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Peripheral blood biomarkers in idiopathic pulmonary fibrosis.

In this article, we review the evidence for peripheral blood biomarkers in idiopathic pulmonary fibrosis (IPF), a life-threatening fibrotic lung disease of unknown etiology. We focus on selected biomarkers present in peripheral blood, as they are easy to obtain, can be measured longitudinally, and have the greatest likelihood of achieving clinical utility.

This article concentrates on biomarkers with mechanistic plausibility that may be directly involved in the development of IPF, including KL-6, surfactant proteins A and D, matrix metalloproteases (MMP) 1 and 7, CCL18, VEGF, YKL-40, osteopontin, circulating fibrocytes, and T cells. After reviewing the evidence base for each, we designate the biomarkers that may have utility as:

  1. diagnostic biomarkers to distinguish IPF from other interstitial lung diseases,
  2. prognostic biomarkers that are correlated with disease progression or mortality,
  3. or biomarkers that can be used as tools for serial monitoring of disease severity.

Although there are no validated biomarkers that are currently available, the need for surrogates of diagnosis, prognosis, and monitoring of disease course with emerging therapies is great.

Exercise may offset nicotine-induced injury in lung tissue: A preliminary histological study.

Nicotine appears to be the primary pharmacologic agent that causes smoking-related pulmonary diseases. An understanding of the effect of nicotine on lungs is essential to develop interventions that can be used to counter smoking-related diseases. Further, it is shown that physical exercise may partially reverse smoking-induced pathological changes in experimental animals. Hence, this study focuses on the pathological changes in rat lung following nicotine administration and the role of exercise in reversing the nicotine-induced lung injury.

This is a randomized controlled trial with 3 groups of rats. Control (CG), nicotine-exposed (NG), and nicotine-exposed and exercise group (NEG). Control group received no intervention. Both NG and NEG were given 1.5 mg/kg nicotine base, daily, subcutaneously, but NEG were also subjected to an intensive daily swimming protocol. The rats were sacrificed and the lung tissue was processed for light and transmission electron microscopic and immunohistochemical studies. Compared with the control group, the nicotine group showed enlargement and destruction of the alveolar septum, cellular hyperplasia and interstitial fibrosis, and interstitial mononuclear cell infiltration with increased intraluminal macrophages. There was only modest morphological change between the nicotine administered and nicotine and exercise groups. Expression of superoxide dismutase (SOD) and catalase showed a mild increase in the NEG, whereas glutathione peroxidase (GPX) showed mild and moderate increase in the expression in the NG and NEG, respectively.

This study shows that nicotine induces substantial pathological changes in the lung and prolonged exercise may have some beneficial effects in partially reversing the nicotine-induced lung injury by inducing the expression of antioxidants.

Optical techniques in pulmonary medicine.

There is ongoing interest in the emerging field of pulmonary photonic-based diagnostics. Potential clinical need areas that are being actively investigated at this time include airway and peripheral lung cancer diagnostics, pulmonary parenchymal and interstitial disorders, alveolar structure function, inhalation injury, ciliary function analysis, asthma and obstructive lung diseases.

Lung cancer staging: a physiological update.

The tumour-node metastasis (TNM) classification system is anatomically based. We investigated whether the addition of simple physiological variables, age and body mass index (BMI), would affect survival curves, i.e. a composite anatomical and physiological staging system.

We retrospectively analysed a prospectively validated thoracic surgery database (n = 1981). Cox multivariate analysis was performed to determine possible significant factors. Kaplan-Meier survival curves were constructed with combined anatomical and physiological factors. Cox multivariate analysis revealed age (P < 0.001) and BMI (P = 0.01) as significant factors affecting survival. Receiver operating curve analysis determined cut-off levels for age of 67 and BMI of 27.6. A composite anatomical and physiological survival curve based on TNM for BMI > 27.6 and age < 67 was produced. Age and BMI criteria resulted in significantly different survival curves, for stage I (P < 0.0001) and stage II (P = 0.0032), but not for stage III (P = 0.06).

Neural network analysis confirmed the importance of BMI and age above cancer stage with regard to long-term survival. Combining age < 67, BMI > 27.6 and TNM anatomical classification results gives very different estimated survival curves from the usual TNM system. Patients from stages I, II and III may have survival equivalent to a stage higher or lower depending on their age and BMI.

Surgical results and staging of non-small cell lung cancer with interlobar pleural invasion.

The aim of this study was to compare the survival rates of non-small cell lung cancer (NSCLC) with interlobar pleural invasion (IPI) with that of patients with other T2 and T3 diseases according to the seventh TNM staging system.

One thousand and one patients with pathologic T2 and T3 NSCLC (according to the seventh staging criteria) treated between 1980 and 2004 were retrospectively evaluated. Among these, 682 patients were pathologically staged as T2 without IPI (T2 group), 25 as T2 with IPI (IPI group) and 294 as T3 (T3 group). The 5-year survival rate for the T2, IPI and T3 groups were 52.0, 31.1 and 36.3%, respectively. In patients without nodal involvement, the 5-year survival rates of the T2N0, IPIN0 and T3N0 groups were 60.9, 40.0 and 45.9%, respectively. The survival rate was significantly different between the T3N0 and T2N0 groups (P < 0.001) and between the IPIN0 and T2N0 (P = 0.020) groups.

There was no significant difference in the survival rate between the IPIN0 and T3N0 groups (P = 0.644). In patients without nodal involvement, the survival of NSCLC with IPI is similar to that of the T3 disease.

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