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BackgroundAsthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. ObjectiveThe primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. MethodsBOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. ResultsThe last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. ConclusionsWe will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed. International Registered Report Identifier (IRRID)DERR1-10.2196/46741

Type-2 low asthma affects 30-50% of people with severe asthma and includes a phenotype characterized by sputum neutrophilia and resistance to corticosteroids. Airways inflammation in type-2 low asthma or COPD is potentially driven by persistent bacterial colonization of the lower airways by bacteria such as non-encapsulated Haemophilus influenzae (NTHi). Although pathogenic in the lower airways, NTHi is a commensal of the upper airways. It is not known to what extent these strains can invade airway epithelial cells, persist intracellularly and activate epithelial cell production of proinflammatory cytokines, and how this differs between the upper and lower airways. We studied NTHi infection of primary human bronchial epithelial cells (PBECs), primary nasal epithelial cells (NECs) and epithelial cell lines from upper and lower airways. NTHi strains differed in propensity for intracellular and paracellular invasion. We found NTHi was internalized within PBECs at 6 h, but live intracellular infection did not persist at 24 h. Confocal microscopy and flow cytometry showed NTHi infected secretory, ciliated and basal PBECs. Infection of PBECs led to induction of CXCL8, interleukin (IL)-1β, IL-6 and TNF. The magnitude of cytokine induction was independent of the degree of intracellular invasion, either by differing strains or by cytochalasin D inhibition of endocytosis, with the exception of the inflammasome-induced mediator IL-1β. NTHi-induced activation of TLR2/4, NOD1/2 and NLR inflammasome pathways was significantly stronger in NECs than in PBECs. These data suggest that NTHi is internalized transiently by airway epithelial cells and has capacity to drive inflammation in airway epithelial cells.

Mucosal associated invariant T (MAIT) cells are innate-like T lymphocytes, strikingly enriched at mucosal surfaces and characterized by a semi-invariant αβ T cell receptor (TCR) recognizing microbial derived intermediates of riboflavin synthesis presented by the MHC-Ib molecule MR1. At barrier sites MAIT cells occupy a prime position for interaction with commensal microorganisms, comprising the microbiota. The microbiota is a rich source of riboflavin derived antigens required in early life to promote intra-thymic MAIT cell development and sustain a life-long population of tissue resident cells. A symbiotic relationship is thought to be maintained in health whereby microbes promote maturation and homeostasis, and in turn MAIT cells can engage a TCR-dependent “tissue repair” program in the presence of commensal organisms conducive to sustaining barrier function and integrity of the microbial community. MAIT cell activation can be induced in a MR1-TCR dependent manner or through MR1-TCR independent mechanisms via pro-inflammatory cytokines interleukin (IL)-12/-15/-18 and type I interferon. MAIT cells provide immunity against bacterial, fungal and viral pathogens. However, MAIT cells may have deleterious effects through insufficient or exacerbated effector activity and have been implicated in autoimmune, inflammatory and allergic conditions in which microbial dysbiosis is a shared feature. In this review we summarize the current knowledge on the role of the microbiota in the development and maintenance of circulating and tissue resident MAIT cells. We also explore how microbial dysbiosis, alongside changes in intestinal permeability and imbalance between pro- and anti-inflammatory components of the immune response are together involved in the potential pathogenicity of MAIT cells. Whilst there have been significant improvements in our understanding of how the microbiota shapes MAIT cell function, human data are relatively lacking, and it remains unknown if MAIT cells can conversely influence the composition of the microbiota. We speculate whether, in a human population, differences in microbiomes might account for the heterogeneity observed in MAIT cell frequency across mucosal sites or between individuals, and response to therapies targeting T cells. Moreover, we speculate whether manipulation of the microbiota, or harnessing MAIT cell ligands within the gut or disease-specific sites could offer novel therapeutic strategies.

