Abstract
Rationale
Telemonitoring has shown benefits during the initiation of home non-invasive ventilation (NIV) but evidence is lacking regarding its use during follow-up. A French national telemonitoring programme incorporating remote support and therapeutic education is designed to improve patient pathways and reduce healthcare resource utilisation. This study investigated the impact of the telemonitoring programme versus usual follow-up on the effectiveness of home NIV.
Methods
The prospective, multicentre, open-label eVENT trial enrolled adults recently started on home NIV. Participants were randomised to the telemonitoring or usual follow-up group. In the telemonitoring group, a CE-marked algorithm generated alerts based on teletransmitted ventilator data. Specialised nurses managed alerts and provided therapeutic education. The primary outcome was mean nocturnal transcutaneous carbon dioxide level (PtCO2) on NIV after 6 months.
Results
56 patients were randomised and 53 were analysed (telemonitoring: n=27, usual follow-up: n=26). At 6 months, mean PtCO2 did not differ significantly between the telemonitoring and usual follow-up groups (42.1±6.1 vs 43.9±6.4 mm Hg; p=0.352) but mean room air partial arterial carbon dioxide pressure (PaCO2) was significantly lower in the telemonitoring versus usual follow-up group (41.7±6.8 vs 46.2±3.5 mm Hg; p=0.003). The proportion of participants without diurnal or nocturnal hypercapnia at 6 months was 82.6% with telemonitoring and 27.3% with usual follow-up (p<0.001). Compared with usual follow-up, the telemonitoring group had greater NIV use, more days with NIV usage ≥4 hour and less non-intentional leaks.
Conclusions
In patients on home NIV, PtCO2 was similar with telemonitoring and usual follow-up, but PaCO2 levels and the quality of ventilatory support were significantly better with telemonitoring.
Trial registration number
Keywords: Assisted Ventilation, COPD Exacerbations, Long Term Oxygen Therapy (LTOT), Non invasive ventilation
WHAT IS ALREADY KNOWN ON THIS TOPIC
Long-term home non-invasive ventilation (NIV) at settings that adequately reduce partial arterial carbon dioxide pressure improves sleep quality, quality of life and survival and reduces exacerbations and hospitalisations in patients with chronic obstructive pulmonary disease. Telemonitoring allows safe at-home initiation of NIV, but its benefit for the long-term follow-up of NIV is not yet clear.
WHAT THIS STUDY ADDS
This study provides real-world data on the impact of a telemonitoring intervention on long-term home NIV in a diverse clinical population. The primary endpoint (transcutaneous carbon dioxide pressure) did not differ significantly between the telemonitoring and usual follow-up groups, but telemonitoring improved control of hypercapnia (based on arterial blood gases) and NIV quality (especially leaks) compared with usual follow-up.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Despite the limitations of this study, the results confirm trends reported in retrospective studies, suggesting that the telemonitoring of long-term NIV therapy allows for an improvement in the quality of therapy and probably also treatment efficacy. Additional studies are needed to confirm these findings.
Introduction
Long-term nocturnal non-invasive ventilation (NIV) is used to treat hypoventilation/chronic respiratory failure (CRF) in several pathologies, including chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS).1 2 In patients with CRF, home NIV at settings that adequately reduce partial arterial carbon dioxide pressure (PaCO2) has been shown to improve sleep quality, quality of life (QoL) and survival and reduce exacerbations and hospitalisations.3 4 However, the quality of NIV and hypercapnia control is often suboptimal,5 6 excessive leakage is common7 8 and compliance is often poor.9 Suboptimal NIV impacts survival outcomes and patient QoL.3 10
Remote monitoring of ventilator data could optimise home NIV quality and care pathways.11 Telemonitoring allows safe at-home initiation of NIV and was non-inferior to inpatient initiation.12,14 However, the benefit of telemonitoring for long-term NIV follow-up is not clear, and the optimal telemonitoring features are unknown.11
In 2018, a national trial of a telemonitoring programme (‘Expérimentations de Télémédecine pour l’Amélioration des Parcours En Santé’ (ETAPES)) was initiated to improve care pathways in patients with CRF requiring NIV, promoted and reimbursed by the French Ministry of Health.15 16 ETAPES combined therapeutic education, daily NIV telemonitoring and remote analysis of NIV data by healthcare professionals. Of an estimated 96 126 patients on NIV in France in 2019,17 about 1000 participated in ETAPES. Observational data highlighted the potential for ETAPES participation to improve home NIV quality.15 However, no randomised controlled trial has been conducted in this setting. The eVENT trial was designed to assess the impact of ETAPES interventions (telemonitoring with remote support/therapeutic education) versus usual follow-up on hypercapnia control, patient-reported outcome measures (PROMs) and healthcare resource utilisation during home NIV therapy in France.
