Assessing catastrophic health expenditure and impoverishment in adult asthma care: a cross-sectional study of patients attending six public health clinics in Klang District, Malaysia.

BACKGROUND: In Malaysia, asthma is a common chronic respiratory illness. Poor asthma control may increase out-of-pocket payment for asthma care, leading to financial hardships Malaysia provides Universal Health Coverage for the population with low user fees in the public health system to reduce financial hardship. We aimed to determine out-of-pocket expenditure on outpatient care for adult patients with asthma visiting government-funded public health clinics. We examined the catastrophic impact and medical impoverishment of these expenses on patients and households in Klang District, Malaysia. METHODS: This is a cross-sectional face-to-face questionnaire survey carried out in six government-funded public health clinics in Klang District, Malaysia. We collected demographic, socio-economic profile, and outpatient asthma-related out-of-pocket payments from 1003 adult patients between July 2019 and January 2020. Incidence of catastrophic health expenditure was estimated as the proportion of patients whose monthly out-of-pocket payments exceeded 10% of their monthly household income. Incidence of poverty was calculated as the proportion of patients whose monthly household income fell below the poverty line stratified for the population of the Klang District. The incidence of medical impoverishment was estimated by the change in the incidence of poverty after out-of-pocket payments were deducted from household income. Predictors of catastrophic health expenditure were determined using multivariate regression analysis. RESULTS: We found the majority (80%) of the public health clinic attendees were from low-income groups, with 41.6% of households living below the poverty line. About two-thirds of the attendees reported personal savings as the main source of health payment. The cost of transportation and complementary-alternative medicine for asthma were the main costs incurred. The incidences of catastrophic expenditure and impoverishment were 1.69% and 0.34% respectively. The only significant predictor of catastrophic health expenditure was household income. Patients in the higher income quintiles (Q2, Q3, Q4) had lower odds of catastrophic risk than the lowest quintile (Q1). Age, gender, ethnicity, and poor asthma control were not significant predictors. CONCLUSION: The public health system in Malaysia provides financial risk protection for adult patients with asthma. Although patients benefited from the heavily subsidised public health services, this study highlighted those in the lowest income quintile still experienced financial catastrophe and impoverishment, and the risk of financial catastrophe was significantly greater in this group. It is crucial to ensure health equity and protect patients of low socio-economic groups from financial hardship.

Predicting the main pollen season of Broussonetia Papyrifera (paper mulberry) tree.

Paper mulberry pollen, declared a pest in several countries including Pakistan, can trigger severe allergies and cause asthma attacks. We aimed to develop an algorithm that could accurately predict high pollen days to underpin an alert system that would allow patients to take timely precautionary measures. We developed and validated two prediction models that take historical pollen and weather data as their input to predict the start date and peak date of the pollen season in Islamabad, the capital city of Pakistan. The first model is based on linear regression and the second one is based on phenological modelling. We tested our models on an original and comprehensive dataset from Islamabad. The mean absolute errors (MAEs) for the start day are 2.3 and 3.7 days for the linear and phenological models, respectively, while for the peak day, the MAEs are 3.3 and 4.0 days, respectively. These encouraging results could be used in a website or app to notify patients and healthcare providers to start preparing for the paper mulberry pollen season. Timely action could reduce the burden of symptoms, mitigate the risk of acute attacks and potentially prevent deaths due to acute pollen-induced allergy.

Latent gammaherpesvirus infection enhances type I IFN response and reduces virus spread in an influenza A virus co-infection model.

Infections with persistent or latent viruses alter host immune homeostasis and have potential to affect the outcome of concomitant acute viral infections such as influenza A virus (IAV). Gammaherpesviruses establish life-long infections and require an on-going immune response to control reactivation. We have used a murine model of co-infection to investigate the response to IAV infection in mice latently infected with the gammaherpesvirus MHV-68. Over the course of infection, latently infected BALB/c mice showed less weight loss, clinical signs, pulmonary cellular infiltration and expression of inflammatory mediators than naïve mice infected with IAV and had significantly more activated CD8+ T cells in the lungs. Four days after IAV infection, virus spread in the lungs of latently infected animals was significantly lower than in naïve animals. By 7 days after IAV infection latently infected lungs express elevated levels of cytokines and chemokines indicating they are primed to respond to the secondary infection. Investigation at an early time point showed that 24 h after IAV infection co-infected animals had higher expression of IFNß and Ddx58 (RIG-I) and a range of ISGs than mice infected with IAV alone suggesting that the type I IFN response plays a role in the protective effect. This effect was mouse strain dependent and did not occur in 129/Sv/Ev mice. These results offer insight into innate immune mechanisms that could be utilized to protect against IAV infection and highlight on-going and persistent viral infections as a significant factor impacting the severity of acute respiratory infections.

