Upper airway pressure distribution during nasal high-flow therapy

Two working mechanisms of Nasal High-Flow Therapy (NHFT) are washout of anatomical dead space and provision of positive end-expiratory pressure (PEEP). The extent of both mechanisms depends on the respiration aerodynamics and the corresponding pressure distribution: at end-expiration the onset of uniform pressure indicates the jet penetration length, and the level of the uniform pressure is the PEEP. The clinical problem is that adequate measurements in patients are presently impossible. In this study, the respiratory pressure distribution is therefore measured in 3D-printed anatomically correct upper-airway models of an adult and an infant. Assuming that elastic fluctuations in airway anatomy are sufficiently small, the aerodynamics in these rigid models will be very similar to the aerodynamics in patients. It appears that, at end-expiration, the jet penetrates into or slightly beyond the nasal cavity, hardly depending on cannula size or NHFT flow rate. PEEP is approximately proportional to the square of the flow rate: it can be doubled by increasing the flow rate by 40%. In the adult model, PEEP is accurately predicted by the dynamic pressure at the prong-exits, but in the infant model this method fails. During respiration, large pressure fluctuations occur when the cannula is relatively large compared to the nostrils

On the relation between tidal and forced spirometry

Spirometry is a lung function test involving deep inhalation and forceful deep exhalation. It is widely used to obtain objective information about airflow limitation and to diagnose lung diseases. In contrast, tidal spirometry is based on normal breathing and therefore much more convenient, but it is hardly used in medical care and its relation with conventional (forced) spirometry is largely unknown. Therefore, the objective of this work is to reveal the relation between tidal and forced spirometry. Employing the strong correspondence between the forced flow-volume curves and the Tiffeneau-Pinelli (TP) index, we present a method to obtain (a) the expected tidal flow-volume curve for a given TP-index, and (b) the expected TP-index for a given tidal curve. For patients with similar values of the TP-index, the tidal curves show a larger spread than the forced curves, but their average shape varies in a characteristic way with varying index. Therefore, just as with forced curves, the TP-index provides a useful objective ranking of the average of tidal curves: upon decreasing TP-index the expiratory flow rate changes in that its peak shifts towards smaller expiratory volumes, and its post-peak part becomes dented.</p

Health outcomes of continuous positive airway pressure versus mandibular advancement device for the treatment of severe obstructive sleep apnea:an individual participant data meta-analysis

Study Objectives: The impact of therapy with continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) has not been directly compared in patients with severe obstructive sleep apnea (OSA). The purpose of this individual participant data meta-analysis was to compare the treatment effects of CPAP and titratable MAD on sleepiness, quality of life, sleep-disordered breathing severity, and sleep structure in patients with severe OSA. Methods: Randomized controlled trials (RCTs) that included severe OSA patients were identified in order to compare the impact of the two treatments. Individual data from severe OSA patients were extracted from the databases and pooled for analysis. Results: Of the seven studies identified, three crossover RCT and one parallel-group RCT corresponding to 151 patients and 249 observations (125 in the CPAP treatment arm and 124 in the MAD treatment arm) were included in the analysis. Titratable MAD had a similar impact to CPAP on major patient-centered outcomes (sleepiness and quality of life). CPAP was more effective in reducing AHI and ODI. However, the two treatments had a similar impact on sleep structure with an increase of N3 and REM sleep. Finally, treatment adherence and preference were largely in favor of MAD. Conclusion: This meta-analysis suggests that MAD represents an effective alternative treatment in severe OSA patients intolerant to CPAP or who prefer alternate therapy

