Background Sarcoidosis and systemic sclerosis (SSc) are both rare multisystem disorders whose aetiology is not fully understood. Their coexistence is uncommon but clinically significant. Nailfold videocapillaroscopy (NVC) is a validated non-invasive technique for assessing peripheral microvascular involvement in SSc, and its potential utility in sarcoidosis/SSc overlap has not been systematically reported. Case presentation We report a 62-year-old female non-smoker with confirmed SSc (anti-Scl-70 positive, anti-Pm/Scl75 positive, sclerodactyly, Raynaud’s phenomenon) and concurrent pulmonary sarcoidosis with hepatic involvement. At multidisciplinary reassessment, NVC revealed tortuous and crossed capillaries, rare inverted apex, rare giant capillaries, slowed flow, oedema, and sparse neoangiogenesis, in the absence of microhaemorrhages -- a mixed pattern compatible with sarcoidosis/SSc overlap and distinguishable from isolated SSc. Rheumatological assessment confirmed SSc in clinical stability; NT-proBNP had markedly improved from 1222 pg/ml to 148 pg/ml at the current reassessment (2.5 years later), indicating significant haemodynamic improvement under combined therapy. Chest HRCT was substantially unchanged. Conclusion This case illustrates the diagnostic value of NVC in characterizing microvascular involvement in sarcoidosis/SSc overlap. NVC can distinguish the overlap pattern from isolated SSc, support longitudinal disease monitoring, and contribute to the multidisciplinary management of this rare condition.

BACKGROUND:The demographic shift of pulmonary arterial hypertension (PAH) patients, the expanding therapeutic armamentarium with new emerging drugs and the heterogenous experience in handling more complex therapies are making the management of PAH increasingly challenging. This project was developed to standardize PAH management across Italian centres and ensure timely access to the optimal therapeutic strategies. METHODS:A consensus document containing 10 statements, mainly focused on the use of parenteral prostanoids, was developed by eight experts in PAH during in-person and web-based meetings. Forty-six physicians were invited online to rate each statement, indicating their agreement, neutrality or disagreement. RESULTS:Forty physicians participated to the survey. There was strong agreement that age and comorbidities significantly influence the choice of PAH-targeted therapies. Agreement was also reached on the use of parenteral prostanoids in the following clinical scenarios: a) treatment-naive patients at high risk; b) newly diagnosed patients classified as intermediate-risk, with severe right ventricular dysfunction assessed invasively and c) prevalent high-risk patients, as defined by the 4-strata risk score. The use of parenteral prostanoids in selected newly diagnosed intermediate-risk patients with severe right ventricular dysfunction assessed by imaging achieved a mild agreement. Three statements did not meet the predefined threshold for consensus. CONCLUSIONS:These consensus statements are intended to support physicians in starting parenteral prostanoids, minimizing delays that could negatively affect patient prognosis.

Ultra-high-resolution propagation-based synchrotron phase-contrast CT is an emerging technique for lung imaging. However, its feasibility and diagnostic potential at radiation doses comparable to those used in standard clinical procedures has yet to be established. This study aims to evaluate the performance of phase-contrast CT in comparison with state-of-the-art high-resolution multislice CT and bronchoscopy, and to validate its diagnostic accuracy histologically using porcine and, for the first time, human lung specimens. Phase-contrast CT experiments were conducted at the Italian synchrotron using lung specimens mounted in a custom-made anthropomorphic chest phantom. Imaging utilized two photon-counting detectors under various acquisition settings, followed by artificial intelligence-based denoising. Sequential imaging by phase-contrast CT, multislice CT, and bronchoscopy was performed prior to formaldehyde vapor fixation and histological dissection. Image quality was assessed quantitatively (contrast-to-noise ratio, edge sharpness, power spectra) and qualitatively via radiological scoring across 14 criteria. Phase-contrast CT achieved effective pixel sizes of 0.067 mm (Hydra detector) and 0.038 mm (LAMBDA detector), at radiation doses near full-dose multislice CT (≈ 12 mGy). Denoising improved contrast without major loss of edge sharpness. Radiological scoring showed phase-contrast CT outperformed multislice CT in visualizing peripheral airways and fine parenchymal structures. Histological validation confirmed imaging accuracy. Limitations from source spot size (≈ 200 μm) were noted but did not prevent significant diagnostic improvements. Phase-contrast CT, combined with artificial intelligence-based denoising, offers detailed, non-invasive imaging of lung microstructures at clinically relevant radiation doses. It complements multislice CT, holds potential for clinical adoption in advanced pulmonary diagnostics, and may reduce reliance on invasive biopsies.

