Endotypes of Exacerbation in Bronchiectasis: An Observational Cohort Study.

Rationale: Bronchiectasis is characterized by acute exacerbations, but the biological mechanisms underlying these events are poorly characterized. Objectives: To investigate the inflammatory and microbial characteristics of exacerbations of bronchiectasis. Methods: A total of 120 patients with bronchiectasis were enrolled and presented with acute exacerbations within 12 months. Spontaneous sputum samples were obtained during a period of clinical stability and again at exacerbation before receipt of antibiotic treatment. A validated rapid PCR assay for bacteria and viruses was used to classify exacerbations as bacterial, viral, or both. Sputum inflammatory assessments included label-free liquid chromatography-tandem mass spectrometry and measurement of sputum cytokines and neutrophil elastase activity. 16 s rRNA sequencing was used to characterize the microbiome. Measurements and Main Results: Bronchiectasis exacerbations showed profound molecular heterogeneity. At least one bacterium was identified in 103 samples (86%), and a high bacterial load (total bacterial load > 107 copies/g) was observed in 81 patients (68%). Respiratory viruses were identified in 55 (46%) patients, with rhinovirus being the most common virus (31%). PCR testing was more sensitive than culture. No consistent change in the microbiome was observed at exacerbation. Exacerbations were associated with increased neutrophil elastase, proteinase-3, IL-1ß, and CXCL8. These markers were particularly associated with bacterial and bacterial plus viral exacerbations. Distinct inflammatory and microbiome profiles were seen between different exacerbation subtypes, including bacterial, viral, and eosinophilic events in both hypothesis-led and hypothesis-free analysis using integrated microbiome and proteomics, demonstrating four subtypes of exacerbation. Conclusions: Bronchiectasis exacerbations are heterogeneous events with contributions from bacteria, viruses, and inflammatory dysregulation.

Airway IL-1ß is related to disease severity and mucociliary function in bronchiectasis.

RATIONALE: The inflammasome is a key regulatory complex of the inflammatory response leading to IL-1ß release and activation. IL-1ß amplifies inflammatory responses and induces mucus secretion and hyperconcentration in other diseases. The role of IL-1ß in bronchiectasis has not been investigated. OBJECTIVES: To characterize the role of airway IL-1ß in bronchiectasis including the association with mucus properties, ciliary function, airway inflammation, microbiome and disease severity. METHODS: Stable bronchiectasis patients were enrolled in an international cohort study (n=269). IL-1ß was measured in sputum supernatant. A validation cohort also had sputum rheology and hydration measured (n=53). For analysis, patients were stratified according to the median value of IL-1ß in the population (High versus Low) to compare disease severity, airway infection, microbiome (16S rRNA sequencing), inflammation and caspase-1 activity. Primary human nasal epithelial cells grown in air-liquid interface culture were used to study IL-1ß effect on cilia function. MEASUREMENTS AND MAIN RESULTS: Patients with high sputum IL-1ß had more severe disease, increased caspase-1 activity and increased Th1, Th2 and neutrophil inflammatory response compared with patients with low IL-1ß. The active-dominant form of IL-1ß was associated with increased disease severity. High IL-1ß was related to higher relative abundance of Proteobacteria in the microbiome and increased mucus solid content and viscoelastic properties. Chronic IL-1ß treatment reduced the functionality of cilia and tight junctions of epithelial cells in-vitro. CONCLUSIONS: A subset of stable bronchiectasis patients show increased airway IL-1ß, suggesting pulmonary inflammasome activation is linked with more severe disease, airway infection, mucus dehydration and epithelial dysfunction.

Inflammatory Molecular Endotypes in Bronchiectasis: A European Multicenter Cohort Study.

