Patients' and carers' preferences in two models of care for acute exacerbations of COPD: results of a randomised controlled trial

BACKGROUND: Patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) were randomised to either hospital at home (HaH) or inpatient management, and patient and carer preferred site of management and satisfaction with care received in the two arms was determined. METHODS: Emergency admissions with an acute exacerbation of COPD were randomised to inpatient care or HaH care. After discharge an independent observer administered a questionnaire to both patients and carers on the preferred site of care and scored satisfaction with the care received. RESULTS: Of 60 patients recruited, 30 were randomised to receive HaH care. Retrospective patient preference for HaH care was 96.3% in the domiciliary arm and 59.3% in the conventional arm; carer preference figures were 85.7% and 42.9%, respectively. There was a higher preference for domiciliary care by both patients and carers in the HaH arm than in the inpatient arm (p=0.001 and p=0.01, respectively). Patients recorded equal satisfaction with care in the two arms (88.1% in the conventional arm, 91.7% in the domiciliary arm); carer scores were 91.3% and 91.9%, respectively. CONCLUSIONS: The results of this study show that both patients and carers were significantly more likely to prefer domiciliary care if they were in the HaH arm. Since patients had to be willing to be looked after at home, both patients' and carers' perceptions of the benefits of HaH care were reinforced by their experience. HaH care of acute exacerbations of COPD is the preferred option in suitable patients.     

Readmission rates and life threatening events in COPD survivors treated with non-invasive ventilation for acute hypercapnic respiratory failure

BACKGROUND: Non-invasive ventilation (NIV) has been shown to reduce intubation and in-hospital mortality in patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure (AHRF). However, little information exists on the outcomes following discharge. A study was undertaken to examine the rates of readmission, recurrent AHRF, and death following discharge and the risk factors associated with them. METHODS: A cohort of COPD patients with AHRF who survived after treatment with NIV in a respiratory high dependency unit was prospectively followed from July 2001 to October 2002. The times to readmission, first recurrent AHRF, and death were recorded and analysed against potential risk factors collected during the index admission. RESULTS: One hundred and ten patients (87 men) of mean (SD) age 73.2 (7.6) years survived AHRF after NIV during the study period. One year after discharge 79.9% had been readmitted, 63.3% had another life threatening event, and 49.1% had died. Survivors spent a median of 12% of the subsequent year in hospital. The number of days in hospital in the previous year (p = 0.016) and a low Katz score (p = 0.018) predicted early readmission; home oxygen use (p = 0.002), APACHE II score (p = 0.006), and a lower body mass index (p = 0.041) predicted early recurrent AHRF or death; the MRC dyspnoea score (p<0.001) predicted early death. CONCLUSIONS: COPD patients with AHRF who survive following treatment with NIV have a high risk of readmission and life threatening events. Further studies are urgently needed to devise strategies to reduce readmission and life threatening events in this group of patients.     

