Normalization of lung function following treatment of secondary usual interstitial pneumonia: a case report.

Usual interstitial pneumonia (UIP) is the most common idiopathic interstitial pneumonia (IIP) and is associated with a poor prognosis and poor responsiveness to immunosuppressive therapy. We present a case of a woman with steroid-responsive biopsy-proven UIP with significant and sustained improvement in pulmonary function. A female in her 40s presented following a one-year history of progressive dyspnea, a 20 lb weight loss, and fatigue. Imaging of the chest with computed tomography (CT) showed bibasilar subpleural reticular opacities and minimal peripheral honeycombing. Comprehensive connective tissue disease (CTD) antibody testing was negative. Pulmonary function testing showed moderate impairment with reduction in forced vital capacity (FVC, 69% predicted), forced expiratory volume in one second (FEV1 73% predicted), and diffusing capacity for carbon monoxide (DLCO, 52% predicted). Surgical lung biopsy showed UIP with prominent inflammatory infiltrates. Following treatment with prednisone and azathioprine, the patient's symptoms resolved, while objective pulmonary function testing showed normalization of lung function, which is sustained at >4 years of follow-up. Improvement in lung function following immunosuppressive therapy is distinctly uncommon in either idiopathic or secondary UIP. This report suggests that occasionally, patients with secondary UIP occurring in the context of otherwise undefinable autoimmune clinical syndromes may be responsive to immunosuppressive therapy.

Correlation of regional emphysema and lung cancer: a lung tissue research consortium-based study.

BACKGROUND: Chronic obstructive pulmonary disease and lung cancer are linked because both airflow obstruction and emphysema, on computer tomography, are independent risk factors for lung cancer. However, the local risk of malignancy relative to development of regional emphysema has not yet been defined. Specifically, it is not known if primary lung cancers are associated with regions of worse emphysema within individual patients. METHODS: We performed a database analysis evaluating the association between the degree of regional emphysema as scored on computer tomography and development of primary lung cancer. We also studied the association between regional emphysema and benign lung nodules. We assembled two distinct cohorts using the National Heart, Lung, and Blood Institute's Lung Tissue Research Consortium database, hypothesizing that lung malignancy will preferentially locate in the regions of the most severe emphysema. RESULTS: In the Lung Tissue Research Consortium database, 624 cases met criteria for the malignant nodule cohort and 64 were included in the benign nodule cohort. When comparing location of a malignant nodule to other lung regions within the same person, the odds of having a more severe emphysema score in the location of lung cancer was 1.342 (95% confidence interval 1.112-1.620; p = 0.0022). When comparing location of a benign nodule to other lung regions within the same person, the odds of having a more severe emphysema score in the location of the benign nodule was 1.118 (95% confidence interval 0.725-1.725; p = 0.6137). CONCLUSIONS: Primary lung cancers are associated with areas of worse regional emphysema.

Osseous sarcoidosis: a case of evolving MR appearances correlating with clinical symptoms.

Osseous sarcoidosis of the axial skeleton is typically asymptomatic and not routinely imaged with MRI. The natural history of sarcoidosis is generally felt to be resolution spontaneously or with treatment, or unremitting progression. We report a case of recurrent active symptomatic disease after an initial response to immunomodulator treatment with an unusual halo of T2-hyperintensity surrounding treated fibrofatty vestigial lesions.

TNF-alpha drives matrix metalloproteinase-9 in squamous oral carcinogenesis.

OBJECTIVES/HYPOTHESIS: It is well known that invasion is a seminal event in the progression of oral and other head and neck carcinoma sites. We have previously demonstrated tumor necrosis factor (TNF)-alpha and its dependent cytokines are upregulated in saliva during oral carcinogenesis. TNF-dependent events stimulate nuclear factor (NF)-kappaB and many NF-kappaB-dependent genes are associated with cancer progression. MATERIALS AND METHODS: In the present study, we examined NF-kappaB stimulation of matrix metalloproteinase (MMP)-9 in a precancerous keratinocyte cell line that models leukoplakia (Rhek cells). We stimulated Rhek cells with both TNF-alpha and phorbol myristate acetate, known stimulants of NF-kappaB. We then assayed MMP-9 transcription and secretion by luciferase reporter genes, quantitative real-time polymerase chain reaction, and fluorometric enzyme-linked immunosorbent serologic assay. RESULTS: We discovered that the MMP-9 promoter was significantly stimulated by phorbol myristate acetate and TNF-alpha on luciferase reporter gene assays. Further, we uncovered that functional MMP-9 promoter activation was accompanied by significant increases in MMP-9 gene expression, as judged by quantitative real-time polymerase chain reaction. Functional activation of the MMP-9 protein was stimulated by TNF-alpha and PMA on a fluorescent enzyme-linked immunosorbent serologic assay. Finally, we searched our salivary proteomic database for increases in MMP-9 and discovered it was the third most significant protein in salivas of oral cavity cancer patients over normal controls. CONCLUSIONS: We conclude the milieu cytokine, TNF-alpha, has the capacity to provide stimulation of events related to early invasion of oral cavity cancer, as judged by its ability to stimulate MMP-9.