Quality of life in patients with chronic respiratory failure on home mechanical ventilation

Pathophysiology

Chronic respiratory failure develops in COPD, obesity and NMD as a consequence of imbalance between respiratory muscle load and capacity accompanied by inadequate neural respiratory drive and a blunted ventilatory response to carbon dioxide and an increase in the arterial partial pressure of carbon dioxide (P_aCO2). The associated increase in hydrogen ions is compensated by renal bicarbonate retention. The pathophysiological mechanisms through which this arises are summarised in table 1. Imbalance in the loads and capacity of the respiratory muscle pump leads to increased ventilatory demand, which may be insufficient, and is perceived by patients as breathlessness. This directly impacts upon HRQoL, as manifested by increased daytime symptom burden at rest, poorer sleep quality and impaired exercise capacity and ability to perform physical tasks to maintain independence.

Factors influencing health perception amongst HMV users

A range of modifiable and nonmodifiable factors are likely to influence patients’ health perception and response to HMV. These include the underlying cause of respiratory failure, disease severity at presentation and trajectory of respiratory failure progression, clinical response to HMV, and the intersectionality of individuals’ demographics. These factors, as well as the inherited or acquired nature of the disease and timing of diagnosis, impact on patients’ health perception and HRQoL.

Early and accurate disease classification is imperative and NMD should be classified as slowly or rapidly progressive and inherited or acquired, since these factors will influence health perception and HRQoL (table 2). For instance, Duchenne muscular dystrophy presents in childhood and is now considered a chronic multisystem disease in which advances in respiratory, cardiac and nutritional therapeutics have extended life expectancy in recent decades [6]. In contrast, the incidence of amyotrophic lateral sclerosis (ALS) is highest in the sixth and seventh decades and death typically occurs 2–4 years after diagnosis, most commonly from respiratory failure caused by respiratory muscle weakness [7, 8]. Patients with obesity-related respiratory failure and COPD present either with acute-on-chronic respiratory failure [9, 10] or in a chronic stable state [11–13], with the acute presentation in obesity more common amongst those who live alone [12]. Clinical trials have demonstrated that HMV improves symptoms, respiratory physiology, physical activity, risk of hospitalisation and survival in patients with chronic and post-acute COPD, inherited and acquired NMD, and obesity-related respiratory failure.

Individual patients’ demographics undoubtedly influence patients’ engagement with HMV and the impact the intervention has on their HRQoL. However, the role of intersectionality in HRQoL amongst HMV users is poorly understood, likely as a consequence of unconscious biases within scientific research [14]. It is imperative that clinicians consider patients’ sex, ethnicity, social support, level of deprivation and healthcare access, which impact upon the timing of disease diagnosis, engagement with the intervention and follow-up, and thus clinical outcomes (figure 1).

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FIGURE 1

Illustration of the complexity and intersectionality of modifiable and nonmodifiable influences on health-related quality of life in patients with chronic respiratory failure, some of which may be addressed using home mechanical ventilation.

Health perception is also influenced by factors modifiable by HMV, including hospital admission and re-admission, daytime fatigue and somnolence, and sleep quality. Sleep quality impacts upon an individual's ability to function during the daytime, including physical activity, concentration and memory, and impaired sleep quality is associated with poorer HRQoL in chronic respiratory disease [15]. The aetiology of sleep disturbance and sleep disordered breathing between different disease groups with chronic respiratory failure is heterogenous, which may partly explain the varied effects of NIV observed on both sleep quality and HRQoL. Sleep disturbance may additionally be compounded by anxiety and depression, which are common comorbidities in patients with chronic respiratory failure. Such patients are more likely to report difficulty falling asleep, racing thoughts at bedtime and being unable to sleep for days compared to matched controls [16].