Chronic non-invasive ventilation for chronic obstructive pulmonary disease

BACKGROUND: Chronic non-invasive ventilation (NIV) is increasingly being used to treat people with COPD who have respiratory failure, but the evidence supporting this treatment has been conflicting.OBJECTIVES: To assess the effects of chronic non-invasive ventilation at home via a facial mask in people with COPD, using a pooled analysis of IPD and meta-analysis.SEARCH METHODS: We searched the Cochrane Airways Register of Trials, MEDLINE, Embase, PsycINFO, CINAHL, AMED, proceedings of respiratory conferences, clinical trial registries and bibliographies of relevant studies. We conducted the latest search on 21 December 2020.SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing chronic NIV for at least five hours per night for three consecutive weeks or more (in addition to standard care) versus standard care alone, in people with COPD. Studies investigating people initiated on NIV in a stable phase and studies investigating NIV commenced after a severe COPD exacerbation were eligible, but we reported and analysed them separately. The primary outcomes were arterial blood gases, health-related quality of life (HRQL), exercise capacity (stable COPD) and admission-free survival (post-exacerbation COPD). Secondary outcomes for both populations were: lung function, COPD exacerbations and admissions, and all-cause mortality. For stable COPD, we also reported respiratory muscle strength, dyspnoea and sleep efficiency.DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. After inclusion of a study, we requested the IPD. We analysed continuous and time-to-event data using linear- and cox-regression mixed-effect models with a random effect on study level. We analysed dichotomous IPD using generalised estimating equations. We adjusted all models for age and sex. We assessed changes in outcomes after three and 12 months. We also conducted a meta-analysis on aggregated trial data.MAIN RESULTS: We included 14 new RCTs in this review update, in addition to the seven previously included. Seventeen studies investigated chronic NIV in stable COPD and four studies investigated chronic NIV commenced after a severe COPD exacerbation. Three studies compared NIV to sham continuous positive airway pressure (2 to 4 cmH2O). Seven studies used a nasal mask, one study used an oronasal mask and eight studies used both interfaces. Five studies did not report the interface. The majority of trials (20/21) were at high risk of performance bias due to an unblinded design. We considered 11 studies to have a low risk of selection bias and 13 to have a low risk of attrition bias. We collected and analysed the IPD from 13 stable COPD studies (n = 778, 68% of the participants included) and from three post-exacerbation studies (n = 364, 96% of the participants included). In the stable COPD group, NIV probably results in a minor benefit on the arterial partial pressure of oxygen (PaO2) after three months (adjusted mean difference (AMD) 0.27 kPa, 95% CI 0.04 to 0.49; 9 studies, 271 participants; moderate-certainty evidence), but there was little to no benefit at 12 months (AMD 0.09 kPa, 95% CI -0.23 to 0.42; 3 studies, 171 participants; low-certainty evidence). The arterial partial pressure of carbon dioxide (PaCO2) was reduced in participants allocated to NIV after three months (AMD -0.61 kPa, 95% CI -0.77 to -0.45; 11 studies, 475 participants; high-certainty evidence) and persisted up to 12 months (AMD -0.42 kPa, 95% CI -0.68 to -0.16; 4 studies, 232 participants; high-certainty evidence). Exercise capacity was measured with the 6-minute walking distance (minimal clinical important difference: 26 m). There was no clinically relevant effect of NIV on exercise capacity (3 months: AMD 15.5 m, 95% CI -0.8 to 31.7; 8 studies, 330 participants; low-certainty evidence; 12 months: AMD 26.4 m, 95% CI -7.6 to 60.5; 3 studies, 134 participants; very low-certainty evidence). HRQL was measured with the Severe Respiratory Insufficiency and the St. Georges's Respiratory Questionnaire and may be improved by NIV, but only after three months (3 months: standardised mean difference (SMD) 0.39, 95% CI 0.15 to 0.62; 5 studies, 259 participants; very low-certainty evidence; 12 months: SMD 0.15, 95% CI -0.13 to 0.43; 4 studies, 200 participants; very low-certainty evidence). Lastly, the risk for all-cause mortality is likely reduced by NIV (adjusted hazard ratio (AHR) 0.75, 95% CI 0.58 to 0.97; 3 studies, 405 participants; moderate-certainty evidence). In the post-exacerbation COPD group, there was little to no benefit on the PaO2 after three months, but there may be a slight decrease after 12 months (3 months: AMD -0.10 kPa, 95% CI -0.65 to 0.45; 3 studies, 234 participants; low-certainty evidence; 12 months: -0.27 kPa, 95% CI -0.86 to 0.32, 3 studies; 170 participants; low-certainty evidence). The PaCO2 was reduced by NIV at both three months (AMD -0.40 kPa, 95% CI -0.70 to -0.09; 3 studies, 241 participants; moderate-certainty evidence) and 12 months (AMD -0.52 kPa, 95% CI -0.87 to -0.18; 3 studies, 175 participants; high-certainty evidence). NIV may have little to no benefit on HRQL (3 months: SMD 0.25, 95% CI -0.01 to 0.51; 2 studies, 219 participants; very low-certainty evidence; 12 months: SMD 0.25, 95% -0.06 to 0.55; 2 studies, 164 participants; very low-certainty evidence). Admission-free survival seems improved with NIV (AHR 0.71, 95% CI 0.54 to 0.94; 2 studies, 317 participants; low-certainty evidence), but the risk for all-cause mortality does not seem to improve (AHR 0.97, 95% CI 0.74 to 1.28; 2 studies, 317 participants; low-certainty evidence).AUTHORS' CONCLUSIONS: Regardless of the timing of initiation, chronic NIV improves daytime hypercapnia. In addition, in stable COPD, survival seems to be improved and there might be a short term HRQL benefit. In people with persistent hypercapnia after a COPD exacerbation, chronic NIV might prolong admission-free survival without a beneficial effect on HRQL. In stable COPD, future RCTs comparing NIV to a control group receiving standard care might no longer be warranted, but research should focus on identifying participant characteristics that would define treatment success. Furthermore, the optimal timing for initiation of NIV after a severe COPD exacerbation is still unknown.</p

