In recent years, home mechanical ventilation (HMV) has become increasingly important in the management of chronic respiratory failure. It is used for several heterogeneous diseases, including restrictive thoracic disorders, neuromuscular disorders, sleep breathing disorders (obesity-hypoventilation syndrome, obstructive sleep apnea syndrome) and chronic obstructive pulmonary disease (COPD) [1,2]. These patients are often in advanced stages of the disease and experience significant functional limitations. Therefore, health-related quality of life (HRQoL) is considered a critical treatment outcome [3]. The Severe Respiratory Insufficiency questionnaire (SRI) is a validated multidimensional tool, developed to assess HRQoL in patients with HMV [4]. However, there is limited evidence on the HRQoL of patients on HMV as they approach their end-of-life (EoL)—a period without a consensual definition characterized by an irreversible decline prior to death and/or a time-based perspective related to predicted life expectancy (usually<6 months) [5]. This study aimed to evaluate the HRQoL in patients on HMV for the past 6 months of life.

We conducted a longitudinal cohort study at the outpatient ventilation clinic of the pulmonology department in a tertiary referral center from August 2022 to April 2024. Adult patients with preserved cognitive function, who had been on HMV for more than 3 months and completed the SRI questionnaire after giving their informed consent, were included. Clinical/demographic data (patients’ characteristics, HMV treatment, pulmonary function and others) and SRI questionnaire scores (from 0 to 100, with higher values reflecting better HRQoL) were collected prospectively from health records. At the 6-month follow-up, health records were reviewed to determine patient outcomes. Patients who had died were allocated to the EoL group, while those who remained alive after this period were allocated to the living patients’ group. Patients with active neoplasm (on therapy or palliative care) were excluded as malignancy could directly influence HRQoL independently of chronic respiratory disease or HMV (Supplementary Fig. 1). Inter-group comparisons were drawn using the independent samples t-test, Mann–Whitney U test, or the chi-square test, as appropriate. Analysis of covariance (ANCOVA) was used to compare the SRI total score and subscales across groups, while adjusting for potential confounding factors—pulmonary function (FEV1 percentage predicted) and comorbidities were included as covariates. A p-value<0.05 was considered statistically significant. A total of 79 patients were included: 23 in the EoL group and 56 in the living patients’ group.

Patients’ data are shown in Table 1. Demographic characteristics were similar across the 2 groups. Most patients were men, with a mean age of 77.5±8.0 years. The main underlying disease was COPD (77.2%) and chronic heart failure was present in 50.6% of the patients, with similar distribution across both groups. Additionally, ventilation parameters and HMV adherence time did not differ.

HRQoL, assessed using the SRI total and subscale scores, is presented in Table 2. Compared with the non-end-of-life group, patients in the end-of-life group had significantly lower scores on the SRI summary scale and all subscales, except for the SRI-Associated Symptoms and Sleep subscale, with an approximate 17-point difference in the summary score. The “SRI-Physical Functioning” subscale had the lowest score in both groups, likely reflecting limitations in activities of daily living due to advanced respiratory disease. The impact was more pronounced in the end-of-life group, with statistical significance. In contrast, “SRI-Social Relationships” yielded the highest scores, which suggests a preserved perception of social and interpersonal relationships, regardless of end-of-life status. Nonetheless, more advanced disease may negatively affect social engagement and interactions.

Furthermore, the EoL group exhibited significantly greater severity of respiratory symptoms, as evidenced by a marked reduction in the “SRI-Respiratory Symptoms” subscale score. This finding highlights that patients in the EoL group not only had more advanced disease but also experienced higher symptomatic burden. In contrast, while these patients faced increased respiratory difficulties, the “SRI-Associated Symptoms and Sleep” subscale did not differ across groups (p=0.645). Since it can be more directly related to HMV treatment and its side effects, this finding may suggest that, despite the overall burden of disease and comorbidities during this period, HMV per se did not have a substantial negative impact in the end-of-life phase. Of note, the “SRI-Anxiety” score was significantly lower in the end-of-life group, with a marked difference of approximately 20 points across groups, which may reflect the psychological impact of prognosis awareness and symptomatic burden experienced by patients with advanced disease despite adequate HMV treatment.

