Katarzyna B. Lewandowska

Post-COVID-19 syndrome is associated with persistent inflammation and an elevated risk of late venous thromboembolism (VTE). The role of proinflammatory cytokines has been well documented in the acute phase of the disease, but their potential role in late post-COVID-19 VTE remains unknown. What is the prevalence of VTE among symptomatic post-COVID-19 patients, and which laboratory parameters could enhance the diagnostic accuracy for VTE in these patients? Consecutive patients with objectively confirmed previous SARS-CoV-2 infection, admitted to a single department of lung diseases in a tertiary hospital due to sustained symptoms of dyspnea and/or exercise intolerance, were included. Clinical assessment and laboratory testing, including cytokine profiling (Il-1β, IL-6, IL-8, IL-10, TNF-α), PAI-1, and ferritin, were performed. VTE events (pulmonary embolism and/or deep vein thrombosis) were confirmed by standard imaging. Clinical and laboratory parameters were compared between participants with and without VTE. 108 patients: 69 (63.9%) males and 39 (36.1%) females, entered the study. VTE episodes were diagnosed in 39.8% (16.7% in the course of COVID-19 and 23.1% after the acute phase of the disease). Patients who entered the study ≤6 months and >6 months from acute COVID-19 infection were compared. Median D-dimer concentration was higher in patients with VTE that occurred within 6 months from the COVID-19 diagnosis compared to the non-VTE group (607 ng/mL vs. 428 ng/mL, borderline significance, p = 0.0595). Median_IL-8 concentration was significantly higher in those who developed VTE more than 6 months after COVID-19 compared to non-VTE patients: 10.19 pg/mL vs. 6.61 pg/mL, respectively, p = 0.048. The same was noted for TNF-α (39.02 pg/mL vs. 24 pg/mL, respectively, p = 0.011). The best diagnostic utility for VTE prediction was obtained for TNF-α concentration in symptomatic patients diagnosed >6 months from acute COVID-19 infection (ROC AUC 0.73, 95% CI 0.57–0.91). TNF-α was an independent risk factor of VTE episodes in the whole study group. Detection of elevated IL-8 and TNF-α levels later than 6 months from acute COVID-19 disease may help to identify patients at increased risk of late venous thromboembolism; nevertheless, further studies are needed to validate this observation.

Idiopathic pulmonary fibrosis (IPF) causes a high symptom burden and low quality of life for patients. Antifibrotic drugs can slow the disease's progression, but their impact on quality of life is limited. Aim: Our study aimed to analyze how quality of life, as measured by the EQ-5D-3L questionnaire, changed over time in IPF patients treated with antifibrotics versus those not treated. Group: Incident cases from the EMPIRE registry with at least two EQ-5D-3L responses were enrolled. The cohort comprised 1635 patients receiving antifibrotic treatment (AF1) and 361 untreated (AF0). Patients in the AF1 group were younger, had higher BMI, more frequently showed a UIP pattern on HRCT, and had lower baseline FVC% pred. and TLco % pred. Results: No differences were found in baseline response distribution across four of the five domains of the EQ-5D-3L questionnaire; in the pain-related question, untreated patients more frequently reported „some problems” and „extreme problems” (p=0.012). A positive nonsignificant trend in the total EQ-5D-3L score was observed in favor of treated subjects (p=0.079). The „health today” status didn’t differ between the groups. The annual decline in the current health assessment did not differ between the AF1 and AF0 groups and was 2.27 and 3.4 points after adjusting for baseline QoL and FVC, respectively. There was a significant difference between groups in the index score (0.058 per year on average in the AF0 group and 0.034 in the AF1 group, p=0.034). Conclusion: The quality of life declined in both groups of patients with IPF, but this was more pronounced in untreated patients. The index score decreased significantly less in the treated group. Antifibrotic drugs may positively affect patients’ quality of life despite the observed side effects of treatment.

