Showing papers in "Thorax in 2006"
TL;DR: The recommendation that COPD patients be encouraged to maintain or increase their levels of regular physical activity should be considered in future COPD guidelines, since it is likely to result in a relevant public health benefit.
Abstract: Background: Information about the influence of regular physical activity on the course of chronic obstructive pulmonary disease (COPD) is scarce. A study was undertaken to examine the association between regular physical activity and both hospital admissions for COPD and all-cause and specific mortality in COPD subjects.
Methods: From a population-based sample recruited in Copenhagen in 1981–3 and 1991–4, 2386 individuals with COPD (according to lung function tests) were identified and followed until 2000. Self-reported regular physical activity at baseline was classified into four categories (very low, low, moderate, and high). Dates and causes of hospital admissions and mortality were obtained from Danish registers. Adjusted associations between physical activity and hospital admissions for COPD and mortality were obtained using negative binomial and Cox regression models, respectively.
Results: After adjustment for relevant confounders, subjects reporting low, moderate or high physical activity had a lower risk of hospital admission for COPD during the follow up period than those who reported very low physical activity (incidence rate ratio 0.72, 95% confidence interval (CI) 0.53 to 0.97). Low, moderate and high levels of regular physical activity were associated with an adjusted lower risk of all-cause mortality (hazard ratio (HR) 0.76, 95% CI 0.65 to 0.90) and respiratory mortality (HR 0.70, 95% CI 0.48 to 1.02). No effect modification was found for sex, age group, COPD severity, or a background of ischaemic heart disease.
Conclusions: Subjects with COPD who perform some level of regular physical activity have a lower risk of both COPD admissions and mortality. The recommendation that COPD patients be encouraged to maintain or increase their levels of regular physical activity should be considered in future COPD guidelines, since it is likely to result in a relevant public health benefit.
1,002 citations
TL;DR: The absolute risk of developing COPD among continuous smokers is at least 25%, which is larger than was previously estimated.
Abstract: Background: Smokers are more prone to develop chronic obstructive pulmonary disease (COPD) than non-smokers, but this finding comes from studies spanning 10 years or less. The aim of this study was to determine the 25 year absolute risk of developing COPD in men and women from the general population. Methods: As part of the Copenhagen City Heart Study, 8045 men and women aged 30–60 years with normal lung function at baseline were followed for 25 years. Lung function measurements were collected and mortality from COPD during the 25 year observation period was analysed. Results: The percentage of men with normal lung function ranged from 96% of never smokers to 59% of continuous smokers; for women the proportions were 91% and 69%, respectively. The 25 year incidence of moderate and severe COPD was 20.7% and 3.6%, respectively, with no apparent difference between men and women. Smoking cessation, especially early in the follow up period, decreased the risk of developing COPD substantially compared with continuous smoking. During the follow up period there were 2912 deaths, 109 of which were from COPD. 92% of the COPD deaths occurred in subjects who were current smokers at the beginning of the follow up period. Conclusion: The absolute risk of developing COPD among continuous smokers is at least 25%, which is larger than was previously estimated.
591 citations
TL;DR: In this paper, the authors used real-time endobronchial ultrasound (EBUS) guidance to increase the ability to sample mediastinal lymph nodes and hence to determine a diagnosis.
Abstract: Background: Transbronchial needle aspiration (TBNA) is an established method for sampling mediastinal lymph nodes to aid in diagnosing lymphadenopathy and in staging lung cancers. Real-time endobronchial ultrasound (EBUS) guidance is a new method of TBNA that may increase the ability to sample these nodes and hence to determine a diagnosis. A descriptive study was conducted to test this new method.
Methods: Consecutive patients referred for TBNA of mediastinal lymph nodes were included in the trial. When a node was detected, a puncture was performed under real-time ultrasound control. The primary end point was the number of successful biopsy specimens. Diagnostic results from the biopsies were compared with operative findings. Lymph node stations were classified according to the recently adopted American Thoracic Society scheme.
Results: From 502 patients (316 men) of mean age 59 years (range 24–82), 572 lymph nodes were punctured and 535 (94%) resulted in a diagnosis. Biopsy specimens were taken from lymph nodes in region 2L (40 nodes), 2R (53 nodes), 3 (35 nodes), 4R (86 nodes), 4L (77 nodes), 7 (127 nodes), 10R (38 nodes), 10L (43 nodes), 11R (40 nodes) and 11L (33 nodes). The mean (SD) diameter of the nodes was 1.6 (0.36) cm and the range was 0.8–3.2 cm (SD range 0.8–4.3). Sensitivity was 94%, specificity 100%, and the positive predictive value was 100% calculated per patient. No complications occurred.
Conclusion: EBUS-TBNA is a promising new method for sampling mediastinal lymph nodes. It appears to permit more and smaller nodes to be sampled than conventional TBNA, and it is safe.
542 citations
TL;DR: The incidence of Idiopathic pulmonary fibrosis has more than doubled between 1990 and 2003; this is not due to the ageing of the UK population or an increased ascertainment of milder cases.
