Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis

Asthma and chronic bronchitis are inflammatory diseases with extracellular matrix (ECM) remodeling and collagen deposition. Collagen homeostasis is controlled by metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We evaluated MMP and TIMP balance in induced sputum of 10 control, 31 untreated asthmatic, and 16 chronic bronchitic subjects. We first performed zymographic analysis to identify the profile of MMPs. Zymography revealed a similar MMPs profile in all populations studied and that MMP-9 was the major enzyme released. We then measured, using enzyme immunoassay, the concentrations of MMP-9 and of its inhibitor TIMP-1 and evaluated whether airflow limitation m…

Lung Compartmentalization of Increased TNF Releasing Ability by Mononuclear Phagocytes in Pulmonary Sarcoidosis

The TNF is a monokine with cytotoxic and tumor-necrosing activities; in addition, TNF may play a role in inflammatory processes. The present study evaluates spontaneous and LPS-mediated release of TNF by AMs and autologous peripheral BMs of normal subjects and patients with pulmonary sarcoidosis. A recently developed cytotoxicity assay, specific for detection of TNF activity, was applied. This study demonstrates that (1) unstimulated mononuclear phagocytes released low levels of TNF with no differences between groups; (2) when effector cells were stimulated with LPS, AMs from patients with active pulmonary sarcoidosis released more TNF than AMs recovered from normal subjects and from patien…

Hypoallergenic fragment of Par j 2 increases functional expression of Toll-like receptors in atopic children.

Background: Parietaria judaica (Par j) is one of the main causes of allergy in the Mediterranean countries. The activation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) inhibits nasal inflammation of atopic children. Objective:  To examine, in vivo and in vitro, the effect of recombinant Par j 2 (rPar j 2) and of its fragments (1–55 and 52–102) on atopic children. Methods:  We used skin prick test for in vivo evaluations. We assessed, in vitro, in peripheral blood mononuclear cells (PBMC), the effect of rPar j 2 and of the two fragments on neutrophil chemotaxis, on CD45RO, on TLR2 and TLR4 expression, on LPS binding and on interferon (IFN)-γ release, by a microchemotaxis chambe…

Autonomic cardiac regulation in obstructive sleep apnea syndrome: evidence from spontaneous baroreflex analysis during sleep

Objective. To assess spontaneous baroreceptor-heart rate reflex sensitivity during sleep in patients with obstructive sleep apnea syndrome, a condition associated with increased cardiovascular morbidity and mortality and characterized by marked sympathetic activation, which is believed to originate from hypoxic chemoreceptor stimulation, although little is known of other possible mechanisms such as baroreflex impairment. Design and methods. In 11 patients with severe obstructive sleep apnea syndrome (mean ± SD age 46.8 ± 8.1 years, apnea/hypopnea index 67.9 ± 19.1 h), who were normotensive or borderline hypertensive during wakefulness by clinic blood pressure measurements, finger blood pres…

Cellular network in airways inflammation and remodelling

Chronic inflammation and airway remodelling are two key steps in asthma pathophysiology. The development of chronic airway inflammation depends upon the continuous recruitment of inflammatory cells from the bloodstream towards the bronchial mucosa and by their subsequent functional activation. The release of inflammatory mediators by activated cells contributes to the generation of a complex network which involves mobile inflammatory cells and structural cells such as epithelial cells, fibroblasts and myofibroblasts. This network is responsible for the amplification and persistence of the inflammatory process as well as for the development of a peculiar microenvironment which can directly m…

Characteristics and Prognostic Value of Morning Dipping of Peak Expiratory Flow Rate in Stable Asthmatic Subjects

Characteristics and prognostic relevance of morning dip of peak expiratory flow rate (PEFR) were evaluated in stable asthmatic subjects. Among 246 outpatients monitored four times daily for two weeks, 38 (group A) showed a significant difference between morning reading of PEFR and each of the others; they were compared to 38 randomly selected patients (group B) not showing morning dip in PEFR. Less frequent seasonal course, extrinsic pathogenesis, and sensitization to mites characterized group A; starting airflow limitation was more severe in those with morning dip, but no significant difference between mean PEFR measured throughout two weeks was found. At 6 to 12 weeks, morning dip was not…

