Exploring Definitions and Predictors of Severe Asthma Clinical Remission Post-Biologic in Adults.

RATIONALE: There is no consensus on criteria to include in an asthma remission definition in real-life. Factors associated with achieving remission post-biologic-initiation remain poorly understood. OBJECTIVES: To quantify the proportion of adults with severe asthma achieving multi-domain-defined remission post-biologic-initiation and identify pre-biologic characteristics associated with achieving remission which may be used to predict it. METHODS: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1-year pre- and post-biologic-initiation. A priori-defined remission cut-offs were: 0 exacerbations/year, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted forced expiratory volume in one second ≥80%. Remission was defined using 2 (exacerbations + LTOCS), 3 (+control or +lung function) and 4 of these domains. The association between pre-biologic characteristics and post-biologic remission was assessed by multivariable analysis. MEASUREMENTS AND MAIN RESULTS: 50.2%, 33.5%, 25.8% and 20.3% of patients met criteria for 2, 3 (+control), 3 (+lung function) and 4-domain-remission, respectively. The odds of achieving 4-domain remission decreased by 15% for every additional 10-years asthma duration (odds ratio: 0.85; 95% CI: 0.73, 1.00). The odds of remission increased in those with fewer exacerbations/year, lower LTOCS daily dose, better control and better lung function pre-biologic-initiation. CONCLUSIONS: One in 5 patients achieved 4-domain remission within 1-year of biologic-initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission post-biologic, indicating that biologic treatment should not be delayed if remission is the goal. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma.

BACKGROUND: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. OBJECTIVE: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. METHODS: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV1]: <50% to ≥80%). RESULTS: Percentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV1. The proportion of patients having improvement post-biologic tended to be greater for anti-IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. CONCLUSION: Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies. TRIAL REGISTRATION: The ISAR database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization studies (ENCEPP/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220).

COVID-19 Hierarchical Classification Using a Deep Learning Multi-Modal.

Coronavirus disease 2019 (COVID-19), originating in China, has rapidly spread worldwide. Physicians must examine infected patients and make timely decisions to isolate them. However, completing these processes is difficult due to limited time and availability of expert radiologists, as well as limitations of the reverse-transcription polymerase chain reaction (RT-PCR) method. Deep learning, a sophisticated machine learning technique, leverages radiological imaging modalities for disease diagnosis and image classification tasks. Previous research on COVID-19 classification has encountered several limitations, including binary classification methods, single-feature modalities, small public datasets, and reliance on CT diagnostic processes. Additionally, studies have often utilized a flat structure, disregarding the hierarchical structure of pneumonia classification. This study aims to overcome these limitations by identifying pneumonia caused by COVID-19, distinguishing it from other types of pneumonia and healthy lungs using chest X-ray (CXR) images and related tabular medical data, and demonstrate the value of incorporating tabular medical data in achieving more accurate diagnoses. Resnet-based and VGG-based pre-trained convolutional neural network (CNN) models were employed to extract features, which were then combined using early fusion for the classification of eight distinct classes. We leveraged the hierarchal structure of pneumonia classification within our approach to achieve improved classification outcomes. Since an imbalanced dataset is common in this field, a variety of versions of generative adversarial networks (GANs) were used to generate synthetic data. The proposed approach tested in our private datasets of 4523 patients achieved a macro-avg F1-score of 95.9% and an F1-score of 87.5% for COVID-19 identification using a Resnet-based structure. In conclusion, in this study, we were able to create an accurate deep learning multi-modal to diagnose COVID-19 and differentiate it from other kinds of pneumonia and normal lungs, which will enhance the radiological diagnostic process.

An International Validation of the "DECAF Score" to Predict Disease Severity and Hospital Mortality in Acute Exacerbation of COPD in the UAE.