Abstract: Background: Idiopathic pulmonary fibrosis (IPF) and sarcoidosis are common diagnoses in patients attending chest clinics, but little is known about the epidemiology of these diseases. We used data from a general practice database to provide information on the current incidence of IPF and sarcoidosis in the UK. Methods: Data were extracted for all patients with a diagnosis of IPF or sarcoidosis between 1991 and 2003. The whole population of the database was used to calculate disease incidence stratified by age, sex, region, and time period. Poisson regression was used to compare the incidence between populations and Cox regression was used to compare survival between populations. Results: 920 cases of IPF (mean age 71 years, 62% male) and 1019 cases of sarcoidosis (mean age 47 years, 47% male) were identified. The overall incidence rate per 100 000 person-years was 4.6 for IPF and 5.0 for sarcoidosis. The incidence of IPF increased progressively between 1991 and 2003 (p Conclusions: The incidence of IPF has more than doubled between 1990 and 2003; this is not due to the ageing of the UK population or an increased ascertainment of milder cases. The incidence of sarcoidosis has not changed during this time period. Our findings suggest that more than 4000 new cases of IPF and 3000 new cases of sarcoidosis are currently diagnosed each year in the UK.
525 citations
TL;DR: The British Thoracic Society Standards of Care Committee agreed to the development of a Working Group tasked with the job of producing a set of guidelines for the management of cough with the following key objectives.
Abstract: ### 1.1 Background
Patients with cough frequently present to clinicians working in both primary and secondary care.1,2 Acute cough, which often follows an upper respiratory tract infection, may be initially disruptive but is usually self-limiting and rarely needs significant medical intervention. Chronic cough is often the key symptom of many important chronic respiratory diseases but may be the sole presenting feature of a number of extrapulmonary conditions, in particular upper airway and gastrointestinal disease. Even with a clear diagnosis, cough can be difficult to control and, for the patient, can be associated with impaired quality of life.3,4 Sessions dedicated to cough at respiratory meetings are popular, suggesting that the pathophysiology, evaluation, and successful treatment of cough remain topics of keen interest to many medical practitioners.
### 1.2 Need and purpose of BTS recommendations on the management of cough
The American College of Chest Physicians (ACCP) and the European Respiratory Society (ERS)5,6 have each endorsed their own set of guidelines on the management of cough; however, criticism7 of their content and breadth suggest the need for further concise recommendations. The British Thoracic Society guidelines cover not only chronic cough but also acute cough and the organisational issues of cough clinics. International differences in delivery of respiratory health care and management strategies support the notion that such guidelines would be desirable. The British Thoracic Society Standards of Care Committee agreed to the development of a Working Group tasked with the job of producing a set of guidelines for the management of cough with the following key objectives:
492 citations
TL;DR: The use of exhaled nitric oxide measurements (FEno) in clinical practice is now coming of age as mentioned in this paper, and there are a number of theoretical and practical factors which have brought this about.
Abstract: The use of exhaled nitric oxide measurements (FEno) in clinical practice is now coming of age. There are a number of theoretical and practical factors which have brought this about. Firstly, FEno is a good surrogate marker for eosinophilic airway inflammation. High FEno levels may be used to distinguish eosinophilic from non-eosinophilic pathologies. This information complements conventional pulmonary function testing in the assessment of patients with non-specific respiratory symptoms. Secondly, eosinophilic airway inflammation is steroid responsive. There are now sufficient data to justify the claim that FEno measurements may be used successfully to identify and monitor steroid response as well as steroid requirements in the diagnosis and management of airways disease. FEno measurements are also helpful in identifying patients who do/do not require ongoing treatment with inhaled steroids. Thirdly, portable nitric oxide analysers are now available, making routine testing a practical possibility. However, a number of issues still need to be resolved, including the diagnostic role of FEno in preschool children and the use of reference values versus individual FEno profiles in managing patients with difficult or severe asthma.
472 citations
TL;DR: Natural virus infection and real life allergen exposure in allergic asthmatic children increase the risk of hospital admission.
Abstract: Background: Asthma exacerbation is the most common cause of hospital admission in children. A study was undertaken to investigate the importance of allergen exposure in sensitised individuals in combination with viral infections and other potentially modifiable risk factors precipitating asthma hospital admission in children. Methods: Eighty four children aged 3–17 years admitted to hospital over a 1 year period with an acute asthma exacerbation (AA) were matched for age and sex with two control groups: stable asthmatics (SA) and children admitted to hospital with non-respiratory conditions (IC). Risk factors were assessed by questionnaires and determination of allergen sensitisation, home allergen exposure, pollen exposure, and respiratory virus infection. Results: Several non-modifiable factors (atopy, duration of asthma) were associated with increased risk. Among the modifiable factors, pet ownership, housing characteristics, and parental smoking did not differ between the groups. Regular inhaled corticosteroid treatment was significantly less common in the AA group than in the SA group (OR 0.2, 95% CI 0.1 to 0.6; p = 0.002). A significantly higher proportion of the AA group were virus infected (44%) and sensitised and highly exposed to sensitising allergen (76%) compared with the SA (18% and 48%) and IC groups (17% and 28%; both p v SA), allergen sensitisation and exposure or virus detection alone were no longer independently associated with hospital admission. However, the combination of virus detection and sensitisation with high allergen exposure substantially increased the risk of admission to hospital (OR 19.4, 95% CI 3.7 to 101.5, p Conclusions: Natural virus infection and real life allergen exposure in allergic asthmatic children increase the risk of hospital admission. Strategies for preventing exacerbations will need to address these factors.
465 citations
TL;DR: There are now sufficient data to justify the claim that FEno measurements may be used successfully to identify and monitor steroid response as well as steroid requirements in the diagnosis and management of airways disease.
