In February 2006 the Department of Health introduced a new home oxygen service with the aim of improving the assessment of patients on oxygen and allowing access to newer technologies such as ambulatory oxygen. Oxygen is provided following completion of a home oxygen order form and is allocated a predetermined tariff according to the delivery device and usage. In South East Essex there are currently 554 patients receiving home oxygen with an annual cost of £668 546.
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OKY 046, a specific thromboxane synthase inhibitor, was used to investigate whether large pulmonary emboli, like microemboli, cause an increase in thromboxane A2 and an associated increase in vascular permeability in sheep. Nineteen sheep were anaesthetised and had cannulas inserted into the afferent lymphatic of the caudal mediastinal lymph node and pulmonary and carotid arteries. Several days later the animals were pretreated with placebo or OKY 046 0.4 mg/kg one hour before being given clotted blood 0.5 g/kg intravenously. After embolisation in the control animals mean pulmonary artery pressure (MPAP) rose from 12 to 34 mm Hg and pulmonary artery wedge pressure (PAWP) fell from 4.4 to 1.5 mm Hg; the cardiac index did not change but the physiological shunt (QS/QT) rose from 17% to 50%. One hour after embolisation the platelet count fell from 76 to 32 x 10(6)/l whereas at 15 minutes thromboxane B2 rose from 116 to 560 pg/ml in plasma and from 324 to 795 pg/ml in lymph (p less than 0.05). By 2 hours the concentration of thromboxane B2 was higher in lymph than in plasma. Lymph flow rose from 8.7 to a maximum of 27.3 ml/h at 15 minutes but despite the increase in flow the lymph:plasma (L:P) protein ratio did not fall, indicating an increased permeability of the blood vessels to protein. Pretreatment with OKY 046 inhibited the rise in plasma and lymph thromboxane B2, and limited the rise of QS/QT. The changes in MPAP, PAWP, cardiac index, platelet count, lymph flow, and L:P protein ratio, however, were no different from those in untreated sheep. These results indicate that a large pulmonary embolus leads to an increase in plasma and lung lymph thromboxane A2, which moderates the rise in QS/QT in part but not the increase in vascular permeability.
Cysteinyl leukotriene release in association with airway inflammation is a feature of clinical asthma. The acute effects of montelukast (MK-0476), a potent, orally administered, specific cysteinyl leukotriene receptor antagonist, on airways obstruction was assessed in patients with mild to moderately severe asthma.
Twenty two asthmatic subjects were randomised to receive montelukast, 100 mg or 250 mg, or placebo in a double blind, three period, crossover trial. Ten of the patients were using concomitant inhaled corticosteroids.
Montelukast increased the forced expiratory volume in one second (FEV1) from predose baseline values compared with placebo, the percentage point differences between montelukast and placebo being 8.6% (95% CI 3.6 to 13.6) and 8.5% (95% CI 3.5 to 13.5) for the 100 mg and 250 mg doses, respectively.
Single oral doses of montelukast 100 mg and 250 mg produced significant increases in FEV1 irrespective of the concurrent use of inhaled corticosteroids in asthmatic subjects with airflow limitation.
The cysteinyl leukotrienes (LTC4, LTD4, and LTE4) have been shown to mediate airway obstruction evoked by several factors which trigger asthmatic reactions--for example, allergen and exercise. Accordingly, drugs which block the action or formation of these leukotrienes are being evaluated as a new treatment of asthma. Elevated production of leukotrienes has been reported in asthmatic subjects who are intolerant to aspirin and related nonsteroidal anti-inflammatory drugs. In this study the influence of the specific leukotriene receptor antagonist MK-0679 was tested on basal airway function in asthmatic patients with documented aspirin intolerance.
The eight subjects in the study had a mean baseline FEV1 of 78% predicted (range 58-99%) and six required treatment with inhaled glucocorticosteroids (400-1200 micrograms budesonide/beclomethasone daily). On two separate days the subjects received either 825 mg MK-0679 or placebo, orally in a double blind, randomised, crossover design.