Introduction Obstructive sleep apnoea syndrome (OSAS) in female patients is an underestimated diagnosis due to its different clinical presentation respect to males. Untreated OSAS has been independently associated with cardiovascular mortality, a worsening health status and higher healthcare costs in female patients compared to males. For all these reasons, improved detection of OSAS in females is crucial. The aim of our study is to identify most reported symptoms and key risk factors in our female patients in order to create a female-tailored screening OSAS tool (OSAS Female Questionnaire, OSAF), across different OSAS severity strata. Methods Three hundred and forty-five patients were enrolled in a prospective multicentre observational study. They underwent Home Sleep Apnea Test (HSAT) and multiple questionnaires. Results OSAS was confirmed in 276 patients: 101 women and 175 men. Female patients more frequently reported the following symptoms: difficulty falling asleep, unrefreshing sleep, nocturia, memory loss, limb movements, difficulty concentrating, anxiety, depression, sleepiness, nocturnal sweats, insomnia, and morning headaches (p < 0.05). Asthma, hypothyroidism, and depression were more prevalent in OSAS female patients. In both mild and severe OSAS, females were more symptomatic than males. Our OSAF questionnaire showed good performance in women with moderate-severe OSAS (AUC 0.76). Conclusions Female patients with OSAS reported more frequently, sleepiness, nocturia and unrefreshing sleep. Compared to their male counterparts, with the same OSAS severity, females were more symptomatic. The OSAF may be a promising screening tool for suspected moderate-severe OSAS women.

Background and Aims The aim of this study was to evaluate whether echocardiography-derived phenotypes describing different degrees of right ventricular (RV) remodelling and dysfunction add prognostic information to that of current risk stratification tools in patients with pulmonary arterial hypertension (PAH) at first follow-up.Methods In 11 centres of the Italian Pulmonary Hypertension NETwork (IPHNET), data were prospectively collected from patients with PAH who underwent re-evaluation between 6 and 12 months after diagnosis. Echocardiographic variables were combined a priori to define four phenotypes representing different degrees of RV dilatation and right ventricular-pulmonary arterial (RV-PA) coupling: a mildly dilated right ventricle with preserved RV-PA coupling defined phenotype-1; a mildly dilated right ventricle with poor RV-PA coupling defined phenotype-2; a severely dilated right ventricle with preserved RV-PA coupling defined phenotype-3; a severely dilated right ventricle with poor RV-PA coupling, either with or without tricuspid regurgitation of moderate degree or more, defined phenotype-4. Patients were followed up for all-cause death for a median of 3.7 years.Results These echocardiographic phenotypes were present in all European Society of Cardiology/European Respiratory Society or REVEAL 2.0 risk groups except for the high-risk groups, which included only phenotype-3 and phenotype-4. In each risk group, RV phenotype-4 identified patients with a poorer prognosis; RV phenotype-1 identified patients with better survival in intermediate risk groups.Conclusions Echocardiography-derived phenotypes describing different degrees of RV remodelling and dysfunction provide prognostic information which is independent of and additional to the clinically defined risk in PAH patients at first follow-up.

