Highlights del 57º Congreso SEPAR

Álvarez-Gutiérrez F.J., Maldonado F.C., Campos G.S., Aparicio M.B., Delgado J., Galo A.P., Quirce S., Plaza V.

The concept of "remission" in asthma has been around for a long time and it has been a controversial topic. Despite the attempts of some studies to characterize this entity, the discussion continues. In the case of asthma there is still no clear definition, either in terms of its meaning or the parameters that should be included or whether it should be divided into clinical or complete remission. To help defining these controversial concepts, SEPAR has advocated the multidisciplinary working group REMAS (REMission in ASthma). Following the Delphi methodology and with the involvement of more than 120 specialists in asthma management, this group has arrived at a consensus on the definitions of remission in asthma and establishing the criteria and characteristics that will be of use in future studies evaluating the efficacy or effectiveness of treatments.

Allende-González J., Antonio Gullón-Blanco J., Sánchez-Vázquez E., García-Coya E., Cascón-Hernández J.

Frantz R.P., McLaughlin V.V., Sahay S., Escribano Subías P., Zolty R.L., Benza R.L., Channick R.N., Chin K.M., Hemnes A.R., Howard L.S., Sitbon O., Vachiéry J., Zamanian R.T., Cravets M., Roscigno R.F., et. al.

Background Morbidity and mortality in pulmonary arterial hypertension (PAH) remain high. Activation of platelet-derived growth factor receptor, colony stimulating factor 1 receptor, and mast or stem cell growth factor receptor kinases stimulates inflammatory, proliferative, and fibrotic pathways driving pulmonary vascular remodelling in PAH. Seralutinib, an inhaled kinase inhibitor, targets these pathways. We aimed to evaluate the efficacy and safety of seralutinib in patients with PAH receiving standard background therapy. Methods The TORREY trial was a phase 2, randomised, multicentre, multinational, double-blind, placebo-controlled study. Patients with PAH from 40 hospital and community sites were randomly assigned 1:1 via interactive response technologies to receive seralutinib (60 mg twice daily for 2 weeks, then increased to 90 mg twice daily as tolerated) or placebo by dry powder inhaler twice daily for 24 weeks. Randomisation was stratified by baseline pulmonary vascular resistance (PVR;

Spinou A., Almagro M., Harris B., Boyd J., Berg T., Herrero-Cortina B., Posthumous A., Aliberti S., Crossley B., Ruddy T.F., Stein N., Crichton M.L., Goeminne P.C., Chalmers J.D., Shteinberg M.

Bucci T., Wat D., Nazareth D., Sibley S., Wootton D., Lip G.Y., Frost F.

Graul E.L., Nordon C., Rhodes K., Marshall J., Menon S., Kallis C., Ioannides A.E., Whittaker H.R., Peters N.S., Quint J.K.

Varricchi G., Brightling C.E., Grainge C., Lambrecht B.N., Chanez P.

Asthma is a chronic, heterogeneous disease of the airways, often characterised by structural changes known collectively as airway remodelling. In response to environmental insults, including pathogens, allergens and pollutants, the epithelium can initiate remodellingviaan inflammatory cascade involving a variety of mediators that have downstream effects on both structural and immune cells. These mediators include the epithelial cytokines thymic stromal lymphopoietin (TSLP), interleukin 33 and interleukin 25, which facilitate airway remodelling through cross-talk between epithelial cells and fibroblasts, and between mast cells and airway smooth muscle cells, as well as through signalling with immune cells like macrophages. The epithelium can also initiate airway remodelling independently of inflammation in response to the mechanical stress present during bronchoconstriction. Furthermore, genetic and epigenetic alterations to epithelial components are believed to influence remodelling. Here, we review recent advances in our understanding of the roles of the epithelium and epithelial cytokines in driving airway remodelling, facilitated by developments in genetic sequencing and imaging techniques. We also explore how new and existing therapeutics that target the epithelium and epithelial cytokines could modify airway remodelling.