RNA-RNA interactions between respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity.

microRNAs (miRNAs) regulate nearly all physiological processes but our understanding of exactly how they function remains incomplete, particularly in the context of viral infections. Here, we adapt a biochemical method (CLEAR-CLIP) and analysis pipeline to identify targets of miRNAs in lung cells infected with Respiratory syncytial virus (RSV). We show that RSV binds directly to miR-26 and miR-27 through seed pairing and demonstrate that these miRNAs target distinct gene networks associated with cell cycle and metabolism (miR-27) and antiviral immunity (miR-26). Many of the targets are de-repressed upon infection and we show that the miR-27 targets most sensitive to miRNA inhibition are those associated with cell cycle. Finally, we demonstrate that high confidence chimeras map to long noncoding RNAs (lncRNAs) and pseudogenes in transcriptional regulatory regions. We validate that a proportion of miR-27 and Argonaute 2 (AGO2) is nuclear and identify a long non-coding RNA (lncRNA) as a miR-27 target that is linked to transcriptional regulation of nearby genes. This work expands the target networks of miR-26 and miR-27 to include direct interactions with RSV and lncRNAs and implicate these miRNAs in regulation of key genes that impact the viral life cycle associated with cell cycle, metabolism, and antiviral immunity.

Cold dispase digestion of murine lungs improves recovery and culture of airway epithelial cells.

Airway epithelial cells (AECs) play a key role in maintaining lung homeostasis, epithelium regeneration and the initiation of pulmonary immune responses. To isolate and study murine AECs investigators have classically used short and hot (1h 37°C) digestion protocols. Here, we present a workflow for efficient AECs isolation and culture, utilizing long and cold (20h 4°C) dispase II digestion of murine lungs. This protocol yields a greater number of viable AECs compared to an established 1h 37°C dispase II digestion. Using a combination of flow cytometry and immunofluorescent microscopy, we demonstrate that compared to the established method, the cold digestion allows for recovery of a 3-fold higher number of CD45-CD31-EpCAM+ cells from murine lungs. Their viability is increased compared to established protocols, they can be isolated in larger numbers by magnetic-activated cell sorting (MACS), and they result in greater numbers of distal airway stem cell (DASC) KRT5+p63+ colonies in vitro. Our findings demonstrate that temperature and duration of murine lung enzymatic digestion have a considerable impact on AEC yield, viability, and ability to form colonies in vitro. We believe this workflow will be helpful for studying lung AECs and their role in the biology of lung.

Immune Mechanisms Underpinning Long COVID: Collegium Internationale Allergologicum Update 2024.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in a prolonged multisystem disorder termed long COVID, which may affect up to 10% of people following coronavirus disease 2019 (COVID-19). It is currently unclear why certain individuals do not fully recover following SARS-CoV-2 infection. SUMMARY: In this review, we examine immunological mechanisms that may underpin the pathophysiology of long COVID. These mechanisms include an inappropriate immune response to acute SARS-CoV-2 infection, immune cell exhaustion, immune cell metabolic reprogramming, a persistent SARS-CoV-2 reservoir, reactivation of other viruses, inflammatory responses impacting the central nervous system, autoimmunity, microbiome dysbiosis, and dietary factors. KEY MESSAGES: Unfortunately, the currently available diagnostic and treatment options for long COVID are inadequate, and more clinical trials are needed that match experimental interventions to underlying immunological mechanisms.

Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper.

The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano-technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in-depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody- (I-III), cell-mediated (IVa-c), tissue-driven mechanisms (V-VI) and direct response to chemicals (VII). Types I-III are linked to classical and newly described clinical conditions. Type IVa-c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V-VI involve epithelial barrier defects and metabolic-induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime.

Eosinophils-from cradle to grave: An EAACI task force paper on new molecular insights and clinical functions of eosinophils and the clinical effects of targeted eosinophil depletion.

Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti-inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy-driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non-immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non-specific eosinophil-targeting therapies. Despite the overall favourable safety profile of the currently available anti-eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences.

Association of asthma exacerbations with paper mulberry (Broussenetia papyrifera) pollen in Islamabad: An observational study.

