Tuberculosis is a human disease caused by Mycobacteriumtuberculosis, and transmitted by airborne pathway. Documented cases of tuberculosis infection in healthcare workers have been reported in both ...developed and developing countries. Early recognition of potentially infectious cases, immediate implementation of airborne precautions and prompt medical treatment of cases, are required to lower the risk of disease transmission. Molecular biology techniques allow earlier diagnosis. In the event of non-compliance with airborne precautions, the investigation will further have to establish exhaustive lists of potentially exposed healthcare workers and patients, looking for cases of latent tuberculosis infections whose treatment should help avoid active tuberculosis disease.
Abstract Background Roflumilast, a phosphodiesterase-4 inhibitor, has an established place in the treatment of chronic obstructive pulmonary disease. Its potential role as a treatment for asthma is ...unclear. Aim We report the results from seven double-blind, parallel group, phase II or III studies designed to compare roflumilast with two anti-inflammatory treatments, beclomethasone dipropionate (BDP) and montelukast, in patients with asthma. Methods The studies of 6–12 week duration were conducted at 309 sites in Europe, North America, South Africa and Australia from 1998 to 2005. Data from 3802 patients, aged 12–70 years who received either roflumilast 100 μg, 250 μg or 500 μg once daily, BDP 400 μg or 500 μg twice daily, or 10 mg montelukast once daily was analyzed. Primary endpoints were mean change and time averaged excess area under the curve in forced expiratory volume in one second (FEV1 ) over the duration of the study. Secondary endpoints included change in forced vital capacity and peak expiratory flow, asthma symptoms and the concomitant use of rescue medication. Results Roflumilast was non-inferior to BDP and montelukast and consistently increased FEV1 . Use of rescue medication and all asthma symptom scores decreased significantly with all treatments, but no statistically significant between-group differences were observed. Secondary lung function endpoints generally supported the conclusions of the primary outcome measure. Conclusions Roflumilast improves FEV1 and asthma symptoms in patients with mild to moderate asthma, and is non-inferior compared with both BDP and montelukast. It deserves further study as a potentially effective anti-inflammatory treatment for asthma.
Somatostatin analogues may have antifibrotic properties in the lung. The aim of this study was to evaluate the expression of the five somatostatin receptors sst1 to sst5 in normal and fibrotic mouse ...lung and the action of SOM230 (pasireotide), a new somatostatin analogue with a long half-life, in bleomycin induced lung fibrosis and in human lung fibroblasts in vitro.
After intratracheal injection of bleomycin, C57Bl6 male mice received one daily subcutaneous injection of SOM230 or saline. The lungs were evaluated on days 3, 7 and 14 after administration of bleomycin.
We found that all somatostatin receptors were expressed in the normal mouse lung. The sst2 receptor mRNA expression was increased after bleomycin. SOM230 improved mice survival (69% vs 44%; p = 0.024), reduced lung collagen content at day 14 and decreased lung collagen-1 mRNA at day 7. SOM230 reduced bronchoalveolar lavage inflammatory cell influx at day 3, decreased lung connective tissue growth factor mRNA and transforming growth factor (TGF) beta mRNA and increased lung hepatocyte growth factor and keratinocyte growth factor mRNA. The sst2 receptor was strongly expressed in the human lung (normal or fibrotic), particularly by fibroblasts. In vitro, SOM230 reduced BrdU incorporation by control human lung fibroblasts cultured under basal conditions or with TGFbeta, and reduced alpha-1 collagen-1 mRNA expression in TGFbeta stimulated fibroblasts.
We conclude that SOM230 attenuates bleomycin induced pulmonary fibrosis in mice and human lung fibroblasts activation. This study points to a potential new approach for treating pulmonary fibrotic disorders.
The aim of this study was to compare two budesonide/formoterol maintenance doses within the budesonide/formoterol maintenance and reliever therapy concept and to identify possible patient ...characteristics at baseline which would predict a better response to a higher than standard maintenance dose. A total of 8,424 patients with symptomatic asthma when using an inhaled corticosteroid (ICS) with or without a long-acting β(2)-agonist were randomised to budesonide/formoterol 160/4.5 μg, one (1 × 2) or two (2 × 2) inhalations b.i.d. Patients used the same inhaler as needed for symptom relief. The primary outcome variable was time to first severe asthma exacerbation. In the total study population, the time to first severe asthma exacerbation was prolonged by 18% with 2 × 2 versus 1 × 2 (hazard ratio 0.82; p = 0.03). Lung function (peak expiratory flow) was the only statistically significant predictor of a better response to 2 × 2. The mean daily ICS doses were 737 and 463 μg in the 2 × 2 and 1 × 2 groups, respectively. In a real-life setting, budesonide/formoterol maintenance and reliever therapy at the 2 × 2 maintenance dose did prolong time to first severe exacerbation but at a higher medication load. Patients with low lung function benefited most from the higher maintenance dose.
To develop a diagnostic predictive model for the identification of patients with presumptive pulmonary tuberculosis (PTB) at high risk for active disease and those requiring nucleic acid ...amplification (NAAT) testing and/or preventive respiratory isolation in low-incidence, high-income countries.
A 1:1 case-control study was conducted in consecutive immunocompetent patients with presumed PTB hospitalised between 2009 and 2012 in Paris, France. Cases were defined as individuals with culture-confirmed PTB, regardless of smear result. Those with presumed PTB and three smear- and culture-negative samples were selected as controls. A score was derived using conditional logistic regression. Internal validity of the score was assessed using the bootstrap method.
