Eotaxin-Rich Proangiogenic Hematopoietic Progenitor Cells and CCR3+ Endothelium in the Atopic Asthmatic Response.

Angiogenesis is closely linked to and precedes eosinophilic infiltration in asthma. Eosinophils are recruited into the airway by chemoattractant eotaxins, which are expressed by endothelial cells, smooth muscles cells, epithelial cells, and hematopoietic cells. We hypothesized that bone marrow-derived proangiogenic progenitor cells that contain eotaxins contribute to the initiation of angiogenesis and inflammation in asthma. Whole-lung allergen challenge of atopic asthma patients revealed vascular activation occurs within hours of challenge and before airway inflammation. The eotaxin receptor CCR3 was expressed at high levels on submucosal endothelial cells in patients and a murine model of asthma. Ex vivo exposure of murine endothelial cells to eotaxins induced migration and angiogenesis. In mechanistic studies, wild-type mice transplanted with eotaxin-1/2-deficient bone marrow had markedly less angiogenesis and inflammation in an atopic asthma model, whereas adoptive transfer of proangiogenic progenitor cells from wild-type mice in an atopic asthma model into the eotaxin-1/2-deficient mice led to angiogenesis and airway inflammation. The findings indicate that Th2-promoting hematopoietic progenitor cells are rapidly recruited to the lung upon allergen exposure and release eotaxins that coordinately activate endothelial cells, angiogenesis, and airway inflammation.

Hyaluronan and Its Heavy Chain Modification in Asthma Severity and Experimental Asthma Exacerbation.

Hyaluronan (HA) is a large (>1500 kDa) polysaccharide of the extracellular matrix that has been linked to severity and inflammation in asthma. During inflammation, HA becomes covalently modified with heavy chains (HC-HA) from inter-α-inhibitor (IαI), which functions to increase its avidity for leukocytes. Our murine model of allergic pulmonary inflammation suggested that HC-HA may contribute to inflammation, adversely effecting lower airway remodeling and asthma severity. Our objective was to characterize the levels of HA and HC-HA in asthmatic subjects and to correlate these levels with asthma severity. We determined the levels and distribution of HA and HC-HA (i) from asthmatic and control lung tissue, (ii) in bronchoalveolar lavage fluid obtained from non-severe and severe asthmatics and controls, and (iii) in serum and urine from atopic asthmatics after an experimental asthma exacerbation. HC-HA distribution was observed (i) in the thickened basement membrane of asthmatic lower airways, (ii) around smooth muscle cells of the asthmatic submucosa, and (iii) around reserve cells of the asthmatic epithelium. Patients with severe asthma had increased HA levels in bronchoalveolar lavage fluid that correlated with pulmonary function and nitric oxide levels, whereas HC-HA was only observed in a patient with non-severe asthma. After an experimental asthma exacerbation, serum HA was increased within 4 h after challenge and remained elevated through 5 days after challenge. Urine HA and HC-HA were not significantly different. These data implicate HA and HC-HA in the pathogenesis of asthma severity that may occur in part due to repetitive asthma exacerbations over the course of the disease.

Using an extended treatment regimen of lanadelumab in the prophylaxis of hereditary angioedema: a single-centre experience.

Aim: To explore and compare the efficacy of standard (300 mg every 2 weeks) and extended (300 mg every 4 weeks) dosing regimens of lanadelumab for long-term prophylaxis of hereditary angioedema (HAE). Methods: We conducted a retrospective chart review of all patients with HAE on lanadelumab, which identified a total of 9 patients: 5 females and 4 males. The median age of patients was 31 years (IQR 20.7). The mean number of attacks per month before starting lanadelumab was 5.9 (SD 6.3). Patients were started on 300 mg of lanadelumab subcutaneously, every 2 weeks (standard group, n = 5) or every 4 weeks (extended group, n = 4). Results: We observed a statistically significant improvement in the number of angioedema attacks per month in all 9 patients (p = 0.007). Five out of 9 patients (56%) achieved complete remission from attacks after starting lanadelumab. The effect of lanadelumab on number of angioedema attacks was significant in both groups; extended group (p = 0.03) and standard group (p = 0.01). Conclusion: Lanadelumab is a safe and effective agent for long-term prophylaxis of HAE. An extended dosing regimen was equally effective as prophylaxis compared to a standard regimen. Further studies are needed to compare the 2 regimens in a larger patient group.

