Health Related Quality of Life and its Associated Factors Among Adults Living with Asthma Attending at Selected Public Hospitals in North-Western, Ethiopia: A Multi-Centered Cross- Sectional Study


 Background: Asthma is a major public health challenge with most of the patients are not diagnosed and treated appropriately. Health related quality of life is an important measure of health outcomes of asthmatic patient that reflects the impact of an illness and its treatment from the patient’s perspective. Hence, the aim of this study was to assess the health-related quality of life and its determinants among asthmatic patient at selected public hospitals in northwestern, EthiopiaMethod: A multicenter facility based cross-sectional study was conducted in North-Western Ethiopia, from May to July, 2021. A systematic random sampling technique was employed to include 409 study participants. Simple and multivariable linear regressions were conducted to determine variables that are the independent predictors of health-related quality of life. A p-value of <0.05 was considered statistically significant.Result: A total of 409 patients were included in the final analysis and more than half (59.2%) of subjects had good quality of life. Concerning to determinants of health-related quality life, asthma control score (β=0.14, P<0.001), insurance user (β=0.15, P=0.04), high role of patient enablement (β= 0.39, P<0.001), belief to asthma medication (β= (-0.23), P=0.001), health care provides non-adherence to guideline (β= (-0.30), P<0.001) and being house wife (β= (-0.21) P=0.04) were some of significant predictor of health-related quality of life of asthmatic patient.Conclusion: The health-related quality of life among adults with asthma was largely dependent to the level of asthma control. Socio- demographic, clinical, health care related and medication related, variables were significantly health related quality of life. Therefore, our study highlights multifaced interventions including comprehensive asthma education along with an integrated treatment plan to improve asthma control and quality of life.

Health related quality of life (HRQoL) is a multidimensional concept that includes global health perspectives, symptom status, functional status, biological and physical variables, individual and environmental characteristics and general health perception [7]. According to the World Health Organization (WHO), Quality of life (QoL) is de ned as an individuals' perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns [8].This de nition considers individuals' satisfaction on their physical, psychological, social relationships, environment, and spiritual aspects of their life [9]. Quality of life is overall sense of well-being, including aspects of happiness and satisfaction with life [10]. It is broader term and remain to be subjective [11].
Quality of life in asthmatic patients is affected by several clinical, socio demographic, treatment related and behavioral factors. Some of the factors that predict QoL of asthmatic patients are being female, level of asthma control, comorbidities, health care provider adherence to guideline usage and insurance user for health care service [7,[12][13][14][15][16][17][18].
Several studies had used generic quality of life instruments as a crucial to measure the burden of asthma as perceived by the patient ,but now a days there are several asthma speci c quality of life measurement that consist of items measuring the individual's functional status (ability to perform daily functions; limitations on daily or desired activities) or health status (frequency and intensity of asthma symptoms, need to use short-acting β-agonist (SABA), need for urgent medical care), and/or social or emotional functioning [19].Its purpose is to measure health outcomes or disease and /or treatment impact.
Many studies have provided important information on HRQoL of asthmatic patient worldwide [7,14,15,[20][21][22][23][24][25]. However, there is knowledge gap on the HRQoL of asthmatic patient in the study area. Therefore, the aim of the present study was to assess the level of HRQoL and its predictor among adult living with asthma at north western Ethiopia.

Study design
Facility based cross-sectional study was employed to determine the HRQoL and its determinant among adult living with asthma who visited the health facilities in Northwest Ethiopia.

