Measuring peak expiratory flow in general practice: comparison of mini Wright peak flow meter and turbine spirometer.

OBJECTIVE--To compare measurements of the peak expiratory flow rate taken by the mini Wright peak flow meter and the turbine spirometer. DESIGN--Pragmatic study with randomised order of use of recording instruments. Phase 1 compared a peak expiratory flow type expiration recorded by the mini Wright peak flow meter with an expiration to forced vital capacity recorded by the turbine spirometer. Phase 2 compared peak expiratory flow type expirations recorded by both meters. Reproducibility was assessed separately. SETTING--Routine surgeries at Aldermoor Health Centre, Southampton. SUBJECTS--212 Patients aged 4 to 78 presenting with asthma or obstructive airways disease. Each patient contributed only once to each phase (105 in phase 1, 107 in phase 2), but some entered both phases on separate occasions. Reproducibility was tested on a further 31 patients. MAIN OUTCOME MEASURE--95% Limits of agreement between measurements on the two meters. RESULTS--208 (98%) Of the readings taken by the mini Wright meter were higher than the corresponding readings taken by the turbine spirometer, but the 95% limits of agreement (mean difference (2 SD] were wide (1 to 173 l/min). Differences due to errors in reproducibility were not sufficient to predict this level of disagreement. Analysis by age, sex, order of use, and the type of expiration did not detect any significant differences. CONCLUSIONS--The two methods of measuring peak expiratory flow rate were not comparable. The mini Wright meter is likely to remain the preferred instrument in general practice.     

Ethyl pyruvate reduces mortality in an endotoxin-induced severe acute lung injury mouse model

Background

Desmosine and Isodesmosine (D/I) are cross-linking amino acids which are present only in mature elastin. Changes in their concentration in body fluids indicate changes in elastin degradation and can be a reflection of tissue elastase activity. This study was undertaken to determine whether continuous therapy with the long-acting bronchodilator Tiotropium bromide (TTP) could result in reductions in D/I as measured by mass spectrometry in plasma, urine and sputum.

Methods

Twelve not currently smoking patients with chronic obstructive pulmonary disease (COPD), never on TTP, were selected for study. Levels of D/I, along with measurements of FVC, FEV₁ and FEV₁/FVC. were determined before starting TTP daily, and then one and two months after.

Results

D/I decreased in plasma (10 of 12 patients), in sputum all (12 of 12), and in the percentage of free D/I in urine (10 of 12). Most patients showed slight increases in FVC and FEV₁ percent predicted over two months.

Conclusion

The results are consistent with an effect of prolonged bronchodilitation by anti-cholinergic blockade to also result in reduced lung elastin degradation.     

Predictors of interstitial lung disease in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort

Introduction

The objective of the present study was to examine the association of baseline demographic and clinical characteristics with sequentially obtained measurements of forced vital capacity (FVC), expressed as a percentage of the predicted value, and to identify predictors of the decline rate in FVC over time in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS).

Methods

To date, 266 patients have been enrolled in GENISOS, a prospective, observational cohort of patients with early systemic sclerosis. In addition to pulmonary function tests (PFTs), clinical and laboratory data were obtained from each patient. We analyzed 926 FVC measurements utilizing generalized linear mixed models. The predictive significance of baseline variables for the decline rate in FVC was investigated by the interaction term between the variable and the follow-up time within the first 3 years after enrollment as well as throughout the entire follow-up time.

Results

The cohort consisted of 125 white, 54 African American, and 77 Hispanic patients with average disease duration of 2.5 years at enrollment. The mean follow-up time was 3.8 years, ranging up to 11.4 years. A number of baseline variables, including antibody status, African American ethnicity, disease type, baseline PFT values, modified Rodnan Skin Score, fibrosis on chest radiograph, and lung and skin subscores of the Severity Index, were associated with serially measured FVC levels. However, only the presence of anti-topoisomerase I antibodies (ATA) was associated with lower FVC levels (P < 0.001) as well as accelerated decline rate in FVC within the first 3 years of follow-up (P = 0.02). None of the baseline variables predicted the rate of decline in FVC on long-term follow-up. Patients with rapidly progressive ILD, however, were under-represented in the long-term follow-up group because the accelerated rate of decline in FVC was associated with poor survival (P = 0.001).

