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2013 annual congress of the European Respiratory Society
News
2013 annual congress of the European Respiratory Society Published Online September 20, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70181-4 For the current guidelines published by the IDSA/ATS see http://www.idsociety.org/ uploadedFiles/IDSA/GuidelinesPatient_Care/PDF_Library/ CAP%20in%20Adults.pdf For the latest results from the U-BIOPRED study see http:// www.europeanlung.org/en/ projects-and-research/projects/ u-biopred/home For the TIOSPIR study see N Engl J Med 2013; published online Aug 30. DOI:10.1056/ NEJMoa1303342 For the UK Biobank Resource see http://www.ukbiobank.ac.uk
Simplifying pneumonia guidelines Current criteria for severe communityacquired pneumonia (CAP) can be simplified without affecting prognostic accuracy, according to researchers from the University of Dundee. Current guidelines published by the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS) use nine criteria (including multilobar infiltrates, confusion, and uraemia) to define severe CAP. “Using a combination of meta-analysis of data from over 6000 patients with pneumonia and a well established database of patients with pneumonia in Scotland, we showed that the criteria could be simplified by excluding predictors such as thrombocytosis and hypothermia”, explains James Chalmers (University of Dundee, UK), one of the study authors. All nine criteria were statistically significantly associated with mortality and admission to an intensive-care unit (ICU); however, leucopenia (<4000 cells/mm³), thrombocytopenia (<100 000 cells/mm³), and hypothermia (<36oC) occurred in less than 5% of cases. When these criteria were excluded, the simplified score did just as well as the full score in predicting mortality and ICU admission (p=0·9). Furthermore, the researchers found that acidosis, which was not one of the original nine criteria, was one of the strongest predictors of outcome. “Simple scores are much more likely to be used in clinical practice and so we think reducing a nine variable score to six variables is a positive advance”, Chalmers concludes. “The IDSA/ATS
guidelines are in the process of being updated at the moment, so we are hoping these data will inform the future definition of severe pneumonia.”
Characterising patients with severe asthma Patients with severe asthma needing oral corticosteroid treatment have high concentrations of sputum eosinophils, according to the latest results from the Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes (U-BIOPRED) study. The aim of U-BIOPRED is to identify different subtypes of severe asthma. So far, the project has recruited 1028 patients (adult and paediatric) with asthma. In a study of 372 adults with severe asthma, 44·4% needed daily oral corticosteroid treatment to control or partially control their symptoms. These patients had a higher exacerbation rate, greater airway inflammation, and needed significantly more asthma medications than did patients who did not require daily oral steroids. Interestingly, patients needing oral steroid treatment also had higher sputum concentrations of eosinophils and neutrophils than did the non-steroid group. The study investigators concluded that this group of patients might represent a steroidinsensitive subgroup. “At present, conventional asthma therapies are suboptimal to manage patients with severe asthma”, comments lead author David Gibeon (Imperial College, London, UK). “There is a clear unmet need in this group. Looking at why patients need steroid treatment and the characteristics of these patients will aid drug development.”
David Mack/Science Photo Library
Tiotropium Respimat versus Handihaler in COPD Tiotropium Respimat and tiotropium Handihaler have similar safety profiles and exacerbation efficacies in patients with chronic obstructive pulmonary disease (COPD), according to the results of a randomised, double-blind, 594
parallel-group trial. In a previous posthoc analysis of four placebo controlled trials, tiotropium Respimat had a higher mortality rate compared with placebo. The aim of the Tiotropium Respimat Inhaler and the Risk of Death in COPD (TIOSPIR) study was therefore to assess the safety and efficacy of tiotropium Respimat (once daily dose of 2·5 μg or 5 μg) compared with tiotropium Handihaler (once daily dose 18 μg) in 17 135 patients with COPD. The primary endpoints were risk of death (all causes) and risk of first exacerbation. Death rates per 100 patients were 3·22 for tiotropium Respimat (5 μg) and 3·36 for tiotropium Handihaler; these results are similar to those reported in the previous post-hoc analysis. Risk of first exacerbation was not significantly different between the tiotropium Respimat (5 μg) and tiotropium Handihaler treatment groups (HR 0·98, 95% CI 0·93–1·03; p=0·42). Incidence of major cardiovascular adverse events and causes of death were similar across all three treatment groups. The investigators conclude that the results from this large-scale trial support the need for caution when interpreting safety outcomes from meta-analyses of small data sets and observational studies.
