Abstract
Background
Patients with fibrotic interstitial lung diseases (ILDs) experience impaired health-related quality of life (HRQoL). The King's Brief Interstitial Lung Disease (KBILD) questionnaire was designed to evaluate disease-specific HRQoL; however, its practical application in real-world clinical settings has not been thoroughly investigated.
Methods
This prospective longitudinal study included 289 patients with fibrotic ILD initiated antifibrotic therapy. Their HRQoL was evaluated using the KBILD questionnaire at baseline, 6 months and 1 year. A total of 289, 164 and 159 patients completed the KBILD assessment at the aforementioned time points, respectively. The associations between the KBILD scores, clinical parameters and mortality risk were evaluated.
Results
The KBILD Total score demonstrated a moderate correlation with dyspnoea scale but a weak or no correlation with pulmonary function test parameters and ILD aetiology. Interestingly, more than 20% of the patients showed significant improvement (≥5 points) at 6 months and 1 year. A lower baseline KBILD Total score was associated with disease progression and reduced survival, independent of the ILD–gender–age–physiology index. In addition, longitudinal assessment showed that the cross-sectional KBILD Total score at 6 months and 1 year and longitudinal decreases in the KBILD Total score at 1 year were associated with increased mortality risk.
Conclusion
Antifibrotic therapy has a positive impact on HRQoL in a subset of patients with fibrotic ILDs. Repeated KBILD assessment may aid in monitoring mortality risk, independent of lung function tests.
Shareable abstract
This study demonstrated that in patients with ILD receiving antifibrotic therapy, cross-sectional measurements of HRQoL using the KBILD questionnaire and longitudinal declines were associated with increased mortality risk, regardless of disease severity https://bit.ly/4uahziD
Introduction
Fibrosing interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), comprise a spectrum of disorders characterised by extent of fibrosis on high-resolution computed tomography (CT), lung function, worsening symptoms, reduced health-related quality of life (HRQoL) and early mortality, despite current therapies [1]. Patients with PPF reportedly have similar prognosis to those with IPF [2, 3]. Therefore, comprehensive assessment of pulmonary function test results, CT images and patient-reported symptoms is crucial for achieving patient-centred care.
Patients with fibrotic ILDs experience a high burden of persistent symptoms, such as cough, dyspnoea, anxiety and psychological stress, all of which result in HRQoL impairment [4–11]. Patient-reported outcome measures (PROMs) play a pivotal role in capturing symptom, physical and psychological condition and HRQoL, offering perspectives beyond those captured by objective measures. PROMs are increasingly recognised as valuable tools for the assessment of disease severity and treatment response [12]. The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a self-administered, ILD-specific measure of HRQoL and symptom burden [13]. It comprises 15 items across three domains (Psychological, Breathlessness and activities, and Chest symptoms) combined into a Total score [13]. The KBILD questionnaire has been shown to be valid, reproducible and responsive to natural longitudinal change [8, 13–15].
The current international guidelines recommend upfront therapy with antifibrotic drugs in patients with IPF and add on therapy for PPF who have progressed [1]. Nintedanib has demonstrated efficacy in reducing the rate of forced vital capacity (FVC) decline in patients with IPF as well as in those with progressive fibrotic ILDs other than IPF [16]. There is currently no curative therapy for progressive lung fibrosis, but antifibrotic agents have been shown to slow down lung function deterioration. Indeed, most study on antifibrotic therapy focused on its associations with lung function decline, incidence of acute exacerbation and mortality [17–22]. However, in real-world settings, the impact of antifibrotic therapy on HRQoL and association between HRQoL and disease severity or clinical outcomes remains unclear. Therefore, this prospective study aimed to evaluate the degree of HRQoL impairment and its longitudinal change using the KBILD questionnaire in patients with fibrotic ILD receiving antifibrotic therapy, and to explore its clinical association and relationship with mortality risk.