Sleep disordered breathing is ubiquitous in obesity hypoventilation syndrome (OHS), with nearly 70% of patients having concomitant severe obstructive sleep apnoea (OSA) [17]. Effective treatment of sleep disordered breathing in OHS patients would therefore be expected to improve sleep quality, which has indeed been confirmed in comparisons of NIV and continuous positive airway pressure (CPAP) (Epworth Sleepiness Scale (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ)), as well as HRQoL (Severe Respiratory Insufficiency (SRI) questionnaire, Short Form 36 (SF-36) and the visual analogue scale (VAS) for wellbeing) [9, 17]. CPAP is relatively inexpensive to set up and monitor compared to NIV. Therefore, since control of hypoventilation and sleep disordered breathing may be achieved with both NIV and CPAP in OHS, healthcare services may opt to initiate patients on CPAP either as first line therapy in patients with severe OSA who are not severely hypercapnic, or as a step down following reversal of respiratory failure with a period of NIV [18, 19]. This practice is supported by short-term data demonstrating no differences in treatment efficacy, HRQoL (SF-36 and SRI) or daytime somnolence (ESS) between CPAP and NIV as initial therapy [9], or changes in ventilatory control, HRQoL (SRI) or sleepiness (ESS and Pittsburgh Sleep Quality Index (PSQI)) when switching from NIV to auto-CPAP in OHS [20].

Different ventilator modes may be used to achieve ventilatory control, which may theoretically influence adherence and sleep quality. When using fixed pressure support ventilation, obese patients require higher pressures to overcome upper airway obstruction and achieve adequate control of hypoventilation [21]. Volume-targeted pressure support ventilation is increasingly used in OHS. This ventilator mode estimates expiratory volume and automatically adjusts delivered pressures to achieve a pre-set target tidal volume. In average volume-assured pressure support (AVAPS) mode, expiratory positive airway pressure (EPAP) and maximum inspiratory positive airway pressure (IPAP) are pre-set and IPAP is auto-titrated. In AVAPS with automated EPAP (AVAPS-AE), EPAP is auto-titrated to overcome upper airway occlusion (for example in OSA) or to offset expiratory flow limitation in COPD. These volume-assured modes have a theoretical risk of causing sleep disturbance due to delivery of variable airway pressures. This does not appear to translate clinically, with no differences observed in objective actigraphy or subjective questionnaire (ESS, VAS, fatigue severity scale (FSS)) measures of sleep quality and HRQoL (SRI summary score and all domains) in superobese (body mass index (BMI) >40 mg·kg⁻²) patients in chronic respiratory failure randomised to either fixed pressure support or AVAPS ventilation [12]. Similarly, AVAPS-AE has been compared to fixed-pressure support ventilation in OHS, with no between-group differences in polysomnographic indices or subjective measures (ESS, RSQI, VAS) of sleep quality or HRQoL (SRI) observed [22]. In both cohorts of obese and super obese, comparable ventilatory control was achieved with fixed-pressure support, AVAPS and AVAPS-AE. It should be noted that there is currently no evidence base guiding the implementation of volume-targeted ventilation as a first-line ventilatory mode [23, 24]. There is increasing recognition of COPD-OSA overlap syndrome, where control of both hypoventilation and abolition of expiratory flow limitation and upper airway occlusion may be required. Nonrandomised data demonstrate that, in COPD-OSA patients established on fixed pressure support HMV, switching to AVAPS-AE is not associated with short-term changes in polysomnography indices of sleep quality after 6 weeks; however, subjective sleep comfort (VAS) improved following mode transition [25]. Furthermore, there were no changes in gas exchange or disease-specific HRQoL measures, including the COPD Assessment Test and the SRI questionnaire. These preliminary data indicate the safety and efficacy of using automated HMV modes in COPD-OSA; however, prospective randomised trials are warranted to understand the effects of different methods of delivering positive airways pressure therapy in this cohort.

The underlying cause of respiratory failure likely influences the psychological impact of the diagnosis and need for HMV. Patterns of HMV setup in different disease categories have evolved over the last two decades. Data from the 2001 Eurovent survey, which included 21 526 HMV users from 16 countries, classified the aetiology of chronic respiratory failure into neuromuscular (which was the largest category), lung/airways disease and thoracic cage disorders, which included OHS [26]. 20 years later, data on 1746 patients from two European specialist ventilation units demonstrate that the underlying disease affecting 30% of HMV users is OHS, with NMD (23%) and obstructive airways disease (19%) accounting for the next largest disease categories [27]. In patients with COPD and progressive NMD, the cause of chronic respiratory failure is progressive and irreversible in nature. Thus, once daytime hypercapnia arises, the need for ventilation is lifelong and may be associated with the accumulation of additional physical disabilities. Patient-centred therapeutic aims when initiating NIV in these patients thus depend on the underlying aetiology of respiratory failure, with the aim of sustaining HRQoL in rapidly progressive disease (such as ALS) and improving it with other conditions (such as COPD or obesity) [28]. This is less true of obesity-related respiratory failure, which is theoretically reversible when patients are provided with lifestyle, pharmacological, rehabilitation and surgical support, where appropriate and available.

