Remotely supervised spirometry versus laboratory-based spirometry during the COVID-19 pandemic: a retrospective analysis.

BACKGROUND: The COVID-19 pandemic has constrained access to spirometry, and the inherent risk of infectious transmission during aerosol-generating procedures has necessitated the rapid development of Remotely Supervised Spirometry (RSS). This innovative approach enables patients to perform spirometry tests at home, using a mobile connected spirometer, all under the real-time supervision of a technician through an online audio or video call. METHODS: In this retrospective study, we examined the quality of RSS in comparison to conventional Laboratory-based Spirometry (LS), using the same device and technician. Our sample included 242 patients, with 129 undergoing RSS and 113 participating in LS. The RSS group comprised 51 females (39.5%) with a median age of 37 years (range: 13-76 years). The LS group included 63 females (55.8%) with a median age of 36 years (range: 12-80 years). RESULTS: When comparing the RSS group to the LS group, the percentage of accurate Forced Expiratory Volume in one second (FEV1) measurements was 78% (n = 101) vs. 86% (n = 97), p = 0.177; for Forced Vital Capacity (FVC) it was 77% (n = 99) vs. 82% (n = 93), p = 0.365; and for both FEV1 and FVC, it was 75% (n = 97) vs. 81% (n = 92), p = 0.312, respectively. CONCLUSIONS: Our findings demonstrate no significant difference in the quality of spirometry testing between RSS and LS, a result that held true across all age groups, including patients aged over 65 years. The principal advantages of remote spirometry include improved access to pulmonary function tests, reduced infectious risk to curtail disease spread, and enhanced convenience for patients.

High-Yield Production of Dihydroxyacetone from Crude Glycerol in Fed-Batch Cultures of Gluconobacter oxydans.

The strain Gluconobacter oxydans LMG 1385 was used for the bioconversion of crude glycerol to dihydroxyacetone. The suitability of fed-batch cultures for the production of dihydroxyacetone was determined, and the influence of the pH of the culture medium and the initial concentration of glycerol on maximizing the concentration of dihydroxyacetone and on the yield and speed of obtaining dihydroxyacetone by bioconversion was examined. The feeding strategy of the substrate (crude glycerol) during the process was based on measuring the dissolved oxygen tension of the culture medium. The highest concentration of dihydroxyacetone PK = 175.8 g·L-1 and the highest yield YP/Sw = 94.3% were obtained when the initial concentration of crude glycerol was S0 = 70.0 g·L-1 and the pH of the substrate was maintained during the process at level 5.0.

Periostin concentration in exhaled breath condensate in children with mild asthma.

OBJECTIVE: Periostin is considered to be a marker of eosinophilic inflammation in patients with asthma. However, there are no literature data on exhaled breath condensate (EBC) periostin level in pediatric patients with asthma. The aim of this study was to analyze EBC periostin concentration in children with mild asthma and to evaluate the potential usefulness of EBC periostin level as a biomarker for the disease. METHODS: EBC and serum periostin concentrations were measured by enzyme-linked immunosorbent assay in 23 children with asthma and 23 healthy controls. RESULTS: EBC periostin concentration was 250- to 780-fold lower than that found in serum. No significant differences between serum nor EBC periostin concentration in asthmatics and the control group were showed. The comparison between children with Th2 and non-Th2 type of asthma did not show significant differences in periostin concentration, both in serum and EBC. Serum periostin concentration inversely correlated with BMI and age not only in asthma patients but also in controls. CONCLUSIONS: In children with mild asthma, periostin may be measured not only in serum but also in EBC. The low periostin level in patients with mild asthma and lack of difference between asthmatic subjects and controls indicate that EBC periostin may not be useful as an asthma biomarker in this group.

Is the composition of exhaled breath condensate a key to explain the course of COVID-19 in children?

INTRODUCTION: The relative resistance of children to severe course of the novel coronavirus infection remains unclear. We hypothesized that there might be a link between this phenomenon and observation from our previous studies concerning an inhibitory or cytotoxic effect of exhaled breath condensate (EBC) on endothelial cell cultures in children. AIM: Since we could not find any data on the similar effect caused by EBC in adults, the aim of our study was to evaluate and compare the biological activity of EBC in adults and children in an experimental in vitro model. Furthermore, in order to identify a putative agent responsible for these properties of EBC in children, we attempted to analyse the composition of selected EBC samples. MATERIAL AND METHODS: The influence of EBC samples on metabolic activity of endothelial cell line C-166 was assessed using colorimetric tetrazolium salt reduction assay (MTT assay). Selected EBC samples were fractionated using size exclusion chromatography and subjected to mass spectrometry analysis. RESULTS: Exhaled breath condensates in healthy children, but not in adults, revealed a cytotoxic effect on in vitro cell cultures. This effect was most significant in condensate fraction, which contained a prominent 4.8 kDa peak in the mass spectra. CONCLUSIONS: Breath condensates of healthy children contain the factor which reveals the inhibitory/cytotoxic effect on endothelial cell cultures. Although the physiological role of this agent remains unclear, its identification may potentially be useful in ongoing research on SARS-CoV-2/COVID-19.