Abstract: The use of exhaled nitric oxide measurements (FEno) in clinical practice is now coming of age. There are a number of theoretical and practical factors which have brought this about. Firstly, FEno is a good surrogate marker for eosinophilic airway inflammation. High FEno levels may be used to distinguish eosinophilic from non‐eosinophilic pathologies. This information complements conventional pulmonary function testing in the assessment of patients with non‐specific respiratory symptoms. Secondly, eosinophilic airway inflammation is steroid responsive. There are now sufficient data to justify the claim that FEno measurements may be used successfully to identify and monitor steroid response as well as steroid requirements in the diagnosis and management of airways disease. FEno measurements are also helpful in identifying patients who do/do not require ongoing treatment with inhaled steroids. Thirdly, portable nitric oxide analysers are now available, making routine testing a practical possibility. However, a number of issues still need to be resolved, including the diagnostic role of FEno in preschool children and the use of reference values versus individual FEno profiles in managing patients with difficult or severe asthma.
462 citations
TL;DR: Previous treatment was the strongest determinant of MDR-TB in Europe, and the risk of MDA in foreign born people needs to be re-evaluated, taking into account any previous treatment.
Abstract: Background: The resurgence of tuberculosis (TB) in western countries has been attributed to the HIV epidemic, immigration, and drug resistance. Multidrug resistant tuberculosis (MDR-TB) is caused by the transmission of multidrug resistant Mycobacterium tuberculosis strains in new cases, or by the selection of single drug resistant strains induced by previous treatment. The aim of this report is to determine risk factors for MDR-TB in Europe. Methods: A systematic review was conducted of published reports of risk factors associated with MDR-TB in Europe. Meta-analysis, meta-regression, and sub-grouping were used to pool risk estimates of MDR-TB and to analyse associations with age, sex, immigrant status, HIV status, occurrence year, study design, and area of Europe. Results: Twenty nine papers were eligible for the review from 123 identified in the search. The pooled risk of MDR-TB was 10.23 times higher in previously treated than in never treated cases, with wide heterogeneity between studies. Study design and geographical area were associated with MDR-TB risk estimates in previously treated patients; the risk estimates were higher in cohort studies carried out in western Europe (RR 12.63; 95% CI 8.20 to 19.45) than in eastern Europe (RR 8.53; 95% CI 6.57 to 11.06). National estimates were possible for six countries. MDR-TB cases were more likely to be foreign born (odds ratio (OR) 2.46; 95% CI 1.86 to 3.24), younger than 65 years (OR 2.53; 95% CI 1.74 to 4.83), male (OR 1.38; 95% CI 1.16 to 1.65), and HIV positive (OR 3.52; 95% CI 2.48 to 5.01). Conclusions: Previous treatment was the strongest determinant of MDR-TB in Europe. Detailed study of the reasons for inadequate treatment could improve control strategies. The risk of MDR-TB in foreign born people needs to be re-evaluated, taking into account any previous treatment.
444 citations
TL;DR: How an exacerbation should be defined, its inflammatory basis, and the importance of exacerbations on disease progression are reviewed, and important aetiologies, with their potential underlying mechanisms, are discussed.
Abstract: Exacerbations of COPD are thought to be caused by complex interactions between the host, bacteria, viruses, and environmental pollution. These factors increase the inflammatory burden in the lower airways, overwhelming the protective anti-inflammatory defences leading to tissue damage. Frequent exacerbations are associated with increased morbidity and mortality, a faster decline in lung function, and poorer health status, so prevention or optimal treatment of exacerbations is a global priority. In order to evolve new treatment strategies there has been great interest in the aetiology and pathophysiology of exacerbations, but progress has been hindered by the heterogeneous nature of these episodes, vague definitions of an exacerbation, and poor stratification of known confounding factors when interpreting results. We review how an exacerbation should be defined, its inflammatory basis, and the importance of exacerbations on disease progression. Important aetiologies, with their potential underlying mechanisms, are discussed and the significance of each aetiology is considered.
405 citations
TL;DR: It is possible to reduce the morbidity of asthma and its impact on individuals as well as on society and improvements would have taken place without the programme, but not of this magnitude.
Abstract: Background: A National Asthma Programme was undertaken in Finland from 1994 to 2004 to improve asthma care and prevent an increase in costs. The main goal was to lessen the burden of asthma to individuals and society. Methods: The action programme focused on implementation of new knowledge, especially for primary care. The main premise underpinning the campaign was that asthma is an inflammatory disease and requires anti-inflammatory treatment from the outset. The key for implementation was an effective network of asthma-responsible professionals and development of a post hoc evaluation strategy. In 1997 Finnish pharmacies were included in the Pharmacy Programme and in 2002 a Childhood Asthma mini-Programme was launched. Results: The incidence of asthma is still increasing, but the burden of asthma has decreased considerably. The number of hospital days has fallen by 54% from 110 000 in 1993 to 51 000 in 2003, 69% in relation to the number of asthmatics (n = 135 363 and 207 757, respectively), with the trend still downwards. In 1993, 7212 patients of working age (9% of 80 133 asthmatics) received a disability pension from the Social Insurance Institution compared with 1741 in 2003 (1.5% of 116 067 asthmatics). The absolute decrease was 76%, and 83% in relation to the number of asthmatics. The increase in the cost of asthma (compensation for disability, drugs, hospital care, and outpatient doctor visits) ended: in 1993 the costs were €218 million which had fallen to €213.5 million in 2003. Costs per patient per year have decreased 36% (from €1611 to €1031). Conclusion: It is possible to reduce the morbidity of asthma and its impact on individuals as well as on society. Improvements would have taken place without the programme, but not of this magnitude.
