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Comorbid asthma in patients with chronic rhinosinusitis with nasal polyps: did dupilumab make a difference?

Al-Ahmad M, Ali A, Khalaf M, Alterki A, Rodriguez-Bouza T

BMC Pulm Med, 2023 Jul 18;23(1):266.
PMID: 37464395 DOI: 10.1186/s12890-023-02556-8

BACKGROUND: The clinical heterogeneity of chronic rhinosinusitis (CRS) and bronchial asthma is attributable to different underlying inflammatory profiles. However, the similarity between CRS with nasal polyps (CRSwNP) and type-2 asthma pathophysiology speculates that one biological therapy could affect both comorbidities. Despite dupilumab, a monoclonal antibody that targets IL-4α and IL-13 receptors, being used in patients with nasal polyps and severe asthma, real-life data about its efficacy in improving the quality of life and patient symptoms is still lacking. This study's primary objective was to evaluate dupilumab treatment's effect on the frequency of olfactory symptoms and health-related quality of life tests as measured by the Sino-nasal outcome test (SNOT-22) in patients with NP. The secondary objective was the effect of dupilumab on asthma symptom control as measured by the asthma control test (ACT).
METHODS: A prospective study was conducted of 166 patients with CRSwNP, with or without asthma. The following variables were collected at baseline and after at least six months of continuous dupilumab therapy; SNOT-22, olfactory symptoms frequency, and ACT score.
RESULTS: Asthma prevalence in patients with CRSwNP was high (59.63%), and being female with a history of frequent use of oral corticosteroid (OCS) courses and repeated unsuccessful nasal and para-nasal surgeries for polyposis increased the likelihood of having underlying asthma by 2, 1 and 4 times more, respectively. Additionally, being asthmatic required a longer duration of dupilumab treatment. However, both the health-related quality of life and olfactory symptoms improved equally in both groups.
CONCLUSION: Even with associated comorbid asthma in patients with CRSwNP, treatment with dupilumab could improve the quality of life, olfactory symptoms, and asthma symptom control.
Fulltext The Kuwait National Primary Immunodeficiency Registry 2004-2018

Al-Herz W, Al-Ahmad M, Al-Khabaz A, Husain A, Sadek A, Othman Y

Front Immunol, 2019;10:1754.
PMID: 31396239 DOI: 10.3389/fimmu.2019.01754

Objective: To present the report from the Kuwait National Primary Immunodeficiency Registry between 2004 and 2018. Methods: The patients were followed prospectively between January 2004 and December 2018 and their collected data included sociodemographic, diagnosis, clinical presentation, laboratory tests, and treatment. Results: A total of 314 PID patients (165 males and 149 females) were registered during the study period. Most of the patients (n = 287, 91.4%) were Kuwaiti nationals and the prevalence among Kuwaitis was 20.27/100,000 with a cumulative incidence of 24.96/100,000 Kuwaitis. The distribution of the patients according to PID categories was as follow: immunodeficiencies affecting cellular and humoral immunity, 100 patients (31.8%); combined immunodeficiencies with associated syndromic features, 68 patients (21.7%); predominantly antibody deficiencies, 56 patients (17.8%); diseases of immune dysregulation, 47 patients (15%); congenital defects of phagocyte number or function, 20 patients (6.4%); autoinflammatory disorders, 1 patient (0.3%); and complement deficiencies, 22 patients (7%). The mean age of the patients at onset of symptoms was 26 months while the mean age at diagnosis was 53 months and the mean delay in diagnosis was 27 months. Most of the patients (n = 272, 86%) had onset of symptoms before the age of 5 years. Parental consanguinity rate within the registered patients was 78% and a positive family history of PID was noticed in 50% of the patients. Genetic testing was performed in 69% of the patients with an overall diagnostic yield of 90%. Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by an autosomal recessive pattern. Intravenous immunoglobulins and stem cell transplantation were used in 58% and 25% of the patients, respectively. There were 81 deaths (26%) among the registered patients with a mean age of death of 25 months. Conclusions: PID is not infrequent in Kuwait and the reported prevalence is the highest in the literature with increased proportion of more severe forms. Collaborative efforts including introduction of newborn screening should be implemented to diagnose such cases earlier and improve the quality of life and prevent premature deaths.
Are Treatment Adherence Factors Apparent in Patients with Asthma and to Physicians? Results from the APPaRENT 3 Survey

Al-Moamary M, Aggarwal B, Al-Ahmad M, Sriprasart T, Koenig S, Levy G, et al.