Epithelial-macrophage-dendritic cell interactions impact alarmins expression in asthma and COPD.

In the respiratory system macrophages and dendritic cells collaborate as sentinels against foreign particulate antigens. The study used a triple-cell co-culture model, utilizing nasal epithelial cells, along with: monocyte derived macrophages (moMφs), and monocyte derived DCs (moDCs). Cell cultures from 15 controls, 14 asthma and 11 COPD patients were stimulated with IL-13 and poly I:C for 24 h. Co-cultivation of epithelial cells with moMφs and moDCs increased TSLP level only in asthma and the effect of IL-13 and poly I:C stimulation differed in all groups. Asthma epithelial cells expressed higher level of receptors TSLPR, ST2 and IL-17RA than controls and increased number of ST2 + ciliated and IL17RA + secretory cells. Cytokine expression in respiratory epithelium may be influenced by structural and immunological cell interaction. TSLP pathway may be associated with secretory, while IL-33 with ciliated cells. The impaired function of respiratory epithelium may impact cell-to-cell interactions in asthma.

A multicentre retrospective observational study on Polish experience of pirfenidone therapy in patients with idiopathic pulmonary fibrosis: the PolExPIR study.

BACKGROUND: Pirfenidone is an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). The drug is available for Polish patients with IPF since 2017. The PolExPIR study aimed to describe the real-world data (RWD) on the Polish experience of pirfenidone therapy in IPF with respect to safety and efficacy profiles. METHODS: This was a multicentre, retrospective, observational study collecting clinical data of patients with IPF receiving pirfenidone from January 2017 to September 2019 across 10 specialized pulmonary centres in Poland. Data collection included baseline characteristics, pulmonary function tests (PFTs) results and six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), treatment persistence, and survival were also collected up to 24 months post-inclusion. RESULTS: A total of 307 patients receiving pirfenidone were identified for analysis. The mean age was 68.83 (8.13) years and 77% were males. The median time from the first symptoms to IPF diagnosis was 15.5 (9.75-30) months and from diagnosis to start of pirfenidone treatment was 6 (2-23) months. Patients were followed on treatment for a median of 17 (12-22.75) months. Seventy-four patients (24.1%) required dose adjustments and 35 (11.4%) were chronically treated with different than the full recommended dose. A total of 141 patients (45.92%) discontinued therapy due to different reasons including ADRs (16.61%), death (8.79%), disease progression (6.51%), patient's own request (5.54%), neoplastic disease (3.91%) and lung transplantation (0.33%). Over up to 24 months of follow-up, the pulmonary function remained largely stable. The median annual decline in forced vital capacity (FVC) during the first year of pirfenidone therapy was -20 ml (-200-100) and during the second year was -120 ml (-340-30). Over a study period, 33 patients (10.75%) died. CONCLUSIONS: The PolExPIR study is a source of longitudinal RWD on pirfenidone therapy in the Polish cohort of patients with IPF supporting its long-term acceptable safety and efficacy profiles and reinforce findings from the previous randomised clinical trials and observational studies.

mRNA expression profile of bronchoalveolar lavage fluid cells from patients with idiopathic pulmonary fibrosis and sarcoidosis.

BACKGROUND: Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are two most frequent forms of interstitial lung diseases (ILDs). Cellular and biochemical composition of bronchoalveolar lavage fluid (BALf) was shown to reflect the fibrotic changes in the lung. However, the usefulness of BALf cellular profile evaluation in the diagnosis of ILDs is limited. The aim of the study was a multivariate, molecular analysis of BALf cells from IPF and sarcoidosis patients. METHODS: Transcriptomic measurements were carried out using Affymetrix Human Gene 2.1 ST ArrayStrip in 21 samples: 9 IPF and 12 sarcoidosis. The mRNA expression for the most significantly differentiating genes was evaluated by real-time PCR in 32 samples (11 IPF and 21 sarcoidosis). RESULTS: The number of genes differentially expressed between IPF and sarcoidosis groups was 4832 (13359 probesets). Cluster analysis indicated that sarcoidosis BALf cells are characterized by increased mRNA expression of genes associated with ribosome biogenesis. Clusters formed by genes with changed mRNA expression in IPF samples were implicated in the processes of cell adhesion and migration, metalloproteinase expression and negative regulation of cell proliferation. The GO analysis indicated that predominant biological processes associated with the differential mRNA gene expression of BALf cells were upregulation of neutrophils in IPF and lymphocytes in sarcoidosis. CONCLUSIONS: Analysis of BALf from sarcoidosis and IPF showed highly different mRNA profile of cells. The most important biological processes observed at the molecular level in BALf cells were associated with ribosome biogenesis and proteasome apparatus in sarcoidosis and neutrophilic dysfunction in IPF.

Relationship between Blood and Induced Sputum Eosinophils, Bronchial Hyperresponsiveness and Reversibility of Airway Obstruction in Mild-to-Moderate Chronic Obstructive Pulmonary Disease.

