Rahul Mukherjee

The effect of domiciliary noninvasive ventilation on clinical outcomes in stable and recently hospitalized patients with COPD: a systematic review and meta-analysis

Introduction Noninvasive ventilation (NIV) improves survival among patients with hypercapnic respiratory failure in hospital, but evidence for its use in domiciliary settings is limited. A patient’s underlying risk of having an exacerbation may affect any potential benefit that can be gained from domiciliary NIV. This is the first comprehensive systematic review to stratify patients based on a proxy for exacerbation risk: patients in a stable state and those immediately post-exacerbation hospitalization. Methods A systematic review of nonrandomized and randomized controlled trials (RCTs) was undertaken in order to compare the relative effectiveness of different types of domiciliary NIV and usual care on hospital admissions, mortality, and health-related quality of life. Standard systematic review methods were used for identifying studies (until September 2014), quality appraisal, and synthesis. Data were presented in forest plots and pooled where appropriate using random-effects meta-analysis. Results Thirty-one studies were included. For stable patients, there was no evidence of a survival benefit from NIV (relative risk [RR] 0.88 [0.55, 1.43], I2=60.4%, n=7 RCTs), but there was a possible trend toward fewer hospitalizations (weighted mean difference −0.46 [−1.02, 0.09], I2=59.2%, n=5 RCTs) and improved health-related quality of life. For posthospital patients, survival benefit could not be demonstrated within the three RCTs (RR 0.89 [0.53, 1.49], I2=25.1%), although there was evidence of benefit from four non-RCTs (RR 0.45 [0.32, 0.65], I2=0%). Effects on hospitalizations were inconsistent. Post hoc analyses suggested that NIV-related improvements in hypercapnia were associated with reduced hospital admissions across both populations. Little data were available comparing different types of NIV. Conclusion The effectiveness of domiciliary NIV remains uncertain; however, some patients may benefit. Further research is required to identify these patients and to explore the relevance of improvements in hypercapnia in influencing clinical outcomes. Optimum time points for commencing domiciliary NIV and equipment settings need to be established.

Utility of respiratory ward-based NIV in acidotic hypercapnic respiratory failure

We sought to elicit predictors of in‐hospital mortality for first and subsequent admissions with acidotic hypercapnic respiratory failure (AHRF) in a cohort of chronic obstructive pulmonary disease patients who have undergone ward‐based non‐invasive ventilation (NIV), and identify features associated with long‐term survival.

Evaluation of oxygen prescription in relation to hospital admission rate in patients with chronic obstructive pulmonary disease

BackgroundLong term oxygen therapy (LTOT) has a strong evidence base in COPD patients with respiratory failure, but prescribing practices are recognized to need reform to ensure appropriate use and minimize costs. In the UK, since February 2006, all Home Oxygen prescription is issued by hospitals, making respiratory specialists totally in charge of home oxygen prescription. It has been widely noted that inappropriate home oxygen, often for intermittent use (“short burst”), is frequently prescribed in patients with COPD and related conditions with the intention to prevent hospital admissions outside of evidence based LTOT guidelines. We participated in a national Lung Improvement Project aimed at making LTOT use more evidence based. We utilised this unique opportunity of studying the effect of removal of oxygen from COPD patients (who did not meet LTOT criteria) on hospital admission rates.MethodsPrimary and secondary care data sources were used to identify patients with COPD in a single primary care trust who were admitted to hospital at least once due to COPD between April 2007 and November 2010. Admission rates were compared between LTOT users and non-users, adjusted for age and COPD severity. LTOT users were further studied for predictors of admission in those appropriately or inappropriately given oxygen according to NICE guidance, and for admissions before and after oxygen receipt, adjusting further for co-morbidity. Mortality and economic analyses were also conducted.ResultsReadmission was more likely in LTOT users (3.18 v 1.67 per patient, p < 0.001) after adjustment for FEV1 and age by multiple regression. When stratifying by appropriateness of LTOT prescription, adjusting also for Charlson index and other covariates, FEV1 predicted admission in appropriate users but there were no predictors in inappropriate users. In longitudinal analyses admission rates did not differ either side of oxygen prescription in appropriate or inappropriate LTOT users. Specialist assessment resulted in cost savings due to reduced use of oxygen.ConclusionsAdmission to hospital is more likely in LTOT users, independent of COPD severity. Oxygen use outside NICE guidance does not appear to prevent admissions.

