Airway Disease Research Articles

Microscopic Small Airway Abnormalities Identified in Early Idiopathic Pulmonary Fibrosis In Vivo Using Endobronchial Optical Coherence Tomography.

Idiopathic pulmonary fibrosis (IPF) affects subpleural lung, but is considered to spare small airways. Micro-CT studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. We use EB-OCT to evaluate small airways in early IPF and control subjects in vivo. EB-OCT was performed in 12 IPF and 5 control subjects (matched by age, sex, smoking-history, height, BMI). IPF subjects had early disease with mild restriction (FVC: 83.5% predicted), diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for UIP present) and less affected (some but not all criteria for UIP present) sites. Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. Compared to control subjects (mean: 11.2 bronchioles/cm3; SD: 6.2), there was significant bronchiole reduction in IPF subjects (42% loss; mean: 6.5/cm3; SD: 3.4; p=0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; p<0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; p=0.024) sites. Stereology metrics showed IPF affected small airways were significantly larger and more distorted/irregular than in IPF less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (p=0.36-1.0). EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30 and 50%), even in areas minimally affected by disease, compared to matched controls. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.

Associations of obesity with chronic inflammatory airway diseases and mortality in adults: a population-based investigation

BackgroundThe association between obesity and respiratory diseases has been confirmed. However, few studies have reported the relationship between obesity and the risk and mortality of chronic inflammatory airway disease (CIAD). The aim of this study was to reveal the association between obesity and the risk of CIAD, and mortality in patients with CIAD.MethodsThe study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2018 among adults aged 20 years and above. All participants were grouped according to body mass index (BMI) and waist circumference (WC) levels to study the relationship between obesity and CIAD. Multivariate logistic regression analysis was utilized to examine the connection between CIAD and obesity in a cross-sectional study. The association between obesity and all-cause mortality in individuals with CIAD was examined using multiple cox regression models and smooth curve fitting in a prospective cohort study.ResultsWhen stratified based on BMI in comparison to the normal weight group, the ORs with 95%CIs of CIAD for underweight and obesity were 1.39 (1.01–1.93) and 1.42 (1.27–1.58), respectively. The OR with 95%CI of CIAD for obesity was 1.20 (1.09–1.31) when stratified according to WC. Additionally, underweight was associated with a higher mortality (HR = 2.44, 95% CI = 1.31–4.55), whereas overweight (HR = 0.58,95% CI = 0.39–0.87) and obesity (HR = 0.59,95% CI = 0.4–0.87) were associated with a lower mortality (P for trend < 0.05). There was a non-linear association between BMI and all-cause mortality (P for non-linear = 0.001). An analysis of a segmentation regression model between BMI and all-cause mortality revealed a BMI turning point value of 32.4 kg/m2. The mortality of CIAD patients was lowest when BMI was 32.4 kg/m2. When BMI ≤ 32.4 kg/m2, BMI was inversely associated with all-cause mortality in patients with CIAD (HR: 0.92, 95%CI:0.88–0.97). However, when BMI > 32.4 kg/m2, there was no association between BMI and all-cause mortality (HR:1.02, 95%CI:0.97–1.06).ConclusionCompared to normal weight, underweight and obesity were associated with the increased risk of CIAD. Underweight was associated with increased all-cause mortality, while overweight was associated with reduced all-cause mortality. There was a non-linear association between BMI and all-cause mortality in patients with CIAD. The all-cause mortality was lowest when BMI was 32.4 kg/m2.

Role of dietary supplements in the treatment of asthma - a narrative review

Introduction: Asthma is a common inflammatory disease of airway affecting both adults and children. In a large number of cases asthma remains poorly controlled. There is a need to find an additional therapeutic demeanour alleviating symptoms and lowering the risk complications in a long-term. Recently, increasing number of studies has been examining dietary supplements in regards to their anti-inflammatory, immunomodulatory, anti-remodelling properties and their use in asthmatic patients. Aim of the Study: The aim of the study was to collect and analyse current literature regarding influence of different dietary supplements on the course of asthma in both adults and children. Methods and Materials: Extensive research was conducted using PubMed and Google Scholar, with the primary focus on literature from the past 5 years. Firstly, potential dietary supplements affecting course of asthma were collected. The names of the substances were juxtaposed with term “Asthma” to gather data regarding their effect on occurrence and control of asthma and potential mechanisms responsible for it. Additionally, references from selected articles were included in the analysis. Results: Dietary supplements show promising results in decreasing asthma symptoms and lowering inflammation of airway. However, our study revealed that in current state of knowledge there is a deficit of studies performed on humans, especially large-scale, prospective studies that assess the efficacy of different doses of dietary supplements. Thus, further research of dietary supplements in asthma is needed, especially large-scale randomised controlled trials.