Study settings and population
From ve comprehensive specialized hospitals found in northwestern Ethiopia, three of them selected randomly. The study was conducted from August, 01/2021 to October, 30/2021 at University of Gondar comprehensive specialized hospital (UOGCSH), Felege Hiwot Comprehensive Specialized Hospital (FHCSH) and Tibebe Ghion Comprehensive Specialized Hospital (TGCSH) ambulatory care. University of Gondar comprehensive specialized hospital is a public comprehensive referral health facility present in northern Ethiopia which serves as a teaching hospital for the University of Gondar, College of medicine and health sciences students. The hospital is located around 738 km far from the capital city of Ethiopia. The asthma follows up run every Monday and reviews at least 280-300 asthmatic patients monthly as per the UOGCSH records [26].
Felege Hiwot Comprehensive Specialized hospital which is found in Bahir Dar city, which is located on in the northwest and 565 km away from the capital of Ethiopia. This is one of the three governmental Hospitals in the city. It has 200 beds and three medical outpatient department (OPD) serves for medical patients of which one serve as referral and follow up clinic for patients with chronic diseases. The chest clinic of the hospital serves for chronic asthma and chronic obstructive pulmonary diseases (COPD) patients. The asthma follow up run from Monday to Friday on average reviews at least 190-200 patients monthly as FHCSH medical records.
Tibebe Ghion Comprehensive Specialized Hospital a teaching hospital under college of medicine and health sciences of Bahir Dar University located in Bahir Dar, Ethiopia. This is one of the 43 governmental hospitals in Amhara region. The hospital serves more than ve million people in the catchment area. This teaching hospital has more than 500 beds, and 2000 patients per day in both inpatient and outpatient services. From the OPD service asthma follow up run every Wednesday and reviews on average 70-80 patients per month as FGSH medical records.
The sample size was determined by using single population proportion formula. Thus, considering as W= marginal error of 5% (w=0.05), Z α/2 = the degree of accuracy required (95% level of signi cance = 1.96), since there was no studies conducted on HRQoL of asthmatic patient in the study area P was taken 50%.
In view of the said points a single proportion formula is calculated as follows: at Felegehiwot and 225 at Tibebe Ghion hospitals were visited and the overall number of patient per three months in all hospitals had 1695. Taking into consideration, the sample was collected within three months, this makes the sampling fraction (k-interval) 1695/422=4 approximately the initial study subject was selected by lottery method and then study participants was chosen by every four person and there corresponding medical records were collected, and relevant data was taken. Side by side the selected respondent was interviewed. For this medical record of study subjects that met the inclusion criteria was considered and whenever one medical record on hand was not eligible, the next immediate one be selected, and the same approach was followed throughout the entire data collection procedure The study populations were Adult asthmatic patients who visited UOGCSH, FHCSH and TGCSH ambulatory care follow up from August to October, 2021. During the study period, Adult asthmatic patients whose age 18 years and above, had a diagnosis for asthma and on treatment for minimum of three months, attended at UOGCSH, FHRH and TGRH ambulatory ward for their asthma routine management and follow-up, provided their verbal informed consent to participate in the study were included in the study. Participants, who were unable to communicate, had incomplete medical records and patients requiring admission were excluded.