Cognitive function in obstructive lung disease People with obstructive lung diseases (OLD), such as chronic obstructive pulmonary disease, have cognitive impairment in specific domains, according to the results of an observational study using the UK Biobank Resource. Researchers from the Center of Expertise for Chronic Organ Failure (Horn, Netherlands) compared different domains of cognitive functioning in 5764 patients with OLD with that of 37 275 people without OLD from the general population. Performance of people with OLD on the prospective www.thelancet.com/respiratory Vol 1 October 2013
News
memory test (p<0·005), the pairs matching test (round 1: p<0·005; round 2: p=0·047), the numeric memory test (p=0·047), and the reaction time test (p<0·01) was significantly worse than participants without OLD. Lead author Fiona Cleutjens stated that health-care professionals need to be aware of the possible effect of cognitive impairment on the self-management, clinical management, and pulmonary rehabilitation of patients with OLD. Possible mechanisms underlying the association between cognitive impairment and OLD might include brain damage due to smoking, inflammation, hypoxia, hypoxaemia, hypercapnia, and atherosclerosis.
High-dose inhaled mannitol for non-CF bronchiectasis Although high-dose inhaled mannitol (Bronchitol) does not significantly reduce exacerbation rate in patients with non-cystic fibrosis (CF) bronchiectasis, it did significantly improve time to first exacerbation in a multicentre phase 3 randomised controlled trial (NCT00669331). Bronchitol (400 mg mannitol twice a day) was compared with a control treatment (50 mg mannitol twice a day) in 461 patients with nonCF bronchiectasis over a 12 month period. The primary efficacy endpoint was pulmonary exacerbation rate, with secondary endpoints of time to first exacerbation, duration of exacerbations, antibiotic use, 24 h sputum weight, and quality of life. The yearly exacerbation rate in the Bronchitol group was 1·69 compared with 1·84 in the control treatment group (p=0·31). However, there was a statistically significant difference between the proportion of patients who remained free from exacerbations during the study period in the Bronchitol group (31·3%) compared with the control treatment group (21·9%; risk ratio 0·88; p=0·027). Duration of antibiotic treatment during exacerbations www.thelancet.com/respiratory Vol 1 October 2013
was lower in the Bronchitol group (p=0·0496), sputum production was higher (p=0·036), and quality of life improved (p=0·046) compared with the control treatment group. The study authors conclude that although the primary endpoint failed to reach significance, significant improvements in secondary endpoints warrant further assessment of Bronchitol in non-CF bronchiectasis.
Antibiotic use in LRTI Researchers from the University of Dundee (UK) reported that the introduction of a new prescribing protocol for duration of antibiotic treatment for lower respiratory tract infections (LRTI) resulted in a reduction in inappropriate antibiotic use and associated adverse events. All patients in a teaching hospital in Scotland who received antibiotic treatment for a LRTI over a 1 year period were included in the study. The researchers recorded mode and duration of antibiotic use in the first part of the study. In the second part, an antibiotic protocol was introduced that incorporated automatic stop dates, duration of treatment guided by severity (5 days for low severity, 7 days for high severity), and pharmacist feedback. Introduction of the new protocol led to a significant reduction in the duration of antibiotic treatment (p<0·001). Consequently, a significant reduction in adverse events was also observed (p<0·0001). The new antibiotic protocol did not have any effect on mortality rate. The study authors conclude that this new antibiotic protocol could reduce inappropriate use of antibiotics, thus reducing adverse events and possibly antibiotic resistance.