Patients with muco-obstructive lung disease (MOLD) exhibit chronic bronchitis and inflammation, along with a progressive decline in lung function. Lung monitoring is typically performed using spirometry, especially by measuring the forced expired volume in the first second (FEV1). However, the limitations of spirometry motivated the exploration of alternative approaches. The spin-spin relaxation time (T2m) and the spin-lattice relaxation time (T1m) of sputum water hydrogens were measured using low-field nuclear magnetic resonance (LF-NMR) in 38 MOLD patients and 16 controls. The levels of TNFα/IL-6, the sputum microbiome composition/amount/indices and FEV1 were determined in parallel. We also investigated the correlation between T2m/T1m and the disease index (ID); ID, calculated relying on patient FEV1/TNFα/IL-6/bacteria concentration Cb values, is a measure of the patient's distance from the average healthy control. We observed the following significant correlations: T2m/T1m with ID, T2m with Cb, a potential correlation of T2m with the bacteria genera Streptococcus and Staphylococcus, T2m with the Shannon index, which reflects the broadness of the bacterial community in the sputum, and T2m with TNFα. FEV1 did not show any correlation. Our noninvasive/radiation-free/portable method of T2m/T1m measurement shows potential value in monitoring lung conditions in MOLD patients and may contribute to improved clinical decision-making.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and progressive respiratory disorder characterized by airflow limitation, chronic inflammation, and structural lung alterations. Despite advances in clinical monitoring, current approaches such as spirometry, symptom scores, and imaging remain limited in capturing disease complexity and early pathophysiological changes. In this context, microRNAs (miRNAs) have emerged as promising molecular biomarkers due to their involvement in key inflammatory and immune pathway regulation. Sputum is gaining attention as a non-invasive and informative matrix for studying COPD. As a surrogate of airway mucus, sputum reflects local pathological processes, including inflammation and tissue damage, and contains biomarkers such as miRNAs. Compared to circulating miRNAs, sputum-derived miRNAs appear to more accurately represent lung-specific alterations. In this review, we focus on works published so far about the identification of miRNAs in COPD sputum. Several miRNAs have been associated with COPD diagnosis, severity, and exacerbations. These findings, including the possible correlation of some miRNAs with sputum biophysical properties, support the value of integrated biomarker approaches. While further large-scale and standardized studies are required to validate the role of COPD miRNAs assessed in sputum, their evaluation in sputum represents a promising tool for improving the diagnosis, phenotyping and monitoring of COPD.

Pulmonary hypertension associated with idiopathic pulmonary fibrosis (PH-IPF) is a frequent and clinically relevant complication that worsens exercise capacity, quality of life, and survival. This narrative review summarizes the epidemiology, pathophysiology, diagnostic approach, and therapeutic landscape of PH-IPF. The development of PH in IPF reflects the combined effects of fibrotic parenchymal destruction, pulmonary vascular remodeling, hypoxic vasoconstriction, endothelial dysfunction, and altered vascular signaling. Diagnosis remains challenging because symptoms often overlap with those of advanced fibrotic lung disease and non-invasive tools have limited sensitivity; right heart catheterization remains the diagnostic gold standard. Antifibrotic agents are central to IPF management but have no established role as PH-targeted therapies. Most pulmonary arterial hypertension therapies have failed to show benefit in PH-IPF or have raised safety concerns, with ambrisentan and riociguat associated with harm. Inhaled treprostinil is currently the only approved therapy with randomized evidence of efficacy in PH associated with interstitial lung disease, including IPF. Supportive care, optimization of comorbidities, referral to expert centers, and timely lung transplantation evaluation remain essential components of management.

Background: Continuous positive airway pressure (CPAP) is the primary treatment for obstructive sleep apnea (OSA). Despite improvements in CPAP technology and management, adherence to therapy remains one of the main challenges to be addressed. Methods: We conducted a narrative review through PubMed (1995-2026). Studies were selected by clinical relevance, methodological quality and expert consensus. Results: OSA treatment outcomes are poor when CPAP adherence is defined as four hours per night. The first step in improving adherence is active patient involvement. This involves explaining what OSA is, its consequences, what PAP therapy is, and its potential benefits. The choice of the right mask is the first personalized step in CPAP adherence. OSA phenotype and endotype traits may help personalize treatment in selected patients, although their role in predicting CPAP adherence needs to be studied in greater depth. Problems during the first night and the first month are the main predictors of future adherence. Strategies such as cognitive behavioral therapy or motivational enhancement can improve adherence, especially during the initial period. Long-term adherence can be predicted from the initial period and maintained through scheduled follow-up. Group meetings, telephone calls and telemedicine interactions are also a valid way of improving adherence. Conclusions: Patients should initially be educated about how their symptoms are related to sleep apnea and how CPAP treatment could resolve them. The key to improving CPAP adherence is involving patients in personalized treatment with scheduled follow-up, particularly during the initial treatment period.

