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author:("alderley, P M")
1.  COPD exacerbations · 4: Prevention 
Thorax  2006;61(5):440-447.
A review of the evidence that the prevention of COPD works and, if so, the effectiveness of this strategy
PMCID: PMC2111200  PMID: 16648352
chronic obstructive pulmonary disease; exacerbations; prevention
2.  Chronic obstructive pulmonary disease past, present and future 
Thorax  2007;62(12):1026-1027.
Progress in the understanding of COPD
PMCID: PMC2094286  PMID: 18025136
3.  Caring for the burden of COPD 
Thorax  2006;61(10):831-832.
How delivery of care affects the subsequent progress of COPD patients
PMCID: PMC2104772  PMID: 17008478
chronic obstructive pulmonary disease; elderly; organisation of care; resources; audit; outcomes
4.  Management of acute ventilatory failure 
Postgraduate Medical Journal  2006;82(969):438-445.
Acute ventilatory failure is a challenging yet increasingly common medical emergency reflecting the growing burden of respiratory disease. It is not a diagnosis in itself but the end result of a diversity of disease processes culminating in arterial hypoxaemia and hypercapnia. This review focuses on key management issues including giving appropriate oxygen therapy, treatment of the underlying aetiology as well as any precipitant factors and provision of assisted ventilation if required. Ventilatory assistance can be provided both invasively and non‐invasively and the indications for either or both forms of assisted ventilation are discussed. Further emphasis is needed regarding advanced directives of care and clinicians should be aware of ethical issues regarding assisted ventilation.
PMCID: PMC2563765  PMID: 16822920
COPD; ventilatory failure; invasive ventilation; non‐invasive ventilation; oxygen therapy
5.  All change for home oxygen services in England and Wales 
Thorax  2006;61(1):7-9.
Changes to the home oxygen service effective from February 2006
PMCID: PMC2080718  PMID: 16396952
chronic obstructive pulmonary disease; home oxygen service
6.  Sleep-related breathing disorders 
Thorax  1995;50(6):682.
PMCID: PMC1021274
8.  Obstructive sleep apnoea with Arnold-Chiari malformation. 
Thorax  1995;50(6):690-697.
A case of obstructive sleep apnoea associated with the Arnold-Chiari malformation is described, in which the loss of pharyngeal sensation seems to have played an important part in the aetiology of the obstruction of the upper airway.
PMCID: PMC1021276  PMID: 7638817
9.  Oxygen desaturation and breathlessness during corridor walking in chronic obstructive pulmonary disease: effect of oxitropium bromide. 
Thorax  1993;48(11):1145-1150.
BACKGROUND--Although exercise induced desaturation can occur in patients with chronic obstructive pulmonary disease (COPD), little is known about its frequency during everyday exercise, or how it relates to dyspnoea or prior drug treatment. METHODS--The effects of 200 micrograms inhaled oxitropium bromide, an anticholinergic bronchodilator drug, on spirometric values, dyspnoea score, and oxygen saturation during corridor walking and cycle ergometry were studied in a double blind, randomised, placebo controlled study. RESULTS--Oxitropium produced a small increase in forced expired volume in one second (FEV1) from 0.76 (0.28) 1 to 0.93 (0.69) 1 and in six minute walking distance from 311 (93) m to 332 (86) m, but did not change progressive cycle exercise duration. Resting and end exercise breathlessness levels were reduced in both forms of exercise after oxitropium. Resting oxygen saturation fell significantly after active bronchodilator from 92.9% (3.7%) to 92.0% (4.1%) but the nadir saturation during exercise was unchanged. The patients desaturated more during corridor walking than cycle ergometry [walking 7.8% (4.4%), cycle ergometry 2.1% (2.1%)]. Baseline walking distance was related to FVC, resting breathlessness and resting oxygen saturation (multiple r2 = 0.46) but only resting saturation correlated with end exercise breathlessness (r2 = -0.25). Improvements in symptoms or exercise performance after oxitropium could not be predicted by changes in spirometric indices or oxygen saturation. CONCLUSIONS--In patients with COPD arterial oxygen desaturation during self-paced walking is common, of greater severity than that during cycle ergometry, but is unaffected by inhaled oxitropium bromide. The factors that predict initial performance are not appropriate markers of functional improvement after an active bronchodilator drug.