Clinical and computed tomography findings in cats with nasopharyngeal stenosis.

Concurrent anomalies are often found in nasopharyngeal stenosis and choanal atresia; some seem to be of primary nature, whereas others may be coincidental. This study aimed to report the computed tomography features and related comorbidities of these diseases. A cross-sectional retrospective study was performed using case and control groups defined according to the presence of signs of upper airway disease and the presence/absence of nasopharyngeal stenosis, respectively. The inclusion criteria were full-head tomography scans and access to clinical records. The exclusion criteria were brachycephalic breed, head trauma and neoplasm. Clinical and computed tomographic findings and relevant comorbidities were recorded. Forty-three cats were included, 23 cases and 20 controls. The case group was significantly younger, had more paranasal sinus anomalies and never had turbinate lysis, also, had significantly more soft palate anomalies, which was significantly shorter. Nasopharyngeal stenosis varied from membrane appearance to partial or complete adhesion of the soft palate to the nasopharynx, was mainly located in the caudal region of the nasopharynx and was imperforated in approximately half of the cases. Imperforated membranes were significantly thicker in the sagittal plane and were significantly associated with nasal obstruction and soft tissue attenuation of the tympanic bulla. Hiatal hernia and ventricular asymmetry were only encountered in three and two cases, respectively, with nasopharyngeal stenosis. Computed tomography in cats with nasopharyngeal stenosis can identify concurrent anomalies, can help to differentiate a possible choanal atresia and evaluate the magnitude of its significance.

The Miasmatic Approach in the Management of Bronchial Asthma in Homoeopathy

Bronchial asthma is a chronic obstructive disease of airways affecting bronchi, resulting in bronchoconstriction, tightening of chest and airway inflammation. Asthma remains a disease with clearly unsatisfactory therapeutics. With the mounting evidence in support of asthma being an inflammatory illness, anti-inflammatory agents have now become prerequisite for the long-term management of asthma. Along with anti-inflammatory agents, there is a need to search for other effective therapies to treat every aspect of the disease. Although asthma is a global disease, there are important differences in epidemiology, clinical spectrum and management practices in India.

Clinical efficacy of bronchoalveolar lavage in the treatment of small airway diseases in children

ObjectiveThis study aimed to evaluate the efficacy of bronchoalveolar lavage (BAL) in the treatment of children with small airway diseases.MethodsChildren [n = 112; boys: 76, girls: 36 (ratio 2.1:1); age range: 1 month–10 years; median age: 12 months] with small airway diseases diagnosed by high-resolution computed tomography (HRCT) were enrolled in this study. The patients were assigned to either the BAL group (BAL and conventional therapy) or the control group (conventional therapy only). The duration of cough, fever, wheezing, hospitalization duration, disease course before admission, treatment cost, HRCT recovery time, and re-hospitalization rate were compared between the two groups.ResultsThe median disease course before admission of the BAL group patients was longer than that of the controls (p = 0.006). The duration of cough and wheezing in the BAL group was significantly longer than that in the control group (p = 0.012 and p = 0.001, respectively). The recovery time of cough, the re-hospitalization rate, and the total expenditure incurred for the BAL group were lower than those for the control group (p = 0.027, p = 0.026, and p = 0.000, respectively). At 2 months after discharge, the small airway lesions were found to be absorbed in 86.2% of BAL group patients vs. 64.1% of control group patients. At 6 months after discharge, the lesions were not fully absorbed in 3.4% of the BAL group patients compared to 20.5% in the control group patients.ConclusionBAL is suitable for patients with a long disease course before admission, a long duration of coughing, and recurrent wheezing. BAL treatment of small airway diseases in children can promote the disappearance of clinical symptoms, accelerate the improvement of imaging, reduce the rate of re-hospitalization, and reduce the cost of treatment.