In patients with advanced disease, clinical progression is frequently accompanied by a deterioration in HRQoL. The SRI questionnaire may be a useful tool for assessing the impact of illness on patients’ daily lives and for identifying individuals who may be approaching the end-of-life period [2,6]. In advanced stages, patients often experience marked physical, psychological, and functional decline, together with reduced responsiveness to treatment. The observed differences in SRI total scores and subscores between patients in the end-of-life group and survivors are consistent with this clinical trajectory.

These findings suggest that the SRI may be valuable not only as a measure of HRQoL but also as a potential indicator of short-term prognosis [5,7]. However, the present study was exploratory in nature and was not designed to formally assess prognostic performance. Accordingly, prospective prognostic studies are warranted to further evaluate the potential role of the SRI as a marker of short-term outcomes.

Similar results have been reported in retrospective studies, in which lower SRI total scores were associated with increased mortality among patients on HMV [2,8]. In one study, the mean difference in SRI summary scores between deceased and surviving patients was approximately 12 points, which is comparable to the difference observed in our cohort (17 points). In addition, a cutoff value of 56.2 was proposed as a threshold for mortality prediction, consistent with our findings [2]. The minimum clinically important difference (MCID) for the SRI total score has been established at 5 points in patients with chronic obstructive pulmonary disease and chronic hypercapnic respiratory failure, further underscoring the clinical relevance of the differences observed between groups [9].

Nearly all SRI subscale scores were significantly lower among patients with a poorer prognosis [2]. The smallest difference was observed in the “SRI-Associated Symptoms and Sleep” subscale, suggesting that HMV may not have a substantial negative impact on this domain and is generally well tolerated, even during the end-of-life period. This finding supports the view that HMV remains a feasible and nonburdensome intervention for patients in terminal stages.

Considering these findings, the SRI questionnaire may offer valuable insights for identifying terminal disease trajectories. Optimizing the use of HRQoL questionnaires in clinical practice is essential, as it can significantly influence the psychological, physical, and social well-being of patients and their families. It may also support targeted interventions, facilitate the initiation or revision of advance care planning, and help establish appropriate goals of care [5,7].

Earlier prospective and retrospective studies, including larger cohorts, have reported comparable associations between SRI scores and mortality [8]. However, retrospective analyses frequently relied on proxy reports or health records, which are susceptible to recall and reporting bias and may not accurately represent the patient's experience [10]. As far was we know, this is the first study to prospectively assess HRQoL in EoL patients receiving HMV. Accordingly, it provides clinically relevant longitudinal evidence supporting the use of SRI scores for prognostic stratification.

Nevertheless, several limitations should be acknowledged. The small overall sample size – particularly the limited number of EoL patients (n=23) – and the lack of additional confounding variables may have introduced bias, increasing the risk of type I and type II errors and compromising the precision and external validity of the findings. Additionally, the exclusion of patients with neoplasm, although intended to reduce prognostic heterogeneity and minimize confounding from cancer-related symptoms, may also have limited the applicability of the results by introducing selection bias. Future research should acknowledge the necessity of larger sample sizes and diverse cohorts to validate and extend these prospective, patient-reported findings.

In addition to these methodological considerations, another important limitation concerns the lack of consensus on the definition of the EoL period in literature. Two main approaches are widely recognized: a patient-center perspective, which defines EoL according to individual characteristics such as functional decline, symptom trajectory, clinical judgment and the underlying disease; and a time-based perspective, which restricts EoL to patients with a limited life expectancy (commonly ≤6 months) [5,11]. Relying solely on a fixed timeframe may have introduced selection bias into the EoL group and limited the applicability of the results to different patient populations. Future research with larger cohorts and formal prognostic validation are necessary to establish more precise, disease-specific EoL definitions. In parallel, validation of MCID values for SRI subscores and conditions other than COPD is required to determine the clinical relevance of HRQoL differences across EoL definitions and to strengthen the interpretability of SRI-based assessments.

In conclusion, the results highlight the potential of HRQoL assessment to support prognostic evaluation and identify the EoL period, as lower scores were observed in these patients. This approach may facilitate the development of appropriate therapeutic strategies aligned with patients’ needs and personalized care planning. Further research is needed to corroborate the results of this exploratory study and to define SRI cut-off thresholds as reliable indicators of EoL status.