|Year : 2021 | Volume
| Issue : 2 | Page : 172-177
|Demographic and clinical patterns of severe asthma in the Middle East
Mohamed Abuzakouk1, Omar Khaled Hassan Attia Ghorab1, Bassam Mahboub2, Ashraf Alzaabi3, Mateen Haider Uzbeck1, Mohsen Nasir1, Zaid Zoumot1, Deepa Grandon1, Yaser Abu El Sameed1, Rajaie Namas4, Ali Saeed Wahla1, Jeffrey Chapman1, Khaled Saleh1, Fulvio Salvo1, Govinda Saicharan Bodi1, Irfan Shafiq1
1 Cleveland Clinic, Respiratory and Allergy Institute, Abu Dhabi, UAE
2 Department of Pulmonary Medicine, Rashid Hospital, Dubai, UAE
3 Division of Respiratory Medicine, Zayed Military Hospital, Abu Dhabi, UAE
4 Cleveland Clinic, Medical Sub-Specialties Institute, Abu Dhabi, UAE
|Date of Submission||06-Apr-2020|
|Date of Acceptance||13-Oct-2020|
|Date of Web Publication||17-Apr-2021|
Prof. Mohamed Abuzakouk
Respiratory Institute, Cleveland Clinic Abu Dhabi
Source of Support: None, Conflict of Interest: None
| Abstract|| |
BACKGROUND: Severe asthma is a major burden on health-economic resources; hence, knoing the epidemiology of these patients is important in planning and provision of asthma care. In addition, identifying and managing the comorbidities helps improve symptoms and reduce associated morbidity and mortality.
OBJECTIVES: Epidemiology of difficult asthma has not been ell studied in the Middle East, so in this study, e present the demographic and clinical characteristics of severe asthma in the United Arab Emirates (UAE).
METHODS: We retrospectively revieed the notes of severe asthma patients attending three tertiary care hospitals beteen May 2015 and December 2019. Data on baseline demographics, asthma characteristics, treatment, and comorbidities ere collected.
RESULTS: We revieed the notes of 458 patients (271 females and 187 males) that fulfilled the 2019 Global Initiative for Asthma guidelines for the diagnosis of severe asthma. The mean age as 47.7 (standard deviation 17.2) years. Males had significantly higher asthma control test scores (17.9 vs. 16, P = 0.01) and mean blood eosinophils (0.401 vs. 0.294, P <0.01) than females. The most common comorbidity observed as allergic rhinitis (52.2%) folloed by gastroesophageal reflux disease (27.1%). In total, 109 (23.8%) patients ere on biological therapies ith most patients being on omalizumab and dupilumab (29 and 18 patients, respectively). Most patients ere nonsmokers (97.2%), and majority ere of TH2-high phenotype (75.7%).
CONCLUSIONS: In this first report of severe asthma characteristics in the UAE, e found a pattern of female preponderance and most patients having a Th2-high phenotype. The findings are likely to help optimize asthma care in the region in the era of biologic therapies.
Keywords: Airflow obstruction, allergic asthma, asthma, asthma epidemiology, severe asthma epidemiology, Th1/Th2
|How to cite this article:|
Abuzakouk M, Ghorab OK, Mahboub B, Alzaabi A, Uzbeck MH, Nasir M, Zoumot Z, Grandon D, El Sameed YA, Namas R, Wahla AS, Chapman J, Saleh K, Salvo F, Bodi GS, Shafiq I. Demographic and clinical patterns of severe asthma in the Middle East. Ann Thorac Med 2021;16:172-7
|How to cite this URL:|
Abuzakouk M, Ghorab OK, Mahboub B, Alzaabi A, Uzbeck MH, Nasir M, Zoumot Z, Grandon D, El Sameed YA, Namas R, Wahla AS, Chapman J, Saleh K, Salvo F, Bodi GS, Shafiq I. Demographic and clinical patterns of severe asthma in the Middle East. Ann Thorac Med [serial online] 2021 [cited 2022 May 28];16:172-7. Available from: https://www.thoracicmedicine.org/text.asp?2021/16/2/172/313935
Asthma is a chronic lung disease characterized by airay inflammation and hyper-responsiveness affecting almost 300 million people orldide. Asthma can be classified as mild, moderate, or severe, based on the intensity of treatment required to achieve asthma control. Severe asthma is defined as asthma that requires treatment ith high-dose inhaled corticosteroids (ICS) to maintain good control or as asthma that is poorly controlled despite the use of maximal optimized therapy and treatment of contributory factors. Severe asthma is reported to affect about 5%–10% of asthmatics. It is important to differentiate severe asthma from difficult-to-treat asthma, hich is defined as asthma that is poorly controlled due to correctable factors such as environmental allergens, comorbidities, poor medication compliance, and incorrect inhaler technique. While severe asthma is less prevalent than milder asthma severities, it remains a major cause of morbidity and mortality, orldide. In addition, it is associated ith a major socioeconomic, psychological, and treatment burden.