The DECAF score (the Dyspnea, Eosinopenia, Consolidation, Academia, and Atrial fibrillation score) has been adopted in some hospitals to predict the severity of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). However, DECAF score has not been widely evaluated or used in Middle Eastern countries. The present study aimed to validate the DECAF score for predicting in-hospital mortality in patients with AECOPD in the United Arab Emirates (UAE). This was a retrospective, observational study conducted in 19 hospitals in the UAE. Data were retrieved from the electronic records of patients admitted for AECOPD in 17 hospitals across the country. Patients aged more than 35 years who were diagnosed with AECOPD were included in the study. The validation of the DECAF Score for inpatient death, 30-days death, and 90-day readmission was conducted using the Area Under the Receiver Operator curve (AUROC). The AUROCDECAF curves for inpatient death, 30-days death, and 90-day readmission were 0.8 (95% CI: 0.8-0.9), 0.8 (95% CI: 0.7-0.8), and 0.8 (95% CI: 0.8-0.8), respectively. The model was a satisfactory fit to the data (Hosmer-Lemeshow statistic = 0.195, Nagelkerke R2 = 31.7%). There were significant differences in means of length of stay across patients with different DECAF score (P = .008). Patients with a DECAF score of 6 had the highest mean length of stay, which was 29.8 ± 31.4 days. Patients with a DECAF score of 0 had the lowest mean length of stay, which was 3.6 ± 2.0 days. The DECAF score is a strong predictive tool for inpatient death, 30 days mortality and 90-day readmission in UAE hospital settings. The DECAF score is an effective tool for predicating mortality and other disease outcomes in patients with AECOPD in the UAE; hence, clinicians would be more empowered to make appropriate clinical decisions by using the DECAF score.

Comparative effectiveness of anti-IL5 and anti-IgE biologic classes in patients with severe asthma eligible for both.

BACKGROUND: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. METHODS: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions. RESULTS: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). CONCLUSIONS: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use.

Budgetary Impact of 20-Valent Pneumococcal Conjugate Vaccine Use for Adult Expatriates Living in Dubai.

Background: Dubai Health Authority currently recommends sequential administration of 13-valent pneumococcal conjugate vaccine (PCV13) followed by (→) 23-valent pneumococcal polysaccharide vaccine (PPV23) to prevent pneumococcal disease among adults at elevated risk of illness. Despite recommendations, disease burden and associated costs remain substantial. A new 20-valent pneumococcal conjugate vaccine (PCV20) recently received regulatory approval in the United Arab Emirates and has the potential to further reduce burden of pneumococcal disease. Objectives: To evaluate budget impact of use of novel PCV20 compared with current recommendations (ie, PCV13→PPV23) among expatriates in Dubai aged 50 to 99 years and those aged 19 to 49 years with risk factors. Methods: A deterministic model depicted 5-year risks and costs of invasive pneumococcal disease and all-cause nonbacteremic pneumonia. Each year of the modeling horizon, persons could be vaccinated with either PCV20 or PCV13→PPV23 or remain unvaccinated; persons vaccinated during the modeling horizon were not eligible for vaccination in subsequent years. Annual vaccine uptake was assumed to be 5% in base cases analyses; higher uptake was considered in scenario analyses. Costs were discounted at 3.5% annually and reported in US dollars. Results: In base case, use of PCV20 alone would prevent an additional 13 cases of invasive pneumococcal disease, 31 cases of inpatient all-cause nonbacteremic pneumonia, 139 cases of outpatient all-cause nonbacteremic pneumonia, and 5 disease-related deaths compared with PCV13→PPV23. Medical care costs would be reduced by $354,000, and total vaccination costs would decrease by $4.4 million. PCV20 would therefore yield net budgetary impact of -$4.8 million, resulting in savings of $2.47 per-person per-year over 5 years. In scenarios with higher vaccine uptake, PCV20 prevented more cases and deaths and yielded greater budget savings (vs PCV13→PPV23). Conclusions: PCV20 would reduce burden and economic costs of pneumococcal disease among expatriates in Dubai compared with PCV13→PPV23 and would therefore be budget saving for private health insurers who cover the majority of this population.

Saliva metabolomic profile of COVID-19 patients associates with disease severity.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is strongly linked to dysregulation of various molecular, cellular, and physiological processes that change abundance of different biomolecules including metabolites that may be ultimately used as biomarkers for disease progression and severity. It is important at early stage to readily distinguish those patients that are likely to progress to moderate and severe stages. OBJECTIVES: This study aimed to investigate the utility of saliva and plasma metabolomic profiles as a potential parameter for risk stratifying COVID-19 patients. METHOD: LC-MS/MS-based untargeted metabolomics were used to profile the changes in saliva and plasma metabolomic profiles of COVID-19 patients with different severities. RESULTS: Saliva and plasma metabolites were screened in 62 COVID-19 patients and 18 non-infected controls. The COVID-19 group included 16 severe, 15 moderate, 16 mild, and 15 asymptomatic cases. Thirty-six differential metabolites were detected in COVID-19 versus control comparisons. SARS-CoV-2 induced metabolic derangement differed with infection severity. The metabolic changes were identified in saliva and plasma, however, saliva showed higher intensity of metabolic changes. Levels of saliva metabolites such as sphingosine and kynurenine were significantly different between COVID-19 infected and non-infected individuals; while linoleic acid and Alpha-ketoisovaleric acid were specifically increased in severe compared to non-severe patients. As expected, the two prognostic biomarkers of C-reactive protein and D-dimer were negatively correlated with sphingosine and 5-Aminolevulinic acid, and positively correlated with L-Tryptophan and L-Kynurenine. CONCLUSION: Saliva disease-specific and severity-specific metabolite could be employed as potential COVID-19 diagnostic and prognostic biomarkers.

