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Biomedical subjects

Klaus F Rabe

Publications and source records attributed to Klaus F Rabe.

At least 19 recordsLinked to original sources
PubMed2007

Small airways dysfunction and neutrophilic inflammation in bronchial biopsies and BAL in COPD.

BACKGROUND: The single-breath N(2) test (sbN(2)-test) is closely related to small airways pathology in resected lung specimens of smokers. We investigated whether uneven ventilation and airway closure are associated with specific markers of airway inflammation as obtained by bronchial biopsies, BAL, and induced sputum in patients with manifest COPD. METHODS: Fifty-one patients with stable COPD not receiving corticosteroids were examined in a cross-sectional study (43 men; mean [SD] age, 63 +/- 8 years; exsmokers and smokers; median pack-years, 41 [interquartile range, 31 to 51 pack-years]). Postbronchodilator spirometry (FEV(1), 63 +/- 8% of predicted) and sbN(2)-test (slope of phase III [DeltaN(2)], closing capacity [CC]/total lung capacity [TLC] percentage of predicted) were performed. Inflammatory cell counts were assessed in bronchial biopsies, BAL (only in the first half of patients), and induced sputum. Neutrophil elastase (NE), secretory leukocyte proteinase inhibitor (SLPI), and interleukin-8 levels were determined in BAL fluid. RESULTS: DeltaN(2) increased with subepithelial neutrophil numbers in bronchial biopsies (rs = 0.337, p = 0.017) and with NE levels (rs = 0.443, p = 0.039), NE/neutrophil ratio (rs = 0.575, p = 0.005) and SLPI levels (rs = 0.484, p = 0.022) in BAL. CC/TLC was associated with BAL neutrophil numbers (rs = 0.448, p = 0.048). The sbN(2)-test was not associated with any other inflammatory cell type in BAL or biopsies, nor with inflammatory cell counts in sputum. Of importance, the correlations between DeltaN(2) and BAL NE/neutrophil ratio, and between CC/TLC and BAL neutrophil numbers remained significant when adjusting for FEV(1) percentage of predicted. CONCLUSIONS: The results of the sbN(2)-test are associated with neutrophilic inflammation in bronchial biopsies and BAL in patients with COPD. Our findings support a role of neutrophilic inflammation in the pathogenesis of small airways dysfunction in COPD.

Biopsy↗
PubMed2006

Exploring host-pathogen interactions at the epithelial surface: application of transcriptomics in lung biology.

The epithelial surface of the airways is the largest barrier-forming interface between the human body and the outside world. It is now well recognized that, at this strategic position, airway epithelial cells play an eminent role in host defense by recognizing and responding to microbial exposure. Conversely, inhaled microorganisms also respond to contact with epithelial cells. Our understanding of this cross talk is limited, requiring sophisticated experimental approaches to analyze these complex interactions. High-throughput technologies, such as DNA microarray analysis and serial analysis of gene expression (SAGE), have been developed to screen for gene expression levels at large scale within single experiments. Since their introduction, these hypothesis-generating technologies have been widely used in diverse areas such as oncology and brain research. Successful application of these genomics-based technologies has also revealed novel insights in host-pathogen interactions in both the host and pathogen. This review aims to provide an overview of the SAGE and microarray technology illustrated by their application in the analysis of host-pathogen interactions. In particular, the interactions between epithelial cells in the human lungs and clinically relevant microorganisms are the central focus of this review.

Epithelial Cells↗
PubMed2006

Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study.