The clinical characteristics and phenotypes of severe asthma patients have been previously reported from various parts of the orld,,, and this knoledge has been particularly important for the development and application of novel biological therapies. In addition, severe asthma registries can be used for genetic profiling to help identify individuals ho are genetically predisposed to severe asthma. Difficult asthma phenotypes, including patients ith severe asthma, have not been ell studied in the Middle Eastern populations. The United Arab Emirates (UAE) has no official severe asthma registry and as yet no published data describing the characteristics of these patients. Undoubtedly, it is necessary to understand local epidemiology and clinical characteristics of severe asthma to make better-informed local guidelines and treatment decisions. Therefore, e took the initiative to examine the demographic and clinical variables of severe asthma in a local population attending three tertiary care hospitals in the UAE beteen May 2015 and December 2019.
| Methods|| |
We performed a retrospective chart revie of all patients diagnosed ith severe asthma according to the 2019 Global Initiative for Asthma (GINA) guidelines attending Cleveland Clinic Abu Dhabi (Abu Dhabi), Rashid Hospital (Dubai), and Zayed Military Hospital (Abu Dhabi), beteen May 2015 and December 2019. Patients ere included if they had at least three visits to the asthma clinic, ith the visits being at least 1 month apart, ere on high-dose ICS ith optimal inhaler technique, shoed good compliance ith medication, and had good control of the contributing/exacerbating factors. Patients ith asthma-chronic obstructive pulmonary disease overlap syndrome and deceased patients ere excluded. We identified a total of 604 patients that met the inclusion/exclusion criteria, of hom 458 ere Emirati citizens and ere used to form the cohort for the current analysis.
The medical records of all participants ere revieed by a study team comprised of one or to researchers at each study site. Apart from basic demographic information, the Asthma Control Test (ACT) scores, fractional exhaled nitric oxide (FeNO) levels, eosinophil counts, and total immunoglobulin E (IgE) levels ere also recorded. Comorbidities including body mass index, cigarette smoking, allergic rhinitis, hypertension, gastroesophageal reflux disease (GERD), hyperlipidemia, diabetes, obesity, obstructive sleep apnea (OSA), nasal polyps, thyroid disease, bronchiectasis, depression, anxiety, osteoporosis, food allergy, eczema, and malignancies ere documented.
Descriptive statistics ere used to summarize the characteristics of the cohort. Comparisons of categorical baseline characteristics in the cohort ere performed using Pearson's Chi-squared test. Comparisons of continuous baseline characteristics ere performed using Welch's to-sample t-test. We considered a p-value less than 0.05 to be statistically significant in our study.
| Results|| |
A total of 604 patients fulfilled the 2019 GINA guidelines for the diagnosis of severe asthma. Among these, 458 patients (75.8%) ere Emirati citizens, hereas 146 patients (24.2%) ere expatriates. Since our objective is to study the demographics of the local Arab population, the expatriates ere excluded from the analysis. Among the 458 patients, there ere 271 females (59.2%) and 187 males (41%) [Table 1]. The mean ± standard deviation age for females as higher than that for males (50.2 ± 16.6 years vs. 44.2 ± 17.4 years, P = 0.002), ith a range beteen 14 and 92 years.
|Table 1: Comparison of severe asthma characteristics between different studies|
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Age of asthma onset as available for 241 patients, of these 111 patients (46.1%) reported having been diagnosed ith asthma in childhood, hereas 130 patients (53.9%) ere diagnosed as adults.
Information about asthma phenotype, i.e., allergic versus nonallergic as available for 242 patients. Out of those, 148 patients (61.2%) ere labeled as having allergic asthma and 35 patients (14.5%) suffered from eosinophilic asthma. Together these to groups made up the Th2 high phenotype (75.7%). The rest of the patients in the cohort (24.3%) ere nonallergic/Th2 lo phenotype.
We carried out statistical comparisons of asthma characteristics beteen males and females and identified significant differences in ACT scores and mean blood eosinophil count [Table 2]. A significantly higher mean ACT score and eosinophil count as observed in males compared to females (17.9 vs. 16, P = 0.01) and (0.401 vs. 0.294, P < 0.01), respectively. The mean IgE and FeNO levels ere not significantly different across genders.