One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration

BACKGROUND: Non-invasive ventilation (NIV) reduces mortality and intubation rates in patients with chronic obstructive pulmonary disease (COPD) admitted to hospital with respiratory acidosis. This study aimed to determine the prevalence of respiratory acidosis in patients admitted with COPD, to draw inferences about oxygen therapy, and to determine the need for NIV services for acute COPD in typical UK hospitals. METHODS: This one year prospective prevalence study identified patients with COPD aged 45-79 years inclusive who were admitted to Leeds General Infirmary, St James's University, and Killingbeck Hospitals, Leeds between 1 March 1997 and 28 February 1998. The prevalence of respiratory acidosis and the relationship with oxygenation are described. Other outcomes included intensive care use and in hospital mortality. From this data population prevalence estimates were determined for respiratory acidosis, from which the need for NIV in a typical district general hospital was modelled. RESULTS: 983 patients were admitted, 11 of whom required immediate intubation. 20% of the remaining 972 had a respiratory acidosis. Acidosis was associated with subsequent admission to the intensive care unit (ICU): pH<7.25, OR 6.10 (95% confidence interval (CI) 1.19 to 31.11); pH 7.25-7.30, OR 8.73 (95% CI 2.11 to 36.06). pH was inversely correlated with arterial oxygen tension (PaO(2)) in the 47% of patients who were hypercapnic, with a PaO(2) of >10 kPa being associated with acidosis in most hypercapnic patients. 80% remained acidotic after initial treatment, giving an age/sex specific prevalence for England and Wales of 75 (95% CI 61 to 90)/100 000/year for men aged 45-79 years and 57 (95% CI 46 to 69)/100 000/year for women. Modelling the need for NIV for all COPD patients indicates that a typical UK hospital will admit 90 patients per year with acidosis of which 72 will require NIV. CONCLUSIONS: In patients with acute COPD the PaO(2) should be maintained at 7.3-10 kPa (SaO(2) 85-92%) to avoid the dangers of hypoxia and acidosis. If all COPD patients with a respiratory acidosis (pH<7.35) after initial treatment are offered NIV, a typical UK hospital will treat 72 patients per year.     

Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often present with severe acute exacerbations requiring hospital treatment. However, little is known about the prognostic consequences of these exacerbations. A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality. METHODS: Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital (visits to the emergency service and admissions), patient age, smoking, body mass index, co-morbidity, long term oxygen therapy, forced spirometric parameters, and arterial blood gas tensions in a prospective cohort of 304 men with COPD followed up for 5 years. The mean (SD) age of the patients was 71 (9) years and forced expiratory volume in 1 second was 46 (17)%. RESULTS: Only older age (hazard ratio (HR) 5.28, 95% CI 1.75 to 15.93), arterial carbon dioxide tension (HR 1.07, 95% CI 1.02 to 1.12), and acute exacerbations of COPD were found to be independent indicators of a poor prognosis. The patients with the greatest mortality risk were those with three or more acute COPD exacerbations (HR 4.13, 95% CI 1.80 to 9.41). CONCLUSIONS: This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis. Mortality increases with the frequency of severe exacerbations, particularly if these require admission to hospital.     

Randomized controlled trial of supported discharge in patients with exacerbations of chronic obstructive pulmonary disease

BACKGROUND: A randomised trial was performed on patients presenting to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD) to compare outcomes in those managed at home with support with those admitted to hospital in the standard manner. METHODS: Over an 18 month period all patients presenting to the Royal Infirmary of Edinburgh on weekdays (n=718) with a diagnosis of an exacerbation of COPD were assessed for inclusion in the trial. Patients with impaired level of consciousness, acute confusion, acute changes on radiography, or an arterial pH of <7.35 or with other serious medical or social reasons for admission were excluded. Patients randomised to home support were discharged with an appropriate treatment package (antibiotics, corticosteroids, nebulised bronchodilators and, if necessary, home oxygen). They were visited by a nurse the following day and thereafter at intervals of 2-3 days until recovery when they were discharged from follow up. Parallel observations were made on patients allocated to normal hospital admission up to the point of discharge. Patients in both groups were assessed at home eight weeks after the initial assessment. RESULTS: Among weekday patients 353 (50%) were considered obligatory admissions, 140 (19%) were admitted because of co-morbidity, 17 (2%) because of poor social circumstances, and 24 (3%) did not consent to the trial. The remaining 184 (26%) were randomised (2:1) either to home support or to a standard hospital admission. The median time to discharge was 7 days for the home support group and 5 days for the admitted group (p<0.01); 25% of the home support group and 34% of the admitted group were readmitted before the final assessment at eight weeks (p>0.05). There were no significant differences between the groups in attendances by GPs and carers or in health status measured eight weeks after the initial assessment. Satisfaction with the service was good. The mean total health service cost per patient was estimated as 877 pounds sterling for the home support group and 1753 pounds sterling for the admitted group. CONCLUSIONS: This study shows that home supported discharge is a well tolerated, safe, and economic alternative to hospital admission for a proportion of patients referred to hospital for admission for an exacerbation of COPD.     

