Real-life effectiveness of asthma treatment with a fixed-dose fluticasone/formoterol pressurised metered-dose inhaler - Results from a non-interventional study.

OBJECTIVE: Prospective, non-interventional study of fixed-dose inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) combination therapy with fluticasone propionate/formoterol fumarate (FP/FORM) across a spectrum of community-based patients with asthma in a real-life setting. METHODS: In FP/FORM-treated patients aged ≥12 years, asthma control (Asthma Control Test™ [ACT]), incidence of severe exacerbations, lung function, quality of life (asthma quality of life questionnaire [AQLQ]) and adverse events (AEs) were assessed over one year. RESULTS: Almost 40% (n = 555) of the full analysis population (N = 1410) were receiving ICS/LABA therapy prior to enrolment; 69.8% completed the study. Asthma control (mean ACT ± standard deviation) improved from 16.3 ± 5.0 at baseline to 19.8 ± 4.5 at study end. ACT scores were significantly (p < 0.0001) higher than baseline at all observation timepoints, including the first assessment at 4-6 weeks. The percentage of patients with asthma control increased (baseline: 30.9%; study end: 62.4%), and the percentage of patients with ≥1 severe asthma exacerbation decreased (12 months before: 35.8%; during study: 5.9%). Lung function (forced expiratory volume in one second, peak expiratory flow) improved from baseline to each observation timepoint (p < 0.0001 for all). Improvement in asthma status was accompanied by ameliorated quality of life: AQLQ scores improved significantly from baseline to all observation timepoints (p < 0.0001 for all). AEs accorded with the summary of product characteristics. After study completion, 70% of patients continued FP/FORM treatment. CONCLUSION: In this one-year study, FP/FORM treatment was associated with clinically relevant improvements in asthma status in a diverse population of patients under real-life conditions.

[Cardiopulmonary Exercise Testing (CPET) in severe COPD--a multicentre comparison of two test protocols]. / Spiroergometrie bei Patienten mit chronisch obstruktiver Lungenerkrankung--multizentrischer Vergleich von zwei Belastungsprotokollen.

Cardiopulmonary exercise testing (CPET) allows a valid evaluation of cardiopulmonary function capability and the recognition of existing limitations in COPD patients. Whereas the measurement of the different parameters of CPET and the evaluation of the results are standardised, this does not apply to the protocols chosen. The aim of this study was to evaluate whether the results of two different exercise protocols were comparable in an outpatient multicentre setting. Ninety COPD patients stages II-IV according to the Gold classification were examined by means of symptom-limited exercise testing on a bicycle with two different ramp protocols (10 Watts vs. 16 Watts/min) within seven days. The results show that a higher acceleration rate of the load was associated with shorter exercise duration and higher achieved exercise capacity. Gas exchange and ventilatory parameters did not show significant differences on comparing both protocols. In pulmonary practices COPD patients of the Gold stages II-IV can be examined safely and with validity by means of CPET. The application of a ramp protocol with a stepwise increase of 16 Watts/minute can be recommended, particularly as for this regimen standardised normal values are available.

Angiogenic markers in breath condensate identify non-small cell lung cancer.

Early recognition of lung cancer is a prerequisite for any strategy to improve lung cancer treatment outcome. Here we report a cross-sectional study intended as a proof of principle investigation using breath based detection (exhaled breath condensate, EBC) of angiogenic markers (VEGF, bFGF, angiogenin), TNF-alpha and IL-8 to discriminate 74 individuals, with confirmed presence or absence (X-ray, CT) of non-small lung cancer (NSCLC). Levels of angiogenic markers bFGF, angiogenin and VEGF in EBC significantly discriminated between 17 individuals with newly detected NSCLC versus stable and exacerbated chronic obstructive pulmonary disease (COPD) patients as well as healthy volunteers. Levels of IL-8 and TNF-alpha in EBC indicated acute inflammation, e.g. in acute exacerbated COPD (AECOPD) and were not indicative of lung cancer. In a different group of patients that were already treated with two cycles of chemotherapy and who responded with at least a 25% reduction in primary tumor diameter, levels of angiogenic markers were lower compared to patients with newly diagnosed NSCLC. We suggest that breath based detection of angiogenic markers may help in the early detection of lung cancer.

[Tuberculosis and travelling]. / Tuberkulose und Reisen.

