The Noninvasive Ventilation Outcomes (NIVO) score: prediction of in-hospital mortality in exacerbations of COPD requiring assisted ventilation.

INTRODUCTION: Acute exacerbations of COPD (AECOPD) complicated by acute (acidaemic) hypercapnic respiratory failure (AHRF) requiring ventilation are common. When applied appropriately, ventilation substantially reduces mortality. Despite this, there is evidence of poor practice and prognostic pessimism. A clinical prediction tool could improve decision making regarding ventilation, but none is routinely used. METHODS: Consecutive patients admitted with AECOPD and AHRF treated with assisted ventilation (principally noninvasive ventilation) were identified in two hospitals serving differing populations. Known and potential prognostic indices were identified a priori. A prediction tool for in-hospital death was derived using multivariable regression analysis. Prospective, external validation was performed in a temporally separate, geographically diverse 10-centre study. The trial methodology adhered to TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) recommendations. RESULTS: Derivation cohort: n=489, in-hospital mortality 25.4%; validation cohort: n=733, in-hospital mortality 20.1%. Using six simple categorised variables (extended Medical Research Council Dyspnoea score 1-4/5a/5b, time from admission to acidaemia >12 h, pH <7.25, presence of atrial fibrillation, Glasgow coma scale ≤14 and chest radiograph consolidation), a simple scoring system with strong prediction of in-hospital mortality is achieved. The resultant Noninvasive Ventilation Outcomes (NIVO) score had area under the receiver operating curve of 0.79 and offers good calibration and discrimination across stratified risk groups in its validation cohort. DISCUSSION: The NIVO score outperformed pre-specified comparator scores. It is validated in a generalisable cohort and works despite the heterogeneity inherent to both this patient group and this intervention. Potential applications include informing discussions with patients and their families, aiding treatment escalation decisions, challenging pessimism and comparing risk-adjusted outcomes across centres.

Patient-reported outcome measures following maxillomandibular advancement surgery in patients with obstructive sleep apnoea syndrome.

Maxillomandibular advancement (MMA) is an effective treatment for obstructive sleep apnoea syndrome (OSAS) that is refractory to conventional treatment. However, it is a highly invasive procedure with several recognised side effects, and we know of few data on its effect on important patient-reported outcome measures (PROMS). Here we describe a case series of patients selected for MMA through our joint respiratory/maxillofacial surgery clinic, detailing the effect of MMA on objective physiological measurements and important PROMS. Patients with confirmed moderate/severe symptomatic OSAS who could not tolerate continuous positive airway pressure (CPAP) or mandibular advancement devices (MAD) were assessed in the clinic for consideration of MMA. Preoperative and postoperative airway measurements, apnoea/hypopnoea index (AHI), Epworth sleepiness scale (ESS) score, and quality of life (10-point Likert scale), were recorded. A customised questionnaire was administered postoperatively to assess selected psychosocial and functional domains (sleep quality, energy levels, appearance, ability to perform daily activities, and mood) and patient satisfaction using five-point Likert scales. Over an 18 month period, 39 patients were referred for consideration of MMA. Ten patients (7 men and 3 women, mean age 49.9, mean BMI 27.5) underwent surgery, which resulted in significant improvements in ESS, quality of life, AHI, and airway diameters. All patients reported improvements in all psychosocial/functional domains except appearance, in which five reported no change or worsened appearance. All subjects felt that MMA provided better symptom control than CPAP. The most commonly reported side effects were facial/lip numbness (9/10) and affected bite (6/10). MMA resulted in significant improvements in ESS, quality of life, and a range of PROMS, with a high level of patient satisfaction.

Assessing the impact of posture on diaphragm morphology and function using an open upright MRI system-A pilot study.

PURPOSE: The diaphragm is the most important muscle of respiration. Disorders of the diaphragm can have a deleterious impact on respiratory function. We aimed to evaluate the use of an open-configuration upright low-field MRI system to assess diaphragm morphology and function in patients with bilateral diaphragm weakness (BDW) and chronic obstructive pulmonary disease (COPD) with hyperinflation. METHOD: The study was approved by the National Research Ethics Committee, and written consent was obtained. We recruited 20 healthy adult volunteers, six subjects with BDW, and five subjects with COPD with hyperinflation. We measured their vital capacity in the upright and supine position, after which they were scanned on the 0.5 T MRI system during 10-s breath-holds at end-expiration and end-inspiration in both positions. We developed and applied image analysis methods to measure the volume under the dome, maximum excursion of hemidiaphragms, and anterior-posterior and left-right extension of the diaphragm. RESULTS: All participants were able to complete the scanning protocol. The patients found scanning in the upright position more comfortable than the supine position. All differences in the supine inspiratory-expiratory parameters, excluding left-right extension, were significantly smaller in the BDW and COPD groups compared with healthy volunteers. No significant correlation was found between the postural change in diaphragm morphology and vital capacity in either group. CONCLUSION: Our combined upright-supine MR imaging approach facilitates the assessment of the impact of posture on diaphragm morphology and function in patients with BDW and those with COPD with hyperinflation.