Comorbidities and modifiable risk factors
The most frequent comorbidity observed as allergic rhinitis (52.2%), folloed by GERD (27.1%), hypertension (26.9%), hyperlipidemia (26.0%), diabetes (25.3%), obesity (20.3%), OSA (14.0%), nasal polyps (11.1%), thyroid disease (9.6%), bronchiectasis (5.5%), eczema (3.9%), food allergy (3.7%), depression (3.5%), anxiety (3.5%), and osteoporosis (3.1%). Sixty-to patients (13%) had a history of past/present smoking. We analyzed the difference beteen genders in terms of comorbidities and found that GERD and depression ere significantly more common in females hile nasal polyps and eczema ere more prevalent among males [Table 3].
A total of 109 (23.8%) patients ere receiving biological therapy for the treatment of severe asthma. The breakdon of the data according to the biological agents shoed 56 (51.4%) patients on omalizumab, 29 (26.6%) patients on dupilumab, 18 (16.5%) patients on benralizumab, and 6 (5.5%) patients on mepolizumab.
Thirteen patients (2.8%) had a history of malignancy; the most common malignancies ere breast, lung, and thyroid cancer, each found in three patients. Colon cancer as found in to patients, and bladder cancer and prostate cancer ere each found in one patient.
| Discussion|| |
The scarcity of data on severe asthma not only in the UAE, but also in the Middle East as a hole necessitated this retrospective revie in hich e evaluated the demographic and clinical characteristics of patients ith severe asthma in the UAE's local Arab population and compared our data ith previously published international cohorts. One of the earliest reports of asthma prevalence in the UAE stated that asthma affects about 13.6% of children in the UAE. Hoever, there is a variation in the asthma prevalence rates recently reported in the UAE; one report suggested that asthma affects at least 9.8% of the total UAE population, another report estimated that it affects 13% of the population and a third report estimated that asthma affects 4.9% of the population. The variation in prevalence rates may be due to the different methodologies used in each of the studies, here asthma definitions have differed from one study to another. With this in mind, it is sensible for us to estimate the asthma prevalence in that the UAE is about 8%–9%, similar to that found in Kuait (9.5%) and Saudi Arabia (8.3%). The economic burden of asthma care in the emirate of Abu Dhabi as reported to be around 29 million USD in 2014; hoever, ith increasing use of biologics in the severe asthma subgroup, this cost is likely to increase significantly.
The mean age of our severe asthma cohort as 47.7 ± 17.2, hich is loer than the three studies e used for comparison [Table 1]. Hoever, data from the Severe Asthma Research Program (SARP) registry reported a mean age of 37 years hich is considerably loer than our cohort. This heterogeneity in the age of difficult asthma is interesting, being as high as 62.3 in Korea as reported by Kim et al. and as lo as 37 in SARP, and it highlights that the care needs for these patient populations may be significantly different in the different parts of the orld.
In our study, almost 54% of the patients had adult onset asthma. It has been reported that age of onset affects the response of severe asthma patients to biological therapy. Patients ith adult onset usually respond better to anti-interleukin 5 (IL-5) or anti IL-5 receptor therapy, hereas patients ith childhood onset disease respond better to anti-IgE therapy., Our cohort as the youngest cohort compared to cohorts from other global studies, and therefore, this could explain hy more than half (51.4%) of our patients receiving biological therapy for severe asthma ere on anti-IgE therapy (Omalizumab).
We observed a female predominance of 59% in our patient cohort hich as no different from the studies e used for comparison. Although our observation is for severe asthma, it is ell-knon that females dominate all asthma severity groups. It has been suggested that sex hormones in females contribute to orse asthma symptoms compared to males, and animal studies have shon that oestrogen increased Th2-mediated airay inflammation, hile androgens reduced it., This is a significant finding as it not only provides an explanation for the difference in asthma prevalence, onset, and severity beteen males and females, but also offers opportunities for further studies to be carried out to assess the difference in inflammatory pathays beteen males and females and potentially consider hormonal therapy for asthma.