The leukotriene antagonist MK-0679 caused bronchodilation which lasted for at least nine hours. The average peak improvement in FEV1 was 18% above the predrug baseline, but the bronchodilator response varied between 34% and 5% and was found to correlate strongly with the severity of asthma and aspirin sensitivity.
The findings indicate that ongoing leukotriene production may be one cause of persistent airway obstruction in aspirin sensitive asthmatic subjects and that they may benefit from treatment with a leukotriene receptor antagonist.
It is not easy to find adequate information about the prognosis in asthma. The condition is notoriously liable to spontaneous variation, the disease is not always clearly defined, and most studies have been small, only covering short periods. In this paper I report a follow-up of 1,000 patients with asthma seen by me over a period of more than 25 years at the Royal Victoria Infirmary, Newcastle.
Occupationally related asthma developing in three patients due specifically to exposure to 1,5-naphthylene di-isocyanate (NDI), a hot curing agent used in manufacturing rubber, has been confirmed for the first time using bronchial provocation testing. This substance has been thought to be safer than toluene di-isocyanate (TDI) and diphenylmethane di-isocyanate (MDI) because of its relatively high melting point (120 degrees C). Each patient worked in the same factory and the circumstances of exposure were similar. Provocation testing was also performed with TDI in concentrations up to 0.018 parts per million (ppm) and MDI in concentrations up to 0.02 ppm, to which the patients had been exposed in the past, but no reactions were elicited. None of the patients had increased bronchial reactivity judged by histamine lability and exercise testing. Each patient was advised to give up his job, but two of the three could not find alternative employment and remained exposed. Three-year follow-up shows that airways narrowing has persisted in those who have remained exposed.
The responses of 20 patients with cystic fribrosis to a B2 agonist, salbutamol, to an anticholinergic agent, SCH 1000, and to a placebo containing difluorodichloroethane and soya lecithin delivered by metered aerosol were compared. Flow rates decreased significantly after placebo (p < 0.05). FEV1 increased significantly after salbutamol (p < 0.05), but the degree of these changes was small. There was a small but significant increase in FVC but no change in flow rates after SCH 1000. Specific conductance increased significantly (p < 0.01) after both salbutamol and SCH 1000. Thoracic gas volume remained unchanged with both drugs and placebo. Four of 20 patients had a clinically significant increase in flow rates with SCH 1000 and three with salbutamol. The consistent increases in sGaw coupled with minimal changes in flow rates, suggest that the physiological effects of both agents is to increase the compressibility of the airway. The results after placebo demonstrate the increased airway reactivity to irritants in cystic fibrosis. In view of this, attention should be paid to the possible irritant effects of inhaled medications.
Glucocorticosteroids are widely used as drugs of first choice in the treatment of moderate to severe asthma. The effects of inhaled steroids in high doses have been compared with oral prednisone in asthmatic patients in a double blind crossover study.
The trial consisted of a two week run in period followed by two four week treatment periods separated by a four week washout. During the treatment period patients took either 1000 micrograms beclomethasone dipropionate twice daily and placebo tablets once daily, or 10 mg prednisone daily in one morning dose and placebo inhaler twice daily. The effects of treatment on the provocative dose of histamine producing a 20% fall in FEV1 (PC20 histamine), peak flow measurements at home, and spirometric measurements in the clinic, as well as on the basal and stimulated plasma cortisol levels were measured.
Seventeen patients with asthma completed the study. After four weeks of treatment beclomethasone dipropionate showed a significantly better effect on morning peak expiratory flow rate than prednisone. There was a trend to a greater improvement in the PC20 histamine in patients receiving beclomethasone dipropionate than in those receiving prednisone. There were no significant differences in spirometric values, symptom scores, or basal and stimulated cortisol levels between the treatments. The within treatment analysis showed a significant effect of prednisone on stimulated cortisol levels but not of beclomethasone dipropionate.
Beclomethasone dipropionate 1000 micrograms twice daily has a slightly greater therapeutic effect in this population of asthmatic patients than 10 mg of prednisone once a day with less effect on adrenocortical function.