Drug resistance in tuberculosis The aim of the Global Consortium for Drug-Resistant TB Diagnostics is to reduce the time needed for drug susceptibility testing and to identify a genetic basis of drug-resistant strains of tuberculosis in areas with high disease burden. Antonino Catanzaro (University
of California San Diego, CA, USA) presented preliminary data from more than 1000 patients from three sites— Mumbai (India), Chisinau (Moldova), and Port Elizabeth (South Africa). The aim of the study was to develop rapid drug resistance detection technologies to reduce the current time to diagnosis of extremely drug-resistant tuberculosis (XDR-TB). Eligibility criteria for the study included active tuberculosis infection, high risk for drug resistance, and ability to produce more than 5 mL of sputum. Drug resistance to isoniazid, rifampicin, moxifloxacin, ofloxacin, amikacin, capreomycin, and kanamycin was assessed in all samples. The researchers identified three tests—microscopic observation of drug susceptibility assay, Hain line probe multidrug-resistance test, and pyrosequencing—as the most promising for rapid identification of drug-resistant tuberculosis.
For more on the Global Consortium for Drug-Resistant TB Diagnostics see http://gcdd. ucsd.edu/
Aclidinium for treatment of COPD Aclidinium bromide significantly improves symptoms of chronic obstructive pulmonary disease (COPD) compared with placebo, according to the results of a phase 3b trial (NCT01462929). 414 patients with COPD were randomly assigned to receive aclinidium (400 μg twice a day), tiotropium (18 μg once a day), or placebo for 6 weeks. The study authors reported a significant improvement in EXACT-respiratory symptoms (E-RS) score in the aclinidium group compared with both the placebo and tiotropium groups. Severity of early morning symptoms was also significantly improved in the aclinidium group compared with placebo and tiotropium. Aclidinium resulted in significant bronchodilation in the first 24 h of treatment compared with placebo or tiotropium, although aclidinium and tiotropium had similar efficacy at the end of the 6 week study period. Additionally, patients preferred aclidinium to tiotropium.
Rebecca Akkermans 595
2013 annual congress of the European Respiratory Society Published Online September 20, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70181-4 For the current guidelines published by the IDSA/ATS see http://www.idsociety.org/ uploadedFiles/IDSA/GuidelinesPatient_Care/PDF_Library/ CAP%20in%20Adults.pdf For the latest results from the U-BIOPRED study see http:// www.europeanlung.org/en/ projects-and-research/projects/ u-biopred/home For the TIOSPIR study see N Engl J Med 2013; published online Aug 30. DOI:10.1056/ NEJMoa1303342 For the UK Biobank Resource see http://www.ukbiobank.ac.uk
Simplifying pneumonia guidelines Current criteria for severe communityacquired pneumonia (CAP) can be simplified without affecting prognostic accuracy, according to researchers from the University of Dundee. Current guidelines published by the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS) use nine criteria (including multilobar infiltrates, confusion, and uraemia) to define severe CAP. “Using a combination of meta-analysis of data from over 6000 patients with pneumonia and a well established database of patients with pneumonia in Scotland, we showed that the criteria could be simplified by excluding predictors such as thrombocytosis and hypothermia”, explains James Chalmers (University of Dundee, UK), one of the study authors. All nine criteria were statistically significantly associated with mortality and admission to an intensive-care unit (ICU); however, leucopenia (<4000 cells/mm³), thrombocytopenia (<100 000 cells/mm³), and hypothermia (<36oC) occurred in less than 5% of cases. When these criteria were excluded, the simplified score did just as well as the full score in predicting mortality and ICU admission (p=0·9). Furthermore, the researchers found that acidosis, which was not one of the original nine criteria, was one of the strongest predictors of outcome. “Simple scores are much more likely to be used in clinical practice and so we think reducing a nine variable score to six variables is a positive advance”, Chalmers concludes. “The IDSA/ATS
guidelines are in the process of being updated at the moment, so we are hoping these data will inform the future definition of severe pneumonia.”