Airway cell composition at rest and after an all-out test in competitive rowers

Med Sci Sports Exerc. 2004 Oct;36(10):1723-9. Airway cell composition at rest and after an all-out test in competitive rowers. Morici G, Bonsignore MR, Zangla D, Riccobono L, Profita M, Bonanno A, Paternò A, Di Giorgi R, Mirabella F, Chimenti L, Benigno A, Vignola AM, Bellia V, Amato G, Bonsignore G. SourceDepartment of Experimental Medicine Italian National Research Council (CNR), Palermo, Italy. Abstract PURPOSES: This study was designed to assess: a) whether rowing affects airway cell composition, and b) the possible relationship between the degree of ventilation during exercise and airway cells. SUBJECTS AND METHODS: In nine young, nonasthmatic competitive rowers (mean age +/- SD: 16.2 …

Endurance training damages small airway epithelium in mice.

RATIONALE: In athletes, airway inflammatory cells were found to be increased in induced sputum or bronchial biopsies. Most data were obtained after exposure to cold and dry air at rest or during exercise. Whether training affects epithelial and inflammatory cells in small airways is unknown. OBJECTIVES: To test whether endurance training under standard environmental conditions causes epithelial damage and inflammation in the small airways of mice. METHODS AND MEASUREMENTS: Formalin-fixed, paraffin-embedded lung sections were obtained in sedentary (n = 14) and endurance-trained (n = 16) Swiss mice at baseline and after 15, 30, and 45 days of training. The following variables were assessed (m…

Increased airway inflammatory cells in endurance athletes: what do they mean?

Background Inflammatory cells are increased in the airways of end urance athletes, but their role in causing exercise-induced respiratory symptoms and bronchoconstriction, or their possible long-term consequences, are uncertain. Aim To put the results of athlete studies in perspective, by analysing the pathogenesis of airway cell changes and their impact on respiratory function. Results Athletes of different endurance sports at rest showed increased airway neutrophils. Elite swimmers and skiers also showed large increases in airway eosinophils and lymphocytes, possibly related to chronic, exercise-related exposure to irritants or cold and dry air, respectively. Post-exercise studies reporte…

Aging and asthma: pathophysiological mechanisms

Release of transforming growth factor-beta (TGF-β) and fibronectin by alveolar macrophages in airway diseases

Abstract Asthma and chronic bronchitis are associated with airway remodelling, and airway macrophages are present in bronchial inflammation. TGF-β and fibronectin released by alveolar macrophages possess a fibrogenic potency. The potential role of alveolar macrophages in airway remodelling was studied in asthma and chronic bronchitis by the release of TGF-β and fibronectin. Alveolar macrophages were isolated by bronchoalveolar lavage in 14 control subjects, 14 asthmatics and 14 chronic bronchitics. The spontaneous and lipopolysaccharide (LPS)- or concanavalin A (Con A)-induced release of TGF-β and fibronectin was measured by ELISA. Alveolar macrophages from chronic bronchitics spontaneously…

Airway remodeling in asthma.

Chronic inflammation and remodeling may follow acute inflammation or may begin insidiously as a low-grade smoldering response, especially in the case of immune reactions. The histologic hallmarks of chronic inflammation and remodeling are as follows: (1) infiltration by macrophages and lymphocytes; (2) proliferation of fibroblasts that may take the form of myofibroblasts; (3) angiogenesis; (4) increased connective tissue (fibrosis); and (5) tissue destruction. It is clear that changes in the extracellular matrix, smooth muscle, and mucous glands have the capacity to influence airway function and reactivity in asthma patients. However, it is not known how each of the many structural changes …

Increased prostaglandin E2 concentrations and cyclooxygenase-2 expression in asthmatic subjects with sputum eosinophilia.

Abstract Background Prostaglandin E 2 (PGE 2 ) is known to be produced within human airways, but it is not clear whether in airway diseases it can play a deleterious or a beneficial role. Recently it has been reported that PGE 2 can enhance eosinophil survival in vitro. Objective To evaluate whether the concentrations of PGE 2 in asthmatic airways correlate with the number of eosinophils and can be responsible for eosinophil-enhanced survival and to identify the cyclooxygenase isoform contributing to the synthesis of PGE 2 by cells present in asthmatic airways. Methods Reversed-phase high-performance liquid chromatography and/or specific radioimmunoassay was used to measure PGE 2 concentrat…

Role of prostaglandin E2 in the invasiveness, growth and protection of cancer cells in malignant pleuritis.