Data collection tools and procedures
The ACT and the Mini-AQLQ tools were employed in this study to measure the levels of asthma control and the HRQoL, respectively. These tools are standardized and are applicable across populations worldwide [27,28]. For this population, the data collectors were interviewed the participants and mitigating against such obstacles as language barrier and low literacy levels Amharic version of the tool were used. The Asthma Control Test (ACT) tool is a simple test for asthmatic patients aged 12 years and above and measures the level of asthma control. It contains 5 questions on a 5-point scale depicting the frequency of asthma symptoms and usage of rescue medication by participants in the previous four weeks. The overall score is in the ranges of 5 (worse control) to 25 (total control) [27].
The mini-AQLQ is a disease speci c tool for measuring the HRQoL due to asthma. It contains 15 questions in sections in four domains: Symptoms, Activity Limitation, Emotional Function and Environmental Stimuli.
Participants were asked about how their conditions had been in the previous two weeks prior to enrollment into the study. Investigators were recorded participant responses to each of the 15 questions on the 7-point scale onto the questionnaire. The overall mini AQLQ score was the mean of all the 15 responses while each domain score were the mean of responses to items in that particular domain [28].
Factors associated with HRQoL were collected based on structured questionnaire that included socio demographic factor, modi able and non-modi able factor, triggers, patient compliance and clinical factors that in uence asthma control and consequently, HRQoL. Medication Adherence Rate Scale (MARS-A) [29] was used to measure adherence of the patient to their medication, old version of Beliefs about Medicine Questionnaire (BMQ) [30] was used to measure the belief of the patient on their medication and other different literatures [2,31] were used to develop other related questions.
A belief about Medicine Questionnaire is a 10-item questionnaire that assesses the patient beliefs to their prescribed medication. It is composed of two-ve item scales that are speci c necessity and speci cconcerns scale. The speci c-necessity scale that assesses patients' beliefs about prescribed medication to maintain their health now and in the future. However, speci c concerns scale assesses patients' perception about adverse consequences of taking medicines related to long term effect and dependence [32]. The patients' level of beliefs about medicine (s) before and during clinical appointments towards their asthma management care were computed using a 5-point Likert-type scale ranging from strongly disagree=1 to strongly agree=5 [33].
Adherence to ICS was measured using the MARS-A, a self-reported adherence tool that demonstrated good test-retest reliability (r=0.65, p-value <0.001), internal consistency reliability of 0.85, sensitivity of 0.82, and speci city of 0.69. The responses were measured using a 5-point Likert scale (1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, 5 = Always). Self-reported adherence is reported as the average score of the 10 items (1-5), where higher scores indicate higher levels of reported adherence. High self-reported adherence was de ned as a MARS-A score of 4.5 or higher) [34].
The modi ed patient enablement index (mPEI) was used to evaluate enablement of the patient and a score of >6 indicate clinically meaningful enablement. It contains six items assess the patient's ability to deal with life, understand the illness, cope with it, keep healthy, remain con dent about health, and help oneself [35]. Comorbidity index was done by using charlsone comorbid index and classi ed as mild, moderate and severe whose comorbidity index score 1 and 2,3 and 4, greater than 4 respectively, to determine the burden of comorbidity on asthma control and HRQOL [36].
All the above tools were translated into Amharic by English and Amharic versed persons. Translation was veri ed for compatibility with the original version in a process of forward and backward translation. Face validity of the survey was assessed among three clinical pharmacy teachers for clarity of the questions. Then, the survey was pretested for content, design, readability, and comprehension on 42 people, and sociocultural adoption were made by using WHO recommendations and modi cations were made based on the response. So that the survey was simple to understand and answer, yet provided accurate data.

Training of research assistants
The principal investigator (PI) identi ed six data collectors (two data collectors for each study area) and trained for two days before commencement of the research. The data collectors were nurses working in the ambulatory care of UOGCSH, FHCSH chest clinic and TGCSH ambulatory care. The training entailed an explanation of the nature of the study, its objectives and importance. Demonstration and practical training of use of the data collection tools was done. Ethical considerations and overall expectation from scienti c research were explained. The competence of the data collectors was assured by the PI during pre-testing before the study commence through. This was done by assessing how correctly the collector extracted data and lled up the questionnaires. Where further training was required, it was provided and reinforced until competence was ascertained. Finally, after the data was checked for its completeness, it was cleaned and analyzed. Pre-test on the 5% (42)

Data analysis and management
The data was checked for its completeness, cleanness, then coded and entered to Epi Info Version 7 database and export to SPSS Version 26 for analysis. Descriptive statistics, means, median, proportions, tables and gures, were used to describe the characteristics of the study patients and displayed the study results. First, the test assumptions (normality test, correlation coe cients tests, linearity tests, outliers, multicollinearity and homoscedasticity) of all the statistical methods for all variables were tested and those ful lled the assumptions were entered in further analysis. Variables such as hospitalization, triggering factor and exercise were excluded from the analysis because they did not met linearity. Linearity was checked by generating separate scatter plots with the dependent variable on the y-axis and the independent variables on the x-axis. The relationship between mean score of HRQoL and another continuous variable was checked by the P-P plot. Similarly, the categorical variables linear relationship was checked by drawing a line between the mid-points of the observations at each level. The variables which had no linear relationship with the outcome were excluded from analysis. The variation around the regression line was tested by examining a plot of the standardised residuals versus standardised predicted values of the dependent variable and it was constant for all values of xi for each X variable. Additionally, histogram ,normal probability plot of the residuals and Shapiro wilk test were done to examine the data distribution and the test indicated that the residuals had approximate to be normally distributed. Results of the regression analysis were expressed in un-standardized coe cient β. Beta coe cients are measured in units of standard deviation and refer to the average change in the dependent variable for a unit increase in the predictor variable. Finally, assumptions of multiple linear regressions met (normality test, correlation coe cients tests, linearity tests, outliers, multicollinearity and homoscedasticity). Then, variables with a pvalue ≤0.2 in bi-variable analysis were entered to multivariable linear regression to identify the independent predictor variables of HRQoL. The statistical signi cance was declared using a p-value less than 0.05. The adequacies of the models were checked by the F-test of goodness of t for linear regression.
Ethical considerations and Con dentiality Ethical clearance was obtained from the Institutional Review Board of University of Gondar. Letter of permission was obtained from each hospital clinical directorate. Study medical records numbers was used in place of patient names during the data collection and analysis process in order to conceal and safeguard participant's identity. All the data collection materials were safely kept in a cabinet under lock and key. The databases were password protected by the PI for limited access during the entire study period. The collected data was used only for the purpose of the study. Verbal consent was taken after the purpose and objective of the study was explained to the selected participants. Moreover, all participants were informed that participation was on voluntary basis and they can withdraw from the study at any time if they are not comfortable about the questionnaire. Any identi ers of the study participants were not recorded.

