R Wood-Baker

Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial

Objectives To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting. Design Cluster randomised controlled parallel group trial. Setting Ambulance service in Hobart, Tasmania, Australia. Participants 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years. Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting. Main outcome measure Prehospital or in-hospital mortality. Results In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97). Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm. Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04). Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure −33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen. Conclusions Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease. These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting. Trial registration Australian New Zealand Clinical Trials Register ACTRN12609000236291.

Monthly Ambient Sunlight, Infections and Relapse Rates in Multiple Sclerosis

Background: Monthly variation in multiple sclerosis (MS) relapses has been found. The relationship between seasonal environmental factors, infections, serum vitamin D [25(OH)D] and MS relapses is undetermined. Methods: We prospectively followed a population-based cohort of relapsing-remitting (RR) MS patients in Southern Tasmania for a mean 2.3 years (January 2002–April 2005). Associations between monthly ambient environmental factors, estimated serum 25(OH)D, upper respiratory tract (URT) infections and relapse rates were examined using weighted Pearson’s correlation and linear regression. Results: Of 199 definite MS patients, 142 had RRMS. The lowest relapse rate of 0.5 per 1,000 days (95% CI: 0.2–1.3) occurred in February (mid-late summer) versus the March–January RR of 1.1 per 1,000 days (95% CI: 0.9–1.3; p = 0.018, weighted regression). Monthly relapse rates correlated with: (1) prior erythemal ultraviolet radiation (EUV): lagged 1.5 months, r = –0.32, p = 0.046; (2) URT infection rate: no lag, r = 0.39, p = 0.014; (3) 25(OH)D: no lag, r = –0.31, p = 0.057. The association between URT infections and relapses was reduced after adjustment for monthly EUV. Conclusions: Relapse rates were inversely associated with EUV and serum 25(OH)D levels and positively associated with URT infections. The demonstrated lag between EUV but not 25(OH)D and relapse rates is consistent with a role for EUV-generated 25(OH)D in the alteration of relapse rates. Future work on the association between URT infections and relapses should be considered in the context of ultraviolet radiation and vitamin D.

Nonsmall cell lung carcinoma with neuroendocrine differentiation--an entity of no clinical or prognostic significance.

The existence of non-small cell lung carcinoma with neuroendocrine differentiation as a distinct entity and its relevance for prognostic and treatment purposes is controversial. This study assesses the frequency and biologic and prognostic significance of neuroendocrine (NE) expression of synaptophysin (SNP), chromogranin (Ch), and neural cell adhesion molecule (N-CAM) using tissue microarray (TMA) and immunohistochemistry. Six hundred nine nonsmall cell lung carcinomas (NSCLCs) were reviewed for subclassification. TMA blocks were made using duplicate 0.6-mm-diameter tissue cores and slides stained with SNP, Ch, and N-CAM. Immunoreactivity was considered if 1% or more of tumor cells were positive. Hematoxylin and eosin-stained sections were subclassified as: 243 adenocarcinoma (ACA), 272 squamous cell carcinoma (SCC), 35 large cell carcinoma, 32 non-small cell carcinoma NOS, and 6 other (carcinosarcoma, giant cell carcinoma). Positivity for either marker was identified in 13.6% of NSCLC (76/558). NSCLC showed reactivity for Ch in 0.4% of cases (2/524), for SNP in 7.5% of cases (39/521) and for N-CAM in 8.6% of cases (44/511), whereas only 0.2% of cases (1/517) showed coexpression of SNP and Ch and none of all 3 markers. The assessment of NE differentiation in NSCLC is unnecessary and expensive and is of no clinical or prognostic significance. SNP or N-CAM stains a small minority of NSCLC, whereas Ch immunoreactivity is less common. Positivity for any 2 NE markers is rare. SNP is more likely to be expressed in adenocarcinoma (P=0.01) and N-CAM in squamous-cell carcinoma (P=0.008). Otherwise there was no correlation between immunoreactivity and tumor morphology. Disease specific and overall survival is not influenced by NE differentiation and therefore non-small cell lung carcinoma with neuroendocrine differentiation should not be a subclass distinct from the other NSCLC.