TL;DR: CRP measurements provide incremental prognostic information beyond that achieved by traditional markers of prognosis in patients with mild to moderate COPD, and may enable more accurate detection of patients at a high risk of mortality.
Abstract: Background: Although C-reactive protein (CRP) levels are increased in chronic obstructive pulmonary disease (COPD), it is not certain whether they are associated with adverse clinical outcomes. Methods: Serum CRP levels were measured in 4803 participants in the Lung Health Study with mild to moderate COPD. The risk of all-cause and disease specific causes of mortality was determined as well as cardiovascular event rates, adjusting for important covariates such as age, sex, cigarette smoking, and lung function. Cardiovascular events were defined as death from coronary heart disease or stroke, or non-fatal myocardial infarction or stroke requiring admission to hospital. Results: CRP levels were associated with all-cause, cardiovascular, and cancer specific causes of mortality. Individuals in the highest quintile of CRP had a relative risk (RR) for all-cause mortality of 1.79 (95% confidence interval (CI) 1.25 to 2.56) compared with those in the lowest quintile of CRP. For cardiovascular events and cancer deaths the corresponding RRs were 1.51 (95% CI 1.20 to 1.90) and 1.85 (95% CI 1.10 to 3.13), respectively. CRP levels were also associated with an accelerated decline in forced expiratory volume in 1 second (p Conclusions: CRP measurements provide incremental prognostic information beyond that achieved by traditional markers of prognosis in patients with mild to moderate COPD, and may enable more accurate detection of patients at a high risk of mortality.
TL;DR: The epidemiology of exacerbations of chronic obstructive pulmonary disease is reviewed with particular reference to the definition, frequency, time course, natural history and seasonality, and their relationship with decline in lung function, disease severity and mortality.
Abstract: The epidemiology of exacerbations of chronic obstructive pulmonary disease (COPD) is reviewed with particular reference to the definition, frequency, time course, natural history and seasonality, and their relationship with decline in lung function, disease severity and mortality. The importance of distinguishing between recurrent and relapsed exacerbations is discussed.
TL;DR: Increasing blood glucose concentrations are associated with adverse clinical outcomes in patients with AECOPD and the risk of adverse outcomes increased with increasing hyperglycaemia independent of age, sex, a previous diagnosis of diabetes, and COPD severity.
Abstract: Background: Hyperglycaemia is associated with poor outcomes from pneumonia, myocardial infarction and stroke, but the effect of blood glucose on outcomes from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has not been established. Recent UK guidelines do not comment on measurement or control of blood glucose in AECOPD. A study was therefore undertaken to determine the relationship between blood glucose concentrations, length of stay in hospital, and mortality in patients admitted with AECOPD.
Methods: Data were retrieved from electronic records for patients admitted with AECOPD with lower respiratory tract infection in 2001–2. The patients were grouped according to blood glucose quartile (group 1, 9.0 mmol/l (n = 71)).
Results: The relative risk (RR) of death or long inpatient stay was significantly increased in group 3 (RR 1.46, 95% CI 1.05 to 2.02, p = 0.02) and group 4 (RR 1.97, 95% CI 1.33 to 2.92, p<0.0001) compared with group 1. For each 1 mmol/l increase in blood glucose the absolute risk of adverse outcomes increased by 15% (95% CI 4 to 27), p = 0.006. The risk of adverse outcomes increased with increasing hyperglycaemia independent of age, sex, a previous diagnosis of diabetes, and COPD severity. Isolation of multiple pathogens and Staphylococcus aureus from sputum also increased with increasing blood glucose.
Conclusion: Increasing blood glucose concentrations are associated with adverse clinical outcomes in patients with AECOPD. Tight control of blood glucose reduces mortality in patients in intensive care or following myocardial infarction. A prospective study is now required to determine whether control of blood glucose can also improve outcomes from AECOPD.
TL;DR: OSA is highly prevalent in men with type 2 diabetes; most are undiagnosed and diabetes itself may be a significant independent contributor to the risk of OSA.
Abstract: BACKGROUND: A study was undertaken to establish the prevalence of obstructive sleep apnoea (OSA) in men with type 2 diabetes. METHODS: Men with type 2 diabetes from local hospital and selected primary care practitioner databases received questionnaires about snoring, apnoeas, and daytime sleepiness based on the Berlin questionnaire. Selected respondents had overnight oximetry to establish whether they had OSA. Comparisons of oximetry were made with those from a previous general population study. HbA1c results were collected. RESULTS: 1682 men were sent questionnaires, 56% of whom replied. 57% scored as "high" and 39% as "low" risk for OSA; 4% were already known to have OSA. Oximetry was performed in 240 respondents from both risk groups: 31% of the "high" and 13% of the "low" risk group had significant OSA (more than 10 >4% Sao(2) dips/hour or Sao(2) tracing consistent with OSA). These results were verified by detailed sleep studies. Extrapolation of the oximetry data to the questionnaire respondent population suggests that 23% had OSA. Comparison of the oximetry results with men from a previous general population study (using only more than 10 >4% Sao(2) dips/hour to define OSA) showed the prevalence of OSA is significantly higher in this diabetes population (17% v 6%, p<0.001). Multiple linear regression revealed BMI and diabetes as significant independent predictors of OSA. Following correction for BMI (which explained 13% of the variance in OSA), diabetes explained a further 8% of the variance (p<0.001). There was a low correlation between OSA severity and HbA1c in the subgroup recruited from the hospital database (r = 0.2, p = 0.006) which remained significant after allowing for obesity (p = 0.03). CONCLUSIONS: OSA is highly prevalent in men with type 2 diabetes; most are undiagnosed. Diabetes itself may be a significant independent contributor to the risk of OSA.