One thousand and one men, aged 35-65 years, were identified from the age-sex register of one group general practice. Over four years 900 men were visited at home and asked questions about symptoms potentially related to sleep apnoea and snoring. Height, weight, neck circumference, resting arterial oxygen saturation (SaO2), and spirometric values were also determined. All night oximetry was then performed at home and the tracing analysed for the number of dips in SaO2 of more than 4%. Subjects with more than five dips of 4% SaO2 or more per hour were invited for sleep laboratory polysomnography. Seventeen per cent of the men admitted to snoring 'often'. Multiple linear regression techniques identified and ranked neck circumference (r2 = 7.2%), cigarette consumption (r2 = 3.4%), and nasal stuffiness (r2 = 2%) as the only significant independent predictors of snoring. Together these account for at least a sixfold variation in the likelihood of being an 'often' snorer. Forty six subjects (5%) had > 4% SaO2 dip rates of over five an hour and 31 of these had full sleep studies. Three subjects had clinically obvious and severe symptomatic obstructive sleep apnoea, giving a prevalence of three per 1001 men (0.3%; 95% confidence interval 0.07-0.9%). Eighteen men had obstructive sleep apnoea only when supine and in 10 the cause of the SaO2 dipping on the original home tracing was not elucidated. The > 4% SaO2 dip rates correlated with the history of snoring. Multiple linear regression techniques identified and ranked neck circumference (r2 = 7.9%), alcohol consumption (r2 = 3.7%), age (r2 = 1%) and obesity (r2 = 1%) as the only significant independent predictors of the rate of overnight hypoxic dipping. This study shows that snoring in this randomly selected population correlates best with neck size, smoking, and nasal stuffiness. Obstructive sleep apnoea, defined by nocturnal hypoxaemia, correlates best with neck size and alcohol, and less so with age and general obesity.
Leukotriene receptor antagonists significantly blunt allergen-induced bronchoconstriction in asthmatic subjects. Inhibitors of leukotriene synthesis should theoretically provide similar protection, but conflicting results have been obtained when synthesis inhibitors have been tested in allergen challenge. BAYx 1005, a new inhibitor of leukotriene synthesis, was therefore evaluated in an allergen bronchoprovocation study.
Ten men with mild allergic asthma and bronchial hyperresponsiveness to histamine were recruited. On two different occasions each subject inhaled a single dose of allergen, previously determined to cause at least a 20% fall in forced expiratory volume in one second (FEV1) four hours after ingestion of 750 mg BAYx 1005 or placebo in a double blind crossover design. Urinary excretion of leukotriene E4 was measured before and during the challenges.
The mean (SE) maximal fall in FEV1 was 7.1 (1.7)% after BAYx 1005 and 21.0 (3.0)% after placebo (p < 0.001). The mean difference between treatments was 13.9 (95% CI 7.0 to 20.8) for the maximal fall in FEV1. All subjects were protected by BAYx 1005, the mean inhibition of the fall in FEV1 being 70.0 (7.0)%. The mean area under the curve (AUC) for urinary excretion of leukotriene E4 in the first two hours after the challenge was 1.7 (0.9) after placebo and 0.4 (0.6) after BAYx 1005 (difference = 1.3 (95% CI-0.1 to 2.7); p < 0.05).
These results indicate that BAYx 1005 is a potent inhibitor of allergen-provoked leukotriene synthesis in asthmatic subjects and lend further support to the suggestion that leukotrienes are important mediators of allergen-induced bronchoconstriction.
Leukotrienes have been implicated in the mediation of airway obstruction induced by hyperventilation of cold dry air in asthmatic subjects. The effect of a novel inhibitor of 5-lipoxygenase activating protein, BAYx 1005, on the bronchospastic response to cold dry air hyperventilation was investigated in asthmatic patients.
After a screening cold dry air hyperventilation challenge to document cold air responsiveness, 16 asthmatic subjects (baseline forced expiratory volume in one second (FEV1) > 60% of predicted) underwent cold air challenge three hours after receiving 750 mg of BAYx 1005 or placebo using a randomised, double blind, crossover design. Leukotriene synthesis inhibition was estimated by measuring the concentration of leukotriene B4 in whole blood stimulated with calcium ionophore A21387.