Rationale: Although inflammation and infection are key disease drivers in bronchiectasis, few studies have integrated host inflammatory and microbiome data to guide precision medicine. Objectives: To identify clusters among patients with bronchiectasis on the basis of inflammatory markers and to assess the association between inflammatory endotypes, microbiome characteristics, and exacerbation risk. Methods: Patients with stable bronchiectasis were enrolled at three European centers, and cluster analysis was used to stratify the patients according to the levels of 33 sputum and serum inflammatory markers. Clusters were compared in terms of microbiome composition (16S ribosomal RNA sequencing) and exacerbation risk over a 12-month follow-up. Measurements and Main Results: A total of 199 patients were enrolled (109 [54.8%] female; median age, 69 yr). Four clusters of patients were defined according to their inflammatory profiles: cluster 1, milder neutrophilic inflammation; cluster 2, mixed-neutrophilic and type 2; cluster 3, most severe neutrophilic; and cluster 4, mixed-epithelial and type 2. Lower microbiome diversity was associated with more severe inflammatory clusters (P < 0.001), and ß-diversity analysis demonstrated distinct microbiome profiles associated with each inflammatory cluster (P = 0.001). Proteobacteria and Pseudomonas at phylum and genus levels, respectively, were more enriched in clusters 2 and 3 than in clusters 1 and 4. Furthermore, patients in cluster 2 (rate ratio [RR], 1.49; 95% confidence interval [CI], 1.16-1.92) and cluster 3 (RR, 1.61; 95% CI, 1.12-2.32) were at higher risk of exacerbation over a 12-month follow-up compared with cluster 1, even after adjustment for prior exacerbation history. Conclusions: Bronchiectasis inflammatory endotypes are associated with distinct microbiome profiles and future exacerbation risk.

Characterization of Eosinophilic Bronchiectasis: A European Multicohort Study.

Rationale: Bronchiectasis is classically considered a neutrophilic disorder, but eosinophilic subtypes have recently been described. Objectives: To use multiple datasets available through the European Multicentre Bronchiectasis Audit and Research Collaboration to characterize eosinophilic bronchiectasis as a clinical entity focusing on the impact of eosinophils on bronchiectasis exacerbations. Methods: Patients were included from five countries to examine the relationships between blood eosinophil counts and clinical phenotypes after excluding coexisting asthma. 16S rRNA sequencing was used to examine relationships between eosinophil counts and the sputum microbiome. A post hoc analysis of the PROMIS (Inhaled Promixin in the Treatment of Non-Cystic Fibrosis Bronchiectasis) phase 2 trial was used to examine the impact of blood eosinophil counts on exacerbations in patients with Pseudomonas aeruginosa infection. Measurements and Main Results: A relationship between sputum and blood eosinophil counts was demonstrated in two cohorts. In analysis of 1,007 patients from five countries, 22.6% of patients had blood eosinophil counts of ⩾300 cells/µl. Counts of <100 cells/µl were associated with higher bronchiectasis severity and increased mortality. There was no clear relationship with exacerbations. Blood eosinophil counts of ⩾300 cells/µl were associated with both Streptococcus- and Pseudomonas-dominated microbiome profiles. To investigate the relationship of eosinophil counts with exacerbations after controlling for the confounding effects of infection, 144 patients were studied in a clinical trial after treatment with antipseudomonal antibiotics. Compared with patients with blood eosinophil counts of <100 cells/µl (reference), elevated eosinophil counts of 100-299 cells/µl (hazard ratio, 2.38; 95% confidence interval, 1.33-4.25; P = 0.003) and ⩾300 cells/µl (hazard ratio, 3.99; 95% confidence interval, 2.20-7.85; P < 0.0001) were associated with shorter time to exacerbation. Conclusions: Eosinophilic bronchiectasis affects approximately 20% of patients. After accounting for infection status, raised blood eosinophil counts are associated with shortened time to exacerbation.

Heterogeneity of treatment response in bronchiectasis clinical trials.