Background/Objectives: Allergic asthma (AA) is a common chronic respiratory disease characterized by airway inflammation and bronchial hyperreactivity triggered by environmental allergens such as pollen and dust mites. Allergen-specific immunotherapy (AIT), particularly its sublingual formulation (SLIT), is the only treatment capable of modifying the disease's natural course by targeting IgE-mediated sensitization mechanisms. Methods: We analyzed demographic, clinical, functional (FEV1, FVC, FEV1/FVC), and immunological data (specific IgE for Phl p1, Phl p5, Der p1, Der p2, Der p23), alongside asthma control parameters (ACT score), reliever use, and exacerbation frequency, in patients undergoing SLIT for grass pollen and dust mite allergens. Results: After at least twelve months of treatment, we observed significant reductions in exacerbation rate (p < 0.01) and reliever use (p = 0.0002). These improvements were particularly evident in the subgroup receiving grass pollen SLIT (p = 0.03 and p = 0.01, respectively). An increase in ACT score was observed but did not reach statistical significance (p = 0.07), likely due to already high baseline control. All patients reported improved rhinitis symptoms. Lung function parameters showed no significant changes. SLIT was well tolerated, with no serious adverse events or discontinuations. The subgroup of patients treated with dust mite SLIT was small, limiting the statistical power and generalizability of these findings. Consequently, the dust mite results should be interpreted cautiously and considered exploratory. The more robust and statistically supported findings pertain to the grass pollen SLIT group, reflecting a more consolidated evidence base for this allergen. Conclusions: SLIT for grass pollen demonstrated promising, statistically supported benefits in reducing exacerbations and improving disease control, supporting its role as an effective adjunct therapy in AA. While dust mite SLIT also showed positive trends, the limited sample size warrants further investigation to confirm these preliminary findings. Overall, SLIT appears to be a safe and potentially beneficial option for patients with AA and allergic rhinitis, but larger studies are needed to substantiate its efficacy across different allergens.

Abstract Introduction In late-onset Pompe disease (LOPD), muscle weakness causes restrictive lung impairment. In murine models, glycogen deposition in lung parenchyma suggests additional causes for restriction that remain poorly understood. We investigated whether oscillometry detects respiratory abnormalities not identified by spirometry and evaluated changes after air-stacking manoeuvres. Methods We prospectively evaluated 16 adults with LOPD from three Italian centres. Alongside spirometry, oscillometry (at 5, 11, and 19 Hz) was performed to assess resistance (R) and reactance (X) across the breathing cycle and by respiratory phase. Measurements were repeated 5 min after an air-stacking manoeuvre. Results Participants (7 men, 9 women; 51.6 ± 12.5 years) had moderate-to-severe restriction (FVC 53.3 ± 19.6% predicted) with preserved FEV1/FVC. Two oscillometric patterns emerged. The first one (seven patients) was characterised by an abnormal increase in expiratory resistance within breaths ([R5exp − R5insp] > 0.70 cmH 2 O·s/L), associated or not with abnormal whole-breath R and intrabreath X changes. The second pattern (nine patients) consisted of normal R and X changes in the breathing cycle. Air-stacking increased FVC (53.3 ± 19.6 to 71.3 ± 19.2% predicted, p < 0.001) without normalising reactance. Conclusion In LOPD, oscillometry detects distinct mechanical patterns not identified by spirometry. Air-stacking increases lung volumes without improving respiratory mechanics.

