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.

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.

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.

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.

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.

High-flow nasal cannula oxygen therapy for admitted COPD-patients. A retrospective cohort study.

BACKGROUND: The use of High-flow nasal cannula (HFNC) is increasing in admitted COPD-patients and could provide a step in between non-invasive ventilation (NIV) and standard oxygen supply. Recent studies demonstrated that HFNC is capable of facilitating secretion removal and reduce the work of breathing. Therefore, it might be of advantage in the treatment of acute exacerbations of COPD (AECOPD). No randomized trials have assessed this for admitted COPD-patients on a regular ward and only limited data from non-randomized studies is available. OBJECTIVES: The aim of our study was to identify the reasons to initiate treatment with HFNC in a group of COPD-patients during an exacerbation, further identify those most likely to benefit from HFNC treatment and to find factors associated with treatment success on the pulmonary ward. MATERIAL AND METHODS: This retrospective study included COPD-patients admitted to the pulmonary ward and treated with HFNC from April 2016 until April 2019. Only patients admitted with severe acute exacerbations were included. Patients who had an indication for NIV-treatment where treated with NIV and were included only if they subsequently needed HFNC, e.g. when they did not tolerate NIV. Known asthma patients were excluded. RESULTS: A total of 173 patients were included. Stasis of sputum was the indication most reported to initiate HFNC-treatment. Treatment was well tolerated in 83% of the patients. Cardiac and vascular co-morbidities were significantly associated with a smaller chance of successful treatment (Respectively OR = 0.435; p = 0.013 and OR = 0.493;p = 0.035). Clinical assessment judged HFNC-treatment to be successful in 61% of the patients. Furthermore, in-hospital treatment with NIV was associated with a higher chance of HFNC failure afterwards (OR = 0.439; p = 0.045). CONCLUSION: This large retrospective study showed that HFNC-treatment in patients with an AECOPD was initiated most often for sputum stasis as primary reason. Factors associated with improved outcomes of HFNC-treatment was the absence of vascular and/or cardiac co-morbidities and no need for in-hospital NIV-treatment.

[High flow nasal oxygen in patients with COVID-19]. / Zuurstoftoediening met hoge nasale flow bij covid-19.

High flow nasal oxygen (HFNO) is proven to be effective in non-COVID-19 hypoxemic respiratory failure. In the beginning of the COVID-19 pandemic, HFNO was quickly introduced into daily clinical practice, although the evidence of its effectiveness in COVID-19 was limited. Randomized controlled trials suggest that HFNO has no effect on survival. However, HFNO may lead to less intubations in comparison with conventional oxygen therapy. The evidence of HFNO use in patients with do-not-intubate orders remains very limited. However, in these patients, improvement in comfort could be an important argument to start treatment with HFNO. Additional research is needed to make an evidence based consideration about the clinical use of HFNO in COVID-19 care.

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.

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.

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.

Long-term noninvasive ventilation in COPD: current evidence and future directions.

Introduction: Long-term noninvasive ventilation (NIV) is an established treatment for end-stage COPD patients suffering from chronic hypercapnic respiratory failure. This is reflected by its prominent position in national and international medical guidelines. Areas covered: In recent years, novel developments in technology such as auto-titrating machines and hybrid modes have emerged, and when combined with advances in information and communication technologies, these developments have served to improve the level of NIV-based care. Such progress has largely been instigated by the fact that healthcare systems are now confronted with an increase in the number of patients, which has led to the need for a change in current infrastructures. This article discusses the current practices and recent trends, and offers a glimpse into the future possibilities and requirements associated with this form of ventilation therapy. Expert opinion: Noninvasive ventilation is an established and increasingly used treatment option for patients with chronic hypercapnic COPD and those with persistent hypercapnia following acute hypercapnic lung failure. The main target is to augment alveolar hypoventilation by reducing PaCO2 to relieve symptoms. Nevertheless, when dealing with severely impaired patients, it appears necessary to switch the focus to patient-related outcomes such as health-related quality of life.

Treatment of severe stable COPD: the multidimensional approach of treatable traits.

Now that additional treatment options for severe chronic obstructive pulmonary disease (COPD) have emerged in recent years, patients with severe COPD should not be left in the rather hopeless situation of "there is nothing to improve" any more. Inertia or fatalism is a disservice to our patients. Ranging from advanced care planning to quite intense and demanding therapies such as multidisciplinary pulmonary rehabilitation, (endoscopic) lung volume reduction, chronic noninvasive ventilation and lung transplantation, caregivers should try to provide a personalised treatment for every severe COPD patient. In this review, we aim to describe the multidimensional approach to these patients at our centre along the lines of treatable traits leading to specific additional treatment modalities on top of standard care.