ABSTRACT Previous metagenomic studies in asthma have been limited by inadequate sequencing depth for species-level bacterial identification and by heterogeneity in clinical phenotyping. We hypothesize that chronic bacterial airways infection is a key “treatable trait” whose prevalence, clinical phenotype and reliable biomarkers need definition. In this study, we have applied a method for Oxford Nanopore sequencing for the unbiased metagenomic characterization of severe asthma. We optimized methods to compare performance of Illumina MiSeq, Nanopore sequencing, and RT-qPCR on total sputum DNA extracts against culture/MALDI-TOF for analysis of induced sputum samples from highly phenotyped severe asthma during clinical stability. In participants with severe asthma (n = 23) H. influenzae was commonly cultured (n = 8) and identified as the dominant bacterial species by metagenomic sequencing using an optimized method for Illumina MiSeq and Oxford Nanopore. Alongside superior operational characteristics, Oxford Nanopore achieved near complete genome coverage of H. influenzae and demonstrated a high level of agreement with Illumina MiSeq data. Clinically significant infection was confirmed with validated H. influenzae plasmid-based quantitative PCR assay. H. influenzae positive patients were found to have sputum neutrophilia and lower FeNO. In conclusion, using an optimized method of direct sequencing of induced sputum samples, H. influenzae was identified as a clinically relevant pathogen in severe asthma and was identified reliably using metagenomic sequencing. Application of these protocols in ongoing analysis of large patient cohorts will allow full characterization of this clinical phenotype. IMPORTANCE The human airways were once thought sterile in health. Now metagenomic techniques suggest bacteria may be present, but their role in asthma is not understood. Traditional culture lacks sensitivity and current sequencing techniques are limited by operational problems and limited ability to identify pathogens at species level. We optimized a new sequencing technique—Oxford Nanopore technologies (ONT)—for use on human sputum samples and compared it with existing methods. We found ONT was effective for rapidly analyzing samples and could identify bacteria at the species level. We used this to show Haemophilus influenzae was a dominant bacterium in the airways in people with severe asthma. The presence of Haemophilus was associated with a “neutrophilic” form of asthma - a subgroup for which we currently lack specific treatments. Therefore, this technique could be used to target chronic antibiotic therapy and in research to characterize the full breadth of bacteria in the airways.

Summary: Background: Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to selected microbes. We designed a study with the aim to discover and investigate the total microbiome of pleural infection and assess the correlation between bacterial patterns and 1-year survival of patients. Methods: We assessed 243 pleural fluid samples from the PILOT study, a prospective observational study on pleural infection, with 16S rRNA next generation sequencing. 20 pleural fluid samples from patients with pleural effusion due to a non-infectious cause and ten PCR-grade water samples were used as controls. Downstream analysis was done with the DADA2 pipeline. We applied multivariate Cox regression analyses to investigate the association between bacterial patterns and 1-year survival of patients with pleural infection. Findings: Pleural infection was predominately polymicrobial (192 [79%] of 243 samples), with diverse bacterial frequencies observed in monomicrobial and polymicrobial disease and in both community-acquired and hospital-acquired infection. Mixed anaerobes and other Gram-negative bacteria predominated in community-acquired polymicrobial infection whereas Streptococcus pneumoniae prevailed in monomicrobial cases. The presence of anaerobes (hazard ratio 0·46, 95% CI 0·24–0·86, p=0·015) or bacteria of the Streptococcus anginosus group (0·43, 0·19–0·97, p=0·043) was associated with better patient survival, whereas the presence (5·80, 2·37–14·21, p