The recurrence of pleural effusions is a common event in a variety of neoplastic diseases. The objective of this study was to identify the mechanisms promoting the homing and growth of cancer cells within the pleural space. A cancer cell line recovered from malignant pleural fluids (lung adenocarcinoma cell line) that constitutively expresses cyclooxygenase 2 (COX-2) and all types of prostaglandin receptors was studied. It was first demonstrated using a matrigel system, that malignant pleural fluids increase the invasiveness of adenocarcinoma cells more than congestive heart failure (CHF) pleural fluids. Moreover, exposure to exudative malignant, but not to CHF pleural fluids, increased the…

Increased Levels of Elastase and α1-Antitrypsin in Sputum of Asthmatic Patients

Asthma and chronic bronchitis are inflammatory diseases associated with remodeling of the extracellular matrix (ECM). Elastin, a major component of the ECM in the airways, has been previously found to be disrupted in asthma and chronic bronchitis. This study was aimed at evaluating whether elastin disruption might be associated with an imbalance between elastase (active and total) and alpha1-proteinase inhibitor (alpha1-PI), the main inhibitor of elastase. We measured elastase and alpha1-PI in induced sputum obtained from 16 control subjects, 10 healthy smokers, 19 asthmatic patients, and 10 chronic bronchitis patients. We also assessed the possible origin of elastase, evaluating its levels…

Theophylline suppresses the release of tumour necrosis factor-alpha by blood monocytes and alveolar macrophages.

The purpose of this study was to evaluate the effect of theophylline on tumour necrosis factor-alpha (TNF-alpha) release by human blood monocytes (BMo), and rat BMo and alveolar macrophages (AM). BMo and AM were incubated in the absence or presence of theophylline, and the cell-free supernatants were harvested and tested for TNF-alpha activity by bioassay. Theophylline dose-dependently reduced TNF-alpha release by human BMo: significant inhibition was observed at 100 microns (41 +/- 5.9% of controls) and at 50 microns (59 +/- 4.8% of controls), while the inhibitory activity of theophylline at 10 microns (71 +/- 8.9% of controls) was not statistically significant. This activity was maximal a…

Upregulation of basic fibroblast growth factor in smokers with chronic bronchitis

The aim of the study was to investigate the expression of basic fibroblast growth factor (bFGF) and its receptor, fibroblast growth factor receptor (FGFR)-1, in the central airways of smokers with chronic bronchitis. The lobar bronchi from 17 subjects undergoing thoracotomy for solitary nodules were examined. All had a history of cigarette smoking, nine had symptoms of chronic bronchitis and airflow limitation, and eight were asymptomatic with normal lung function. Using immunohistochemical methods, bFGF and FGFR-1 expression in the total airway wall and the different airway compartments, i.e. bronchial glands, submucosal vessels and smooth muscle, was quantified. Moreover, to investigate t…

Effect of age and asthma duration upon elastase and alpha1-antitrypsin levels in adult asthmatics

In asthmatic subjects an imbalance between elastase and alpha1-antitrypsin (alpha1-PI) exists. This study aims to evaluate whether ageing per se affects the levels of elastase. Both young and elderly asthmatics with comparable severity and duration of disease, as well as young and elderly healthy subjects, underwent an induced sputum procedure to measure levels of elastase and alpha1-PI. The percentage of sputum neutrophils and eosinophils was higher in young and elderly asthmatics than in young and elderly controls. The levels of both total and active elastase were significantly higher in young and elderly asthmatics than in young and elderly controls, and directly correlated with the perc…

Urinary leukotriene E4 in the assessment of nocturnal asthma

Urinary leukotriene E4 (LTE4) is a marker of the body's production of cysteinyl LTs, important mediators of airway inflammation. The role of the latter in nocturnal asthma is a topic of increasing interest.This investigation was aimed at determining whether nighttime attacks are associated with increased release of LTs, expressed by urinary LTE4, and the relationship between the two phenomena.Three groups were studied: group A, seven control subjects; group B, nine asthmatic patients without nocturnal attacks; and group C, nine asthmatic patients with a comparable daytime FEV1 but who were experiencing nocturnal exacerbations (morning dips in peak expiratory flow greater than 20%). Urine wa…

Bronchial hyperresponsiveness in children with atopic rhinitis: a 7-year follow-up

