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Association between anti-TNF-α therapy and interstitial lung disease.

Pharmacoepidemiol Drug Saf. 2013 Jan 29;

Authors: Herrinton LJ, Harrold LR, Liu L, Raebel MA, Taharka A, Winthrop KL, Solomon DH, Curtis JR, Lewis JD, Saag KG

Abstract
BACKGROUND: Anti-tumor necrosis factor-α (TNF-α) agents have been hypothesized to increase the risk of interstitial lung disease (ILD), including its most severe manifestation, pulmonary fibrosis. METHODS: We conducted a cohort study among autoimmune disease patients who were members of Kaiser Permanente Northern California, 1998-2007. We obtained therapies from pharmacy data and diagnoses of ILD from review of X-ray and computed tomography reports. We compared new users of anti-TNF-α agents to new users of non-biologic therapies using Cox proportional hazards analysis to adjust for baseline propensity scores and time-varying use of glucocorticoids. We also made head-to-head comparisons between anti-TNF-α agents. RESULTS: Among the 8417 persons included in the analysis, 38 (0.4%) received a diagnostic code for ILD by the end of follow-up, including 23 of 4200 (0.5%) who used anti-TNF-α during study follow-up, and 15 of 5423 (0.3%) who used only non-biologic therapies. The age-standardized and gender-standardized incidence rate of ILD, per 100 person-years, was 0.21 [95% confidence interval (CI) 0-0.43] for rheumatoid arthritis and appreciably lower for other autoimmune diseases. Compared with the use of non-biologic therapies, use of anti-TNF-α therapy was not associated with a diagnosis of ILD among patients with rheumatoid arthritis (adjusted hazard ratio, 1.03; 95%CI 0.51-2.07), nor did head-to-head comparisons across anti-TNF-α agents suggest important differences in risk, although the number of cases available for analysis was limited. CONCLUSION: The study provides evidence that compared with non-biologic therapies, anti-TNF-α therapy does not increase the occurrence of ILD among patients with autoimmune diseases and informs research design of future safety studies of ILD. Copyright © 2013 John Wiley & Sons, Ltd.

PMID: 23359391 [PubMed - as supplied by publisher]

The role of hypoxia in pulmonary vascular diseases: a perspective.

Am J Physiol Lung Cell Mol Physiol. 2013 Feb 1;

Authors: Voelkel NF, Mizuno S, Bogaard HJ

Abstract
From the discovery of hypoxic pulmonary vasoconstriction, responses to hypoxia have been considered as representative for the many alterations in lung vessels that occur in several chronic lung diseases, including pulmonary hypertension, interstitial pulmonary fibrosis, acute respiratory distress syndrome and COPD. An essential part of preclinical research to explain the pathobiology of these diseases has been centered around the exposure of small and large animals to hypoxia. This review aims to summarize pivotal results of clinical and preclinical research on hypoxia, which still have important implications for researchers today.

PMID: 23377344 [PubMed - as supplied by publisher]

Serum Interleukin 6 Is Predictive of Early Functional Decline and Mortality in Interstitial Lung Disease Associated with Systemic Sclerosis.

J Rheumatol. 2013 Feb 1;

Authors: De Lauretis A, Sestini P, Pantelidis P, Hoyles R, Hansell DM, Goh NS, Zappala CJ, Visca D, Maher TM, Denton CP, Ong VH, Abraham DJ, Kelleher P, Hector L, Wells AU, Renzoni EA

Abstract
OBJECTIVE: Biomarkers of progression of interstitial lung disease (ILD) are needed to allow early therapeutic intervention in patients with scleroderma-associated disease (SSc-ILD). METHODS: A panel of 8 serum cytokines [interleukin 6 (IL-6), IL-8, IL-10, CCL2, CXCL10, vascular endothelial growth factor, fibroblast growth factor 2, and CX3CL1] was assessed by Luminex bead technology in exploratory cohorts of 74 patients with SSc and 58 patients with idiopathic pulmonary fibrosis (IPF). Mortality and significant lung function decline [forced vital capacity (FVC) ≥ 10%; DLCO ≥ 15%] from date of serum collection were evaluated by proportional hazards analysis. Based on these findings, the prognostic value of serum IL-6, evaluated by ELISA, was assessed in a larger test cohort of 212 patients with SSc-ILD. RESULTS: In the exploratory cohort, only serum IL-6 was an independent predictor of DLCO decline in both IPF and SSc-ILD. The IL-6 threshold level most predictive of DLCO decline within a year was 7.67 pg/ml. In the larger test cohort, serum IL-6 > 7.67 pg/ml was predictive of decline in FVC (HR 2.58 ± 0.98, p = 0.01) and in DLCO (HR 3.2 ± 1.7, p = 0.02) within the first year, and predictive of death within the first 30 months (HR 2.69 ± 0.96, p = 0.005). When stratified according to severity (FVC < 70%), serum IL-6 > 7.67 pg/ml was predictive of functional decline or death within the first year in patients with milder disease (OR 3.1, 95% CI 1.4-7.2, p = 0.007), but not in those with severe ILD. CONCLUSION: In SSc-ILD, serum IL-6 levels appear to be predictive of early disease progression in patients with mild ILD, and could be used to target treatment in this group, if confirmed by prospective studies.

PMID: 23378460 [PubMed - as supplied by publisher]

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Clinical experience in invasive fungal infections.

Clin Drug Investig. 2013 Feb;33 Suppl 1:23-6

Authors: Pacheco P, Ventura AS, Branco T, Gonçalves L, Carvalho C

Abstract
Lung infections caused by invasive filamentous fungi are very rare conditions in AIDS, but must be considered in patients with profound immune suppression especially in the presence of additional risk factors, such as hematologic malignancies, corticosteroid therapy, neutropenia, and chemotherapy. The authors report a case of dual lung infection caused by Aspergillus and Mucor, which occurred in a 34-year-old AIDS patient who was treated with chemotherapy for oral plasmablastic lymphoma. The case presented clinically with low grade fever and pulmonary cavitation, which suggested tuberculosis. After extensive investigation the diagnosis of mucormycosis was established and the patient was treated sequentially with liposomal amphotericin B and posaconazole. Despite a reduction in the size of the pulmonary cavitation, improvement of the lung interstitial infiltrates and clinical recovery, the patient was submitted to cardiothoracic surgery given the aggressive behavior of this invasive fungus. Histology of the surgical specimen showed numerous hyphae with a morphologic pattern compatible with Aspergillus as well as hyphae that were suggestive of Mucor.

PMID: 23381980 [PubMed - in process]