Rationale: Hypersensitivity pneumonitis (HP) is an increasingly recognized interstitial lung disease caused by exposure to inhaled, mostly organic, antigens. The non-fibrotic type of HP generally follows a benign course. We present 3 patients with a rare presentation of non-fibrotic HP—acute respiratory failure. Patient concerns: 2 females and 1 male, presented to the pulmonary department due to resting dyspnea, cough and low-grade fever. Arterial blood gases revealed profound hypoxemia. No relevant abnormalities were found in the blood tests. In high-resolution computed tomography (HRCT), signs of extensive interstitial lung disease were present. Infection was excluded based on genetic testing and cultures. Pulmonary function tests revealed decrease in forced vital capacity (FVC) and transfer factor of the lungs for carbon monoxide (TLco). Diagnoses: Non-fibrotic HP was diagnosed based on positive exposure to organic antigens, characteristic lung HRCT pattern, and bronchoalveolar lavage lymphocytosis (in 2 cases). Interventions: Oxygen therapy was implemented through the nasal tube, accompanied by intravenous and subsequently oral steroids, gradually tapered. Outcomes: Rapid clinical improvement, near-complete regression of interstitial lung disease, significant increase in lung volumes and lung transfer factor for carbon monoxide were observed and maintained with low-dose therapy. Lessons: Non-fibrotic HP rarely presents as a life-threatening interstitial lung disease, requiring immediate immunosuppressive treatment. In some patients with extensive lung involvement, prolonged steroid therapy is necessary to achieve complete resolution of lung opacities and clinical improvement.

Background: Despite advancements in pharmacological therapy, lung transplantation (LuTX) remains the only life-prolonging treatment in end-stage idiopathic pulmonary fibrosis (IPF). However, real-world referral patterns in Central and Eastern European (CEE) countries remain poorly characterized. We aimed to comprehensively review factors influencing referral and identify systemic barriers to LuTX access. Methods: Baseline characteristics of IPF patients potentially eligible for LuTX, enrolled in the European MultiPartner IPF Registry between 2012 and 2022 (n = 1256), were retrospectively analyzed. LuTX (n = 94) and potentially eligible but not transplanted (n = 1162) subgroups were compared. National experts also completed a questionnaire assessing transplant referral and listing practices across different healthcare systems. Results: Only 7.5% of potentially eligible subjects were transplanted, revealing substantial geographic disparities, with Israel having the highest rates (43.1%), followed by Austria (9.5%), Hungary (7.8%), and the Czech Republic (4.6%). LuTX patients were younger (60.2 ± 7.4 vs. 62.6 ± 6.2 years, p < 0.001), had worse lung function (FVC 60 ± 15 vs. 74 ± 21% predicted; p < 0.001, TLCO 41 ± 15 vs. 49 ± 19% predicted; p < 0.001), and were more likely to receive antifibrotic and oxygen therapies. The most frequent reasons for exclusion from referral/listing were age > 70 years and concomitant heart/renal failure. Conclusions: This first comprehensive CEE analysis demonstrates low IPF transplant rates with high inter-country variability. Patients presenting early with functionally advanced disease are more likely transplanted, while advanced age remains the primary exclusion factor, highlighting critical access gaps potentially contributing to regional outcome differences.