"A randomized trial of initiation of chronic non-invasive mechanical ventilation at home vs in-hospital in patients with Neuromuscular Disease and thoracic cage disorder":The Dutch Homerun Trial

Background: There is an increasing demand for home mechanical ventilation (HMV) in patients with chronic respiratory insufficiency. At present, noninvasive ventilation is exclusively initiated in a clinical setting at all four centers for HMV in the Netherlands. In addition to its high societal costs and patient discomfort, commencing HMV is often delayed because of a lack of hospital bed capacity. Research Question: Is HMV initiation at home, using a telemonitoring approach, noninferior to in-hospital initiation in a nationwide study? Study Design and Methods: We conducted a nationwide, randomized controlled noninferiority trial, in which every HMV center recruited 24 patients (home [n = 12] vs hospital [n = 12]) with a neuromuscular disease or thoracic cage disorder, all with an indication to start HMV. Change in arterial CO 2 (PaCO 2) over a 6-month period was considered the primary outcome, and quality of life and costs were assessed as secondary outcomes. Results: A total of 96 patients were randomized, most of them diagnosed with neuromuscular disease. We found a significant improvement in PaCO 2 within both groups (home: from 6.1 to 5.6 kPa [P <.01]; hospital: from 6.3 to 5.6 kPa [P <.01]), with no significant differences between groups. Health-related quality of life showed significant improvement on various subscales; however, no significant differences were observed between the home and hospital groups. From a societal perspective, a cost reduction of more than €3,200 ($3,793) per patient was evident in the home group. Interpretation: This nationwide, multicenter study shows that HMV initiation at home is noninferior to hospital initiation, as it shows the same improvement in gas exchange and health-related quality of life. In fact, from a patient's perspective, it might even be a more attractive approach. In addition, starting at home saves over €3,200 ($3,793) per patient over a 6-month period. Trial Registry: ClinicalTrials.gov; No.: NCT03203577; URL: www.clinicaltrials.gov

Improvement in hypercapnia does not predict survival in COPD patients on chronic noninvasive ventilation

Purpose: It has recently been shown that chronic noninvasive ventilation (NIV) improves a number of outcomes including survival, in patients with stable hypercapnic COPD. However, the mechanisms responsible for these improved outcomes are still unknown. The aim of the present study was to identify parameters associated with: 1) an improved arterial partial pressure of carbon dioxide (PaCO2) and 2) survival, in a cohort of hypercapnic COPD patients treated with chronic NIV. Patients and methods: Data from 240 COPD patients treated with chronic NIV were analyzed. Predictors for the change in PaCO2 and survival were investigated using multivariate linear and Cox regression models, respectively. Results: A higher level of bicarbonate before NIV initiation, the use of higher inspiratory ventilator pressures, the presence of anxiety symptoms, and NIV initiated following an exacerbation compared to NIV initiated in stable disease were associated with a larger reduction in PaCO2. A higher body mass index, a higher FEV1, a lower bicarbonate before NIV initiation, and younger age and NIV initiation in stable condition were independently associated with better survival. The change in PaCO2 was not associated with survival, neither in a subgroup of patients with a PaCO2 >7.0 kPa before the initiation of NIV. Conclusion: Patients with anxiety symptoms and a high bicarbonate level at NIV initiation are potentially good responders in terms of an improvement in hypercapnia. Also, higher inspiratory ventilator pressures are associated with a larger reduction in PaCO2. However, the improvement in hypercapnia does not seem to be associated with an improved survival and emphasizes the need to look beyond PaCO2 when considering NIV initiation