Methods
Study design and randomisation
The prospective, multicentre (n=11), open-label, parallel-group eVENT trial (NCT04615078) randomised patients on home NIV (1:1) to usual follow-up alone or usual follow-up plus ETAPES (telemonitoring group). Randomisation was performed using computer-based minimisation, stratified by centre and primary respiratory pathology (COPD, OHS and other). All participants provided written informed consent.
A blinded study with a sham control group was not possible due to the nature of the intervention. Participants and investigators were aware of the study group, but homecare technicians were not. Blinded data review was performed by an independent scientific committee (see online supplement).
Participants
Patients aged ≥18 years eligible in the ETAPES programme (see online supplement) and who started home NIV for hypercapnic CRF within the previous 2 months were eligible. Those who had already participated in ETAPES, were participating in another interventional study or were ineligible for ETAPES (see online supplement for details) were excluded.
NIV therapy and ETAPES interventions
NIV initiation criteria and settings, respiratory therapies, consultations and hospitalisations were at the discretion of the treating physician. NIV home services were provided by Air Liquide Healthcare affiliates according to national regulations. All patients used the Lumis 150 VPAP-ST ResMed bilevel positive airway pressure device.
The ETAPES programme was implemented using the Chronic Care Connect Pneumology technical and organisational solution (Air Liquide Healthcare, Bagneux, France), as detailed elsewhere15 and included a therapeutic education component (see online supplement). Daily NIV data were processed by a CE-marked algorithm (ALMAS-NIV). Alerts were generated when data were not transmitted or when, over a period of 7 days, average mean NIV usage was <4 hours/day, median non-intentional leaks were >24 L/min, or the apnoea–hypopnoea index (AHI) was ≥10 events/hour. To detect COPD exacerbations early, the algorithm generated COPD-specific alerts based on changes in respiratory rate or NIV use.15 During working hours, a centralised team of specialist homecare provider nurses monitored alerts; nurses managed motivation issues or simple technical issues that could be solved by phone (eg, leaks related to mask positioning) or could generate a technician visit for more complex problem-solving. COPD-specific alerts were further assessed by phone using the Exascore questionnaire.18 The medical team was contacted if the Exascore was ≥9 or if there was an unresolved NIV quality issue. Physicians checked alerts after they had been filtered by nursing staff, and nurses had made a phone call to the patient. Physicians could check NIV data, alerts and actions at any time and could modify NIV settings, the patient pathway and/or medication, or request educational sessions as required. From a payer perspective, the amounts reimbursed for the three components of the ETAPES programme are provided in online supplement.
Study procedures
Study-specific visits were planned at inclusion and 6 months (plus another at 12 months for patients with COPD). Relevant demographic, disease-related, healthcare utilisation and safety data were collected at each visit (see online supplement for details). Arterial blood gases (ABGs) in room air were determined at the 6-month visit (online supplemental figure S1).
Nocturnal transcutaneous capnography (Sentec AG, Switzerland) was performed at home while on NIV by the provider’s technician before the 6-month visit (≥4 weeks from an exacerbation and/or acute hospitalisation). Provider interventions, questionnaire responses, NIV settings and daily NIV teletransmitted data were routinely collected in the provider’s database, plus alerts and Exascores for the telemonitoring group.
In the telemonitoring group, lifestyle goals were agreed between the patient and the educational nurse (see online supplement for full details), and patients who had the therapeutic education sessions performed by the homecare provider were provided with a patient satisfaction questionnaire at 6 months.
Outcomes and assessments
The primary outcome was mean nocturnal transcutaneous carbon dioxide pressure (PtCO2) on NIV at 6 months. Associated outcomes were ABGs on room air and the absence of nocturnal or diurnal hypercapnia.19 Nocturnal hypercapnia control was defined as mean PtCO2≤50 mm Hg, and diurnal hypercapnia control was defined as PaCO2<48/<45 mm Hg (COPD/non-COPD) or a ≥20% decrease from baseline.20,22
Secondary exploratory outcomes included NIV quality, PROMs, COPD exacerbations and healthcare resource utilisation. NIV was considered to be ‘successful’ when usage was ≥4 hours/day, non-intentional leaks were ≤24 L/min and AHI was <10 events/hour.15 PROMs were the Disability Related to COPD Tool (DIRECT23; mandated by ETAPES for all patients) and S3-NIV24 questionnaires. The 10-item DIRECT questionnaire was completed by phone every 2 months; scores range from 0 (no daily respiratory disability) to 34 (high daily disability)23; a≥2-point decrease is considered clinically significant.25 The 11-item S3-NIV questionnaire was completed at each technician visit; scores range from 0 (highest impact of disease and NIV treatment) to 10 (lowest impact).24
Sample size and statistical analysis
The target sample size was arbitrarily defined as ≥100 evaluable patients (≥60 with COPD). This provides 80% power for detection of a between-group effect size of 0.57 for the primary outcome. All analyses were performed on an intention-to-treat (ITT) basis; the ITT population included patients who started home NIV and had a follow-up of ≥6/≥2 (COPD/non-COPD) months. Data are presented as mean±SD, median (quartile (Q) Q1; Q3) or number (%).