Autonomy, the ability to make and enact informed decisions about individuals’ healthcare, is directly associated with HRQoL. Decision making regarding medical interventions must take patients’ preferences and priorities into account. These may relate to the practicalities of engaging with HMV, including technical issues surrounding novel medical devices, as well as the restrictions or burdens it may impose upon patients’ home setup, ability to eat, communicate and travel, as well as the impact on bedpartners, relatives and caregivers. Qualitative interviews reveal that the increased dependence on others precipitated by HMV, surveillance by carers and the reliance on technology can also impede autonomy [29]. Furthermore, HMV users commonly express a preference to remain in their home environment, rather than a care facility, to promote independence and normalisation of their lives as much as possible [30]. Interestingly, a study undertaken by Klingshirn et al. [31], which sought to explore differences in care quality between HMV delivered in private homes and shared living communities, found no quantitively ascertained HRQoL differences (SRI summary score and all subdomains). This discrepancy may reflect the limitations of current questionnaires in identifying nuances of the psychological impacts of HMV.

Assumptions and judgements may be made by healthcare professionals regarding patients’ HRQoL based on their level of disability, which may influence medical decision-making and information provided on therapeutic options [32]. This discordance can detrimentally impact upon patients’ satisfaction with their healthcare providers and autonomy and could lead to breakdown in professional relationships between patients, their caregiver and healthcare professionals [33]. Interviews with HMV users reveal the feeling of being compelled to commence NIV. In some, this was due to the desire to sustain life and so HMV initiation was deemed a necessity, not a choice [34]. Conversely, others describe implicit pressure from family or healthcare professionals to accept HMV and subsequently feeling trapped by the machine [35]. Autonomy impairment, as perceived by healthcare professionals, has been shown to impact around 50% of COPD patients on HMV and is associated with poorer HRQoL, using the SRI [36]. It is important to recognise the limitations in quantitative measures of quality of life that do not necessarily capture individuals’ ability to engage with activities important to them. These may include social visits with friends, completing higher education, attending sporting or religious events and eating at restaurants [37], which should be enquired about during HMV initiation decision-making conversations. The impact of economic implications associated with HMV use must also be acknowledged, including formal costs of increased electricity usage, care support and travel to regular hospital appointments, as well as informal care costs [38].

Self-efficacy refers to individuals’ confidence in their capacity to undertake behaviours that lead to desired outcomes and is a mechanism through which effective disease education and self-management can be promoted [39]. Self-efficacy may be lower in patients with higher disease burden and poorer self-efficacy is associated with worse HRQoL, as measured using the EuroQol-Five Dimensions-Five Levels (EQ-5D-5L) and the EuroQol-Visual Analogue Scale [40]. Data routinely collected from ventilators, including adherence, leaks, apnoea–hypopnoea index (AHI) and ventilatory parameters, may be used to optimise patients’ HMV interfaces and settings remotely and potentially avoid future respiratory deterioration and emergency healthcare attendance. Interestingly, however, additional support provided through daily telemonitoring using simple physiological observations and symptom reporting may impair self-efficacy and lead to excess healthcare utilisation [41].

Anxiety is a common comorbidity in chronic respiratory disease and is independently related to HRQoL [42]. HMV appears to have a beneficial effect on anxiety, as quantified using the anxiety component of the SRI, with greatest improvements observed in patients with OHS and restrictive thoracic disease and more modest improvements in those with COPD and NMD 12 months post-setup. This is corroborated by qualitative interview data, in which HMV users report multidimensional improvements in HRQoL. These include both physical benefits, including renewed vitality, more refreshing sleep and fewer morning headaches, as well as psychological improvements relating to a renewed sense of being, safety and a diminished fear of death [30]. Disease education, including explaining the rationale for HMV and its intended benefits, is important in how acceptable HMV is deemed by patients. Additional psychological support, in the form of a specialist cognitive behavioural therapy programme on awareness and control of physical and emotional symptoms, has been shown to improve HMV adherence as well as HRQoL compared to educational videos [43].