Spinou A., Hererro-Cortina B., Aliberti S., Goeminne P.C., Polverino E., Dimakou K., Haworth C.S., Loebinger M.R., De Soyza A., Vendrell M., Burgel P.R., McDonnell M., Sutharsan S., Skrgat S., Maiz-Carro L., et. al.

BackgroundInternational guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use.MethodsThis was a prospective observational study using data from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) Registry between January 2015 and April 2022. Prespecified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs.Results16 723 people with bronchiectasis from 28 countries were included in the study. The mean age was 67 years (interquartile range 57–74 years, range 18–100 years) and 61% were female. 72% of the participants reported daily sputum expectoration and 52% (95% CI 51–53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the participants and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Participants who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume, compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in participants with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe.ConclusionsOnly a half of people with bronchiectasis in Europe use airway clearance management. Use of and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.

Gibbons E., Taya M., Wu H., Lopa S.H., Moss J., Henske E.P., Mccormack F.X., Hammes S.R.

Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (TSC) genes. mTORC1 inhibition slows but does not stop LAM advancement. Furthermore, monitoring disease progression is hindered by insufficient biomarkers. Therefore, new treatment options and biomarkers are needed. LAM cells express melanocytic markers, including glycoprotein non-metastatic melanoma protein B (GPNMB). The function of GPNMB in LAM is currently unknown; however, GPNMB’s unique cell surface expression on tumor versus benign cells makes GPNMB a potential therapeutic target, and persistent release of its extracellular ectodomain suggests potential as a serum biomarker. Here, we establish that GPNMB expression is dependent on mTORC1 signaling, and that GPNMB regulates TSC2-null tumor cell invasion in vitro. Further, we demonstrate that GPNMB enhances TSC2-null xenograft tumor growth in vivo, and that ectodomain release is required for this xenograft growth. We also show that GPNMB’s ectodomain is released from the cell surface of TSC2-null cells by proteases ADAM10 and 17, and we identify the protease target sequence on GPNMB. Finally, we demonstrate that GPNMB’s ectodomain is present at higher levels in LAM patient serum compared to healthy controls and that ectodomain levels decrease with mTORC1 inhibition, making it a potential LAM biomarker.

Vaidy A., Vahdatpour C.A., Mazurek J.

Pulmonary hypertension (PH), defined by a mean pulmonary artery pressure of >20 mm Hg, often presents with non-specific symptoms such as dyspnea and exercise intolerance, making it difficult to diagnose early before the onset of right heart dysfunction. Therefore, exercise testing can be of great utility for clinicians who are evaluating patients with an unclear etiology of exercise intolerance by helping identify the underlying mechanisms of their disease. The presence of PH is associated with adverse clinical outcomes, with distinct differences and patterns in the cardiovascular and ventilatory responses to exercise across various PH phenotypes. We discuss the role of exercise-invasive hemodynamic testing, cardiopulmonary exercise testing, and exercise stress echocardiography modalities across the spectrum of PH.

Almagro P., Soler-Cataluña J.J., Huerta A., González-Segura D., Cosío B.G.