Background: Cardiac involvement, one of the most life-threatening complications of sarcoidosis, remains under-recognized due to its oligo-symptomatic presentation in some patients. This retrospective study aimed to evaluate the utility of various clinical predictors of cardiac sarcoidosis (CS) development. Methods: The study included patients with pulmonary sarcoidosis diagnosed according to the recent ATS guidelines between January 2020 and July 2024 who underwent cardiac magnetic resonance (CMR) due to clinical suspicion of CS. The original Lake Louise criteria were used to identify active myocarditis. Results: Out of 393 patients diagnosed with pulmonary sarcoidosis, CMR was performed in 92 patients. Cardiac sarcoidosis was confirmed in 48 patients (52%, CS+), and excluded in 44 patients (48%, CS−). CS(+) patients demonstrated significantly more frequent Holter ECG abnormalities and liver/spleen sarcoidosis compared to CS(−) patients. Stage IV pulmonary disease, ECG abnormalities, and hypercalcemia were more common in CS(+) than in CS(−) patients; however, these differences did not reach statistical significance. Multivariate analysis identified Holter ECG abnormalities and liver/spleen involvement as significant predictive factors for CS, increasing the risk of cardiac involvement by approximately 4- and 6-fold, respectively. An AI-assisted simple scoring system based on five parameters: ECG abnormalities, Holter ECG abnormalities, liver/spleen involvement, gender, and stage of sarcoidosis predicted CS with a sensitivity of 76% and specificity of 74%, using an optimal cut-off value of ≥7.6 points. Conclusions: In patients with pulmonary sarcoidosis, an AI-assisted scoring algorithm derived from L1-regularized logistic regression results accurately predicted cardiac involvement on CMR with high specificity and sensitivity. Prospective validation of this algorithm is necessary to confirm its clinical utility in predicting cardiac sarcoidosis.

Background: Pulmonary function tests (PFTs) are essential for predicting outcomes in interstitial lung disease (ILD). In 2022, an expert panel recommended using z-scores instead of the traditional % predicted cut-off values to interpret the severity of PFT abnormalities which may lead to discordant classifications in some patients. To assess the magnitude and prognostic impact of this phenomenon we compared these two approaches in predicting all-cause mortality in a large cohort of patients with ILDs. Methods and findings: We retrospectively analyzed data from a tertiary referral center for patients with ILDs. Absolute FEV₁, FVC, TLC, and TLCO values from patients’ first presentations were transformed and presented as % predicted and z-scores using the most recent global lung initiative (GLI) reference values. Results were categorized for severity according to % predicted and z-score levels. Predictors of all-cause mortality over a 14-year follow-up were determined using Kaplan–Meier survival analysis and Cox proportional hazards regression. Between January 2009 and March 2023, 6,808 patients with ILDs were evaluated at the National TB and Lung Diseases Research Institute in Warsaw, Poland. Most were diagnosed with sarcoidosis, fibrotic ILD, or non-fibrotic ILD. At their first presentation, 13.2% had airway obstruction, 23.1% had low FVC (indicative of restriction by spirometry), and 45.6% had a reduced lung transfer factor (TLCO). Reclassification of spirometric indices occurred in 26.8% of patients for FEV₁ and 24.6% for FVC among those with abnormal results, with most being reassigned to a less severe categories. For TLCO, 28.1% of patients with reduced values were reclassified, with most shifting to more severe categories. During the follow-up, 1,525 (22.4%) of patients died. Both low FVC and low TLCO predicted all-cause mortality, with z-score thresholds showing stronger associations with mortality. A one-unit decrease in the FVC z-score was associated with a 10.3% increase in the risk of death, while a one-unit decrease in TLCO z-score was linked to an over 30% increase in mortality risk. Limitations of this retrospective single-center study include lack of data on cause-specific mortality, potential residual confounding, and limited generalizability to non-Caucasian or younger populations. Conclusions: The recently recommended use of z-scores leads to significant reclassification of lung function results in patients with ILDs, largely driven by age. This approach is justified by its stronger prognostic associations. Severe TLCO impairment remains a robust predictor of mortality in ILDs.