BACKGROUND: Recent randomised clinical trials in bronchiectasis have failed to reach their primary end-points, suggesting a need to reassess how we measure treatment response. Exacerbations, quality of life (QoL) and lung function are the most common end-points evaluated in bronchiectasis clinical trials. We aimed to determine the relationship between responses in terms of reduced exacerbations, improved symptoms and lung function in bronchiectasis. METHODS: We evaluated treatment response in three randomised clinical trials that evaluated mucoactive therapy (inhaled mannitol), an oral anti-inflammatory/antibiotic (azithromycin) and an inhaled antibiotic (aztreonam). Treatment response was defined by an absence of exacerbations during follow-up, an improvement of QoL above the minimum clinically important difference and an improvement in forced expiratory volume in 1 s (FEV1) of ≥100 mL from baseline. RESULTS: Cumulatively the three trials included 984 patients. Changes in FEV1, QoL and exacerbations were heterogeneous in all trials analysed. Improvements in QoL were not correlated to changes in FEV1 in the azithromycin and aztreonam trials (r= -0.17, p=0.1 and r=0.04, p=0.4, respectively) and weakly correlated in the mannitol trial (r=0.22, p<0.0001). An important placebo effect was observed in all trials, especially regarding improvements in QoL. Clinical meaningful lung function improvements were rare across all trials evaluated, suggesting that FEV1 is not a responsive measure in bronchiectasis. CONCLUSIONS: Improvements in lung function, symptoms and exacerbation frequency are dissociated in bronchiectasis. FEV1 is poorly responsive and poorly correlated with other key outcome measures. Clinical parameters are poorly predictive of treatment response, suggesting the need to develop biomarkers to identify responders.

Elevated plasma levels of epithelial and endothelial cell markers in COVID-19 survivors with reduced lung diffusing capacity six months after hospital discharge.

BACKGROUND: Some COVID-19 survivors present lung function abnormalities during follow-up, particularly reduced carbon monoxide lung diffusing capacity (DLCO). To investigate risk factors and underlying pathophysiology, we compared the clinical characteristics and levels of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or reduced DLCO 6 months after discharge. METHODS: Prospective, observational study. Clinical characteristics during hospitalization, and spirometry, DLCO and plasma levels of epithelial (surfactant protein (SP) A (SP-A), SP-D, Club cell secretory protein-16 (CC16) and secretory leukocyte protease inhibitor (SLPI)), and endothelial (soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and Angiopoietin-2) 6 months after hospital discharge were determined in 215 COVID-19 survivors. RESULTS: DLCO was < 80% ref. in 125 (58%) of patients, who were older, more frequently smokers, had hypertension, suffered more severe COVID-19 during hospitalization and refer persistent dyspnoea 6 months after discharge. Multivariate regression analysis showed that age ≥ 60 years and severity score of the acute episode ≥ 6 were independent risk factors of reduced DLCO 6 months after discharge. Levels of epithelial (SP-A, SP-D and SLPI) and endothelial (sICAM-1 and angiopoietin-2) markers were higher in patients with reduced DLCO, particularly in those with DLCO ≤ 50% ref. Circulating SP-A levels were associated with the occurrence of acute respiratory distress syndrome (ARDS), organizing pneumonia and pulmonary embolisms during hospitalization. CONCLUSIONS: Reduced DLCO is common in COVID-19 survivors 6 months after hospital discharge, especially in those older than 60 years with very severe acute disease. In these individuals, elevated levels of epithelial and endothelial markers suggest persistent lung damage.

Circulating leukocyte-platelet complexes as a predictive biomarker for the development of immune-related adverse events in advanced non-small cell lung cancer patients receiving anti-PD-(L)1 blocking agents.

BACKGROUND: Anti-PD-(L)1 blocking agents can induce immune-related adverse events (irAEs), which can compromise treatment continuation. Since circulating leukocyte-platelet (PLT) complexes contribute to inflammatory and autoimmune diseases, we aimed to analyze the role of these complexes as predictors of irAEs in non-small cell lung cancer (NSCLC) patients receiving anti-PD-(L)1. MATERIALS AND METHODS: Twenty-six healthy donors (HD) and 87 consecutive advanced NSCLC patients treated with anti-PD-(L)1 were prospectively included. Percentages of circulating leukocyte-PLT complexes were analyzed by flow cytometry and compared between HD and NSCLC patients. The association of leukocyte-PLT complexes with the presence and severity of irAEs was analyzed. RESULTS: NSCLC patients had higher percentages of circulating leukocyte-PLT complexes. Higher percentages of monocytes with bound PLT (CD14 + PLT +) were observed in patients who received prior therapies while CD4 + T lymphocytes with bound PLT (CD4 + PLT +) correlated with platelets counts. The CD4 + PLT + high percentage group presented a higher rate of dermatological irAEs while the CD4 + PLT + low percentage group showed a higher rate of non-dermatological irAEs (p < 0.001). A lower frequency of grade ≥ 2 irAEs was observed in the CD4 + PLT + high percentage group (p < 0.05). Patients with CD4 + PLT + low and CD14 + PLT + high percentages presented a higher rate of grade ≥ 3 irAEs and predominantly developed non-dermatological irAEs (p < 0.01). CONCLUSIONS: Our results suggest that circulating leukocyte-PLT complexes and the combination of CD4 + PLT + and CD14 + PLT + percentages can be used as a predictive biomarker of the development and severity of irAEs in advanced NSCLC patients receiving anti-PD-(L)1 agents.