After checking for normality of distribution, between-group comparison of the primary outcome was performed using a two-way parametric analysis of variance model adjusted for primary respiratory pathology (COPD/non-COPD). Other secondary outcomes were compared between groups using the Wilcoxon test (quantitative variables) or the χ2 or Fisher’s exact test (qualitative variables, as appropriate depending on their distribution). Teletransmitted NIV data were evaluated monthly from 1 to 6 months after NIV initiation. Mean values for each parameter at each timepoint were calculated from those taken during the previous 30 days. Sankey plots were used to visualise individual changes in the three predefined categories of NIV quality over time by study group. Boxplots were used to show NIV usage at 6 months in patients with PtCO2≤50 mm Hg and PaCO2<45 vs ≥45 mm Hg.
The statistical significance level was set at 5%. No adjustment for multiplicity was performed. Statistical analyses were performed using the latest version of JMP software (SAS Institute).
Results
Participants
56 patients (28/group) were enrolled between January and December 2021 (figure 1). Patient enrolment was stopped early (31 December 2021), mainly due to disruptions caused by the COVID-19 pandemic and the scheduled end of the ETAPES programme in 2022. Mean follow-up was 8.0±3.0 months. Of the 56 patients randomised, three were not included in the ITT population: one in the telemonitoring group who never received home NIV and two with COPD in the usual follow-up group who had follow-up of <6 months. No patient in the ITT population was lost to follow-up. The groups were well balanced for baseline parameters, but the proportion with OSA was higher in the telemonitoring versus usual follow-up group (table 1, online supplemental table S1). Ventilator settings were comparable between groups (table 1).
Figure 1. CONSORT flow diagram. ABGs, arterial blood gases; CONSORT, Consolidated Standards of Reporting Trials; COPD, chronic obstructive pulmonary disease; ITT, intention to treat; NIV, non-invasive ventilation; PtCO2, transcutaneous carbon dioxide level (nocturnal).
Table 1. Demographic and clinical characteristics at baseline, overall and by study group.
| Characteristic | TM group (n=27) | UF group (n=26) | Overall (n=53) |
|---|---|---|---|
| Age, years | 64.6±9.7 | 67.5±16.5 | 66.0±13.4 |
| Female sex, n (%) | 14 (51.9) | 15 (57.7) | 29 (54.7) |
| Primary respiratory disease, n (%) | |||
| COPD | 12 (44.4) | 11 (42.3) | 23 (43.4) |
| OHS | 12 (44.4) | 12 (46.2) | 24 (45.3) |
| Other* | 3 (11.1) | 3 (11.5) | 6 (11.3) |
| BMI, kg/m2† | 38.1 (26.5; 44.8) | 33.0 (26.7; 37.5) | 34.9 (26.8; 39.9) |
| Patients with OSA, n (%) | 21 (77.8) | 9 (34.6) | 30 (56.6) |
| Common non-respiratory comorbidities‡, n (%) | |||
| Hypertension | 13 (48.1) | 18 (69.2) | 31 (58.5) |
| Cardiac or cerebrovascular disease | 10 (37.0) | 12 (46.2) | 22 (41.5) |
| Diabetes | 8 (29.6) | 7 (26.9) | 15 (28.3) |
| Smoking status | |||
| Previous smoker, n (%) | 11 (40.7) | 7 (26.9) | 18 (34.0) |
| Current smoker, n (%) | 8 (29.6) | 5 (19.2) | 13 (24.5) |
| Pack-years | 32.3±18.1 | 38.6±20.7 | 34.7±19.1 |
| Presence of caregiver at home§, n (%) | 11 (50.0) | 5 (45.5) | 16 (48.5) |
| Hospitalised with CRF in the previous year, n (%) | 8 (29.6) | 11 (42.3) | 19 (35.8) |
| COPD patients hospitalised for an acute respiratory episode in the previous 2 months, n (%) | 4 (14.8) | 4 (15.4) | 8 (15.1) |
| Pulmonary function tests | |||
| FEV1/FVC, % | 69.2±14.8 | 66.1±17.7 | 67.6±16.2 |
| FEV1, % predicted | 64.6±24.6 | 56.5±23.5 | 60.5±24.1 |
| PaO2 in room air before NIV, mm Hg | 64.7±11.4 | 67.0±8.9 | 65.8±10.2 |
| PaCO2 in room air before NIV, mm Hg | 51.0±7.6 | 52.6±5.1 | 51.8±6.45 |
| Characteristics of NIV | |||
| Use of an oronasal mask, n (%) | 15 (55.6) | 16 (61.5) | 31 (58.5) |
| IPAP, cmH2O | 15.6±2.4 | 16.2±3.6 | 15.9±3.0 |
| EPAP, cmH2O | 6.9±1.8 | 6.9±2.0 | 6.9±1.9 |
| Concomitant oxygen therapy, n (%) | 4 (14.8) | 2 (7.7) | 6 (11.3) |
Data are presented as mean±SD, median (quartile (Q) Q1; Q3) or number of patients (%) where the denominator was the number of patients without missing data.