Conclusions

Presence of ATA was the only baseline variable associated with differential FVC levels, predicting the rate of decline in FVC within the first 3 years of follow-up. The association of faster decline in FVC with poor survival further emphasizes the need for identification of predictive biomarkers by collection of genetic information and serial blood samples in cohort studies.     

No difference in between-country variability in use of newly approved orphan and non- orphan medicinal products - a pilot study

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which rapidly leads to chronic respiratory failure requiring mechanical ventilation. Currently, forced vital capacity (FVC) < 50% is considered as physiologic marker for admitting patients to Noninvasive Positive Pressure Ventilation (NPPV) intervention, although it has been recently shown the median survival of patients with baseline FVC < 75% much shorter than median survival of patients with baseline FVC > 75%, independently by any treatment.

Aim

To assess the role of NPPV in improving outcome of ALS, a retrospective analysis was performed to investigate 1 year survival of ALS patients with FVC < 75% and nocturnal respiratory insufficiency, treated with NPPV, compared to a well-matched population of ALS patients, who refused or was intolerant to NPPV.

Methods

We investigated seventy-two consecutive ALS patients who underwent pulmonary function test. Forty-four presented a FVC > 75% and served as control group. Twenty-eight patients presented a FVC < 75% and showed, at polysomnography analysis, nocturnal respiratory insufficiency, requiring NPPV; sixteen were treated with NPPV, while twelve refused or were intolerant.

Results

Increased survival rate at 1 year in patients with FVC < 75% treated with NPPV, as compared to those who refused or could not tolerate NPPV (p = 0.02), was observed. The median rate of decline in FVC% was slower in NPPV patients than in patients who did not use NPPV (95% CI: 0.72 to 1.85; p < 0.0001).

Conclusion

This report demonstrates that early treatment with NPPV prolongs survival and reduces decline of FVC% in ALS.     

Enzyme estimates of infarct size correlate with functional and clinical outcomes in the setting of ST-segment elevation myocardial infarction

Background

Cardiac biomarkers are routinely obtained in the setting of suspected myocardial ischemia and infarction. Evidence suggests these markers may correlate with functional and clinical outcomes, but the strength of this correlation is unclear. The relationship between enzyme measures of myocardial necrosis and left ventricular performance and adverse clinical outcomes were explored.

Methods

Creatine kinase (CK) and CK-MB data were analyzed, as were left ventricular ejection fraction (LVEF) by angiogram, and infarct size by single-photon emission computed tomography (SPECT) imaging in patients in 2 trials: Prompt Reperfusion In Myocardial-infarction Evolution (PRIME), and Efegatran and Streptokinase to Canalize Arteries Like Accelerated Tissue plasminogen activator (ESCALAT). Both trials evaluated efegatran combined with thrombolysis for treating acute ST-segment elevation myocardial infarction (STEMI).

Results

Peak CK and CK area-under-the-curve (AUC) correlated significantly with SPECT-determined infarct size 5 to 10 days after enrollment. Peak CK had a statistically significant correlation with LVEF, but CK-AUC and LVEF correlation were less robust. Statistically significant correlations exist between SPECT-determined infarct size and peak CK-MB and CK-MB AUC. However, there was no correlation with LVEF for peak CK-MB and CK-MB AUC. The combined outcome of congestive heart failure and death were significantly associated with CK AUC, CK-MB AUC, peak CK, and peak CK-MB measurements.

Conclusion

Peak CK and CK-MB values and AUC calculations have significant correlation with functional outcomes (LVEF- and SPECT-determined infarct size) and death or CHF outcomes in the setting of STEMI. Cardiac biomarkers provide prognostic information and may serve as valid endpoint measurements for phase II clinical trials.     