Background:  A high prevalence of bronchial hyperresponsiveness (BHR) was found in atopic subjects with rhinitis. Those subjects may be at higher risk for developing bronchial asthma. We evaluated, in a 7-year follow-up, BHR and atopy in a homogeneous population of nonasthmatic children with allergic rhinitis (AR), and their role in asthma development. Methods:  Twenty-eight children (6–15 years) with AR were studied. At enrollment (T0), skin tests, total serum IgE assay, peak expiratory flow (PEF) monitoring and methacholine (Mch) bronchial challenge were performed. BHR was computed as the Mch dose causing a 20% forced expiratory volume (FEV)1 fall (PD20FEV1) and as dose–response slope (DR…

15-Lipoxygenase expression and 15(S)-hydroxyeicoisatetraenoic acid release and reincorporation in induced sputum of asthmatic subjects

Recent evidence shows that 15(S)-hydroxy-eicoisatetraenoic acid (15[S]-HETE) can be released and rapidly reincorporated into cellular lipids. These mechanisms exert several immunoregulatory functions that may be relevant in airway inflammation.Our purpose was to evaluate the levels of both soluble and cell-associated 15(S)-HETE and to examine 15-lipoxygenase (15-LO) messenger RNA (mRNA) expression in sputum samples obtained from 10 control and 18 asthmatic subjects.Levels of 15(S)-HETE were measured by reverse-phase HPLC separation followed by RIA in supernatants and in cell membrane-extracted phospholipids after acid hydrolysis. 15-LO mRNA was evaluated by primed in situ hybridization (PRI…

Noninvasive methods for the detection of upper and lower airway inflammation in atopic children

Background Exhaled nitric oxide (FE NO ) and exhaled breath condensate (EBC) are noninvasive methods to assess inflammation. Objective To investigate the role of the FE NO and of the EBC pH and IL-5 levels in atopic children. Methods We evaluated oral and nasal FE NO and the pH and IL-5 of oral and nasal EBC in children with atopic dermatitis (AD; n=18), allergic rhinitis (AR; n=18), intermittent asthma (n = 21), moderate persistent asthma (n = 18), and healthy controls (HCs; n=16). Results Oral FE NO was significantly increased in asthma, whereas the nasal values were increased in AR and asthma in comparison with HCs. The pH of oral EBC was lower in AD and asthma than in AR and HCs, wherea…

Effect of age upon airway obstruction and reversibility in adult patients with asthma.

In a cross-sectional study we evaluated the effect of aging (separately from that of duration of disease) on airway obstruction and reversibility by comparing two groups of non-smoker patients with asthma.We compared two groups of patients: group A, which had 50 subjects (8 men and 42 women) aged 59.7+/-4.6 years (mean +/- SD), and group B, comprised of 51 subjects (19 men and 32 women) who were 35.7+/-7.4 years old. The groups were selected because of comparable baseline degree of obstruction (FEV1 % of predicted, 67.8+/-20.3 in group A; 73.0+/-19.6 in group B, NS) and duration of the disease (14.0+/-11.7 years vs 11.2+/-9.1, NS). Spirometric examination, with a bronchodilator test, was pe…

Baroreflex control of heart rate during sleep in severe obstructive sleep apnoea: effects of acute CPAP

Baroreflex control of heart rate during sleep (baroreflex sensitivity; BRS) has been shown to be depressed in obstructive sleep apnoea (OSA), and improved after treatment with continuous positive airway pressure (CPAP). Whether CPAP also acutely affects BRS during sleep in uncomplicated severe OSA is still debatable. Blood pressure was monitored during nocturnal polysomnography in 18 patients at baseline and during first-time CPAP application. Spontaneous BRS was analysed by the sequence method, and estimated as the mean sequence slope. CPAP did not acutely affect mean blood pressure or heart rate but decreased cardiovascular variability during sleep. Mean BRS increased slightly during CPAP…

Circulating CD34+ cells are decreased in chronic obstructive pulmonary disease.