Evidence of improvement in symptoms, physiology, healthcare utilisation and survival

To assess the trajectory of change in HRQoL in the three patient groups, we have focussed on those clinical studies, both observational and clinical trials, which demonstrate that HMV improves symptoms, respiratory physiology, physical activity, hospitalisation and survival.

COPD

• a) In chronic stable hypercapnic patients with preserved exercise capacity and low exacerbation frequency, HMV in addition to oxygen therapy has been shown to improve all-cause survival compared to standard care [11].

• b) In post-acute patients with persistent severe hypercapnia following an acute exacerbation with decompensated respiratory failure requiring acute NIV, HMV with home oxygen therapy increases the time to readmission or death compared to home oxygen therapy alone [10].

Obesity

Obesity-related respiratory failure in superobese patients with hypercapnia secondary to OHS and severe OSA have shown improvement in overnight and daytime carbon dioxide levels with CPAP, pressure support ventilation with a back-up rate and volume-targeted pressure support ventilation either started as an inpatient or outpatient [44–46]. These improvements in gas exchange and lung function are accompanied by changes in HRQoL and sleep quality, with no differences observed between pressure-targeted and volume-targeted modes of ventilation [12, 47].

NMD

HMV has been shown to improve survival in congenital neuromuscular and restrictive chest wall disease [27, 48–50]. ALS patients have demonstrated improvement in survival in patients with orthopnoea, nocturnal hypoventilation, respiratory muscle weakness without severe bulbar impairment, with or without daytime hypercapnia, compared to conventional medical care when treated with HMV [51].

HMV is conventionally initiated on an inpatient basis, involving patient and caregiver education and training, interface selection and acclimatisation. Setup and follow-up may involve long-distance travel to a specialist centre, which requires patient and caregiver time and resources to transport required medical equipment. Emerging data support outpatient and domiciliary setups, which may achieve comparable control of hypoventilation without additional cost implications [13, 52], and advances in remote ventilator monitoring may facilitate fewer in-person follow-up visits.

Disease-specific effects of HMV on HRQoL

OHS

Early observational data indicated that NIV improves breathlessness, sleep quality (FOSQ) and daytime sleepiness, which were subsequently explored in randomised controlled trials [104, 105]. The Pickwick Project was a long-term clinical trial that compared the effects of lifestyle modification, CPAP and NIV in OHS, defined as obesity (BMI ≥30 kg·m⁻²) with daytime hypercapnia. Patients with and without severe OSA (AHI ≥30 events per hour) were evaluated separately. Masa et al. [17] identified that both CPAP and NIV are associated with short-term improvements in sleep quality (using the ESS and FOSQ) and both physical and mental wellbeing (based on SF-36 and a VAS). These benefits are also present in obese subjects without comorbid severe OSA (polysomnographic AHI ≥30 events per hour), in whom home NIV is associated with greater short-term improvements in patient-reported tiredness and refreshing sleep, as well as objective indices of sleep quality, including AHI, arousal and desaturation indices and nocturnal oxygenation [94]. In the long term, the Pickwick Project identified that there were no differences in indices of HRQoL or sleep quality, using the SF-36, ESS or FOSQ between NIV and CPAP in obese patients with chronic respiratory failure and severe OSA over 5 years [44].

NMD

Respiratory failure in ALS is inevitable and HMV is an essential part of treatment 30 months after symptom onset [106]. The nonspecific presentation of the disease commonly results in late diagnosis and patients are often initiated on HMV shortly after receiving the diagnosis. HMV likely confers a survival advantage in patients with ALS following the development of respiratory failure (orthopnoea with maximal inspiratory pressure <60% predicted or daytime hypercapnia), particularly in those without severe bulbar weakness [51]. However, it can be difficult to establish in patients with moderate and severe bulbar weakness and these patients demonstrate lower treatment adherence than those with normal or mild impairment of bulbar function [107]. This may be due to difficulties obtaining an adequate seal leading to mask leaks, which are noisy and uncomfortable, and pooling of upper airway secretions in the interface.

