Matthew J Pavitt

Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomised controlled trial

BACKGROUND In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia. METHODS AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the Kings Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed. FINDINGS Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p<0·0001), and scores in breathlessness and activity (mean difference 8·6 [95% CI 4·7 to 12·5]; p<0·0001) and chest symptoms (7·6 [1·9 to 13·2]; p=0·009) subdomains. However, the effect on the psychological subdomain was not significant (2·4 [-0·6 to 5·5]; p=0·12). The most common adverse events were upper respiratory tract infections (three in the oxygen group and one in the no-treatment group). Five serious adverse events, including two deaths (one in each group) occurred, but none were considered to be related to treatment. INTERPRETATION Ambulatory oxygen seemed to be associated with improved HRQOL in patients with interstitial lung disease with isolated exertional hypoxia and could be an effective intervention in this patient group, who have few therapeutic options. However, further studies are needed to confirm this finding. FUNDING UK National Institute for Health Research.

Choking on a foreign body: a physiological study of the effectiveness of abdominal thrust manoeuvres to increase thoracic pressure

The Heimlich manoeuvre is a well-known intervention for the management of choking due to foreign body airway occlusion, but the evidence base for guidance on this topic is limited and guidelines differ. We measured pressures during abdominal thrusts in healthy volunteers. The angle at which thrusts were performed (upthrust vs circumferential) did not affect intrathoracic pressure. Self-administered abdominal thrusts produced similar pressures to those performed by another person. Chair thrusts, where the subject pushed their upper abdomen against a chair back, produced higher pressures than other manoeuvres. Both approaches should be included in basic life support teaching.

Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction

Exercise-induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. The objective of this study was to evaluate exercise-related changes in laryngeal aperture on ventilation, pulmonary mechanics, and respiratory neural drive. We prospectively evaluated 12 subjects (6 with EILO and 6 healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video and gastric, esophageal, and transdiaphragmatic pressures, diaphragm electromyography, and respiratory airflow. The EILO and control groups had similar peak work rates and minute ventilation (V̇e) (work rate: 227 ± 35 vs. 237 ± 35 W; V̇e: 103 ± 20 vs. 98 ± 23 l/min; P > 0.05). At submaximal work rates (140-240 W), subjects with EILO demonstrated increased work of breathing ( P < 0.05) and respiratory neural drive ( P < 0.05), developing in close temporal association with onset of endoscopic evidence of laryngeal closure ( P < 0.05). Unexpectedly, a ventilatory increase ( P < 0.05), driven by augmented tidal volume ( P < 0.05), was seen in subjects with EILO before the onset of laryngeal closure; there were however no differences in dyspnea intensity between groups. Using simultaneous measurements of respiratory mechanics and diaphragm electromyography with endoscopic video, we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation. NEW & NOTEWORTHY Exercise-induced laryngeal obstruction is a prevalent cause of exertional dyspnea in young individuals; yet, how laryngeal closure affects breathing is unknown. In this study we synchronized endoscopic video with respiratory physiological measurements, thus providing the first detailed commensurate assessment of respiratory mechanics and neural drive in relation to laryngeal closure. Laryngeal closure was associated with increased work of breathing and respiratory neural drive preceded by an augmented tidal volume and a rise in minute ventilation.

S57 Predictors of uptake of ambulatory oxygen on completion of the ambox trial, a study to assess effects of ambulatory oxygen on quality of life in patients with fibrotic interstitial lung disease

Background There are no ILD specific guidelines on the use of ambulatory oxygen. The AmbOx trial is a multicenter, randomised, cross-over controlled trial (NCT02286063), to assess quality of life during two weeks on ambulatory oxygen compared to two weeks off oxygen, in patients with fibrotic ILD. Methods Individuals with fibrotic ILD whose oxygen saturation was normal at rest, but dropped to ≤88% on a 6MWT, with stable symptoms during a two week run-in period, were recruited and randomised. Primary outcome: health status assessed by King’s Brief ILD questionnaire (KBILD). A simple question on whether breathlessness had changed (better, same, worse) over the previous two weeks was a key secondary outcome. Patients‘ experiences with portable oxygen were explored through interviews in a subgroup. At the end of the four week trial period, patients were asked if they wished to continue with the ambulatory oxygen. Results Out of 84 randomised patients, 76 completed the trial. Mean age 64.5±1.1 years, 58 males, 53 ever smokers, FVC 73.3%±19.1%, DLCO 38.7%±12.8%. 43 patients had possible/definite IPF. Ambulatory oxygen, compared to no oxygen, was associated with improvements in total KBILD score (p<0.0001). At the end of the two weeks on oxygen, the majority of patients reported improved breathlessness (better:52/76 – same:23/76 – worse:1/76), compared to the two weeks on no oxygen (better 1/76 – same:57/76 – worse:18/76). On trial completion, 51/76 (67%) of patients chose to continue on ambulatory oxygen. On multivariate analysis, factors independently predictive of the patient’s decision to continue, included younger age (64.8 vs 72.8 years, p=0.002), more severe disease (CPI 55.5 vs 49.1, p=0.003) and patient’s global assessment of improvement in breathlessness (OR 3.2, p=0.018). Despite symptomatic improvements in the majority, ambulatory oxygen was also associated with a number of patient-reported challenges, explored in the patient interviews.

