The validity of shortened multiple-breath washout testing using sulfur hexafluoride in the assessment of patients with COPD.

INTRODUCTION: COPD affects the small airways and is associated with ventilation heterogeneity. There are little data on the multiple-breath washout (MBW) in patients with COPD, particularly the variability over 8 weeks, using a shortened sulfur hexafluoride (SF6) washout. This work evaluated the repeatability of the lung clearance index (LCI)1/40 and LCI1/20 among subjects with COPD and compared to spirometry and clinical markers. METHODS: The MBW was performed on patients with COPD to determine ventilation heterogeneity globally (LCI), at conductive (Scond) and acinar (Sacin) levels. The LCI was repeated in triplicate and measured at a traditional 1/40th washout and retrofitted to a shortened 1/20th end tidal SF6 concentration washout. Tests were repeated after 20 min and 8  weeks to determine within and between visit repeatability and compared with spirometry. RESULTS: Eighty-four subjects were recruited to perform LCI and spirometry with 20 subjects performing the repeatability protocol. There were weak correlations between forced expiratory volume in 1 s ( FEV1) per cent predicted and LCI1/40th r=-0.311 (p=0.02), and LCI1/20th r=-0.40 (p<0.01). The LCI demonstrated excellent within and good between visit repeatability for both a 1/40th and 1/20th washout (intraclass correlation coefficient (ICC)≥0.80). There was a statistically significant strong correlation between LCI1/40th and a shortened LCI1/20 of 0.86 (p<0.01). CONCLUSIONS: The LCI is repeatable within and between visits. There are weak correlations with measures of spirometry. A shortened LCI1/20th starting concentration correlates highly with a 1/40th washout, which may encourage clinical use.

Standardisation of Clinical Assessment, Management and Follow-Up of Acute Hospitalised Exacerbation of COPD: A Europe-Wide Consensus.

BACKGROUND: Despite hospitalization for exacerbation being a high-risk event for morbidity and mortality, there is little consensus globally regarding the assessment and management of hospitalised exacerbations of COPD. We aimed to establish a consensus list of symptoms, physiological measures, clinical scores, patient questionnaires and investigations to be obtained at time of hospitalised COPD exacerbation and follow-up. METHODS: A modified Delphi online survey with pre-defined consensus of importance, feasibility and frequency of measures at hospitalisation and follow-up of a COPD exacerbation was undertaken. FINDINGS: A total of 25 COPD experts from 18 countries contributed to all 3 rounds of the survey. Experts agreed that a detailed history and examination were needed. Experts also agreed on which treatments are needed and how soon these should be delivered. Experts recommended that a full blood count, renal function, C-reactive protein and cardiac blood biomarkers (BNP and troponin) should be measured within 4 hours of admission and that the modified Medical Research Council dyspnoea scale (mMRC) and COPD assessment test (CAT) should be performed at time of exacerbation and follow-up. Experts encouraged COPD clinicians to strongly consider discussing palliative care, if indicated, at time of hospitalisation. INTERPRETATION: This Europe-wide consensus document is the first attempt to standardise the assessment and care of patients hospitalised for COPD exacerbations. This should be regarded as the starting point to build knowledge and evidence on patients hospitalised for COPD exacerbations.

Assessment of breath volatile organic compounds in acute cardiorespiratory breathlessness: a protocol describing a prospective real-world observational study.