TL;DR: There is great heterogeneity in the clinical manifestations of cystic fibrosis (CF).
Abstract: There is great heterogeneity in the clinical manifestations of cystic fibrosis (CF). Some patients may have all the classical manifestations of CF from infancy and have a relatively poor prognosis, while others have much milder or even atypical disease manifestations and still carry mutations on each of the CFTR genes. It is important to distinguish between these categories of patients. The European Diagnostic Working Group proposes the following terminology. Patients are diagnosed with classic or typical CF if they have one or more phenotypic characteristics and a sweat chloride concentration of >60 mmol/l. The vast majority of CF patients fall into this category. Usually one established mutation causing CF can be identified on each CFTR gene. Patients with classic CF can have exocrine pancreatic insufficiency or pancreatic sufficiency. The disease can have a severe course with rapid progression of symptoms or a milder course with very little deterioration over time. Patients with non-classic or atypical CF have a CF phenotype in at least one organ system and a normal (<30 mmol/l) or borderline (30-60 mmol/l) sweat chloride level. In these patients confirmation of the diagnosis of CF requires detection of one disease causing mutation on each CFTR gene or direct quantification of CFTR dysfunction by nasal potential difference measurement. Non-classic CF includes patients with multiorgan or single organ involvement. Most of these patients have exocrine pancreatic sufficiency and milder lung disease. Algorithms for a structured diagnostic process are proposed.
TL;DR: COPD is common among adults in England and is predominantly undiagnosed, and in smokers it is associated with higher degrees of cigarette dependence but not with a greater motivation to stop smoking.
Abstract: Background: Chronic obstructive pulmonary disease ( COPD) is the fourth most common cause of death worldwide. It is caused primarily by cigarette smoking. Given its importance, it is remarkable that reliable national prevalence data are lacking for most countries. This study provides estimates of the national prevalence of COPD in England, the extent of under-detection of the disorder, and patterns of cigarette smoking, dependence, and motivation to stop smoking in those with the disease.Methods: Data from 8215 adults over the age of 35 who participated in the Health Survey for England were analysed. Information was obtained on self-reported and cotinine validated smoking status, cigarette dependence, motivation to stop smoking, COPD defined by spirometry using joint American Thoracic Society and European Respiratory Society criteria, and self-reports of diagnosis with respiratory disorders.Results: Spirometry-defined COPD was present in 13.3% (95% CI 12.6 to 14.0) of participants, over 80% of whom reported no respiratory diagnosis. Even among people with severe or very severe COPD by spirometric assessment, only 46.8% (95% CI 39.1 to 54.6) reported any diagnosed respiratory disease. A total of 34.9% (95% CI 32.1 to 37.8) of people with spirometry-defined COPD were smokers compared with 22.4% (95% CI 21.4 to 23.4) of those without, and smoking prevalence increased with disease severity. Smokers with spirometry-defined COPD were more cigarette dependent but had no greater desire to quit than other smokers.Conclusion: COPD is common among adults in England and is predominantly undiagnosed. In smokers it is associated with higher degrees of cigarette dependence but not with a greater motivation to stop smoking.
TL;DR: No significant associations between exacerbations during pregnancy and preterm delivery or pre-eclampsia were identified, and inhaled corticosteroid use may reduce the risk of exacerbation during pregnancy.
Abstract: Exacerbations of asthma during pregnancy represent a significant clinical problem and may be related to poor pregnancy outcomes. A systematic review of the literature was conducted for publications related to exacerbations during pregnancy. Four studies with a control group (no asthma) and two groups of women with asthma (exacerbation, no exacerbation) were included in meta-analyses using fixed effects models. During pregnancy, exacerbations of asthma which require medical intervention occur in about 20% of women, with approximately 6% of women being admitted to hospital. Exacerbations during pregnancy occur primarily in the late second trimester; the major triggers are viral infection and non-adherence to inhaled corticosteroid medication. Women who have a severe exacerbation during pregnancy are at a significantly increased risk of having a low birth weight baby compared with women without asthma. No significant associations between exacerbations during pregnancy and preterm delivery or pre-eclampsia were identified. Inhaled corticosteroid use may reduce the risk of exacerbations during pregnancy. Pregnant women may be less likely to receive oral steroids for the emergency management of asthma. The effective management and prevention of asthma exacerbations during pregnancy is important for the health of both the mother and fetus.
TL;DR: Further investigations are needed to marry the different clinical phenotypes of COPD to their respective inflammatory profiles in the airways and thus improve the understanding of the pathogenesis of the disease as a whole.