Airway cells after swimming outdoors or in the sea in nonasthmatic athletes

BONSIGNORE, M. R., G. MORICI, L. RICCOBONO, M. PROFITA, A. BONANNO, A. PATERNO, R. DI GIORGI, L. CHIMENTI, P. ABATE, F. MIRABELLA, A. M. VIGNOLA, and G. BONSIGNORE. Airway Cells after Swimming Outdoors or in the Sea in Nonasthmatic Athletes. Med. Sci. Sports Exerc., Vol. 35, No. 7, pp. 1146–1152, 2003. Marathon runners and elite swimmers showed increased inflammatory cells in the airways at baseline. Although airway neutrophils increase further after a marathon race, the airway response to swimming is unknown. The aim of this study was to assess the effects of swimming on airway cells. To avoid the concomitant effects of chronic exposure to chlorine, the study was conducted in seven nonasth…

Effects of three different water temperatures on dehydration in competitive swimmers

Summary Aims The purpose of this study was to evaluate the effects of three different water temperatures on physiological responses (dehydration, sweat rate, urine output, rectal temperature and plasma electrolytes) of competitive athletes during a “simulated” race of 5 km in an indoor swimming pool. Methods Nine male competitive master swimmers swam 5 km with the water at temperatures of 23, 27 and 32 C. Immediately before (Pre) and after (Post) each trial, samples of blood and urine were collected, body weight was recorded and rectal temperature was measured. The dehydration percentage and sweat rate were the highest at 32 C and the lowest at 23 C (23 C: −0.9 ± 0.5; 27 C: −1.3 ± 0.6; 32 C…

LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space

SUMMARY The pleural space is a virtual compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells during a variety of respiratory diseases. Here, we study the potential role of the eicosanoid metabolite leukotriene B4 (LTB4) in disparate diseases leading to acute (pneumonia) or chronic (tuberculosis, cancer) inflammation of the pleural space. LTB4 concentrations were significantly higher in pleural fluid due to pneumonia, tuberculosis and cancer with respect to congestive heart failure and correlated with neutrophil elastase, which is used as an indication of state of activation of neutrophils in the pleural space. Moreover, pleural LTB4 was biological…

Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD patients.

Background:  Acetylcholine (ACh) plays an important role in smooth muscle contraction and in the development of airway narrowing; preliminary evidences led us to hypothesize that ACh might also play a role in the development of airways inflammation in chronic obstructive pulmonary disease (COPD). Methods:  We evaluated the concentrations of leukotriene B4 (LTB4) in induced sputum, and the expression of Ach M1, M2, and M3 receptors in sputum cells (SC) obtained from 16 patients with COPD, 11 smokers, and 14 control subjects. The SC were also treated with ACh and the production of LTB4 assessed in the presence or absence of a muscarinic antagonist (oxitropium). In blood monocytes, we evaluate…

Blood pressure responsiveness to obstructive events during sleep after chronic CPAP

The aim of this study was to investigate whether chronic continuous positive airway pressure (CPAP) affects blood pressure (BP) responsiveness to obstructive events occurring on the first night of CPAP withdrawal in obstructive sleep apnoea (OSA) after chronic treatment. Thirteen male subjects with severe OSA underwent nocturnal polysomnography with beat­by­beat BP monitoring before treatment and after 4.9±3.4 months of home CPAP (mean daily use 5.1±1.7 h). Variations in oxyhaemoglobin saturation (Δ S a,O2), systolic (Δ P s), and diastolic (Δ P d) BP within nonrapid eye movement apnoeas and hypopnoeas were measured on a sample of pre­ and post­treatment events. In addition, a pretreatment s…

Clinical and Biological Heterogeneity in Children with Moderate Asthma

To evaluate the relationship between inflammatory markers and severity of asthma in children, the amount of interleukin-8 (IL-8) and granulocyte/macrophage colony-stimulating factor (GM-CSF) released by peripheral blood mononuclear cells, exhaled nitric oxide (FE NO) levels, p65 nuclear factor-kappaB subunit, and phosphorylated IkBalpha expression by peripheral blood mononuclear cells were assessed in six control subjects, 12 steroid-naives subjects with intermittent asthma, and 17 children with moderate asthma. To investigate their predictive value, biomarker levels were correlated with the number of exacerbations during a 18-month follow-up period. We found that GM-CSF release was higher …

Hypoxemia during Sleep

In most normal subjects arterial oxyhemoglobin saturation (SaO2) remains substantially stable throughout all sleep time: some exceptions however, may be observed especially in elderly subjects, who may show desaturations, sometimes associated with apneas (Block et al., 1979; Krieger et al., 1983; Catterall et al., 1985). Conversely, SaO2 drops during part of, or even the whole sleep time, are a common finding in pathological conditions like obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD).