Tuberculosis (TB) in Germany in the year 2007 with 5020 reported cases (incidence: 6.1 newly diagnosed cases per 100 000 inhabitants) was continuously in decline. 43.1 % of these persons were from countries with a higher TB incidence as compared to Germany. However, not only migration but also personal journeys from low- to high-incidence countries carries an increased risk of infection with M. tuberculosis (MTB). An early active TB follows only rarely, more common, however, is a latent TB infection (LTBI). Not only the active form of TB but also LTBI, with a potential for reactivation years or decades later, can be of enormous relevance for the individual and the social environment. The early detection of an MTB infection and its possible sequelae are decisive for a continued successful battle against tuberculous diseases, especially in view of increasing travel activities.

[Modern impulse oscillometry in the spectrum of pulmonary function testing methods]. / Die moderne Impulsoszillometrie im Spektrum lungenfunktioneller Messmethoden.

Impulse oscillometry (IOS) is a computer supported method for the measurement of complex mechanical airway characteristics. Bronchial obstructions can reliably be diagnosed by IOS when more complex parameters such as frequency dependence of resistance (FDR) and lung reactance (X5) are evaluated in cases with more severe obstruction. Parameters of conventional methods like pneumotachography, spirometry, and bodyplethysmography show relatively low correlations due to the different measurement principles, not only in comparison to IOS, but also in between one another. The IOS is a convenient method for patients with a low dependency on cooperation for the evaluation of obstructive airway diseases complementary to the established standard methods. Furthermore, IOS may provide a sensitive screening tool for the early detection of bronchial obstructions not only in paediatrics but also in occupational medicine.

[Impulse oscillometry in the diagnosis of the severity of obstructive pulmonary disease]. / Die Impulsoszillometrie in der Schweregraddiagnostik obstruktiver Lungenerkrankungen.

Impulse oscillometry (IOS) is a computer-supported method for the measurement of complex mechanical airway characteristics. The aim of this study was to evaluate the applicability of IOS in the diagnosis of obstructive airway diseases in comparison to the standard methods of spirometry, pneumotachymetry, and bodyplethysmography. 244 patients (age 61.5 +/- 13.6 years; 61 % men) with bronchial asthma (n = 65) and chronic obstructive pulmonary disease (COPD) (n = 179) were retrospectively analysed. By means of body plethysmography (Srtot < 120%pred) an obstruction was diagnosed in 94%, by pneumotachymetry (FEV1 < 80%pred) in 78 %, and by IOS depending on the parameter chosen in 87-94% of patients. Mild and medium obstructions could be identified by means of all IOS parameters except for R20: severe obstructions, however, were better detected by means of the frequency-dependent resistance FDR and reactance at 5 Hz, X5. The parameters R5, X5, and Zrs, however, showed a tendency to underestimate the degree of obstruction. Bronchial obstruction can reliably be diagnosed by IOS when, in cases of severe obstruction, more complex parameters like FDR and X5 are included. The parameters of the standard methods (body plethysmography and pneumotachymetry) show relatively low correlations due to the different measurement methods not only in comparison to IOS but also to one another. In summary, IOS is a convenient method for patients with a low dependency on cooperation for the evaluation of obstructive airway diseases complementary to the established standard methods and, in addition, is useful as a sensitive screening tool for the early detection of bronchial obstruction.

[Friend or foe: combination therapy with inhaled corticosteroids and long-acting beta2-agonists in chronic obstructive pulmonary disease (COPD)]. / Indikationen und Limitationen einer fixen Kombinationstherapie mit inhalativen Kortikosteroiden und langwirksamen beta2-Mimetika bei der chronisch-obstruktiven Lungenerkrankung (COPD).

Inhaled corticosteroids (ICS) used in COPD (chronic obstructive pulmonary disease) are recommended only in combination with a long-acting beta2-agonist (LABA) in stage 3 and higher in COPD treatment guidelines. In comparison to placebo and the single components, a superior control by means of the ICS/LABA fixed combination therapy has been demonstrated for clinical improvement in the following parameters: reduction of exacerbation rate and hospitalisations, reduction of dyspnoea and improvement of forced expiratory volume in one second (FEV1). In contrast to data from database studies, the large prospective TORCH (Towards a Revolution in COPD Health) trial found in the ICS/LABA group a beneficial effect on the reduction of mortality only as a trend in the ICS/LABA group, which did not reach statistical significance. In long-term trials, ICS treated patients experienced up to 10% oral and/or pharyngeal candidiasis. ICS was associated with an excess risk of pneumonia, which doubles the pneumonia incidence in patients not receiving ICS. The probability of having pneumonia reported as an adverse event was 18-19 % in the ICS groups and resulted in a 1.7-2.2 elevated pneumonia risk. Because ICS therapy is recommended only in conjunction with a bronchodilator, fixed ICS/LABA combinations are a logical consequence for COPD long-term therapy.

