Katerina M. Antoniou

Pulmonary Hypertension (PH) in patients with Interstitial Lung Disease (ILD) is a critical, yet underrecognized, complication that affects patients’ quality of life and increases mortality. Emerging evidence further suggests that PH-ILD is not merely a consequence of hypoxia and parenchymal fibrosis, as the severity of pulmonary vascular disease often correlates poorly with the extent of fibrotic lung involvement, indicating more complex underlying pathophysiological mechanisms. Diagnosis requires a high index of suspicion when symptoms appear “disproportionate” to the degree of parenchymal lung disease. Key indicators include diffusing capacity for carbon monoxide (DLCO) < 45%, a forced vital capacity to diffusing capacity for carbon monoxide ratio (FVC/DLCO) > 1.6, and radiological findings of increased pulmonary artery diameter. While echocardiography and circulating biomarkers serve as useful screening tools, right heart catheterization remains the gold standard for definitive diagnosis. Early identification is essential for risk stratification, lung transplant evaluation, and determining eligibility for targeted pharmacological interventions, as this group of patients remains one of the most therapeutically challenging forms of pulmonary vascular disease. Ongoing research and advances in diagnostic tools are increasingly focused on refining phenotypic classification, identifying valuable biomarkers, and elucidating molecular drivers that may enable personalized treatment strategies in this heterogeneous patient group.

Background and Aims: Plasma fibrinogen and fractional exhaled nitric oxide (FeNO) reflect neutrophilic and eosinophilic airway inflammation, respectively, and are associated with disease activity and severity in different directions in bronchiectasis. This study aimed to concurrently investigate fibrinogen and FeNO and further evaluate the clinical importance of fibrinogen-to-FeNO ratio (FFR) as a composite biomarker in bronchiectasis. Methods: This was a two-centre, observational, cross-sectional study involving stable bronchiectasis patients. Fibrinogen, FeNO, and the ratio of their normalised values (FFR) were investigated in relation to clinical indicators of disease activity and severity, including respiratory symptoms, inflammatory markers, pulmonary function, radiological extent, airway infection, severity scores, and patient-reported outcomes. Results: FFR was correlated with both circulating neutrophils (r = 0.36, p = 0.04) and eosinophils (r = −0.39, p = 0.03) and, more strongly compared to fibrinogen and FeNO, with the percentage of predicted forced expiratory volume in the 1st second (r = −0.61, p < 0.001). Interestingly, only FFR was found to be higher in patients with Pseudomonas aeruginosa isolation in respiratory secretions (p < 0.01). In receiver operating characteristic curves, FFR showed good discriminatory ability to differentiate patients with any level (AUC: 0.80, 95% CI: 0.64–0.96) or a severe level (AUC: 0.83, 95% CI: 0.64–1.00) of pulmonary functional impairment and patients with severe disease (AUC: 0.78, 95% CI: 0.62–0.94). Conclusions: FFR emerges as a candidate biomarker capturing the balance between neutrophilic and eosinophilic inflammation and the net disease activity and severity in bronchiectasis.

Background/Aim: Chronic airway diseases, including chronic obstructive pulmonary disease (COPD), asthma, and asthma COPD overlap (ACO), are characterized by complex inflammatory processes in which Activin A–a key member of the TGF-β superfamily–is implicated. Although its role in the stable state of these diseases has been extensively studied, data regarding its involvement during exacerbations remain limited. Our objective was to investigate the dynamics of Activin A in sputum and serum during acute exacerbations and subsequent convalescence in patients with chronic airway diseases. Patients and Methods: In this prospective study, 53 patients with asthma, COPD, and ACO, aged 14 years and older were recruited upon hospitalization for an acute exacerbation. Sputum and peripheral blood samples were collected at admission, hospital discharge, one month, and four months post-exacerbation. Protein levels of Activin A were quantified by ELISA were compared among the patient groups and the kinetics of Activin A expression following exacerbation events were examined. Results: Baseline Activin A levels were comparable across the patient groups. However, during exacerbations, sputum Activin A levels increased markedly and subsequently declined during convalescence, while serum levels exhibited an inverse pattern-being lower during exacerbations and rising during stable periods. Notably, COPD patients with recurrent exacerbations maintained persistently elevated sputum Activin A levels throughout the study period, suggesting that sustained local inflammation may predispose these patients to frequent exacerbations. Conclusion: These findings reveal a compartment-specific regulation of Activin A in chronic airway diseases, underscoring its potential as a biomarker for disease activity and exacerbation risk.