Heat-killed Akkermansia muciniphila ameliorates allergic airway inflammation in mice

Allergic asthma (AA) is a common inflammatory airway disease characterized by increased airway hyper-responsiveness (AHR), inflammation, and remodeling. Akkermansia muciniphila is a strictly anaerobic bacterium residing in the gut and is a promising next-generation probiotic to improve metabolic inflammatory syndrome. A recent study suggested the beneficial effect of live A. muciniphila on allergic airway inflammation (AAI) in mice. However, whether the heat-killed form can improve AAI requires further investigation. Mice sensitized and challenged with house dust mites (HDM) develop AA hallmarks including inflammatory cell infiltration, goblet cell hyperplasia, and subepithelial collagen deposition in the lungs. These phenomena were reversed by oral administration of the heat-killed A. muciniphila strain EB-AMDK19 (AMDK19-HK) isolated from the feces of healthy Koreans. Furthermore, AMDK19-HK diminished the HDM-induced AHR to inhaled methacholine, lung mast cell accumulation, and serum HDM-specific IgE levels. It also led to the overall suppression of IL-4, IL-13, and eotaxin production in bronchoalveolar lavage fluids, and Il4, Il5, Il13, and Ccl17 gene expression in lung tissues. Moreover, AMDK19-HK suppressed Th2-associated cytokine production in the splenocytes of HDM-sensitized mice in vitro. Additionally, a combination of 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis in cecal samples revealed that AMDK19-HK modulated the relative abundance of circulating SCFA-associated gut genera, including a positive correlation with Lachnospiraceae_ NK4A136_group and a negative correlation with Lachnoclostridium and significantly increased cecal SCFA concentrations. Finally, AMDK19-HK improved intestinal mucosal barrier function. These results suggest that the oral administration of AMDK19-HK ameliorates HDM-induced AAI in mice by suppressing Th2-mediated immune responses and could have a protective effect against AA development.

Unraveling the Genetic Basis of Combined Deafness and Male Infertility Phenotypes through High‐Throughput Sequencing in a Unique Cohort from South India

AbstractThe co‐occurrence of sensorineural hearing loss and male infertility has been reported in several instances, suggesting potential shared genetic underpinnings. One such example is the contiguous gene deletion of CATSPER2 and STRC genes, previously associated with deafness‐infertility syndrome (DIS) in males. Fifteen males with both hearing loss and infertility from southern India after exclusion for the DIS contiguous gene deletion and the FOXI1 gene mutations are subjected to exome sequencing. This resolves the genetic etiology in four probands for both the phenotypes; In the remaining 11 probands, two each conclusively accounted for deafness and male infertility etiologies. Genetic heterogeneity is well reflected in both phenotypes. Four recessive (TRIOBP, SLC26A4, GJB2, COL4A3) and one dominant (SOX10) for the deafness; six recessive genes (LRGUK, DNAH9, ARMC4, DNAH2, RSPH6A, and ACE) for male infertility can be conclusively ascribed. LRGUK and RSPH6A genes are implicated earlier only in mice models, while the ARMC4 gene is implicated in chronic destructive airway diseases due to primary ciliary dyskinesia. This study would be the first to document the role of these genes in the male infertility phenotype in humans. The result suggests that deafness and infertility are independent events and do not segregate together among the probands.

Interstitial Lung Disease and Progressive Pulmonary Fibrosis: a World Trade Center Cohort 20-Year Longitudinal Study.