Results
Socio-demographic characteristics of the study population 409 participants were included with a response of 96.7%. The mean (±SD) age of the study participants was 49.82 (±16.1) and most of them were in a range of 35-64 years. More than half (60.1%) of them were females. More than two-thirds (71.9%) of the respondents were married and about three-fourth (73.3%) were urban dwellers. The majority of the respondents (88.5%) had biomass fuel user for cooking food and from these Charcoal and wood were used as a main sources of food preparations (82.4 %). Majority (87.5%) of study subjects had no smoking history (Table1).

Clinical characteristics and the triggering factors of asthma exacerbations
More than three-fourth (76%) of the study participants were diagnosed for asthma after their 12 years of age. The mean (±SD) duration on the medications after the onset of the condition was 5.4 (±5.8) years. In the last one-year period, more than half (53.1%) had at least one episode of asthma exacerbation and 95.4% of them had at least one triggering factor for their exacerbations. More than half (53.5%) of them had exacerbated their symptoms during exercise which is the leading causes for asthma exacerbation followed by the dust particles combined with cold weather and the cold weather alone which accounts (44.5%) and 22.5%, respectively. Regarding the female respondents, only (8.1%) of them had menstruation induced asthma exacerbations ( gure 1). After maintenance therapy has been initiated, the median (IQR) time to visit an emergency department was 11.95 (±13.6) months. Most patients had taken medication 1-5 years. Almost one-third (33.3%) of the patients were hospitalized in the last 12 months and of these 6.1% were sent to the ICU unit. Concerning the medication experiences, more than one-third (37.2%) used oral steroids. According to GINA based severity classi cations, (56.7%) of the respondents had moderately persistent and (26.2%) had mild persistent asthma ( Table 2).

Pattern of Antiasthmatic Drug use
Drug utilization pattern suggested that multiple-drug therapy (two or three) drug combinations were used by almost all patients (99 %). More than three-fourth (76.5%) had Salbutamol puff PRN and Beclomethasone puff Bid followed by Salbutamol puff PRN and Beclomethasone puff Bid and Prednisolone (11.5%). Medication Adherence Rating Scale showed that (13.9%) patients had high level of adherent to the prescribed controller medication (s). A large proportion 305 (74.6%) respondents were on optimal dosage of asthma medication at various steps. Asthma medication combination therapy were appropriately selected for (71.1%) of subjects. In prescribing pattern, about 21.8% of prescribers had not adherent to current guideline recommendation. Nearly three fourth 74.3% of the respondent was adequately educated about their asthmatic state and its management. From the participants 91.7% and 89.5% were good relationship with health care providers and had satis ed by the care respectively (Table 3).

Comorbidities and concurrent medications
Regarding the Charleston comorbidity index (CCI), almost sixty percent of the respondents were found in the mild range of categorizations and about forty percent of the individuals had comorbidities. More than onethird (38.3 %) of patients were prescribed with concurrent medications (Table 4). In this study, a number of comorbidities were documented. Large proportion of participant had (21.5%) cardiovascular disease followed by Diabetes meatus (10%) and also the two most commonly used class of concurrent medication were cardiovascular drugs 18.6% followed by endocrine drugs 10.5% ( gure 2).
Beliefs about medicines in the study population  (Table 5).