Obstructive sleep apnea (OSA) and idiopathic pulmonary fibrosis (IPF) frequently coexist. Elevated levels of Krebs von den Lungen‑6 (KL‑6), endothelin‑1 (ET‑1) and S100 calcium‑binding protein A9 (S100A9) have been observed in patients with IPF, suggesting their potential role as biomarkers for lung fibrosis. The aim of the present study was to measure the levels of KL‑6, ET‑1 and S100A9 in patients with IPF‑OSA and to test the potential of these biomarkers as a characteristic OSA signature with diagnostic and prognostic potential for IPF. A total of 55 subjects with newly‑diagnosed IPF participated in the present cross‑sectional study. In addition to performing overnight attended polysomnography and pulmonary function tests, serum and bronchoalveolar lavage (BAL) levels of KL‑6, along with serum levels of ET‑1 and S100A9, were also assessed. A total of 15 patients with IPF and 40 patients with IPF‑OSA were included. Age, sex, comorbidities and pulmonary function tests did not differ between the groups. Although there was no significant difference between groups in the levels of KL‑6, ET‑1 and S100A9 (P>0.05), the serum ET‑1 levels tended to be elevated in patients with OSA‑IPF compared with patients with IPF (1.78 vs. 1.07 pg/ml; P=0.06). Additionally, a significant association was observed between serum KL‑6 levels and the severity of IPF, and also between BAL KL‑6 levels and nocturnal mean SaO₂ levels, even after taking into account factors such as obesity and smoking. S100A9 levels were associated with the oxygen desaturation index, even after adjustments for obesity, smoking and the gender‑age‑physiology index, only in the IPF‑OSA group. Conclusively, the present findings suggested significant associations between serum ET‑1, S100A9 and BAL KL‑6 levels and specific OSA severity parameters in the IPF‑OSA group. This evidence suggested that these molecules could serve as biomarkers for the identification of patients with IPF‑OSA, offering a distinct OSA signature that has diagnostic and potential treatment value. Larger studies are crucial to substantiate the present findings and reinforce this hypothesis.

Background: Suspected Interstitial Lung Disease (ILD) patients may be referred to an ILD-specialist centre or non-ILD-specialist centre for diagnosis and treatment. Early referral and management of patients at ILD-specialist centres has been shown to improve survival and reduce hospitalisations. The COVID-19 pandemic has affected the ILD patient diagnostic pathway and prompted centres to adapt.Aims: This study investigates and contrasts ILD patient pathways in ILD-specialist and non-ILD-specialist centres, focusing on referrals, caseloads, diagnostic tools, multi-disciplinary team (MDT) meeting practices, and resource accessibility.Methods: Conducted as a cross-sectional study, a global self-selecting survey ran from September 2022 to January 2023. Participants included ILD specialists and healthcare professionals (HCPs) from ILD-specialist centres and non-ILD-specialist centres.Results: Of 363 unique respondents from 64 countries, 259 were from ILD-specialist centres and 104 from non-ILD-specialist centres. ILD centres had better resource availability, exhibiting higher utilisation of diagnostic tests (median: 12 tests), than non-ILD centres (9 tests); and better access to specialist professions attending MDTs (median: 6 professions at meeting) in specialist centres than non-ILD centres (3 professions at meeting). Transitioning to virtual MDTs allowed HCPs from outside of centres to join meetings in nearly 90% of all centres, increasing regular participation in 60% of specialist centres and 72% of non-ILD centres. For treatment of patients, specialist centres had better access to antifibrotic drugs (91%) compared to non-ILD centres (60%).Conclusions: Diagnostic pathways for ILD patients diverged between specialist centres and non-ILD centres. Disparities in resource and specialist availability existed between centres.