BACKGROUND: The contributions of as-needed inhaled corticosteroids and long-acting beta2 agonists (LABA) to asthma control have not been fully established. We compared the efficacy and safety of three reliever strategies: a traditional short-acting beta2 agonist; a rapid-onset LABA (formoterol); and a combination of LABA and an inhaled corticosteroid (budesonide-formoterol) in symptomatic patients receiving budesonide-formoterol maintenance therapy. METHODS: We did a 12-month, double-blind, parallel-group study in 3394 patients (aged 12 years or older), in 289 centres in 20 countries, who were using inhaled corticosteroids at study entry and symptomatic on budesonide-formoterol (160 microg and 4.5 microg, respectively), one inhalation twice daily, during a 2-week run-in. After run-in, patients were randomly assigned budesonide-formoterol maintenance therapy plus one of three alternative as-needed medications-terbutaline (0.4 mg), formoterol (4.5 microg), or budesonide-formoterol (160 microg and 4.5 microg). The primary outcome was time to first severe exacerbation, defined as an event resulting in hospitalisation, emergency room treatment, or both, or the need for oral steroids for 3 days or more. FINDINGS: Time to first severe exacerbation was longer with as-needed budesonide-formoterol versus formoterol (p=0.0048; log-rank test) and with as-needed formoterol versus terbutaline (p=0.0051). The rate of severe exacerbations was 37, 29, and 19 per 100 patients per year with as-needed terbutaline, formoterol, and budesonide-formoterol, respectively (rate ratios budesonide-formoterol versus formoterol 0.67 [95% CI 0.56-0.80; p<0.0001]; budesonide-formoterol versus terbutaline 0.52 [0.44-0.62; p<0.0001]; formoterol versus terbutaline 0.78 [0.67-0.91; p=0.0012]). Asthma control days increased to a similar extent in all treatment groups. As-needed formoterol did not significantly improve symptoms compared with as-needed terbutaline. All treatments were well tolerated. INTERPRETATION: Both monocomponents of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance.

Adolescent↗
PubMed2006

Differential distribution of inflammatory cells in large and small airways in smokers.

BACKGROUND: Smoking induces structural changes in the airways, and is considered a major factor in the development of airflow obstruction in chronic obstructive pulmonary disease. However, differences in inflammatory cell distribution between large airways (LA) and small airways (SA) have not been systematically explored in smokers. HYPOTHESIS: The content of cells infiltrating the airway wall differs between LA and SA. AIMS: To compare the content of neutrophils, macrophages, lymphocytes and mast cells infiltrating LA and SA in smokers who underwent surgery for lung cancer. METHODS: Lung tissue from 15 smokers was analysed. Inflammatory cells in the lamina propria were identified by immunohistochemical analysis, quantified by digital image analysis and expressed as number of cells per surface area. RESULTS: The number of neutrophils infiltrating the lamina propria of SA (median 225.3 cells/mm(2)) was higher than that in the lamina propria of LA (median 60.2 cells/mm(2); p<0.001). Similar results were observed for mast cells: 313.3 and 133.7 cells/mm(2) in the SA and LA, respectively (p<0.001). In contrast, the number of CD4 cells was higher in LA compared with SA (median 217.8 vs 80.5 cells/mm(2); p = 0.042). CONCLUSIONS: These findings indicate a non-uniform distribution of neutrophils and mast cells throughout the bronchial tree, and suggest that these cells may be involved in the development of smoking-related peripheral lung injury.

Cell Count↗
PubMed2006

Epithelial differentiation is a determinant in the production of eotaxin-2 and -3 by bronchial epithelial cells in response to IL-4 and IL-13.

