the relatively low incidence of AIP.

Febrile-range hyperthermia augments pulmonary neutrophil recruitment and amplifies pulmonary oxygen toxicity.

Febrile-range hyperthermia (FRH) improves survival in experimental infections by accelerating pathogen clearance, but may also increase collateral tissue injury. We hypothesized that FRH would worsen the outcome of inflammation stimulated by a non-replicating agonist and tested this hypothesis in a murine model of pulmonary oxygen toxicity. Using a conscious, temperature-controlled mouse model, we showed that maintaining a core temperature at FRH (39 degrees C to 40 degrees C) rather than at euthermic levels (36.5 degrees C to 37 degrees C) during hyperoxia exposure accelerated lethal pulmonary vascular endothelial injury, reduced the inspired oxygen threshold for lethality, induced expression of granulocyte-colony stimulating factor, and expanded the circulating neutrophil pool. In these same mice, FRH augmented pulmonary expression of the ELR(+) CXC chemokines, KC and LPS-induced CXC chemokine, enhanced recruitment of neutrophils, and changed the histological pattern of lung injury to a neutrophilic interstitial pneumonitis. Immunoblockade of CXC receptor-2 abrogated neutrophil recruitment, reduced pulmonary vascular injury, and delayed death. These combined data demonstrate that FRH may enlist distinct mediators and effector cells to profoundly shift the host response to a defined injurious stimulus, in part by augmenting delivery of neutrophils to sites of inflammation, such as may occur in infections. In certain conditions, such as in the hyperoxic lung, this process may be deleterious.