The World Health Organization (WHO) has recognized thalassemia, which is found in more than 60 countries, as the most prevalent genetic blood disorder globally [1]. Studies have reported that 3% to 10% of the population of the world carries a thalassemia gene [1]. Approximately 200,000 patients with thalassemia have been documented in the world, and each year approximately 60,000 people are added to this number [2,3].Thalassemia can occur in almost all races, but areas with high incidence (known as the thalassemia belt) are found in the Mediterranean region (Italy, Spain, Portugal, Greece, parts of Russia, and Cyprus), north and west Africa, the Middle East (Saudi Arabia, Iran, Turkey, and Syria), the Indian subcontinent (India and Pakistan), southeast Asia (Bangladesh, Indonesia, Thailand, Malaysia, and southern China), and South America [4]. Approximately 240 million people worldwide carry beta-thalassemia (β-thalassemia) [2]. β-thalassemia is a global health problem in the Mediterranean region, Middle East, Indian subcontinent, and southeast Asia [3,5]. Iran is a country located in the thalassemia belt, with an average thalassemia gene prevalence rate of 4% (approximately 3 million people) [2,6]. In Iran, approximately 26,000 people have thalassemia and approximately 800 people are added to this number annually [2].

Achievements in biomedical sciences and technology have led to significant improvements in health-related quality of life (QoL) for thalassemia patients. Enhanced survival in these patients poses issues related to their QoL [3]. Some of the major clinical and psychological aspects of thalassemia are expected to have an effect on the QoL of patients with thalassemia, including (1) having a chronic condition and the subjective feeling of being different; (2) changes in appearance, such as bone deformities and short stature, which lead to a poor self-image; (3) treatment, which involves frequent hospital visits for transfusions and iron chelation therapy; (4) delayed or absent sexual development and problems related to fertility; (5) complications such as heart disease, bone disease, diabetes, and infections; (6) uncertainties about the future and problems related to long-term planning [7,8].

Studies have emphasized that, in addition to controlling the symptoms of the disease, it is very important to improve QoL as part of the treatment of a chronic disease such as thalassemia [3,9]. Additionally, studies have shown that patients with thalassemia reported lower mean scores of QoL than healthy subjects [8,9]. With access to better methods of blood transfusions and iron chelation therapy, better management of complications and supportive care are available for patients with thalassemia, and they now have a near-normal lifespan with a good QoL [10]. Some studies have evaluated the QoL of patients with thalassemia, but the factors affecting QoL in these patients are largely unknown [3,11,12]. Understanding the factors associated with QoL in patients with thalassemia has direct implications for the design and implementation of clinical, counseling, and supportive interventions to enhance treatment outcomes and QoL among these patients [12].

One of the primary objectives of the Healthy People 2010 initiative (US Department of Health and Human Services, 2006), was to improve the QoL of adults with chronic diseases. Preserving a satisfactory QoL is considered to be a major objective of nursing care. Health-promoting behavior, particularly when integrated into a healthy lifestyle that pervades all aspects of living, should result in improved health, enhanced functional ability, and better QoL at all stages of development [13]. Studies show that a health-promoting lifestyle (HPL) is a factor affecting QoL [13-15]. A healthy lifestyle consists of six domains, including physical activity, nutrition, health responsibility, spiritual growth, interpersonal relations, and stress management [16]. Since QoL in patients with thalassemia is affected by lifestyle [17], and given the lack of studies of this issue, this study aimed to determine the association between HPL and QoL in adults with β-thalassemia.

This cross-sectional (descriptive-analytic) study was conducted between March 2015 and July 2016. The participants were adult patients with thalassemia major who were referred to thalassemia centers at hospitals affiliated with the Tehran University of Medical Sciences (TUMS), Iran University of Medical Sciences (IUMS), or the Iranian Blood Transfusion Organization (IBTO) in Tehran, the capital of Iran. The inclusion criteria were being more than 18 years old, having a definitive diagnosis of β-thalassemia major, providing informed consent to participate in the study, and having no other serious physical or mental health problems. A total of 389 patients were selected using stratified random sampling. Among nine thalassemia centers at hospitals affiliated with TUMS, IUMS, and IBTO, the centers that had more than 50 adult patients with thalassemia (Zafar Adult Thalassemia Clinic, Baharloo Hospital, Ali Asghar Children Hospital, and Children’s Medical Center Hospital) were identified as strata. Proportional to the number of patients in each stratum, the required samples were then selected randomly within in each center. We obtained the sampling frame of each center from the list of patients of each center. Simple random sampling was then used to select the required sample within each center. Random selection was performed using the SPSS select case menu. Ethical approval was obtained from TUMS (IR.TUMS.REC.1394. 1153).