Abstract Background Chronic obstructive pulmonary disease (COPD) frequently coexists with other chronic diseases, namely comorbidities. They negatively impact prognosis, exacerbations and quality of life in COPD patients. However, no studies have been performed to explore the impact of these comorbidities on COPD clinical control criteria. Research question Determine the relationship between individualized comorbidities and COPD clinical control criteria. Study design and methods Observational, multicenter, cross-sectional study performed in Spain involving 4801 patients with severe COPD (< 50 predicted forced expiratory volume in the first second [FEV1%]). Clinical control criteria were defined by the combination of COPD assessment test (CAT) scores (≤16 vs ≥17) and exacerbations in the previous three months (none vs ≥1). Binary logistic regression adjusted by age and FEV1% was performed to identify comorbidities potentially associated with the lack of control of COPD. Secondary endpoints were the relationship between individualized comorbidities with COPD assessment test and exacerbations within the last three months. Results Most frequent comorbidities were arterial hypertension (51.2%), dyslipidemia (36.0%), diabetes (24.9%), obstructive sleep apnea-hypopnea syndrome (14.9%), anxiety (14.1%), heart failure (11.6%), depression (11.8%), atrial fibrillation (11.5%), peripheral arterial vascular disease (10.4%) and ischemic heart disease (10.1%). After age and FEV1% adjustment, comorbidities related to lack of clinical control were cardiovascular diseases (heart failure, peripheral vascular disease and atrial fibrillation; p < 0.0001), psychologic disorders (anxiety and depression; all p < 0.0001), metabolic diseases (diabetes, arterial hypertension and abdominal obesity; all p < 0.001), sleep disorders (p < 0.0001), anemia (p = 0.015) and gastroesophageal reflux (p < 0.0001). These comorbidities were also related to previous exacerbations and COPD assessment test scores. Interpretation Comorbidities are frequent in patients with severe COPD, negatively impacting COPD clinical control criteria. They are related to health-related quality of life measured by the COPD assessment test. Our results suggest that comorbidities should be investigated and treated in these patients to improve their clinical control. Take-home points Study question: What is the impact of comorbidities on COPD clinical control criteria? Results: Among 4801 patients with severe COPD (27.5% controlled and 72.5% uncontrolled), after adjustment by age and FEV1%, comorbidities related to lack of clinical control were cardiovascular diseases (heart failure, peripheral vascular disease and atrial fibrillation; p < 0.0001), psychologic disorders (anxiety and depression; p < 0.0001), metabolic diseases (diabetes, arterial hypertension and abdominal obesity; p < 0.001), obstructive sleep apnea-hypopnea syndrome (p < 0.0001), anaemia (p = 0.015) and gastroesophageal reflux (p < 0.0001), which were related to previous exacerbations and COPD assessment test scores. Interpretation: Comorbidities are related to health-related quality of life measured by the COPD assessment test scores and history of exacerbations in the previous three months.

Candia C., Lombardi C., Merola C., Ambrosino P., D’Anna S.E., Vicario A., De Marco S., Molino A., Maniscalco M.

High-flow nasal cannula (HFNC) has recently emerged as a crucial therapeutic strategy for hypoxemic patients both in acute and chronic settings. Indeed, HFNC therapy is able to deliver higher fractions of inspired oxygen (FiO2) with a heated and humidified gas flow ranging from 20 up to 60 L per minute, in a more comfortable way for the patient in comparison with Conventional Oxygen Therapy (COT). In fact, the flow keeps the epithelium of the airways adequately moisturized, thus positively affecting the mucus clearance. Finally, the flow is able to wash out the carbon dioxide in the dead space of the airways; this is also enhanced by a modest positive end-expiratory pressure (PEEP) effect. Recent evidence has shown applications of HFNC in exercise training and chronic settings with promising results. In this narrative review, we explored how HFNC might contribute to enhancing outcomes of exercise training and pulmonary rehabilitation among patients dealing with chronic obstructive pulmonary disease, interstitial lung diseases, and lung cancer.

Moretti A., Pietersen P.I., Hassan M., Shafiek H., Prosch H., Tanoki A.D., Annema J.T., Munavvar M., Bonta P.I., de Wever W., Juul A.D.

The Clinical Techniques, Imaging and Endoscopy Assembly is involved in the diagnosis and treatment of several pulmonary diseases, as demonstrated at the 2023 European Respiratory Society (ERS) International Congress in Milan, Italy.From interventional pulmonology, the congress included several exciting results for the use of bronchoscopy in lung cancer, including augmented fluoroscopy, robotic-assisted bronchoscopy and cryobiopsies. In obstructive lung disease, the latest results on bronchoscopic treatment of emphysema with hyperinflation and chronic bronchitis were presented. Research on using cryobiopsies to diagnose interstitial lung disease was further explored, with the aims of elevating diagnostic yield and minimising risk.For imaging, the latest updates in using artificial intelligence to overcome the increased workload of radiologists were of great interest. Novel imaging in sarcoidosis explored the use of magnetic resonance imaging, photon-counting computed tomography and positron emission tomography/computed tomography in the diagnostic work-up. Lung cancer screening is still a hot topic and new results were presented regarding incorporation of biomarkers, identifying knowledge gaps and improving screening programmes.The use of ultrasound in respiratory medicine is an expanding field, which was demonstrated by the large variety in studies presented at the 2023 ERS Congress. Ultrasound of the diaphragm in patients with amyotrophic lateral sclerosis and myasthenia gravis was used to assess movements and predict respiratory fatigue. Furthermore, studies using ultrasound to diagnose or monitor pulmonary disease were presented. The congress also included studies regarding the training and assessment of competencies as an important part of implementing ultrasound in clinical practice.