Effect of exacerbations on quality of life in patients with chronic obstructive pulmonary disease: a 2 year follow up study

BACKGROUND: A study was undertaken to evaluate exacerbations and their impact on the health related quality of life (HRQL) of patients with chronic obstructive pulmonary disease (COPD). METHODS: A 2 year follow up study was performed in 336 patients with COPD of mean (SD) age 66 (8.2) years and mean (SD) forced expiratory volume in 1 second (FEV(1)) 33 (8)% predicted. Spirometric tests, questions regarding exacerbations of COPD, and HRQL measurements (St George's Respiratory Questionnaire (SGRQ) and SF-12 Health Survey) were conducted at 6 month intervals. RESULTS: A total of 1015 exacerbations were recorded, and 103 (30.7%) patients required at least one hospital admission during the study. After adjustment for baseline characteristics and season of assessment, frequent exacerbations had a negative effect on HRQL in patients with moderate COPD (FEV(1) 35-50% predicted); the change in SGRQ total score of moderate patients with > or =3 exacerbations was almost two points per year greater (worse) than those with <3 exacerbations during the follow up (p = 0.042). For patients with severe COPD (FEV(1) <35% predicted) exacerbations had no effect on HRQL. The change in SGRQ total score of patients admitted to hospital was almost 2 points per year greater (worse) than patients not admitted, but this effect failed to show statistical significance in any severity group. There was a significant and independent seasonal effect on HRQL since SGRQ total scores were, on average, 3 points better in measurements performed in spring/summer than in those measured in the winter (p<0.001). CONCLUSIONS: Frequent exacerbations significantly impair HRQL of patients with moderate COPD. A significant and independent effect of seasonality was also observed.     

The pulmonary physician in critical care. 11: critical care management of respiratory failure resulting from COPD

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.     

UK National COPD Audit 2003: Impact of hospital resources and organisation of care on patient outcome following admission for acute COPD exacerbation

BACKGROUND: Acute chronic obstructive pulmonary disease (COPD) exacerbations use many hospital bed days and have a high rate of mortality. Previous audits have shown wide variability in the length of stay and mortality between units not explained by patient factors. This study aimed to explore associations between resources and organisation of care and patient outcomes. METHODS: 234 UK acute hospitals each prospectively identified 40 consecutive acute COPD admissions, documenting process of care and outcomes from a retrospective case note audit. Units also completed a resources and organisation of care proforma. RESULTS: Data for 7529 patients were received. Inpatient mortality was 7.4% and mortality at 90 days was 15.3%; the readmission rate was 31.4%. Mean length of stay for discharged patients was 8.7 days (median 6 days). Wide variation was observed in all outcomes between hospitals. Both inpatient mortality (odds ratio (OR) 0.67, CI 0.50 to 0.90) and 90 day mortality (OR 0.75, CI 0.60 to 0.94) were associated with a staff ratio of four or more respiratory consultants per 1000 hospital beds. The length of stay was reduced in units with more respiratory consultants, better organisation of care scores, an early discharge scheme, and local COPD management guidelines. CONCLUSIONS: Units with more respiratory consultants and better quality organised care have lower mortality and reduced length of hospital stay. This may reflect unit resource richness. Dissemination of good organisational practice and recruitment of more respiratory specialists offers the potential for improved outcomes for hospitalised COPD patients.     

Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD

BACKGROUND: A study was undertaken to record exacerbations and health resource use in patients with COPD during 6 months of treatment with tiotropium, salmeterol, or matching placebos. METHODS: Patients with COPD were enrolled in two 6-month randomised, placebo controlled, double blind, double dummy studies of tiotropium 18 micro g once daily via HandiHaler or salmeterol 50 micro g twice daily via a metered dose inhaler. The two trials were combined for analysis of heath outcomes consisting of exacerbations, health resource use, dyspnoea (assessed by the transitional dyspnoea index, TDI), health related quality of life (assessed by St George's Respiratory Questionnaire, SGRQ), and spirometry. RESULTS: 1207 patients participated in the study (tiotropium 402, salmeterol 405, placebo 400). Compared with placebo, tiotropium but not salmeterol was associated with a significant delay in the time to onset of the first exacerbation. Fewer COPD exacerbations/patient year occurred in the tiotropium group (1.07) than in the placebo group (1.49, p<0.05); the salmeterol group (1.23 events/year) did not differ from placebo. The tiotropium group had 0.10 hospital admissions per patient year for COPD exacerbations compared with 0.17 for salmeterol and 0.15 for placebo (not statistically different). For all causes (respiratory and non-respiratory) tiotropium, but not salmeterol, was associated with fewer hospital admissions while both groups had fewer days in hospital than the placebo group. The number of days during which patients were unable to perform their usual daily activities was lowest in the tiotropium group (tiotropium 8.3 (0.8), salmeterol 11.1 (0.8), placebo 10.9 (0.8), p<0.05). SGRQ total score improved by 4.2 (0.7), 2.8 (0.7) and 1.5 (0.7) units during the 6 month trial for the tiotropium, salmeterol and placebo groups, respectively (p<0.01 tiotropium v placebo). Compared with placebo, TDI focal score improved in both the tiotropium group (1.1 (0.3) units, p<0.001) and the salmeterol group (0.7 (0.3) units, p<0.05). Evaluation of morning pre-dose FEV(1), peak FEV(1) and mean FEV(1) (0-3 hours) showed that tiotropium was superior to salmeterol while both active drugs were more effective than placebo. CONCLUSIONS: Exacerbations of COPD and health resource usage were positively affected by daily treatment with tiotropium. With the exception of the number of hospital days associated with all causes, salmeterol twice daily resulted in no significant changes compared with placebo. Tiotropium also improved health related quality of life, dyspnoea, and lung function in patients with COPD.     

Hepatic resection for colorectal liver metastases: A cost-effectiveness analysis

OBJECTIVE: To analyze the cost-effectiveness of resection for liver metastases compared with standard nonsurgical cytotoxic treatment. SUMMARY BACKGROUND DATA: The efficacy of hepatic resection for metastases from colorectal cancer has been debated, despite reported 5-year survival rates of 20% to 40%. Resection is confined to specialized centers and is not widely available, perhaps because of lack of appropriate expertise, resources, or awareness of its efficacy. The cost-effectiveness of resection is important from the perspective of managed care in the United States and for the commissioning of health services in the United Kingdom. METHODS: A simple decision-based model was developed to evaluate the marginal costs and health benefits of hepatic resection. Estimates of resectability for liver metastases were taken from UK-reported case series data. The results of 100 hepatic resections conducted in Sheffield from 1997 to 1999 were used for the cost calculation of liver resection. Survival data from published series of resections were compiled to estimate the incremental cost per life-year gained (LYG) because of the short period of follow-up in the Sheffield series. RESULTS: Hepatic resection for colorectal liver metastases provides an estimated marginal benefit of 1.6 life-years (undiscounted) at a marginal cost of 6,742 pound sterling++. If 17% of patients have only palliative resections, the overall cost per LYG is approximately 5,236 pound sterling (5,985 pound sterling with discounted benefits). If potential benefits are extended to include 20-year survival rates, these figures fall to approximately 1,821 pound sterling (2,793 pound sterling with discounted benefits). Further univariate sensitivity analysis of key model parameters showed the cost per LYG to be consistently less than 15,000 pound sterling. CONCLUSION: In this model, hepatic resection appears highly cost-effective compared with nonsurgical treatments for colorectal-related liver metastases.     

Do check X-rays influence the management of patients who have undergone hip fracture fixation using image intensifier guidance?