Reticular basement membrane fragmentation and potential epithelial mesenchymal transition is exaggerated in the airways of smokers with chronic obstructive pulmonary disease

Background and objective:  In COPD, the airways are chronically inflamed, and we have now observed fragmentation of the reticular basement membrane (Rbm). This appears to be a hallmark of the process known as epithelial mesenchymal transition (EMT), in which epithelial cells migrate through the Rbm and differentiate into fibroblasts. The aim of this study was to confirm the extent and relevance of Rbm fragmentation in smokers and patients with COPD, and to undertake a preliminary analysis of some classical markers of EMT.

The Interplay between the Effects of Lifetime Asthma, Smoking, and Atopy on Fixed Airflow Obstruction in Middle Age

RATIONALE The contribution by asthma to the development of fixed airflow obstruction (AO) and the nature of its effect combined with active smoking and atopy remain unclear. OBJECTIVES To investigate the prevalence and relative influence of lifetime asthma, active smoking, and atopy on fixed AO in middle age. METHODS The population-based Tasmanian Longitudinal Health Study cohort born in 1961 (n = 8,583) and studied with prebronchodilator spirometry in 1968 was retraced (n = 7,312) and resurveyed (n = 5,729 responses) from 2002 to 2005. A sample enriched for asthma and chronic bronchitis underwent a further questionnaire, pre- and post-bronchodilator spirometry (n = 1,389), skin prick testing, lung volumes, and diffusing capacity measurements. Prevalence estimates were reweighted for sampling fractions. Multiple linear and logistic regression were used to assess the relevant associations. MEASUREMENTS AND MAIN RESULTS Main effects and interactions between lifetime asthma, active smoking, and atopy as they relate to fixed AO were measured. The prevalence of fixed AO was 6.0% (95% confidence interval [CI], 4.5-7.5%). Its association with early-onset current clinical asthma was equivalent to a 33 pack-year history of smoking (odds ratio, 3.7; 95% CI, 1.5-9.3; P = 0.005), compared with a 24 pack-year history for late-onset current clinical asthma (odds ratio, 2.6; 95% CI, 1.03-6.5; P = 0.042). An interaction (multiplicative effect) was present between asthma and active smoking as it relates to the ratio of post-bronchodilator FEV(1)/FVC, but only among those with atopic sensitization. CONCLUSIONS Active smoking and current clinical asthma both contribute substantially to fixed AO in middle age, especially among those with atopy. The interaction between these factors provides another compelling reason for atopic individuals with current asthma who smoke to quit.

A mixed methods study to compare models of spirometry delivery in primary care for patients at risk of COPD

Background: To increase recognition of airflow obstruction in primary care, we compared two models of spirometry delivery in a target group at risk of chronic obstructive pulmonary disease (COPD). Methods: A 6 month qualitative/quantitative cluster randomised study in eight practices compared opportunistic spirometry by “visiting trained nurses” (TN) with optimised “usual care” (UC) from general practitioners (GPs) for smokers and ex-smokers, aged over 35 years. Outcomes were: spirometry uptake and quality, new diagnoses of COPD and GPs’ experiences of spirometry. Results: In the eligible target population, 531/904 (59%) patients underwent spirometry in the TN model and 87/1130 (8%) patients in the UC model (p<0.0001). ATS spirometry standards for acceptability and reproducibility were met by 76% and 44% of tests in the TN and UC models, respectively (p<0.0001). 125 (24%) patients tested with the TN model and 38 (44%) with the UC model reported a pre-existing respiratory diagnosis (p<0.0001). Three months after spirometry, when the ratio of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) was <0.7 and no prior COPD diagnosis was reported, nine (8%) participants had a new doctor recorded COPD diagnosis in practices with the TN model and two (8%) participants in practices with the UC model. Mislabelling of participants with a diagnosis of COPD when FEV1/FVC was ⩾0.7 was present in both models prior to and after spirometry. GPs valued high quality spirometry and increased testing of patients at risk of COPD in the TN model. They identified limitations, including the need for better systematic follow-up of abnormal spirometry and support with interpretation, which may explain persisting underdiagnosis of COPD in practice records. Conclusions: Although opportunistic testing by visiting trained nurses substantially increased and improved spirometry performance compared with usual care, translating increased detection of airflow obstruction into diagnosis of COPD requires further development of the model. Trial registration number: Australian Clinical Trials Registry: registration No 12605000019606.