[Clinical features and diagnosis of bronchopulmonary infections in the elderly]. / Klinik und Diagnose bronchopulmonaler Infektionen im Alter.

Diseases of the lung are one of the main causes of morbidity and mortality in the elderly. The risk of respiratory infections is increased due to structural changes, malnutrition, co-morbidity, and a variety of other factors. Bacterial and viral pathogens cause acute bronchitis and exacerbations of chronic bronchitis (AECB). Community acquired pneumonias (CAP) show a different spectrum of pathogens and clinical course in comparison to nosocomial pneumonias (hospital acquired pneumonia, HAP). Institutionalised patients are at risk of a health care associated pneumonia (HCAP), with often a different spectrum of pathogens in comparison to CAP and HAP. Elderly patients with cerebrovascular disease and impairment of swallowing or cough reflexes often suffer from aspiration pneumonias. The mortality is highest in the elderly, comorbid, and immunocompromised patient with nosocomial pneumonia. Important preventive measures include influenza and pneumococcal vaccination, avoidance of immobility, oral hygiene, and sufficient nutrition.

Treatment of invasive pulmonary aspergillosis in neutropenic patients by additional bronchoscopic amphotericin B instillation.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a life-threatening condition despite systemic antifungal therapy. OBJECTIVES: This retrospective analysis investigated whether additional bronchoscopic instillation of amphotericin B (amB) would improve efficacy of antifungal treatment in patients with haematological malignancies suffering from IPA. METHODS: Twenty patients (40.6 +/- 14.2 years, 14 male) with preceding chemotherapy, bone marrow or stem cell transplantation complicated by severe IPA who did not respond sufficiently to systemic antifungal therapy were additionally treated by repeated bronchoscopic instillations of amB solution (91 instillations, on average 4.6 +/- 2.2 instillations per patient over a period of 24.1 +/- 21.0 days). Therapeutic response to this combined treatment regimen was monitored by chest X-ray and CT scan. RESULTS: The mean infiltration sizes during systemic antifungal therapy alone (mean duration 11.9 +/- 9.9 days) did not change significantly. However, after additional bronchoscopic instillation of amB solution infiltration sizes were reduced significantly (p < 0.05). A total resolution of infiltrates was seen in 3 and a partial reduction in 13 of 20 patients. Mean duration of total antifungal treatment was 50.1 +/- 24.0 days. The mean follow-up period was 34.1 +/- 31.2 months. The IPA-related mortality rate was 18.8% (3 of 16 patients). CONCLUSIONS: Additional bronchoscopic instillation of amB may improve the efficacy of systemic antifungal therapy in patients with haematological malignancies complicated by severe IPA. Bronchoscopic instillation of amB should be considered as an additional treatment option in cases with IPA unresponsive to systemic therapy.

Transgenes sustain epigeal insect biodiversity in diversified vegetable farm systems.

Many ecological studies have focused on the effects of transgenes in field crops, but few have considered multiple transgenes in diversified vegetable systems. We compared the epigeal, or soil surface-dwelling, communities of Coleoptera and Formicidae between transgenic and isoline vegetable systems consisting of sweet corn, potato, and acorn squash, with transgenic cultivars expressing Cry1(A)b, Cry3, or viral coat proteins. Vegetables were grown in replicated split plots over 2 yr with integrated pest management (IPM) standards defining insecticide use patterns. More than 77.6% of 11,925 insects from 1,512 pitfall traps were identified to species, and activity density was used to compare dominance distribution, species richness, and community composition. Measures of epigeal biodiversity were always equal in transgenic vegetables, which required fewer insecticide applications than their near isolines. There were no differences in species richness between transgenic and isoline treatments at the farm system and individual crop level. Dominance distributions were also similar between transgenic and isoline farming systems. Crop type, and not genotype, had a significant influence on Carabidae and Staphylinidae community composition in the first year, but there were no treatment effects in the second year, possibly because of homogenizing effects of crop rotations. Communities were more influenced by crop type, and possibly crop rotation, than by genotype. The heterogeneity of crops and rotations in diversified vegetable farms seems to aid in preserving epigeal biodiversity, which may be supplemented by reductions in insecticide use associated with transgenic cultivars.

[Avian influenza and the Severe Acute Respiratory Syndrome (SARS) - experiences and perspectives]. / Aviäre Influenza und das Schwere Akute Respiratorische Syndrom (SARS) - Erfahrungen und Perspektiven.