Methods
Ethical approval of the study protocol
This multicentre prospective study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the ethics committee of the following institutions: Hamamatsu University School of Medicine, Seirei-Hamamatsu Hospital, Iwata City Hospital, Shizuoka General Hospital, Seirei-Mikatahara Hospital, Fujieda City Hospital, Hamamatsu Rosai Hospital, Shizuoka City Shizuoka Hospital, Tenryu Hospital, Shizuoka Saiseikai Hospital, Hamamatsu Medical Center, Enshu Hospital and Shizuoka Red Cross Hospital. All subjects provided written informed consent. The study was registered in the University Hospital Medical Information Network in Japan (UMIN000039664).
Patients
A total of 290 consecutive patients with fibrotic ILD receiving pirfenidone or nintedanib treatment were prospectively enrolled in this study between March 2020 and June 2023. The observation period spanned from the initiation of antifibrotic therapy to the patient's final follow-up (date of censoring or death). The patients were censored if they were alive until 31 May 2025. One patient who did not undergo KBILD assessment at baseline was excluded from the study. Ultimately, 289 patients were included in the final analysis. The primary outcome of this study was to evaluate the association between the degree of HRQoL impairment, as assessed by KBILD questionnaire at the initiation of antifibrotic therapy, and all-cause of mortality risk. The secondary outcomes were to evaluate the association between KBILD score and disease progression, to assess the relationship between longitudinal changes in KBILD score and all-cause of mortality risk.
IPF [1, 23]; other idiopathic interstitial pneumonias (IIPs) [24], such as unclassifiable IIP, idiopathic pleuroparenchymal fibroelastosis (iPPFE), and nonspecific interstitial pneumonia; and fibrotic hypersensitivity pneumonitis [25] were diagnosed based on the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association criteria [1, 23–25]. In contrast, connective tissue disease (CTD) was diagnosed based on the published diagnostic or classification criteria [26–31], whereas acute exacerbation (AE) was diagnosed based on the American Thoracic Society guidelines [32].
Data collection
The following clinical information was collected from the patients’ medical records at the initiation of antifibrotic therapy: age, sex, body mass index (BMI), smoking history, AE history, modified Medical Research Council Dyspnoea Scale (mMRC) and 6-min walk test (6MWT). The results of the blood test and pulmonary function test (PFT) were evaluated at baseline and 6 months and 1 year after the initiation of antifibrotic therapy, if available.
Assessment of the KBILD and ILD-GAP index
The KBILD questionnaire is a brief, self-administered questionnaire consisting of 15 items, a seven-point Likert scale and three domains: Psychological, Breathlessness and activities, and Chest symptoms [13]. The scores of KBILD Total and its domains ranged from 0 to 100, with higher scores indicating better HRQoL. A non-commercial licence agreement for the KBILD questionnaire was obtained, and a Japanese version of the KBILD questionnaire was linguistically validated and used in this study [33]. KBILD assessment was conducted at the therapy initiation, at 6 months, and at 1 year, if available. Patients completed the KBILD questionnaire upon arrival for their regularly scheduled clinical visit, before their consultation and any pulmonary function tests. The ILD–gender–age–physiology index (GAP) score was calculated based on data at the therapy initiation, as previously described [34].
Statistical analysis
Discrete variables were expressed as total (percentage) and continuous variables as median (interquartile range). Unmatched and matched continuous variables were compared using the Mann–Whitney U-test. In contrast, categorical variables and correlations were compared using Fisher's exact test of independence and Spearman correlation coefficient (r), respectively. The overall survival time was measured from the initiation of antifibrotic therapy, unless otherwise specified. The first tertile or first quartile values of the KBILD Total score were determined as cut-off points analysing risk for disease progression and mortality. Using the Kaplan–Meier method, cumulative survival probabilities were calculated, with differences evaluated using the log-rank test. Logistic regression analyses and Cox proportional-hazards regression models were used to assess the association of the KBILD Total score with increased risk for disease progression and mortality, respectively, with adjustment for ILD-GAP stage. An absolute decline of ≥10% in FVC or the occurrence of all-cause mortality was considered to indicate disease progression. To account for missing data in the longitudinal analyses, two advanced statistical approaches were performed: a joint model and a mixed-effects model for repeated measures combined with multiple imputation. Missing values were imputed using a multiple imputation approach. These sensitivity analyses addressed 1) whether lower KBILD Total scores were associated with disease progression and 2) the trajectory of KBILD scores over time. R v.4.5.1 (Saitama Medical Center, Jichi Medical University, Saitama, Japan) was used to conduct all statistical analyses [35]. All analyses were two-tailed, with statistical significance defined as p<0.05.