Prevalence of asthma among the adult general population of five Middle Eastern countries: results of the SNAPSHOT program.

BACKGROUND: Asthma is a common chronic respiratory disease leading to morbidity, mortality and impaired quality of life worldwide. Information on asthma prevalence in the Middle East is fragmented and relatively out-dated. The SNAPSHOT program was conducted to obtain updated information. METHODS: SNAPSHOT is a cross-sectional epidemiological program carried out in five Middle Eastern countries (Egypt, Turkey, Kuwait, Saudi Arabia, and the United Arab Emirates, the latter three grouped into a Gulf cluster) to collect data on asthma, allergic rhinitis, benign prostatic hyperplasia and bipolar disorder. The survey was carried out by telephone in a random sample of the adult general population with quotas defined according to country demographics. The analysis presented in this paper focuses on asthma. Subjects were screened for asthma based on criteria from the global Asthma Insights and Reality studies. Current prevalence (last 12 months) was estimated. Multivariate logistic regression analyses were used to investigate risk factors related to asthma and the association with allergic rhinitis and other co-morbidities. Quality of life was assessed using the three-level EQ-5D questionnaire. RESULTS: 2124 out of the 33,486 subjects enrolled in the SNAPSHOT program fulfilled the criteria for asthma. The adjusted prevalence of asthma ranged from 4.4% [95% CI: 4.0-4.8%] in Turkey, to 6.7% [95% CI: 6.2-7.2%] in Egypt and 7.6% [95% CI: 7.1-8.0%] in the Gulf cluster. Prevalence was higher (p < 0.0001) in women than men and increased with age (p < 0.0001). Co-morbidities occurred more frequently in asthma subjects compared to the non-asthma population (38% vs. 15% p < 0.0001). Subjects with asthma reported a lower (p < 0.0001) EQ-VAS score (68.2 ± 22.9) compared to the general population (78.1 ± 17.5). The risk factors associated with asthma were age, gender, country, and certain co-morbidities, namely respiratory, cardiovascular, gastrointestinal, nervous, and neurological diseases. CONCLUSION: The observed adjusted prevalence of asthma in the Middle East ranges from 4.4% to 7.6%, which is comparatively lower than the reported prevalence in Europe and North America. Asthma has a negative impact on quality of life, and is associated with high levels of co-morbid diseases, indicating a need for physicians to check for co-morbidities and ensure they are managed correctly in all asthma patients.

Patients' satisfaction as a dimension of quality: a survey on outpatients' care in Dubai.

PURPOSE: The last few years have seen a stronger emphasis on patient-centred care within the international healthcare setting. Patient-centred care is clearly perceived to be important to optimise the satisfaction and well-being of patients. The purpose of this paper is to review current patient-centred practices for outpatients in both private clinics and public hospitals in Dubai. Such a comparison contributes to the identification of best management practices as a means of enhancing healthcare delivery. DESIGN/METHODOLOGY/APPROACH: This study is based on an independent survey consisting of self-administered questionnaires, in which patients were asked to rate several aspects of private clinics or government hospitals in Dubai. The questionnaire used has been drawn from the Consumer Assessment of Healthcare Providers and Systems Clinician and Group Survey, Version 3.0. Responses from 420 patients form a data set that is analysed quantitatively. FINDINGS: In total, 420 respondents took part in this survey. The results of the survey show that there is a considerable difference between the expectation levels of patients from government hospitals and patients from private clinics. Patients from government hospitals consistently show that time is a critical aspect of the service received, with 68 per cent of the respondents reporting this issue. Additionally, poor customer care, as reported by 14 per cent of the respondents, is also a critical issue. Timely service and appointments are among the main factors that contribute to patient satisfaction. Patients in private clinics, instead, particularly value clear explanations from doctors and nurses - this is corroborated by the fact that 11 per cent of the respondents reported appreciation of this type of service. PRACTICAL IMPLICATIONS: This paper draws attention to a patient-centric perspective of healthcare, and highlights the importance of educating patients through clear explanations. ORIGINALITY/VALUE: Little evidence exists on the standards of healthcare in Dubai. The authors explore this area and present direct evidence on quality standard implementation, identify implementation shortcomings and make recommendations for future research and practice.