Lung function decline in relation to diagnostic criteria for airflow obstruction in respiratory symptomatic subjects

Background

Current COPD guidelines advocate a fixed < 0.70 FEV1/FVC cutpoint to define airflow obstruction. We compared rate of lung function decline in respiratory symptomatic 40+ subjects who were 'obstructive' or 'non-obstructive' according to the fixed and/or age and gender specific lower limit of normal (LLN) FEV1/FVC cutpoints.

Methods

We studied 3,324 respiratory symptomatic subjects referred to primary care diagnostic centres for spirometry. The cohort was subdivided into four categories based on presence or absence of obstruction according to the fixed and LLN FEV1/FVC cutpoints. Postbronchodilator FEV1 decline served as primary outcome to compare subjects between the respective categories.

Results

918 subjects were obstructive according to the fixed FEV1/FVC cutpoint; 389 (42%) of them were non-obstructive according to the LLN cutpoint. In smokers, postbronchodilator FEV1 decline was 21 (SE 3) ml/year in those non-obstructive according to both cutpoints, 21 (7) ml/year in those obstructive according to the fixed but not according to the LLN cutpoint, and 50 (5) ml/year in those obstructive according to both cutpoints (p = 0.004).

Conclusion

This study showed that respiratory symptomatic 40+ smokers and non-smokers who show FEV1/FVC values below the fixed 0.70 cutpoint but above their age/gender specific LLN value did not show accelerated FEV1 decline, in contrast with those showing FEV1/FVC values below their LLN cutpoint.     

Rapid effects of extrafine beclomethasone dipropionate/formoterol fixed combination inhaler on airway inflammation and bronchoconstriction in asthma: a randomised controlled trial

Background

Airway Bypass is a catheter-based, bronchoscopic procedure in which new passageways are created that bypass the collapsed airways, enabling trapped air to exit the lungs. The Exhale Airway Stents for Emphysema (EASE) Trial was designed to investigate whether Exhale^® Drug-Eluting Stents, placed in new passageways in the lungs, can improve pulmonary function and reduce breathlessness in severely hyperinflated, homogeneous emphysema patients (NCT00391612).

Methods/Design

The multi-center, randomized, double-blind, sham-controlled trial design was posted on http://www.clinicaltrials.gov in October 2006. Because Bayesian statistics are used for the analysis, the proposed enrollment ranged from 225 up to 450 subjects at up to 45 institutions. Inclusion criteria are: high resolution CT scan with evidence of homogeneous emphysema, post-bronchodilator pulmonary function tests showing: a ratio of FEV₁/FVC < 70%, FEV₁≤50% of predicted or FEV₁ < 1 liter, RV/TLC≥0.65 at screening, marked dyspnea score ≥2 on the modified Medical Research Council scale of 0-4, a smoking history of at least 20 pack years and stopped smoking for at least 8 weeks prior to enrollment. Following 16 to 20 supervised pulmonary rehabilitation sessions, subjects were randomized 2:1 to receive either a treatment (Exhale^® Drug-Eluting Stent) or a sham bronchoscopy. A responder analysis will evaluate the co-primary endpoints of an FVC improvement ≥12% of the patient baseline value and modified Medical Research Council dyspnea scale improvement (reduction) ≥1 point at the 6-month follow-up visit.

Discussion

If through the EASE Trial, Airway Bypass is shown to improve pulmonary function and reduce dyspnea while demonstrating an acceptable safety profile, then homogeneous patients will have a minimally invasive treatment option with meaningful clinical benefit.

Trial Registration

ClinicalTrials.gov: NCT00391612     

Turbine flowmeter vs. Fleisch pneumotachometer: a comparative study for exercise testing

The purpose of this study was to investigate the characteristics of a newly developed turbine flowmeter (Alpha Technologies, model VMM-2) for use in an exercise testing system by comparing its measurement of expiratory flow (VE), O2 uptake (VO2), and CO2 output (VCO2) with the Fleisch pneumotachometer. An IBM PC/AT-based breath-by-breath system was developed, with turbine flowmeter and dual-Fleisch pneumotachometers connected in series. A normal subject was tested twice at rest, 100-W, and 175-W of exercise. Expired gas of 24-32 breaths was collected in a Douglas bag. VE was within 4% accuracy for both flowmeter systems. The Fleisch pneumotachometer system had 5% accuracy for VO2 and VCO2 at rest and exercise. The turbine flowmeter system had up to 20% error for VO2 and VCO2 at rest. Errors decreased as work load increased. Visual observations of the flow curves revealed the turbine signal always lagged the Fleisch signal at the beginning of inspiration or expiration. At the end of inspiration or expiration, the turbine signal continued after the Fleisch signal had returned to zero. The "lag-before-start" and "spin-after-stop" effects of the turbine flowmeter resulted in larger than acceptable error for the VO2 and VCO2 measurements at low flow rates.     