OBJECTIVE: To determine if postoperative check X-rays influence the management of patients who have undergone hip fracture fixation using image intensifier guidance and the possible economic impact. A fractured neck of femur is the commonest fracture sustained in the UK amongst the elderly population, with internal fixation commonly carried out under image intensifier guidance, producing high quality intraoperative images. In the postoperative period, patients often receive a subsequent check X-ray, although recent evidence has suggested little additional information is gained. METHODS: We examined the X-rays of 100 patients who underwent internal fixation (using image intensifier guidance) for a fractured neck of femur. RESULTS: Twenty-four patients received a postoperative check X-ray, although none of these patients had their management altered by this subsequent X-ray. CONCLUSION: If these check X-rays are avoided, there is a potential saving of over 2000 sterling pound in our hospital and 38,800 sterling pound in Scotland per annum.     

Estimation of the additional costs of chemotherapy for patients with advanced non-small cell lung cancer

BACKGROUND: A large multicentre randomised trial, the Big Lung Trial, which in part compared supportive care with or without cisplatin-based chemotherapy in patients with advanced non-small cell lung cancer, provided an opportunity to evaluate the impact on the UK National Health Service of the costs incurred with the use of chemotherapy. METHODS: This costing study was based on the retrospective collection of resource use data from hospital records. Case notes from 194 patients (98 chemotherapy + supportive care (C), 96 supportive care alone (NoC)) were inspected in eight centres recruiting the largest numbers of patients into the Big Lung Trial. Quantities were multiplied by fixed unit costs to calculate a total cost for each patient. The main outcome measure was the total cost incurred by the use of secondary care resources (including investigations, chemotherapy, radiotherapy, surgical procedures, inpatient days, outpatient attendances, and hospice inpatient care) in the two groups. RESULTS: Patients randomised to receive cisplatin-based chemotherapy had an average of 3.4 more inpatient bed days than the mean of 11.9 days for patients randomised to supportive care alone, and more outpatient attendances. NoC patients were more likely to have received palliative radiotherapy. The mean total cost for C patients was 5355 sterling pound compared with 3595 sterling pound for the NoC group, difference 760 sterling pound (95% CI 781 sterling pound to 2742 sterling pound ). When split, the cost in the C group associated with the administration of chemotherapy was 1233 sterling pound and non-chemotherapy costs were 4122 sterling pound . CONCLUSION: The additional cost of chemotherapy was not offset by a reduction in subsequent costs (as the non-chemotherapy costs were similar), so the survival benefit of about 10 weeks observed in the C group was achieved with the cost of chemotherapy administration.     

Non-invasive ventilation assists chest physiotherapy in adults with acute exacerbations of cystic fibrosis

BACKGROUND: Chest physiotherapy is essential to the management of cystic fibrosis (CF). However, respiratory muscle fatigue and oxygen desaturation during treatment have been reported. The aim of this study was to determine whether non-invasive ventilation (NIV) during chest physiotherapy could prevent these adverse effects in adults with exacerbations of CF. METHODS: Twenty six patients of mean (SD) age 27 (6) years and forced expiratory volume in 1 second (FEV1) 34 (12)% predicted completed a randomised crossover trial comparing standard treatment (active cycle of breathing technique, ACBT) with ACBT + NIV. Respiratory muscle strength (PImax, PEmax), spirometric parameters, and dyspnoea were measured before and after treatment. Pulse oximetry (SpO2) was recorded during treatment. Sputum production during treatment and 4 and 24 hours after treatment was evaluated. RESULTS: There was a significant reduction in PImax following standard treatment that was correlated with baseline PImax (r=0.73, p<0.001). PImax was maintained following NIV (mean difference from standard treatment 9.04 cm H2O, 95% confidence interval (CI) 4.25 to 13.83 cm H2O, p=0.006). A significant increase in PEmax was observed following the NIV session (8.04 cm H2O, 95% CI 0.61 to 15.46 cm H2O, p=0.02). The proportion of treatment time with SpO2 < or =90% was correlated with FEV1 (r=-0.65, p<0.001). NIV improved mean SpO2 (p<0.001) and reduced dyspnoea (p=0.02). There were no differences in FEV1, forced vital capacity (FVC) or sputum weight, but FEF(25-75) increased following NIV (p=0.006). CONCLUSION: Reduced inspiratory muscle strength and oxygen desaturation during chest physiotherapy are associated with inspiratory muscle weakness and severity of lung disease in adults with exacerbations of CF. Addition of NIV improves inspiratory muscle function, oxygen saturation and small airway function and reduces dyspnoea.     

