Stephen C Bourke

Noninvasive ventilation in ALS Indications and effect on quality of life

Background: Noninvasive ventilation (NIV) probably improves survival in ALS, but the magnitude and duration of any improvement in quality of life (QoL) and the optimal criteria for initiating treatment are unclear. Methods: QoL (Short Form-36 [SF-36], Chronic Respiratory Disease Questionnaire, Sleep Apnea Quality of Life Index) and respiratory function were assessed every 2 months and polysomnography every 4 months in 22 subjects with ALS. A trial of NIV was offered when subjects met one or more predefined criteria: orthopnea, daytime sleepiness, unrefreshing sleep, daytime hypercapnia, nocturnal desaturation, or an apnea–hypopnea index (AHI) of >10. Seventeen subjects were offered a trial of NIV; 15 accepted, and 10 continued treatment subsequently. Outcome was assessed by changes in QoL and NIV compliance (h/day). Subjects were followed to death or for at least 26 months. Results: QoL domains assessing sleep-related problems and mental health improved (effect sizes 0.88 to 1.77, p < 0.05) and were maintained for 252 to 458 days. Median survival following successful initiation of NIV was 512 days, and survival and duration of QoL benefit were strongly related to NIV compliance. Vital capacity declined more slowly following initiation of NIV. Orthopnea was the best predictor of benefit from, and compliance with, NIV. Daytime hypercapnia and nocturnal desaturation also predicted benefit but were less sensitive. Sleep-related symptoms were less specific, and AHI > 10 was unhelpful. Moderate or severe bulbar weakness was associated with lower compliance and less improvement in QoL. Conclusions: NIV use was associated with improved QoL and survival. Subjects with orthopnea and preserved bulbar function showed the largest benefit.

Sleep and Breathing in Neuromuscular Disease

Respiratory muscle weakness in neuromuscular disease causes significant morbidity and mortality. The published data on respiratory muscle activity and breathing during sleep in normal subjects, the impact of respiratory muscle weakness on sleep and breathing and the relations to daytime respiratory function in neuromuscular disease are reviewed here. In normal subjects during sleep upper airway resistance increases, chemosensitivity is reduced and the wakefulness drive to breathe is lost, resulting in a fall in ventilation. During rapid eye movement (REM) sleep, ribcage and accessory breathing muscles are suppressed, particularly during bursts of eye movements, and breathing is more irregular, rapid and shallow, with a further fall in ventilation. In subjects with respiratory muscle weakness sleep is fragmented, with shorter total sleep time, frequent arousals, an increase in stage 1 sleep and a reduction in, or complete suppression of, REM sleep. Sleepdisordered breathing and nocturnal desaturation are common and most severe during REM sleep. Correlations between daytime respiratory function and nocturnal desaturation are moderate or weak, but daytime respiratory function has greater prognostic value than nocturnal measurements. Noninvasive ventilation improves sleep quality and breathing in subjects with respiratory muscle weakness. However, the optimal criteria for initiation of ventilation and its role in rapidly progressive neuromuscular diseases are unclear.

The DECAF Score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease

Background Despite exacerbations of chronic obstructive pulmonary disease (COPD) being both common and often fatal, accurate prognostication of patients hospitalised with an exacerbation is difficult. For exacerbations complicated by pneumonia, the CURB-65 prognostic tool is frequently used but its use in this population is suboptimal. Methods Consecutive patients hospitalised with an exacerbation of COPD were recruited. Admission clinical data and inhospital death rates were recorded. Independent predictors of outcome were identified by logistic regression analysis and incorporated into a clinical prediction tool. Results 920 patients were recruited: mean (SD) age was 73.1 (10.0) years; 53.9% were female subjects; mean (SD) forced expiratory volume in one second was 43.6 (17.2) % predicted; and 96 patients (10.4%) died in hospital. The five strongest predictors of mortality (extended MRC Dyspnoea Score, eosinopenia, consolidation, acidaemia, and atrial fibrillation) were combined to form the Dyspnoea, Eosinopenia, Consolidation, Acidaemia and atrial Fibrillation (DECAF) Score. The Score, which underwent internal bootstrap validation, showed excellent discrimination for mortality (area under the receiver operator characteristic curve =0.86, 95% CI 0.82 to 0.89) and performed more strongly than other clinical prediction tools. In the subgroup of patients with coexistent pneumonia (n=299), DECAF was a significantly stronger predictor of mortality than CURB-65. Conclusions The DECAF Score is a simple yet effective predictor of mortality in patients hospitalised with an exacerbation of COPD and has the potential to help clinicians more accurately predict prognosis, and triage place and level of care to improve outcome in this common condition.