In this study, e found that males had significantly higher mean blood eosinophil count and ACT scores than females (P < 0.01 and P = 0.01, respectively); this is in concordance ith the previously reported data., This is an interesting observation firstly as previous studies have reported no gender-based differences in asthma control, and secondly because females in our cohort ere older and more obese, hich are parameters associated ith orse asthma control.,
Allergic rhinitis as the most prevalent comorbidity in our cohort (52.2%) as observed in other severe asthma cohorts., Allergic rhinitis is ell knon to coexist ith asthma and according to some authors more than 80% of asthmatics have a diagnosis of allergic rhinitis. In addition, the presence of allergic rhinitis is thought to be associated ith increased asthma severity., This connection beteen allergic rhinitis and asthma is not surprising as the “united airay disease” theory suggests that the upper and the loer airay are functionally a singular unit and the inflammatory/allergic disorders in one are bound to have similar effects on the other., Hence, it is not surprising that treatment of allergic rhinitis ith nasal corticosteroids and the leukotriene receptor antagonists also seems to reduce asthma exacerbations and asthma-related respiratory symptoms.,
Similar to other cohorts,, GERD as the second most common co-morbidity observed in our patients (27.1%), and it is knon to be more prevalent among asthmatics compared to the general population. We also observed a statistically significant difference in the prevalence of GERD beteen females and males (68.5% vs. 31.5%, respectively, P = 0.013). This finding has been reported in to other studies previously, and is possibly due to the effect of estrogen on the loer esophageal sphincter; hoever, the mechanism is not entirely clear.
Anxiety and depression ere each present in 3.5% of the patients. Previously, Kim et al. had reported a somehat similar prevalence of anxiety and depression in their study hich as 1.7% and 3.7%, respectively. We also observed a significant difference in the prevalence of depression beteen males and females ith a female preponderance (females 87.5%, males 12.5%, P = 0.02) hich is in accordance ith a higher prevalence of depression in omen in the general population.
These findings are important as depression is reported to be a risk factor for developing asthma, and both anxiety and depression are associated ith poor asthma control.
The prevalence of nasal polyposis in the Middle East including the UAE has not been previously reported. In our patient population, nasal polyposis as present in 11.1% of the total cohort hile Wang et al. reported the prevalence of nasal polyposis to be 7.3%. Nasal polyposis has been reported to be associated ith greater asthma severity; hoever, e did not observe a significant difference in ACT scores beteen asthma patients ith and ithout nasal polyps (P = 0.5). Interestingly, e observed a significant difference in the prevalence of nasal polyposis beteen males and females (P = 0.013), here males had a higher prevalence (56.9% vs. 43.1%, P = 0.013) hich is in concordance ith previously reported data.
The choice of biologics for the treatment of asthma is expanding and phenotyping difficult asthma is the necessary first step in deciding the need and the choice of biologic therapy. Omalizumab is an anti-IgE monoclonal antibody that is approved by the Food and Drug Agency (FDA) in the treatment of moderate-to-severe allergic asthma. Mepolizumab (anti-IL5), Benralizumab (anti-IL5R), and Dupilumab (anti-IL4) are FDA approved for the treatment of severe eosinophilic asthma., Allergic asthma is ell knon to be the most common asthma phenotype orldide, and in our cohort as ell, asthma as predominantly allergic (61.2%). Wang et al. suggested that early onset asthma combined ith high IgE levels predisposes patients to develop allergic asthma later on. Our cohort had the higher mean blood IgE levels than the compared studies [Table 1], and almost 50% of the patients ere diagnosed ith asthma during childhood, therefore, our findings support this suggestion by Wang et al. On the other hand, nonallergic asthma is suggested to be defined by late disease onset combined ith loer IgE levels, as seen in one study. The patients ho ere identified as having nonallergic asthma in our study ere predominantly diagnosed in adulthood and had a loer mean blood IgE compared to patients ith allergic asthma; hoever, the difference in mean blood IgE levels as not statistically significant.
Our study is focused on the Emirati population and completely excludes the expatriate population. The genetic makeup of Emiratis could be different to the expatriate population, hich ould reflect on the prevalence of the different severe asthma phenotypes. The UAE government provides its citizens ith a good quality health-care system administered by its Federal Ministry of Health, and this may explain the lo prevalence of severe asthma in the country. In addition, hile our study measures the prevalence of severe asthma across three major health-care centers in the UAE, the figure e report is not conclusive, as there may be patients receiving asthma care elsehere in the country. Moreover, data on the prevalence of comorbidities among UAE nationals is not available; therefore, e ere not able to determine hether the comorbidities e identified ere truly raised in the Emirati population ith severe asthma.
| Conclusion|| |
In summary, our study is the first to report the demographics, clinical phenotypes and treatment variables in a large cohort of Emirati patients diagnosed ith severe asthma. Our findings provide important information regarding the understanding of the disease in the region and highlight the need for establishing a national registry to identify the true prevalence and help improve the management of severe asthma in the UAE.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]