Hypersensitivity pneumonitis (HP) is a complex interstitial lung disease caused by chronic inhalation of a wide variety of antigens in susceptible and sensitized individuals, commonly associated with an occupational exposure. An impressive number of inciting antigens causing hypersensitivity pneumonitis have been found to cover a wide range of occupations. As working practices have changed over time, especially in industrialized countries, new names for occupational HP have emerged. This review emphasizes the main diagnostic issues arising from the high variability of clinical presentation and the broad spectrum of causal antigens. Furthermore, it provides an overview of current methods to unveil possible causes of hypersensitivity pneumonitis, highlights HP’s current diagnostic and treatment challenges and the remaining areas of uncertainty, and presents prevention strategies.

Background: Overnight desaturation predicts poor prognosis across interstitial lung diseases (ILDs). The aim of the present study was to investigate whether nocturnal desaturation is associated with pulmonary vasculopathy and mortality.Methods: A retrospective single centre study of 397 new ILD patients was carried out including patients with idiopathic pulmonary fibrosis (IPF) (n=107) and patients with non-IPF fibrotic ILD (n=290). This is the largest study to date of the effect of significant nocturnal desaturation (SND) (≥10% of total sleep time with oxygen saturation ≤90% measured by pulse oximetry).Results: The prevalence of SND was 28/107 (26.2%) in IPF and 80/290 (27.6%) in non-IPF ILD. The prevalence of SND was higher in non-IPF ILDs than in IPF (p=0.025) in multivariate analysis. SND was associated with noninvasive markers of pulmonary hypertension (PH): tricuspid regurgitation velocity (TRV) (p<0.0001), brain natriuretic peptide (p<0.007), carbon monoxide transfer coefficient (p<0.0001), A–a gradient (p4% in 6-min walking test (p<0.03) and pulmonary artery diameter (p<0.005). SND was independently associated with high echocardiographic PH probability in the entire cohort (OR 2.865, 95% CI 1.486–5.522, p<0.002) and in non-IPF fibrotic ILD (OR 3.492, 95% CI 1.597–7.636, p<0.002) in multivariate analysis. In multivariate analysis, SND was associated with mortality in the entire cohort (OR 1.734, 95% CI 1.202–2.499, p=0.003) and in IPF (OR 1.908, 95% CI 1.120–3.251, p=0.017) and non-IPF fibrotic ILD (OR 1.663, 95% CI 1.000–2.819, p=0.041). Separate models with exclusion of each one of the diagnostic subgroups showed that no subgroup was responsible for this finding in non-IPF ILDs. SND was a stronger marker of 5-year mortality than markers of PH.Conclusion: SND was associated with high echocardiographic probability and mortality and was a stronger predictor of mortality in IPF and non-IPF ILDs grouped together to power the study.

This article summarises a selection of scientific highlights in the field of interstitial lung diseases (ILDs) presented at the International Congress of the European Respiratory Society in 2023. Translational and clinical studies focused on the whole spectrum of ILDs, from (ultra)rare ILDs to sarcoidosis, ILDs associated with connective tissue disease and idiopathic pulmonary fibrosis. The main topics of the 2023 Congress presentations were improving the diagnostic process of ILDs, better prediction of disease course and investigation of novel treatment options.

Tweetable abstract Individuals with IPF who follow a MUFA diet report a lower incidence of pirfenidone gastrointestinal adverse events than those that follow a SFA diet, which could explain the different prevalence in GI pirfenidone AEs reported by countries in IPF cohortshttps://bit.ly/3LuzAUJ

Pulmonary hypertension (PH) is a frequent complication of interstitial lung disease (ILD). Although PH has mostly been described in idiopathic pulmonary fibrosis, it can manifest in association with many other forms of ILD. Associated pathogenetic mechanisms are complex and incompletely understood but there is evidence of disruption of molecular and genetic pathways, with panvascular histopathologic changes, multiple pathophysiologic sequelae, and profound clinical ramifications. While there are some recognized clinical phenotypes such as combined pulmonary fibrosis and emphysema and some possible phenotypes such as connective tissue disease associated with ILD and PH, the identification of further phenotypes of PH in ILD has thus far proven elusive. This statement reviews the current evidence on the pathogenesis, recognized patterns, and useful diagnostic tools to detect phenotypes of PH in ILD. Distinct phenotypes warrant recognition if they are characterized through either a distinct presentation, clinical course, or treatment response. Furthermore, we propose a set of recommendations for future studies that might enable the recognition of new phenotypes.