Abstract Background Azithromycin is an orally active synthetic macrolide antibiotic with a wide range of anti-bacterial, anti-inflammatory and antiviral properties. It is a safe, inexpensive, generic licenced drug available worldwide and manufactured to scale and is a potential candidate therapy for pandemic coronavirus disease 2019 (COVID-19). Azithromycin was widely used to treat severe SARS-CoV and MERS-CoV, but to date, no randomised data are available in any coronavirus infections. Other ongoing trials are exploring short courses of azithromycin either in early disease, within the first 7 days of symptoms, when azithromycin’s antiviral properties may be important, or late in disease when anti-bacterial properties may reduce the risk of secondary bacterial infection. However, the molecule’s anti-inflammatory properties, including suppression of pulmonary macrophage-derived pro-inflammatory cytokines such as interleukins-1β, -6, -8, and -18 and cytokines G-CSF and GM-CSF may provide a distinct therapeutic benefit if given in as a prolonged course during the period of progression from moderate to severe disease. Methods ATOMIC2 is a phase II/III, multi-centre, prospective, open-label, two-arm randomised superiority clinical trial of azithromycin versus standard care for adults presenting to hospital with COVID-19 symptoms who are not admitted at initial presentation. We will enrol adults, ≥ 18 years of age assessed in acute hospitals in the UK with clinical diagnosis of COVID-19 infection where management on an ambulatory care pathway is deemed appropriate. Participants will be randomised in a 1:1 ratio to usual care or to azithromycin 500 mg orally daily for 14 days with telephone follow-up at days 14 and 28. The primary objective is to compare the proportion with either death or respiratory failure requiring invasive or non-invasive mechanical ventilation over 28 days from randomisation. Secondary objectives include mortality/respiratory failure in those with a PCR-confirmed diagnosis; all-cause mortality; progression to pneumonia; progression to severe pneumonia; peak severity of illness and mechanistic analysis of blood and nasal biomarkers. Discussion This trial will determine the clinical utility of azithromycin in patients with moderately severe, clinically diagnosed COVID-19 and could be rapidly applicable worldwide. Trial registration ClinicalTrials.gov NCT04381962 . Registered on 11 May 2020. EudraCT identifier 2020-001740-26 . Opened for accrual on 29 May 2020.

Mucosal associated invariant T (MAIT) cells are striking in their abundance and their strict conservation across 150 million years of mammalian evolution, implying they must fulfill critical immunological function(s). MAIT cells are defined by their expression of a semi-invariant αβ TCR which recognizes biosynthetic derivatives of riboflavin synthesis presented on MR1. Initial studies focused on their role in detecting predominantly intracellular bacterial and mycobacterial infections. However, it is now recognized that there are several modes of MAIT cell activation and these are related to activation of distinct transcriptional programmes, each associated with distinct functional roles. In this minireview, we summarize current knowledge from human and animal studies of MAIT cell activation induced (1) in an MR1-TCR dependent manner in the context of inflammatory danger signals and associated with antibacterial host defense; (2) in an MR1-TCR independent manner by the cytokines interleukin(IL)-12/-15/-18 and type I interferon, which is associated with antiviral responses; and (3) a recently-described TCR-dependent “tissue repair” programme which is associated with accelerated wound healing in the context of commensal microbiota. Because of this capability for diverse functional responses in diverse immunological contexts, these intriguing cells now appear to be multifunctional effectors central to the interface of innate and adaptive immunity.

MAIT cells are abundant in the lungs and confer protection against bacterial pathogens. Whilst activation of these cells has been described during viral infections, here van Wilgenburg and colleagues show that in a murine model MAIT cells contribute to the protective host immune response to influenza virus infection.

Mucosal associated invariant T (MAIT) cells have been implicated in antibacterial responses. Here the authors show MAIT cells confer IFN-γ-mediated protection from lethal infection in a mouse model of Legionella infection, which can be enhanced by synthetic MR1 ligands.

Type-2 low asthma affects 30-50% of people with severe asthma and includes a phenotype characterized by sputum neutrophilia and resistance to corticosteroids. Airways inflammation in type-2 low asthma or COPD is potentially driven by persistent bacterial colonization of the lower airways by bacteria such as non-encapsulated Haemophilus influenzae (NTHi). Although pathogenic in the lower airways, NTHi is a commensal of the upper airways. It is not known to what extent these strains can invade airway epithelial cells, persist intracellularly and activate epithelial cell production of proinflammatory cytokines, and how this differs between the upper and lower airways. We studied NTHi infection of primary human bronchial epithelial cells (PBECs), primary nasal epithelial cells (NECs) and epithelial cell lines from upper and lower airways. NTHi strains differed in propensity for intracellular and paracellular invasion. We found NTHi was internalized within PBECs at 6 h, but live intracellular infection did not persist at 24 h. Confocal microscopy and flow cytometry showed NTHi infected secretory, ciliated and basal PBECs. Infection of PBECs led to induction of CXCL8, interleukin (IL)-1β, IL-6 and TNF. The magnitude of cytokine induction was independent of the degree of intracellular invasion, either by differing strains or by cytochalasin D inhibition of endocytosis, with the exception of the inflammasome-induced mediator IL1β. NTHi-induced activation of TLR2/4, NOD1/2 and NLR inflammasome pathways was significantly stronger in NECs than in PBECs. These data suggest that NTHi is internalized transiently by airway epithelial cells and has capacity to drive inflammation in airway epithelial cells. [ABSTRACT FROM AUTHOR]