Characterising patients with severe asthma Patients with severe asthma needing oral corticosteroid treatment have high concentrations of sputum eosinophils, according to the latest results from the Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes (U-BIOPRED) study. The aim of U-BIOPRED is to identify different subtypes of severe asthma. So far, the project has recruited 1028 patients (adult and paediatric) with asthma. In a study of 372 adults with severe asthma, 44·4% needed daily oral corticosteroid treatment to control or partially control their symptoms. These patients had a higher exacerbation rate, greater airway inflammation, and needed significantly more asthma medications than did patients who did not require daily oral steroids. Interestingly, patients needing oral steroid treatment also had higher sputum concentrations of eosinophils and neutrophils than did the non-steroid group. The study investigators concluded that this group of patients might represent a steroidinsensitive subgroup. “At present, conventional asthma therapies are suboptimal to manage patients with severe asthma”, comments lead author David Gibeon (Imperial College, London, UK). “There is a clear unmet need in this group. Looking at why patients need steroid treatment and the characteristics of these patients will aid drug development.”
David Mack/Science Photo Library
Tiotropium Respimat versus Handihaler in COPD Tiotropium Respimat and tiotropium Handihaler have similar safety profiles and exacerbation efficacies in patients with chronic obstructive pulmonary disease (COPD), according to the results of a randomised, double-blind, 594
parallel-group trial. In a previous posthoc analysis of four placebo controlled trials, tiotropium Respimat had a higher mortality rate compared with placebo. The aim of the Tiotropium Respimat Inhaler and the Risk of Death in COPD (TIOSPIR) study was therefore to assess the safety and efficacy of tiotropium Respimat (once daily dose of 2·5 μg or 5 μg) compared with tiotropium Handihaler (once daily dose 18 μg) in 17 135 patients with COPD. The primary endpoints were risk of death (all causes) and risk of first exacerbation. Death rates per 100 patients were 3·22 for tiotropium Respimat (5 μg) and 3·36 for tiotropium Handihaler; these results are similar to those reported in the previous post-hoc analysis. Risk of first exacerbation was not significantly different between the tiotropium Respimat (5 μg) and tiotropium Handihaler treatment groups (HR 0·98, 95% CI 0·93–1·03; p=0·42). Incidence of major cardiovascular adverse events and causes of death were similar across all three treatment groups. The investigators conclude that the results from this large-scale trial support the need for caution when interpreting safety outcomes from meta-analyses of small data sets and observational studies.
Cognitive function in obstructive lung disease People with obstructive lung diseases (OLD), such as chronic obstructive pulmonary disease, have cognitive impairment in specific domains, according to the results of an observational study using the UK Biobank Resource. Researchers from the Center of Expertise for Chronic Organ Failure (Horn, Netherlands) compared different domains of cognitive functioning in 5764 patients with OLD with that of 37 275 people without OLD from the general population. Performance of people with OLD on the prospective www.thelancet.com/respiratory Vol 1 October 2013
News
memory test (p<0·005), the pairs matching test (round 1: p<0·005; round 2: p=0·047), the numeric memory test (p=0·047), and the reaction time test (p<0·01) was significantly worse than participants without OLD. Lead author Fiona Cleutjens stated that health-care professionals need to be aware of the possible effect of cognitive impairment on the self-management, clinical management, and pulmonary rehabilitation of patients with OLD. Possible mechanisms underlying the association between cognitive impairment and OLD might include brain damage due to smoking, inflammation, hypoxia, hypoxaemia, hypercapnia, and atherosclerosis.
