Clinical practice of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Non-invasive ventilation (NIV) is an evidence-based treatment for acute respiratory failure in chronic obstructive pulmonary disease (COPD). However, suboptimal application of NIV in clinical practice, possibly due to poor guideline adherence, can impact patient outcomes. This study aims to evaluate guideline adherence to NIV for acute COPD exacerbations and explore its impact on mortality. METHODS: This retrospective study was performed in two Dutch medical centers from 2019 to 2021. All patients admitted to the pulmonary ward or intensive care unit with a COPD exacerbation were included. An indication for NIV was considered in the event of a respiratory acidosis. RESULTS: A total of 1162 admissions (668 unique patients) were included. NIV was started in 154 of the 204 admissions (76%) where NIV was indicated upon admission. Among 78 admissions where patients deteriorated later on, NIV was started in 51 admissions (65%). Considering patients not receiving NIV due to contra-indications or patient refusal, the overall guideline adherence rate was 82%. Common reasons for not starting NIV when indicated included no perceived signs of respiratory distress, opting for comfort care only, and choosing a watchful waiting approach. Better survival was observed in patients who received NIV when indicated compared to those who did not. CONCLUSIONS: The adherence to guidelines regarding NIV initiation is good. Nevertheless, further improving NIV treatment in clinical practice could be achieved through training healthcare professionals to increase awareness and reduce reluctance in utilizing NIV. By addressing these factors, patient outcomes may be further enhanced.

Nasal versus oronasal masks for home non-invasive ventilation in patients with chronic hypercapnia: a systematic review and individual participant data meta-analysis.

BACKGROUND: The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS). METHODS: We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month's duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO2, PaO2 and NIV adherence (PROSPERO CRD42019132398). FINDINGS: Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO2 (0.61 mm Hg (95% CI -2.15 to 3.38); p=0.68), PaO2 (-0.00 mm Hg (95% CI -4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI -0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome. INTERPRETATION: Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks.

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.

Home initiation of chronic non-invasive ventilation in COPD patients with chronic hypercapnic respiratory failure: a randomised controlled trial.

INTRODUCTION: Chronic non-invasive ventilation (NIV) has become evidence-based care for stable hypercapnic COPD patients. While the number of patients increases, home initiation of NIV would greatly alleviate the healthcare burden. We hypothesise that home initiation of NIV with the use of telemedicine in stable hypercapnic COPD is non-inferior to in-hospital NIV initiation. METHODS: Sixty-seven stable hypercapnic COPD patients were randomised to initiation of NIV in the hospital or at home using telemedicine. Primary outcome was daytime arterial carbon dioxide pressure (PaCO2) reduction after 6 months NIV, with a non-inferiority margin of 0.4 kPa. Secondary outcomes were health-related quality of life (HRQoL) and costs. RESULTS: Home NIV initiation was non-inferior to in-hospital initiation (adjusted mean difference in PaCO2 change home vs in-hospital: 0.04 kPa (95% CI -0.31 to 0.38 kPa), with both groups showing a PaCO2 reduction at 6 months compared with baseline (home: from 7.3±0.9 to 6.4±0.8 kPa (p<0.001) and in-hospital: from 7.4±1.0 to 6.4±0.6 kPa (p<0.001)). In both groups, HRQoL improved without a difference in change between groups (Clinical COPD Questionnaire total score-adjusted mean difference 0.0 (95% CI -0.4 to 0.5)). Furthermore, home NIV initiation was significantly cheaper (home: median €3768 (IQR €3546-€4163) vs in-hospital: median €8537 (IQR €7540-€9175); p<0.001). DISCUSSION: This is the first study showing that home initiation of chronic NIV in stable hypercapnic COPD patients, with the use of telemedicine, is non-inferior to in-hospital initiation, safe and reduces costs by over 50%. TRIAL REGISTRATION NUMBER: NCT02652559.

Obesity hypoventilation syndrome treated with non-invasive ventilation: Is a switch to CPAP therapy feasible?