He G., Han Y., Zhan Y., Yao Y., Zhou H., Zheng X.

BackgroundA variety of parameters and diaphragmatic ultrasound in ventilator weaning has been studied extensively, and the findings yield inconsistent conclusions. The parasternal intercostal muscle holds important substantial respiratory reserve capacity when the central drive is enhanced, the predictive value of combining parasternal intercostal muscle ultrasound parameters with P0.1(airway occlusion pressure at 100 msec) in assessing ventilator weaning outcomes is still unknown.ObjectivesOur study aimed to evaluate the predictive efficacy of parasternal intercostal muscle ultrasound in conjunction with P0.1 in determining weaning failure.MethodsWe recruited patients who had been admitted to ICU and had been receiving mechanical ventilation for over two days. All patients underwent a half-hour spontaneous breathing trial (SBT) with low-level pressure support ventilation (PSV). They were positioned semi-upright for parasternal intercostal muscle ultrasound evaluations, including parasternal intercostal muscle thickness (PIMT), and parasternal intercostal muscle thickening fraction (PIMTF); P0.1 was obtained from the ventilator. Weaning failure was defined as the need for non-invasive positive pressure ventilation or re-intubation within 48 h post-weaning.ResultsOf the 56 enrolled patients with a mean age of 63.04 ± 15.80 years, 13 (23.2%) experienced weaning failure. There were differences in P0.1 (P = .001) and PIMTF (P = .017) between the two groups, but also in patients with a diaphragm thickness ≥ 2 mm. The predictive threshold values were PIMTF ≥ 13.15% and P0.1 ≥ 3.9 cmH2O for weaning failure. The AUROC for predicting weaning failure was 0.721 for PIMTF, 0.792 for P0.1, and 0.869 for the combination of PIMTF and P0.1.ConclusionsThe parasternal intercostal muscle thickening fraction and P0.1 are independently linked to weaning failure, especially in patients with normal diaphragm thickness. The combination of parasternal intercostal muscle thickening fraction and P0.1 can serve as a valuable tool for the precise clinical prediction of weaning outcomes.Trial registrationChinese Clinical Trial Registry website (ChiCTR2200065422).

Guzmán-David C.A., Ruiz-Ávila H.A., Camargo-Rojas D.A., Gómez-Alegría C.J., Hernández-Álvarez E.D.

Abstract Purpose Muscular atrophy implies structural and functional alterations related to muscular force production and movement. This condition has been reported to be the main reason for generalized muscle weakness; it reflects the severity of the disease and can have a profound impact on short- and long-term clinical outcomes. The purpose of this study was to determine whether muscle atrophy ultrasound parameters early predict muscle weakness, morbidity, or 28-days mortality. Methods This was a prospective, observational single center cohort study. Ultrasound was used to determine the cross-sectional area and muscle thickness of the rectus femoris on the first and third day of ICU stay. The main outcome was the incidence of significant muscle atrophy (≥ 10%). Results Ultrasound measurements were made in 31 patients, 58% (18/31) of which showed significant muscle atrophy. The relative loss of muscle mass per day was 1.78 at 5% per day. The presence of muscle atrophy presents increased risk for limb muscle weakness and handgrip weakness. The 28-days mortality rate was similar in both subgroups. Conclusion The presence of muscle atrophy presents an increased clinical risk for the development of limb ICUAW and handgrip, although these observations were not statistically significant. The results could be used to plan future studies on this topic.

García R.M., Fernández-Martínez M.N., Sedano A.C., Villoria M.G., Sastre E.A., Fernández-García D.