Waterpipe Use in the Middle East and North Africa: Data From the Breathe Study.

INTRODUCTION: In recent decades, waterpipe use has gained popularity, notably in the Middle East and North Africa (MENA) region. This study describes waterpipe use and characteristics of waterpipe users among the general population of the MENA region. METHODS: This study was a sub-analysis of the BREATHE study, a cross-sectional survey of chronic obstructive respiratory disease conducted in the general population of 11 countries of the MENA region. The study population consisted of subjects aged ≥40 years who completed the screening questionnaire and who reported waterpipe use (alone or with cigarettes). This questionnaire collected data on demographics, self-reported respiratory symptoms (breathlessness and productive cough), smoking habits (cigarettes or waterpipe) and diagnosis of chronic obstructive respiratory disease, chronic bronchitis or emphysema. RESULTS: Of the 62 086 subjects screened in the BREATHE study, waterpipe use was reported by 2173 subjects (3.5% [95% CI: 3.4%-3.6%]), of whom 934 subjects (43.0%) smoked both waterpipes and cigarettes. The majority of waterpipe users were men (82%) and aged from 40 to 49 years (53.7%). Over 90% of users smoked their waterpipe for ≥1 hour per day. Waterpipe use was associated with an increased risk of productive cough (odds ratio [OR]: 1.49), breathlessness (OR: 1.33), and chronic bronchitis (OR: 1.43), independently of the risk associated with cigarette smoking. In subjects using waterpipe alone (N = 1239), breathlessness was the most frequently self-reported symptom (11.3%), followed by productive cough (6.0%) and chronic bronchitis (2.2%). CONCLUSIONS: Waterpipe smoking in the region is widespread and is associated with an increased risk of respiratory pathology independently of cigarette smoking. IMPLICATIONS: This large general population study reports an elevated risk of respiratory disease associated with waterpipe use independently of cigarette smoking; this finding emphasizes the need for public health policies to curtail the growing spread of waterpipe use by young people in the MENA region.

Rs37972 and rs37973 single-nucleotide polymorphisms in the glucocorticoid-inducible 1 gene are not associated with asthma risk in a Saudi Arabian population.

OBJECTIVE: Rs37972 and rs37973 variants in the glucocorticoid-induced transcript 1 gene have been associated with inhaled glucocorticosteroid responsiveness in asthmatics; however, some discrepancies have been also reported. This study aims to determine whether rs37972 and rs37973 SNPs are associated with asthma risk in Saudi Arabian asthmatics. METHODS: Two-hundred seventy-one diagnosed asthmatics (3-65 years old) and 387 healthy control subjects of equivalent age were recruited. DNA from peripheral blood was purified, and genotyping of rs37972 and rs37973 SNPs was performed by PCR amplification of segments of interest, followed by Sanger sequencing. RESULTS: The global frequencies of the minor (risk) alleles were 28% ("T" allele, rs37972) and 30% ("G" allele, rs37973). Yates-corrected Chi-square (χ(2)) tests revealed significant differences between asthmatic and healthy groups, in allele frequencies for rs37973 SNP only (χ(2) = 3.98, Yates' p value = 0.046). Regarding genotype frequencies, a significant difference between asthmatic and healthy groups was observed for variant rs37972 only (χ(2) = 8.19, Yates' p value = 0.016). To determine a possible association of the minor "T" and "G" alleles with asthma, both the recessive and dominant genetic models were tested. For rs37973, none of the genotypes were significantly associated with asthma. Concerning rs37972, the dominant model (C/T + T/T versus C/C) indicated a significant "protective" association with asthma, in which C/T + T/T individuals had lower odds of being asthmatics than C/C individuals (OR = 0.67; 95% CI = 0.48-0.94; p = 0.019*). CONCLUSIONS: The minor alleles "T" and "G" of rs37972 and rs37973 SNPs, respectively, were not significantly associated with increased asthma risk in asthma patients from Saudi Arabia.