Mucosal associated invariant T (MAIT) cells are innate-like T lymphocytes, strikingly enriched at mucosal surfaces and characterized by a semi-invariant ab T cell receptor (TCR) recognizing microbial derived intermediates of riboflavin synthesis presented by the MHC-Ib molecule MR1. At barrier sites MAIT cells occupy a prime position for interaction with commensal microorganisms, comprising the microbiota. The microbiota is a rich source of riboflavin derived antigens required in early life to promote intra-thymic MAIT cell development and sustain a life-long population of tissue resident cells. A symbiotic relationship is thought to be maintained in health whereby microbes promote maturation and homeostasis, and in turn MAIT cells can engage a TCRdependent "tissue repair" program in the presence of commensal organisms conducive to sustaining barrier function and integrity of the microbial community. MAIT cell activation can be induced in a MR1-TCR dependent manner or through MR1-TCR independent mechanisms via pro-inflammatory cytokines interleukin (IL)-12/-15/-18 and type I interferon. MAIT cells provide immunity against bacterial, fungal and viral pathogens. However, MAIT cells may have deleterious effects through insufficient or exacerbated effector activity and have been implicated in autoimmune, inflammatory and allergic conditions in which microbial dysbiosis is a shared feature. In this review we summarize the current knowledge on the role of the microbiota in the development and maintenance of circulating and tissue resident MAIT cells. We also explore how microbial dysbiosis, alongside changes in intestinal permeability and imbalance between pro- and anti-inflammatory components of the immune response are together involved in the potential pathogenicity of MAIT cells. Whilst there have been significant improvements in our understanding of how the microbiota shapes MAIT cell function, human data are relatively lacking, and it remains unknown if MAIT cells can conversely influence the composition of the microbiota. We speculate whether, in a human population, differences in microbiomes might account for the heterogeneity observed in MAIT cell frequency across mucosal sites or between individuals, and response to therapies targeting T cells. Moreover, we speculate whether manipulation of the microbiota, or harnessing MAIT cell ligands within the gut or disease-specific sites could offer novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Abbreviations: ALEX SP 2 sp , Allergy Explorer, version 2; Cor a 1, hazelnut allergen; ISAC, ImmunoCAP ISAC; Mal d 1, apple allergen; OAS, oral allergy syndrome; sIgE, specific IgE; SPT, skin prick test. GRAPH RECOMBINANT MULTIMERIC DOG ALLERGEN PREVENTS AIRWAY HYPERRESPONSIVENESS IN A MODEL OF ASTHMA... Julian M. Stark, Jielu Liu, Christopher A. Tibbitt, Murray Christian, Junjie Ma, Anna Wintersand, Josefine Dunst, Taras Kreslavsky, Ben Murrell, Mikael Adner, Hans Grönlund, Guro Gafvelin, Jonathan M. Coquet Intranasal administration of dog allergen extracts induces airway hyperresponsiveness and robust T SB H sb 17 cell-driven neutrophilia. Yuhan Xing, Maggie H. Wang, Ting-Fan Leung, Chun-Kwok Wong, Marjut Roponen, Bianca Schaub, Jing Li, Gary W. K. Wong The prevalence of asthma and related atopic disorders was significantly lower in rural children when compared to their urban counterparts. [Extracted from the article]