In the TM group, the three patients concerned had OSA and asthma, OSA and kyphoscoliosis or OSA and bronchiectasis; in the UF group, the three patients concerned had kyphoscoliosis, OHS, kyphoscoliosis and bronchiolitis, or OSA, kyphoscoliosis and pulmonary embolism.
Data missing for one patient in the UF group.
Multiple responses possible.
Data missing for 5 patients in the TM group and 15 patients in the UF group.
BMI, body mass index; COPD, chronic obstructive pulmonary disease; CRF, chronic respiratory failure; EPAP, expiratory positive airway pressure; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; IPAP, inspiratory positive airway pressure; NIV, non-invasive ventilation; OHS, obesity hypoventilation syndrome; OSA, obstructive sleep apnoea; PaCO2, partial arterial carbon dioxide pressure; PaO2, partial arterial oxygen pressure; TM, telemonitoring; UF, usual follow-up.
Telemonitoring alerts and therapeutic education
During the first 6 months of home NIV, alerts were mainly generated due to NIV usage <4 hours/night (81.5% of patients, mean 3.7 alerts per patient), transmission default (44.4% of patients, mean 1.4 alerts per patient), variation in respiratory rate (33.3% of patients, mean 3.6 alerts per patient) and variation in NIV use (22.2% of patients, mean 1.4 alerts per patient) (online supplemental table S2). Of the two telemonitored patients with COPD exacerbations, one did not use NIV (preventing generation of exacerbation alerts) and one had alerts before three moderate exacerbations (two for respiratory rate variation and one for low NIV use). However, Exascores were all <9 and, therefore, did not trigger alerts to the medical team.
Telemonitored patients received 2.5±0.9 educational sessions during the first 6 months. Education concerned physical activities and healthier lifestyle (n=19), NIV use and knowledge (n=18), nutrition and weight (n=18), disease knowledge (n=15), comorbidities (n=15), sleep (n=9), smoking (n=9) and emotional states (n=8). Based on the objectives for each patient, all those who agreed to increase their physical activity did so, two of the three with a smoking-related objective reduced or stopped smoking, half of those with a weight-related goal either lost or gained weight as agreed, and half with a goal of increasing NIV usage did so during the study. 11 participants in the telemonitoring group answered the questionnaire relating to satisfaction with the educational sessions. Response details are provided in the online supplement. Compared with usual follow-up, more telemonitored patients stopped smoking (3/6 vs 1/5) and mean weight loss in obese patients was 2.8±3.7 kg in telemonitored patients vs 0.5±4.2 kg in the usual follow-up group.
Primary outcome: hypercapnia control at 6 months
Mean nocturnal PtCO2 at 6 months did not differ significantly between the telemonitoring and usual follow-up groups (difference: 1.71 mm Hg, 95% CI –1.96, 5.39) (table 2). PaCO2 at 6 months was significantly lower in the telemonitoring versus usual follow-up group (table 2). Compared with usual follow-up, significantly more patients in the telemonitoring group achieved a PaCO2<45 mm Hg (table 2).
Table 2. Non-invasive ventilation effectiveness and quality at 6-month follow-up.
| Outcomes | TM group (n=27) | UF group (n=26) | p-value |
|---|---|---|---|
| NIV effectiveness | |||
| Nocturnal capnography on NIV | |||
| n | 23 | 23 | |
| Mean PtCO2, mm Hg | 42.1±6.1 | 43.9±6.4 | 0.352* |
| Patients with mean PtCO2≤50 mm Hg, n (%) | 21 (91.3) | 19 (82.6) | 0.665† |
| Time with PtCO2>50 mm Hg, % recording time | 10.7±26.0 | 15.5±29.5 | 0.281‡ |
| Time with SpO2<90%, % recording time | 14.4±24.4 | 13.3±20.8 | 0.733‡ |
| Arterial blood gases in room air | |||
| n | 23§ | 19¶ | |
| PaO2, mm Hg | 77.2±13.1 | 76.1±17.6 | 0.463‡ |
| PaCO2, mm Hg | 41.7±6.8 | 46.2±3.5 | 0.003‡ |
| Patients with PaCO2<45 mm Hg, n (%) | 18 (78.3) | 6 (31.6) | 0.002** |
| Absence of diurnal or nocturnal hypercapnia | |||
| N | 23 | 22 | |
| Achieved††, n (%) | 19 (82.6) | 6 (27.3) | <0.001** |
| NIV quality | |||
|---|---|---|---|
| NIV use | |||
| n | 22 | 21 | |
| NIV use, hour/day | 6.2±3.3 | 4.1±3.3 | 0.0504‡ |
| Number of days of≥4 hours/day of NIV use | 22.0±11.2 | 16.3±12.6 | 0.305‡ |
| Patients with mean NIV use ≥4 hours/day, n (%) | 17 (77.3) | 10 (47.6) | 0.044** |
| Non-intentional leaks | |||
| n | 20 | 14 | |
| Median, L/min | 2.6±2.8 | 9.7±9.7 | 0.007‡ |
| 95th percentile, L/min | 16.7±12.7 | 30.6±21.5 | 0.018‡ |
| Patients with mean median leaks ≤24 L/min, n (%) | 14 (70.0) | 8 (57.1) | 0.487† |
| AHI | |||
| n | 20 | 14 | |
| Mean, events/hour | 2.1±2.4 | 3.6±5.4 | 0.517‡ |
| Patients with mean AHI <10 events/hour, n (%) | 20 (100.0) | 13 (92.9) | 0.412† |
| Successful NIV quality | |||
| N | 22 | 21 | |
| Achieved‡‡, n (%) | 12 (54.5) | 6 (28.6) | 0.084** |
Data are presented as mean±SD or number of patients (%) where the denominator was the number of patients without missing data.