Influenza vaccine effectiveness against hospitalisation with confirmed influenza in the 2010-11 seasons: a test-negative observational study.

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons.

Exercise-induced bronchial hyperresponsiveness and parental ISAAC questionnaire responses.

The predictive value of parental questionnaire responses for exercise-induced bronchoconstriction in childhood asthma has not been fully clarified. The aim of this study was to compare exercise-induced bronchial hyperresponsiveness in 7 year old children with parental responses to core questions in the International Study of Asthma and Allergies in Childhood (ISAAC) study. A cross-sectional study was conducted on 191 (91% of eligible) children from seven randomly selected schools in Southern Tasmania. Study measurements included a parental questionnaire and exercise challenge testing, using a recently validated 6 min free-running protocol. The response to exercise was assessed using forced expiratory volume in one second (FEV1) measurement. The median percentage fall in FEV1 was significantly higher in children whose parents responded positively to ISAAC questions on a history of wheeze (p = 0.0031) or asthma (p = 0.0005), recent wheeze (p = 0.0005), sleep disturbance due to wheeze (p = 0.0005), or exercise-induced wheeze (p = 0.0015). Receiver operating characteristic (ROC) curve analysis showed exercise-induced bronchial hyperresponsiveness to be a good indicator of current asthma status. Using a 12% or greater fall in FEV1 postexercise as a positive test response, the exercise challenge had sensitivity and specificity estimates for current asthma and exercise-induced wheeze of (0.58 and 0.77) and (0.60 and 0.77), respectively. In conclusion, the respiratory response to exercise was consistent with parental responses to the ISAAC questionnaire in a population-based sample of 7 year old children. These findings will assist interpretation of large ISAAC studies in terms of asthma prevalence.

Stability of the EasyOne ultrasonic spirometer for use in general practice.

Objective and background:  Spirometry is recommended for the diagnosis and management of chronic respiratory diseases in the community. Spirometer accuracy is critical, but few general practitioners meet the American Thoracic Society and European Respiratory Society (ATS/ERS) recommendation for daily calibration. The aim of this study was to assess the accuracy and stability of a portable ultrasonic spirometer (EasyOne) that the manufacturer claims does not require regular calibration.

Factors associated with misdiagnosis of COPD in primary care

AIMS To assess the misclassification of chronic obstructive pulmonary disease (COPD) in Australian primary care. METHODS A cross-sectional study was performed in 31 (19%) practices in one Australian state. 341 patients with COPD (database diagnosis or current use of tiotropium plus GP confirmation) completed spirometry and questionnaires. Predictors of misclassification were investigated with multi-level mixed-effects logistic regression allowing for clustering by practice. RESULTS Spirometric confirmation of COPD (forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7) was not present in 107 (31%) patients; 60 (56%) had normal lung function, seven (7%) had scalloped flow-volume curves and FEV1 <80% predicted, 40 (37%) had restriction (FVC <80% predicted). Among 107 misclassified patients the bronchodilators used were tiotropium in 26% and long-acting β2-agonists in 22%. The likelihood of misclassification increased with overweight/obesity (odds ratio (OR) 2.66; 95% CI 1.50 to 4.70) and self-reported allergic rhinitis/hay fever (OR 1.72; 95% CI 1.13 to 2.64) after adjustment for age, gender, and smoking. CONCLUSIONS Symptom-based diagnosis of COPD in primary care is unreliable, especially if patients are overweight, so diagnostic spirometry is essential to avoid inappropriate management.