BACKGROUND AND OBJECTIVE: Obesity hypoventilation syndrome (OHS) can be treated with either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) therapy; the device choice has important economic and operational implications. METHODS: This multicentre interventional trial investigated the safety and short-term efficacy of switching stable OHS patients who were on successful NIV therapy for ≥3 months to CPAP therapy. Patients underwent an autotitrating CPAP night under polysomnography (PSG); if the ensuing parameters were acceptable, they were sent home on a fixed CPAP for a 4-6-week period. It was hypothesized that blood gas analysis, PSG parameters and lung function tests would remain unchanged. RESULTS: A total of 42 OHS patients were recruited, of whom 37 patients were switched to CPAP therapy. All patients had a history of severe obstructive sleep apnoea syndrome; chronic obstructive pulmonary disease (COPD) (Global Initiative for Obstructive Lung Disease (GOLD) I/II) was present in 52%. Regarding the primary outcome, 30 of 42 patients (71%, 95% CI: 55-84%) maintained daytime partial pressure of carbon dioxide (PaCO2 ) levels ≤45 mm Hg after the home CPAP period. There was no further impairment in quality of life, sleep parameters or lung function. Interestingly, 24 patients (65%) preferred CPAP as their long-term therapy, despite the high pressure levels used (mean: 13.8 ± 1.8 mbar). After the CPAP period, 7 of 37 patients were categorized as CPAP failure, albeit only due to mild hypercapnia (mean: 47.9 ± 2.7 mm Hg). CONCLUSION: It is feasible to switch most stable OHS patients from NIV to CPAP therapy, a step that could significantly reduce health-related costs. The auto-adjusted CPAP device, used in combination with the analysis of the PSG and capnometry, is a valid titration method in OHS patients.

Clinical Evidence of Nasal High-Flow Therapy in Chronic Obstructive Pulmonary Disease Patients.

Nasal high-flow therapy (NHFT) is an upcoming treatment for chronic obstructive pulmonary disease (COPD) patients. It supplies heated, humidified, and, desirably, oxygen-enriched air through a nasal cannula at flow rates up to 60 L/min. Several studies examined the effect of NHFT in COPD patients, but a clear overview is lacking. The present review aimed to give an overview of the clinical evidence of NHFT in 3 aspects of COPD care: long-term use in stable COPD patients, use for treatment of COPD exacerbations, and use during exercise therapy in COPD. For each topic, a specific literature search was performed up to December 9, 2019. Studies show promising results, with most evidence for its long-term use in hypoxemic COPD patients that frequently exacerbate, and very limited evidence for its use during COPD exacerbations or as a worthwhile adjunct to exercise training. More evidence is therefore needed to know how to incorporate NHFT in standard clinical practice.

High-intensity non-invasive ventilation in stable hypercapnic COPD: Evidence of efficacy and practical advice.

Patients with end-stage chronic obstructive pulmonary disease (COPD) frequently develop chronic hypercapnic respiratory failure (CHRF), with disabling symptoms and poor survival. The use of long-term nocturnal non-invasive ventilation (NIV) to treat CHRF in COPD has long been subject of debate due to conflicting evidence. However, since the introduction of high-intensity NIV (HI-NIV) in COPD, physiological and clinical benefits have been shown. HI-NIV refers to specific ventilator settings used for NIV aimed at achieving normocapnia or the lowest partial arterial carbon dioxide pressure (PaCO2 ) values as possible. This review will provide an overview of existing evidence of the efficacy of HI-NIV stable COPD patients with CHRF. Secondly, we will discuss hypotheses underlying NIV benefit in stable hypercapnic COPD, providing insight into better patient selection and hopefully more individually titrated HI-NIV. Finally, we will provide practical advice on how to initiate and follow-up patients on HI-NIV, with special emphasis on monitoring that should be available during the initiation and follow-up of HI-NIV, and will discuss more extended monitoring techniques that could improve HI-NIV treatment in the future.