Spontaneous gastroesophageal reflux and airway patency during the night in adult asthmatics

Controversies still exist on the role of nighttime gastroesophageal reflux (GER) in precipitating nocturnal asthma. We tested the relationship between GER and nocturnal bronchoconstriction by continuously and simultaneously monitoring both respiratory resistances and esophageal pH in seven asthmatics with moderate to severe GER disease. Twenty-nine GER episodes were found during the study night lasting more than 5 min (LGER) and 72 not longer than 5 min (SGER). Both long (LGER) and short (SGER) gastroesophageal refluxes were able to maintain significantly higher lower respiratory resistances (RLR) at the resolution of each GER episode (RLR(e)) with respect to baseline values. RLR, expressed…

DOES LEPTIN PLAY A CYTOKINE-LIKE ROLE WITHIN THE AIRWAYS OF COPD PATIENTS?

The leptin-leptin receptor system might be up-regulated in the airways of chronic obstructive pulmonary disease (COPD). In bronchial biopsies obtained from normal subjects and smokers, with and without COPD, the present study examined leptin and leptin-receptor expression and their co-localisation in airway and inflammatory cells. Combining immunohistochemistry with terminal deoxynucleotidyl transferase dUTP nick end-labelling techniques, apoptosis in airway and inflammatory cells and in leptin and leptin-receptor expressing cells was investigated. In the epithelial cells both leptin and leptin-receptor expression was higher in normal subjects than in smokers and COPD subjects. By contrast,…

15(S)-HETE modulates LTB(4) production and neutrophil chemotaxis in chronic bronchitis.

We evaluated the levels of 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] and the expression of 15-lipoxygenase (15-LO) mRNA in induced sputum obtained from 10 control and 15 chronic bronchitis subjects. 15(S)-HETE was evaluated by reverse phase high-performance liquid chromatography separation followed by specific RIA. 15-LO mRNA expression was determined by primed in situ labeling. The levels of both soluble and cell-associated 15(S)-HETE resulted significantly higher in chronic bronchitis than in control subjects. The percentage of cells expressing 15-LO mRNA was significantly higher in chronic bronchitis than in control subjects ( P < 0.01). Double staining for specific cell type ma…

Cigarette smoke increases Toll-like receptor 4 and modifies lipopolysaccharide-mediated responses in airway epithelial cells.

Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke. The main goal of this study was to explore the effects of cigarette smoke extracts (CSE) on Toll-like receptor (TLR) expression and activation in a human bronchial epithelial cell line (16-HBE). The CSE increased the expression of TLR4 and the lipopolysaccharide (LPS) binding, the nuclear factor-kappaB (NF-kappaB) activation, the release of interleukin-8 (IL-8) and the chemotactic activity toward neutrophils. It did not induce TLR2 expression or extracellular signal-regulated signal kinase 1/2 (ERK1/2) activation. The LPS increased the expression of TLR4 and induced bot…

Thymosin α1 and α-Inteferon with Cisplatin and Etoposide in Advanced Non-Small-Cell Lung Cancer: A Phase II Study

In recent years, biological response modifiers (BRMs) have emerged as an important new class of agents for treating cancer. Agents such as interferon (IFN) and interleukin 2 (IL-2) have been reported to induce significant tumor regression in various types of cancer usually resistant to chemotherapy (1,12), but their use in non-small-cell lung cancer (NSCLC) has received little attention.

Alveolar Gas Mixing in Chronic Pulmonary Hyperinflation

It is well known that in chronic pulmonary hyperinflation defects in intrapulmo-nary gas mixing and in V/Q ratio are likely to occur.

Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma

Background In asthma T cells are characterized by an increased activation state and by reduced apoptosis. Objective Because the clinical efficacy of inhaled corticosteroids combined with long-acting β 2 -agonists has been widely demonstrated in asthma, we studied, in vitro , the effect of fluticasone propionate (FP) and salmeterol alone and in combination on the activation and apoptosis of peripheral blood T cells (PBTs), on the expression of phosphorylated nuclear factor κB inhibitor (IκBα), and on the nuclear translocation of glucocorticoid receptor (GR) in PBTs from asthmatic subjects. Methods Apoptosis was evaluated on the basis of annexin V binding, whereas the expression of caspases 8…