PMCID: PMC464903  PMID: 8296259
10.  Clinicopathological correlations in cor pulmonale. 
Thorax  1992;47(7):494-498.
BACKGROUND: The relation between pulmonary disease and physiological abnormality in patients with hypoxic cor pulmonale is controversial and the association between arterial hypoxaemia and right ventricular hypertrophy has been challenged. To address these problems matched patients treated with and without domiciliary oxygen were studied. METHODS: Necropsy data were obtained on 19 patients (14 male), 10 of whom had been treated with domiciliary oxygen. Pulmonary artery pressure and total pulmonary vascular resistance as well as blood gas tensions during the breathing of air and oxygen were available for the six months before death. Formalin fixed lung slices were assessed for panacinar and centriacinar emphysema. Right and left ventricular weights were measured and their ratio (LV&S/RV) was used as an index of right ventricular hypertrophy. Carotid body weights were available in 14 cases. RESULTS: Fourteen patients died of respiratory failure and antemortem thrombus was found in the pulmonary arteries of eight cases. Physiological measurements were unrelated to the degree of macroscopic emphysema, pulmonary hypertension, or daytime blood gas tensions. When allowance was made for the higher "ambient" arterial oxygen tension (PaO2) of those who had oxygen, PaO2 was correlated with LV&S/RV (r = 0.79), absolute right ventricular weight (r = -0.53), and carotid body weight (r = 0.68). CONCLUSIONS: These data show that in hypoxic cor pulmonale in vivo physiological disturbances are poor indicators of the underlying disease process. The relation of "ambient" PaO2 to right ventricular hypertrophy and carotid body weight suggests that domiciliary oxygen therapy might lead to regression of such established disease.
PMCID: PMC463856  PMID: 1412090
11.  Assessment of reversibility of airway obstruction in patients with chronic obstructive airways disease. 
Thorax  1990;45(3):190-194.
Spirometry before and after an inhaled beta agonist or a course of oral prednisolone is widely used to detect reversible airflow limitation in patients with chronic obstructive lung disease. How many of these patients have a response and how the response to beta agonists relates to the response to corticosteroids is not clear. In 127 outpatients (mean (SD) FEV1 0.92 (0.38) 1) who had a clinical diagnosis of chronic obstructive lung disease (continuous breathlessness for more than six months and an FEV1/forced vital capacity (FVC) ratio less than 60%) and who appeared to be stable, the change in FEV1 was measured after salbutamol 200 micrograms from a metered dose inhaler and 5 mg from a nebuliser. Symptoms and spirometric values were recorded before and after two weeks of oral prednisolone 30 mg. Reversibility was defined as a response in FEV1 of 15% or more from baseline alone and as a 15% change and a minimum increase of at least 200 ml. The latter gave results that showed greater internal consistency between the drug regimens. On the basis of this criterion 56 patients (44%) had no response to salbutamol or prednisolone, 71 responded to salbutamol (including all 27 steroid responders), and 25 patients had a response to salbutamol 5 mg but not to 200 micrograms. In general, the largest increase in FEV1 after salbutamol occurred in the subjects with greatest improvement after prednisolone. Subjects showing a response in FEV1 after two weeks' prednisolone had a fall in total symptom score, unlike those who had no response to any treatment or a response to salbutamol only. These data show that reversibility in response to beta agonists is common in patients diagnosed on clinical grounds as having stable chronic obstructive lung disease, that it can be substantial, and that it is best detected by using a larger dose of salbutamol. Salbutamol responders were those most likely to improve after a trial of oral prednisolone. Allowance should be made for the variability of FEV1 in the calculation of the percentage response at low baseline values (less than 1 litre).