Abstract: Airway inflammation is central to the pathogenesis of both airway remodelling and parenchymal destruction in chronic obstructive pulmonary disease (COPD). Neutrophils, macrophages, and CD8+ T lymphocytes have been implicated in a number of studies, but a detailed profile of disease-phenotype specific inflammation has yet to emerge. The heterogeneity of the disease has hindered data interpretation while extrapolation of the results of relatively non-invasive studies to the actual pathology found in the distal lung is difficult. Moreover, prominent studies have had frequently conflicting results. Further investigations are needed to marry the different clinical phenotypes of COPD to their respective inflammatory profiles in the airways and thus improve our understanding of the pathogenesis of the disease as a whole.
TL;DR: Evidence from both clinical studies and animal models showing that stromal and inflammatory cell MMP expression leads to immunopathology is examined, and the mechanisms by which excess MMP activity may be targeted to improve clinical outcomes are discussed.
Abstract: Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that have a number of important physiological roles including remodelling of the extracellular matrix, facilitating cell migration, cleaving cytokines, and activating defensins. However, excess MMP activity may lead to tissue destruction. The biology of MMP and the role of these proteases in normal pulmonary immunity are reviewed, and evidence that implicates excess MMP activity in causing matrix breakdown in chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), sarcoidosis, and tuberculosis is discussed. Evidence from both clinical studies and animal models showing that stromal and inflammatory cell MMP expression leads to immunopathology is examined, and the mechanisms by which excess MMP activity may be targeted to improve clinical outcomes are discussed.
TL;DR: Up to 40% of children with severe RSV bronchiolitis requiring admission to the PICU were infected with bacteria in their lower airways and were at increased risk for bacterial pneumonia.
Abstract: Background: Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTI). Viral LRTI is a risk factor for bacterial superinfection, having an escalating incidence with increasing severity of respiratory illness. A study was undertaken to determine the incidence of pulmonary bacterial co-infection in infants and children with severe RSV bronchiolitis, using paediatric intensive care unit (PICU) admission as a surrogate marker of severity, and to study the impact of the co-infection on morbidity and mortality. Methods: A prospective microbiological analysis was made of lower airways secretions on all RSV positive bronchiolitis patients on admission to the PICU during three consecutive RSV seasons. Results: One hundred and sixty five children (median age 1.6 months, IQR 0.5–4.6) admitted to the PICU with RSV bronchiolitis were enrolled in the study. Seventy (42.4%) had lower airway secretions positive for bacteria: 36 (21.8%) were co-infected and 34 (20.6%) had low bacterial growth/possible co-infection. All were mechanically ventilated (median 5.0 days, IQR 3.0–7.3). Those with bacterial co-infection required ventilatory support for longer than those with only RSV (p Conclusions: Up to 40% of children with severe RSV bronchiolitis requiring admission to the PICU were infected with bacteria in their lower airways and were at increased risk for bacterial pneumonia.
TL;DR: Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression, even before infection with Pseudomonas aeruginosa.
Abstract: Background: Macrolides display immunomodulatory effects that may be beneficial in chronic inflammatory pulmonary diseases. The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis. Methods: A multicentre, randomised, double blind, placebo controlled trial was conducted from October 2001 to June 2003. The criteria for enrolment were age older than 6 years and forced expiratory volume in 1 second (FEV 1 ) of 40% or more. The active group received either 250 mg or 500 mg (body weight 1 . Results: Eighty two patients of mean (SD) age 11.0 (3.3) years and mean (SD) FEV 1 85 (22)% predicted were randomised: 40 in the azithromycin group and 42 in the placebo group. Nineteen patients were infected with Pseudomonas aeruginosa . The relative change in FEV 1 at month 12 did not differ significantly between the two groups. The number of pulmonary exacerbations (count ratio 0.50 (95% CI 0.32 to 0.79), p Conclusion: Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression, even before infection with Pseudomonas aeruginosa .
TL;DR: Tiotropium reduced COPD exacerbations and related hospitalisations, improved quality of life and symptoms, and may have slowed the decline in FEV1.
Abstract: Background: A systematic review was undertaken to evaluate the efficacy of tiotropium, a long acting anticholinergic drug, on clinical events, symptom scales, pulmonary function, and adverse events in stable chronic obstructive pulmonary disease (COPD).
Methods: A systematic search was made of the Cochrane trials database, MEDLINE, EMBASE, CINAHL, and a hand search of 20 respiratory journals. Missing data were obtained from authors and the manufacturer. Randomised controlled trials of ⩾12 weeks’ duration comparing tiotropium with placebo, ipratropium bromide, or long acting β2 agonists (LABA) were reviewed. Studies were pooled to yield odds ratios (OR) or weighted mean differences with 95% confidence intervals (CI).
Results: Nine trials (8002 patients) met the inclusion criteria. Tiotropium reduced the odds of a COPD exacerbation (OR 0.73; 95% CI 0.66 to 0.81) and related hospitalisation (OR 0.68; 95% CI 0.54 to 0.84) but not pulmonary (OR 0.50; 95% CI 0.19 to 1.29) or all-cause (OR 0.96; 95% CI 0.63 to 1.47) mortality compared with placebo and ipratropium. Reductions in exacerbations and hospitalisations compared with LABA were not statistically significant. Similar patterns were evident for quality of life and symptom scales. Tiotropium yielded greater increases in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline to 6–12 months than did placebo, ipratropium, and LABA. Decline in FEV1 over 1 year was 30 ml (95% CI 7 to 53) slower with tiotropium than with placebo and ipratropium (data were not available for LABA). Reports of dry mouth and urinary tract infections were increased with tiotropium.