T3 Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction

Background Exercise induced laryngeal obstruction (EILO), a clinical phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnoea in young individuals and is often misdiagnosed as asthma. The physiological ventilatory impact of EILO and its relationship with dyspnoea has not been studied and we therefore sought to provide new insight by developing a methodology to facilitate synchronous evaluation of exercise related changes in laryngeal aperture on breathing pattern, pulmonary mechanics and respiratory neural drive. Methods We prospectively evaluated six subjects with EILO and six healthy age- and gender-matched control subjects. Subjects underwent detailed physiological assessment and a symptom-limited incremental exercise test with simultaneous and synchronised laryngoscopic video, gastric-, oesophageal- and transdiaphragmatic pressures, diaphragm electromyography and respiratory airflow. Results The EILO and control groups had a similar peak power output and minute ventilation (VE) (power: 227±35 vs. 237±35 watts; VE: 103±20 vs. 98±23 L/min; p>0.05). At submaximal work rates (140–240 W) subjects with EILO demonstrated increased work of breathing (p<0.05) and respiratory neural drive (p<0.05), developing in close temporal association with onset of endoscopic evidence of laryngeal closure (p<0.05). Unexpectedly, there were no differences in dyspnoea intensity whilst a ventilatory increase, driven by augmented tidal volume (p<0.05), was seen in subjects with EILO, before the onset of laryngeal closure. Conclusions Using novel methodology, we found respiratory work and respiratory neural drive increases in close association with paradoxical laryngeal closure; highlighting the importance of the upper airway contribution to respiratory loading. Abstract T3 Figure 1

Time-course of changes to intrathoracic pressure induced by CPAP in normal subjects

Introduction: An understanding of the changes in intra-thoracic pressure in response to application of CPAP (Continuous Positive Airway Pressure) is important in the study of airway and ventilator mechanics. It is unclear how quickly intrathoracic pressure measured directly with balloon catheters responds to change in CPAP. We have studied the time course of stabilisation of pressures in normal subjects.. Methods: Mouth pressure (Pmo) was measured directly at the facemask with a NIPPY 3 CPAP; oesophageal (Poes) and gastric(Pga) pressures were measured with balloon catheters in 5 normal subjects, aged 32-65, seated at rest, with 10 minutes no CPAP, then 20 minutes at CPAP 5cmH 2 O, then 10cm H 2 O and then 10 minutes no CPAP. Results: Mouth pressure (Pmo) at the facemask was lower than prescribed CPAP; CPAP 5cmH 2 O=Pmo 4.3cm H 2 O;CPAP 10cmH 2 O=8.14cmH 2 O. Change in prescribed CPAP pressure was followed by change in Pmo and Poes within 60 seconds for all pressure changes, but the corresponding change in Pga was more variable; up to 470 seconds to stabilise. Conclusions: Mouth pressure with CPAP is less than prescribed through leakage. Gastric pressure change in response to change in CPAP takes longer and varies more than for Pmo and Poes. This may reflect variation in diaphragm tonicity as noted before (Am J Respir Crit Care Med 1999;160:513-22).It may have methodological implications for studying the impact of pressure change with CPAP.

London ambulance source data on choking incidence for the calendar year 2016: an observational study

Introduction Complete foreign body airway obstruction is a life-threatening emergency, but there are limited data on its epidemiology. Methods We conducted a retrospective analysis of data collected routinely from London Ambulance Service calls coded as being for choking was undertaken for the calendar year of 2016. Results There were 1916 choking episodes of significant severity to call for emergency assessment in London during 2016, 0.2% of total calls requiring an ambulance response, an average of 5.2 per day. The incidence increased at the extremes of age. Calls coded as choking occurred at times consistent with lunch and dinner and less frequently at breakfast. Peak incidence occurred at Sunday lunchtimes and on Wednesday evenings. Conclusions Choking is a substantial health problem for Londoners to seek emergency assistance. Choking is more frequent at the extremes of age with a higher incidence at lunch and dinner time. Greater public awareness of choking and its management could help to prevent avoidable deaths.