HRQoL outcomes
The Mini-AQLQ mean score was 4.1(±0.9). In individual domains, emotional, environmental, and symptom stimulation had the lowest mean score. Determination of HRQoL was made using the mini-AQLQ questionnaire. Out of the 409 participants, 242 (59.2%) had good HRQoL mean score ≥ 4.1 while 167 (40.8%) had poor HRQoL the scored was below 4.1 (Table 6). Further data analysis was conducted to identify the independent predictor of HRQoL by using linear regression. Pearson correlation analysis was done to assesses the relationship between min-AQLQ score of participants and ACT score and the results showed our dependent variable were strongly associated (r=0.59; P< 0.01). Mini-AQLQ increased with the increasing level of asthma control.

Factors associated with HRQoL
A linear regression analysis was employed to identify potential variables determining quality of life of asthmatic patient. The model tness of the linear regression was run and signi cantly associated (F=11.68; P<0.001). A multivariable analysis has identi ed factors that potentially associate with HRQoL are occupation, health care service, role of patient enablement, adherence to guideline, total asthma control score and belief to anti-asthmatic medication. The results of the regression indicated that the model explained by 45

Discussion
In this multicenter public institutional based study, the min-AQLQ measurement tools were applied to present the HRQoL among asthmatic patients. This study ndings reported that the overall mean (±SD) HRQoL was 4.1 ±0.9 (out of 7).
The HRQoL status of the current study revealed that about 60% of the asthmatic patients had scored the mean (±SD) of 4.1 ±0.9 and more than this score. This nding is coincided to the study results reported in Iran , in which 53% of patients had a good quality of life [37]. In contrast , it was much higher than the ndings from Pakistan where only 28.6% of study subjects had good quality of life [38]. The possible explanations for the higher numbers of patients who had good quality of life in the present study might be the mean age levels of the respondents in which their age were in middle ranges compared with those Pakistan where their age ranges were found in older groups.
For the factors associated with HRQoL the following variables were disclosed; health insured patients, having advanced role of patient enablement and improved in the asthma control levels were signi cantly increased the HRQoL status. On the other hand, being housewife, patients not treated with as per the guidelines and individuals positively believed to their medication were signi cantly declined the HRQOL status.
According to the result of this study patients those who uses health insurance were correlated signi cantly with HRQoL. This positive association between health insurance and HRQoL were supported by other studies [12,24,25,[39][40][41][42][43][44]. The possible explanation for this positive association might be mainly to high levels of adherence, reduce out pocket cost for drug and use of treatment as per guidelines increased in health insured participants. Additionally , might be due to insurance users have less risk of asthma exacerbation because which reduce stress, increase adherence to medication and it would have impact on over all hospital cost minimization [45].
The present study revealed that, the role of patient enablement had signi cantly associated with mini-Asthma QoL; which is supported by some evidence that the mPEI may be sensitive enough to detect changes in the patients quality of life, as shown by United Kingdom study [35]. There are several possible reasons why measures of patient enablement had signi cantly associated with quality of life. Although selfmanagement training programs may bring about only mild to moderate outcome for selected chronic diseases [46], but may improve asthma control in patients compared with usual care [47]. They can improve trust in treatment, improving adherence to therapeutic plans [48],which indirectly leads to increase quality of life in asthmatic patient.
High level of asthma control was identi ed as positive independent predictor of HRQoL. This ndings correspond with those of multiple relevant studies conducted worldwide for instance in Brazilian and United Kingdom, researchers found that the degree to which asthma was controlled had a signi cant impact on a patient's HRQoL [15,49,50]. Asthma control re ects the disease's effect in a patient as arrested by uctuations in their symptoms, limitations in their range of activities, their environmental as well as emotional functioning. The relationship between asthma control and HRQoL was also emphasized by the results of an Italian study which found that close to one-third of their population had optimal HRQoL and it was neither associated with the duration of severity of asthma nor rhinitis, but the degree of asthma control [39]. Similar study, in a France and UK study, it was reported that poor asthma control was the only factor that independently impacted HRQoL [42]. These consistent outcomes con rm that asthma control is indeed the single most important determinant factor of an individual's HRQoL. The negative impact of asthma on patients' HRQoL could be reduced if patient care focused on achievement of good control of the disease. To achieve optimal control therefore, variables that signi cantly impact it in populations need to be identi ed and addressed, so that patients can live near normal lives The nding of this study indicated that history of occupational risk exposure to asthma triggers like house wife worker had poor HRQoL that was signi cantly associated. This ndings interrelated with a similar study in the United States which indicated that individuals with work related asthma were signi cantly more likely to have poor HRQoL as compared to those with non-work-related asthma [51] . The possible explanation for this is being house wife increases exposure for asthma triggers like bakery, rubber/plastic work, cleaning, spray painting and food processing. Additionally, being female is more exposed for asthma trigger due to the natural hormone associated with estrogen and increased asthma exacerbation during menstruation [52], which leads to negative impact on HRQOL.
This study found a signi cant association between HRQoL and guideline usage by the prescribers. Our results were comparable to those of a study based on GINA guidelines where investigators found that well controlled patients who had achieved guideline-based asthma control reported consistently higher overall HRQoL than their uncontrolled counterparts in whom guidelines were not followed [13]. In another cross-sectional study where half the treatment regimens were considered non-adherent to guideline recommendations, only those patients in whom treatment was in accordance to guidelines had signi cantly higher HRQoL [16]. In this study 21% of the patients had not treated based on guideline in whom guidelines were not followed either had their controller medications prescribed once daily, were on SABA only instead of combination with controller medication, or their asthma severity level required step-up to a higher dose or addition of other medications to the ones they had been put on. Therefore, non-adherence to guideline would reduce the level of asthma control and by extension, HRQoL of asthmatic patient.
In this study belief to asthmatic medication had identi ed as independent predictor of HRQoL, Which is supported by another study [53].The reason behind is belief to medication have impact on quality of life by increase stress and stimulating positive/negative illness perceptions and might be impact on adherence, which in turn might lead to compromised disease control and impaired HRQoL.