Noninvasive Mechanical Ventilation in Valencia,Spain: From Theory to Practice

ObjectiveTo obtain representative data on the type, frequency of use, and availability of resources for noninvasive mechanical ventilation (NIV) in hospitals (acute respiratory failure) and at home (chronic respiratory failure).MethodWe sent a purpose-designed questionnaire to all the hospitals in the Autonomous Community of Valencia, Spain and followed up with a telephone interview.ResultsSeventy percent of the hospitals responded to the survey. NIV was used to treat patients with acute respiratory episodes in 100% of the intensive care units and in 88% of the respiratory medicine departments. The most common diseases were chronic obstructive pulmonary disease (COPD) (mean [SD] 60% [20%]), obesity hypoventilation syndrome (22% [12%]), neuromuscular diseases (6.5% [8%]), and kyphoscoliosis (6.5% [7%]). Other diseases accounted for 4% [11%] of cases. Emergency departments used NIV in 69% of patients, internal medicine departments in 37%, hospital-based home care units in 19%, and other departments in 12%. None of the hospitals that responded to the survey had an intermediate care unit and considerable differences were found in terms of NIV systems used. Home NIV was provided by 88% of hospitals. Patients using home NIV had COPD (31% [18%]), obesity hypoventilation syndrome (30% [18%]), neuromuscular diseases (16% [23%]), kyphoscoliosis (12% [10%]), and other diseases (11% [17%]). Patient numbers varied greatly from one hospital to the next. Home NIV was delivered using a nasal interface in 65% (32%) of cases, an oral-nasal interface in 33% (33%), a tracheostomy tube in 2% (3%), and a mouthpiece in 1% (3%). Only 31.3% of hospitals has a specialized home NIV unit. Home monitoring was performed mainly by service providers. We calculated that home NIV was used in 29 individuals per 100 000 population. Only 50% of the respiratory medicine departments surveyed had written NIV protocols; the corresponding percentages for other departments were 44% for home care units, 19% for emergency departments, and 12% for internal medicine departments.ConclusionsWe observed differences in the type of equipment used, and considerable deficiencies in the availability of human and material resources and support systems. Although NIV is mostly used in hospitals to treat patients with acute respiratory failure, home NIV is also very common and is characterized by greater variability in terms of the number and type of patients. We also observed deficiencies in terms of written protocols for patients with acute and chronic disease.     

Long-term survival following emergency abdominal aortic aneurysm repair

Survival following emergency surgery for ruptured abdominal aortic aneurysm remains poor and is in stark contrast to that for elective repair. We have carried out a 5-year retrospective observational study to determine the long-term (5-year) survival of patients following emergency surgery for ruptured abdominal aortic aneurysm at a district general hospital in East Anglia. A total of 99 patients presented to the operating theatre for emergency repair of ruptured abdominal aortic aneurysm in this 5-year study period. In-hospital mortality was 70% and was unchanged over the 5 years. Overall long-term survival in those patients discharged from hospital was good. The ICU cost per long-term survivor was calculated to be pound sterling 36750.     