Demographic and clinical patterns of severe asthma in the Middle East.

BACKGROUND: Severe asthma is a major burden on health-economic resources; hence, knowing 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 well studied in the Middle East, so in this study, we present the demographic and clinical characteristics of severe asthma in the United Arab Emirates (UAE). METHODS: We retrospectively reviewed the notes of severe asthma patients attending three tertiary care hospitals between May 2015 and December 2019. Data on baseline demographics, asthma characteristics, treatment, and comorbidities were collected. RESULTS: We reviewed 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 was 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 was allergic rhinitis (52.2%) followed by gastroesophageal reflux disease (27.1%). In total, 109 (23.8%) patients were on biological therapies with most patients being on omalizumab and dupilumab (29 and 18 patients, respectively). Most patients were nonsmokers (97.2%), and majority were of TH2-high phenotype (75.7%). CONCLUSIONS: In this first report of severe asthma characteristics in the UAE, we 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.

How are patients with chronic urticaria interested in using information and communication technologies to guide their healthcare? A UCARE study.

BACKGROUND: Patients with chronic urticaria (CU) are increasingly using information and communication technologies (ICTs) to manage their health. What CU patients expect from ICTs and which ICTs they prefer remains unknown. We assessed why CU patients use ICTs, which ones they prefer, and what drives their expectations and choices. METHODS: In this cross-sectional study, 1841 patients across 17 countries were recruited at UCAREs (Urticaria Centers of Reference and Excellence). Patients with CU who were >12 years old completed a 23-item questionnaire. RESULTS: Most patients were interested in receiving disease information (87.3%), asking physicians about CU (84.1%), and communicating with other patients through ICTs (65.6%). For receiving disease information, patients preferred one-to-one and one-to-many ICTs, especially web browsers. One-to-one ICTs were also the ICTs of choice for asking physicians about urticaria and for communicating with other patients, and e-mail and WhatsApp were the preferred ICTs, respectively. Many-to-many ICTs such as Facebook, Instagram, LinkedIn, and Twitter were least preferred for all 3 purposes. Living in rural areas and higher education were linked to higher odds of being interested in receiving disease information, asking physicians, and communicating with patients through ICTs. CONCLUSIONS: Most patients and especially patients with higher education who live in rural areas are interested in using ICTs for their healthcare, but prefer different ICTs for different purposes, ie, web browsers for obtaining information, e-mail for asking physicians, and WhatsApp for communicating with other patients. Our findings may help to improve ICTs for CU.

Chronic urticaria patients are interested in apps to monitor their disease activity and control: A UCARE CURICT analysis.

BACKGROUND: Information/communication technologies such as mobile phone applications (apps) would enable chronic urticaria (CU) patients to self-evaluate their disease activity and control. Yet, recently Antó et al (2021) reported a global paucity of such apps for patients with CU. In this analysis, we assessed patient interest in using apps to monitor CU disease activity and control using questions from the chronic urticaria information and communication technologies (CURICT) study. METHODS: The methodology for CURICT has been reported. Briefly, a 23-item questionnaire was completed by 1841 CU patients from 17 UCAREs across 17 countries. Here, we analyzed patient responses to the CURICT questions on the use of apps for urticaria-related purposes. RESULTS: As previously published, the majority of respondents had chronic spontaneous urticaria (CSU; 63%; 18% chronic inducible urticaria (CIndU) [CIndu]; 19% with both), were female (70%) and in urban areas (75%). Over half of patients were very/extremely interested in an app to monitor disease activity (51%) and control (53%), while only ∼1/10 were not. Patients with both urticaria types versus those with CSU only (odds ratio [OR], 1.36 [1.03-1.79]) and females versus males (OR [95% CI], 1.47 [1.17-1.85]) were more likely to be very to extremely interested in an app to assess disease control. CONCLUSIONS: Overall, half of the patients with CU were very to extremely interested in using an app to assess their disease activity and control. Development of well-designed apps, specific to disease types (CSU, CIndU, CSU + CIndU, etc), validated by experts across platforms would help improve the management and possibly outcomes of CU treatment while providing important patient information to be used in future research.