Respiratory function vs sleep-disordered breathing as predictors of QOL in ALS

Background: Most patients with ALS have evidence of respiratory muscle weakness at diagnosis, and death is usually due to respiratory failure. Sleep disruption, possibly due to apneas, hypopneas, orthopnea, or REM-related desaturation, is common. The relative impact of these factors on quality of life has not been established. Methods: The authors recruited 23 subjects with probable or definite ALS. Quality of life was assessed using generic and specific instruments, and respiratory muscle strength by measurement of vital capacity, maximum static pressures, and sniff nasal inspiratory pressure. Twenty-two subjects underwent polysomnography. Overall limb and axial muscle strength was estimated using a summated muscle score based on the Medical Research Council clinical scale. Results: On univariate analysis, there were moderate to strong correlations between quality of life and all measurements of respiratory muscle function (R = 0.42–0.82). The correlations with selected polysomnographic indices were weaker and less consistent (R = 0.44–0.59). Multivariate analysis showed that maximum static inspiratory pressure was the strongest independent predictor of quality of life. Conclusion: Quality of life was strongly and independently related to respiratory muscle function. Relations with polysomnographic indices were weaker and were attributable to respiratory muscle weakness. Respiratory muscle weakness is much more important than the frequency of apneas and hypopneas in determining quality of life in ALS.

Effects of long-term low-dose azithromycin in patients with non-CF bronchiectasis

UNLABELLED We describe our institutional efficacy experience of azithromycin 250 mg thrice weekly in adult non-cystic fibrosis bronchiectasis. METHODS Eligibility criteria for prophylactic azithromycin included 3 exacerbations requiring rescue antibiotics over the previous 6 months. The clinical records of 56 bronchiectasis patients on azithromycin were retrospectively reviewed. Exacerbation frequency, sputum microbiology, self-reported change in sputum volume, and spirometry results were recorded. RESULTS Mean length of treatment was 9.1 months (7.5) and 50 patients had treatment > or = 3 months. Spirometry, pre- and post-azithromycin in 29 patients, who had 3 or more months of treatment, showed a mean increase in FEV(1) of 83 ml (0.14) (P=0.005) from 1.560 to 1.643l. There was a decrease in the exacerbation frequency from 0.81/month (SD) (0.32) pre-azithromycin to 0.41/month (0.45) (P<0.001) post-azithromycin. Clinically significant suppression of previous sputum microbial isolates was also observed. CONCLUSION Azithromycin improves exacerbation frequency, spirometry, and sputum microbiology in bronchiectasis.

Predicting outcomes following hospitalization for acute exacerbations of COPD.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a frequent cause of hospital admission and are associated with significant morbidity, mortality, high readmission rates and high resource utilization. More accurate prediction of survival and readmission in patients hospitalized with AECOPD should help to optimize clinical management and allocation of resources, including targeting of palliative care and strategies to reduce readmissions. We have reviewed the published retrospective and prospective studies in this field to identify the factors most likely to be of value in predicting in-hospital and post-discharge mortality, and readmission of patients hospitalized for AECOPD. The prognostic factors which appear most important vary with the particular outcome under consideration. In-hospital mortality is related most clearly to the patients acute physiological state and to the development of acute comorbidity, while post-discharge mortality particularly reflects the severity of the underlying COPD, as well as specific comorbidities, especially cardiac disease. Important factors influencing the frequency of readmission include functional limitation and poor health-related quality of life. Large prospective studies which incorporate all the potentially relevant variables are required to refine prediction of the important outcomes of AECOPD and thus to inform clinical decision making, for example on escalation of care, facilitated discharge and provision of palliative care.