World Trade Center (WTC) exposure is associated with obstructive airway diseases and sarcoidosis. There is limited research regarding the incidence and progression of non-sarcoidosis interstitial lung diseases (ILD) after WTC-exposure. ILD encompasses parenchymal diseases which may lead to progressive pulmonary fibrosis (PPF). We used the Fire Department of the City of New York's (FDNY's) WTC Health Program cohort to estimate ILD incidence and progression. This longitudinal study included 14,525 responders without ILD prior to 9/11/2001. ILD incidence and prevalence were estimated and standardized to the US 2014 population. Poisson regression modeled risk factors, including WTC-exposure and forced vital capacity (FVC), associated with ILD. Follow-up time ended at the earliest of incident diagnosis, end of study period/case ascertainment, transplant or death. ILD developed in 80/14,525 FDNY WTC responders. Age, smoking, and gastroesophageal reflux disease (GERD) prior to diagnosis were associated with incident ILD, though FVC was not. PPF developed in 40/80 ILD cases. Among the 80 cases, the average follow-up time after ILD diagnosis was 8.5 years with the majority of deaths occurring among those with PPF (PPF: n = 13; ILD without PPF: n = 6). The prevalence of post-9/11 ILD was more than two-fold greater than the general population. An exposure-response gradient could not be demonstrated. Half the ILD cases developed PPF, higher than previously reported. Age, smoking, and GERD were risk factors for ILD and PPF, while lung function was not. This may indicate that lung function measured after respirable exposures would not identify those at risk for ILD or PPF.

Pulmonary Function, Computed Tomography Lung Abnormalities, and Small Airway Disease after COVID-19: 3-, 6-, and 9-Month Follow-Up

Background/Objectives: Coronavirus disease 2019 (COVID-19) course may differ among individuals—in particular, those with comorbidities may have severe pneumonia, requiring oxygen supplementation or mechanical ventilation. Post-COVID-19 long-term structural changes in imaging studies can contribute to persistent respiratory disturbance. This study aimed to investigate COVID-19 sequels affecting the possibility of persistent structural lung tissue abnormalities and their influence on the respiratory function of peripheral airways and gas transfer. Methods: Patients were divided into two groups according to severity grades described by the World Health Organization. Among the 176 hospitalized patients were 154 patients with mask oxygen supplementation and 22 patients with high-flow nasal cannula (HFNC) or mechanical ventilation. All tests were performed at 3, 6, and 9 months post-hospitalization. Results: Patients in the severe/critical group had lower lung volumes in FVC, FVC%, FEV1, FEV1%, LC, TLC%, and DLCO% at three months post-hospitalization. At 6 and 9 months, neither group had significant FVC and FEV1 value improvements. The MEF 25–75 values were not significantly higher in the mild/moderate group than in the severe/critical group at three months. There were weak significant correlations between FVC and FEV1, MEF50, MEF 75, plethysmography TLC, disturbances in DLCO, and total CT abnormalities in the severe/critical group at three months. In a mild/moderate group, there was a significant negative correlation between the spirometry, plethysmography parameters, and CT lesions in all periods. Conclusions: Persistent respiratory symptoms post-COVID-19 can result from fibrotic lung parenchyma and post-infectious stenotic small airway changes not visible in CT, probably due to persistent inflammation.

Fiber rich food suppressed airway inflammation, GATA3 + Th2 cells, and FcεRIα+ eosinophils in asthma

BackgroundAllergic Asthma is a disease presenting various endotypes and no current therapies act curative but alleviate disease symptoms. Dietary interventions are gaining increasing importance in regulating immune responses. Furthermore, short chain fatty acids (SFCA), as the main products of dietary fiber’s fermentation by the gut bacteria, ameliorate the pathogenesis and disease burden of different illnesses including asthma. Nevertheless, the connection and crosstalk between the gut and lung is poorly understood.ObjectiveIn this work, the role of high fiber diet on the development of allergic asthma at baseline and after exacerbation of disease induced by respiratory viruses was investigated.MethodsHereby, SCFA in serum of asthmatic and non-asthmatic pre-school children before and after airway disease symptoms were analyzed. Moreover, the effect of high fiber diet in vivo in a murine model of house dust mite extract (HDM) induced allergic asthma and in the end in isolated lung and spleen cells infected ex vivo with Rhinovirus was analyzed.ResultsIn this study, a decrease of the SCFA 3-Hydroxybutyric acid in serum of asthmatic children after symptomatic episodes at convalescent visit as compared to asthmatic and control children at baseline visit was observed. In experimental asthma, in mice fed with high fiber diet, a reduced lung GATA3 + Th2 type mediated inflammation, mucus production and collagen deposition and expression of Fc epsilon receptor Ia (FcεRIa) in eosinophils was observed. By contrast, the CD8+ memory effector T cells were induced in the lungs of asthmatic mice fed with high fiber diet. Then, total lung cells from these asthmatic mice fed with either standard food or with fiber rich food were infected with RV ex vivo. Here, RV1b mRNA was found significantly reduced in the lung cells derived from fiber rich food fed mice as compared to those derived from standard food fed asthmatic mice. Looking for the mechanism, an increase in CD8+ T cells in RV infected spleen cells derived from fiber rich fed asthmatic mice, was observed.ConclusionConvalescent preschool asthmatic children after a symptomatic episode have less serum ß-Hydroxybutyric acid as compared to control and asthmatic children at baseline visit. Fiber rich diet associated with anti-inflammatory effects as well as anti-allergic effects by decreasing Type 2 and IgE mediated immune responses and inducing CD8+ memory effector T cells in a murine model of allergic asthma. Finally, ex vivo infection with Rhinovirus (RV) of total lung cells from asthmatic mice fed with fiber rich food led to a decreased RV load as compared to mice fed with standard food. Moreover, spleen cells derived from asthmatic mice fed with fiber rich food induced CD8+ T cells after ex vivo infection with RV.Clinical implicationsDietary interventions with increased content in natural fibers like pectins would ameliorate asthma exacerbations. Moreover, respiratory infection in asthma downregulated SCFA in the gut contributing to asthma exacerbations.

