Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide in the emergency department improved the evaluation and treatment of patients with acute dyspnea and thereby reduced the time to discharge and the total cost of treatment.

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The influence of pulmonary resection on functional capacity can be assessed in different ways. The aim of this study was to compare the effect of lobectomy and pneumonectomy on pulmonary function tests (PFT), exercise capacity and perception of symptoms.Sixty eight patients underwent functional assessment with PFT and exercise testing before (Preop), and 3 and 6 months after lung resection. In 50 (36 males and 14 females; mean age 61 yrs) a lobectomy was performed and in 18 (13 males and 5 females; mean age 59 yrs) a pneumonectomy was performed.Three months after lobectomy, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), total lung capacity (TLC), transfer factor of the lungs for carbon monoxide (TL,CO) and maximal oxygen uptake (V'O 2 ,max) were significantly lower than Preop values, increasing significantly from 3 to 6 months after resection. Three months after pneumonectomy, all parameters were significantly lower than Preop values and significantly lower than postlobectomy values and did not recover from 3 to 6 months after resection. At 6 months after resection significant deficits persisted in comparison with Preop: for FVC 7% and 36%, FEV1 9% and 34%, TLC 10% and 33% for lobectomy and pneumonectomy, respectively; and V'O 2 ,max 20% after pneumonectomy only. Exercise was limited by leg muscle fatigue in 53% of all patients at Preop. This was not altered by lobectomy, but there was a switch to dyspnoea as the limiting factor after pneumonectomy (61% of patients at 3 months and 50% at 6 months after resection). Furthermore, pneumonectomy compared to lobectomy led to a significantly smaller breathing reserve (mean±SD) (28±13 vs 37±16% at 3 months; and 24±11% vs 33±12% at 6 months post resection) and lower arterial oxygen tension at peak exercise 10.1±1.5 vs 11.5±1.6 kPa (76±11 vs 86±12 mmHg) at 3 months; 10.1±1.3 vs 11.3±1.6 kPa (76±10 vs 85±12 mmHg) at 6 months postresection.We conclude that measurements of conventional pulmonary function tests alone overestimate the decrease in functional capacity after lung resection. Exercise capacity after lobectomy is unchanged, whereas pneumonectomy leads to a 20% decrease, probably due to the reduced area of gas exchange.

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Transforming growth factor (TGF)-␤1 induces extracellular matrix deposition and proliferation of mesenchymal cells. We recently reported that interleukin (IL)-6 is an essential mediator of growth factor-induced proliferation of lung fibroblasts. Here, we demonstrate by reverse transcriptase polymerase chain reaction and enzyme-linked immunoassay that TGF-␤1 is a potent inducer of IL-6 mRNA and protein in primary human lung fibroblasts. Transient transfections of fibroblasts with a luciferase reporter gene construct containing nucleotides ؊651 to ؉1 of the human IL-6 promoter revealed that TGF-␤1 also potently activated IL-6 promoter activity. Progressive 5-deletions and sitedirected mutagenesis of the parental construct located the TGF-␤1-responsive cis-regulatory element to a known activating protein-1 (AP-1) sequence (nucleotides ؊284 to ؊276). Gel shift analyses revealed that AP-1 DNA binding activity in nuclear extracts was increased 30 min after stimulation with TGF-␤1. In contrast, neither CCAAT enhancer-binding protein-␤, NF-B, nor Sp1 were activated by TGF-␤1. Supershift analyses demonstrated that the AP-1 complex induced by TGF-␤1 was composed of Jun isoforms and absent of Fos isoforms. Moreover, this complex was found to be a JunD homodimer. Our data thus demonstrate that TGF-␤1 is a potent inducer of IL-6 in primary human lung fibroblasts. The TGF-␤1-activated JunD homodimer may be essential for a majority of the biological effects induced by TGF-␤1 in this cell type, such as proliferation and extracellular matrix synthesis.

Increased collagen and extracellular matrix (ECM) deposition within the lung is a characteristic feature of lung fibrosis. Transforming growth factor (TGF)-β isoforms play a pivotal role in the production of collagen and ECM. In this study, we investigated the effects of TGF-β1 and TGF-β3 on the main processes controlling ECM deposition using primary human lung fibroblasts. We analyzed 1) collagen metabolism by [3H]proline incorporation, 2) matrix metalloproteinase (MMP) expression by substrate gel zymography, and 3) tissue inhibitor of metalloproteinases (TIMP) expression by Western blot analysis. TGF-β1 and TGF-β3 increased the percentage of secreted collagens in supernatants of primary fibroblasts from 8.0 ± 1.2 (control) to 23.6 ± 4.6 and 22.3 ± 1.3%, respectively. The collagen percentage in deposited ECM was increased from 5.8 ± 0.3 (control) to 9.0 ± 0.5 and 8.8 ± 0.5% by TGF-β1 and TGF-β3, respectively. Secretion of MMP-1 (interstitial collagenase) by fibroblasts was reduced by both TGF-β isoforms, whereas secretion of MMP-2 (gelatinase A) was unaffected by either of the two isoforms. Both TGF-β isoforms increased TIMP-1 protein expression, whereas TIMP-2 protein was decreased. We thus conclude that TGF-β1 and TGF-β3 are equally potent in increasing ECM deposition. Their fibrotic effect in lung fibroblasts results from 1) an increase in the secretion and deposition of total ECM and collagens, 2) a decrease in MMP-1 secretion, and 3) an increase of TIMP-1 expression.

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