Simon Bourne

British Thoracic Society guidelines for home oxygen use in adults

The British Thoracic Society (BTS) Home Oxygen Guideline provides detailed evidence-based guidance for the use of home oxygen for patients out of hospital. Although the majority of evidence comes from the use of oxygen in patients with chronic obstructive pulmonary disease, the scope of the guidance includes patients with a variety of long-term respiratory illnesses and other groups in whom oxygen is currently ordered, such as those with cardiac failure, cancer and end-stage cardiorespiratory disease, terminal illness or cluster headache. It explores the evidence base for the use of different modalities of oxygen therapy and patient-related outcomes such as mortality, symptoms and quality of life. The guideline also makes recommendations for assessment and follow-up protocols, and risk assessments, particularly in the clinically challenging area of home oxygen users who smoke. The guideline development group is aware of the potential for confusion sometimes caused by the current nomenclature for different types of home oxygen, and rather than renaming them, has adopted the approach of clarifying those definitions, and in particular emphasising what is meant by long-term oxygen therapy and palliative oxygen therapy. The home oxygen guideline provides expert consensus opinion in areas where clinical evidence is lacking, and seeks to deliver improved prescribing practice, leading to improved compliance and improved patient outcomes, with consequent increased value to the health service.

Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD

Background Matrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and drive tissue remodelling, key processes in the pathogenesis of COPD. The development of small airway disease has been identified as a critical mechanism in the early development of airflow obstruction but the contribution of MMPs in human disease is poorly characterised. Objectives We investigated the role of MMPs and inflammatory cytokines in the lung by quantifying levels and determining relationships with the key pathological components of COPD in patients and healthy controls. Methods We analysed levels of MMPs and inflammatory cytokines in bronchoalveolar lavage from 24 COPD and 8 control subjects. Each subject underwent spirometry and high-resolution CT. Image analysis quantitatively assessed emphysema, bronchial wall thickening and small airways disease. Results Multiple MMPs (MMP-1, -2, -3, -8, -9 and -10) and cytokines (interleukin (IL) 6 and IL-8) were elevated in lungs of subjects with COPD. MMP-3, -7, -8, -9, -10 and -12 concentrations closely associated with CT markers of small airways disease. Emphysema severity was also associated with MMP-3, -7 and -10. However, there were no strong relationships between MMPs and bronchial wall thickness of the larger airways. Conclusions Pulmonary MMP concentrations are directly associated with the extent of gas trapping and small airways disease identified on CT scan. This study suggests that MMPs play a significant role in small airways remodelling, a key feature in the pathogenesis of COPD. Trial registration number NCT01701869

A prospective, observational cohort study of the seasonal dynamics of airway pathogens in the aetiology of exacerbations in COPD

Background The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood. Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events. Methods In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40–85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses. Results are presented for subjects in the full cohort, followed for 1 year. Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses. Findings The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50). At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus. Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)). When NTHi was detected, the increased risk of exacerbation was greater in high season (October–March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)). Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%). A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031). Conclusions AECOPD aetiology varies with season. Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection. Trial registration number Results, NCT01360398.

Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort

Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) predicts response to treatment, especially corticosteroids. We studied the nature of eosinophilic inflammation in COPD prospectively to examine the stability of this phenotype and its dynamics across exacerbations, and its associations with clinical phenotype, exacerbations and infection. 127 patients aged 40–85 years with moderate to very severe COPD underwent repeated blood and sputum sampling at stable visits and within 72 h of exacerbation for 1 year. Blood eosinophils ≥2% was prevalent at baseline, and predicted both predominantly raised stable-state eosinophils across the year (area under the curve 0.841, 95% CI 0.755–0.928) and increased risk of eosinophilic inflammation at exacerbation (OR 9.16; p<0.001). Eosinophils ≥2% at exacerbation and eosinophil predominance at stable visits were associated with a lower risk of bacterial presence at exacerbation (OR 0.49; p=0.049 and OR 0.25; p=0.065, respectively). Bacterial infection at exacerbation was highly seasonal (winter versus summer OR 4.74; p=0.011) in predominantly eosinophilic patients. Eosinophilic inflammation is a common and stable phenotype in COPD. Blood eosinophil counts in the stable state can predict the nature of inflammation at future exacerbations, which when combined with an understanding of seasonal variation provides the basis for the development of new treatment paradigms for this important condition. Blood eosinophil levels in COPD predict the nature of inflammation at future exacerbations and may guide therapy http://ow.ly/W10o30dNQiq

Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases.

BackgroundEmphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology. Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema. However, the relationship between MMPs and emphysema sub-type is unknown. We investigated the role of MMPs and their inhibitors in the development of emphysema sub-types by quantifying levels and determining relationships with these sub-types in mild-moderate COPD patients and ex/current smokers with preserved lung function. MethodsTwenty-four mild-moderate COPD and 8 ex/current smokers with preserved lung function underwent high resolution CT and distinct emphysema sub-types were quantified using novel local histogram-based assessment of lung density. We analysed levels of MMPs and tissue inhibitors of MMPs (TIMPs) in bronchoalveolar lavage (BAL) and assessed their relationship with these emphysema sub-types.ResultsThe most prevalent emphysema subtypes in COPD subjects were mild and moderate centrilobular (CLE) emphysema, while only small amounts of severe centrilobular emphysema, paraseptal emphysema (PSE) and panlobular emphysema (PLE) were present. MMP-3, and -10 associated with all emphysema sub-types other than mild CLE, while MMP-7 and -8 had associations with moderate and severe CLE and PSE. MMP-9 also had associations with moderate CLE and paraseptal emphysema. Mild CLE occurred in substantial quantities irrespective of whether airflow obstruction was present and did not show any associations with MMPs.ConclusionMultiple MMPs are directly associated with emphysema sub-types identified by CT imaging, apart from mild CLE. This suggests that MMPs play a significant role in the tissue destruction seen in the more severe sub-types of emphysema, whereas early emphysematous change may be driven by a different mechanism.Trial registrationTrial registration number NCT01701869.

Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study

Introduction The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) remains incompletely understood and strategies for treatment and prevention have not altered significantly for many years. Improved understanding of the role of respiratory pathogens in acute exacerbations of COPD (AECOPD) is required and the use of molecular microbiological techniques may lead to insights into host–pathogen interactions and the development of more targeted therapeutic approaches. Methods and analyses Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) is a longitudinal epidemiological study to assess how changes in the COPD airway microbiome contribute to the incidence and severity of AECOPD. Patients with COPD aged 40–85 are followed monthly for 2 years, and reviewed within 72 h of onset of symptoms of AECOPD. Exacerbations are detected using daily electronic diary cards. Blood, sputum, nasopharyngeal and urine samples are collected at prespecified timepoints. Molecular diagnostic and typing techniques are used to describe the dynamics of airway infection during AECOPD and stable disease, and associations with clinical outcome. This study aims to refine the case definition of AECOPD to reflect the possible microbiological aetiology. AERIS will assess the impact of AECOPD on health-related quality of life and healthcare resource utilisation, and the possible interactions between nutritional status, infection and immune responses. Ethics and dissemination AERIS is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice, and has been approved by the institutional ethics and review board. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. Discussion Few other studies have addressed the complexity of the microbiological and systemic components of COPD or employed real-time electronic tracking of symptoms to identify AECOPD and potential aetiological triggers. Results Results of AERIS will increase our understanding of the contribution of pathogens to AECOPD, potentially leading to new targeted therapeutic and preventative interventions. Trial registration number ClinicalTrials.gov NCT01360398.

The Management of Acute Diarrhoea in a Healthy Adult Population Deploying on Military Operations

Acute diarrhoea is consistently the number one presentation to secondary care facilities on UK military operational deployments. It can result in potentially life threatening consequences as seen on Operation Herrick in 2002, where a Norwalk-like virus caused 3 cases of meningo-encephalitis. Due to the circumstances of communal accommodation, ablutions and dining facilities, even mild cases are admitted at role 2, and personnel are not discharged until fully recovered in order to prevent potential outbreaks. This literature review examines the management of acute diarrhoea in healthy adults relating to UK military operations, and presents a management algorithm suitable for any theatre. The importance of the initial assessment is highlighted and allows the severity of the condition to be assessed using three key parameters. We recommend the selective use of stool culturing for severe cases and outbreaks. The use of oral re-hydration solutions vs. intravenous fluids, and the indication for the safe use of anti motility agents and antibiotics for diarrhoea are discussed. Where pathogens are yielded local sensitivities should guide the choice of treatment. Salmonella spp and Shiga toxinproducing E.coli (STEC) should receive supportive care only.

Reducing hospital admissions and improving the diagnosis of COPD in Southampton City: methods and results of a 12-month service improvement project

Background:The British Lung Foundation highlighted Southampton City as a hotspot for patients at future risk of chronic obstructive pulmonary disease (COPD) exacerbations due to severe deprivation levels and a high undiagnosed level of disease based on health economic modelling. We developed a strategy spanning primary and secondary care to reduce emergency admissions of patients with acute exacerbations of COPD and increase the diagnosed prevalence of COPD on general practitioner (GP) registers closer to that predicted from local modelling.Methods:A comprehensive 3-year audit of admissions was performed. Patients who had been admitted with an exacerbation to University Hospital Southampton three or more times in the previous 12 months were cohorted and cared for in a consultant-led, but community based, COPD service. Within primary care, a programme of education and case-based finding was delivered to most practices within the city.Results:Thirty-four patients were found to be responsible for 176 admissions (22% of total COPD admissions) to the hospital. These 34 patients required 185 active interventions during the 12-month period but only 39 hospital admissions. The 30-day readmission rate dropped from 13.4 to 1.9% (P<0.01), confirming the contribution the cohort made to readmissions. Prior to the project, the registered Quality Outcomes Framework prevalence of COPD within the city was 1.5; after just 1 year of the project, the prevalence increased from 1.5 to 2.27%.Conclusions:The use of medical intelligence to investigate the underlying processes of COPD hospital admissions led to an effective intervention delivered in a consultant-led model.