Two-way parametric ANOVA
Fisher exact test
Wilcoxon test;
In the TM group at 6 months, 1 patient had arterial blood gases on oxygen with PaCO2 of 25.1 mmHg.
In the UF group at 6 months, 2 patients had arterial blood gases on oxygen with PaCO2 values of 50.0 and 55.0 mmHg.
Chi2 test.
The absence of nocturnal or diurnal hypercapnia was defined as a mean PtCO2 ≤50 mmHg and control of hypercapnia on arterial blood gases (PaCO2 <48 mmHg for patients with COPD or <45 mmHg for patients without COPD, or a decrease of ≥20% in PaCO2 compared with baseline). NIV use, non-intentional leaks and AHI are means of daily teletransmitted data over the prior 30 day-period.
#Successful NIV quality was defined as achieving NIV use ≥4 h/day, non-intentional leaks ≤24 L/min and AHI <10 events/h.
AHI, apnoea–hypopnoea index; ANOVA, analysis of variance; NIV, non-invasive ventilation; PaCO2, partial arterial carbon dioxide pressure; PaO2, partial arterial oxygen pressure; PtCO2, transcutaneous carbon dioxide pressure; SpO2, pulsed oxygen saturation; TM, telemonitoring; UF, usual follow-up.
In 45 patients with capnography and ABG data at 6 months, the proportion without diurnal or nocturnal hypercapnia was significantly higher in the telemonitoring versus usual follow-up group (table 2). Most telemonitored patients had PtCO2≤50 mm Hg and PaCO2<45 mm Hg, while the majority who had PtCO2≤50 mm Hg and PaCO2≥45 mm Hg received usual follow-up (online supplemental figure S2). Median (Q1; Q3) NIV use at 6 months was higher in patients with PtCO2≤50 mm Hg/PaCO2<45 mm Hg vs PtCO2≤50 mm Hg/PaCO2≥45 mm Hg (6.9 (4.3; 8.1) vs 5.1 (0.5; 7.6) hours/day) (online supplemental figure S3).
NIV quality
The proportion of patients with successful NIV was significantly higher in the telemonitoring group at 3-month follow-up (56.0% vs 26.9%; p=0.035) but not at 6 months (table 2, figure 2). This was largely due to a higher proportion with NIV use ≥4 hours/day and significantly lower median and 95th percentile non-intentional leaks in the telemonitoring versus usual follow-up group (table 2, figure 2). Most patients in the telemonitoring group satisfied the three criteria in the first month of therapy, and this was sustained at 6 months; in the usual follow-up group, more patients continued to have or developed greater leaks or low compliance (figure 3).
Figure 2. Non-invasive ventilation (NIV) daily usage (A), days with NIV usage of ≥4 hours (B), median non-intentional leaks (C), 95th percentile leaks (D), apnoea–hypopnoea index (E) and the proportion of patients successfully treated with NIV (defined as mean usage ≥4 h/day, mean non-intentional leaks ≤24 L/min and mean apnoea–hypopnoea index <10 event/h) (F). Data are mean values over the previous 30 days at each time point (1, 3 and 6 months) and vertical lines indicate the SD. *Only statistically significant p values are shown (p<0.05). TM, telemonitoring; UF, usual follow-up.
Figure 3. Sankey plots showing changes in the quality of non-invasive ventilation (NIV) therapy over time in the telemonitoring (TM) and usual follow-up (UF) groups. The colour of the lines indicates the quality of NIV therapy as defined below the Sankey plots, and the thickness of the lines represents the number of patients. Values in parentheses indicate the numbers of patients in each NIV quality category at each time point. AHI, apnoea–hypopnoea index.
The greater the number of NIV quality criteria met, the better the hypercapnia control: the proportion of individuals who had controlled nocturnal and diurnal hypercapnia was 75% (12/16) in those who satisfied all three criteria, 62.5% (5/8) for those who had NIV use ≥4 hours/day but high leaks or AHI, and 31.3% (5/16) for those who had NIV use <4 hours/day.