Background: Although the role of airborne plant pollen in causing allergic rhinitis has been established, the association of concentrations of paper mulberry (Broussenetia papyrifera) pollens in the air and incidence of asthma exacerbations has not, despite an observed increase in the number of asthma patients attending physician clinics and hospital Accident and Emergency (A&E) Departments during the paper mulberry pollen season. We aimed to assess the association between paper mulberry pollen concentrations (typically peaking in March each year) and asthma exacerbations in the city of Islamabad. Methods: We used three approaches to investigate the correlation of paper mulberry pollen concentration with asthma exacerbations: A retrospective analysis of historical records (2000-2019) of asthma exacerbations of patients from the Allergy and Asthma Institute, Pakistan (n = 284), an analysis of daily nebulisations in patients attending the A&E Department of the Pakistan Institute of Medical Sciences (March 2020 to July 2021), a prospective peak expiratory flow rate (PEFR) diary from participants (n = 40) with or without asthma and with or without paper mulberry sensitisation. We examined associations between pollen data and asthma exacerbations using Pearson correlation. Results: We found a strong positive correlation between mean paper mulberry pollen counts and clinical records of asthma exacerbations in patients sensitised to paper mulberry (Pearson correlation coefficient (r) = 0.86; P < 0.001), but not in non-sensitised patients (r = 0.32; P = 0.3). There was a moderate positive correlation between monthly nebulisation counts and pollen counts (r = 0.56; P = 0.03), and a strong negative correlation between percent predicted PEFR and pollen counts in sensitised asthma patients (r = -0.72, P < 0.001). However, these correlations were of low magnitude in the non-sensitised asthma (r = -0.16; P < 0.001) and sensitised non-asthma (r = -0.28; P < 0.001) groups. Conclusions: Our three approaches to analysis all showed an association between high paper mulberry pollen concentration in Islamabad and asthma exacerbations. Predicting pollen peaks could enable alerts and mobilise strategies to proactively manage these peaks of asthma exacerbations.

Asthma control and care among six public health clinic attenders in Malaysia: A cross-sectional study.

Background and Aims: Asthma is common in Malaysia but neglected. Achieving optimal asthma control and care is a challenge in the primary care setting. In this study, we aimed to identify the risk factors for poor asthma control and pattern of care among adults and children (5-17 years old) with asthma attending six public health clinics in Klang District, Malaysia. Methods: We conducted a cross-sectional study collecting patients' sociodemographic characteristics, asthma control, trigger factors, healthcare use, asthma treatment, and monitoring and use of asthma action plan. Descriptive statistics and stepwise logistic regression were used in data analysis. Results: A total of 1280 patients were recruited; 85.3% adults and 14.7% children aged 5-17 years old. Only 34.1% of adults had well-controlled asthma, 36.5% had partly controlled asthma, and 29.4% had uncontrolled asthma. In children, 54.3% had well-controlled asthma, 31.9% had partly controlled, and 13.8% had uncontrolled asthma. More than half had experienced one or more exacerbations in the last 1 year, with a mean of six exacerbations in adults and three in children. Main triggers for poor control in adults were haze (odds ratio [OR] 1.51; 95% confidence interval [CI] 1.13-2.01); cold food (OR 1.54; 95% CI 1.15-2.07), extreme emotion (OR 1.90; 95% CI 1.26-2.89); air-conditioning (OR 1.63; 95% CI 1.20-2.22); and physical activity (OR 2.85; 95% CI 2.13-3.82). In children, hot weather (OR 3.14; 95% CI 1.22-8.11), and allergic rhinitis (OR 2.57; 95% CI 1.13-5.82) contributed to poor control. The majority (81.7% of adults and 64.4% of children) were prescribed controller medications, but only 42.4% and 29.8% of the respective groups were compliant with the treatment. The importance of an asthma action plan was reported less emphasized in asthma education. Conclusion: Asthma control remains suboptimal. Several triggers, compliance to controller medications, and asthma action plan use require attention during asthma reviews for better asthma outcomes.

Healthcare resources, organisational support and practice in asthma in six public health clinics in Malaysia.