Systemic and bronchodilator effects of inhaled rac-formoterol in subjects with chronic obstructive pulmonary disease: a dose-response study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The long-acting inhaled beta(2)-agonist formoterol has systemic effects when taken in high doses. It can be used as relief medication in asthma and there is interest in this approach in chronic obstructive pulmonary disease (COPD). Relief medication can involve high doses, and in subjects with COPD who have limited ability to bronchodilate the adverse effects can outweigh the benefits. There are concerns with the overall safety of high-dose beta(2)-agonists in subjects with COPD, and this study looks at the balance of beneficial and adverse effects of a range of doses of inhaled formoterol. WHAT THIS STUDY ADDS: Among subjects with COPD, high-dose inhaled formoterol produced a dose-related increase in forced expiratory volume in 1 s without a corresponding reduction in dyspnoea or increase in walk distance. Systemic effects were modest, however, and high doses did not appear to reduce patient satisfaction. Although further safety data are needed, inhaled formoterol may have a role as relief medication in COPD. AIMS Rac-formoterol is effective as maintenance treatment for both asthma and chronic obstructive pulmonary disease (COPD) and is now used as relief therapy in asthma. Using rac-formoterol for relief and maintenance treatment could involve inhalation of high doses, and whether this is of benefit in COPD is uncertain. Our aim was to determine whether higher doses of inhaled rac-formoterol produce systemic adverse effects that outweigh the limited bronchodilator benefit seen in subjects with COPD. METHODS: We examined airway and systemic effects of 6, 12, 24 and 48 microg rac-formoterol and placebo on separate days in 20 subjects with symptomatic COPD [forced expiratory volume in 1 s (FEV(1)) 47% predicted]. FEV(1), oxygen saturation, dyspnoea, 6-min walk distance, patient satisfaction and systemic effects were measured and treatment was assessed against placebo and for dose-response effects. RESULTS: FEV(1)[area under the time-response curve (AUC)] and satisfaction scores increased with all formoterol doses compared with placebo, as did AUC tremor with the 24- and 48-microg doses and AUC heart rate with the 48-microg dose. A dose-response relationship was seen with FEV(1) and tremor, but not with satisfaction scores. There was no difference between placebo and rac-formoterol for other variables. CONCLUSIONS: Our results show that in patients with COPD rac-formoterol improves FEV(1) and patient satisfaction without a corresponding reduction in dyspnoea. Since the systemic effects from a relatively high dose were minimal, its use as relief medication in COPD merits further evaluation.

Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help?

BACKGROUND: Poor adherence with inhaled corticosteroids is an important problem in asthma management. Previous approaches to improving adherence have had limited success. AIM: To determine whether treatment with a single inhaler containing a long-acting beta(2)-agonist and a corticosteroid for maintenance treatment and symptom relief can overcome the problem of poor adherence with inhaled corticosteroids. DESIGN OF STUDY: Randomised, parallel group, open-label trial. SETTING: Forty-four general practices in Nottinghamshire. METHOD: Participants who used less than 70% of their prescribed dose of inhaled corticosteroid and had poorly controlled asthma were randomised to budesonide 200 microg one puff twice daily plus their own short-acting beta(2)-agonist as required (control group), or budesonide/formoterol 200/6 microg one puff once daily and as required (active group) for 6 months. The primary outcome was inhaled corticosteroid dose. RESULTS: Seventy-one participants (35 control, 36 active group) were randomised. Adherence with budesonide in the control group was approximately 60% of the prescribed dose. Participants in the active group used approximately 80% more budesonide than participants in the control group (448 versus 252 microg/day, mean difference 196 mug, 95% confidence interval 113 to 279; P<0.001) and were less likely to withdraw from the study (3 versus 13; P<0.01). No safety issues were identified. CONCLUSION: Using a single inhaler for both maintenance treatment and symptom relief approximately doubled the dose of inhaled corticosteroid taken, suggesting this could be a useful strategy to overcome the problems related to poor adherence with inhaled corticosteroids.

What is the potential role of transcutaneous carbon dioxide in guiding acute noninvasive ventilation?

BACKGROUND: Transcutaneous carbon dioxide (PtcCO2 ) monitoring is rarely used in the acute hospital setting, where serial samples of arterial blood are instead taken to measure carbon dioxide tension (PaCO2 ). In this pilot observational study, we assessed the potential of PtcCO2 monitoring to calculate pH and guide management of acute noninvasive ventilation (NIV). METHODS: Ten subjects with acute hypercapnic respiratory failure were recruited. All had arterial lines placed to guide acute NIV. PtcCO2 was monitored for 12 h (TOSCA TCM4) and compared with PaCO2 . Noninvasive transcutaneous pH was determined from PtcCO2 and calculated bicarbonate and then compared with true arterial pH. Agreements between PCO2 and pH methods were assessed using Bland-Altman analysis of limits of agreement and Pearson correlation coefficients. Hypothetical adjustments to acute NIV settings were based on transcutaneous data alone and evaluated in comparison with true management. Pain scores for each method were compared using the Wilcoxon signed-rank test. RESULTS: PCO2 time trends were concordant. Mean PCO2 bias was -2.33 (95% limits of agreement of -9.60 to 5.03) mm Hg, and r = 0.89 (P < .001). Mean pH bias was 0.012 (95% limits of agreement of -0.070 to 0.094), and r = 0.84 (P < .001). Hypothetical clinical decisions based on transcutaneous data alone matched true management on 85% of 34 occasions. Initiation of transcutaneous monitoring was less painful than the arterial equivalent (P = .008). CONCLUSIONS: This pilot study demonstrates that PtcCO2 monitoring provides a continuous and reliable trend and also allows pH prediction. This patient-friendly approach is a promising alternative to repeated arterial blood gas sampling in patients requiring NIV for acute hypercapnic respiratory failure.