The composition of the airway epithelium is dynamic and epithelial differentiation is regulated by endogenous mediators as well as inhaled substances. In atopic asthma the differentiation of the epithelium is altered. Various studies have addressed the ability of cultured airway epithelial cells to release the eosinophil-attractant chemokines eotaxin, eotaxin-2 and eotaxin-3 using epithelial cell lines or poorly differentiated primary cells. Since little is known about the role of the epithelial differentiation state in the response of epithelial cells to stimuli that increase production of mediators such as the eotaxins, we analyzed the effect of differentiation state on the production of the eotaxins. In particular, we investigated the effects of the Th2 cytokines IL-4 and IL-13 on eotaxin-2 and -3 production by primary human bronchial epithelial cells and examined whether their production is affected by epithelial cell differentiation using both submerged and air-liquid interface (ALI) cultures. The results show that both IL-4 and IL-13 increase eotaxin-2 and -3 mRNA expression and protein release in submerged- and ALI-cultures. Moreover, epithelial differentiation in ALI-cultures appeared an important determinant in the regulation of eotaxin-2 and -3. Mucociliary differentiation of the epithelial cells was induced by culture in the presence of a high concentration of retinoic acid (RA), whereas low concentrations of RA resulted in a flattened squamous epithelial phenotype. Mucociliary differentiated ALI-cultures expressed and released more eotaxin-3 upon stimulation with IL-4/IL-13, whereas eotaxin-2 production was predominantly found in squamous differentiated ALI-cultures. TNFalpha reduced IL-4-induced eotaxin-2 release in submerged cultures but not in ALI-cultures; no effects on eotaxin-3 synthesis were observed. The results indicate that epithelial differentiation is an important determinant in Th2 cytokine-induced eotaxin-2 and -3 release by airway epithelial cells. These findings may provide new insights into the role of airway epithelial differentiation and Th2 cytokines in the pathogenesis of inflammatory lung disorders such as asthma.

Bronchi↗
PubMed2006

Markers of exacerbation severity in chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can experience 'exacerbations' of their conditions. An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management. There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies. Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD. In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event. METHODS: We have searched standard databases between 1966 to July 2004 using major keywords and terms. Studies that provided demographics, spirometry, potential markers, and clear eligibility criteria were included in this study. Central tendencies and dispersions for all the variables and markers reported and collected by us were first tabulated according to sample size and ATS/ERS 2004 Exacerbation Severity Levels I to III criteria. Due to the possible similarity of patients in Levels II and III, the data was also redefined into categories of exacerbations, namely out-patient (Level I) and in-patient (Levels II & III combined). For both approaches, we performed a fixed effect meta-analysis on each of the reported variables. RESULTS: We included a total of 268 studies reported between 1979 to July 2004. These studies investigated 142,407 patients with COPD. Arterial carbon dioxide tension and breathing rate were statistically different between all levels of exacerbation severity and between in out- and in-patient settings. Most other measures showed weak relationships with either level or setting, or they had insufficient data to permit meta-analysis. CONCLUSION: Arterial carbon dioxide and breathing rate varied in a consistent manner with exacerbation severity and patient setting. Many other measures showed weak correlations that should be further explored in future longitudinal studies or assessed using suggested mathematical modelling techniques.

Arteries↗
PubMed2006

Human cathelicidin LL-37 is a chemoattractant for eosinophils and neutrophils that acts via formyl-peptide receptors.

BACKGROUND: Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by the presence of eosinophils and neutrophils. However, the mechanisms that mediate the influx of these cells are incompletely understood. Neutrophil products, including neutrophil elastase and antimicrobial peptides such as neutrophil defensins and LL-37, have been demonstrated to display chemotactic activity towards cells from both innate and adaptive immunity. However, chemotactic activity of LL-37 towards eosinophils has not been reported. Therefore, the aim of the present study was to investigate the chemotactic activity of LL-37 for eosinophils and to explore the mechanisms involved in LL-37-mediated attraction of neutrophils and eosinophils. METHODS: Neutrophils and eosinophils were obtained from venous blood of healthy donors. Chemotaxis was studied using a modified Boyden chamber technique. Involvement of formyl-peptide receptors (FPRs) was studied using the antagonistic peptide tBoc-MLP. Activation of the mitogen-activated protein kinase (MAPK) ERK1/2 was studied by Western blotting using antibodies directed against phosphorylated ERK1/2. RESULTS: Our results show that LL-37 chemoattracts both eosinophils and neutrophils. The FPR antagonistic peptide tBoc-MLP inhibited LL-37-induced chemotaxis. Whereas the FPR agonist fMLP activated ERK1/2 in neutrophils, LL-37 did not, indicating that fMLP and LL-37 deliver different signals through FPRs. CONCLUSIONS: LL-37 displays chemotactic activity for eosinophils and neutrophils, and this activity is mediated via an FPR. These results suggest that LL-37 may play a role in inflammatory lung diseases such as asthma and COPD.