Results
Clinical characteristics
The patients’ clinical characteristics at the initiation of antifibrotic therapy are presented in table 1 and supplementary table S1. Among the 289 patients, 163 (56.1%) had IPF, 44 (15.2%) had unclassifiable IIP, 40 (13.8%) had CTD-ILD and 17 (5.9%) had fibrotic hypersensitivity pneumonitis. The majority of the patients were approximately 70 years old, and more than 70% of them were men. Over 95% of the patients were started on nintedanib. Approximately 80% of the patients experienced dyspnoea (mMRC≥1) and 67.4% exhibited <90% oxygen desaturation on 6MWT. Most patients had severe-to-moderate pulmonary function impairment, with a median FVC of 72.9% and diffusing capacity of the lung for carbon monoxide (DLCO) of 59.9%. Among the patients, 25.3%, 26.0% and 10.4% were prescribed long-term oxygen therapy, prednisolone and immunosuppressants, respectively. The patients’ baseline characteristics in each aetiology are presented in supplementary table S2.
TABLE 1.
Baseline clinical characteristics
| Total cohort (n=289) | |
|---|---|
| Age, years | 72 (67–77) |
| Sex, male/female | 209 (72.3%)/80 (27.7%) |
| Observation period, months | 30.5 (20.2–42.9) |
| PFD/NTD | 10 (3.5%)/279 (96.5%) |
| History of AE | 15 (5.2%) |
| Never/former and current smoker | 85 (29.4%)/205 (70.6%) |
| BMI, kg·m−2 | 23.4 (20.8–25.3) |
| mMRC (0, 1, 2, 3, 4) | 49 (17.0%), 106 (36.7%), 77 (26.6%), 51 (17.6%), 6 (2.1%) |
| 6MWT, Min SpO2 < 90% (n=264) | 178 (67.4%) |
| Pulmonary function test | |
| FVC, % pred | 72.9 (59.9–83.9) |
| DLCO, % (n=269) | 59.9 (46.5–76.4) |
| ILD-GAP (0–1, 2–3, 4–5, 6–8) | 41 (14.2%), 124 (42.9%), 94 (32.5%), 30 (10.4%) |
| Treatment | |
| LTOT | 74 (25.7%) |
| Prednisolone | 75 (26.0%) |
| Immunosuppressants | 30 (10.4%) |
| None of the above | 167 (58.2%) |
| KBILD | |
| KBILD Total score | 74.8 (48.5–60.6) |
| Breathlessness and activity score | 43.9 (35.6–52.5) |
| Psychological score | 50.5 (42.5–58.8) |
| Chest symptoms score | 73.4 (63.7–85.2) |
Data are presented as median (quartile) or n (%). PFD: pirfenidone; NTD: nintedanib; AE: acute exacerbation; BMI: body mass index; mMRC: Modified Medical Research Council Dyspnoea Scale; 6MWT: 6-min walk test; SpO2: peripheral oxygen saturation; FVC: forced vital capacity; DLCO: diffuse capacity of the lung for carbon monoxide; ILD: interstitial lung disease; GAP: gender–age–physiology; LTOT: long-term oxygen therapy; KBILD: The King's Brief Interstitial Lung Disease Questionnaire.
Baseline KBILD score
The distribution of the baseline KBILD scores (Total, Psychological, Breathlessness and activities, and Chest symptoms) is presented in supplementary figure S1a,b. Among the three domains, Breathlessness and activities had the lowest score, whereas Chest symptoms had the highest. Subsequently, the KBILD Total score was evaluated based on the ILD-GAP stage and ILD aetiologies. Compared with patients with ILD-GAP 0–1, those with severe disease (ILD-GAP 4–5 or ILD-GAP 6–8) had lower KBILD Total score (figure 1a). However, no significant difference was observed between patients with ILD-GAP 0–1 and those with ILD-GAP 2–3, or between patients with ILD-GAP 4–5 and those with ILD-GAP 6–8. Meanwhile, the KBILD Total score did not exhibit significant difference across the ILD aetiologies (figure 1b). The baseline scores for Psychological, Breathlessness and activities, and Chest symptoms domains, stratified by ILD-GAP stages were shown in supplementary figure S2.