Patient-reported outcome measures
The median (Q1; Q3) DIRECT score (n=32) decreased from 10.0 (5.3; 16.0) at baseline to 7.0 (4.3; 12.8) at follow-up, with no significant between-group differences. Results were similar in the COPD subgroup (from 9.5 (4.5; 16.3) (n=14) to 7.5 (4.8; 15.5) (n=16)).
Baseline total S3-NIV scores were 7.8±1.5 in the telemonitoring group (n=24) and 7.1±1.7 in the usual follow-up group (n=24). The baseline score was 7.0±1.7 in COPD patients (n=21), who mainly reported breathlessness and sputum production, and 7.8±1.6 in non-COPD patients (n=27), who mainly reported breathlessness and NIV side effects (leaks, nasal/oral dryness). S3-NIV scores at 6 months did not differ significantly between the telemonitoring and usual follow-up groups (7.4±1.9 (n=23) vs 8.0±1.5 (n=20); p=0.358); respiratory and sleep quality/NIV side effects scores at 6 months were also similar between groups.
Dropouts, mortality and safety
Six patients (two telemonitoring, four usual follow-up) discontinued NIV; reasons were intolerance (n=4) and patient decision (n=2) (online supplemental table S1). Two patients with COPD died: one in the telemonitoring group during palliative hospitalisation and one in the usual follow-up group by suicide. Non-fatal serious adverse events were reported in two patients in the usual follow-up group (cardiorespiratory decompensation and bronchial carcinoma in one patient each).
COPD exacerbations and healthcare resource utilisation
The number and severity of COPD exacerbations, pulmonologist consultations, hospitalisations and homecare provider interventions were similar in the telemonitoring and usual follow-up groups (table 3).
Table 3. Follow-up duration, hospitalisations, healthcare resource utilisation and COPD exacerbations.
| TM group | UF group | |
|---|---|---|
| Overall ITT population | n=27 | n=26 |
| Follow-up duration, months | 8.1±2.7 | 8.5±2.8 |
| Hospitalisation for another reason than a COPD exacerbation | ||
| Patients affected, n | 0 | 1 |
| Hospitalisations (total), n | 0 | 1 |
| Medical consultations with pulmonologist | ||
| Patients affected, n (%) | 15 (62.5) | 21 (84.0) |
| Consultations (total), n | 18 | 25 |
| Consultations (per patient), n | 1.2±0.4 | 1.2±0.4 |
| Homecare provider interventions during the first 6 months, per patient | ||
| Home visit by a technician | 6.6±2.4 | 7.2±3.6 |
| Changes in NIV settings | 2.3±1.6 | 2.4±1.6 |
| Changes of mask | 1.6±0.7 | 1.6±1.1 |
| Phone calls by a nurse* | 5.1±4.3 | 1.2±0.5 |
| Patients with COPD | n=12 | n=11 |
|---|---|---|
| Follow-up duration, months | 10.0±2.9 | 11.1±2.1 |
| Moderate exacerbations | ||
| Patients affected, n | 1 | 3 |
| Exacerbations (total), n | 3 | 3 |
| Exacerbation requiring hospitalisation | ||
| Patients affected, n | 1 | 3 |
| Exacerbations (total), n | 3 | 3 |
Data are presented as mean ±SD, n or number of patients (%).
Excluding therapeutic education sessions.
COPD, chronic obstructive pulmonary disease; ITT, intention to treat; NIV, non-invasive ventilation; TM, telemonitoring; UF, usual follow-up.
Discussion
This study found no significant difference in PtCO2 on NIV at 6 months between groups who had home NIV managed with telemonitoring compared with usual follow-up. However, hypercapnia control and ventilatory support quality may improve with telemonitoring. Nevertheless, the lack of a statistically significant between-group difference in the primary endpoint and small sample size mean that the data should be considered hypothesis generating.
Use of an intervention that included telemonitoring was also recently evaluated in a randomised trial of 148 patients with stable hypercapnic COPD from Jiang et al.26 Disease-specific QoL (determined using the Severe Respiratory Insufficiency questionnaire; primary endpoint) was significantly improved and the 12-month risk of hospital readmission significantly reduced in the intervention versus control group.26 However, mean PaCO2 at 6-month follow-up did not differ significantly between groups and remained high (57.27 and 55.43 mm Hg in the intervention and control groups, respectively). It is difficult to compare the findings from our study and the study by Jiang et al due to the different healthcare systems (France vs China) and patient populations (mixed population with a clinical indication for home NIV vs an older, predominantly male, lean population with severe COPD), and differences in ‘usual follow-up’ (ie, in-patient training on ventilator use and a helpline to contact the provider in case of technical issues in the study by Jiang et al versus in-patient NIV initiation, provider home visits every 2–4 months and a 24/7 helpline in our study). Therefore, our study is more representative of the effectiveness of telemonitoring because the between-group difference in patient follow-up is much smaller in our study than in the study by Jiang et al.