Conclusions: Tiotropium reduced COPD exacerbations and related hospitalisations, improved quality of life and symptoms, and may have slowed the decline in FEV1. Long term trials are warranted to evaluate the effects of tiotropium on decline in FEV1 and to clarify its role compared with LABA.
TL;DR: The results of this large population based study support the hypothesis that leptin is associated with asthma in women and suggest that leptin contributes significantly to this association.
Abstract: Background: Leptin, a pro-inflammatory cytokine produced by adipose tissue, has previously been shown to be associated with asthma in children. We hypothesised that high serum leptin concentrations would also be associated with asthma in adults. Methods: The Third National Health and Nutrition Examination Survey is a cross sectional study that included fasting serum leptin concentrations and self-report of doctor diagnosed asthma. Data were analysed using multivariable logistic regression analysis. Results: Of 5876 participants, those with current asthma had a higher mean unadjusted leptin concentration than those who had never had asthma (geometric mean (SE) 9.2 (0.6) μg/l v 7.6 (0.2) μg/l; p = 0.02). After adjustment for triceps skinfold thickness and other covariates, the association between leptin and asthma appeared stronger in women than in men, and in premenopausal women than in postmenopausal women. Body mass index (BMI) was also associated with current asthma in women, but this association was not significantly affected by adjustment for leptin concentrations. Conclusions: The results of this large population based study support the hypothesis that leptin is associated with asthma in women. In addition, while BMI also is related to asthma in women, this study does not support the suggestion that leptin contributes significantly to this association.
TL;DR: MMP-12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP- 12 in the development of COPD in smokers.
Abstract: Background: Several matrix metalloproteinases (MMPs) are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). In mice, MMP-12 plays a crucial role in the development of cigarette smoke induced emphysema. A study was undertaken to investigate the role of MMP-12 in the development of COPD in human smokers. Methods: Induced sputum samples were collected from patients with stable COPD (n = 28), healthy smokers (n = 14), never smokers (n = 20), and former smokers (n = 14). MMP-12 protein levels in induced sputum were determined by ELISA and compared between the four study groups. MMP-12 enzymatic activity in induced sputum was evaluated by casein zymography and by cleaving of a fluorescence quenched substrate. Results: Median (IQR) MMP-12 levels were significantly higher in COPD patients than in healthy smokers, never smokers, and former smokers (17.5 (7.1–42.1) v 6.7 (3.9–10.4) v 4.2 (2.4–11.3) v 6.1 (4.5–7.6) ng/ml, p = 0.0002). MMP-12 enzymatic activity was significantly higher in patients with COPD than in controls (4.11 (1.4–8.0) v 0.14 (0.1–0.2) μg/μl, p = 0.0002). Conclusion: MMP-12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP-12 in the development of COPD in smokers.
TL;DR: Epidemiologically, the degree of asthma control achieved by asthmatics is an important predictor of the likelihood of disease exacerbation including respiratory failure, death, and health service consumption.
Abstract: Asthma exacerbations may be triggered by a number of atmospheric and domiciliary environmental factors as well as by those encountered in schools and workplaces. The majority of exacerbations, particularly in children, coincide with respiratory viral infections, most commonly rhinovirus. As most respiratory viruses and many aeroallergens appear in seasonal patterns, asthma exacerbations, particularly those requiring emergency treatment, show analogous seasonal cycles which differ in form in children and adults. While similar in form between the sexes, they differ in amplitude, with boys having higher risks of exacerbation in childhood and women in adult life. Simultaneous exposure of asthmatics with respiratory viral infections to allergens or air pollutants may significantly increase the risks of exacerbation. Access to and compliance with inhaled corticosteroid treatment is an important predictor of the likelihood of asthma exacerbations occurring, including those that occur during respiratory viral infections. Epidemiologically, the degree of asthma control achieved by asthmatics is an important predictor of the likelihood of disease exacerbation including respiratory failure, death, and health service consumption.
TL;DR: Simple smoking cessation advice combined with spirometric testing resulted in good 1 year cessation rates, especially in subjects with airway obstruction, after correction for age, sex, nicotine dependence, number of cigarettes smoked daily, and lung function.
Abstract: Background: Chronic obstructive pulmonary disease (COPD), usually caused by tobacco smoking, is one of the leading causes of morbidity and mortality. Smoking cessation at an early stage of the disease usually stops further progression. A study was undertaken to determine if diagnosis of airway obstruction was associated with subsequent success in smoking cessation, as advised by a physician. Methods: 4494 current smokers (57.4% men) with a history of at least 10 pack-years of smoking were recruited from 100 000 subjects screened by spirometric testing for signs of airway obstruction. At the time of screening all received simple smoking cessation advice. 1177 (26.2%) subjects had airway obstruction and were told that they had COPD and that smoking cessation would halt rapid progression of their lung disease. No pharmacological treatment was proposed. After 1 year all subjects were invited for a follow up visit. Smoking status was assessed by history and validated by exhaled carbon monoxide level. Results: Nearly 70% attended a follow up visit (n = 3077): 61% were men, mean (SD) age was 52 (10) years, mean (SD) tobacco exposure 30 (17) pack-years, and 33.3% had airway obstruction during the baseline examination. The validated smoking cessation rate in those with airway obstruction was 16.3% compared with 12.0% in those with normal spirometric parameters (p = 0.0003). After correction for age, sex, nicotine dependence, number of cigarettes smoked daily, and lung function, success in smoking cessation was predicted by lower lung function, lower nicotine dependence, and lower tobacco exposure. Conclusions: Simple smoking cessation advice combined with spirometric testing resulted in good 1 year cessation rates, especially in subjects with airway obstruction.