Adv Ther, 2025 Feb 06.
PMID: 39912987 DOI: 10.1007/s12325-025-03105-x

INTRODUCTION: Patient adherence to regular controller medication is critical for improving clinical outcomes in asthma, which is consistently associated with underlying pathophysiological inflammation. This survey aimed to identify types of treatment nonadherence and associated factors, including patient characteristics that predict poor adherence, in patients with asthma.
METHODS: This cross-sectional online survey involved patients with asthma and physicians managing such patients from Southeast Asia (Indonesia, Malaysia, Philippines, Thailand and Vietnam) and the Middle East (Saudi Arabia and United Arab Emirates) included in the Asthma Patients' and Physicians' Perspectives on the Burden and Management of Asthma (APPaRENT) 3 study. Patients and physicians shared their attitudes and beliefs regarding treatment and adherence in asthma management.
RESULTS: Most patients (82%, 1108/1354) reported having ever received treatment with daily controller inhalers, whereas 38% used inhaled relievers at least once daily for symptomatic relief. Among those prescribed maintenance and reliever therapy, 93% were prescribed a separate inhaled reliever, with significant variation by country (P
Fulltext Expert Opinion on Biological Treatment of Chronic Rhinosinusitis with Nasal Polyps in the Gulf Region

Al-Ahmad M, Alsaleh S, Al-Reefy H, Al Abduwani J, Nasr I, Al Abri R, et al.

J Asthma Allergy, 2022;15:1-12.
PMID: 35018101 DOI: 10.2147/JAA.S321017

Chronic rhinosinusitis (CRS) is defined as the inflammation of nose and paranasal sinuses, affecting the patients' quality of life and productivity. Chronic rhinosinusitis with nasal polyps (CRSwNP) is a principal clinical entity confirmed by the existence of chronic sinonasal inflammation and is characterized by anterior or posterior rhinorrhea, nasal congestion, hyposmia and/or facial pressure or facial pain. Several epidemiologic studies have revealed wide variations in the incidence of CRS among regions globally ranging from 4.6% to 12%. The Gulf countries are also witnessing an unprecedented burden of CRSwNP. According to the current clinical guidelines, glucocorticosteroids and antibiotics are the principal pharmacotherapeutic approaches. Endoscopic sinus surgery is recommended for those who have failed maximal pharmacotherapy. Recently, biologics are considered as an alternative best approach due to the complications associated with medical therapy and surgery. However, precise data on the clinical position of biologic agents in the management of CRSwNP in the Gulf region is not available. The present review article addresses the current diagnostic and management approaches for CRSwNP and also emphasizes the role of emerging biologics in the current treatment strategies for CRSwNP in the Gulf region. Further, a consensus protocol was convened to rationalize the guideline recommendations, strategize the best practices with biologics, and develop clinical practice guidelines for all primary-care specialists in the Gulf region. The consensus-based report will be a useful reference tool for primary-care physicians in primary-healthcare settings, regarding the appropriate time for the initiation of biological treatment in the Gulf region.
Fulltext Gulf Asthma Diagnosis and Management in Adults: Expert Review and Recommendations

Al Busaidi N, Alweqayyan A, Al Zaabi A, Mahboub B, Al-Huraish F, Hameed M, et al.

Open Respir Med J, 2022;16:e187430642205230.
PMID: 37273945 DOI: 10.2174/18743064-v16-e2205230

The prevalence and incidence of asthma are increasing globally because of genetic and environmental influences. Prevalence of asthma in the Gulf has been reported to range from 4.7% to 32.0% and has a substantial economic burden. In this paper, we summarize current asthma management guidance for adults, present insights, and recommendations by key opinion leaders (KOLs) in the Gulf region, and key performance indicators for guiding clinical practice for asthma diagnosis, management, and treatment in the Gulf. While it is recommended that the Global Initiative for Asthma (GINA) guidelines should be followed wherever possible for the management of asthma, KOLs in the Gulf region have presented additional recommendations based on regional challenges and insights. There is a need for better diagnosis using objective testing, increased efforts in tackling the burden of comorbidities in the region, and greater provision of the necessary tools for phenotyping severe asthma. Furthermore, there is a need for greater education for physicians regarding asthma treatment, including the importance of inhaled-corticosteroid-containing controller medication. Regionally, there is also a need for specialist asthma clinics and asthma educators, which would serve to educate physicians and their patients as well as to improve the management of patients. Finally, the use of asthma registries, digital devices, and electronic templates would be of benefit in the management of asthma patients in the region.
Fulltext APPaRENT 3: Asthma Patients' and Physicians' Perspectives on the Burden and Management of Asthma in Seven Countries

Aggarwal B, Al-Moamary M, Allehebi R, Alzaabi A, Al-Ahmad M, Amin M, et al.