Mechanical strain promotes osteoblast ECM formation and improves its osteoinductive potential

Background

Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT.

Methods

Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated.

Results

EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques.

Conclusion

EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.     

Matrix metalloproteinase 28, a novel matrix metalloproteinase, is constitutively expressed in human intervertebral disc tissue and is present in matrix of more degenerated discs

Introduction

Comparison of intra-articular bacterial-derived hyaluronic acid (Hyalubrix^®) (HA) with local analgesia (mepivacaine) for osteoarthritis (OA) of the hip.

Methods

A pilot prospective, double-blind, 6-month randomized trial of 42 patients with hip OA. HA or mepivacaine was administered twice (once a month) under ultrasound guidance. Efficacy measurements included the Lequesne's algofunctional index, a visual analog scale for pain, concomitant use of analgesia, patient and physician global measurement, and safety.

Results

Patients in the HA group exhibited a significantly reduced Lequesne's algofunctional index 3 and 6 months after treatment (P < 0.001) and significantly reduced visual analog scale pain scores 3 and 6 months after treatment (P < 0.05) compared with the local anesthetic group. All primary and secondary measures were significantly improved versus baseline, but other than the above were not different from each other at 3 or 6 months. Adverse effects were minimal.

Conclusions

This comparative study suggests a beneficial effect and safety of intra-articular HA in the management of hip OA.

Trial registration number

ISRCTN39397064.     

Changes in oxygen partial pressure of brain tissue in an animal model of obstructive apnea

Background

Prolonged weaning from mechanical ventilation has a major impact on ICU bed occupancy and patient outcome, and has significant cost implications. There is evidence in patients around the period of extubation that helium-oxygen leads to a reduction in the work of breathing. Therefore breathing helium-oxygen during weaning may be a useful adjunct to facilitate weaning. We hypothesised that breathing helium-oxygen would reduce carbon dioxide production during the weaning phase of mechanical ventilation.

Materials/patients and methods

We performed a prospective randomised controlled single blinded cross-over trial on 19 adult intensive care patients without significant airways disease who fulfilled criteria for weaning with CPAP. Patients were randomised to helium-oxygen and air-oxygen delivered during a 2 hour period of CPAP ventilation. Carbon dioxide production (VCO₂) was measured using a near patient main stream infrared carbon dioxide sensor and fixed orifice pneumotachograph.

Results

Compared to air-oxygen, helium-oxygen significantly decreased VCO₂ production at the end of the 2 hour period of CPAP ventilation; there was a mean difference in CO₂ production of 48.9 ml/min (95% CI 18.7-79.2 p = 0.003) between the groups. There were no significant differences in other respiratory and haemodynamic parameters.

Conclusion

This study shows that breathing a helium-oxygen mixture during weaning reduces carbon dioxide production. This physiological study supports the need for a clinical trial of helium-oxygen mixture during the weaning phase of mechanical ventilation with duration of weaning as the primary outcome.

Trial registration

ISRCTN56470948     

Prediction and course of symptoms and lung function around an exacerbation in chronic obstructive pulmonary disease

Background

Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD). We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD.

Methods

In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF), and salbutamol use and assessed their course during exacerbations.

Results

There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively), whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70.

Conclusions

Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice.     

Influence of degree of specific allergic sensitivity on severity of rhinitis and asthma in Chinese allergic patients

Background

The clinical manifestations of severe asthma are heterogeneous. Some individuals with severe asthma develop irreversible fixed airway obstruction, which is associated with poor outcomes. We therefore investigated the factors associated with fixed airway obstruction in Korean patients with severe asthma.