PMCID: PMC462381  PMID: 2330551
12.  Respiratory effort perception at rest and during carbon dioxide rebreathing in patients with dystrophia myotonica. 
Thorax  1994;49(3):240-244.
BACKGROUND--Breathlessness appears to be closely related to the perception of the outgoing motor command to breathe and should be increased in the presence of muscle weakness. However, breathlessness is not a common symptom in patients with chronic muscle disease who have weak respiratory muscles. The factors that determine the perception of respiratory effort in such patients have not been examined. METHODS--The inspiratory effort sensation during resting breathing and progressive hypercapnia was investigated in 12 patients with dystrophia myotonica with weak respiratory muscles (nine men and three women of mean (SD) age 41.1 (10.5) years; maximum inspiratory pressure 43.1 (17.2) cm H2O) and an age and sex matched control group of normal subjects of mean age 39.6 (10.6) years and a maximum inspiratory pressure of 123 (15.2) cm H2O. RESULTS--During resting breathing with a mouthpiece no differences were seen in inspiratory effort sensation, mouth occlusion pressure, or tidal volume, but inspiratory time and cycle duration were significantly shorter in the patients with dystrophia. Minute ventilation (VE) was significantly higher in the patients (15.8 (4.0) l/min v 12.5 (2.6) l/min), while resting breathing was no more variable in the patients than in controls. The ventilatory response to carbon dioxide (VE/PCO2) was not significantly lower in the patients (14.9 (6.9) l/min/kPa) than in the controls (17.4 (4.3) l/min/kPa). Effort sensation responses to carbon dioxide driven breathing were similar in the control subjects and the patients. With regression analysis of pooled data neither maximum inspiratory pressure nor disease state contributed to perceived inspiratory effort during hypercapnia. CONCLUSIONS--Moderately severe global respiratory muscle weakness does not appear to influence the ventilatory response to rising carbon dioxide tension or the perception of inspiratory effort in patients with dystrophia myotonica.
PMCID: PMC1021152  PMID: 8202880
13.  Protriptyline treatment of sleep hypoxaemia in Duchenne muscular dystrophy. 
Thorax  1989;44(12):1002-1005.
Protriptyline 20 mg daily reduced the total time spent in rapid eye movement sleep in an open study in four subjects with Duchenne muscular dystrophy. Sleep related hypoxaemia and episodes of desaturation were reduced. Anticholinergic side effects were prominent, however, in these patients, precluding its use for regular treatment.
PMCID: PMC1020872  PMID: 2617440
14.  Oxygen treatment of sleep hypoxaemia in Duchenne muscular dystrophy. 
Thorax  1989;44(12):997-1001.
Patients with Duchenne muscular dystrophy develop progressive ventilatory muscle weakness and often die of respiratory complications. Recurrent, often profound, hypoxaemia has been shown in a previous study by this group to occur during rapid eye movement (REM) sleep in these patients before they develop sleep symptoms. In this study the efficacy and physiological effects of nocturnal oxygen in such patients have been assessed. Seven patients with Duchenne muscular dystrophy (age range 16-22 years; mean vital capacity 1.37 litres) with normal arterial blood gas tensions when awake were investigated by standard overnight polysomnography on an acclimatization night followed by two successive nights on which they received room air and nasal oxygen (2 litres/min) respectively in random order. Total sleep time, proportion of REM and non-REM sleep, and frequency and duration of arousals were similar on the two nights. When breathing air six of the seven subjects developed oxygen desaturation of more than 5% during REM sleep. With oxygen only one subject showed any oxygen desaturation exceeding 2.5%. Oxygen desaturation was associated with periods of hypopnoea or cessation of respiratory effort. The mean duration of episodes of hypopnoea and apnoea was prolonged during oxygen breathing by 19% and the mean duration of episodes during REM sleep by 33% (the proportion of REM sleep associated with hypopnoea and apnoea increased in all subjects). Heart rate in non-REM sleep fell by 9.3%; heart rate variation in REM and non-REM sleep was unchanged. These acute studies show that oxygen reduces the sleep hypoxaemia associated with respiratory muscle weakness; whether long term treatment will be possible or desirable is not clear as oxygen potentiates the underlying ventilatory disturbance.