Intravenous aminophylline in patients admitted to hospital with non-acidotic exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial

BACKGROUND: Intravenous aminophylline is commonly used in the treatment of exacerbations of chronic obstructive pulmonary disease (COPD), despite limited evidence for its efficacy and known risks of toxicity. We hypothesised that adding intravenous aminophylline to conventional treatment would not produce clinically important changes in the speed of spirometric or symptomatic recovery or shorten hospital stay in patients with exacerbations of COPD. METHODS: Eighty patients admitted to hospital with non-acidotic exacerbations of COPD were recruited at admission to a randomised, double blind, placebo controlled study comparing intravenous aminophylline 0.5 mg/kg/hour after an appropriate loading dose with an equivalent volume of 0.9% saline. The primary outcome was the change in post-bronchodilator forced expiratory volume in 1 second (FEV(1)) over the first 5 days of the admission. Secondary end points were changes in self-reported breathlessness, arterial blood gas tensions, forced vital capacity (FVC), and length of hospital stay. RESULTS: There was no difference in the post-bronchodilator FEV(1) over the first 5 days between the aminophylline and placebo groups. In the aminophylline group, 2 hours of treatment produced a small but significant rise in arterial pH (p = 0.001) and a fall in arterial carbon dioxide tension (p = 0.01) compared with placebo treatment. There were no differences in the severity of breathlessness, post-bronchodilator FVC, or length of hospital stay between the groups. Nausea was a more frequent side effect in the aminophylline group (46% v 22%; p<0.05), but palpitations and headache were noted equally in both groups. CONCLUSIONS: Although intravenous aminophylline produced small improvements in acid-base balance, these did not influence the subsequent clinical course. No evidence was found for any clinically important additional effect of aminophylline treatment when used with high dose nebulised bronchodilators and oral corticosteroids. Given its known toxicity, we cannot therefore recommend the use of intravenous aminophylline in the treatment of non-acidotic COPD exacerbations.     

Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by both an accelerated decline in lung function and periods of acute deterioration in symptoms termed exacerbations. The aim of this study was to investigate whether these are related. METHODS: Over 4 years, peak expiratory flow (PEF) and symptoms were measured at home daily by 109 patients with COPD (81 men; median (IQR) age 68.1 (63-74) years; arterial oxygen tension (PaO(2)) 9.00 (8.3-9.5) kPa, forced expiratory volume in 1 second (FEV(1)) 1.00 (0.7-1.3) l, forced vital capacity (FVC) 2.51 (1.9-3.0) l); of these, 32 (29 men) recorded daily FEV(1). Exacerbations were identified from symptoms and the effect of frequent or infrequent exacerbations (> or < 2.92 per year) on lung function decline was examined using cross sectional, random effects models. RESULTS: The 109 patients experienced 757 exacerbations. Patients with frequent exacerbations had a significantly faster decline in FEV(1) and peak expiratory flow (PEF) of -40.1 ml/year (n=16) and -2.9 l/min/year (n=46) than infrequent exacerbators in whom FEV(1) changed by -32.1 ml/year (n=16) and PEF by -0.7 l/min/year (n=63). Frequent exacerbators also had a greater decline in FEV(1) if allowance was made for smoking status. Patients with frequent exacerbations were more often admitted to hospital with longer length of stay. Frequent exacerbations were a consistent feature within a patient, with their number positively correlated (between years 1 and 2, 2 and 3, 3 and 4). CONCLUSIONS: These results suggest that the frequency of exacerbations contributes to long term decline in lung function of patients with moderate to severe COPD.     