Background: The most recognizable phenotype of severe asthma comprises people who are blood eosinophil and FeNO‐high, driven by type 2 (T2) cytokine biology, which responds to targeted biological therapies. However, in many people with severe asthma, these T2 biomarkers are suppressed but poorly controlled asthma persists. The mechanisms driving asthma in the absence of T2 biology are poorly understood. Objectives: To explore airway pathology in T2 biomarker‐high and ‐low severe asthma. Methods: T2 biomarker‐high severe asthma (T2‐high, n = 17) was compared with biomarker‐intermediate (T2‐intermediate, n = 21) and biomarker‐low (T2‐low, n = 20) severe asthma and healthy controls (n = 28). Bronchoscopy samples were processed for immunohistochemistry, and sputum for cytokines, PGD2 and LTE4 measurements. Results: Tissue eosinophil, neutrophil and mast cell counts were similar across severe asthma phenotypes and not increased when compared to healthy controls. In contrast, the remodelling features of airway smooth muscle mass and MUC5AC expression were increased in all asthma groups compared with health, but similar across asthma subgroups. Submucosal glands were increased in T2‐intermediate and T2‐low asthma. In spite of similar tissue cellular inflammation, sputum IL‐4, IL‐5 and CCL26 were increased in T2‐high versus T2‐low asthma, and several further T2‐associated cytokines, PGD2 and LTE4, were increased in T2‐high and T2‐intermediate asthma compared with healthy controls. Conclusions: Eosinophilic tissue inflammation within proximal airways is suppressed in T2 biomarker‐high and T2‐low severe asthma, but inflammatory and structural cell activation is present, with sputum T2‐associated cytokines highest in T2 biomarker‐high patients. Airway remodelling persists and may be important for residual disease expression beyond eosinophilic exacerbations. Registered at ClincialTrials.gov: NCT02883530. [ABSTRACT FROM AUTHOR]

Asthma is a complex, heterogeneous condition that affects over 350 million people globally. It is characterised by bronchial hyperreactivity and airways inflammation. A subset display marked airway neutrophilia, associated with worse lung function, higher morbidity and poor response to treatment. In these individuals, recent metagenomic studies have identified persistent bacterial infection, particularly with non-encapsulated strains of the Gram-negative bacterium Haemophilus influenzae. Here we review knowledge of non-typeable H. influenzae (NTHi) in the microbiology of asthma, the immune consequences of mucosal NTHi infection, various immune evasion mechanisms, and the clinical implications of NTHi infection for phenotyping and targeted therapies in neutrophilic asthma. Airway neutrophilia is associated with production of neutrophil chemokines and proinflammatory cytokines in the airways, including interleukin (IL)-1β, IL-6, IL-8, IL-12, IL-17A and tumour necrosis factor. NTHi adheres to and invades the lower respiratory tract epithelium, inducing the NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes. NTHi reduces expression of tight-junction proteins, impairing epithelial integrity, and can persist intracellularly. NTHi interacts with rhinoviruses synergistically via upregulation of intracellular cell adhesion molecule 1 and promotion of a neutrophilic environment, to which NTHi is adapted. We highlight the clinical relevance of this emerging pathogen and its relevance for the efficacy of long-term macrolide therapy in airways diseases, we identify important unanswered questions and we propose future directions for research. [ABSTRACT FROM AUTHOR]

The main functional consequence of type-2 inflammation is airflow limitation as a result of airway mucus plugging, airway wall oedema and thickening, airway smooth muscle hyperplasia and the induction of airway hyperresponsiveness. Keywords: airway markers; asthma; eosinophils; inflammation; nitric oxide EN airway markers asthma eosinophils inflammation nitric oxide 573 577 5 07/19/22 20220801 NES 220801 Biologic therapies targeting components of the type-2 inflammatory response seen in many patients with obstructive airways disease have had a dramatic impact in the clinic. Type-2 airway inflammation is detected in clinical practice by assessing fractional exhaled nitric oxide (reflecting airway IL-13 activity) and blood eosinophils (reflecting systemic IL-5 activity). Sub-stratification of type-2 high airway disease for therapeutic decision-making: A "bomb" (blood eosinophils) meets "magnet" (FeNO) framework. [Extracted from the article]

The article presents a study on the association of fractional exhaled nitric oxide and blood eosinophils with inflammation observed in the sputum and blood compartments in severe asthma. Topics discussed include the prognostic information on the occurrence of severe asthma attacks being provided by fractional exhaled nitric oxide and the blood eosinophil, the methods used in the study, and limitations of the study.