Our primary objective was to assess correction of alveolar ventilation with telemonitoring and patient support in addition to usual care. Thus, we chose to assess hypercapnia control using two different parameters: PtCO2 (primary endpoint) and PaCO2 because it was previously shown that diurnal ABGs can underestimate sleep hypoventilation in patients with chronic lung disorders, and this also applies to ventilated patients.27 However, as shown in online supplemental figure S2, some participants in our study (counterintuitively) had PaCO2>45 mm Hg but normal PtCO2. We have several hypotheses for these findings. This may be because the two assessments were not performed on the same day (and therefore not necessarily under the same duration of NIV usage), and because the protocol specified that the capnography data were only valid if testing was performed during a night with NIV usage of ≥4 hours. We observed that some participants increased their NIV usage on the night of capnography, following the technician’s instructions. Indeed, at 6 months, a significantly higher proportion of patients in the telemonitoring group (77.3%) than in the usual follow-up group (47.6%) had a monthly device usage ≥4 hours/night (p=0.044; table 2), and the number of days with NIV usage ≥4 hours/night was numerically higher in the telemonitoring versus usual follow-up group (table 2). However, 23 PtCO2 readings were valid in both groups, indicating an NIV duration of ≥4 hours on the night of the recording. This means that PtCO2 provides a single timepoint measure on a night with optimal device usage, reflecting the true effect of NIV therapy on the night of measurement, whereas PaCO2 gives a more overall indication of the impact of NIV and longer-term compliance with therapy (online supplemental figure S3).
There is also a potential physiologically based explanation for our findings. It has recently been reported that a relatively low proportion of individuals with severe stable COPD undergoing chronic NIV therapy who achieve nocturnal PtCO2 targets also show a substantial reduction in daytime PaCO2.28 This could be due to a rise in CO2 levels during the day even if they are adequately controlled at night. Such a relationship would be particularly dependent on overnight NIV usage hours, with less device usage meaning that daytime levels might rise to a greater extent (even if nocturnal PtCO2 targets are achieved). Night-time NIV usage in our study was less than that in the recent paper by Ravelling et al,28 and our study population was more diverse in terms of underlying pathology and included more individuals with obesity. Therefore, variations in nightly NIV usage could have had a more marked effect on the relationship between nocturnal PtCO2 and daytime PaCO2, whereby nights with adequate NIV usage would be followed by days with better ongoing ventilatory control during the day and vice versa.
Another important point is that the benefit of home NIV therapy in patients with stable COPD requires settings that adequately reduce PaCO2.3 4 However, although mean inspiratory and expiratory positive airway pressure settings in our study were below those used in high-intensity NIV designed to achieve normocapnia, they were similar to those used in the study by Jiang et al26 and did control hypercapnia based on PaCO2 and PtCO2 in almost all patients who complied with their NIV treatment. The settings used in our study reflect the characteristics of the study population, which mainly included people with OHS and obese individuals with COPD who were likely to have overlap syndrome. Indeed, median body mass index ((BMI) 31.5 kg/m2) and mean per cent predicted forced expiratory volume in 1 s ((FEV1) 43.2%) in our COPD population differed from those in the previous study by Köhnlein et al21 (mean BMI 24.5–24.8 kg/m2 and mean per cent predicted FEV1 26%–27.5%) and the proportion of patients on long-term oxygen therapy in our study was low.
With respect to the quality of NIV, there was better device usage and less leak during use of the telemonitoring intervention. This makes sense because the system was designed to trigger alerts around these parameters, meaning that providers would take action to address the issues. The observational TELVENT study, including 343 patients receiving the ETAPES intervention starting after about 3 years of home NIV usage, used the same composite criterion for NIV success (device use, leaks and AHI).15 In that study, 76% of patients had successful NIV at 15 days after the start of telemonitoring, increasing to 87% at 6 and 12 months.15 Our study included patients who had recently started home NIV and found that 34.8% had successful NIV after 1–2 months of telemonitoring, which increased to 54.5% at 6 months. Not surprisingly, successful NIV in our study was associated with better control of diurnal and nocturnal hypercapnia.
The PROMs evaluated in our study did not show any significant differences between the telemonitoring and usual care group after 6 months, despite more NIV usage and less leak in the telemonitoring group. This may be due to the use of the COPD-specific DIRECT questionnaire in a largely non-COPD population, lack of statistical power or because these PROMs may reflect underlying respiratory disease evolution but might not be sensitive enough to assess changes in symptoms and perceptions related to NIV treatment effectiveness or quality.10
We also did not find any significant impact of the ETAPES intervention on healthcare utilisation, which contrasts with the study by Jiang et al.26 This could be due to variations in healthcare utilisation based on underlying pathology and the heterogeneous nature of our study population (mostly obese/overlap COPD or OHS). Patients with COPD made up about 43% of our total population. Although fewer patients in the telemonitoring group had COPD exacerbations, were hospitalised or consulted a pulmonologist, the limited number of events prevents robust conclusions from being made. Furthermore, the observation period was too short to fully assess the impact of the intervention on the number of COPD exacerbations, which are influenced by a wide range of factors in addition to the quality of ventilatory support. We could not determine whether exacerbation detection alerts in the telemonitoring system worked well or not because of the small number of events and because alerts can only be generated if the patient is using the ventilator.