The research instrument included a questionnaire consisting of three parts. The first component addressed demographic characteristics (11 items). The second component was the Persian version of the Short-Form Health Survey (SF-12) [18], including two main domains (the physical component summary [PCS] and the mental component summary [MCS]), as well as eight scales for assessing the eight dimensions of physical functioning (2 items), physical role (2 items), social role (1 item), emotional role (2 items), bodily pain (1 item), general health (1 item), vitality (1 item), and mental health (2 items). Scores on this instrument range from 0 to 100, where 0 indicates the worst condition and 100 indicates the best possible condition. The SF-12, as a shorter alternative to the SF-36, is widely used in health outcome surveys [18].Third, the Health-Promoting Lifestyle Profile (HPLP-II) was designed by Walker et al. [19] in 1978. In the current study, the validated and reliable Persian version of the HPLP-II [20] was used. The original version of this questionnaire consists of 52 items that measure HPL in six dimensions: nutrition (9 items), physical activity (8 items), health responsibility (9 items), stress management (8 items), interpersonal relations (9 items), and spiritual growth (9 items). These questions are given responses on a 4-point Likert scale (never, sometimes, often, and routinely). Overall, the score for HPL and the behavioral aspects was calculated using the mean of the responses for all 52 items and for each dimension (8 or 9 items). The scores ranged from 52 to 208 [20].

In this study, the dimensions of nutrition and physical activity were changed in accordance with the specific circumstances of thalassemia patients. For this reason, the validity and reliability of the final version of the data collection instruments were assessed again. Content validity was checked by five academic members of TUMS who were experts in the fields of health education and promotion, and five physicians who had worked in thalassemia clinics. The Cronbach alpha was calculated and the test-retest method was used to determine the reliability (with a 2-week interval for 20 patients). The intraclass correlation coefficient (ICC) for the SF-12 scale was 0.74 (95% confidence interval [CI], 0.45 to 0.89) and for the HPLP-II scale it was 0.92 (95% CI, 0.82 to 0.97). The alpha coefficient for the SF-12 was 0.88, and for the HPLP-II it was 0.89. These 20 patients were excluded from the main study.

Data were analyzed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA) through descriptive methods (frequencies, percentage, mean, and standard deviation [SD]) and Pearson correlation coefficient multilevel linear regression. Parametric tests were used according to the kurtosis, skewness, and normalization of the data. When the study participants are clustered within a team or center, they are expected to have a within-center (or within-team) correlation in their response, which means that the results within a center are generally more homogenous than results obtained from multiple centers. This should be accounted for in the calculation of the standard error of estimations, so we used a multilevel model. These models can take the hierarchical structure of data into account by considering a random effect in addition to the fixed effect in their formulas. Centers in this model introduce a random effect, and in this way difference between centers were considered. Samples within each center shared a single or multiple random effect(s) that was/were different from center to center. The distribution of this random effect was univariate or multivariate normal with mean 0 and a variance (or covariance matrix) that could change from a random effect to another one [21]. Results were considered significant at the conventional level of p<0.05.

Based on results of this study, the QoL among the participants was moderate in the three domains under study (total QoL score, physical component summary score, and mental component summary score). However, this result is not very good, and the participants in this study had lower mean QoL scores than have been reported in surveys of healthy Iranian individuals. For example, in a study conducted by Montazeri et al. [22] on healthy Iranian individuals, the mean scores for QoL dimensions ranged from 65.6±41.4 to 85.3±20.8 (the lowest score was for emotional role dimension [65.6±41.4] and the highest score was for physical functioning dimension [85.3±20.8]). Additionally, in a study conducted by Fallahzadeh et al. [23] among Iranian university students, the mean QoL score was 64.2±10.2. The results of these studies indicate that the patients with thalassemia in our study had a lower QoL than healthy individuals. Such a large difference in the QoL of healthy individuals and patients with thalassemia is not surprising, because many factors have a negative impact on QoL in patients with thalassemia, such as having a chronic condition and the subjective sensation of being different; frequent hospital visits for transfusions and iron chelation therapy, delayed or absent sexual development and problems related to fertility, and complications such as heart disease, bone disease, diabetes, and infections [7,8].