Adrenergic beta-Agonists↗
PubMed2006

Novel concepts of neuropeptide-based drug therapy: vasoactive intestinal polypeptide and its receptors.

Chronic inflammatory airway diseases such as bronchial asthma or chronic obstructive pulmonary disease (COPD) are major contributors to the global burden of disease. Although inflammatory cells play the central role in the pathogenesis of the diseases, recent observations indicate that also resident respiratory cells represent important targets for pulmonary drug development. Especially targeting airway neuromediators offers a possible mechanism by which respiratory diseases may be treated in the future. Among numerous peptide mediators such as tachykinins, calcitonin gene-related peptide, neurotrophins or opioids, vasoactive intestinal polypeptide (VIP) is one of the most abundant molecules found in the respiratory tract. In human airways, it influences many respiratory functions via the receptors VPAC1, VPAC2 and PAC1. VIP-expressing nerve fibers are present in the tracheobronchial smooth muscle layer, submucosal glands and in the walls of pulmonary and bronchial arteries and veins. Next to its strong bronchodilator effects, VIP potently relaxes pulmonary vessels, and plays a pivotal role in the mediation of immune mechanisms. A therapy utilizing the respiratory effects of VIP would offer potential benefits in the treatment of obstructive and inflammatory diseases and long acting VIP-based synthetic non-peptide compounds may represent a novel target for drug development.

Animals↗
PubMed2006

A molecular signature of epithelial host defense: comparative gene expression analysis of cultured bronchial epithelial cells and keratinocytes.

BACKGROUND: Epithelia are barrier-forming tissues that protect the organism against external noxious stimuli. Despite the similarity in function of epithelia, only few common protective mechanisms that are employed by these tissues have been systematically studied. Comparative analysis of genome-wide expression profiles generated by means of Serial Analysis of Gene Expression (SAGE) is a powerful approach to yield further insight into epithelial host defense mechanisms. We performed an extensive comparative analysis of previously published SAGE data sets of two types of epithelial cells, namely bronchial epithelial cells and keratinocytes, in which the response to pro-inflammatory cytokines was assessed. These data sets were used to elucidate a common denominator in epithelial host defense. RESULTS: Bronchial epithelial cells and keratinocytes were found to have a high degree of overlap in gene expression. Using an in silico approach, an epithelial-specific molecular signature of gene expression was identified in bronchial epithelial cells and keratinocytes comprising of family members of keratins, small proline-rich proteins and proteinase inhibitors. Whereas some of the identified genes were known to be involved in inflammation, the majority of the signature represented genes that were previously not associated with host defense. Using polymerase chain reaction, presence of expression of selected tissue-specific genes was validated. CONCLUSION: Our comparative analysis of gene transcription reveals that bronchial epithelial cells and keratinocytes both express a subset of genes that is likely to be essential in epithelial barrier formation in these cell types. The expression of these genes is specific for bronchial epithelial cells and keratinocytes and is not seen in non-epithelial cells. We show that bronchial epithelial cells, similar to keratinocytes, express components that are able to form a cross-linked protein envelope that may contribute to an effective barrier against noxious stimuli and pathogens.

Algorithms↗
PubMed2006

The antimicrobial peptide LL-37 enhances IL-8 release by human airway smooth muscle cells.