Real life management of community-acquired Pneumonia in adults in the Gulf region and comparison with practice guidelines: a prospective study.

BACKGROUND: Very few data exist on the management of community-acquired pneumonia (CAP) in patients admitted to hospitals in the Gulf region. The objectives of this study were to describe treatment patterns for CAP in 38 hospitals in five Gulf countries (United Arab Emirates, Kuwait, Bahrain, Oman, and Qatar) and to compare the findings to the most recent Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines. METHODS: This was a prospective, observational study conducted between January 2009 and February 2011. Adult patients hospitalised (excluding intensive care units) for CAP and subsequently discharged were included. Data were collected retrospectively at hospital discharge, and prospectively during two follow-up visits. Data on medical history, mortality-risk scores, diagnostic criteria, antibiotic treatment, isolated pathogens and clinical and radiographic outcomes were collected. Care practices were compared to the IDSA/ATS guidelines. RESULTS: A total of 684 patients were included. The majority (82.9 %) of patients were classified as low risk for mortality (pneumonia severity index II and III). The majority of patients fulfilled criteria for treatment success at discharge, although only 77.6 % presented a normalised leukocyte count. Overall, the management of CAP in Gulf countries is in line with the IDSA/ATS guidelines. This applied to the diagnosis of CAP, to the identification of high-risk CAP patients, to the identification of etiologic agent responsible for CAP and to the type of treatment despite the fact that combinations of antimicrobial agents were not consistent with the guidelines in 10 % of patients. In all patients, information about Gram's staining was not captured as recommended by the IDSA/ATS and in the majority of patients (>85 %) chest radiography was not systematically performed at the post-discharge follow-up visits. DISCUSSION: The management of CAP in the Gulf region is globally in line with current IDSA/ATS guidelines, although rates of pathogen characterisation and post-discharge follow-up need to be improved. CONCLUSION: Compliance with established guidelines should be encouraged in order to improve the management of the disease in this region.

Assessing the impact of storage conditions on RNA from human saliva and its application to the identification of mRNA biomarkers for asthma.

Introduction: Human saliva was used to develop non-invasive liquid biopsy biomarkers to establish saliva as an alternate to blood and plasma in translational research. The present study focused on understanding the impact of sample storage conditions on the extraction of RNA from saliva and the RNA yield, to be applied in clinical diagnosis. In this study, genes related to asthma were used to test the method developed. Methods: Salivary RNA was extracted from three subjects using the Qiazol® based method and quantified by both spectrophotometric (NanoDrop) and fluorometric (Qubit®) methods. RNA integrity was measured using a bioanalyzer. Quantitative PCR was used to monitor the impact of storage conditions on the expression of housekeeping genes: GAPDH and ß-actin, and the asthma related genes: POSTN and FBN2. In addition, an independent cohort of 38 asthmatics and 10 healthy controls were used to validate the expression of POSTN and FBN2 as mRNA salivary biomarkers. Results: Approximately 2 µg of total RNA was obtained from the saliva stored at 40°C without any preservative for 2 weeks showing consistent gene expression with RNA stored at room temperature (RT) for 48 h with RNAlater. Although saliva stored with RNAlater showed a substantial increase in the yield (110 to 234 ng/µL), a similar Cq (15.6 ± 1.4) for the 18s rRNA gene from saliva without preservative showed that the RNA was stable enough. Gene expression analysis from the degraded RNA can be performed by designing the assay using a smaller fragment size spanning a single exon as described below in the case of the POSTN and FBN2 genes in the asthma cohort. Conclusion: This study showed that samples stored at room temperature up to a temperature of 40°C without any preservative for 2 weeks yielded relatively stable RNA. The methodology developed can be employed to transport samples from the point of collection to the laboratory, under non-stringent storage conditions enabling the execution of gene expression studies in a cost effective and efficient manner.

LINCATRA: Two-cycle method to amplify RNA for transcriptome analysis from formalin-fixed paraffin-embedded tissue.