Dyspnoea severity and pneumonia as predictors of in-hospital mortality and early readmission in acute exacerbations of COPD

Background Rates of mortality and readmission are high in patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In this population, the prognostic value of the Medical Research Council Dyspnoea Scale (MRCD) is uncertain, and an extended MRCD (eMRCD) scale has been proposed to improve its utility. Coexistent pneumonia is common and, although the CURB-65 prediction tool is used, its discriminatory value has not been reported. Methods Clinical and demographic data were collected on consecutive patients hospitalised with AECOPD. The relationship of stable-state dyspnoea severity to in-hospital mortality and 28-day readmission was assessed. The discriminatory value of CURB-65, MRCD and eMRCD, in the prediction of in-hospital mortality, was assessed and compared. Results 920 patients were recruited. 10.4% died in-hospital and 19.1% of the 824 survivors were readmitted within 28 days of discharge. During their stable state prior to admission, 34.2% of patients were too breathless to leave the house. Mortality was significantly higher in pneumonic than in non-pneumonic exacerbations (20.1% vs 5.8%, p<0.001). eMRCD was a significantly better discriminator than either CURB-65 or the traditional MRCD scale for predicting in-hospital mortality, and was a stronger prognostic tool than CURB-65 in the subgroup of patients with pneumonic AECOPD. Conclusions The severity of dyspnoea in the stable state predicts important clinical outcomes in patients hospitalised with AECOPD. The eMRCD scale identifies a subgroup of patients at a particularly high risk of in-hospital mortality and is a better predictor of mortality risk than CURB-65 in exacerbations complicated by pneumonia.

Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial

Importance Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants A randomized clinical trial of patients with persistent hypercapnia (PaCO2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. Interventions There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute. Main Outcomes and Measures Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. Results A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] PaCO2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group. Conclusions and Relevance Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months. Trial Registration clinicaltrials.gov Identifier: NCT00990132

Non-invasive ventilation in motor neuron disease: an update of current UK practice

Background In motor neurone disease (MND), respiratory muscle weakness causes substantial morbidity, and death is usually due to respiratory failure. Non-invasive ventilation (NIV) improves symptoms, quality of life and survival, but previous surveys showed that few patients with MND received NIV. Methods A postal survey was conducted of the clinical application of NIV in MND among consultant neurologists in the UK. The results were compared with those of a similar survey done in 2000. Findings Over 12 months, 612 patients were referred for NIV of whom 444 were successfully established on treatment (72.5% success rate). 38% of responding neurologists assessed respiratory function at presentation and 20% routinely monitored respiratory function; 32% relied on symptoms as the only criterion for NIV referral and 43% used a combination of symptoms and physiological impairment. 75% of responding neurologists accessed specialist palliative care services for their patients towards the end of life and 69% at an earlier stage. Interpretation Compared with 2000, there has been a marked increase in the number of patients referred for, and currently using, NIV (2.6 and 3.4-fold, respectively). The proportion successfully established on NIV has also increased, suggesting more appropriate selection and/or improvement in the methods of using NIV in this challenging group of patients. However, monitoring of respiratory function is suboptimal and uncontrolled oxygen is sometimes used inappropriately before the terminal phase.

Efficacy of nebulised colomycin in patients with non-cystic fibrosis bronchiectasis colonised with Pseudomonas aeruginosa

Colonisation with Pseudomonas aeruginosa is a feature of bronchiectasis and is associated with more severe disease and lower quality of life.1 Nebulised colomycin, a polymixin, bactericidal antibiotic with potent activity against most Gram-negative organisms, including P aeruginosa , is frequently employed in these patients, but evidence is lacking for this approach. We have retrospectively assessed the efficacy of nebulised colomycin in P aeruginosa -colonised patients receiving a minimum of 6 months treatment. Patients who received concomitant prophylactic macrolide treatment for >4 weeks were excluded. Bronchiectasis was confirmed in all patients by standard high-resolution CT criteria, and all received nebulised colomycin 1–2 megaunits twice daily through a standard jet nebuliser …