The greatest difference in homecare provider interventions between the telemonitoring and usual follow-up groups in this study was the number of phone calls by a nurse, which was >4 fold higher in the telemonitoring group and represented an acceptable burden for the team responsible for the telemonitoring. We speculate that the ability of nurses to resolve numerous issues without additional medical expertise is one potential way that the ETAPES intervention could optimise medical resource utilisation. In addition, resolving alerts is likely to reinforce therapeutic education and patient autonomy, and some repeat alerts for similar issues could be resolved by the patients themselves. Another key point is that we cannot clearly determine the contribution of therapeutic education to the study findings. As most telemonitored patients met their objectives of a more active lifestyle and smoking cessation, it can be assumed that education is an important pillar to successful telemonitoring schemes.15 29
The trial has several limitations. First, despite randomisation, stratified by primary CRF pathology, the proportion with OSA was not similar between groups, and this may have influenced our results.30 However, the number of participants with obesity was the same in both groups. Borel et al reported better prognosis in obese versus non-obese individuals undergoing NIV, and this was independent of coexisting OSA.30 Second, our trial population was smaller than planned, and there were varying degrees of missing data for some endpoints. This limits statistical power and could account for the lack of statistically significant difference in the primary endpoint, PROMs and hospitalisations/exacerbations between groups. Third, in contrast to the only previous randomised trial in this field,26 we had a diverse patient population that reflects real-world implementation of home NIV in clinical practice. However, some patient groups were not eligible for the ETAPES programme, including those with neuromuscular disease, so the results can only be generalised to groups that are similar to the patient population of this study. Furthermore, the generalisability of our findings is limited by the fact that the patients with COPD in our study were often obese and likely to have overlap syndrome, which is a different group to COPD with severe respiratory phenotype, who are lean and have worse lung function. More research is needed to extend our findings to a respiratory COPD phenotype population requiring higher ventilator settings. In addition, although control of hypercapnia was often achieved with the individually chosen NIV settings used in this study, higher-intensity NIV could have yielded different results, and this is something that warrants further investigation. Fourth, because people treated with NIV in the current study had a variety of indications (mainly COPD and OHS), the specific effects of NIV in each subgroup cannot be precisely determined. The external generalisability of the findings is also limited by the fact that all participants were from one country/healthcare system (France). The inclusion and reimbursement of telemonitoring might differ between healthcare systems (telemonitoring and therapeutic education have been reimbursed by the French healthcare system since 1 July 2023). Finally, our trial assessed patients who recently started NIV and had limited follow-up. Therefore, the optimal duration of the intervention could not be assessed.
Conclusions
Although the primary outcome measure (PtCO2 on NIV) did not differ significantly between the telemonitoring and usual follow-up groups, the current findings indicate that there might be potential for telemonitoring and support (including therapeutic education) to improve hypercapnia control and the quality of home NIV therapy when added to usual care. However, additional studies with a larger patient population are needed to better define the role of telemonitoring in long-term NIV management in a variety of patient populations. Several areas of improvement are being considered, including better interaction with the patient during alerts, improvement of threshold values and possibly personalisation of the alert algorithm.
Supplementary material
Acknowledgements
The authors would like to thank the home healthcare provider’s nurses from VitalAire, ADEP Assistance, ARAIR Assistance and ADAIR Assistance (HHP Subsidiaries of Air Liquide); All study investigators and their teams for patient recruitment; Air Liquide Santé International project team and particularly Marie Danielle Milcent, for her involvement as Clinical Project Manager, Sabine Low-Hong for her data management expertise; Aurélie Formentin and Sylvie Blais, on behalf of Air Liquide Santé International for their involvement as, respectively, Clinical Study Manager and Clinical Data Manager; as well as the clinical research organisation team of SLB Pharma. Medical writing and editorial assistance in the preparation of this paper was provided by Trevor Stanbury, Pro-Pens, France and Nicola Ryan, independent medical writer, funded by Air Liquide Santé International.
Footnotes
Funding: The study was supported by Air Liquide Santé International (no award/grant number).
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Not applicable.
Ethics approval: The trial was conducted in accordance with the Declaration of Helsinki, and European and local laws. This study involves human participants and was approved by 'Comité de Protection des Personnes Ile de France X' (No ID-RCB: 2020-A02150-39/Ref CPP: Protocol 75-2020). Participants gave informed consent to participate in the study before taking part.
Data availability free text: The data are not publicly available due to privacy or ethical restrictions.
Data availability statement
No data are available.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
No data are available.