Summary: Azithromycin (AZM) is a synthetic macrolide antibiotic effective against a broad range of bacterial and mycobacterial infections. Due to an additional range of anti‐viral and anti‐inflammatory properties, it has been given to patients with the coronaviruses SARS‐CoV or MERS‐CoV. It is now being investigated as a potential candidate treatment for SARS‐CoV‐2 having been identified as a candidate therapeutic for this virus by both in vitro and in silico drug screens. To date there are no randomised trial data on its use in any novel coronavirus infection, although a large number of trials are currently in progress. In this review, we summarise data from in vitro, murine and human clinical studies on the anti‐viral and anti‐inflammatory properties of macrolides, particularly AZM. AZM reduces in vitro replication of several classes of viruses including rhinovirus, influenza A, Zika virus, Ebola, enteroviruses and coronaviruses, via several mechanisms. AZM enhances expression of anti‐viral pattern recognition receptors and induction of anti‐viral type I and III interferon responses. Of relevance to severe coronavirus‐19 disease (COVID‐19), which is characterised by an over‐exuberant innate inflammatory response, AZM also has anti‐inflammatory properties including suppression of IL‐1beta, IL‐2, TNF and GM‐CSF. AZM inhibits T cells by inhibiting calcineurin signalling, mammalian target of rapamycin activity and NFκB activation. AZM particularly targets granulocytes where it concentrates markedly in lysosomes, particularly affecting accumulation, adhesion, degranulation and apoptosis of neutrophils. Given its proven safety, affordability and global availability, tempered by significant concerns about antimicrobial stewardship, there is an urgent mandate to perform well‐designed and conducted randomised clinical trials. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a new rapidly spreading infectious disease. Current guidance from the World Health Organization (WHO) highlights asthmatics as a high-risk group for severe illness from COVID-19. Viruses are common triggers of asthma exacerbations and the current SARS-CoV-2 pandemic raises several questions regarding the optimum management strategies. Here, we discuss the contentious issue of whether the mainstay therapy systemic corticosteroids should be used in the routine management of COVID-19-associated asthma exacerbations. Recent guidance from the WHO has advised against the use of corticosteroids if COVID-19 is suspected due to concerns that these agents may impair protective innate antiviral immune responses. This may not be appropriate in the unique case of asthma exacerbation, a syndrome associated with augmented type 2 inflammation, a disease feature that is known to directly inhibit antiviral immunity. Corticosteroids, through their suppressive effects on type 2 inflammation, are thus likely to restore impaired antiviral immunity in asthma and, in contrast to non-asthmatic subjects, have beneficial clinical effects in the context of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Dupilumab shows improvement in validated disease specific quality of life scores compared with placebo Larger studies are needed to improve the certainty of evidence for Omalizumab and Mepolizumab Further data on longer term outcomes, cost effectiveness and those with less severe disease are needed Chronic rhinosinusitis (CRS) refers to inflammation of the nasal sinuses and mucosa, with persistence of sinus inflammation and clinical manifestations beyond 12 weeks.1 CRS affects between 6 and 12% of adults and is a cause of reduced quality of life (QoL) and high healthcare costs.2 Management consisted of topical and systemic glucocorticoids, antibiotics and often repeated sinus surgery. The review found evidence of improvement in disease-specific health-related quality of life and disease severity for patients with severe CRSwNP treated with all three classes of biologics compared with placebo. [Extracted from the article]

A correction is presented to the article "COVID-19 related Genes in Sputum Cells in Asthma: Relationship to Demographic Features and Corticosteroids" which appeared in the July 1, 2020 issue.

The article informs that eosinophilic airway inflammation is present in approximately half of patients with asthma, and it is particularly associated with asthma attacks. Topics include the two anti– Interleukin 5 (IL5) monoclonal antibodies are licensed for use in asthma and can be administered subcutaneously are mepolizumab, and benralizumab; and both anti–IL-5 monoclonal antibodies have proven efficacy in decreasing the frequency of asthma exacerbations.