Treatment with BAYx 1005 produced a 34% (95% CI 11 to 63) increase in the amount of cold air minute ventilation required for a 10% decrease in FEV1 (PD10VE) compared with placebo (mean (SE) 37.6 (1.12) 1/min compared with 28.0 (1.13) 1/min, p < 0.006). The PD20VE increased 19% (95% CI 8 to 31) after treatment with BAYx 1005 compared with placebo (57.3(1.10)1/min versus 48.1 (1.10) 1/min, p < 0.002). Treatment with BAYx 1005 produced a 15.4% decrease in ionophore-stimulated LTB4 production, while treatment with placebo produced a 7.1% increase in ex vivo LTB4 (p < 0.02).
Treatment with BAYx 1005, a novel inhibitor of leukotriene synthesis, produced a significant blunting of cold dry air responsiveness consistent with the hypothesis that leukotrienes mediate part of the bronchoconstriction induced by hyperventilation of cold dry air.
The cysteinyl leukotrienes (LTC4, LTD4 and LTE4) have been implicated in the pathogenesis of allergen-induced airway responses. The effects of pretreatment with BAYx 1005, an inhibitor of leukotriene biosynthesis via antagonism of 5-lipoxygenase activating protein, on allergen-induced early and late asthmatic responses has been evaluated.
Eight atopic subjects with mild asthma participated in a two period, double blind, placebo controlled, cross-over trial. Subjects were selected on the basis of a forced expiratory volume in one second (FEV1) of > 70% predicted, a methacholine provocative concentration causing a 20% fall in FEV1 (PC20) of < 32 mg/ ml, a documented allergen-induced early response (EAR, > 15% fall in FEV1 0-1 hour after allergen inhalation) and late response (LAR, > 15% fall in FEV1 3-7 hours after allergen inhalation), and allergen-induced airway hyperresponsiveness (at least a doubling dose reduction in the methacholine PC20 30 hours after allergen inhalation). During the treatment periods subjects received BAYx 1005 (500 mg twice daily) or placebo for 3.5 days; treatment periods were separated by at least two weeks. On the third day of treatment, two hours after administration of medication, subjects performed an allergen inhalation challenge and FEV1 was measured for seven hours.
Treatment with BAYx 1005 attenuated the magnitude of both the allergen-induced early and late asthmatic responses. The mean (SE) maximal fall in FEV1 during the EAR was 26.6 (3.3)% during placebo treatment and 11.4 (3.3)% during treatment with BAYx 1005 (mean difference 15.2 (95% confidence interval (CI) 9.4 to 21.00) with a mean protection afforded by BAYx 1005 of 57.1%. The mean (SE) maximal fall in FEV1 during the LAR was 19.8 (5.7)% during placebo treatment and 10.7 (4.4)% during BAYx 1005 treatment (mean difference 9.2 (95% CI 1.4 to 17.0) with a mean protection afforded by BAYx 1005 of 46.0%. The area under the time response curve (AUC0-3) was also reduced after treatment with BAYx 1005 compared with placebo by 86.5%.h (mean difference 26.3 (95% CI 17.1 to 38.5)) and the AUC3-7 by 59.6%.h (mean difference 26.9 (95% CI-3.8 to 57.6)).
These results show that antagonism of 5-lipoxygenase activating protein can attenuate allergen-induced bronchoconstrictor responses and support an important role for the cysteinyl leukotrienes in mediating these asthmatic responses.
A prospective study to determine the incidence of hiatus hernia and gastro-oesophageal reflux in 1030 consecutive symptomatic adult Nigerian patients undergoing barium meal examination is reported. The results show a very low incidence of hiatus hernia (0-39%) and an equally low incidence of gastro-oesophageal reflux (2-2%) when compared with similar studies in Europe and America. There was a high incidence of duodenal ulcer (23-3%) and a low incidence of gastric ulcer (1-8%), the duodenal/gastric ulcer ratio of 12-1:1 being much higher than in Europe.