BACKGROUND: Human airway smooth muscle (HASM) cells release various chemokines that are involved in recruitment of inflammatory cells, which can be found within or in the vicinity of the airway smooth muscle layer in patients with inflammatory lung diseases. Inflammatory cells contain antimicrobial peptides including the cathelicidin LL-37 and neutrophil defensins (HNP1-3). OBJECTIVE: The aim of the study was to determine the effects of antimicrobial peptides on IL-8 (CXC chemokine ligand 8) release by HASM cells, and to study the underlying mechanisms. METHODS: Human airway smooth muscle cells were stimulated with LL-37 and HNP1-3, and IL-8 protein and mRNA levels were determined by sandwich ELISA and PCR. Phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was detected by using Western blot. RESULTS: LL-37 enhanced IL-8 release by HASM cells, which was dependent on ERK1/2 activation. Receptors known to be involved in LL-37-induced signaling, including the epidermal growth factor receptor and formyl peptide receptors, were not involved in LL-37 signaling in HASM cells. The purinergic receptor antagonist suramin did block LL-37-induced ERK1/2 phosphorylation and IL-8 release, and expression of mRNA for the purinergic receptor P2X(7) was detected in HASM cells. HNP1-3 did increase ERK1/2 phosphorylation, but did not enhance IL-8 release by HASM cells. CONCLUSION: These data show that HASM cells respond to the antimicrobial peptide LL-37 by releasing IL-8, suggesting that LL-37 is a regulator of the inflammatory process in various inflammatory lung diseases by enhancing IL-8 production. CLINICAL IMPLICATIONS: LL-37 released by inflammatory cells may amplify inflammation through induction of IL-8 release by airway smooth muscle.

Antimicrobial Cationic Peptides↗
PubMed2006

Budesonide/formoterol in a single inhaler for maintenance and relief in mild-to-moderate asthma: a randomized, double-blind trial.

STUDY OBJECTIVE: To compare a novel asthma management strategy--budesonide/formoterol in a single inhaler for both maintenance therapy and symptom relief--with a higher dose of budesonide plus as-needed terbutaline. METHODS: This was a 6-month, randomized, double-blind, parallel-group study in patients with mild-to-moderate asthma (n = 697; mean age, 38 years [range, 11 to 79 years]; mean baseline FEV1, 75% of predicted; mean inhaled corticosteroid [ICS] dosage, 348 microg/d). Following a 2-week run-in period, all patients received two blinded, dry powder inhalers, one containing maintenance medication and one containing medication to be used as needed for the relief of symptoms. Patients were randomized to receive either budesonide/formoterol (80 microg/4.5 microg, two inhalations qd) for maintenance plus additional inhalations as needed for symptom relief, or budesonide (160 microg, two inhalations qd) for maintenance medication plus terbutaline (0.4 mg) as needed. The primary efficacy variable was morning peak expiratory flow (PEF). RESULTS: Patients receiving budesonide/formoterol showed greater improvements in morning PEF than patients receiving budesonide (increases of 34.5 L/min vs 9.5 L/min, respectively; p < 0.001). The risk of having a severe exacerbation (hospitalization/emergency department [ED] treatment, oral steroids for asthma, or a > or = 30% decrease from baseline in morning PEF on 2 consecutive days) was 54% lower with budesonide/formoterol vs budesonide (p = 0.0011). Budesonide/formoterol patients experienced 90% fewer hospitalizations/ED treatments due to asthma than budesonide patients (1 vs 10, respectively; p = 0.026). The increased efficacy with budesonide/formoterol was achieved with less ICS than was used in the budesonide group (mean dose, 240 microg/d vs 320 microg/d, respectively) and with 77% fewer oral steroid treatment days vs budesonide (114 days vs 498 days, respectively). Both treatments were well tolerated. CONCLUSIONS: Budesonide/formoterol for both maintenance and relief improves asthma control with a lower steroid load compared with a higher dose of budesonide plus terbutaline.

Administration, Inhalation↗
PubMed2006

Improving dyspnea in chronic obstructive pulmonary disease: optimal treatment strategies.