Relationship of CT-quantified emphysema, small airways disease and bronchial wall dimensions with physiological, inflammatory and infective measures in COPD

BackgroundCOPD is a complex, heterogeneous disease characterised by progressive development of airflow limitation. Spirometry provides little information about key aspects of pathology and is poorly related to clinical outcome, so other tools are required to investigate the disease. We sought to explore the relationships between quantitative CT analysis with functional, inflammatory and infective assessments of disease to identify the utility of imaging to stratify disease to better predict outcomes and disease response.MethodsPatients from the AERIS study with moderate-very severe COPD underwent HRCT, with image analysis determining the quantity of emphysema (%LAA<− 950), small airways disease (E/I MLD) and bronchial wall thickening (Pi10). At enrolment subjects underwent lung function testing, six-minute walk testing (6MWT), blood sampling for inflammatory markers and sputum sampling for white cell differential and microbiological culture and PCR.Results122 subjects were included in this analysis. Emphysema and small airways disease had independent associations with airflow obstruction (β = − 0.34, p < 0.001 and β = − 0.56, p < 0.001). %LAA<− 950 had independent associations with gas transfer (β = − 0.37, p < 0.001) and E/I MLD with RV/TLC (β = 0.30, p =0.003). The distance walked during the 6MWT was not associated with CT parameters, but exertional desaturation was independently associated with emphysema (β = 0.73, p < 0.001). Pi10 did not show any independent associations with lung function or functional parameters.No CT parameters had any associations with sputum inflammatory cells. Greater emphysema was associated with lower levels of systemic inflammation (CRP β = − 0.34, p < 0.001 and fibrinogen β = − 0.28, p =0.003). There was no significant difference in any of the CT parameters between subjects where potentially pathogenic bacteria were detected in sputum and those where it was not.ConclusionsThis study provides further validation for the use of quantitative CT measures of emphysema and small airways disease in COPD as they showed strong associations with pulmonary physiology and functional status. In contrast to this quantitative CT measures showed few convincing associations with biological measures of disease, suggesting it is not an effective tool at measuring disease activity.

S37 The persistence of eosinophilic inflammation in copd over time – aeris cohort

Introduction The importance of eosinophilic inflammation in COPD is in its ability to predict an enhanced response to treatment, such as corticosteroids. However, little is know about the persistence of higher eosinophils, or its associations with infectious aetiology during clinical stability and exacerbation. We investigated the natural history of eosinophilic inflammation over time and studied eosinophil-associated acute exacerbations of COPD and the impact of seasonality in a cohort of COPD patients. Methods 127 subjects with moderate to very severe COPD were enrolled into the AERIS cohort (NCT01360398) and were reviewed monthly for scheduled visits and during exacerbations. Blood sampling was performed quarterly and at exacerbations. Higher blood eosinophils (BE) were defined as ≥2%. Based on frequency of higher BE over the study, subjects were divided into predominantly (PE), intermittent (IE) and rarely eosinophilic (RE) groups. Results Blood eosinophil levels ≥2% were prevalent at baseline (68.3%) and at exacerbations (51.1%). Over the study 57.6% of subjects had predominantly, 16.16% intermittently and 26.26% rarely ≥2% blood eosinophils. Higher BE at enrolment was strongly associated with a predominantly high BE profile for the year (AUC 0.841 p < 0.001) and with greater odds of ≥2% eosinophils at exacerbation (OR 9.60 p < 0.001). The odds of ≥2% BE at exacerbation were higher in the PE group compared to the rarely group (OR 12.00, p < 0.001). A larger proportion of exacerbations were eosinophilic in the Summer than Winter (OR 2.57, p = 0.001). The odds of bacterial presence at exacerbation was higher in Winter than Summer among those in the PE group (OR 4.74, CI: 1.43; 15.71, p = 0.011), but not among those in the RE group (OR 1.15, CI: 0.29; 4.56, p = 0.838). Conclusion Our data suggests that it is possible to stratify COPD patients by stable state blood eosinophil levels. This measure is easily accessible and provides important insights into the longitudinal inflammatory phenotype of COPD. Persistent higher blood eosinophil levels were associated with risk of bacterial infection at exacerbation, and seasonality of exacerbation. Intervention studies are required to establish clear treatment algorithms utilising this measure to stratify therapy.