Efficacy and Safety of Biologic Agents in Chronic Urticaria, Asthma and Atopic Dermatitis - A Real-life Experience.

INTRODUCTION: Several biologic agents have been approved for the treatment of asthma, chronic urticaria and atopic dermatitis. These therapeutic agents are especially useful for patients with severe or refractory symptoms. We present the real-life experience of four of the commonly used biologic agents in the United Arab Emirates. METHODS: In this retrospective observational study, we reviewed the demographic, clinical, laboratory and treatment parameters for all patients treated with biologic agents. RESULTS: 270 patients received biologics at our centre between May 2015 and December 2019 with a median age of 36.5 years. Omalizumab was the most prescribed agent (n=183, 67.8%) followed by dupilumab (n=54, 20%), benralizumab (n=22, 8.1%) and mepolizumab (n=11, 4.1%). Urticaria was the commonest treatment indication (n=148, 55%) followed by asthma (n=105, 39%) and atopic dermatitis (n=13, 5%). All chronic urticaria patients were treated with omalizumab and showed improvement in the mean urticaria control test score from 6.7±4.47 to 12.02±4.17, with a p-value of 0.001. Dupilumab was found to be the most commonly prescribed drug for asthma (37%), followed by omalizumab (32%), benralizumab (21%) and mepolizumab (10%). The mean Asthma control test score for all asthmatics combined increased from 17.06 ± 5.4 to 19.44 ± 5.6, with p-value 0.0012 with treatment; FeNO reduced from 60.02 ± 45.74 to 29.11 ± 27.92, with p-value 0.001 and mean FEV1 improved from 2.38L ± 0.8 to 2.67L ± 0.78, with p-value 0.045. Only 4 patients in the entire cohort reported adverse events. CONCLUSION: Our study demonstrated that biological agents are a safe and effective treatment for atopic asthma, chronic urticaria and atopic dermatitis.

The usage, quality and relevance of information and communications technologies in patients with chronic urticaria: A UCARE study.

BACKGROUND: Chronic urticaria (CU) is characterized by itchy recurrent wheals, angioedema, or both for 6 weeks or longer. CU can greatly impact patients' physical and emotional quality of life. Patients with chronic conditions are increasingly seeking information from information and communications technologies (ICTs) to manage their health. The objective of this study was to assess the frequency of usage and preference of ICTs from the perspective of patients with CU. METHODS: In this cross-sectional study, 1800 patients were recruited from primary healthcare centers, university hospitals or specialized clinics that form part of the UCARE (Urticaria Centers of Reference and Excellence) network throughout 16 countries. Patients were >12 years old and had physician-diagnosed chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CIndU). Patients completed a 23-item questionnaire containing questions about ICT usage, including the type, frequency, preference, and quality, answers to which were recorded in a standardized database at each center. For analysis, ICTs were categorized into 3 groups as follows: one-to-one: SMS, WhatsApp, Skype, and email; one-to-many: YouTube, web browsers, and blogs or forums; many-to-many: Instagram, Twitter, Facebook, and LinkedIn. RESULTS: Overall, 99.6% of CU patients had access to ICT platforms and 96.7% had internet access. Daily, 85.4% patients used one-to-one ICT platforms most often, followed by one-to-many ICTs (75.5%) and many-to-many ICTs (59.2%). The daily ICT usage was highest for web browsers (72.7%) and WhatsApp (70.0%). The general usage of ICT platforms increased in patients with higher levels of education. One-to-many was the preferred ICT category for obtaining general health information (78.3%) and for CU-related information (75.4%). A web browser (77.6%) was by far the most commonly used ICT to obtain general health information, followed by YouTube (25.8%) and Facebook (16.3%). Similarly, for CU-specific information, 3 out of 4 patients (74.6%) used a web browser, 20.9% used YouTube, and 13.6% used Facebook. One in 5 (21.6%) patients did not use any form of ICT for obtaining information on CU. The quality of the information obtained from one-to-many ICTs was rated much more often as very interesting and of good quality for general health information (53.5%) and CU-related information (51.5%) as compared to the other categories. CONCLUSIONS: Usage of ICTs for health and CU-specific information is extremely high in all countries analyzed, with web browsers being the preferred ICT platform.