Long-Term Antibiotics in Bronchiectasis.

A significant proportion of bronchiectasis patients are chronically infected by potentially pathogenic microorganisms which may lead to frequent exacerbations and worse clinical outcomes. Current bronchiectasis guidelines recommend long-term inhaled antibiotics and/or oral macrolides as a part of patient management. In recent years, an increasing amount of evidence assessing the impact of these treatments on patient outcomes has been collected. Inhaled antibiotics have demonstrated significant improvements in sputum bacterial load, but their impact on patient quality of life, lung function, and exacerbation rate has not been consistent across trials. In this regard, recent post hoc analyses of inhaled antibiotics trials in bronchiectasis patients have shown that sputum bacterial load may be a key biomarker to predict treatment response in these patients. Oral macrolides, on the other hand, have proven to reduce exacerbation frequency and improve quality of life, but potential drug-related adverse effects and the increase in bacterial resistance are relevant. This review aims to summarize current important evidence for long-term antibiotic treatment in bronchiectasis patients.

Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity.

BACKGROUND: For still unclear reasons, chronic airway infection often occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), particularly in those with more severe airflow limitation. Fatty-acid binding protein 4 (FABP4) is an adipokine involved in the innate immune response against infection produced by alveolar macrophages (Mɸ). We hypothesized that airway levels of FABP4 may be altered in COPD patients with chronic airway infection. METHODS: In this prospective and controlled study we: (1) compared airway FABP4 levels (ELISA) in induced sputum, bronchoalveolar lavage fluid (BALF) and plasma samples in 52 clinically stable COPD patients (65.2 ± 7.9 years, FEV1 59 ± 16% predicted) and 29 healthy volunteers (55.0 ± 12.3 years, FEV1 97 ± 16% predicted); (2) explored their relationship with the presence of bacterial airway infection, defined by the presence of potentially pathogenic bacteria (PPB) at ≥103 colony-forming units/ml in BALF; (3) investigated their relationship with the quantity and proportion of Mɸ in BALF (flow cytometry); and, (4) studied their relationship with the severity of airflow limitation (FEV1), GOLD grade and level of symptoms (CAT questionnaire). RESULTS: We found that: (1) airway levels of FABP4 (but not plasma ones) were reduced in COPD patients vs. controls [219.2 (96.0-319.6) vs. 273.4 (203.1-426.7) (pg/ml)/protein, p = 0.03 in BALF]; (2) COPD patients with airway infection had lower sputum FABP4 levels [0.73 (0.35-15.3) vs. 15.6 (2.0-29.4) ng/ml, p = 0.02]; (3) in COPD patients, the number and proportion of Mɸ were positively related with FABP4 levels in BALF; (4) BALF and sputum FABP4 levels were positively related with FEV1, negatively with the CAT score, and lowest in GOLD grade D patients. CONCLUSIONS: Airway FABP4 levels are reduced in COPD patients, especially in those with airway infection and more severe disease. The relationship observed between Mɸ and airway FABP4 levels supports a role for FABP4 in the pathogenesis of airway infection and disease severity in COPD.

Airway Bacterial Load and Inhaled Antibiotic Response in Bronchiectasis.

