Is bronchiectasis really a disease?

The definition of a disease requires that distinguishing signs and symptoms are present that are common, and that the constellation of signs and symptoms differentiate the condition from other causes. In bronchiectasis, anatomical changes, airways inflammation and airway infection are the distinguishing features that are common to this disease. However, bronchiectasis is a heterogenous disease: signs and symptoms are shared with other airway diseases, there are multiple aetiologies and certain phenotypes of bronchiectasis have distinct clinical and laboratory features that are not common to all people with bronchiectasis. Furthermore, response to therapeutic interventions in clinical trials is not uniform. The concept of bronchiectasis as a treatable trait has been suggested, but this may be too restrictive in view of the heterogeneity of bronchiectasis. It is our opinion that bronchiectasis should be defined as a disease in its own right, but one that shares several pathophysiological features and “treatable traits” with other airway diseases. These traits define the large heterogeneity in the pathogenesis and clinical features and suggest a more targeted approach to therapy

Respiratory healthcare professionals’ views on long-term recommendations of interventions to prevent acute respiratory illnesses after the COVID-19 pandemic

Respiratory professionals support the continuing use of protective measures for respiratory patients following the #COVID19 pandemic. The optimal use of these measures should be considered in clinical guidelines and public health recommendations. https://bit.ly/3IVL2p

Eradication treatment for Pseudomonas aeruginosa infection in adults with bronchiectasis:a systematic review and meta-analysis

INTRODUCTION: Pseudomonas aeruginosa is the most commonly isolated pathogen in bronchiectasis and is associated with worse outcomes. Eradication treatment is recommended by guidelines, but the evidence base is limited. The expected success rate of eradication in clinical practice is not known.METHODS: We conducted a systematic review and meta-analysis according to Meta-Analysis of Observational Studies in Epidemiology guidelines. PubMed, Embase, the Cochrane Database of Systematic Reviews and Clinicaltrials.gov were searched for studies investigating P. aeruginosa eradication treatment using antibiotics (systemic or inhaled) in patients with bronchiectasis. The primary outcome was the percentage of patients negative for P. aeruginosa at 12 months after eradication treatment. Cystic fibrosis was excluded.RESULTS: Six observational studies including 289 patients were included in the meta-analysis. Our meta-analysis found a 12-month P. aeruginosa eradication rate of 40% (95% CI 34-45%; p&lt;0.00001), with no significant heterogeneity (I2=0%). Combined systemic and inhaled antibiotic treatment was associated with a higher eradication rate (48%, 95% CI 41-55%) than systemic antibiotics alone (27%, 13-45%).CONCLUSION: Eradication treatment in bronchiectasis results in eradication of P. aeruginosa from sputum in ∼40% of cases at 12 months. Combined systemic and inhaled antibiotics achieve higher eradication rates than systemic antibiotics alone.</p

The association between obesity, mortality and filling pressures in pulmonary hypertension patients; the “obesity paradox”

SummaryBackgroundThe term “obesity paradox”, refers to lower mortality rates in obese patients, and is evident in various chronic cardiovascular disorders. There is however, only scarce data regarding the clinical implication of obesity and pulmonary hypertension (PH). Therefore, in the current study, we evaluated the possible prognostic implications of obesity in PH patients.MethodsWe assessed 105 consecutive PH patients for clinical and hemodynamic parameters, focusing on the possible association between Body Mass Index (BMI) and mortality. Follow-up period was 19 ± 13 months.ResultsSixty-one patients (58%) had pre-capillary PH and 39 patients (37%) out-of-proportion post-capillary PH. During follow-up period, 30 patients (29%) died. Death was associated with reduced functional-class, inverse-relation with BMI, higher pulmonary artery and right atrial pressures, pulmonary vascular resistance and signs of right ventricular failure. In multivariate analysis, obesity (BMI ≥ 30 kg/m²), was the variable most significantly correlated with improved survival [H.R 0.2, 95% C.I 0.1–0.6; p = 0.004], even after adjustment for baseline characteristics. Obese and very-obese (BMI ≥ 35 kg/m²) patients had significantly less mortality rates during follow-up (12% and 8%, respectively) than non-obese patients (41%), p = 0.01. The tendency of survival benefit for the obese vs. non-obese patients was maintained both in the pre-capillary (10% vs. 46% mortality, p = 0.008) and disproportional post-capillary PH patients (11% vs. 40% mortality, p = 0.04).ConclusionsObesity was significantly associated with lower mortality in both pre-capillary and disproportional post-capillary PH patients. It seems that in PH, similarly to other chronic clinical cardiovascular disease states, there may be a protective effect of obesity, compatible with the “obesity paradox”

What is important for people with nontuberculous mycobacterial disease? An EMBARC-ELF patient survey

Experiencias de los pacientes; Enfermedad pulmonarExperiències dels pacients; Malaltia pulmonarPatient experiences; Lung diseasePatients' experiences of NTM pulmonary disease highlight important and unmet needs for better pharmacological treatment and education of medical staffEuropean Respiratory Society (EMBARC Clinical Research Collaboration