Chronic obstructive pulmonary disease (COPD) is a common disease with a global impact in terms of morbidity and mortality. Patients usually consult their doctor because of symptoms, and among those, dyspnea at rest or under exercise is one of the most common. The sensation of dyspnea is experienced differently among individuals with COPD and may be based on diverse factors, such as muscle fatigue, patient perception, or trapped volumes. Treatment algorithms for COPD emphasize a stepwise approach to therapy depending on the severity of the disease, which, for reasons of convenience, is primarily based on spirometric impairment. Drugs that alter bronchial smooth muscle tone and increase inspiratory capacity have clinical efficacy for the dyspneic patient, most likely based on their effect on lung function, whereas the effects of antiinflammatory therapy with inhaled corticosteroids is more difficult to explain. The following short review aims to give an overview of the available clinical information of clinical trials performed over the last couple of years.

Adrenergic beta-Agonists↗
PubMed2006

Guidelines for chronic obstructive pulmonary disease treatment and issues of implementation.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Treatment advances over the last decade, although limited, have precipitated the development of clinical practice guidelines, with the aim of improving the quality of care received by patients through fostering evidence-based decision making and accelerating the application of new advances to everyday practice. Of the COPD guidelines that have been developed, those developed through the Global Initiative for Chronic Obstructive Lung Disease (GOLD), initially a joint activity between the U.S. National Heart, Lung, and Blood Institute and the World Health Organization, and the National Institute of Clinical Excellence (NICE) in the United Kingdom have both published their methods for evaluation of evidence. These comprehensive guidelines cover all aspects of the disease, with the aim of providing the basis for local care pathways. The guideline development process includes evaluation of the evidence, development of the guideline, and dissemination of the findings. Efforts to enhance guideline effectiveness have focused on improving the methods and approaches to implementation, which requires an appreciation of the issues that stop translation of guideline definitions of best practice into improved patient care. A variety of questions remain unanswered in the clinical management of COPD, including the definition of outcome measures that move beyond lung function, the potential application of multidimensional grading systems that assess respiratory and systemic expressions of COPD and that could possibly better categorize and predict outcome in these patients, and the impact of new clinical trial findings. Large ongoing outcome studies may also have an effect on defining best practice within future guideline recommendations.

Practice Guidelines as Topic↗
PubMed2005

Effects of cigarette smoke condensate on proliferation and wound closure of bronchial epithelial cells in vitro: role of glutathione.

BACKGROUND: Increased airway epithelial proliferation is frequently observed in smokers. To elucidate the molecular mechanisms leading to these epithelial changes, we studied the effect of cigarette smoke condensate (CSC) on cell proliferation, wound closure and mitogen activated protein kinase (MAPK) activation. We also studied whether modulation of intracellular glutathione/thiol levels could attenuate CSC-induced cell proliferation. METHODS: Cells of the bronchial epithelial cell line NCI-H292 and subcultures of primary bronchial epithelial cells were used for the present study. The effect of CSC on epithelial proliferation was assessed using 5-bromo-2-deoxyuridine (BrdU) incorporation. Modulation of epithelial wound repair was studied by analysis of closure of 3 mm circular scrape wounds during 72 hours of culture. Wound closure was calculated from digital images obtained at 24 h intervals. Activation of mitogen-activated protein kinases was assessed by Western blotting using phospho-specific antibodies. RESULTS: At low concentrations CSC increased proliferation of NCI-H292 cells, whereas high concentrations were inhibitory as a result of cytotoxicity. Low concentrations of CSC also increased epithelial wound closure of both NCI-H292 and PBEC, whereas at high concentrations closure was inhibited. At low, mitogenic concentrations, CSC caused persistent activation of ERK1/2, a MAPK involved in cell proliferation. Inhibition of cell proliferation by high concentrations of CSC was associated with activation of the pro-apoptotic MAP kinases p38 and JNK. Modulation of intracellular glutathione (GSH)/thiol levels using N-acetyl-L-cysteine, GSH or buthionine sulphoximine (BSO), demonstrated that both the stimulatory and the inhibitory effects of CSC were regulated in part by intracellular GSH levels. CONCLUSION: These results indicate that CSC may increase cell proliferation and wound closure dependent on the local concentration of cigarette smoke and the anti-oxidant status. These findings are consistent with increased epithelial proliferation in smokers, and may provide further insight in the development of lung cancer.

