Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma.

BACKGROUND AND OBJECTIVES: Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. METHODS: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. RESULTS: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/ TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤-0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. CONCLUSIONS: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH.

Anti-inflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD.

The anti-inflammatory effects of salmeterol/fluticasone (SFP), tiotropium/fluticasone (Tio+FP) and tiotropium (Tio) alone were investigated on the inflammatory cells and mediators in sputum induced from chronic obstructive pulmonary disease patients. Subjects were either newly diagnosed or had not taken any medication for 3 months prior to the study. Subjects (n = 99) were randomised (not double blinded) and received either SFP (100/1,000 microg daily), Tio+FP (18/1,000 microg daily) or Tio (18 microg daily) for 12 weeks. Induced sputum and serum C-reactive protein (CRP) were analysed prior to and at the end of treatment. The results showed that treatment with SFP caused a significant reduction in interleukin (IL)-8 and matrix metalloprotease (MMP)-9 in induced sputum, compared with treatment with Tio alone. There were no treatment differences between the SFP and Tio+FP groups in decreasing IL-8 and MMP-9 levels. The reduction in IL-8 showed significant association with the reduction in MMP-9. All treatment groups failed to significantly reduce the numbers of total cells, neutrophils, macrophages and eosinophils in induced sputum; in addition, there were no treatment differences in terms of improvement of forced expiratory volume in one second, forced vital capacity, CRP or quality of life between the three groups. The anti-inflammatory effects of salmeterol/fluticasone probably contribute to the clinical benefits seen in chronic obstructive pulmonary disease patients.

Pen ch 13 allergen induces secretion of mediators and degradation of occludin protein of human lung epithelial cells.

BACKGROUND: Alkaline serine proteases from six prevalent airborne Penicillium and Aspergillus species have been identified as a group of major allergens (group 13). After entering human airways, the allergens are in initial contacts with respiratory epithelial cells. The purpose of this study is to investigate interactions between the Pen ch 13 allergen from P. chrysogenum and human lung epithelial cells. METHODS: A549 cells, 16HBE14o- cells and primary cultures of human bronchial epithelial cells (HBEpC) were exposed to purified Pen ch 13 and mediators released into culture supernatants were assayed with enzyme-linked immunosorbent assay (ELISA) kits. Cleavage of occludin in 16HBE14o- cells was analysed by immunofluorescent staining of whole cells and immunoblot analysis of whole cell extracts. Fragments generated by incubating Pen ch 13 and a synthetic peptide carrying the occludin sequence were analysed by mass spectrometry. RESULTS: Pen ch 13 induced productions of prostaglandin-E2 (PGE2), interleukin (IL)-8 and transforming growth factor (TGF)-beta1 by A549 cells, 16HBE14o- cells and primary cultures of HBEpC. The protease activity of Pen ch 13 is needed for the induction of PGE2 IL-8, TGF-beta1 and cyclo-oxygenase (COX)-2 expression. A tight junction protein occludin of 16HBE14o- cells can be cleaved by Pen ch 13 at Gln202 and Gln211 which are within the second extracellular domain of the protein. CONCLUSION: Pen ch 13 may contribute to asthma by damaging the barrier formed by the airway epithelium and stimulating the release of mediators that orchestrate local immune responses and inflammatory process from HBEpC.

Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells.

Airway remodeling with smooth muscle cell (SMC) hyperplasia is a feature of chronic asthma. We investigated the potential for tryptase, the major secretory product of human mast cells, to act as a growth factor for human airway SMCs. Because this serine protease can activate proteinase-activated receptor-2 (PAR-2), we also examined the actions of SLIGKV, a peptide agonist of PAR-2. Incubation with lung tryptase provoked a twofold increase in [(3)H]thymidine incorporation; a similar increase in cell numbers was found when we used the MTS assay. The effect was catalytic site dependent, being abolished by the protease inhibitors leupeptin and benzamidine and by heat inactivation of the enzyme. Tryptase-induced DNA synthesis was inhibited by preincubation of the cells with pertussis toxin, calphostin C, or genistein. Transduction mechanisms are thus likely to involve a pertussis toxin-sensitive G protein, protein kinase C, and tyrosine kinase. SLIGKV elicited a response on SMCs similar to that of tryptase. Tryptase could provide an important stimulus for SMC proliferation in asthmatic airways, by acting on PAR-2.

The variation of cell type distribution in lung cancer: a study of 10,910 cases at a medical center in Taiwan between 1970 and 1993.

The rise in the incidence of lung cancer has been associated with shifts in histologic distribution. A study was conducted to investigate changes in the cell type distribution in lung cancer in relation to age, sex, and smoking history, based on a retrospective analysis of 10,910 proven cases of lung cancer at the Veterans General Hospital-Taipei during the period from 1970 to 1993. The diagnosis in each case was substantiated by histologic samples from the original tumor site in the lung. Detailed smoking histories were obtained by personal interview at the time of the first admission. Adenocarcinoma (38.3%) was the most common type of lung cancer, followed by squamous cell carcinoma (37.1%) and small cell carcinoma (12.2%). Over the study period, the incidence of squamous cell carcinoma decreased from 46.4% to 36.2% in men (P < 0.005), adenocarcinoma increased from 30% to 36% in men (P = 0.001) and 50.7% to 64.8% in women (P = 0.008), and small cell carcinoma increased from 7% to 14% in men but showed no significant change in women. Adenocarcinoma exhibited a marked increase in both men and women, and surpassed squamous cell carcinoma as the most frequent type of lung cancer. Lung cancer among younger men, and among non-smoking older men and women, was more often adenocarcinoma. Small cell carcinoma showed a significant increase among males, differing from the trend for squamous cell carcinoma in men, though both are strongly associated with smoking. These findings suggest factors other then cigarette smoking could influence the development and distribution of lung cancer.

Cutaneous metastasis of lung cancer: an ominous prognostic sign.

BACKGROUND: Cutaneous metastases in primary lung cancer rarely occurs in comparison with other organ involvement. Because of the absence of any uniform or pathognomic feature, they are often mistaken as a variety of benign lesions so that the outcome is extremely different. In this study, sixty-three cases of lung cancer with cutaneous metastases were retrospectively analyzed to determine the clinical pictures and length of survival. METHODS: Retrospective analyses were performed for 5539 cases of proven lung cancer collected at the Cancer Treatment Center in Veterans General Hospital-Taipei during the period from January 1984 to May 1994. Seventy-two cases were documented cutaneous metastases. Nine of them were excluded due to inadequate medical records on clinical course. RESULTS: Group A included the majority (48/63, 76.2%) of patients who had primary lung cancer with subsequent cutaneous metastases. The other 15 patients with cutaneous metastases as the initial presentations were classified as group B. (15/63, 23.8%). There were four major clinical presentations; solitary nodules, cluster of nodules, erythematous papule and bulging mass. Solitary nodule was the most frequent pattern (41/63 65.1%), ranging in size from 0.5 x 0.5 cm to 25 x 15 cm in surface area. The chest wall and abdominal wall were the regions most likely to develop cutaneous metastases. Metastatic lesions were occasionally found over the scrotum, lip and perianal region. Adenocarcinoma was the predominant cell type of cutaneous spread (25/63, 39.7%). The survival after diagnosis of cutaneous metastasis ranged from 3 weeks to 14 months, without significant difference between two groups of patients. Twenty-two patients (35%) survived no more than one month. The median survival was 3 months. CONCLUSIONS: Cutaneous metastasis, as observed in our study, is an ominous sign indicating a poor prognosis with imminent death. Physicians should be alert to its characteristics and prognostic significance.