Reversibility after administration of an inhaled bronchodilator is not always demonstrable in patients with asthma. Bronchodilator aerosol-induced bronchoconstriction has also been reported to occur in some patients.
Fifteen selected patients showing < 10% improvement in forced expiratory volume in one second (FEV1) when tested with four doses of salbutamol (0.1 mg/dose) or terbutaline (0.25 mg/dose) from a pressurised metered dose inhaler (MDI) participated in two randomised, double blind studies. They received 2.0 mg terbutaline (4 x 2 doses of 0.25 mg) or a corresponding placebo from an MDI connected to a 750 ml spacer, and 1.0 mg (2 x 0.5 mg) terbutaline or placebo from a multidose dry powder inhaler free of additives (Turbohaler).
Inhalation of placebo MDI resulted in a mean (SD) decrease in FEV1 of 20.5 (14.1)% (range -42.9% to +2.6%). In 14 patients inhalation of 2.0 mg terbutaline MDI with spacer resulted in < 10% improvement (mean increase 3.1 (6.0)%). One mg of terbutaline via a Turbohaler resulted in improvements in FEV1 of > 15% in eight patients (mean increase 16.0 (9.7)%). The improvement was < 10% in four patients. Use of placebo Turbohaler did not affect airway calibre (mean change 0.2 (2.9)%).
Additives of MDIs may cause bronchoconstriction in some patients with asthma. In these patients inhalation from a pressurised metered dose inhaler is more likely to decrease the bronchodilator response than inhalation from an additive-free inhaler. The frequency of this phenomenon is unknown.
Of 1055 patients treated surgically for pulmonary hydatid disease, most (950) had isolated lung cysts, the other 105 having both liver and lung cysts. The chest radiograph was most valuable in diagnosis; the Casoni and Weinberg tests and blood eosinophil counts were found to be diagnostically unreliable. One thousand and seventy seven primary operations were performed. Cystotomy and capitonnage were carried out in 906 patients, 40 of whom also had decortication of the pleura. Other procedures included cystotomy with wedge resection of locally damaged lung (29 patients) and cyst removal with capitonnage by Ugon's method (33) or the Perez-Fontana procedure (8) and with costal resection for osteomyelitis in two cases. More radical surgery was carried out in 99 patients for longstanding infection or severe lung destruction. Postoperative complications occurred in 37 patients (3.5%) and the 30 day mortality rate was 1.7%. It is concluded that a lung conserving surgical operation is the treatment of choice for most patients with pulmonary hydatid disease. In patients with coexisting liver cysts the thoracic transpleural approach allowed the lung and liver cysts to be removed at the same session.
Evidence for an association between road traffic pollution and asthma is inconclusive. We report a case-control study of hospital admissions for asthma and respiratory illness among children aged 5-14 in relation to proxy markers of traffic related pollution.
The study was based on routine hospital admissions data in 1992/3 and 1993/4 for North Thames (West) health region within the M25 motorway. Cases were defined as emergency admissions for asthma (n = 1380) or all respiratory illness including asthma (n = 2131), and controls (n = 5703) were other emergency admissions excluding accidents. Cases and controls were compared with respect to distance of residence from nearest main road or roads with peak hour traffic >1000 vehicles and traffic volume within 150 m of residence, obtained by Geographical Information System techniques. Statistical analysis included adjustment for age, sex, admitting hospital, and a deprivation score for the census enumeration district of residence.
Adjusted odds ratios of hospital admission for asthma and respiratory illness for children living within 150 m of a main road compared with those living further away were, respectively, 0.93 (95% CI 0.82 to 1.06) and 1.02 (95% CI 0.92 to 1.14).
This study showed no association between risk of hospital admission for asthma or respiratory illness among children aged 5-14 and proxy markers of road traffic pollution.
For most passengers, even those with respiratory disease, air travel is safe and comfortable. Some patients with COPD may be at risk but, with screening, these patients can be identified and most can travel safely with supplemental oxygen.