FIGURE 1.
Baseline King's Brief Interstitial Lung Disease Questionnaire (KBILD) Total score according to the interstitial lung disease (ILD)-gender–age–physiology (GAP) stage and ILD aetiology. KBILD Total score according to the a) ILD-GAP stage and b) ILD aetiology. Each line indicates the median point. IPF: idiopathic pulmonary fibrosis; iPPFE: idiopathic pleuroparenchymal fibroelastosis; NSIP: nonspecific interstitial pneumonia; CTD-ILD: connective tissue disease-related interstitial lung disease; fHP: fibrotic hypersensitivity pneumonitis. **: p<0.01; NS: not significant.
Correlations between the baseline KBILD score and clinical parameters
The KBILD Total score and Breathlessness and activities demonstrated a moderate correlation with mMRC, whereas Psychological and Chest symptoms exhibited a weak correlation. KBILD Total and its three domains showed a weak correlation with PFT parameters, including FVC (%) and DLCO (%), but no significant association with age or BMI (supplementary table S3).
Lower KBILD total score and disease progression
Next, whether low HRQoL, measured using the KBILD questionnaire, was associated with increased risk for disease progression (a ≥10% decline in FVC or the occurrence of all-cause mortality within 6 months and 1 year after the initiation of antifibrotic therapy) was determined. Within 6 months, 15 patients had died and 28 demonstrated a ≥10% decline in FVC, resulting in a total of 43 patients who experienced disease progression. Within 1 year, 33 patients had died and 46 demonstrated a ≥10% decline in FVC, leading to a total of 79 patients who experienced disease progression. A logistic regression analysis revealed that patients in the lowest tertile of the KBILD Total score (≤50.4) exhibited increased risk for disease progression independent of the ILD-GAP stage at 6 months and 1 year (odds ratio 4.419 (2.151–9.302) and 3.078 (1.637–5.708), respectively; figure 2). Similar results were obtained when the lowest quartile of the KBILD Total score (≤48.5) was used (odds ratio 3.036 (1.422–6.438) and 2.239 (1.157–4.340), respectively; figure 2).
FIGURE 2.
Odds ratio of King's Brief Interstitial Lung Disease Questionnaire (KBILD) Total score to disease progression in patients with interstitial lung diseases (ILDs) receiving antifibrotic therapy. The odds ratio of KBILD Total score to disease progression within 6 months and 1 year after the initiation of antifibrotic therapy is presented, respectively. The cut-off points were determined based on the first tertile point (≤50.4) and first quartile point (≤48.5). The p-values were determined via logistic regression analyses after adjustment for the ILD-gender–age–physiology (GAP) stage.
Association between KBILD total score and survival
The association between KBILD and increased mortality risk was also investigated. As anticipated, patients with lower tertile or quartile of the KBILD Total score (≤50.4 and ≤48.5, respectively) exhibited increased risk for mortality compared with the other groups (figure 3 and supplementary figure S3).
FIGURE 3.
Kaplan–Meier curves of patients with interstitial lung diseases (ILDs) receiving antifibrotic therapy according to the baseline King's Brief Interstitial Lung Disease Questionnaire (KBILD) Total score. Kaplan–Meier curves of patients with ILDs receiving antifibrotic therapy based on the KBILD Total score at the initiation of antifibrotic therapy. The cut-off point was determined by the tertile points. The p-values were determined using a log-rank test. Each bar represents the odds ratio with 95% confidence interval.
Cox proportional-hazards regression analyses revealed that the KBILD Total score was a significant factor for mortality independent of the ILD-GAP stage (table 2).
TABLE 2.