A total of 354 patients were included in the analysis (177 cases, 177 controls). Among the 177 cases, 74 (42%) were smear-negative but culture-positive. Factors independently associated with PTB were age <50 years (adjusted OR aOR 4.7, 95%CI 1.8-12), diabetes (aOR 3.2, 95%CI 1.1-9.8), absence of cough with or without sputum (aOR 3.7, 95%CI 1.7-8.3), fever >15 days (aOR 3.5, 95%CI 1.3-9.5), apical infiltration without cavity (aOR 3.4, 95%CI 1.4-8.5) and cavitation or miliary pattern (aOR 19.7, 95%CI 7.6-51.1). Score C-index was 0.84 (95%CI 0.79-0.88). Calibration for the overall population (P = 0.770) and in smear-negative patients (P = 0.980) was appropriate. A score of 3.3 had 90% sensitivity, 50% specificity and 79% (IQR 28-95) median probability of PTB.
This score could be used to build an algorithm to determine the need for respiratory isolation and/or NAAT use in PTB disease.
The aim of the study was to compare the safety and effectiveness of as-needed formoterol with salbutamol in a large international real-life asthma study. Children and adults (n=18,124) were ...randomised to 6 months as-needed treatment with open-label formoterol 4.5 microg Turbuhaler or salbutamol 200 microg pressurised metered dose inhaler or equivalent. Primary safety variables were asthma-related and nonasthma-related serious adverse events (SAE)s and adverse events (AE)s resulting in discontinuation (DAE)s. The primary efficacy variable was time to first asthma exacerbation. The incidences of AEs, SAEs and DAEs arising from SAEs were not significantly different between treatments. DAEs for nonserious AEs were higher with formoterol. Asthma-related AEs decreased with formoterol (1,098 (12.3%) versus 1,206 (13.5%)), asthma-related SAEs were similar (108 (1.2%) versus 121 (1.4%)) but more asthma-related DAEs occurred in the formoterol group (89 (1.0%) versus 48 (0.5%)). Time to first exacerbation was prolonged (hazard ratio 0.86) and less as-needed and maintenance medication was used with formoterol. Reductions of exacerbations with as-needed formoterol versus salbutamol increased with increasing age and asthma medication level. This real-life study demonstrates that formoterol as-needed has a similar safety profile to salbutamol, and its use as a reliever therapy is associated with fewer asthma symptoms and exacerbations.
•Hospital attractiveness has been insufficiently evaluated.•We propose an evaluation method of hospital and emergency department (ED) attractiveness.•ED quality indicators were included in the ...attractiveness evaluation.•Differences on ED activities may be explained by attractiveness and primary care availability in the ED surroundings.
Background: Roflumilast is an oral, once‐daily phosphodiesterase 4 inhibitor with anti‐inflammatory activity in development for the treatment of asthma. Roflumilast was compared with inhaled ...beclomethasone dipropionate (BDP) in patients with asthma.
Methods: In a double blind, double‐dummy, randomized, noninferiority study, 499 patients (forced expiratory volume in 1 s FEV1 = 50–85% predicted) received roflumilast 500 μg once daily or BDP 200 μg twice daily (400 μg/day) for 12 weeks. Lung function and adverse events were monitored.
Results: Roflumilast and BDP significantly improved FEV1 by 12% (270 ± 30 ml) and 14% (320 ± 30 ml), respectively (P < 0.0001 vs baseline). Roflumilast and BDP also significantly improved forced vital capacity (FVC) (P < 0.0001 vs baseline). There were no significant differences between roflumilast and BDP with regard to improvement in FEV1 and FVC. Roflumilast and BDP showed small improvements in median asthma symptom scores (–0.82 and −1.00, respectively) and reduced rescue medication use (−1.00 and −1.15 median puffs/day, respectively; P < 0.0001 vs baseline). These small differences between roflumilast and BDP were not considered clinically relevant. Both agents were well tolerated.
Conclusions: Once daily, oral roflumilast 500 μg was comparable with inhaled twice‐daily BDP (400 μg/day) in improving pulmonary function and asthma symptoms, and reducing rescue medication use in patients with asthma.
Summary A randomised 6-month study compared two maintenance doses of budesonide/formoterol (Symbicort® Turbuhaler® ) maintenance and reliever therapy (Symbicort SMART® ), 160/4.5 μg 1 × 2 and 2 × 2, ...in 8053 asthmatics with symptoms despite treatment with inhaled corticosteroids ± inhaled long-acting β2 -agonists. This analysis compared response to the two treatments in elderly patients, ≥65 years, with that in younger patients. Elderly patients with early- or late-onset asthma were also compared. Elderly patients had lower post-bronchodilator FEV1 percentage predicted normal at baseline than younger patients (85.6% vs. 91.0%, respectively). The elderly had more exacerbations and risk of first severe exacerbation was increased by 55.3% (hazard ratio 1.553; 95% confidence interval: 1.249–1.931, p < 0.0001). However, no differences in exacerbations were seen between 1 × 2 or 2 × 2 budesonide/formoterol maintenance and reliever therapy treatment in the elderly. Five-item Asthma Control Questionnaire (ACQ-5) scores improved equally in the two age groups. Changes in mean ACQ-5 scores between 1 × 2 and 2 × 2 were significant in both age groups but not clinically relevant (≥65 years, 0.12; p = 0.018; <65 years, 0.09; p < 0.0001). Elderly patients with early- and late-onset asthma responded equally well to treatment. Budesonide/formoterol maintenance and reliever therapy (1 × 2 or 2 × 2) is an effective, well-tolerated and practical treatment concept in elderly and younger asthmatic patients. Clinical trial registration: NCT00463866
PDF