Long-term noninvasive ventilation in patients with chronic hypercapnic respiratory failure: assisting the diaphragm, but threatening the heart?

PURPOSE OF REVIEW: To summarize and discuss the available studies on the effects of long-term noninvasive ventilation (NIV) on cardiac function in patients with chronic hypercapnic respiratory failure. RECENT FINDINGS: A total of nine studies investigated the acute and long-term effects of NIV on cardiac performance in patients with chronic hypercapnic respiratory failure. SUMMARY: Both the application of expiratory airway pressure and (higher) inspiratory pressures may acutely decrease cardiac output during the initiation of NIV. However, the meaning of this effect in the long term is not clear. Apparently, natriuretic peptides decrease after a certain period of NIV use and heart rate variability seems to improve. Probably, a decreased cardiac output might not be disadvantageous and reflects a decreased work of breathing. Furthermore, the hemodynamic effects of long-term NIV are dependent on the underlying cardiac comorbidities. This is important in patients with chronic obstructive pulmonary disease, where cardiac comorbidities are frequent.Considering the available physiological data, future studies should focus on the impact of long-term NIV on heart performance and clinical outcomes. Second, further studies are needed investigating the cardiac long-term effects of different NIV modes, pressures (low and high) and breathing frequencies, especially when underlying cardiac comorbidity is present.

Changes in the endurance shuttle walk test in COPD patients with chronic respiratory failure after pulmonary rehabilitation: the minimal important difference obtained with anchor- and distribution-based method.

BACKGROUND: Although the endurance shuttle walk test (ESWT) has proven to be responsive to change in exercise capacity after pulmonary rehabilitation (PR) for COPD, the minimally important difference (MID) has not yet been established. We aimed to establish the MID of the ESWT in patients with severe COPD and chronic hypercapnic respiratory failure following PR. METHODS: Data were derived from a randomized controlled trial, investigating the value of noninvasive positive pressure ventilation added to PR. Fifty-five patients with stable COPD, GOLD stage IV, with chronic respiratory failure were included (mean (SD) FEV1 31.1 (12.0) % pred, age 62 (9) y). MID estimates of the ESWT in seconds, percentage and meters change were calculated with anchor based and distribution based methods. Six minute walking distance (6MWD), peak work rate on bicycle ergometry (Wpeak) and Chronic Respiratory Questionnaire (CRQ) were used as anchors and Cohen's effect size was used as distribution based method. RESULTS: The estimated MID of the ESWT with the different anchors ranged from 186-199 s, 76-82% and 154-164 m. Using the distribution based method the MID was 144 s, 61% and 137 m. CONCLUSIONS: Estimates of the MID for the ESWT after PR showed only small differences using different anchors in patients with COPD and chronic respiratory failure. Therefore we recommend using a range of 186-199 s, 76-82% or 154-164 m as MID of the ESWT in COPD patients with chronic respiratory failure. Further research in larger populations should elucidate whether this cut-off value is also valid in other COPD populations and with other interventions. TRIAL REGISTRATION: ClinicalTrials.Gov (ID NCT00135538).

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.

Home noninvasive ventilation in severe COPD: in whom does it work and how?

