Maxime Patout

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

Does training respiratory physicians in clinical respiratory physiology and interpretation of pulmonary function tests improve core knowledge

Lung function tests have a major role in respiratory medicine. Training in lung function tests is variable within the European Union. In this study, we have shown that an internship in a lung function tests laboratory significantly improved the technical and diagnostic skills of French respiratory trainees.

In- and ex-vivo molecular imaging of apoptosis to assess sensitivity of non-small cell lung cancer to EGFR inhibitors using probe-based confocal laser endomicroscopy

Background Prediction of treatment outcome of non-small cell lung cancer (NSCLC) with EGFR inhibitors on the basis of the genetic analysis of the tumor can be incorrect in case of rare or complex mutations, bypass molecular activation pathways, or pharmacodynamic variations. The aim of this study was to develop an ex vivo and in vivo real-time quantitative imaging test for EGFR inhibitors sensitivity assessment. Methods Erlotinib resistant (A549, H460, H1975), insensitive (H1650) and hypersensitive (HCC827) cell lines were injected subcutaneously in Nude mice. Tumor xenografts from mice treated with Erlotinib were imaged ex vivo and in vivo using probe-based confocal laser endomicroscopy (pCLE) and NucView 488 Caspase 3 substrate, a fluorescent probe specific for the activated caspase 3. Results Assessment of apoptosis at 24h post treatment, both ex vivo in explanted tumor xenografts and in vivo, showed a significant difference between resistant cell lines (A549, H460 and H1975) and insensitive (H1650) or hypersensitive (HCC827) ones (p<0.05 for ex vivo imaging, p≤0.02 for in vivo imaging). There was also a significant difference between insensitive and hypersensitive cell lines, both ex vivo (p<0.05) and in vivo (p = 0.01). Conclusion Real-time in vivo and ex vivo assessment of apoptosis using pCLE differentiates resistant from sensitive NSCLC xenografts to Erlotinib.

Polysomnography versus limited respiratory monitoring and nurse-led titration to optimise non-invasive ventilation set-up: a pilot randomised clinical trial

Polysomnography (PSG) is recommended for non-invasive ventilation (NIV) set-up in patients with chronic respiratory failure. In this pilot randomised clinical trial, we compared the physiological effectiveness of NIV set-up guided by PSG to limited respiratory monitoring (LRM) and nurse-led titration in patients with COPD–obstructive sleep apnoea (OSA) overlap. The principal outcome of interest was change in daytime arterial partial pressure of carbon dioxide (PaCO2) at 3 months. Fourteen patients with daytime PaCO2 >6 kPa and body mass index >30 kg/m2 were recruited. At 3 months, PaCO2 was reduced by −0.88 kPa (95% CI −1.52 to −0.24 kPa) in the LRM group and by −0.36 kPa (95% CI −0.96 to 0.24 kPa) in the PSG group. These pilot data provide support to undertake a clinical trial investigating the clinical effectiveness of attended limited respiratory monitoring and PSG to establish NIV in patients with COPD–OSA overlap. Trial number Results, NCT02444806.

Prediction of severe acute exacerbation using changes in breathing pattern of COPD patients on home noninvasive ventilation

Introduction Acute exacerbation of COPD (AECOPD) is associated with poor outcome. Noninvasive ventilation (NIV) is recommended to treat end-stage COPD. We hypothesized that changing breathing pattern of COPD patients on NIV could identify patients with severe AECOPD prior to admission. Methods This is a prospective monocentric study including all patients with COPD treated with long-term home NIV. Patients were divided in two groups: a stable group in which patients were admitted for the usual respiratory review and an exacerbation group in which patients were admitted for inpatient care of severe AECOPD. Data from the ventilator were downloaded and analyzed over the course of the 10 days that preceded the admission. Results A total of 62 patients were included: 41 (67%) in the stable group and 21 (33%) in the exacerbation group. Respiratory rate was higher in the exacerbation group than in the stable group over the 10 days preceding inclusion (18.2±0.5 vs 16.3±0.5 breaths/min, respectively) (P=0.034). For 2 consecutive days, a respiratory rate outside the interquartile limit of the respiratory rate calculated over the 4 preceding days was associated with an increased risk of severe AECOPD of 2.8 (95% CI: 1.4–5.5) (P<0.001). This assessment had the sensitivity, specificity, positive predictive, and negative predictive values of 57.1, 80.5, 60.0, and 78.6% respectively. Over the 10 days’ period, a standard deviation (SD) of the daily use of NIV >1.0845 was associated with an increased risk of severe AECOPD of 4.0 (95% CI: 1.5–10.5) (P=0.001). This assessment had the sensitivity, specificity, positive predictive, and negative predictive values of 81.0, 63.4, 53.1, and 86.7%, respectively. Conclusion Data from NIV can identify a change in breathing patterns that predicts severe AECOPD.

S134 Effect of continuous positive airway pressure on neural respiratory drive and functional capacity in excessive dynamic airway collapse patients

Excessive dynamic airway collapse (EDAC) and tracheobronchomalacia (TBM) occur due to weakening of the walls of the central airways leading to airway collapse on expiration. Positive airway pressure provides a pneumatic stent maintaining airway patency. CPAP is used to prevent airway collapse during sleep, but could also facilitate improved exercise capacity in this patient group. The aim of this study was to investigate the effect of ambulatory continuous positive airway pressure (CPAP) on neural respiratory drive and exercise capacity. Patients with CT or bronchoscopic evidence of EDAC or TBM underwent baseline testing and 6 min walk test (6MWT). Physiological testing was performed with patients self-ventilating and on CPAP at 4, 7 and 10 cm H2O to identify optimal ambulatory CPAP pressure. Patients then underwent repeat 6MWT on sham or active CPAP in a random order. Neural respiratory drive index (NRDI) was assessed by surface electromyography of the parasternal intercostals (EMGpara%max χ respiratory rate) while self-ventilating and on CPAP. We studied 20 (9 male), ambulatory adult patients with EDAC and/or TBM: mean ±SD age 60±13 years, height 1.67±0.86 m, and BMI 34.1±6.6 kg/m2. The NRDI was 356±182 AU while self-ventilating and reduced when CPAP was applied (231±122 AU; p<0.001). The 6MWT while on optimal CPAP was increased comparing to self-ventilation and sham CPAP (296±112 m vs 264±120 m vs 252±125 m, respectively; p<0.001) (figure 1). The treatment effect between sham and optimal CPAP was 31±39 m (95% CI: 13 to 50 m). While on optimal CPAP, 12 patients increased their 6MWT more than 30 m compared to self-ventilation (responders). Comparing responders with non-responders, differences were identified for NRDI (−167±110 AU vs. −63±90 AU, respectively; p=0.039) and 6MWT while self-ventilating (203±94 m vs. 336±133 m, respectively; p=0.022). In conclusion, CPAP reduces neural respiratory drive and increases exercise capacity in patients with EDAC/TBM. Furthermore, the degree of functional limitation and off-loading of the respiratory muscles on CPAP can identify those likely to have a reduction in neural respiratory drive and enhanced exercise tolerance. Abstract S134 Figure 1 The 6MWT while on optimal CPAP was increased comparing to self-ventilation and sham CPAP.