Muco-obstructive lung diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and bronchiectasis, are characterized by the accumulation of highly viscoelastic mucus that compromises mucociliary clearance and fosters infection and inflammation. Mucoactive therapy, encompassing both true mucolytics and non-cleaving agents, seeks to restore airway patency by altering mucus structure, hydration, and transport properties, yet its clinical impact remains variable. This narrative review provides a critical reappraisal of the pharmacological actions and therapeutic outcomes of the main mucolytic agents: N-acetylcysteine (NAC), erdosteine, carbocisteine, bromhexine, ambroxol, and dornase alfa. Beyond their classical role in reducing mucus viscosity, these drugs exhibit pleiotropic effects, including antioxidant, anti-inflammatory, and immunomodulatory activities. Specifically, for thiol-based compounds, the action consists of breaking the disulfide bonds that stabilize the mucin network; for carbocisteine, it lies in modulating mucin glycosylation and chloride transport. Ambroxol and bromhexine act by stimulating surfactant secretion and enhancing mucociliary clearance. Finally, dornase alfa exerts an enzymatic effect on extracellular DNA, a key contributor to the tenacity of mucus in cystic fibrosis. Clinical evidence indicates that NAC and erdosteine can reduce exacerbation rates in COPD, carbocisteine shows benefit with prolonged administration, and dornase alfa remains a cornerstone in CF management. However, therapeutic efficacy is constrained by heterogeneous mucus composition, pharmacokinetic limitations, and disease-specific variability. A key interpretative message is that clinical benefit appears greatest when the dominant biophysical determinant of mucus pathology is specifically targeted, supporting a transition from broad disease-label prescribing to mechanism-informed, phenotype-aware mucolytic therapy. Emerging strategies, such as agents targeting mucin-DNA interactions and advanced inhalation delivery systems, promise improved specificity and durability. By integrating mechanistic insights with clinical data, this review underscores the need for personalized mucolytic therapy and innovative approaches to overcome current challenges in managing muco-obstructive lung diseases.

Accurate diagnosis and characterization of lung disease increasingly rely on advanced imaging modalities capable of resolving fine microstructural details while minimizing radiation exposure. Phase-sensitive computed tomography (CT), particularly propagation-based imaging (PBI), offers superior soft tissue contrast but has historically been limited by the lack of compatible fixation techniques that preserve lung architecture post-excision. We present an adapted formaldehyde (FA) vapour fixation protocol designed to maintain human-sized lungs in a physiologically inflated and morphologically stable state. This approach prevents collapse of the delicate air–tissue interfaces, a major barrier to high-fidelity phase-contrast imaging and histological correlation. Our method enables high-resolution, multiscale imaging from whole-organ PBI at 67 µm voxel size to localized subcellular synchrotron PBI at 650 nm voxel size on the same specimen, with preserved spatial relationships critical for accurate validation of imaging findings. In porcine models, FA vapour fixation maintained alveolar integrity and radiological contrast without compromising histological detail, while also avoiding the artifacts associated with liquid fixation. Crucially, the protocol allows regulation of inflation and fixation dynamics, addressing longstanding challenges in ex vivo lung imaging and enabling consistent specimen preparation across studies. This fixation technique supports biosafe stabilization of freshly explanted human lungs–such as those from transplant procedures creating new opportunities for translational research on pathological tissue. By bridging high-resolution radiology and histopathology, our scalable fixation protocol establishes a standardized foundation for multimodal lung imaging and offers a critical tool for advancing both fundamental lung research and clinical diagnostics.

Non-small cell lung cancer (NSCLC) represents a heterogeneous group of malignancies characterised by diverse histological and molecular features. Some NSCLCs, particularly adenocarcinomas, harbour genomic alterations in receptor tyrosine kinases or downstream RAS/RAF signalling pathways, which are targets of effective therapies. NSCLCs lacking actionable genomic alterations often benefit from immune checkpoint inhibitors, though only a minority of patients achieve long-term survival. These tumours often carry alterations in tumour suppressor genes like TP53, KEAP1, STK11, or NF1, for which pharmacological strategies are still under investigation. This review explores emerging therapeutic opportunities unveiled by multi-omics studies in NSCLCs without actionable genomic alterations. Proteogenomic approaches—integrating genomic, transcriptomic and proteomic data—enable a comprehensive understanding of NSCLC molecular landscapes and signalling network dysregulation, helping to identify distinct tumour subtypes and potential therapeutic targets. These tumours exhibit alterations in cell cycle regulation, DNA repair, immune signalling, epigenetic modulation and metabolic and redox pathways. Although therapies targeting tumour suppressor genes like p53 remain highly anticipated, extending our understanding of the broader molecular landscape in these tumours may reveal novel vulnerabilities and inform the development of novel drugs or combination strategies. This could further advance precision oncology for NSCLC.