Rationale: The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. Objectives: To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. Methods: We performed three studies. Studies 1 and 2 were prospective studies including adults with bronchiectasis. Study 3 was a post hoc analysis of a randomized trial of inhaled aztreonam. A priori patients were divided into low (<105 cfu/g), moderate (105-106 cfu/g), and high bacterial load (≥107 cfu/g) using quantitative sputum culture. Measurements and Main Results: Bacterial load was a stable trait associated with worse quality of life and more airway inflammation in studies 1, 2, and 3. In study 3, patients with high bacterial load showed an improvement in the primary endpoint (Quality of Life-Bronchiectasis-Respiratory Symptoms Score at Week 4) in favor of aztreonam (mean difference of 9.7 points; 95% confidence interval, 3.4-16.0; P = 0.003). The proportion of patients who achieved an increase above the minimum clinically important difference was higher in the aztreonam group at Week 4 (63% vs. 37%; P = 0.01) and at Week 12 (62% vs. 38%; P = 0.01) only in high bacterial load patients. Conclusions: Improvement of quality of life with inhaled aztreonam was only evident in patients with high bacterial load. Bacterial load may be a useful biomarker of severity of disease and treatment response.

Antimicrobial peptides, disease severity and exacerbations in bronchiectasis.

RATIONALE: Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease. OBJECTIVES: To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis. METHODS: A total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk. MEASUREMENTS AND MAIN RESULTS: AMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months. CONCLUSIONS: Patients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis.

A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation.

INTRODUCTION: Neutrophil elastase activity in sputum can identify patients at high risk of airway infection and exacerbations in bronchiectasis. Application of this biomarker in clinical practice is limited, because no point-of-care test is available. We tested whether a novel semi-quantitative lateral flow device (neutrophil elastase airway test stick - NEATstik®) can stratify bronchiectasis patients according to severity, airway infection and exacerbation risk. METHODS: Sputum samples from 124 patients with stable bronchiectasis enrolled in the UK and Spain were tested using the NEATstik®, which scores neutrophil elastase concentration from 0 (<8 µg·mL-1 elastase activity) to 10 (maximum detectable neutrophil elastase activity). High neutrophil elastase activity was regarded as a NEATstik® grade >6. Severity of disease, airway infection from sputum culture and exacerbations over the 12 months were recorded. An independent validation was conducted in 50 patients from Milan, Italy. MEASUREMENTS AND MAIN RESULTS: Patients had a median age of 69 years and forced expiratory volume in 1 s (FEV1) 69%. High neutrophil elastase activity was associated with worse bronchiectasis severity using the bronchiectasis severity index (p=0.0007) and FEV1 (p=0.02). A high NEATstik® grade was associated with a significant increase in exacerbation frequency, incident rate ratio 2.75 (95% CI 1.63-4.64, p<0.001). The median time to next exacerbation for patients with a NEATstik® grade >6 was 103 days compared to 278 days. The hazard ratio was 2.59 (95% CI 1.71-3.94, p<0.001). Results were confirmed in the independent validation cohort. CONCLUSIONS: A novel lateral flow device provides assessment of neutrophil elastase activity from sputum in minutes and identifies patients at increasing risk of airway infection and future exacerbations.

Association of Platelet Binding to Lymphocytes with B Cell Abnormalities and Clinical Manifestations in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.

Pseudomonas aeruginosa in Chronic Obstructive Pulmonary Disease Patients with Frequent Hospitalized Exacerbations: A Prospective Multicentre Study.

BACKGROUND: Pseudomonas aeruginosa (PA) is a common microorganism related to severe exacerbations in Chronic Obstructive Pulmonary Disease (COPD). However, their role in COPD patients with frequent hospitalized exacerbations (FHE) is not well described. OBJECTIVES: We aimed to determine prevalence, risk factors, susceptibility patterns and impact on outcomes of PA in COPD patients with FHE. METHODS: Prospective observational multicentre study that included COPD patients with FHE. The cohort was stratified in 2 groups according to the presence or absence of PA isolation in sputum. Patients were followed up for 12 months. RESULTS: We enrolled 207 COPD patients with FHE. In 119 patients (57%), a valid sputum culture was collected. Of them, PA was isolated in 21 patients (18%). The risk factors associated with PA were prior use of systemic corticosteroids (OR 3.3, 95% CI 1.2-9.7, p = 0.01) and prior isolation of PA (OR 4.36, 95% CI 1.4-13.4, p < 0.01). Patients with PA had an increased risk of having ≥3 readmissions (OR 4.1, 95% CI 1.3-12.8, p = 0.01) and higher PA isolation rate (OR 7.7, 95% CI 2.4-24.6, p < 0.001) during the follow-up period. In 14 patients (67%), PA was resistant to at least one antibiotic tested. PA persisted in the sputum in 70% of patients. CONCLUSIONS: The presence of PA was related to 3 or more readmissions during the 1-year follow-up and PA persisted in the sputum despite an appropriate antibiotic treatment. This finding suggested an important role of PA in the course of the disease of COPD patients with FHE.