Whole transcriptome analysis (WTA) using RNA extracted from Formalin Fixed Paraffin Embedded (FFPE) tissue is an invaluable tool to understand the molecular pathology of disease. RNA extracted from FFPE tissue is either degraded and/or in very low quantities hampering gene expression analysis. Earlier studies described protocols applied for cellular RNA using poly-A primer-based linear amplification. The current study describes a method, LINCATRA (LINear amplifiCAtion of RNA for whole TRAnscriptome analysis). It employs random nonamer primer based method which can amplify short, fragmented RNA with high fidelity from as low as 5 ng to obtain enough material for WTA. The two-cycle method significantly amplified RNA at ∼1000 folds (p < 0.0001) improving the mean read lengths (p < 0.05) in WTA. Overall, increased mean read length positively correlated with on-target reads (Pearson's r = 0.71, p < 0.0001) in both amplified and unamplified RNA-seq analysis. Gene expression analysis compared between unamplified and amplified group displayed substantial overlap of the differentially expressed genes (DEGs) (log2 fold change cut-off < -2 and >2, p < 0.05) identified between lung cancer and asthma cohorts validating the method developed. This method is applicable in clinical molecular pathology field for both diagnostics and elucidation of disease mechanisms.

Recommended approaches for screening and early detection of lung cancer in the Middle East and Africa (MEA) region: a consensus statement.

Background: The prevalence of lung cancer in the Middle East and Africa (MEA) region has steadily increased in recent years and is generally associated with a poor prognosis due to the late detection of most of the cases. We explored the factors leading to delayed diagnoses, as well as the challenges and gaps in the early screening, detection, and referral framework for lung cancer in the MEA. Methods: A steering committee meeting was convened in October 2022, attended by a panel of ten key external experts in the field of oncology from the Kingdom of Saudi Arabia, United Arab Emirates, South Africa, Egypt, Lebanon, Jordan, and Turkey, who critically and extensively analyzed the current unmet needs and challenges in the screening and early diagnosis of lung cancer in the region. Results: As per the experts' opinion, lack of awareness about disease symptoms, misdiagnosis, limited screening initiatives, and late referral to specialists were the primary reasons for delayed diagnoses emphasizing the need for national-level lung cancer screening programs in the MEA region. Screening guidelines recommend low-dose computerized tomography (LDCT) for lung cancer screening in patients with a high risk of malignancy. However, high cost and lack of awareness among the public as well as healthcare providers prevented the judicious use of LDCT in the MEA region. Well-established screening and referral guidelines were available in only a few of the MEA countries and needed to be implemented in others to identify suspected cases early and provide timely intervention thus improving patient outcomes. Conclusions: There is a great need for large-scale screening programs, preferably integrated with tobacco-control programs and awareness programs for physicians and patients, which may facilitate higher adherence to lung cancer screening and improve survival outcomes.

Epidemiological and Clinical Characteristics Associated with COVID-19 Severity Among Hospitalized Patients in the United Arab Emirates: A Retrospective Multicentre Study.

OBJECTIVES: To investigate the clinical and epidemiological factors associated with severe COVID-19 cases in hospitalized patients across two emirates within the United Arab Emirates (UAE). METHODS: A retrospective observational analytical study analysed data from 738 medical records and conducted 573 in-depth interviews with patients hospitalized across multiple healthcare centers in the UAE, between 29 January 2020 and 14 October 2021. Regression analysis predicted risk factors for COVID-19 severity. RESULTS: Main risk factors identified were crowding (aOR 1.919; 95%CI 1.144, 3.221), obesity (aOR 2.383; 95%CI 1.332, 4.263), diabetes (aOR 11.14; 95%CI 2.653-46.797), severe dehydration (aOR 3.219; 95%CI 2.161, 4.795), cough or sore throat (aOR 1.607; 95%CI 1.032, 2.502), shortness of breath (aOR 1.921; 95%CI 1.294, 2.853), increased days from symptom onset to admission (aOR 1.055; 95%CI 1.006, 1.105), elevated ANC (aOR 1.263, 95%CI 1.121, 1.424), and AST/SGOT (aOR 1.055, 95% CI 1.016, 1.095). Protective factors included smoking (aOR 0.367; 95%CI 0.182, 0.740), first dose of COVID-19 vaccination (aOR 0.595; 95%CI 0.377, 0.93), higher oxygen saturation (aOR 0.853; 95%CI: 0.801, 0.907) and elevated ALC (aOR 0.540; 95%CI 0.323, 0.905). CONCLUSION: Identifying risk factors is crucial for high-risk individuals who may require closer monitoring to improve their outcomes. This can provide guidance for surveillance systems and early detection strategies to mitigate the impact of future outbreaks.

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma.

BACKGROUND: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. RESULTS: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. CONCLUSIONS: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.

International Variation in Severe Exacerbation Rates in Patients With Severe Asthma.

BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbation rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.