Adv Ther, 2024 Aug;41(8):3089-3118.
PMID: 38874879 DOI: 10.1007/s12325-024-02900-2

INTRODUCTION: Asthma management is strongly dependent on physician and patient beliefs and perceptions about the disease and its long-term treatment. The APPaRENT 3 study was conducted to explore factors influencing treatment choice and to understand patients' and physicians' attitudes and perspectives on the use of controller inhalers in regular versus flexible dosing for asthma management.
METHODS: This cross-sectional survey of patients with asthma and treating physicians was conducted in seven countries: Indonesia, Malaysia, Philippines, Thailand, Vietnam (patient survey only), Saudi Arabia, and the United Arab Emirates. Assessment was carried out through an online/face-to-face questionnaire, where patients' viewpoints were focused on their attitudes and beliefs about asthma and treatment adherence, whereas physicians' viewpoints were gathered on their attitudes and beliefs about asthma management, knowledge of and adherence to asthma treatment guidelines, and asthma treatment regimens.
RESULTS: Overall, 1400 patients (mean age, 34 years) and 599 physicians (mean age, 43 years) were included in the survey. Physicians similarly prioritised symptom control (39%) and exacerbation reduction (40%) in moderate asthma, whereas patients prioritised symptom control (41%) over exacerbation reduction (22%). Although both groups (physicians, 86%; patients, 84%) perceived asthma as well-controlled, poor management was evident based on Asthma Control Test (ACT) scores (mean, 15.7; standard deviation, 4.14; 82% had an ACT score
The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity

Baris S, Abolhassani H, Massaad MJ, Al-Nesf M, Chavoshzadeh Z, Keles S, et al.

J Allergy Clin Immunol Pract, 2023 Jan;11(1):158-180.e11.
PMID: 36265766 DOI: 10.1016/j.jaip.2022.10.003

Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders. This area also exhibits more severe disease phenotypes compared with other regions, probably due to the delay in diagnosis. The MENA-IEI registry network has designed protocols and guidelines for the diagnosis and treatment of IEI, taking into consideration the variable regional expertise and resources. These guidelines are primarily meant to improve the care of patients within the region, but can also be followed in other regions with similar patient populations.
Fulltext Management of anaphylaxis due to COVID-19 vaccines in the elderly

Bousquet J, Agache I, Blain H, Jutel M, Ventura MT, Worm M, et al.

Allergy, 2021 10;76(10):2952-2964.
PMID: 33811358 DOI: 10.1111/all.14838

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.
Fulltext Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis

Bousquet J, Melén E, Haahtela T, Koppelman GH, Togias A, Valenta R, et al.

Allergy, 2023 May;78(5):1169-1203.
PMID: 36799120 DOI: 10.1111/all.15679

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.
Fulltext Concepts for the development of person-centred, digitally-enabled, Artificial Intelligence-assisted ARIA care pathways (ARIA 2024)

Bousquet J, Schünemann HJ, Sousa-Pinto B, Zuberbier T, Togias A, Samolinski B, et al.

J Allergy Clin Immunol Pract, 2024 Jul 04.
PMID: 38971567 DOI: 10.1016/j.jaip.2024.06.040

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own life based on their lived experiences. Improving healthcare safety, quality and coordination, as well as quality of life, are important aims in the care of patients with chronic conditions. Person-centred care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (i) digital care pathways for rhinitis and asthma multimorbidity and (ii) digitally-enabled person-centred care (1). It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally-enabled, patient-centred care. The paper includes (i) Allergic Rhinitis and its Impact on Asthma (ARIA), a two-decade journey, (ii) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (iii) mHealth impact on airway diseases, (iv) from guidelines to digital care pathways, (v) embedding Planetary Health, (vi) novel classification of rhinitis and asthma, (vi) embedding real-life data with population-based studies, (vii) the ARIA-EAACI strategy for the management of airway diseases using digital biomarkers, (viii) Artificial Intelligence, (ix) the development of digitally-enabled ARIA Person-Centred Care and (x) the political agenda. The ultimate goal is to propose ARIA 2024 guidelines centred around the patient in order to make them more applicable and sustainable.

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