Strengths and Limitations
The study has several strengths. It was real-life study and used well validated tools to measure outcomes and it was multi-centered study which increases generalizability. The study location being a referral institution was well capable in terms of resources. In addition, the systematic sampling technique was used. It could have reduced source of bias in this study.
The ndings of this article will be interpreted with the following limitations. Some of the responses in the questionnaires were patient subjective reports which could have been biased either by under-reporting or exaggeration. Lack of objective measurement (spirometer or peak ow meter) which have for better assessment of asthma control. Despite these limitations, our study was adequately powered and ndings compared well with those of other similar studies conducted worldwide.

Conclusion
Our study revealed that slightly over half of study participants have reported good HRQoL. Health related quality of life outcome among patients was largely dependent upon the degree to which asthma was controlled. Regarding to the factors associated with the HRQoL of asthmatic patients, being house wise, health care provider non-adherence to guide usage and belief to anti-asthmatic medication were signi cantly decrease HRQoL. On the other hand, insurance user for health care service, higher role of patient enablement and total asthma control score were signi cantly increase HRQoL. So respective hospitals would be prepare schedule for client's education on patients' behavior like the importance of adherence and its medication by each team on weekly base and future researchers would be worked on HRQoL and its associated factors in asthmatic patients on at lower health care facilities that may not have the infrastructure and resources available in higher level facilities.

Abbreviations
Ethics approval and consent to participate Ethical clearance was obtained from Institutional Review Board of University of Gondar (SOP/131/2021). Then o cial letter obtained from clinical director of University of Gondar comprehensive specialized hospital, FHCSH and TGSCH. The purpose of study was well explained to the study participants and informed consents were obtained. Con dentiality was maintained at all levels of the study by avoiding use of name and other identi ers. Participants' involvement in the study was on voluntary basis; participants who were unwilling to participate in the study and those who wish to quit their participation were informed to do so without any restriction    3.6 (±0.9) Sum of mean score of speci c-Concerns Scale 1. ± 4.9 Over all medication belief mean score 3.54±0.54 Table 6 The mini-asthma QoL outcome measures   Type of comorbidity and commonly used class of concurrent medication among adult asthmatic patients CVD: cardiovascular GI: gastrointestinal