The Possible Roles of IL-4/IL-13 in the Development of Eosinophil-Predominant Severe Asthma

Bronchial asthma is characterized by airway inflammation, airway hyperresponsiveness, and reversible airway obstruction. Eosinophils contribute to the pathogenesis of airway disease mainly by releasing eosinophil-specific granules, lipid mediators, superoxide anions, and their DNA. Type-2 cytokines such as interleukin (IL)-4 and IL-13 also play roles in the development of bronchial asthma. Among these cytokines, IL-4 is involved in T-cell differentiation, B-cell activation, B-cell differentiation into plasma cells, and the production of immunoglobulin E. Although IL-13 has similar effects to IL-4, IL-13 mainly affects structural cells, such as epithelial cells, smooth muscle cells, and fibroblasts. IL-13 induces the differentiation of goblet cells that produce mucus and induces the airway remodeling, including smooth muscle hypertrophy. IL-4 and IL-13 do not directly activate the effector functions of eosinophils; however, they can induce eosinophilic airway inflammation by upregulating the expression of vascular cell adhesion molecule-1 (for adhesion) and CC chemokine receptor 3 ligands (for migration). Dupilumab, a human anti-IL-4 receptor α monoclonal antibody that inhibits IL-4 and IL-13 signaling, decreases asthma exacerbations and mucus plugs and increases lung function in moderate to severe asthma. In addition, dupilumab is effective for chronic rhinosinusitis with nasal polyps and for atopic dermatitis, and IL-4/IL-13 blocking is expected to suppress allergen sensitization, including transcutaneous sensitization and atopic march.

Increased adiposity to muscle ratio and severity of sinusitis affect quality of life in asthma—Computed tomographic analysis—

BackgroundDeteriorated sinusitis and increased adiposity relative to muscle mass may affect the quality of life(QoL) in patients with asthma. However, whether these effects are observed regardless of intra-pulmonary pathology is unknown. ObjectivesTo evaluate the correlation of the cross-sectional ratio of abdominal visceral fat (VF) to erector spinae muscle (ESM) and sinus findings based on Lund-Mackey scoring system (LMS) on computed tomography (CT) with the impaired score of the Asthma Quality of Life Questionnaire (AQLQ), regardless of airway and parenchymal disease, in patients with asthma. MethodsParticipants from the Hokkaido-based severe asthma cohort who had completed AQLQ and CT examination at the entry. The participants were divided into high (highest) and low (other quartiles) groups based on the extra-pulmonary indices. The multivariate analysis examined the association of VF/ESM for the adiposity-to-muscle ratio, LMS with AQLQ, after adjusting for the airway fractal dimension for airway index, %low attenuation volume for parenchymal index. ResultsNo significant differences were observed in VF/ESM and LMS in terms of sex. The AQLQ score in the high VF/ESM group and high LMS group was lower than those in low VF/ESM group and low LMS group (N:Male/Female, 63/100). High VF/ESM (estimate [95% confidence interval], (-0.43[-0.61,-0.25]) and high LMS scores (-0.22(-0.41, -0.03)) were associated with low AQLQ scores, adjusted for age, body mass index, smoking status, blood eosinophil counts, and intra pulmonary CT indices. ConclusionsIncreased VF relative to ESM mass and high LMS may deteriorate asthma related QoL, regardless of intra-pulmonary disease.