Idiopathic pulmonary fibrosis (IPF) is a rare disorder concerning elderly people, predominantly men, active or former smokers, with a progressive nature and leading to premature mortality. The cause of the disease is unknown. However, there are some risk factors, among which genetic predisposition plays a role. The aim of our single-centered observational study was to assess the correlation between single nucleotide polymorphism (SNP) of the MUC5B gene (rs35705950) and the disease course, antifibrotic treatment effect, and survival in patients with IPF. A total of 93 patients entered the study, of whom 88 were treated with either nintedanib or pirfenidone. The GG genotype was found in 28 (30.1%) subjects, while the GT or TT genotypes were found in the remaining 65 (63.4%) and 6 (6.5%) patients, respectively. The T allele minor allele frequency (MAF) accounted for 38.2% of the whole group. Patients with different genotypes did not differ significantly regarding age, sex, pulmonary function tests’ results, response to the antifibrotic treatment, or survival. However, we found a survival advantage in female patients and patients with higher pre-treatment TL,co. Treatment with antifibrotics significantly decreased the magnitude of FVC and TL,co decline compared to the time before treatment initiation, regardless of MUC5B status. In conclusion, we found high prevalence of T allele of MUC5B gene in patients with IPF; however, it showed no influence on disease trajectory, survival, or antifibrotic treatment effect in the presented cohort.

Background. Hypersensitivity pneumonitis (HP) is an increasingly recognized interstitial lung disease, developing as a result of exposition to inhaled, mostly organic, antigens. Two types of the disease are presently distinguished based on HRCT pattern and/or lung biopsy: fibrotic and non-fibrotic (non-fHP). Complete antigen avoidance is the principle of non-fHP treatment. The indications for steroids use in non-fHP depend on the clinical course of the disease. Case presentations. We present three patients in whom acute respiratory failure was diagnosed as the first sign of non-fHP. Intravenous prednisolone, followed by oral therapy with prednisone in diminishing doses, resulted in marked clinical improvement. Respiratory failure subsided within a few days, but regression of lung opacities lasted from 3 to 7 months. In one patient, the discrete reticular opacities, suggestive of the early phase of lung fibrosis, were present on HRCT, but complete regression of lung disease was achieved in the course of treatment. The patients were instructed to avoid antigens exposure; nevertheless, in one of them, a relapse of the disease, requiring a temporal increase of prednisone dose, was observed. Conclusions. Non-fHP may present as sudden-onset hypoxemic respiratory failure. In such patients, the diagnosis is based on medical history concerning the exposition to inciting antigens and characteristic HRCT pattern. Intravenous therapy with prednisolone results in quick resolution of respiratory failure, and BAL performed with a few days of delay may still be of diagnostic value. Ground glass opacities and air trapping may persist for months from exposure.

Introduction: Hypersensitivity pneumonitis (HP) is an interstitial inflammatory lung disease that develops as a result of exposition to various, mostly organic antigens. In some patients, fibrotic HP is diagnosed. Factors predisposing to the development of fibrotic lung disease in HP patients are not well documented in the literature. The genetic susceptibility of the patient, type of inciting antigen, and type of exposure, as well as various demographic and clinical variables, may influence the fibrotic process. Aim: The aim of the present study was to investigate whether the type of inciting antigen increases the risk of fibrotic lung disease in HP patients. Methods: Clinical data of consecutive patients with HP diagnosed between 2019 and 2023 were retrospectively reviewed. The exposition to the inciting antigens was investigated by the standardized questionnaire. Recent HP classification into fibrotic (fHP) and non-fibrotic (non-fHP) types was applied. Results: Sixty-six patients diagnosed with HP were analyzed. All patients filled out the exposure questionnaire, and 62 (94%) reported at least one possible exposure. The most prevalent exposures reported were avian, water systems, feather duvets, and hay/straw. Exposure to avian antigens as well as to coal/biomass heating were significantly more prevalent among patients with fHP compared to those with non-fHP (70% vs. 40%, p = 0.03 and 27% vs. 5%, p = 0.04, respectively). Nevertheless, in the multivariate analysis, older age at diagnosis was the only factor influencing the development of fHP (OR 1.064, 95% CI 1.004 to 1.138, p = 0.04). Reported avian antigen exposure correlated well with positive precipitins to avian antigens, whereas no correlation was found between hay/straw exposure and positive antibodies to termophilic actinomycetes. Conclusions: Exposure to birds and coal heating was the most frequently present factor in subjects with fHP, but only older age at diagnosis remained a significant fHP predictor in the multifactor analysis.