Methods

Severe asthma patients from a Korean adult asthma cohort were divided into two groups according to the results of serial pulmonary function tests. One group had fixed airway obstruction (FAO) [forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio < 0.7, n = 119] and the other had reversible airway obstruction (RAO) [FEV1/FVC ratio ≥ 0.7, n = 116]. Clinical and demographic parameters were compared between the two groups.

Results

Multivariate analysis showed that longer duration of disease, greater amount of cigarette smoking and absence of rhinosinusitis were significantly related to the development of FAO in severe asthmatics. Other parameters, including atopic status, pattern of airway inflammatory cells in induced sputum, and frequency of asthma exacerbations did not differ between the FAO and RAO groups.

Conclusion

Severe asthma patients with longer disease duration and the absence of rhinosinusitis are more likely to develop FAO. This study also demonstrates the importance of quitting smoking in order to prevent irreversible airway obstruction. Further investigation is required to determine the mechanism by which these factors can modify the disease course in Korean patients with severe asthma.     

Adherence with tobramycin inhaled solution and health care utilization

Background

To produce a conceptually equivalent Arabic version to the original Self-Administered Chronic Respiratory Disease Questionnaire with standardized dyspnea domain (CRQ-SAS) and to assess its reliability.

Methods

The study was carried out in two stages: stage I which was the translation of the CRQ-SAS questionnaire from the English to the Arabic language, and stage II which represented the test-retest reliability for patients receiving usual care for COPD who were not yet admitted to the pulmonary rehabilitation program.

Results

Forty five patients with stable COPD were enrolled in this study. Strong test-retest reliability was found for the four domains of the CRQ-SAS, with the intra-class correlation coefficient of 0.97 for each of the domains. The association between most parameters and the four domains of CRQ-SAS were not found to be statistically significant, as measured by Pearson correlation. The number of exacerbations was negatively correlated with the dyspnea domain (correlation = -0.36, p-value = 0.02). The disease duration was negatively correlated with the domain fatigue (correlation = -0.35, p-value = 0.02). The correlation between FEV1/FVC ratio and emotion domain was -0.30 (p-value = 0.05). The mastery domain was negatively correlated with FEV1/FVC ratio with a correlation of -0.27 with borderline statistical significance (p-value = 0.07).

Conclusion

The Arabic translation of the CRQ-SAS was found to be reliable to assess the quality of life among patients with COPD.     

The non-invasive documentation of coronary microcirculation impairment: role of transthoracic echocardiography

Background

Multiples indices have been described using tissue Doppler imaging (DTI) capabilities. The aim of this study was to assess the capability of one or several regional DTI parameters in separating control from ischemic myocardium.

Methods

Twenty-eight patients with acute myocardial infarction were imaged within 24-hour following an emergent coronary angioplasty. Seventeen controls without any coronary artery or myocardial disease were also explored. Global and regional left ventricular functions were assessed. High frame rate color DTI cineloop recordings were made in apical 4 and 2-chamber for subsequent analysis. Peak velocity during isovolumic contraction time (IVC), ejection time, isovolumic relaxation (IVR) and filling time were measured at the mitral annulus and the basal, mid and apical segments of each of the walls studied as well as peak systolic displacement and peak of strain.

Results

DTI-analysis enabled us to discriminate between the 3 populations (controls, inferior and anterior AMI). Even in non-ischemic segments, velocities and displacements were reduced in the 2 AMI populations. Peak systolic displacement was the best parameter to discriminate controls from AMI groups (wall by wall, p was systematically < 0.01). The combination IVC + and IVR< 1 discriminated ischemic from non-ischemic segments with 82% sensitivity and 85% specificity.

Conclusion

DTI-analysis appears to be valuable in ischemic heart disease assessment. Its clinical impact remains to be established. However this simple index might really help in intensive care unit routine practice.     

