The objective of the present research was to develop and validate a QOL measurement tool specifically adapted to HHT disease – the QoL-HHT (Quality of Life - Hereditary Hemorrhagic Telangiectasia): A simple and quick tool to fill in for self-assessment. The results of the factorial structure, (Exploratory Factorial Analysis EFAs, Confirmatory Factorial Analysis CFA, Exploratory Structural Equation Modeling ESEM) reliability, and convergent validity of the QoL-HHT scores provided strong evidence of construct validity, indicating that the QoL-HHT is a promising scale developed for and in collaboration with HHT patients to allow assessment of the impact of HHT on the QOL of patients. The salient factors emerging from the factorial analyses of QoL-HHT scores referred to physical limitations, social relationships, concern about bleeding, relationship with the medical profession, experience of symptoms and concern about the evolution of the disease. Indeed, QoL-HHT scores (24 items) fitted well with CFA and ESEM models. The pattern of cross-loadings and the standardized factor loadings of the six subscales of the QoL-HHT provided evidence for the structural validity of the QoL-HHT scores. Test-retests provided evidence for the reliability and stability of the QoL-HHT scores over a one-month period. The six subscales would allow example the relationships between specific symptoms related to quality of life of HHT patients and other theoretically-relevant constructs or outcomes, as they provide an in-depth assessment of the multidimensional construct of QOL with six interrelated but distinct dimensions specific to the HHT disease. The bifactor model did not allow us to provide evidence for an overall quality of life score as the factorial structure of the QoL-HHT scores did not fit to a bifactor structure.
The physical limitations dimension refers to the physical consequences of the disease. The consequences of physical symptoms can result in significant fatigue in daily activities, especially at work, limiting physical activities . The literature highlighted that the physical factor is inherent to most of the genetic diseases and is a salient dimension of the QOL of individuals with genetic diseases [10, 12, 13]. The salient consequences of the physical domain allow understanding the experiences of people with HHT disease and provides further evidence of the importance of this theme within the HHT disease [7, 14].
The concern about nosebleeds dimension refers to the experience of the most frequent symptom of the disease. This experience is often marked by an uncertainty about the onset of epistaxis, which can occur at any time, thus creating anxiety in the eyes of others. It can also lead to feelings of insecurity and loss of confidence in one’s body, which sometimes make patients feeling helpless and out of control [14, 44]. Because of these irregular, spontaneous and above all unpredictable manifestations, it is essential to pay particular attention to this area that is central to QOL of HHT patients [7, 13, 45].
The social relations dimension refers to the quality of relationships with family and friends in terms of communication about the disease, sharing of experiences and support. This quality of relationships has been mentioned as a source of well-being where interactions allow patients to feel supported and understood in relation to their disease . Being able to share daily life with those around HHT patients could reduce certain psychosocial concerns (e.g., taboo subject, hereditary character), especially since the disease is considered by patients as an integral part of their identity [7, 41, 42, 43, 44]. Thus, this rare genetic disease highlighted that the issue of self-acceptance and acceptance of others is a key dimension of quality of (social) life .
The relationship with the medical profession dimension refers to the assistance provided by the caregivers. In the qualitative study conducted by Martinent et al. , most patients experienced feelings of helplessness and incomprehension in the face of the rarity of this genetic disease and the lack of knowledge of health professionals on the subject. Although patients are personally experts on their own disease, the involvement of caregivers in the disease would allow them to have a better relational quality, to be more involved in their care and to be more serene. In addition, one of the factors associated with the severity of epistaxis in HHT is the attention of the medical profession to the disease, so management and follow-up are aimed at avoiding the development of complications .
The experience of symptoms dimension represents the subjective way of living the disease. It is about how patients perceive the impact of the disease on their daily lives and adapt psychologically to the symptoms. Coping theories are useful for better understanding QOL . Models of stress and coping posit that in response to a stressor, such as having a genetic problem, individuals make cognitive and emotional appraisals of that stressor . These appraisals include perceptions of the personal weight of the stressor (sensitivity to the stress, its causes, its severity, its relevance to life) as well as perceptions of one's ability to cope with the problems and emotions generated by the stressor . The more the individual adapts to living with the genetic disease, the better the QOL is .