A benefit-risk assessment of inhaled long-acting beta2-agonists in the management of obstructive pulmonary disease.

The two inhaled long-acting beta2-adrenoceptor agonists, salmeterol and formoterol, have been studied extensively since their introduction in the early 1990s. In this review we consider the evidence for their efficacy and safety in adults with asthma and chronic obstructive pulmonary disease (COPD), by reviewing long-term prospective studies in which these drugs have been compared with placebo or an alternative bronchodilator. We have also assessed safety, including data from postmarketing surveillance studies and case-control studies using large databases. In patients with asthma, salmeterol and formoterol increase lung function, reduce asthmatic symptoms and improve quality of life when compared with placebo. Both drugs protect against exercise-induced asthma, although some tolerance develops with regular use. Tolerance to the bronchodilator effects of formoterol has also been seen, although this is small and most of the beneficial effects are maintained long-term. Both drugs have been shown to reduce asthma exacerbations but only in studies in which most patients were taking an inhaled corticosteroid. Adding a long-acting beta2-agonist provided better control than increasing the dose of inhaled corticosteroid in several studies. Long-acting beta2-agonists also provide better asthma control than use of regular short-acting beta2-agonists and theophylline. Their relative efficacy compared with leukotriene antagonists is uncertain as yet. Formoterol appears to be at least as safe and effective as a short-acting beta2-agonist when used on an 'as required' basis. In patients with COPD, both salmeterol and formoterol offer improved lung function and reduced COPD symptoms compared with placebo, and quality of life has been improved in some studies. Some tolerance to the bronchodilating effect of salmeterol was seen in one study. Most studies have not found a significant reduction in exacerbations in COPD. Both drugs have provided greater benefit than ipratropium bromide or theophylline; there are limited data on tiotropium bromide. The long-acting beta2-agonists cause predictable adverse effects including headache, tremor, palpitations, muscle cramps and a fall in serum potassium concentration. Salmeterol can also cause paradoxical bronchospasm. There is some evidence that serious adverse events including dysrhythmias and life-threatening asthma episodes can occur; however, the incidence of such events is very low but may be increased in patients not taking an inhaled corticosteroid. Salmeterol 50 microg twice daily and formoterol 12 microg twice daily are effective and safe in treating patients with asthma and COPD. Higher doses cause more adverse effects, although serious adverse events are rare.

Effects of rac-albuterol on arterial blood gases in patients with stable hypercapnic chronic obstructive pulmonary disease.

AIMS: Many patients with chronic obstructive pulmonary disease (COPD) are treated with high dose beta(2)-adrenoceptor agonists, which can increase ventilation/perfusion mismatching, and tremor and cardiac output, thereby increasing oxygen uptake and carbon dioxide output (VCO(2)). Patients with severe COPD and hypercapnia may be unable to increase ventilation in response to increased VCO(2), in which case arterial carbon dioxide tension (P(a)CO(2)) may rise. Our aim was to determine whether high dose nebulized rac-albuterol could increase P(a)CO(2) in patients with COPD, limited bronchodilator reversibilty and hypercapnia. METHODS: We compared 10 mg and 400 microg rac-albuterol, given in two doses 1 h apart on nonconsecutive days, in a double-blind randomized crossover study in 14 patients with severe COPD. P(a)CO(2), arterial oxygen tension (P(a)O(2)) and heart rate were measured over 120 min and change from baseline was plotted against time to obtain an area under the curve. RESULTS: Mean P(a)CO(2) fell slightly over 120 min, with no difference between treatments (0.03 kPa h(-1) (95% confidence interval 0.02, 0.04)) and only three subjects had an increase in P(a)CO(2) after high dose rac-albuterol. High dose rac-albuterol caused a greater fall in P(a)O(2)[0.1 kPa h(-1) (95% confidence interval 0, 0.2)] and increase in heart rate than the low dose, although the differences were small. CONCLUSIONS: Under stable conditions most subjects with severe COPD and hypercapnia will have a fall in P(a)CO(2) and P(a)O(2) following 10 mg rac-albuterol, suggesting that they maintain capacity to respond to any increase in VCO(2) and prevent a rise in P(a)CO(2).