Asthma, a common chronic respiratory illness is mostly managed in primary care. We aimed to determine healthcare resources, organisational support, and doctors' practice in managing asthma in a Malaysian primary care setting. A total of six public health clinics participated. We found four clinics had dedicated asthma services. There was only one clinic which had a tracing defaulter system. Long-term controller medications were available in all clinics, but not adequately provided. Resources, educational materials, and equipment for asthma management were present, though restricted in number and not placed in main locations of the clinic. To diagnose asthma, most doctors used clinical judgement and peak flow metre measurements with reversibility test. Although spirometry is recommended to diagnose asthma, it was less practiced, being inaccessible and unskilled in using as the main reasons. Most doctors reported providing asthma self-management; asthma action plan, but for only half of the patients that they encountered. In conclusion, there is still room for improvement in the provision of clinic resources and support for asthma care. Utilising peak flow metre measurement and reversibility test suggest practical alternative in low resource for spirometry. Reinforcing education on asthma action plan is vital to ensure optimal asthma care.

Metabolic regulation by prostaglandin E2 impairs lung group 2 innate lymphoid cell responses.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) play a critical role in asthma pathogenesis. Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is associated with reduced signaling via EP2, a receptor for prostaglandin E2 (PGE2 ). However, the respective roles for the PGE2 receptors EP2 and EP4 (both share same downstream signaling) in the regulation of lung ILC2 responses has yet been deciphered. METHODS: The roles of PGE2 receptors EP2 and EP4 on ILC2-mediated lung inflammation were investigated using genetically modified mouse lines and pharmacological approaches in IL-33-induced lung allergy model. The effects of PGE2 receptors and downstream signals on ILC2 metabolic activation and effector function were examined using in vitro cell cultures. RESULTS: Deficiency of EP2 rather than EP4 augments IL-33-induced mouse lung ILC2 responses and eosinophilic inflammation in vivo. In contrast, exogenous agonism of EP4 and EP2 or inhibition of phosphodiesterase markedly restricts IL-33-induced lung ILC2 responses. Mechanistically, PGE2 directly suppresses IL-33-dependent ILC2 activation through the EP2/EP4-cAMP pathway, which downregulates STAT5 and MYC pathway gene expression and ILC2 energy metabolism. Blocking glycolysis diminishes IL-33-dependent ILC2 responses in mice where endogenous PG synthesis or EP2 signaling is blocked but not in mice with intact PGE2 -EP2 signaling. CONCLUSION: We have defined a mechanism for optimal suppression of mouse lung ILC2 responses by endogenous PGE2 -EP2 signaling which underpins the clinical findings of defective EP2 signaling in patients with NERD. Our findings also indicate that exogenously targeting the PGE2 -EP4-cAMP and energy metabolic pathways may provide novel opportunities for treating the ILC2-initiated lung inflammation in asthma and NERD.

Influences on indoor environmental trigger remediation uptake for children and young people with asthma: A scoping review.

INTRODUCTION: Children and young people (CYP) with asthma can benefit from reduced exposure to indoor environmental allergens and triggers but may not consistently have avoidance strategies implemented. To inform future interventions to increase trigger and allergen avoidance and enhance asthma control, a greater understanding of the influences on avoidance behaviours is necessary. METHODS: A systematic scoping review was selected to summarize evidence on what influences family uptake of indoor environmental asthma trigger avoidance strategies for CYP with asthma and identify research gaps. Primary studies of any design, including CYP (≤18 years) with asthma, and/or parent-carers, available in English and conducted since 1993, were eligible. Searches included nine databases, hand-searching reference lists and citation searching. FINDINGS: Thirty-three articles were included and are summarized narratively due to heterogeneity. Influences appear complex and multifactorial and include barriers to strategy uptake, health beliefs and personal motivation. Research specifically related to family understanding of allergic sensitisation status and exposure risks, and how these may inform avoidance implementation is required. Patient and public involvement (PPI) was not reported in included articles, although two studies used participatory methods. CONCLUSION: There is limited research on family asthma trigger management, particularly what influences current management behaviours. Variation in families' ability to identify important triggers, understand exposure risk and consistently reduce exposures warrants further exploratory research to explain how families reach avoidance decisions, and what future interventions should aim to address. Further PPI-informed research to address such gaps, could enable theory-based, person-centred interventions to improve the uptake of asthma trigger remediation. PATIENT OR PUBLIC CONTRIBUTION: An asthma-specific PPI group contributed to the decision-making for the funding for the wider project this review sits within. The findings of this scoping review have informed the subsequent phases of the project, and this was discussed with PPI groups (both adult and CYP groups) when proposing the next phases of the project.

Guidelines for the prevention and management of children and adolescents with COVID-19.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Mixed-methods evaluation of a nurse-led allergy clinic model in primary care: Feasibility trial.