Multivariate Cox-proportion analysis for mortality
| Hazard ratio | 95% CI | p–value | |
|---|---|---|---|
| Multivariate analysis 1 | |||
| ILD-GAP stage, per one-stage increase | 2.052 | 1.685–2.502 | <0.001 |
| KBILD total score ≤50.4 (first tertile) | 1.716 | 1.229–2.389 | 0.001 |
| Multivariate analysis 2 | |||
| ILD-GAP stage, per one-stage increase | 2.074 | 1.700–2.531 | <0.001 |
| KBILD total score ≤48.5 (first quartile) | 1.597 | 1.123–2.247 | 0.008 |
| Multivariate analysis 3 | |||
| ILD-GAP stage, per one-stage increase | 2.030 | 1.661–2.485 | <0.001 |
| KBILD total score, continuous variable | 0.982 | 0.968–0.997 | 0.020 |
ILD: interstitial lung disease; GAP: gender–age–physiology; KBILD: The King's Brief Interstitial Lung Disease Questionnaire.
HRQoL status at 6 months and 1 year after the initiation of antifibrotic therapy
Among the 289 patients, 164 and 159 underwent KBILD assessment at 6 months and at 1 year, respectively, whereas 127 underwent the assessment at both time points. The overall trajectory of the KBILD questionnaire is illustrated in supplementary figure S4a. There were no significant differences in the KBILD Total score after accounting for missing data using the joint model analysis and a mixed-effects model for repeated measures combined with multiple imputation (supplementary table S4). According to a previous study [36], a cut-off of 5 points was set. As shown in supplementary figure S4b, 34 (20.7%) and 43 (27.0%) patients exhibited a decline in the KBILD Total score (≤−5) at 6 months and 1 year, respectively. In contrast, a significant improvement in the KBILD Total score (≥5 points) was observed in 42 (25.6%) and 38 (23.9%) patients 6 months and 1 year after the initiation of antifibrotic therapy, respectively (supplementary figure S4b). Clinical characteristics according to longitudinal changes of KBILD Total score were presented in supplementary tables S5 and S6. No significance differences were observed in the initiation of long-term oxygen therapy or corticosteroid therapy during the period among the subgroups defined by longitudinal changes in KBILD Total score (data not shown).
Longitudinal KBILD assessment and mortality risk
This study determined 1) whether the KBILD Total score at 6 months and 1 year was consistently associated with mortality risk and evaluated 2) the association between longitudinal changes in the KBILD score and mortality risk. As presented in figure 4a,b, lower cross-sectional KBILD Total scores at 6 months and 1 year after the initiation of antifibrotic therapy were associated with shorter survival time independent of the baseline ILD-GAP stage (17.7 months versus 51.8 months, hazard ratio (HR) 2.353 (1.379–3.929) and 16.2 and 46.0 months, HR 3.080 (1.756–5.359). As a sensitive analysis, a joint model analysis adjusted for ILD-GAP showed that lower KBILD Total scores at each timepoint were consistently associated with disease progression (absolute FVC decline≥ 10% or death) (HR 0.650 (0.470–0.890); p=0.007).
FIGURE 4.
Longitudinal assessment of King's Brief Interstitial Lung Disease Questionnaire (KBILD) in patients with interstitial lung diseases (ILDs) receiving antifibrotic therapy. a,b) Kaplan–Meier curves of patients with ILDs receiving antifibrotic therapy based on the KBILD Total score at a) 6 months and b) 1 year after the initiation of antifibrotic therapy. The cut-off point was determined by the tertile points of the KBILD Total score at the therapy initiation. The survival time was measured from the date of KBILD assessment at 6 months and 1 year after the therapy initiation, respectively. The p-values were determined by a log-rank test.
Patients who exhibited a longitudinal decline of ≥5 points in the KBILD Total score at 6 months and 1 year had shorter survival times than those who did not (supplementary figure S4c,d; median 34.3 versus 51.8 months at 6 months, and 21.7 versus 46.0 months at 1 year). KBILD Toral scores as baseline, 6 months, and 1 year were each associated with mortality risk, reflected by hazard ratios and C-indices. This pattern was consistent across the analyses using continuous values, categorical classifications, and ΔKBILD values (supplementary table S7).