PMCID: PMC1020871  PMID: 2617453
15.  Critical evaluation of computerised x ray planimetry for the measurement of lung volumes. 
Thorax  1995;50(4):383-386.
BACKGROUND--Computerised x-ray planimetry has been advocated as an alternative to body plethysmography and helium dilution for measuring static lung volumes. The accuracy and reproducibility of this method has been assessed in comparison with these standard methods. METHODS--Plethysmographic and planimetric measurements of total lung capacity (TLC) and functional residual capacity (FRC) were made in 10 normal subjects and in 12 patients with chronic obstructive pulmonary disease (COPD), with additional helium dilution measurements in the latter 12 patients. RESULTS--Mean lung volumes (TLC and FRC) for groups of subjects measured by planimetry and by plethysmography were similar in both groups and larger than the helium dilution measurement in patients with COPD. Intraindividual agreement between planimetry and plethysmography was poor, however, with a wide confidence interval (-2.2 to +2.31). The planimeter did not measure reliably changes in volume from TLC to FRC in individuals. CONCLUSIONS--Mean lung volumes measured by planimetry in a group of patients probably reflect a regression to the mean of the computer algorithm rather than accurate TLC estimation. The technique is not yet robust enough to replace the established techniques of helium dilution or plethysmography.
PMCID: PMC474286  PMID: 7785011
16.  Simultaneous tracheal and oesophageal pH measurements in asthmatic patients with gastro-oesophageal reflux. 
Thorax  1995;50(2):201-204.
BACKGROUND--An association between asthma and gastro-oesophageal reflux is well recognised but the underlying mechanism is unclear. One suggestion is that gastric juice is aspirated into the tracheal and upper airways but detection of these events is difficult and involves radioisotopic studies. A new method of making direct measurements of tracheal and oesophageal pH over a 24 hour period is described, together with its application to patients with asthma. METHODS--The technique involves insertion of simultaneous tracheal and oesophageal pH probes under general anaesthesia. Continuous monitoring of pH over a 24 hour period is possible, permitting comparison with peak flow readings during wakefulness and at night should the patient be disturbed. Representative data from four patients with asthma (mean FEV1 62% predicted) and symptomatic gastro-oesophageal reflux, together with data from three non-asthmatics, is presented. RESULTS--Thirty seven episodes of gastro-oesophageal reflux lasting more than five minutes were recorded. Of these, five were closely followed by a fall in tracheal pH from a mean (SE) of 7.1 (0.2) to 4.1 (0.4) and a fall in peak expiratory flow (PEFR) of 84 (16) l/min. When gastro-oesophageal reflux occurred without tracheal aspiration the fall in PEFR was 8 (4) l/min. CONCLUSIONS--This new technique was well tolerated and allowed quantitation of the number, duration, and timing of episodes of tracheal micro-aspiration. Unlike acid reflux without aspiration, these events appear to be related to significant acute changes in lung function in asthmatic patients. Further studies with this new method may elucidate the role of gastro-oesophageal reflux in asthma.
PMCID: PMC473925  PMID: 7701464
17.  A mask to modify inspired air temperature and humidity and its effect on exercise induced asthma. 
Thorax  1992;47(6):446-450.