New respiratory viruses associated with pneumonia have in the past few years been detected in humans. The sudden appearance of the severe acute respiratory syndrome (SARS) in 2003 demonstrated that an emerging and highly infectious disease caused by a hitherto unknown virus was able to spread rapidly, but could finally be contained by stringent measures. The avian influenza A-H5N1-virus of high pathogenicity has crossed in multiple instances the species barriers between humans, mammals, and birds posing a serious pandemic threat. The application of the so far learnt and the continued development of preventive strategies, efficient vaccines, and antiviral substances are besides worldwide surveillance decisive to rapidly detect the repeated, enforced, or new appearance of viruses like the SARS-CoV, influenza A-H5N1 virus, or of new viruses, to contain their spread, and to defeat them.

Coccinellids, aphids, and pollen in diversified vegetable fields with transgenic and isoline cultivars.

The influence of concurrent introduction of three transgenic vegetable cultivars on seasonal dynamics of coccinellids and their food, aphids and pollen, was examined within diversified farm systems practicing insect pest management in northeastern US agroecosystems. The transgenic cultivars used included sweet corn, potato, and winter squash, expressing Cry1(A)b, Cry3A, and plant viral coat proteins that target Lepidoptera, Coleoptera, and aphid-transmitted viruses, respectively. Transgenic systems reduced insecticides by 25%. Weekly differences in coccinellid density between transgenic and isoline crops were rare and transitory, governed by timing of at-planting or foliar insecticide use patterns; however cumulative frequencies for three of the six coccinellid species differed between transgenic and isoline crops. At a multicrop, farm systems level, seasonal dynamics of the coccinellids and aphids tracked dynamics in the sweet corn, which far surpassed the other crops in abundance of coccinellids and pollen, and harbored consistently higher aphid densities. Although these results warrant further study, the patterns suggest that diversified transgenic vegetable crops under current commercial management demonstrated transitory conservation of coccinellids, and that integration with selective insecticides or other IPM tactics could increase this potential.

[Acute bronchitis: when are antibiotics, and when is symptomatic treatment indicated?]. / Akute Bronchitis. Wann symptomatisch, wann mit Antibiotika behandeln?

Acute bronchitis is usually caused by a virus, while the chronic form is due to inhalative noxae (in most cases decades of cigarette smoking). Both varieties are diagnosed on a clinical basis. Treatment of acute bronchitis is symptomatic. A sore throat is treated locally, and a troublesome, in particular nocturnal, cough with antitussive agents applied for a limited period (14 days). If bronchial mucus is viscous and difficult to clear, short-term treatment with a secretolytic or mucolytic substance is justified. Management of chronic bronchitis consists primarily in the elimination of the noxae. Treatment with antibiotics (usually oral) makes good sense only when there is a bacteriological infection of the upper or lower airways in an acute stage, such as infection-driven exacerbation of chronic obstructive bronchitis (COPD).

[Health significance of inhaled particles]. / Gesundheitliche Bedeutung inhalierter Stäube.

Particulates refer to particles, dust, dirt, soot and aerosol mists that has suspended in the surrounding air. They may consist of solids of various forms including fibres or liquids. Long term exposure to silicon dioxide containing dusts (crystalline silica: quartz, tridymite, cristobalite, coesite, stishovite) may cause pneumoconiosis in the form of acute or/either chronic silicosis. Asbestos refers to a divers family of crystalline hydrated fibrous siliates typically exhibiting a greater tha 3:1 length ot diameter ratio. It is subdivided into serpentine (Chrysotile) and amphibole (crocidolite, amosite, anthophyllite, tremolite, actinolite). Exposure to asbestos fibres may cause lung fibrosis and promote cancer of the lung or the pleura. Besides the induction of malignant diseases dust exposure may result in obstructive as well as restrictive lung diseases which may be compensate in case of the recognition as a occupational diseases. Other occupational exposures leading to pneumoconiosis are caused be talc, or metals including aluminium containing dusts. Also the group of man-made mineral (MMMFs) or vitreous fibres (MMVFs), including glass wool, rock wool, slag wool, glass filaments, microfibres, refractory ceramic fibres are bioactive under certain experimental conditions. Although it has been shown that MMMFs may cause malignancies when injected intraperitoneally in high quantities in rodents, inhalation trials and human studies could not reproduce these results in the same precision. Fine particles (particulate matter = PM) comprise one of the most widespread and harmful air pollutants in the industrialized world. PM may cause worsening of asthma and other respiratory diseases, reduce lung function development in children, potentially increased the risk of premature death in the elderly and enhance mortality from cardiac diseases. Because of the small size PM2.5 is seen to be even more hazardous than PM10.