INTRODUCTION: It is now widely acknowledged that there are serious shortcomings in allergy care provision for patients seen in primary care. We sought to assess the feasibility of delivering and evaluating a new nurse-led allergy service in primary care, measured by recruitment, retention and estimates of the potential impact of the intervention on disease-specific quality of life. METHODS: Mixed-methods evaluation of a nurse-led primary care-based allergy clinic in Edinburgh, UK undertaken during the period 2017-2021 with a focus on suspected food allergy and atopic eczema in young children, allergic rhinitis in children and young people, and suspected anaphylaxis in adults. Prior to March 2020, patients were seen face-to-face (Phase 1). Due to COVID-19 pandemic restrictions, recruitment was halted between March-August 2020, and a remote clinic was restarted in September 2020 (Phase 2). Disease-specific quality of life was measured at baseline and 6-12 weeks post intervention using validated instruments. Quantitative data were descriptively analysed. We undertook interviews with 16 carers/patients and nine healthcare professionals, which were thematically analysed. RESULTS: During Phase 1, 426/506 (84%) referred patients met the eligibility criteria; 40/46 (87%) of Phase 2 referrals were eligible. Males and females were recruited in approximately equal numbers. The majority (83%) of referrals were for possible food allergy or anaphylaxis. Complete data were available for 338/426 (79%) patients seen in Phase 1 and 30/40 (75%) in Phase 2. Compared with baseline assessments, there were improvements in disease-specific quality of life for most categories of patients. Patients/carers and healthcare professionals reported high levels of satisfaction, this being reinforced by the qualitative interviews in which convenience and speed of access to expert opinion, the quality of the consultation, and patient/care empowerment were particularly emphasised. CONCLUSION: This large feasibility trial has demonstrated that it is possible to recruit, deliver and retain individuals into a nurse-led allergy clinic with both face-to-face and remote consultations. Our data indicate that the intervention was considered acceptable to patients/carers and healthcare professionals. The before-after data of disease-specific quality of life suggest that the intervention may prove effective, but this now needs to be confirmed through a formal randomised controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov reference NCT03826953.

Community-based asthma assessment in young children: adaptations for a multicentre longitudinal study in South Asia.

Background: Systematic assessment of childhood asthma is challenging in low- and middle-income country (LMIC) settings due to the lack of standardised and validated methodologies. We describe the contextual challenges and adaptation strategies in the implementation of a community-based asthma assessment in four resource-constrained settings in Bangladesh, India, and Pakistan. Method: We followed a group of children of age 6-8 years for 12 months to record their respiratory health outcomes. The study participants were enrolled at four study sites of the 'Aetiology of Neonatal Infection in South Asia (ANISA)' study. We standardised the research methods for the sites, trained field staff for uniform data collection and provided a 'Child Card' to the caregiver to record the illness history of the participants. We visited the children on three different occasions to collect data on respiratory-related illnesses. The lung function of the children was assessed in the outreach clinics using portable spirometers before and after 6-minute exercise, and capillary blood was examined under light microscopes to determine eosinophil levels. Results: We enrolled 1512 children, 95.5% (1476/1512) of them completed the follow-up, and 81.5% (1232/1512) participants attended the lung function assessment tests. Pre- and post-exercise spirometry was performed successfully in 88.6% (1091/1232) and 85.7% (1056/1232) of children who attempted these tests. Limited access to health care services, shortage of skilled human resources, and cultural diversity were the main challenges in adopting uniform procedures across all sites. Designing the study implementation plan based on the local contexts and providing extensive training of the healthcare workers helped us to overcome these challenges. Conclusion: This study can be seen as a large-scale feasibility assessment of applying spirometry and exercise challenge tests in community settings of LMICs and provides confidence to build capacity to evaluate children's respiratory outcomes in future translational research studies.

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation.

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

Effects of non-steroidal anti-inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses: EAACI task force on eicosanoids consensus report in times of COVID-19.

Non-steroidal anti-inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti-inflammatory, antipyretic, and analgesic effects are applied against symptoms of respiratory infections, including SARS-CoV-2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID-19 also revealed the gaps in our understanding of their mechanism of action, selectivity, and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs-exacerbated respiratory disease (NERD). In this context, the consensus report summarizes currently available knowledge, novel discoveries, and controversies regarding the use of NSAIDs in COVID-19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID-19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarize the major knowledge gaps and unmet needs in current eicosanoid research.