Addition of salmeterol to existing treatment in patients with COPD: a 12 month study

BACKGROUND: This study investigated the addition of salmeterol to existing treatment for exacerbations in patients with poorly reversible chronic obstructive pulmonary disease (COPD). METHODS: 634 patients aged >40 years with a history of COPD exacerbations (including at least two in the previous year) and poor reversibility of airflow obstruction (< or =10% predicted forced expiratory volume in 1 second) received either salmeterol 50 mug or placebo twice daily from a Diskus inhaler for 12 months. The primary outcome was the number of moderate and severe exacerbations. RESULTS: The median rate of moderate or severe exacerbations in the intent-to-treat (ITT) population was lower in the salmeterol group (0.00, range 0.0-9.8, n = 316) than in the placebo group (0.93, range 0.0-13.0, n = 318), but the difference was not statistically significant (p = 0.27). The median rate of exacerbations in the per protocol population (>90% compliance) was also found to be lower in the salmeterol group (0.00, range 0.0-5.0, n = 206) than in the placebo group (0.93, range 0.0-5.6, n = 195) and did reach statistical significance (p = 0.007). For secondary end points, patients receiving salmeterol had significant improvement in lung hyperinflation measured by inspiratory capacity which was evident at 4 weeks and maintained over 12 months (p = 0.035), and a significant improvement in health status measured by the St George's Respiratory Questionnaire at 12 months (p = 0.002). CONCLUSION: Salmeterol has a positive effect on symptoms and health status of patients with COPD when added to usual treatment. Exacerbations are only reduced in patients who comply with treatment.     

Cost effectiveness of inhaled steroid withdrawal in outpatients with chronic obstructive pulmonary disease

BACKGROUND: The evidence for the effectiveness and safety of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is inconclusive. This study determined the cost effectiveness of withdrawing fluticasone propionate (FP) in outpatients with COPD. METHODS: The cost effectiveness analysis was based on a randomised, placebo controlled FP withdrawal study. After a 4 month run in period on FP, patients were randomly assigned to continue FP 500 microg twice daily or to receive placebo for 6 months. A decision analytical model evaluated the 6 month incremental cost effectiveness of the ICS versus ICS withdrawal strategy. One way sensitivity analyses and a Monte Carlo simulation were performed to evaluate the robustness of the findings. RESULTS: The average patient with COPD in the FP group generated 511 in direct medical costs, including 238 for FP. The cost of the placebo strategy was 456. The higher direct drug cost of 212 per patient for the FP strategy during the 6 month follow up period compared with the placebo group was partially offset by a lower exacerbation and hospital admission cost of 157. The 6 month incremental cost effectiveness of the FP strategy compared with placebo was 110 per exacerbation prevented and 1286 per hospital admission prevented. CONCLUSIONS: Over a 6 month period, withdrawing FP in a pre-selected trial population of COPD patients led to absolute cost savings but with a higher rate of exacerbations and hospital admissions.     

Factors predicting successful noninvasive ventilation in acute lung injury

PURPOSE: Noninvasive ventilation (NIV) has been successfully used to treat various forms of acute respiratory failure. It remains unclear whether NIV has potential as an effective therapeutic method in patients with acute lung injury (ALI). The aims of this study were to determine factors predicting the need for endotracheal intubation in ALI patients treated with NIV, and to promote the selection of patients suitable for NIV. METHODS: We conducted a retrospective study of all patients admitted to the intensive care unit (ICU) of the Nippon Medical School Hospital from 2000 to 2006 with a diagnosis of ALI, in whom NIV was initiated. RESULTS: A total of 47 patients with ALI received NIV, and 33 patients (70%) successfully avoided endotracheal intubation. Patients who required endotracheal intubation had a significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and a significantly higher Simplified Acute Physiology Score (SAPS) II, and a significantly lower arterial pH. The respiratory rate decreased significantly within 1 h of starting NIV only in patients successfully treated with NIV. An APACHE II score of more than 17 (P = 0.022) and a respiratory rate of more than 25 breaths x min(-1) after 1 h of NIV (P = 0.024) were independent factors associated with the need for endotracheal intubation. Patients who avoided endotracheal intubation had a significantly lower ICU mortality rate and in-hospital mortality rate than patients who required endotracheal intubation. CONCLUSION: We determined an APACHE II score of more than 17 and a respiratory rate of more than 25 breaths x min(-1) after 1 h of NIV as factors predicting the need for endotracheal intubation in ALI patients treated with NIV.