Imaging of all three coronary arteries by transthoracic echocardiography. an illustrated guide

Background

Improvements in ultrasound technology has enabled direct, transthoracic visualization of long portions of coronary arteries : the left anterior descending (LAD), circumflex (Cx) and right coronary artery (RCA). Transthoracic measurements of coronary flow velocity were proved to be highly reproducible and correlated with invasive measurements. While clinical applications of transthoracic echocardiography (TTE) of principal coronary arteries are still very limited they will likely grow. The echocardiographers may therefore be interested to know the ultrasonic views, technique of examination and be aware where to look for coronary arteries and how to optimize the images.

Methods

A step-by-step approach to direct, transthoracic visualization of the LAD, Cx and RCA is presented. The technique of examination is discussed, correlations with basic coronary angiography views and heart anatomy are shown and extensively illustrated with photographs and movie-pictures. Hints concerning optimization of ultrasound images are presented and artifacts of imaging are discussed.

Conclusions

Direct, transthoracic examination of the LAD, Cx and RCA in adults is possible and may become a useful adjunct to other methods of coronary artery examination but studies are needed to establish its role.     

Development and prospective validation of a model for predicting weaning in chronic ventilator dependent patients

Background

HTLV-I infection has been linked to lung pathology and HTLV-II has been associated with an increased incidence of pneumonia and acute bronchitis. However it is unknown whether HTLV-I or -II infection alters pulmonary function.

Methods

We performed pulmonary function testing on HTLV-I, HTLV-II and HTLV seronegative subjects from the HTLV outcomes study (HOST), including vital capacity (VC), forced expiratory volume in one second (FEV₁), and diffusing lung capacity for carbon monoxide (DLCO) corrected for hemoglobin and lung volume. Multivariable analysis adjusted for differences in age, gender, race/ethnicity, height and smoking history.

Results

Mean (standard deviation) pulmonary function values among the 257 subjects were as follows: FVC = 3.74 (0.89) L, FEV₁ = 2.93 (0.67) L, DLCO_corr = 23.82 (5.89) ml/min/mmHg, alveolar ventilation (VA) = 5.25 (1.20) L and DLCO_corr/VA = 4.54 (0.87) ml/min/mmHg/L. There were no differences in FVC, FEV1 and DLCO_corr/VA by HTLV status. For DLCO_corr, HTLV-I and HTLV-II subjects had slightly lower values than seronegatives, but neither difference was statistically significant after adjustment for confounding.

Conclusions

There was no difference in measured pulmonary function and diffusing capacity in generally healthy HTLV-I and HTLV-II subjects compared to seronegatives. These results suggest that previously described HTLV-associated abnormalities in bronchoalveolar cells and fluid may not affect pulmonary function.     

The Darlington and Northallerton Long Term Asthma Study: pulmonary function

Background

The Darlington and Northallerton Asthma Study is an observational cohort study started in 1983. At that time little was published about long term outcome in asthma and the contribution of change in reversible disease or airway remodelling to any excess deterioration in function. The study design included regular review of overall and fixed function lung. We report the trends over fifteen years.

Methods

All asthmatics attending secondary care in 1983, 1988 and 1993 were recruited. Pulmonary function was recorded at attendance and potential best function estimated according to protocol. Rate of decline was calculated over each 5-year period and by linear regression analysis in those seen every time. The influence of potential explanatory variables on this decline was explored.

Results

1724 satisfactory 5-year measurements were obtained in 912 subjects and in 200 subjects on all occasions. Overall rate of decline (ml/year (95%CI)) calculated from 5-year periods was FEV1 ♂41.0 (34.7–47.3), ♀28.9 (23.2–34.6) and best FVC ♂63.1 (55.1–71.2)ml/year, ♀45.8 (40.0–51.6).The principal association was with age. A dominant cubic factor suggested fluctuations in the rate of change in middle life with less rapid decline in youth and more rapid decline in the elderly. Rapid decline was possibly associated with short duration. Treatment step did not predict rate of deterioration.

Conclusions

Function declined non-linearly and more rapidly than predicted from normal subjects. It reports for the first time a cubic relationship between age and pulmonary function. This should be taken into account when interpreting other articles reporting change in function over time.     