Survival to hospital discharge of patients suffering exacerbations of COPD is better than other medical causes for ICU admission. Although non-invasive ventilation (NIV) may prevent progression to tracheal intubation, its failure in most cases should lead to a period of controlled mechanical ventilation aiming for early extubation, possibly supported by NIV and tracheostomy if this fails. A greater understanding of the physiological principles behind ventilatory support of patients with COPD should reduce patient-ventilator disharmony and avoid the excessive use of sedation. The risk of nosocomial infection increases with the length of time the patient remains in the ICU and commonly further prolongs the period of ventilator dependency. Weaning centres with an emphasis on general rehabilitation may offer the best support for such individuals.
There is evidence of a positive association between asthma and obesity in adults and in children. We investigated, in a large sample of English and Scottish primary school children, whether there is a consistent association between fatness and asthma symptoms in Britain.
A cross sectional analysis was made of 18 218 children aged 4-11 years who participated in the 1993 or 1994 surveys of the National Study of Health and Growth (NSHG). Children belonged either to English or Scottish representative samples, or an English inner city sample. Asthma attacks in the previous year, occasional wheeze, or persistent wheeze were the symptoms used in the analysis. Body mass index (BMI) and the sum of triceps and subscapular skinfolds converted to standard deviation scores (SDS) were used to assess levels of fatness.
A total of 14 908 children (81.8%) were included in the analysis. In the multiple logistic analysis BMI and asthma (asthma attacks or wheeze) were associated in the representative sample (OR for the comparison of the 10th and 90th centiles of BMI 1.28, 95% CI 1.11 to 1.48), but sum of skinfolds was unrelated to asthma symptoms in most analyses. The association between asthma and BMI was stronger in girls than in boys in the inner city sample, but less convincingly in the representative sample.
Levels of obesity are associated with asthma symptoms regardless of ethnicity. The association is more consistent for BMI than for sum of skinfolds, partly because obese children are more advanced in their maturation than other children. There is some evidence that, as in adults, the association is stronger in girls than in boys, but only in the multiethnic inner city sample.
A review is presented of key clinical papers published in Thorax and elsewhere between 2008 and April 2011 which have advanced our understanding of cystic fibrosis (CF), primary ciliary dyskinesia and non-CF bronchiectasis. Studies were identified through searches of the Thorax archive and the Medline database. Within the field of CF, the following key themes were studied: diagnosis in equivocal CF, assessment of CF lung disease, novel therapies addressing the basic defect in CF, maintenance pulmonary therapies, management of early Pseudomonas infection, the microbiology of CF lung disease, renal impairment in CF and controversies in lung transplantation in CF.
Williams, Faith M., Draffan, G. H., Dollery, C. T., Clark, J. C., Palmer, A. J., and Vernon, P. (1974).Thorax, 29, 99-103. Use of 18F labelled fluorocarbon-11 to investigate the fate of inhaled fluorocarbons in man and in the rat. The distribution and elimination of 18F labelled fluorocarbon-11 has been followed in a group of rats killed after air breathing following six minutes' exposure to 18F fluorocarbon-11. Whole body and individual organ count rates were measured. In four volunteers the fate of 18F labelled fluorocarbon-11 was followed by both whole body counting and gamma camera measurement of the activity in the lung and mouth region after inhalation from a specially loaded aerosol dispenser.In the rat there was a high initial level in high blood flow organs and in the adrenals and fat: the level in blood and high blood flow organs fell rapidly. Elimination from fat was slow but the adrenal level had fallen within one hour. The fall in whole body count rate was similar to that in fat.In man, the fall in lung concentration was consistent with rapid uptake into tissues followed by slow elimination; the whole body count rate curve also indicated slow elimination. There was no evidence of deposition of droplets of fluorocarbon in the mouth region after use of the aerosol.
During the last decade several long term studies of interventions in patients with COPD have been published. This review analyses the potential of these interventions to alter the progression of the condition. The only treatment that has unequivocally been shown to reduce the rate of decline in FEV(1) is smoking cessation. Active psychological intervention in combination with pharmacotherapy is required. Other treatments may have an effect on the rate of decline in FEV(1) but this appears to be very small, at most. Several treatments affect the exacerbation rate and therefore might affect the progression of the disease. Further studies are warranted to examine this effect.