The cost-effectiveness of domiciliary non-invasive ventilation in patients with end-stage chronic obstructive pulmonary disease: a systematic review and economic evaluation

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease characterised by non-reversible airflow obstruction. Exacerbations are a key cause of morbidity and mortality and place a considerable burden on health-care systems. While there is evidence that patients benefit from non-invasive ventilation (NIV) in hospital during an acute exacerbation, evidence supporting home use for more stable COPD patients is limited. In the U.K., domiciliary NIV is considered on health economic grounds in patients after three hospital admissions for acute hypercapnic respiratory failure. OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of domiciliary NIV by systematic review and economic evaluation. DATA SOURCES Bibliographic databases, conference proceedings and ongoing trial registries up to September 2014. METHODS Standard systematic review methods were used for identifying relevant clinical effectiveness and cost-effectiveness studies assessing NIV compared with usual care or comparing different types of NIV. Risk of bias was assessed using Cochrane guidelines and relevant economic checklists. Results for primary effectiveness outcomes (mortality, hospitalisations, exacerbations and quality of life) were presented, where possible, in forest plots. A speculative Markov decision model was developed to compare the cost-effectiveness of domiciliary NIV with usual care from a UK perspective for post-hospital and more stable populations separately. RESULTS Thirty-one controlled effectiveness studies were identified, which report a variety of outcomes. For stable patients, a modest volume of evidence found no benefit from domiciliary NIV for survival and some non-significant beneficial trends for hospitalisations and quality of life. For post-hospital patients, no benefit from NIV could be shown in terms of survival (from randomised controlled trials) and findings for hospital admissions were inconsistent and based on limited evidence. No conclusions could be drawn regarding potential benefit from different types of NIV. No cost-effectiveness studies of domiciliary NIV were identified. Economic modelling suggested that NIV may be cost-effective in a stable population at a threshold of £30,000 per quality-adjusted life-year (QALY) gained (incremental cost-effectiveness ratio £28,162), but this is associated with uncertainty. In the case of the post-hospital population, results for three separate base cases ranged from usual care dominating to NIV being cost-effective, with an incremental cost-effectiveness ratio of less than £10,000 per QALY gained. All estimates were sensitive to effectiveness estimates, length of benefit from NIV (currently unknown) and some costs. Modelling suggested that reductions in the rate of hospital admissions per patient per year of 24% and 15% in the stable and post-hospital populations, respectively, are required for NIV to be cost-effective. LIMITATIONS Evidence on key clinical outcomes remains limited, particularly quality-of-life and long-term (> 2 years) effects. Economic modelling should be viewed as speculative because of uncertainty around effect estimates, baseline risks, length of benefit of NIV and limited quality-of-life/utility data. CONCLUSIONS The cost-effectiveness of domiciliary NIV remains uncertain and the findings in this report are sensitive to emergent data. Further evidence is required to identify patients most likely to benefit from domiciliary NIV and to establish optimum time points for starting NIV and equipment settings. FUTURE WORK RECOMMENDATIONS The results from this report will need to be re-examined in the light of any new trial results, particularly in terms of reducing the uncertainty in the economic model. Any new randomised controlled trials should consider including a sham non-invasive ventilation arm and/or a higher- and lower-pressure arm. Individual participant data analyses may help to determine whether or not there are any patient characteristics or equipment settings that are predictive of a benefit of NIV and to establish optimum time points for starting (and potentially discounting) NIV. STUDY REGISTRATION This study is registered as PROSPERO CRD42012003286. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Chronic airflow limitation in a rural Indian population: etiology and relationship to body mass index