The impact of HMV on HRQoL in ALS is variable, and likely related to bulbar function. Studies of patients with rapidly progressive NMD are challenging to perform for ethical and practical reasons. The landmark clinical trial by Bourke et al. [51] used HRQoL, specifically the SF-36 mental component summary and Sleep Apnoea Quality of Life Index (SAQLI) symptoms domain (given the expected decline in physical function), as the primary outcome. Patients with normal or moderate bulbar weakness who received HMV were found to maintain better HRQoL than those who received standard medical care alone, quantified in all total and domain scores for the CRQ and SAQLI, and the SF-36 domains of mental health, energy vitality, general health perception, emotional and social function and the physical component summary. HMV-related improvements in HRQoL in those patients with severe bulbar weakness were less pronounced, with improvements observed in only the CRQ dyspnoea and SAQLI daily functioning, social isolation and symptoms components. Interestingly, those patients who received NIV had 50% lower rapid eye movement sleep than controls, indicating more sleep disruption, but this was not reflected in subjective measures of sleep quality. Prior work by the same group identified that the peak improvement in HRQoL was achieved 3–5 months after HMV initiation [107]. In contrast, a prospective cross-sectional evaluation which explored predictors of HRQoL in ALS identified that need for mechanical ventilation, as well as disease severity, reduced social activities and comorbid anxiety or depression, were associated with worse HRQoL [108]. This poorer HRQoL amongst patients with more severe disease appears to be positively influenced by HMV, with improvements in ALS Assessment Questionnaire 5 and EQ-5D-5L scores reported by Peseschkian et al. [109] at each disease stage. The limited data available thus indicate that there is likely a cohort of patients in whom HMV will enable a plateau or decelerated decline in HRQoL. Patients with preserved bulbar function are most likely to benefit, likely as a consequence of improved interface fit, which permits minimisation of leak and optimal delivery of positive airway pressures. An individualised approach with respect to patients’ needs and preferences regarding place of ventilation setup, interface selection, ventilator settings and secretion management should improve both survival and HRQoL [110].

There are few clinical trials evaluating the impact of HMV in slowly progressive NMDs. Observational data in Duchenne muscular dystrophy indicate that HMV does not impede patients’ ability to participate in education and social activities and that SF-36 domains of health perception, social function, physical and mental function and mental health are comparable to scores from patients with scoliosis and post-polio syndrome [111]. HRQoL data prospectively collected from patients with adult Pompe disease, which is an inherited glycogen storage disease that causes progressive myopathy, indicate potentially detrimental effects of HMV in this cohort [112]. Patients established on HMV during study participation had a longer disease duration and had correspondingly higher levels of physical disability and resting breathlessness than those who were not ventilated. Despite comparison of different disease stages, no differences were observed in sleep quality, fatigue or mental health (quantified with PSQI, FSS, ESS and SF-36) between ventilated and nonventilated patients. However, those patients who also required daytime ventilation were observed to have lower HRQoL, poorer sleep quality and more intense fatigue. Furthermore, daily time spent on ventilation was inversely related to the physical and mental components of the SF-36. Observational data has demonstrated that nocturnal HMV does not adversely impact upon the patients’ abilities to continue with daily activities that are important to them. However, the need for daytime use of HMV may adversely affect HRQoL.

Elderly population

Eligibility criteria for HMV clinical trials typically exclude elderly patients due to the likely introduction of confounding factors that may influence study outcomes, notably physical comorbidities, cognitive impairment and age-related changes in sleep patterns and architecture. Data on the effects of NIV in older patients are therefore lacking. A prospective evaluation undertaken by Tissot et al. [113] sought to evaluate trends in HRQoL and sleep following NIV initiation for chronic respiratory failure and compared outcomes between elderly (aged 75 years and above) and younger patients. They identified a higher prevalence of OHS amongst the elderly and stability of HRQoL measured with SF-36 between HMV setup and 6 months post-setup in contrast to the improvements in all SF-36 domains observed in younger patients. Comparable improvements in sleep quality, measured with ESS and PSQI, were observed in the older and younger patients, as was reduction in P_aCO2.