INTRODUCTION: Patients presenting with acute undifferentiated breathlessness are commonly encountered in admissions units across the UK. Existing blood biomarkers have clinical utility in distinguishing patients with single organ pathologies but have poor discriminatory power in multifactorial presentations. Evaluation of volatile organic compounds (VOCs) in exhaled breath offers the potential to develop biomarkers of disease states that underpin acute cardiorespiratory breathlessness, owing to their proximity to the cardiorespiratory system. To date, there has been no systematic evaluation of VOC in acute cardiorespiratory breathlessness. The proposed study will seek to use both offline and online VOC technologies to evaluate the predictive value of VOC in identifying common conditions that present with acute cardiorespiratory breathlessness. METHODS AND ANALYSIS: A prospective real-world observational study carried out across three acute admissions units within Leicestershire. Participants with self-reported acute breathlessness, with a confirmed primary diagnosis of either acute heart failure, community-acquired pneumonia and acute exacerbation of asthma or chronic obstructive pulmonary disease will be recruited within 24 hours of admission. Additionally, school-age children admitted with severe asthma will be evaluated. All participants will undergo breath sampling on admission and on recovery following discharge. A range of online technologies including: proton transfer reaction mass spectrometry, gas chromatography ion mobility spectrometry, atmospheric pressure chemical ionisation-mass spectrometry and offline technologies including gas chromatography mass spectroscopy and comprehensive two-dimensional gas chromatography-mass spectrometry will be used for VOC discovery and replication. For offline technologies, a standardised CE-marked breath sampling device (ReCIVA) will be used. All recruited participants will be characterised using existing blood biomarkers including C reactive protein, brain-derived natriuretic peptide, troponin-I and blood eosinophil levels and further evaluated using a range of standardised questionnaires, lung function testing, sputum cell counts and other diagnostic tests pertinent to acute disease. ETHICS AND DISSEMINATION: The National Research Ethics Service Committee East Midlands has approved the study protocol (REC number: 16/LO/1747). Integrated Research Approval System (IRAS) 198921. Findings will be presented at academic conferences and published in peer-reviewed scientific journals. Dissemination will be facilitated via a partnership with the East Midlands Academic Health Sciences Network and via interaction with all UK-funded Medical Research Council and Engineering and Physical Sciences Research Council molecular pathology nodes. TRIAL REGISTRATION NUMBER: NCT03672994.

Influence of muscle mass in the assessment of lower limb strength in COPD: validation of the prediction equation.

Absence of established reference values limits application of quadriceps maximal voluntary contraction (QMVC) measurement. The impact of muscle mass inclusion in predictions is unclear. Prediction equations encompassing gender, age and size with (FFM+) and without (FFM-), derived in healthy adults (n=175), are presented and compared in two COPD cohorts recruited from primary care (COPD-PC, n=112) and a complex care COPD clinic (COPD-CC, n=189). Explained variance was comparable between the prediction models (R2: FFM+: 0.59, FFM-: 0.60) as were per cent predictions in COPD-PC (88.8%, 88.3%). However, fat-free mass inclusion reduced the prevalence of weakness in COPD, particularly in COPD-CC where 11.9% fewer were deemed weak.

Bedside assessment of quadriceps muscle by ultrasound after admission for acute exacerbations of chronic respiratory disease.

RATIONALE: Hospitalization represents a major event for the patient with chronic respiratory disease. There is a high risk of readmission, which over the longer term may be related more closely to the underlying condition of the patient, such as skeletal muscle dysfunction. OBJECTIVES: We assessed the risk of hospital readmission at 1 year, including measures of lower limb muscle as part of a larger clinical trial. METHODS: Patients hospitalized with an exacerbation of chronic respiratory disease underwent measures of muscle function including quadriceps ultrasound. Independent factors influencing time to hospital readmission or death were identified. Patients were classified into four quartiles based on quadriceps size and compared. MEASUREMENTS AND MAIN RESULTS: One hundred and ninety-one patients (mean age, 71.6 [SD, 9.1] yr) were recruited. One hundred and thirty (68%) were either readmitted or died. Factors associated with readmission or death were age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.08; P = 0.015), Medical Research Council (MRC) dyspnea grade (OR, 4.57; 95% CI, 2.62-7.95; P < 0.001), home oxygen use (OR, 12.4; 95% CI, 4.53-33.77; P < 0.001), quadriceps (rectus femoris) cross-sectional area (Qcsa) (OR, 0.34; 95% CI, 0.17-0.65; P = 0.001), and hospitalization in the previous year (OR, 4.82; 95% CI, 2.42-9.58; P < 0.001). In the multivariate analyses, home oxygen use (OR, 4.80; 95% CI, 1.68-13.69; P = 0.003), MRC dyspnea grade (OR, 2.57; 95% CI, 1.44-4.59; P = 0.001), Qcsa (OR, 0.46; 95% CI, 0.22-0.95; P = 0.035), and previous hospitalization (OR, 3.04; 95% CI, 1.47-6.29; P = 0.003) were independently associated with readmission or death. Patients with the smallest muscle spent more days in hospital than those with largest muscle (28.1 [SD, 33.9] vs. 12.2 [SD, 23.5] d; P = 0.007). CONCLUSIONS: Smaller quadriceps muscle size, as measured by ultrasound in the acute care setting, is an independent risk factor for unscheduled readmission or death, which may have value both in clinical practice and for risk stratification.