Bronchi↗
PubMed2005

Endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of lung cancer and its impact on surgical staging.

PURPOSE: The diagnosis and staging of lung cancer critically depends on surgical procedures. Endoscopic ultrasound (EUS) -guided fine-needle aspiration (FNA) is an accurate, safe, and minimally invasive technique for the analysis of mediastinal lymph nodes (LNs) and can additionally detect tumor invasion (T4) in patients with centrally located tumors. The goal of this study was to assess to what extent EUS-FNA could prevent surgical interventions. PATIENTS AND METHODS: Two hundred forty two consecutive patients with suspected (n = 142) or proven (n = 100) lung cancer and enlarged (> 1 cm) mediastinal LNs at chest computed tomography were scheduled for mediastinoscopy/tomy (94%) or exploratory thoracotomy (6%). Before surgery, all patients underwent EUS-FNA. If EUS-FNA established LN metastases, tumor invasion, or small-cell lung cancer (SCLC), scheduled surgical interventions were cancelled. Surgical-pathologic verification occurred when EUS-FNA did not demonstrate advanced disease. Cancelled surgical interventions because of EUS findings was the primary end point. RESULTS: EUS-FNA prevented 70% of scheduled surgical procedures because of the demonstration of LN metastases in non-small-cell lung cancer (52%), tumor invasion (T4) (4%), tumor invasion and LN metastases (5%), SCLC (8%), or benign diagnoses (1%). Sensitivity, specificity, and accuracy for EUS in mediastinal analysis were 91%, 100% and 93%, respectively. No complications were recorded. CONCLUSION: EUS-FNA qualifies as the initial staging procedure of choice for patients with (suspected) lung cancer and enlarged mediastinal LNs. Implementation of EUS-FNA in staging algorithms for lung cancer might reduce the number of surgical staging procedures considerably.

Adult↗
PubMed2005

Formoterol for maintenance and as-needed treatment of chronic obstructive pulmonary disease.

Formoterol is a long-acting beta2-agonist with a rapid onset of effect in patients with chronic obstructive pulmonary disease (COPD), making it potentially suitable for both maintenance and as-needed bronchodilator treatment. To evaluate the efficacy and tolerability of maintenance formoterol in patients with COPD and to compare the effects of additional formoterol as needed with terbutaline. In this 6-month, double-blind study, 657 patients with COPD (40 years, forced expiratory volume in 1s [FEV1] 40-70% predicted normal) were randomized to formoterol 9 microg twice daily (bid) plus terbutaline 0.5 mg as needed (FORM bid), formoterol 9 microg bid plus formoterol 4.5 microg as needed (FORM bid+prn), or placebo bid plus terbutaline 0.5 mg as needed (placebo), all administered via Turbuhaler. Primary efficacy variables were FEV1 and the sum of breathlessness and chest tightness scores combined symptom score. Formoterol significantly (P<0.01) increased FEV(1) compared with placebo: FORM bid 6.5% (95% CI: 2.5, 10.7%); FORM bid+prn 11.8% (95% CI: 7.7, 16.2%). Combined symptom score decreased significantly in both formoterol groups compared with placebo: FORM bid -0.27 (95% CI: -0.49, -0.06; P=0.012); FORM bid+prn -0.32 (95% CI: -0.53, -0.11; P=0.0026). Similar significant (P<0.05) improvements were seen in both formoterol groups for morning peak expiratory flow, cough and sleep scores, and reliever use. In this study, formoterol 9 microg bid via Turbuhaler as maintenance therapy, with either formoterol or terbutaline as rescue medication, provided sustained improvements in lung function and COPD symptoms. Both formoterol regimens were well tolerated with no differences in adverse events or electrocardiogram profiles.

Adrenal Cortex Hormones↗