Evaluating inhaler technique, patient preferences and opportunities for improvement in hospitals in the UK

Inhalers are a key aspect of managing airways disease, with effective use they can reduce symptoms, reduce the frequency of exacerbations and thus reduce usage of healthcare services.1 Inhalers are associated with a significant carbon footprint, accounting for 3% of NHS carbon emissions.2 We aimed to audit inhaler technique, patient preferences and inhaler prescribing/disposal to identify areas for improving the sustainability of respiratory care. An audit tool was created, and patient interviews conducted across 8 different sites. Our data demonstrates that inhaler users, while self-reporting high levels of confidence in their inhaler technique, frequently make errors in inhaler technique. Additionally, the majority of patients consider the carbon footprint of their inhalers important and would consider changing to a lower carbon alternative. The majority of patients surveyed were not disposing of their inhalers correctly. This short audit has identified key areas for improvement in the quality and sustainability of respiratory care.

Interstitial lung disease; a need for oxygen concentrator rental business in Nigeria?

Background: Patients with chronic obstructive airway diseases often need domiciliary oxygen supply. Case report: We report an elderly woman with interstitial lung disease that was dependent on intranasal oxygen. We discuss the need for rental oxygen concentrator business in Nigeria. Key Message: Rental oxygen concentrator business will make oxygen concentrators affordable in Nigeria

An aberrant right subclavian artery in a chronic obstructive airway disease patient

Background: A seventy-six year old man, known hypertensive, presented with chest pain of five years duration, associated with exertional breathlessness, wheeze, cough, leg swelling and fatigue. His chest radiograph showed signs of hyperinflation, and chest computer tomography showed an aberrant right subclavian artery. We discuss the implications of this finding to diagnosis, and clinical management.

Short- and mid-term morbidity and primary-care burden due to infant respiratory syncytial virus infection: A Spanish 6-year population-based longitudinal study.

The morbidity burden of respiratory syncytial virus (RSV) in infants extends beyond hospitalization. Defining the RSV burden before implementing prophylaxis programs is essential for evaluating any potential impact on short- to mid-term morbidity and the utilization of primary healthcare (PHC) and emergency services (ES). We established this reference data using a population-based cohort approach. Infants hospitalized for RSV from January 2016 to March 2023 were matched with non-hospitalized ones based on birthdate and sex. We defined the exposure as severe RSV hospitalization. The main study outcomes were as follows: (1) PHC and ES visits for RSV, categorized using the International Classification of Primary Care codes, (2) prescriptions for respiratory airway obstructive disease, and (3) antibacterial prescriptions. Participants were followed up from 30 days before hospitalization for severe RSV until the outcome occurrence or end of the study. Adjusted incidence rate ratios (IRRs) of the outcomes along with their 95% confidence intervals (CI) were estimated using Poisson regression models. Stratified analyses by type of PHC visit (nurse, pediatrician, or pharmacy) and follow-up period were undertaken. We defined mid-term outcomes as those taking place up to 24 months of follow-up period. The study included 6626 children (3313 RSV-hospitalized; 3313 non-hospitalized) with a median follow-up of 53.7 months (IQR = 27.9, 69.4). After a 3-month follow-up, severe RSV was associated with a considerable increase in PHC visits for wheezing/asthma (IRR = 4.31, 95% CI: 3.84-4.84), lower respiratory infections (IRR = 4.91, 95% CI: 4.34-5.58), and bronchiolitis (IRR = 4.68, 95% CI: 2.93-7.65). Severe RSV was also associated with more PHC visits for the pediatrician (IRR = 2.00, 95% CI: 1.96-2.05), nurse (IRR = 1.89, 95% CI: 1.75-1.92), hospital emergency (IRR = 2.39, 95% CI: 2.17-2.63), primary healthcare emergency (IRR: 1.54, 95% CI: 1.31-1.82), as well as with important increase in prescriptions for obstructive airway diseases (IRR = 5.98, 95% CI: 5.43-6.60) and antibacterials (IRR = 4.02, 95% CI: 3.38-4.81). All findings remained substantial until 2 years of post-infection. Severe RSV infection in infants significantly increases short- to mid-term respiratory morbidity leading to an escalation in healthcare utilization (PHC/ES attendance) and medication prescriptions for up to 2 years afterward. Our approach could be useful in assessing the impact and cost-effectiveness of RSV prevention programs.