Pathophysiology and genomics of bronchiectasis.

Bronchiectasis is a complex and heterogeneous inflammatory chronic respiratory disease with an unknown cause in around 30-40% of patients. The presence of airway infection together with chronic inflammation, airway mucociliary dysfunction and lung damage are key components of the vicious vortex model that better describes its pathophysiology. Although bronchiectasis research has significantly increased over the past years and different endotypes have been identified, there are still major gaps in the understanding of the pathophysiology. Genomic approaches may help to identify new endotypes, as has been shown in other chronic airway diseases, such as COPD.Different studies have started to work in this direction, and significant contributions to the understanding of the microbiome and proteome diversity have been made in bronchiectasis in recent years. However, the systematic application of omics approaches to identify new molecular insights into the pathophysiology of bronchiectasis (endotypes) is still limited compared with other respiratory diseases.Given the complexity and diversity of these technologies, this review describes the key components of the pathophysiology of bronchiectasis and how genomics can be applied to increase our knowledge, including the study of new techniques such as proteomics, metabolomics and epigenomics. Furthermore, we propose that the novel concept of trained innate immunity, which is driven by microbiome exposures leading to epigenetic modifications, can complement our current understanding of the vicious vortex. Finally, we discuss the challenges, opportunities and implications of genomics application in clinical practice for better patient stratification into new therapies.

ERS International Congress 2023: highlights from the Respiratory Infections Assembly.

The 2023 European Respiratory Society Congress took place on a hybrid platform, with participants joining online and in-person in Milan, Italy. The congress welcomed over 20 000 attendees, bringing together exciting updates in respiratory science and medicine from around the world. In this article, early career members of Assembly 10 (Respiratory Infections) summarise a selection of sessions across a broad range of topics, including presentations on bronchiectasis, nontuberculous mycobacteria, tuberculosis, cystic fibrosis and coronavirus disease 2019.

Pathophysiology of Chronic Bronchial Infection in Bronchiectasis.

Bronchiectasis is a complex and heterogeneous disease. Its pathophysiology is poorly understood, but chronic bronchial infection plays an important role in its natural history, and is associated with poor quality of life, more exacerbations and increased mortality. Pseudomonas aeruginosa, Haemophilus influenzae and Staphylococcus aureus are the most common bacteria related to chronic bronchial infection. Non-tuberculous mycobacteria, fungi and respiratory viruses are also present during clinical stability, and may increase the risk of acute exacerbation. Chronic inflammation is present in bronchiectasis, especially neutrophilic inflammation. However, macrophages and eosinophils also play a key role in the disease. Finally, airway epithelium has innate mechanisms such as mucociliary clearance and antibacterial molecules like mucins and antimicrobial peptides that protect the airways from pathogens. This review addresses how the persistence of microorganisms in the airways and the imbalance of the immune system contribute to the development of chronic bronchial infection in bronchiectasis.

Persistence of a SARS-CoV-2 T-cell response in patients with long COVID and lung sequelae after COVID-19.

1 year after an acute COVID-19 episode, patients with either lung sequelae or long COVID show a stronger SARS-CoV-2-specific T-cell response than fully recovered individuals, suggesting persistent cell stimulation by residual viral reservoirs https://bit.ly/40bPZm7.

ERS International Congress 2022: highlights from the Respiratory Infections Assembly.

The European Respiratory Society International Congress took place both in person, in Barcelona, Spain, and online in 2022. The congress welcomed over 19 000 attendees on this hybrid platform, bringing together exciting updates in respiratory science and medicine from around the world. In this article, Early Career Members of the Respiratory Infections Assembly (Assembly 10) summarise a selection of sessions across a broad range of topics, including presentations on bronchiectasis, nontuberculous mycobacteria, tuberculosis, cystic fibrosis and coronavirus disease 2019.