Discussion
In this study, the degree of HRQoL impairment and clinical associations were evaluated using the KBILD questionnaire in patients with fibrotic ILD receiving antifibrotic therapy. Patients with mild disease had higher KBILD Total scores than those with severe disease; however, no significant differences were observed between the aetiologies. The KBILD scores demonstrated a moderate association with dyspnoea, which was evaluated using the mMRC scale, but weak correlations with PFT parameters. Notably, over 20% of the patients showed an improvement in the KBILD Total score (≥5 points) over a 1-year period, indicating that HRQoL improvement may occur in a subset of patients during antifibrotic therapy. This study also showed that a lower baseline KBILD Total score was associated with an increased risk for disease progression at 6 months and 1 year, resulting in an increased risk for mortality independent of the ILD-GAP stage. Moreover, longitudinal decline in KBILD Total scores had a higher risk for mortality. These results indicate the importance of HRQoL assessment and might be useful for managing patients with fibrotic ILD receiving antifibrotic therapy.
The KBILD questionnaire, which consists of 15 items, with scores ranging from 0 to 100, was developed to evaluate ILD-specific HRQoL [13]. As regards the clinical implication of PROMs in antifibrotic therapy, the results of the INBUILD study, assessed using the KBILD [8, 37] and Living with Pulmonary Fibrosis (L-PF) questionnaire [38, 39], have been reported. However, to the best of our knowledge, no real-world study has evaluated PROMs in patients receiving antifibrotic therapy, and their associations with increased mortality risk were not clearly described. As previously reported [8], the KBILD Total score and its three domains showed a weak correlation with FVC (%). While KBILD Total score tend to decrease with increasing disease severity. This decrease was not associated with the aetiology of ILD but was strongly correlated with the mMRC scores. These results indicated that symptom burden in ILD plays a more pivotal role in HRQoL decline than FVC decline, highlighting the importance of PROMs in ILD assessment.
Nintedanib was reported to significantly inhibit the worsening of the L-PF Total score, symptoms, dyspnoea, fatigue, cough and impact score compared with placebo at 52 weeks [39]. Furthermore, over 20% of the patients exhibited an increase in the KBILD Total score by ≥5 points. As the minimal clinically important difference of the KBILD has been reported to range between 2 and 8 points [8, 14, 36], these patients were considered to have achieved significant improvements in HRQoL while receiving antifibrotic therapy. These results indicated that aside from inhibiting FVC decline, antifibrotic therapy could have a positive impact on HRQoL, despite the progressive nature of fibrotic ILD.
An important aspect of this study was the prognostic value of KBILD. A lower baseline KBILD Total score was found to be associated with disease progression and shorter survival time. Furthermore, a longitudinal decrease in KBILD score showed an association with increased mortality risk. Consistent with our results, a Finnish registry consisting of 245 patients with IPF, 26% of whom were prescribed antifibrotic agents, reported that those with the highest quartile of the KBILD Total score at baseline had significantly longer survival time than the remaining three groups [40]. A ≥5-point decline in the KBILD Total score at 1 and 2 years showed an association with poor survival outcomes [40]. Notably, this study showed that a lower KBILD Total score was associated with increased risk for disease progression and mortality, even after adjustment for the ILD-GAP stage. Therefore, physicians should acknowledge the importance of assessing symptom burden and HRQoL in ILD management, in addition to assessing disease severity through PFTs and disease extent via radiographical imaging.
A notable advantage of PROMs, such as KBILD, is their noninvasive and repeatable nature. Our study uniquely demonstrated that KBILD Total score was consistently associated with increased mortality risk at baseline and 6 months and 1 year after the initiation of antifibrotic therapy. This finding suggests that KBILD holds promise as a dynamic prognostic tool that may not require comparison to prior values. In addition, compared with the L-PF questionnaire, the KBILD questionnaire appears to be less influenced by ethnicity. In the INBUILD study, the overall cohort had a mean L-PF score of 39.0, whereas Japanese participants had a significantly improved HRQoL with a mean L-PF score of 29.7 [38, 39]. In contrast, the mean KBILD Total scores of the overall and Asian subpopulations of the INBUILD study were comparable (52.4 and 54.5, respectively) [8, 37]. In the present study, the median KBILD Total score was 54.8, further supporting the cultural applicability of the KBILD questionnaire.