Finally, concern about the disease evolution refers to the progression of the disease over time and the familial nature of the disease. One of the uncertainties experienced by patients concerns the evolution of the disease as it evolves silently and its complications are insidious . This raises the question of the difficulties in making short, medium and long-term plans . Linked to this is the feeling of anxiety and guilt associated with heredity and transmission, of seeing an elder with an unfavorable clinical course, of seeing oneself in a similar negative situation and of seeing one's children living with the disease [7, 14, 41, 42]. Thus, for many, the experience of this disease leads to apprehension with no real possibility of control.
The results of correlational analyses provided evidence of the convergent validity of the QoL-HHT scores. In addition, the pattern of correlations of QoL-HHT subscales with theoretically relevant external variables examined in the present study is consistent with the literature. In particular, our results showed that a high quality of life (i.e., high scores for the dimensions of social relationships, relationship with the medical profession and experience of symptoms) was positively linked to adapted emotional regulations (e.g., positive focus, focus on action, positive reappraisal and putting it into perspective) and negatively correlated with anxiety and depression. Moreover, low quality of life (i.e., high scores for the dimensions of physical limitations, concern about bleeding and concern about the evolution of the disease) was significantly and positively linked to inadequate regulation (e.g., rumination, dramatization), anxiety and depression. The scores of the generic QOL scale SF-36 was strongly related to the QOL dimensions of the QoL-HHT (except for the social dimensions (i.e., social relationships and relationship with the medical profession)), providing strong evidence for the construct validity of the QoL-HHT scores.
The present study highlighted that factors related to health status, particularly in terms of experiencing the symptoms of the disease (especially fatigue and epistaxis), are essential to determine the quality of life of patients with HHT. This confirms the results of several studies on rare genetic diseases [10, 14] as well as the statements of Patrick and Erickson  specifying that the value attributed to life expectancy is affected by deteriorations, states of functioning, perceptions and social opportunities that are influenced by the disease, injury, treatment and/or policy. Beyond health status, this study also investigated and confirmed the importance of psychosocial factors in determining the quality of life of patients with HHT . These factors refer to the subjective experience of the patients, particularly in terms of knowledge and recognition of the disease by their family, friends, professional, medical and social environment, the evolution of the disease and the questions regarding the transmission. Psychosocial factors have been highlighted to determine the QOL of people with rare genetic diseases .
This scale (original version validated in French in additional file 4) could be used by all practitioners receiving patients with HHT disease during consultations, during therapeutic trials or as an indirect measure of the evolution of symptoms. It would allow identifying and quantifying the aspects of the QOL more particularly impacted in HHT patients in order to be able to propose them a "tailor-made" accompaniment and/or orientation: Specialized consultations, psychologist, social worker, departmental house of the handicapped persons, drafting of mails or information documents. The scale would also make it possible to highlight the areas of the QOL (medical, physical, social, psychological) to which it is important to pay more attention in the context of the individualized follow-up of patients.
The study has several limitations. The first is that this study was carried out only on adults, so it does not guarantee the transferability of the questionnaire to a population under 18 years old. Certainly, it would be interesting to study also the most determining dimensions in the QOL of young people with HHT disease because the QOL can be seen and experienced differently and the psychological management of the disease is probably less mature among adolescents in comparison to adults. Nevertheless, it should be noted that young people with HHT mostly experience less severe symptoms of the disease than adults but the impact of seeing disabled relatives could be burdensome. The second limitation is that this study only used self-reported questionnaires. Despite its advantages in terms of ease of interpretation, low cost and speed of data collection , it has the disadvantage of not considering other approaches that may influence patient response such as behavioral or physiological approaches to obtain a more finely representation of the concept of quality of life in HHT disease . Each method should be formally established as any measurement in psychology is susceptible to bias and error . Thus, further studies conducted on the HHT patients could adopt a measurement approach encompassing self-report questionnaires, physiological and behavioral measurements. Finally, it would be particularly useful to validate the QoL-HHT questionnaire in English to ensure its transferability to other non-French speaking populations.