Obstructive Sleep Apnea (OSA) is the most common sleep- related breathing disorder. In recent years, evidence have shown that patients with OSA may have this disorder for different reasons, with different symptoms and comorbidities. Therefore, treatment should be individualized [1]. This has led to a growing interest in the characterization of the disease into phenotypes. OSA in elderly patients is often a challenge for clinician in terms of diagnosis, as symptoms may be masked, but also for treatment in terms of efficacy and adherence. However, aging is a pathophysiological factor that predisposes to obstructive sleep apnea, and the two conditions share symptoms and comorbidities to such an extent that it becomes very difficult to establish a casual link between the two. We summarize the recent evidence in OSA elderly patients, particularly in terms of pathophysiology, symptoms and main comorbidities.

INTRODUCTION:The occurrence of Raynaud's phenomenon in patients with multiple sclerosis (MS) is infrequently documented in the literature. Some cases have been attributed to interferon-β therapy, while others have emerged in MS patients who sub-sequently developed Raynaud's phenomenon and/or systemic sclerosis. The association between microangiopathic damage and both Raynaud's phenomenon and systemic sclerosis is well-established, leading to the adoption of nailfold video-capillaroscopy (NVC) as a non invasive diagnostic tool for the initial clinical assessment of these conditions. CASE PRESENTATION:We present a case study of a 42-year-old female patient with Raynaud's phenomenon in MS. The patient underwent NVC in 2023 showing microvascular impairment and after one year and Natalizumab treatment she repeated NVC evaluation with significant improvement in previous microangiopathic changes. A comprehensive literature review regarding the relationship between MS and Raynaud's phenomenon was conducted using electronic databases (PUBMED, UpToDate, Google Scholar, ResearchGate), along with manual searches for relevant articles published up to December 2024. DISCUSSION:This case highlights the potential utility of NVC in the ongoing evaluation of microangiopathic damage in MS patients exhibiting Raynaud's phenomenon. By elucidating the overlap between these conditions, NVC may serve as a valuable tool in the clinical management of affected individuals.

BACKGROUND AND AIM:Sarcoidosis is a systemic granulomatous inflammatory disease that can affect virtually any organ, with a predilection for the lungs. It may present vasculitic features involving small, medium, or large vessels. Microvascular alterations in sarcoidosis can be assessed using nailfold videocapillaroscopy (NVC), a tool widely applied in the diagnosis and monitoring of systemic sclerosis, among other conditions. The aim of our study was to detect microcirculatory changes in patients with sarcoidosis and investigate their potential correlation with organ involvement. METHODS:We conducted a single-center, retrospective case-control study involving three groups: 51 patients diagnosed with sarcoidosis, 51 healthy volunteers serving as controls, and 51 patients with systemic sclerosis. The groups were similar in sex and age. All participants underwent nailfold videocapillaroscopy (NVC) to assess microvascular changes. RESULTS:This study confirmed the presence of non-specific microcirculatory abnormalities in patients with sarcoidosis, particularly in terms of reduced capillary density, the presence of angiogenesis, and slowed capillary flow. Although these alterations do not currently appear to correlate with specific clinical aspects of the disease, (e.g. the presence of autoantibodies, laboratory parameters and variables of lung function). CONCLUSIONS:Our findings confirm the presence of non-specific microvascular abnormalities in sarcoidosis. However, the identification of these capillaroscopic alterations as specific to sarcoidosis requires further confirmation. Ongoing studies aim to explore the potential role of NVC as a diagnostic marker and to investigate its correlation with the clinical manifestations of sarcoidosis.