BACKGROUND: Heat and moisture loss from the respiratory tract during exercise are important triggers of exercise induced asthma. METHODS: A new heat and moisture exchange mask has been developed which both recovers exhaled heat and water and has a sufficiently low resistance for use during exercise. The effect of the mask on inspired air temperature was studied in four normal subjects. Eight asthmatic subjects performed identical exercise protocols on three separate days, breathing room air through a conventional mouthpiece, a dummy mask, and the new heat and moisture exchange mask. Seven different asthmatic subjects exercised while breathing cold air at -13 degrees C through a dummy or active mask. RESULTS: All subjects found the new mask comfortable to wear. The mean inspired temperature when the mask was used rose to 32.5 (1.4) degrees C when normal subjects breathed room air at 24 degrees C and to 19.1 (2.7) degrees C when they inhaled subfreezing air at -13 degrees C. The heat and moisture exchange mask significantly reduced the median fall in forced expiratory volume in one second (FEV1) after exercise to 13% (range 0-49%) when asthmatic subjects breathed room air compared with 33% (10-65%) with the dummy mask and 28% (21-70%) with the mouthpiece. The fall in FEV1 when the asthmatic subjects breathed cold air was 10% (0-26%) with the heat and moisture exchange mask compared with 22% (13-51%) with the dummy mask. CONCLUSION: Use of a heat and moisture exchange mask can raise the inspired temperature and humidity and ameliorate the severity of exercise induced asthma. The mask may be of practical value in non-contact sport or for people working in subzero temperatures.
PMCID: PMC463810  PMID: 1496504
18.  Heroin inhalation and asthma. 
BMJ : British Medical Journal  1988;297(6662):1511-1512.
Opiate addiction is an increasing social problem, and there has been a change from taking opiates intravenously to inhaling them in many areas of Britain. Three patients with asthma who required mechanical ventilation soon after heroin inhalation were described. Two subsequently died of acute severe asthma. The patients were reluctant to admit to their addiction and persisted inhaling heroin despite medical advice and counselling. Opiate inhalation can provoke life threatening asthmatic attacks and should be considered in patients at risk of abusing drugs who have poorly controlled asthma.
PMCID: PMC1835195  PMID: 3147049
19.  Carbon monoxide and exercise tolerance in chronic bronchitis and emphysema. 
The effects of carbon monoxide on exercise tolerance as assessed by the distance walked in 12 minutes were studied in 15 patients with severe chronic bronchitis and emphysema (mean forced expiratory volume in one second 0.56 1, mean forced vital capacity 1.54 1). Each subject walked breathing air and oxygen before and after exposure to sufficient carbon monoxide to raise their venous carboxyhaemoglobin concentration by 9%. There was a significant reduction in the walking distance when the patients breathed air after exposure to carbon monoxide (p less than 0.01), and the significant increase in walking distance seen after exercise when breathing oxygen at 2 1/minute via nasal cannulae was abolished if carbon monoxide has previously been administered. Thus concentrations of carboxyhaemoglobin frequently found in bronchitic patients who smoke may reduce their tolerance of everyday exercise, possibly by interfering with the transport of oxygen to exercising muscles.
PMCID: PMC1507111  PMID: 6793157
20.  “Hospital at home” versus hospital care in patients with exacerbations of chronic obstructive pulmonary disease: prospective randomised controlled trial 
BMJ : British Medical Journal  2000;321(7271):1265-1268.
To compare “hospital at home” and hospital care as an inpatient in acute exacerbations of chronic obstructive pulmonary disease.
Prospective randomised controlled trial with three months' follow up.
University teaching hospital offering secondary care service to 350 000 patients.
Selected patients with an exacerbation of chronic obstructive pulmonary disease where hospital admission had been recommended after medical assessment.
Nurse administered home care was provided as an alternative to inpatient admission.
Main outcome measures
Readmission rates at two weeks and three months, changes in forced expiratory volume in one second (FEV1) from baseline at these times and mortality.
583 patients with chronic obstructive pulmonary disease referred for admission were assessed. 192 met the criteria for home care, and 42 refused to enter the trial. 100 were randomised to home care and 50 to hospital care. On admission, FEV1 after use of a bronchodilator was 36.1% (95% confidence interval 2.4% to 69.8%) predicted in home care and 35.1% (6.3% to 63.9%) predicted in hospital care. No significant difference was found in FEV1 after use of a bronchodilator at two weeks (42.6%, 3.4% to 81.8% versus 42.1%, 5.1% to 79.1%) or three months (41.5%, 8.2% to 74.8% versus 41.9%, 6.2% to 77.6%) between the groups. 37% of patients receiving home care and 34% receiving hospital care were readmitted at three months. No significant difference was found in mortality between the groups at three months (9% versus 8%).