Purpose Respiratory conditions remain a source of morbidity globally. As such, this study aimed to explore factors associated with the development of airflow obstruction (AFO) in a rural Indian setting and, using spirometry, study whether underweight is linked to AFO. Methods Patients > 35 years old attending a rural clinic in West Bengal, India, took a structured questionnaire, had their body mass index (BMI) measured, and had spirometry performed by an ancillary health care worker. Results In total, 416 patients completed the study; spirometry was acceptable for analysis of forced expiratory volume in 1 second in 286 cases (69%); 16% were noted to exhibit AFO. Factors associated with AFO were: increasing age (95% confidence interval (CI) 0.004–0.011; P = 0.005), smoking history (95% CI 0.07–0.174; P = 0.006), male gender (95% CI 0.19–0.47; P = 0.012), reduced BMI (95% CI 0.19–0.65; P = 0.02), and occupation (95% CI 0.12–0.84; P = 0.08). The mean BMI in males who currently smoked (n = 60; 19.29 kg/m2; standard deviation [SD] 3.46) was significantly lower than in male never smokers (n = 33; 21.15 kg/m2 SD 3.38; P < 0.001). AFO was observed in 27% of subjects with a BMI <18.5 kg/m2, falling to 13% with a BMI ≥18.5 kg/m2 (P = 0.013). AFO was observed in 11% of housewives, 22% of farm laborers, and 31% of cotton/jute workers (P = 0.035). Conclusion In a rural Indian setting, AFO was related to advancing age, current or previous smoking, male gender, reduced BMI, and occupation. The data also suggest that being under-weight is linked with AFO and that a mechanistic relationship exists between low body weight, smoking tobacco, and development of AFO.

Reforming respiratory outpatient services: a before-and-after observational study assessing the impact of a quality improvement project applying British Thoracic Society criteria to the discharge of patients to primary care.

Background: Secondary care physicians caring for people with long-term conditions (LTCs) are under increasing pressure to discharge long-term follow-up patients to primary care. In respiratory medicine, the 2008 British Thoracic Society (BTS) statement on criteria for specialist referral, admission, discharge, and follow-up for adults with respiratory disease remains the only available basis for this dialogue. There is widespread concern about reforming outpatient clinics to meet these demands and the impact of discharging people with respiratory LTCs to primary care. Aims: To examine the impact of implementing BTS guidance on secondary care follow-up of patients with respiratory disease. Methods: We undertook a clinic reform project, which included one-stop medical reviews, providing more open access appointments, and implementing the BTS criteria. The impact on patients was assessed by patient survey, and the impact on GPs was assessed by an analysis of referral patterns pre- and post-reform. Results: There was a significant improvement in commissioner-mandated performance through reduction in follow-up (p=0.006) and the unscheduled hospital admission rate decreased significantly (p=0.021). However, many patients were dissatisfied with the process and re-referral rates rose. Conclusions: Our findings suggest that the delivery of a responsive service capable of sustainable management of respiratory LTCs can be achieved using the BTS criteria. It seems to be efficacious within secondary care, increasing the quality and value of the clinic activity, although hidden impacts on primary care will require further prospective studies.

S115 Hot-hmv uk trial secondary outcome analysis: early readmission is reduced by the addition of home mechanical ventilation to home oxygen therapy in copd patients with chronic respiratory failure following a life-threatening exacerbation

Introduction Hospital readmission following treatment for a life-threatening exacerbation of COPD with acute NIV is frequent and associated with an adverse impact in terms of lung function and health related quality of life. They have been identified as a priority area in the NHS with financial penalties for any patient readmitted within 28 days following discharge. Method A multicentre open labelled randomised controlled trial recruited patients with persistent hypercapnia (PaCO2 > 7 kPa) 2–4 weeks following resolution of acute acidosis. Patients were randomised to either home oxygen therapy (HOT) or HOT and home mechanical ventilation (HOT-HMV). HMV was titrated overnight to control nocturnal hypercapnia. Follow up was for 12 months. The primary outcome, 12-month admission free survival, has been reported previously demonstrating a significant treatment effect (ERS 2016). Secondary outcome analysis included 28-day all-cause hospital readmission and 12 month exacerbation rate. Results 116 patients were randomised (HOT = 59, HOT-HMV = 57), age 67 ± 10 years, FEV1 0.6 ± 0.2 L, PaCO2 7.9 ± 0.9 kPa. 28-day readmission was 22 (37%) in the HOT and 7 (12%) in the HOT-HMV arm (unadjusted HR 0.27, 0.12 to 0.63, p = 0.003; adjusted HR 0.26, 0.11 to 0.61, p = 0.002) (Figure 1). 12 month exacerbation rate was reduced from median 5 (1 to 9) per year in the HOT arm to 4 (2to 6) in the HOT-HMV arm (unadjusted HR 0.64 (0.44 to 0.94); p = 0.022; adjusted HR 0.66, 0.46 to 0.95, p = 0.026). Conclusion The addition of HMV to HOT in patients with persistent hypercapnia following an acute life-threatening exacerbation of COPD reduces both 28-day readmission and 12 month exacerbation frequency. These data strongly support a change in clinical practice in the management of patients with severe COPD and persistent hypercapnia. Abstract S115 Figure 1 Time to hospital re-admission by treatment arm

Effect of enzyme replacement therapy (ERT) added to Home Mechanical Ventilation (HMV) in Adult Pompe disease.