Background Despite several randomised controlled trials (RCTs) on the use of adjuvant treatment with corticosteroids in patients with community-acquired pneumonia (CAP), the effect of this intervention on mortality remains controversial. We aimed to evaluate heterogeneity of treatment effect (HTE) of adjuvant treatment with corticosteroids on 30-day mortality in patients with CAP. Methods In this individual patient data meta-analysis, we included RCTs published before July 1, 2024, comparing adjuvant treatment with corticosteroids versus placebo in patients hospitalised with CAP. The primary endpoint was 30-day all-cause mortality, collected across all trials, and analyses followed the intention-to-treat principle. We analysed HTE using risk and effect modelling. For risk modelling, patients were classified as having less severe or severe CAP based on the pneumonia severity index (PSI), comparing PSI class I-III versus class IV-V. For effect modelling, we trained a corticosteroid-effect model on six trials and externally validated it using data from two trials, received after model preregistration. This model classified patients into two groups: no predicted benefit and predicted benefit from adjuvant treatment with corticosteroids. The literature search was registered on PROSPERO, CRD42022380746. Findings We included eight RCTs with 3224 patients. Across all eight trials, 246 (76%) patients died within 30 days (106 [66%] of 1618 in the corticosteroid group vs 140 [87%] of 1606 in the placebo group; odds ratio [OR] 072 [95% CI 056-094], p=0017). The corticosteroid-effect model, which selected C-reactive protein (CRP), showed significant HTE during external validation in the two most recent trials. In these trials, 154 (114%) of 1355 patients died within 30 days (88 [131%] of 671 in the placebo group vs 66 [96%] of 684 in the corticosteroid group; OR 071 [95% CI 050-099], p=0044). Among patients predicted to have no benefit (CRP <= 204 mg/L, n=725), no significant effect was observed (OR 098 [95% CI 063-150]), whereas for those with predicted benefit (CRP >204 mg/L, n=630), 39 (130%) of 301 patients died in the placebo group compared with 20 (61%) of 329 in the corticosteroid group (043 [025-076], p(interaction)=0026). No significant HTE was found between less severe CAP (PSI class I-III, n=229) and severe CAP (PSI class IV-V, n=1126). Corticosteroid therapy significantly increased hyperglycaemia risk (44 [128%] of 344 in the placebo group vs 84 [248%] of 339 in the corticosteroid group; OR 250 [95% CI 163-383], p<00001) and hospital re-admission risk (30 [37%] of 814 in the placebo group vs 57 [70%] of 819 in the corticosteroid group; 195 [124-307], p=00038). Interpretation Overall, adjuvant therapy with corticosteroids significantly reduces 30-day mortality in patients hospitalised with CAP. The treatment effect varied significantly among subgroups based on CRP concentrations, with a substantial mortality reduction observed only in patients with high baseline CRP. Copyright (c) 2025 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND:As most cystic fibrosis (CF) patients progress to respiratory failure, lung functionality assessment is pivotal. We previously developed a test that monitors airways measuring the spin-spin relaxation time (T2m) of water hydrogens present in sputum using Low Field-Nuclear Magnetic resonance (LF-NMR). OBJECTIVES:To investigate further the significance of T2m exploring: 1) T2m correlation with the effects of chest physiotherapy (CP); 2) the influence of sputum contamination by saliva on T2m; 3) T2m relation with sputum mesh size; 4) T2m correlation with the effects of the CFTR-modulator Elexa-caftor/Tezacaftor/Ivacaftor (ETI). METHODS:T2m was measured in the sputum of 16 CF-patients before/after CP and in 9/16 patients before/after ETI administration. FEV1/C reactive protein (CRP)/erythrocyte-sedimentation rate (ESR) and sweat chloride concentration were measured using standard techniques. Sputum contamination by saliva/sputum mesh size were determined mathematically. RESULTS:We prove that T2m can be used to detect the lack of significant effects on lung function by CP (confirmed by FEV1). Moreover, we developed of a mathematical approach to correct T2m value in sputum samples contaminated by saliva and to determine the relationship between T2m and sputum mesh size. Finally, we show that T2m can effectively detect the positive effects of ETI on lung function (evaluated by FEV1) and that T2m inversely correlates with the CRP/ESR/chloride sweat concentration. CONCLUSION:This data strengthens the rationale for T2m employment in CF lung disease monitoring and show that T2m can be profitably used to complement the FEV1 test.