Hospital at home care is a practical alternative to emergency admission in selected patients with exacerbations of chronic obstructive pulmonary disease.
PMCID: PMC27532  PMID: 11082090
21.  Cryptogenic fibrosing alveolitis with preserved lung volumes 
Thorax  1997;52(11):998-1002.
BACKGROUND: Cryptogenic fibrosing alveolitis (CFA) is an uncommon disorder of unknown aetiology characterised by interstitial fibrosis which typically shows a restrictive pattern on pulmonary function testing. Some patients with CFA and relative preservation of lung volumes have been described and it has been suggested that their volume preservation may be due to concomitant emphysema. In a retrospective study the relative frequency of preserved lung volumes in CFA, its relationship to emphysema determined by CT scanning, its clinical features, and its subsequent natural history were investigated. METHODS: Using predefined characteristics 48 patients with CFA were identified from pulmonary function records over a three year period. Volume preservation was defined as a forced vital capacity (FVC) of > 80% predicted at presentation. Patients with relative volume preservation were compared with those with more typical pulmonary restriction and clinical data at presentation, and details of their subsequent prognosis, treatment and loss of lung function with time were obtained. Where available, computed tomographic (CT) scans for the two groups were compared in a blinded fashion to score the extent of fibrosis and the presence of concomitant emphysema. RESULTS: Twenty one (44%) of the patients with CFA had a FVC of > 80% predicted. They were more likely to be male (76% versus 48%) and to be current smokers (57% versus 22%) with a heavier life time cigarette consumption than the restricted patients (mean (SE) 38 (4.6) versus 25 (4.5) pack years). There were no significant differences in prognosis and subsequent treatment between the groups. Comparable HRCT scans were available in 23 subjects (seven preserved, 16 restricted). They showed no difference in extent of the pulmonary fibrosis but patients with volume preservation were more likely to show concomitant emphysema (86% versus 19%). Patients with emphysema on HRCT scans were heavier smokers (41(10) versus 21(17) pack years) than those without emphysema but there was no difference in the extent of CFA score between the two groups. CONCLUSIONS: In this area of high smoking prevalence a significant number of patients with CFA presented with relative preservation of lung volumes and FEV1/FVC ratio. In many of these subjects this appears to reflect coincidental emphysema. This may make interpretation of gas transfer factor used to monitor progression in CFA difficult. However, there was no evidence that lung volumes at presentation were of prognostic significance. 

PMCID: PMC1758455  PMID: 9487350
22.  Obstructive sleep apnoea: a progressive disorder? 
Thorax  1997;52(10):843-844.
PMCID: PMC1758437  PMID: 9404368
23.  Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial 
BMJ : British Medical Journal  2000;320(7245):1297-1303.
To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease.
Double blind, placebo controlled study.
Eighteen UK hospitals.
751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV1) 50% of predicted normal.
Inhaled fluticasone propionate 500 μg twice daily from a metered dose inhaler or identical placebo.
Main outcome measures
Efficacy measures: rate of decline in FEV1 after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events.
There was no significant difference in the annual rate of decline in FEV1 (P=0.16). Mean FEV1 after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P<0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P=0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P=0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P=0.034).
Fluticasone propionate 500 μg twice daily did not affect the rate of decline in FEV1 but did produce a small increase in FEV1. Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.
PMCID: PMC27372  PMID: 10807619
24.  Lung volume reduction surgery in chronic obstructive pulmonary disease. 
Thorax  1996;51(Suppl 2):S29-S34.
PMCID: PMC1090703  PMID: 8869349
Thorax  1994;49(11):1181.
PMCID: PMC475291

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