Adult Pompe disease/acid maltase deficiency is an autosomal recessive disorder resulting in accumulation of glycogen in skeletal muscles, leading to myopathy frequently involving respiratory muscles. This involvement can cause respiratory insufficiency that may present as acute hypercapnic respiratory failure. Enzyme replacement therapy (ERT) with alpha – glucosidase alfa, the only disease‐specific treatment, has been available as treatment option since 2006. ERT has shown efficacy concerning muscle strength and pulmonary function in adult patients as well as positive association with survival. We present two cases where addition of ERT to Home Mechanical Ventilation (HMV) showed improvements in lung function and gas exchange that may not be entirely attributable to nocturnal HMV and therefore may further indicate the beneficial role of ERT in conjunction with HMV in Adult Pompe disease.

P121 Feasibility of performing valid spirometry in rural India: preliminary results from a population study assessing the prevalence of COPD

Introduction Spirometry remains the cornerstone in the diagnosis of Chronic Obstructive Pulmonary Disease (COPD). Little is known regarding the determinants and prevalence of COPD in rural India. We undertook a population-based study in Howrah District, West Bengal,India at a community-based primary care clinic of a voluntary organisation to test the feasibility of spirometric estimation of the prevalence of COPD. Methods Spirometry was performed on all adults >35 years attending the clinic. Questionnaire data (capturing respiratory symptoms, occupation, tobacco smoking history, indoor stove use) were gathered for each subject. All spirometric data were examined by an independent UK-based clinical scientist. Results Spirometry was performed in 315 patients over 3 months; 18% (58/315) of measurements were deemed good quality as per ERS guidelines; 45% (143/315) had the correct shaped curve; hence 64% (201/315) of all spirometries were deemed adequate for FEV1 analysis. Poor quality traces were noted in 36% (n=114) and hence were excluded from analysis. Of the adequate spirometries (n=201, mean age 51 years (SD 12.1); 39% male), 84 (42%) were normal, 102 (51%) exhibited mild airflow obstruction, 12 (6%) moderate airflow obstruction and 3 (1.5%) severe airflow obstruction according to British guidelines. Difference in FEV1% predicted between never/ex smokers and current smokers was significant (p=0.029). Indoor stove use was ubiquitous in this population and did not correlate with FEV1 percent predicted. Conclusion In a rural Indian setting, valid spirometry can be obtained in two-thirds of adult patients attending a community clinic with 58% of patients in this sample exhibiting at least mild COPD with a history of current smoking being associated with the development of airflow obstruction.

Early ward-based acute noninvasive ventilation: a paper that changed practice

Noninvasive ventilation (NIV) is now an established evidence-based treatment for acute hypercapnic respiratory failure (AHRF), predominantly for defined patients admitted with exacerbations of chronic obstructive pulmonary disease (COPD), but also a range of other conditions including obesity-related respiratory failure and chest wall deformities requiring an acute hospital admission. Over the past two decades, there has been a significant shift towards greater use of NIV in place of invasive mechanical ventilation (IMV) in this group of patients. Here we set out to discuss a landmark paper in this respect: the report of the YONIV trial (Yorkshire Noninvasive Ventilation Trial), published in June 2000, which addressed the key practical questions around the early use of ward-based NIV at the time [1]. A recent narrative review on the epidemiology of NIV for acute respiratory failure in COPD patients concluded that this dramatic increase in NIV use is probably due to the increased experience of the medical teams, treating sicker patients with comorbidities and utilising NIV outside the intensive care unit (ICU), further confirming the pivotal role of the original trial enabling the early use of acute NIV on medical wards [2]. The landmark YONIV trial addressed key practical questions surrounding the early use of ward-based noninvasive ventilation, which is now an established evidence-based treatment for acute hypercapnic respiratory failure http://ow.ly/BDC530iWhne