Anecdotal,Historical and Critical Commentaries on Genetics: Wright and Fisher on Inbreeding and Random Drift

Sewall Wright and R. A. Fisher often differed, including on the meaning of inbreeding and random gene frequency drift. Fisher regarded them as quite distinct processes, whereas Wright thought that because his inbreeding coefficient measured both they should be regarded as the same. Since the effective population numbers for inbreeding and random drift are different, this would argue for the Fisher view.SEWALL Wright and R. A. Fisher were central figures in mathematical population genetics; along with J. B. S. Haldane they effectively invented the field and dominated it for many years. On most issues the three were in agreement. In particular, all favored a neo-Darwinian gradualist approach and believed in the importance of a mathematical theory for understanding the evolutionary process. Yet on a few questions Fisher and Wright differed profoundly and argued vehemently. Fisher was contentious and was often involved in controversy, frequently attacking his opponents mercilessly. Wright, in contrast, was very gentle to most people. But there were a few exceptions and Fisher was one. Haldane mostly stayed out of the arguments between them.One question on which the two disagreed was the importance of random gene frequency drift and its role in Wright''s shifting-balance theory of evolution. Wright thought that a structured population with many partially isolated subpopulations, within which there was random drift and among which there was an appropriate amount of migration, offered the greatest chance for evolutionary novelty and could greatly increase the speed of evolution. Fisher thought that a large panmictic population offered the best chance for advantageous genes and gene combinations to spread through the population, unimpeded by random processes. They also disagreed on dominance, Fisher believing that it evolved by selection of dominance modifiers and Wright that it was a consequence of the nature of gene action. These differences were widely argued by population geneticists in the middle third of the twentieth century, and the interested community divided into two camps. Although the issues are not settled, Wright''s shifting-balance theory has less support than it formerly had. As for dominance, there is general quantitative disagreement with Fisher''s explanation of modifiers, but other mechanisms (e.g., selection for more active alleles) have to some extent replaced it. Wright''s theory remains popular and has been generalized and extended (Kacser and Burns 1973).     

Assessing product environmental performance with PEF methodology: reliability,comparability, and cost concerns

Purpose

The Product Environmental Footprint (PEF) method was launched by the European Commission to harmonize the measurement of the product’s environmental performance. The PEF aims to increase the supply of green products in EU markets by lowering the cost of measuring the product’s environmental performance, enabling reliable environmental claims, and conducting proper product comparison. This study assesses whether the methodological choices of PEF enable reliable and comparable PEF studies to be conducted in a cost-efficient way.

Methods

The PEF was compared with ISO 14044, ISO/TS 14067, and the Greenhouse Gas Protocol Product Standard to identify the differences in the methodological choices. From a practical perspective, the possible challenges for PEF that could not be identified by a method comparison were obtained via interviews. The interviewees were company representatives participating in a 3-year PEF pilot phase to create Product Environmental Footprint Category Rules (PEFCR). To discover the possible advantages and disadvantages of the PEF, the methodological choices for PEF itself were assessed from the standpoints of reliability, comparability, and cost. In conclusion, some proposals for improvements have been suggested.

Results and discussion

The impact assessment phase, i.e., some of the predefined impact assessment methods, together with a selected normalization method include disadvantages as regards reliability and comparability. They are not sufficiently mature to properly reflect both the product studied and its potential environmental impact. From a cost perspective, the inventory analysis phase increases the workload due to the cutoff ban, the numerous predefined impact assessment categories, and the data quality assessment of all data. However, the predefined issues, e.g., requirements for data quality to be determined in PEFCRs, could also increase the comparability and lower the costs of the PEF study, since these need not be determined separately for each study. Additionally, the reliability maybe increased due to the data quality assessment of all data.

Conclusions

Currently, in the PEFs 3-year pilot phase, both advantages and disadvantages exist as regards reliability, costs, and comparability. Since PEF aims are important, the Commission and PEFCR developers should devote time to finding the most appropriate methodological choices and continue developing the method further. It is important to find a balance between comparability, reliability, and costs. Additionally, the current issues and characteristics of EU green products market should be taken into account when implementing PEF.