Multi-Disciplinary Expert Perspective on the Management of Type 2 Inflammation-Driven Severe CRSwNP: A Brief Overview of Pathophysiology and Recent Clinical Insights.

Severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a disabling airway disease that significantly impacts patients' lives through the severity of symptoms, the need for long-term medical treatment and the high risk of recurrence post-surgery. Biological agents targeting type 2 immune responses underlying the pathogenesis of CRSwNP have shown effectiveness in reducing polyp size and eosinophilic infiltrate, and in decreasing the need for additional sinus surgeries. However, despite recent progress in understanding and treating the disease, type 2 inflammation-driven severe CRSwNP continues to pose challenges to clinical management due to several factors such as persistent inflammation, polyp recurrence, heterogeneity of disease, and comorbidities. This article presents the findings of a scientific discussion involving a panel of ear, nose and throat (ENT) specialists and pulmonologists across Sweden and Finland. The discussion aimed to explore current management practices for type 2 inflammation-driven severe CRSwNP in the Nordic region. The main topics examined encompassed screening and referral, measurements of disease control, treatment goals, and future perspectives. The experts emphasized the importance of a collaborative approach in the management of this challenging patient population. The discussion also revealed a need to broaden treatment options for patients with type 2 inflammation-driven CRSwNP and comorbid conditions with shared type 2 pathophysiology. In light of the supporting evidence, a shift in the disease model from the presence of polyps to that of type 2 inflammation may be warranted. Overall, this discussion provides valuable insights for the scientific community and can potentially guide the future management of CRSwNP.

CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV

Eosinophil recruitment is a pathological hallmark of many allergic and helminthic diseases. Here, we investigated chemokine receptor CCR3-induced eosinophil recruitment in sialyltransferase St3gal4-/- mice. We found a marked decrease in eosinophil extravasation into CCL11-stimulated cremaster muscles and into the inflamed peritoneal cavity of St3gal4-/- mice. Ex vivo flow chamber assays uncovered reduced adhesion of St3gal4-/- compared to wild type eosinophils. Using flow cytometry, we show reduced binding of CCL11 to St3gal4-/- eosinophils. Further, we noted reduced binding of CCL11 to its chemokine receptor CCR3 isolated from St3gal4-/- eosinophils. This was accompanied by almost absent CCR3 internalization of CCL11-stimulated St3gal4-/- eosinophils. Applying an ovalbumin-induced allergic airway disease model, we found a dramatic reduction in eosinophil numbers in bronchoalveolar lavage fluid following intratracheal challenge with ovalbumin in St3gal4-deficient mice. Finally, we also investigated tissue-resident eosinophils under homeostatic conditions and found reduced resident eosinophil numbers in the thymus and adipose tissue in the absence of ST3Gal-IV. Taken together, our results demonstrate an important role of ST3Gal-IV in CCR3-induced eosinophil recruitment in vivo rendering this enzyme an attractive target in reducing unwanted eosinophil infiltration in various disorders including allergic diseases.

Association between arachidonate lipoxygenase 15,c.-292 C > T gene polymorphism and non-cystic fibrosis bronchiectasis in children: a pilot study on the effects on airway lipoxin A4 and disease phenotype

BackgroundPersistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators, including lipoxins that regulate airway inflammation. Mutations at various positions in ALOX-15 gene can influence airway disease development. We investigated association between ALOX-15,c.-292 C > T gene polymorphism and bronchiectasis unrelated to cystic fibrosis in Egyptian children. Also, lipoxin A4 (LXA4) level in bronchoalveolar lavage (BAL) was studied in relation to polymorphism genotypes and disease phenotypes determined by clinical, pulmonary functions, and radiological severity parameters.MethodsThis was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method.ResultsThere was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53–5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6–1510) ng/ml compared to controls, median (IQR) of 1675 (536.8–2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005).ConclusionsLow airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production.