Background: Not all hypercapnic COPD patients benefit from home noninvasive ventilation (NIV), and mechanisms through which NIV improves clinical outcomes remain uncertain. We aimed to identify "responders" to home NIV, denoted by a beneficial effect of NIV on arterial partial pressure of carbon dioxide (PaCO2), health-related quality of life (HRQoL) and survival, and investigated whether NIV achieves its beneficial effect through an improved PaCO2. Methods: We used individual patient data from previous published trials collated for a systematic review. Linear mixed-effect models were conducted to compare the effect of NIV on PaCO2, HRQoL and survival, within subgroups defined by patient and treatment characteristics. Secondly, we conducted a causal mediation analysis to investigate whether the effect of NIV is mediated by a change in PaCO2. Findings: Data of 1142 participants from 16 studies were used. Participants treated with lower pressure support (<14 versus ≥14 cmH2O) and with lower adherence (<5 versus ≥5 h·day-1) had less improvement in PaCO2 (mean difference (MD) -0.30 kPa, p<0.001 and -0.29 kPa, p<0.001, respectively) and HRQoL (standardised MD 0.10, p=0.002 and 0.11, p=0.02, respectively), but this effect did not persist to survival. PaCO2 improved more in patients with severe dyspnoea (MD -0.30, p=0.02), and HRQoL improved only in participants with fewer than three exacerbations (standardised MD 0.52, p=0.03). The results of the mediation analysis showed that the effect on HRQoL is mediated partially (23%) by a change in PaCO2. Interpretation: With greater pressure support and better daily NIV usage, a larger improvement in PaCO2 and HRQoL is achieved. Importantly, we demonstrated that the beneficial effect of home NIV on HRQoL is only partially mediated through a reduction in diurnal PaCO2.

Pneumothorax in patients with COPD and emphysema receiving home chronic non-invasive ventilation: is it the emphysema phenotype or ventilator setting?

We describe three patients with chronic obstructive pulmonary disease (COPD) and emphysema who developed a pneumothorax while receiving chronic home non-invasive ventilation (NIV). These cases raise the question whether the high alveolar pressures given by NIV may have contributed to the development of their pneumothorax by barotrauma. Pneumothorax in patients with COPD receiving NIV is uncommon, the pressures in our patients with COPD who developed pneumothorax were not extremely high and time to development of pneumothorax was relatively long after the initiation of NIV. Further, in our patients, the CT scan showed paraseptal emphysema, a known risk factor for pneumothorax. This suggests that COPD/emphysema phenotype is probably a more important factor for indicating pneumothorax risk than ventilator settings. Better phenotyping of patients with COPD in whom benefits of NIV can be expected at minimal risk of serious side-effects is needed to inform our patients properly and bring the field of chronic NIV in COPD forward.

Home ventilation for patients with end-stage chronic obstructive pulmonary disease.

PURPOSE OF THE REVIEW: The number of patients with end-stage chronic obstructive pulmonary disease (COPD) treated with chronic non-invasive ventilation (NIV) has greatly increased. In this review, the authors summarize the evidence for nocturnal NIV and NIV during exercise. The authors discuss the multidisciplinary and advanced care of patients with end-stage COPD treated with NIV. RECENT FINDINGS: Nocturnal NIV improves gas exchange, health-related quality of life and survival in stable hypercapnic COPD patients. Improvements in care delivery have been achieved by relocating care from the hospital to home based; home initiation of chronic NIV is feasible, non-inferior regarding efficacy and cost-effective compared to in-hospital initiation. However, the effect of NIV on symptoms is variable, and applying optimal NIV for end-stage COPD is complex. While exercise-induced dyspnoea is a prominent complaint in end-stage COPD, nocturnal NIV will not change this. However, NIV applied solely during exercise might improve exercise tolerance and dyspnoea. While chronic NIV is often a long-standing treatment, patient expectations should be discussed early and be managed continuously during the treatment. Further, integration of advance care planning requires a multidisciplinary approach. SUMMARY: Although chronic NIV is an effective treatment in end-stage COPD with persistent hypercapnia, there are still important questions that need to be answered to improve care of these severely ill patients.

The role of telemonitoring in patients on home mechanical ventilation.

There is a growing number of patients being treated with long-term home mechanical ventilation (HMV). This poses a challenge for the healthcare system because in-hospital resources are decreasing. The application of digital health to assist HMV care might help. In this narrative review we discuss the evidence for using telemonitoring to assist in initiation and follow-up of patients on long-term HMV. We also give an overview of available technology and discuss which parameters can be measured and how often this should be done. To get a telemonitoring solution implemented in clinical practice is often complex; we discuss which factors contribute to that. We discuss patients' opinions regarding the use of telemonitoring in HMV. Finally, future perspectives for this rapidly growing and evolving field will be discussed.