[Matrix metalloproteinases and their inhibitors in lung cancer with malignant pleural effusion]. / Matrix-Metalloproteinasen und deren Inhibitoren bei Lungenkarzinomen mit malignem Pleuraerguss.

UNLABELLED: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) play a crucial role in physiological and pathological matrix turnover. This study aimed to determine the occurrence of MMP and TIMP in lung cancer patients with malignant pleural effusions (CA). METHODS: MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1, and IMP-2 oncentrations were determined by ELISA and zymography in pleural effusions and plasma of 31 CA and 14 congestive heart failure (CHF) patients and in plasma of 18 healthy controls (CON). RESULTS: MMP-2, TIMP-1, and TIMP-2 ELISA-concentrations were increased in CA pleural fluid vs. CA plasma (p < 0.005, p < 0.005, p < 0.05), in contrast to MMP-9 being higher in plasma (p < 0.005). Pleural fluid MMP-1 and MMP-8 were increased in CA vs. CHF (p < 0.05, p < 0.005). MMP and TIMP plasma concentrations were not different in CA vs. CHF, but MMP-9, TIMP-1, and TIMP-2 were increased vs. CON (p < 0.005, each). Gelatine zymography MMP-9/MMP-2 ratios were increased in CA plasma vs. effusion fluid (p < 0.005), in CA vs. CHF plasma, CA vs. CHF effusions (p < 0.005 each), and in CA vs. CON plasma (p < 0.05). CONCLUSIONS: MMP-2, TIMP-1, and TIMP-2 accumulate in the pleural compartment in CA and CHF, probably reflecting an unspecific pleural reaction. MMP-1 and MMP-8 are increased in cellular rich CA pleural effusions only. The determination of MMP-9/MMP-2 ratios in pleural fluid may contribute to differentiate CHF from CA effusions.

Vascular endothelial growth factor in pleural effusions of different origin.

This study aimed to determine the diagnostic relevance of vascular endothelial growth factor (VEGF) in the pleural fluid and serum of patients with pleural effusions of different aetiology. VEGF was quantified in the pleural effusion fluid and serum of 96 patients with malignancies (58 lung cancers (CA) and 38 tumours with secondaries to the lung (TM)), 45 with congestive heart failure (CHF), 28 with tuberculosis (TB), 45 with acute infections (INF), and in the serum of 20 healthy controls. VEGF pleural effusion concentrations were significantly different in the main diagnostic groups. VEGF was higher in effusions of patients with malignancies (CA as well as TM) in comparison with INF, TB or CHF. In serum, however, high VEGF concentrations indicated CA, TM or INF, but not TB or CHF. Despite significant differences of VEGF levels in different patient groups, receiver-operating characteristic analysis revealed insufficient diagnostic value of VEGF for differential diagnosis of pleural effusions. In conclusion, vascular endothelial growth factor serum concentration is highly suggestive of the presence of lung disease in general, except for tuberculosis. In effusion fluid, the presence of vascular endothelial growth factor clearly indicates inflammatory or malignant origin. However, for diagnostic use, additional parameters besides vascular endothelial growth factor are mandatory.

[Immunohistochemical localization of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in tuberculous pleuritis]. / Immunhistochemische Lokalisation von Matrixmetalloproteinasen (MMP) und ihrer Inhibitoren (tissue inhibitors of metalloproteinases, TIMP) bei tuberkulöser Pleuritis.

Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been found by ELISA and gelatine zymography in different concentrations in pleural fluid in tuberculous (TB) pleuritis. For further differentiation MMP and TIMP were localized in pleural biopsies by immunhistochemical staining with antibodies directed against MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 using the Labelled-Avidin-Biotin (LAB). Immunohistological reactivity of MMP-1 was found in epitheloidcellular histiocytes, Langhans' giant cells, lymphocytes, macrophages, as well as in fibroblasts of granulomatous reactions. MMP-2 was found in a few epitheloid cellular histiocytes, fibroblasts, and inflammatory cells. MMP-3 was weakly positive in a few lymphocytes only. MMP-9 was found in a few fibroblasts, epitheloid cells, and inflammatory cells, foremost, however, in pleural mesothial cells. A few fibroblasts only showed immunoreactivity of TIMP-1 and TIMP-2. The observed inhomogenous staining pattern could be explained by the different state of activation of individual cellular units. In conclusion, the immunohistochemical demonstration of MMP and TIMP in pleural cells and tissue structures indicates their local involvement in fibrosing reactions in TB-pleuritis.