TL;DR: Chronic cough is a common symptom in the general population and its strong association with gastrointestinal disease may have aetiological significance.
Abstract: Background: The prevalence and severity of chronic cough in the community is uncertain. In a large population of representative normal subjects, we explored the relationship between self-reported cough severity and frequency, and factors known to be related to the aetiology of chronic cough. In particular, we have examined the relative association between cough and symptoms of gastrointestinal disease. Methods: A cross-sectional survey was undertaken in 36 general practices with subjects randomly selected from practice computer databases. Baseline lifestyle and demographic characteristics were recorded. Participants were asked how often in the previous 2 months they had experienced bouts or spasms of coughing. Cough symptom status was dichotomised into symptomatic using a cut off of bouts or spasms of coughing at a frequency of between once a week and once a day or above. Gastrointestinal data were collected using validated methodology. Results: Questionnaires were sent to 6416 subjects and 4003 (62%) responded. The prevalence of chronic cough was 12%, and was severe in 7%. Following multivariate analysis, regurgitation (OR 1.71; 99% CI 1.20 to 2.45) and irritable bowel syndrome (OR 2.00; 99% CI 1.47 to 2.72) were strong predictors of cough. Smoking (OR 1.61; 99% CI 1.18 to 2.19), declining social class (OR 1.63; 99% CI 1.04 to 2.57), and quality of life at baseline (OR 1.63; 99% CI 1.13 to 2.35) were also significantly associated. Conclusion: Chronic cough is a common symptom in the general population. Its strong association with gastrointestinal disease may have aetiological significance.
TL;DR: The length of stay was reduced in units with more respiratory consultants, better organisation of care scores, an early discharge scheme, and local COPD management guidelines.
Abstract: Background: Acute chronic obstructive pulmonary disease (COPD) exacerbations use many hospital bed days and have a high rate of mortality. Previous audits have shown wide variability in the length of stay and mortality between units not explained by patient factors. This study aimed to explore associations between resources and organisation of care and patient outcomes. Methods: 234 UK acute hospitals each prospectively identified 40 consecutive acute COPD admissions, documenting process of care and outcomes from a retrospective case note audit. Units also completed a resources and organisation of care proforma. Results: Data for 7529 patients were received. Inpatient mortality was 7.4% and mortality at 90 days was 15.3%; the readmission rate was 31.4%. Mean length of stay for discharged patients was 8.7 days (median 6 days). Wide variation was observed in all outcomes between hospitals. Both inpatient mortality (odds ratio (OR) 0.67, CI 0.50 to 0.90) and 90 day mortality (OR 0.75, CI 0.60 to 0.94) were associated with a staff ratio of four or more respiratory consultants per 1000 hospital beds. The length of stay was reduced in units with more respiratory consultants, better organisation of care scores, an early discharge scheme, and local COPD management guidelines. Conclusions: Units with more respiratory consultants and better quality organised care have lower mortality and reduced length of hospital stay. This may reflect unit resource richness. Dissemination of good organisational practice and recruitment of more respiratory specialists offers the potential for improved outcomes for hospitalised COPD patients.
TL;DR: PPV is effective in preventing CAP in patients with COPD aged less than 65 years and in those with severe airflow obstruction, as well as in the subgroup aged <65 years.
Abstract: (COPD). Methods: A randomised controlled trial was carried out in 596 patients with COPD of mean (SD) age 65.8 (9.7) years, 298 of whom received PPV. The main outcome was radiographically proven community acquired pneumonia (CAP) of pneumococcal or unknown aetiology after a mean period of 979 days (range 20-1454). Results: There were 58 first episodes of CAP caused by pneumococcus or of unknown aetiology, 25 in the intervention group and 33 in the non-intervention group. Kaplan-Meier survival curves for CAP did not show significant differences between the intervention and non-intervention arms (log rank test = 1.15, p = 0.28) in the whole group of patients. The efficacy of PPV in all patients was 24% (95% CI 224 to 54; p = 0.333). In the subgroup aged ,65 years the efficacy of PPV was 76% (95% CI 20 to 93; p = 0.013), while in those with severe functional obstruction (forced expiratory volume in 1 second ,40%) it was 48% (95% CI 27 to 80; p = 0.076). In younger patients with severe airflow obstruction the efficacy was 91% (95% CI 35 to 99; p = 0.002). There were only five cases of non-bacteraemic pneumococcal CAP, all in the non-intervention group (log rank test = 5.03; p = 0.025). Multivariate analysis gave a hazard ratio for unknown and pneumococcal CAP in the vaccinated group, adjusted for age, of 0.20 (95% CI 0.06 to 0.68; p = 0.01). Conclusions: PPV is effective in preventing CAP in patients with COPD aged less than 65 years and in those with severe airflow obstruction. No differences were found among the other groups of patients with COPD.