High-dose inhaled mannitol for non-CF bronchiectasis Although high-dose inhaled mannitol (Bronchitol) does not significantly reduce exacerbation rate in patients with non-cystic fibrosis (CF) bronchiectasis, it did significantly improve time to first exacerbation in a multicentre phase 3 randomised controlled trial (NCT00669331). Bronchitol (400 mg mannitol twice a day) was compared with a control treatment (50 mg mannitol twice a day) in 461 patients with nonCF bronchiectasis over a 12 month period. The primary efficacy endpoint was pulmonary exacerbation rate, with secondary endpoints of time to first exacerbation, duration of exacerbations, antibiotic use, 24 h sputum weight, and quality of life. The yearly exacerbation rate in the Bronchitol group was 1·69 compared with 1·84 in the control treatment group (p=0·31). However, there was a statistically significant difference between the proportion of patients who remained free from exacerbations during the study period in the Bronchitol group (31·3%) compared with the control treatment group (21·9%; risk ratio 0·88; p=0·027). Duration of antibiotic treatment during exacerbations www.thelancet.com/respiratory Vol 1 October 2013
was lower in the Bronchitol group (p=0·0496), sputum production was higher (p=0·036), and quality of life improved (p=0·046) compared with the control treatment group. The study authors conclude that although the primary endpoint failed to reach significance, significant improvements in secondary endpoints warrant further assessment of Bronchitol in non-CF bronchiectasis.
Antibiotic use in LRTI Researchers from the University of Dundee (UK) reported that the introduction of a new prescribing protocol for duration of antibiotic treatment for lower respiratory tract infections (LRTI) resulted in a reduction in inappropriate antibiotic use and associated adverse events. All patients in a teaching hospital in Scotland who received antibiotic treatment for a LRTI over a 1 year period were included in the study. The researchers recorded mode and duration of antibiotic use in the first part of the study. In the second part, an antibiotic protocol was introduced that incorporated automatic stop dates, duration of treatment guided by severity (5 days for low severity, 7 days for high severity), and pharmacist feedback. Introduction of the new protocol led to a significant reduction in the duration of antibiotic treatment (p<0·001). Consequently, a significant reduction in adverse events was also observed (p<0·0001). The new antibiotic protocol did not have any effect on mortality rate. The study authors conclude that this new antibiotic protocol could reduce inappropriate use of antibiotics, thus reducing adverse events and possibly antibiotic resistance.
Drug resistance in tuberculosis The aim of the Global Consortium for Drug-Resistant TB Diagnostics is to reduce the time needed for drug susceptibility testing and to identify a genetic basis of drug-resistant strains of tuberculosis in areas with high disease burden. Antonino Catanzaro (University
of California San Diego, CA, USA) presented preliminary data from more than 1000 patients from three sites— Mumbai (India), Chisinau (Moldova), and Port Elizabeth (South Africa). The aim of the study was to develop rapid drug resistance detection technologies to reduce the current time to diagnosis of extremely drug-resistant tuberculosis (XDR-TB). Eligibility criteria for the study included active tuberculosis infection, high risk for drug resistance, and ability to produce more than 5 mL of sputum. Drug resistance to isoniazid, rifampicin, moxifloxacin, ofloxacin, amikacin, capreomycin, and kanamycin was assessed in all samples. The researchers identified three tests—microscopic observation of drug susceptibility assay, Hain line probe multidrug-resistance test, and pyrosequencing—as the most promising for rapid identification of drug-resistant tuberculosis.
For more on the Global Consortium for Drug-Resistant TB Diagnostics see http://gcdd. ucsd.edu/
Aclidinium for treatment of COPD Aclidinium bromide significantly improves symptoms of chronic obstructive pulmonary disease (COPD) compared with placebo, according to the results of a phase 3b trial (NCT01462929). 414 patients with COPD were randomly assigned to receive aclinidium (400 μg twice a day), tiotropium (18 μg once a day), or placebo for 6 weeks. The study authors reported a significant improvement in EXACT-respiratory symptoms (E-RS) score in the aclinidium group compared with both the placebo and tiotropium groups. Severity of early morning symptoms was also significantly improved in the aclinidium group compared with placebo and tiotropium. Aclidinium resulted in significant bronchodilation in the first 24 h of treatment compared with placebo or tiotropium, although aclidinium and tiotropium had similar efficacy at the end of the 6 week study period. Additionally, patients preferred aclidinium to tiotropium.
Rebecca Akkermans 595