This study had several limitations. First, despite the prospective nature of the study, longitudinal KBILD assessment was not conducted on some patients. Second, missing data at 6 and 12 months, likely due to informative dropout, limited the reliability of the longitudinal analyses, and the potential impact of this dropout warrants cautious interpretation. Third, due to ethical considerations, we were unable to include a control group of patients with fibrotic ILDs who were not treated with antifibrotic therapy, and thus could not directly compare HRQoL outcomes between treated and untreated patients. Fourth, although disease progression was defined as a ≥10% decline in FVC or the occurrence of all-cause mortality, standardised criteria for disease progression after the initiation of antifibrotic therapy remain to be established. Fifth, this study used the first tertile of the KBILD Total score and 5 as a cut-off point based on previous study [36]; however, the optimal cut-off point for the KBILD Total score remains to be determined. To overcome these limitations, the results should be cautiously interpreted, and further studies should be conducted. In addition, assessment of symptom burden and impaired HRQoL in patients with ILD may lead to enhanced satisfaction for the patients and their families. This is particularly important for patients with advanced disease urgently requiring palliative care.
In conclusion, this study demonstrated that HRQoL in patients with fibrotic ILDs showed a moderate correlation with dyspnoea scale but a weak correlation with disease severity and PFT parameters. A lower KBILD Total score was associated with increased risk for disease progression and mortality. Notably, this study showed that the initiation of antifibrotic therapy had a positive impact on HRQoL in a certain patient population. Moreover, the KBILD measurements consistently demonstrated prognostic significance across distinct time points. These results suggest that HRQoL assessment using the KBILD questionnaire may aid in evaluating the efficacy of antifibrotic therapy, similar to PFTs.
Acknowledgements
We thank Enago for editing a draft of the manuscript.
Footnotes
Provenance: Submitted article, peer reviewed.
Ethics statement: This multicentre prospective study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the ethics committee of the following institutions: Hamamatsu University School of Medicine, Seirei-Hamamatsu Hospital, Iwata City Hospital, Shizuoka General Hospital, Seirei-Mikatahara Hospital, Fujieda City Hospital, Hamamatsu Rosai Hospital, Shizuoka City Shizuoka Hospital, Tenryu Hospital, Shizuoka Saiseikai Hospital, Hamamatsu Medical Center, Enshu Hospital and Shizuoka Red Cross Hospital. All subjects provided written informed consent. The study was registered in the University Hospital Medical Information Network in Japan (UMIN000039664).
No generative artificial intelligence tools were used in the preparation of this manuscript.
Author contributions: Y. Suzuki: conceptualisation, data curation, formal analysis, project administration, resources, writing (original draft), funding acquisition and final approval of the manuscript. M. Kono, S. Matsushima, S. Kato, K. Suzuki, K. Tanaka, K. Koda, T. Masuda, M. Kanai, M. Ikeda, M. Niwa, Y. Kaida, H. Matsuda, M. Harada, D. Hashimoto, K. Asada, K. Yokomura and M. Toyoshima: conceptualisation, data curation, formal analysis, resources and writing (review and editing). K. Mori, Y. Inoue, H. Yasui, H. Hozumi, M. Karayama, K. Furuhashi, N. Enomoto, T. Fujisawa, N. Inui and T. Suda: data curation, formal analysis, resources, supervision and writing (review and editing).
Conflict of interest: Y. Suzuki reports support for the present study from the Japan Society for the Promotion of Science. All other authors report no conflicts of interest.
Support statement: This work was supported by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (grant number 22K08279 and 25K11428 received by Y. Suzuki).
Supplementary material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Supplementary material
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Figure S1b
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Data availability
The data that support the findings of this study are available from the corresponding authors upon reasonable request.
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Associated Data
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Supplementary Materials
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Supplementary material
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Data Availability Statement
The data that support the findings of this study are available from the corresponding authors upon reasonable request.