Prescribing preferences and availability of nebulisers and inhalers for inhaled medications in bronchiectasis:results of a specialist survey

Specialists caring for people with bronchiectasis recommend specialised nebulisers for inhaled antibiotics, but are often limited by availability and cost of nebulisation devices https://bit.ly/40FvFdZ.</p

ROSE: radiology, obstruction, symptoms and exposure – a Delphi consensus definition of the association of COPD and bronchiectasis by the EMBARC Airways Working Group

Consensus; COPD; Clinical practiceConsenso; EPOC; Práctica clínicaConsens; MPOC; Pràctica clínicaIntroduction The coexistence of COPD and bronchiectasis seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians. Methods We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the “COPD– [bronchiectasis] BE association”. A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and sex distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds. Results 102 (72.3%) out of 141 invited experts participated in the first round. Their response rate in the second round was 81%. The final consensus definition of “COPD–BE association” was: “The coexistence of (1) specific radiological findings (abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry ([forced expiratory volume in 1 s] FEV1/[forced vital capacity] FVC <0.7), (3) at least two characteristic symptoms (cough, expectoration, dyspnoea, fatigue, frequent infections) and (4) current or past exposure to smoke (≥10 pack-years) or other toxic agents (biomass, etc.)”. These criteria form the acronym “ROSE” (Radiology, Obstruction, Symptoms, Exposure). Conclusions The Delphi process formulated a European consensus definition of “COPD–BE association”. We hope this definition will have broad applicability across clinical practice and research in the future

Proof-of-concept for effective antiviral activity of an in silico designed decoy synthetic mRNA against SARS-CoV-2 in the Vero E6 cell-based infection model

The positive-sense single-stranded (ss) RNA viruses of the Betacoronavirus (beta-CoV) genus can spillover from mammals to humans and are an ongoing threat to global health and commerce, as demonstrated by the current zoonotic pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current anti-viral strategies focus on vaccination or targeting key viral proteins with antibodies and drugs. However, the ongoing evolution of new variants that evade vaccination or may become drug-resistant is a major challenge. Thus, antiviral compounds that circumvent these obstacles are needed. Here we describe an innovative antiviral modality based on in silico designed fully synthetic mRNA that is replication incompetent in uninfected cells (termed herein PSCT: parasitic anti-SARS-CoV-2 transcript). The PSCT sequence was engineered to include key untranslated cis-acting regulatory RNA elements of the SARS-CoV-2 genome, so as to effectively compete for replication and packaging with the standard viral genome. Using the Vero E6 cell-culture based SARS-CoV-2 infection model, we determined that the intracellular delivery of liposome-encapsulated PSCT at 1 hour post infection significantly reduced intercellular SARS-CoV-2 replication and release into the extracellular milieu as compared to mock treatment. In summary, our findings are a proof-of-concept for the therapeutic feasibility of in silico designed mRNA compounds formulated to hinder the replication and packaging of ssRNA viruses sharing a comparable genomic-structure with beta-CoVs

A Phase 2 randomised study to establish efficacy, safety and dosing of a novel oral cathepsin C inhibitor, BI 1291583, in adults with bronchiectasis:Airleaf

New therapies are needed to prevent exacerbations, improve quality of life and slow disease progression in bronchiectasis. Inhibition of cathepsin C (CatC) activity has the potential to decrease activation of neutrophil-derived serine proteases in patients with bronchiectasis, thereby reducing airway inflammation, improving symptoms, reducing exacerbations and preventing further airway damage. Here we present the design of a phase 2 trial (Airleaf™; NCT05238675) assessing the efficacy and safety of a novel CatC inhibitor, BI 1291583, in adult patients with bronchiectasis. This multinational, randomised, double-blind, placebo-controlled, parallel-group, dose-finding study has a screening period of at least 6 weeks, a treatment period of 24–48 weeks and a follow-up period of 4 weeks. ∼240 adults with bronchiectasis of multiple aetiologies will be randomised to placebo once daily, or BI 1291583 1 mg once daily, 2.5 mg once daily or 5 mg once daily in a 2:1:1:2 ratio, stratified by Pseudomonas aeruginosa infection and maintenance use of macrolides. The primary efficacy objective is to evaluate the dose–response relationship for the three oral doses of BI 1291583 versus placebo on time to first pulmonary exacerbation up to Week 48 (the primary end-point). Efficacy will be assessed using exacerbations, patient-reported outcomes, measures of symptoms, sputum neutrophil elastase activity and pulmonary function testing. Safety assessment will include adverse event reporting, physical examination, monitoring of vital signs, safety laboratory parameters, 12-lead electrocardiogram, and periodontal and dermatological assessments. If efficacy and safety are demonstrated, results will support further investigation of BI 1291583 in phase 3 trials