Similar to the findings of this study, Haghpanah et al. [24], and Safizadeh et al. [25] reported lower QoL scores in patients with thalassemia in Iran. Compared with the results of a study that was carried out by Safizadeh et al. [25] of the QoL of thalassemia patients aged 16 years and older, higher mean scores of QoL were found in this study, whereas our findings were lower than the results of Haghpanah et al. [24] and Amani et al. [26]. The results of this study were primarily compared with the results of other studies conducted in Iran, because culture is an independent factor that influences the QoL of thalassemia patients [24,27]. However, the results of this study were also compared with those of foreign studies, and our findings are in agreement with the results of some of them [27]. Since the QoL of patients with thalassemia was not at an acceptable level, educational interventions are necessary to enhance the QoL of patients with thalassemia. Health education and promotion can be powerful tools for improving the QoL for all members of the population, including patients with thalassemia; therefore, applying these techniques seems reasonable due to their influence on health-promoting behaviors and improvements in QoL [28, 29].

The HPL scores obtained in this study were slightly lower than moderate [30-32]. Many studies have been performed to assess the HPL of healthy individuals, and have found moderate mean HPL scores [32,33]. The results of our study indicated that the extent of HPL among patients with thalassemia was not at an acceptable level. Therefore, conducting health education programs to improve HPL and establishing counseling centers for education about HPL for patients with thalassemia is necessary. For this reason, educational and health promotion interventions based on predictors of QoL are recommended to improve HPL in thalassemia patients.

The participants in this study showed relatively high scores for spiritual growth, interpersonal relations, and health responsibility, and lower scores for nutrition and stress management. The lowest score corresponded to physical activity. In a study of couples referred to an infertility clinic, the highest scores were obtained on the nutrition, spiritual growth, and interpersonal relations dimensions, while the lowest scores were for the health responsibility, physical activity, and stress management dimensions [34]. Similar to findings of this study, a study conducted among academic staff showed that participants obtained relatively high scores for spiritual growth, interpersonal relations, and nutrition, but relatively low scores for health responsibility and stress management, and the lowest score corresponded to physical activity [32]. Since this study found that the mean score for physical activity was lower than the scores of other dimensions, attention should be directed towards addressing both the challenges of individuals and providing supportive relationships for behavioral changes (physical activity) when designing interventions.

In this study, we found that spiritual growth, physical activity, interpersonal relations, and health responsibility were significant predictive factors of QoL in adults with thalassemia. In a study conducted by Şenol et al. [14], spiritual growth was a significant predictive factor of QoL. Likewise, Rakhshani et al. [31] concluded in their study that three dimensions of HPL (physical activity, spiritual growth, and stress management) were significant predictive factors of QoL. In this study, spiritual growth, physical activity, and interpersonal relations were independently and positively associated with QoL, while health responsibility was independently and negatively associated with QoL. Therefore, aspects of spiritual growth, physical activity, and interpersonal relations must be included in health interventions in order to improve QoL in patients with thalassemia. To achieve these goals, it is recommended to make use of the capabilities of health education and promotion experts and psychologists in thalassemia treatment centers. One of the strengths of this study was that it assessed the associations between the dimensions of HPL and QoL in patients with thalassemia. Due to the lack of similar studies in this field, this study can be considered as a source of guidance and a basis for future research, especially for interventional studies. However, this study has some limitations. First, in cross-sectional studies, the existence of alternative explanations for the results due to confounding must be carefully considered. Second, the results of this study were compared with the results of studies conducted among other groups, such as infertile couples, academic staff, the elderly, and nursing home residents. Third, self-reported data were collected, and it is possible that the results may not reflect an exact estimation. Fourth, due to the nature of the study sample, it is possible that thalassemia patients in cities other than Tehran show different trends than those sampled in this study. Fifth, the results of this study were compared with the results of other studies that were conducted in Iran, because thalassemia is endemic in Iran and culture is an independent factor that influences the QoL of thalassemia patients.

In general, the results of our study indicate that the QoL and HPL of patients with thalassemia were not at acceptable levels. Spiritual growth, physical activity, and interpersonal relations were found to be relatively strong predictors of QoL in this study. Therefore, it is necessary to implement health education programs with an emphasis on spiritual growth, physical activity, and interpersonal relations, as well as to establish counseling centers for the education of patients with thalassemia regarding HPL.