Blood eosinophilia has been proposed as a surrogate marker for airway eosinophilia and as a predictor of treatment response in chronic obstructive pulmonary disease (COPD). The aim of the study was to assess the relationship between blood and sputum eosinophils and to investigate the association between blood and sputum eosinophil count and clinical features of mild-to-moderate COPD. We performed a retrospective analysis of blood and sputum eosinophil count, as well as demographic and lung function data in a cohort of 90 stable, steroid-naive (Global Initiative for Chronic Obstructive Lung Disease 1 or 2) COPD patients and 20 control subjects. Blood and sputum eosinophil count did not correlate both in patients with COPD (r = -0.04 p = 0.705) and in controls (r = 0.05, p = 0.838). Sputum eosinophilia (≥3%) was present in 40% of COPD patients. The median blood eosinophil count in patients with COPD was 180 (interquartile range 90-270)/µL; patients with low blood eosinophils (<180/µL) did not differ from those with high blood eosinophils (≥180/µL) in terms of forced expiratory volume in 1 second, bronchial reversibility or hyperresponsiveness. This was also the case when COPD patients with and without sputum eosinophilia were compared. At the same time, positive bronchial reversibility and positive bronchial hyperresponsiveness were observed in 2 (11%) COPD patients with high blood eosinophils and in 1 (5%) patient with sputum eosinophilia. There was a weak, albeit significant correlation (r = 0.22 p = 0.041) between blood eosinophil count and age in patients with COPD. Peripheral eosinophil count poorly reflects sputum eosinophils and lung function in stable steroid-naive mild-to-moderate COPD patients.

Severe mitral stenosis secondary to eosinophilic granulomatosis resolving after pharmacological treatment.

We present a case of 44-year-old woman who underwent effective pharmacological treatment of severe mitral stenosis. The patient was hospitalized due to rapidly progressive dyspnea. Her medical history included asthma, perennial rhinitis, and nasal polyps. Echocardiography showed a mass of the left ventricle involving the mitral valve; cardiac MRI suggested acute endocarditis. Severe peripheral blood eosinophilia was found. Eosinophilic granulomatosis with polyangiitis was diagnosed; treatment with prednisone and cyclophosphamide was started. Despite the clinical improvement, severe mitral stenosis persisted, surgical treatment was planned. However, evaluation after 6 cycles of cyclophosphamide pulse therapy revealed a significant regression of the valvular disease.

Expression of Inflammatory Mediators in Induced Sputum: Comparative Study in Asthma and COPD.

Asthma and COPD are the most common obstructive lung diseases characterized by inflammation in the lower airways which contribute to airflow limitation. Different inflammatory mediators are thought to play a key role in these diseases. This study was conducted in 13 patients with asthma, 12 patients with COPD, and 13 control subjects. The expression of mRNA of IL-6, IL-13, CXCL8, TSLP, IL-33, IL-25, IL-17, ECP, mast cell tryptase, CCL24, and CCL26 was assessed in induced sputum cells by real time PCR. We found that CXCL8 was strongly related to the neutrophil percentage but differed significantly in COPD and asthma patients. The expression of IL-17 was lower in patients with atopic asthma compared to non-atopic asthma. The percentage of macrophages correlated negatively with the expression of mast cell tryptase and ECP in COPD, and with CXCL8 in asthma. The expression of ECP correlated negatively with the severity of COPD symptoms measured by CAT. We conclude that asthma and COPD demonstrate a significant overlap in the airway cytokine profile. Thus, differentiation between the two diseases is difficult as based on a single cytokine, which suggests the coexistence of phenotypes sharing a common cytokine network in these obstructive lung diseases.

Comparative Study of IL-33 and IL-6 Levels in Different Respiratory Samples in Mild-to-Moderate Asthma and COPD.

IL-6 and IL-33 are involved in the inflammatory process in obstructive lung diseases. In contrast to IL-6, few data on the expression of IL-33 in different biological samples from asthma and COPD patients are available. The aim was to evaluate the expressions of IL-33 and IL-6 in bronchial mucosa and to compare these expressions with the concentrations of both cytokines in various respiratory samples from patients with mild-to-moderate asthma and COPD. Serum, induced sputum and exhaled breath condensate IL-6 and IL-33 levels, as well as their expression in bronchial mucosa were evaluated in 22 asthma and 33 COPD patients. There were significant differences between bronchial mucosa IL-6, but not IL-33 expression in asthma and COPD. Serum and IS IL-6 concentrations were higher in COPD than in asthma (3.4 vs. 2.02 pg/mL, p = 0.002 and 16.5 vs. 12.7 pg/mL, p = 0.007, respectively); IL-33 levels reached similar values in asthma and COPD in all investigated samples. In both diseases, the lowest levels of IL-6 and IL-33 were found in EBC. EBC levels of both cytokines did not correlate with their expression in other materials. The IL-33 and IL-6 are detectable in serum, IS and EBC not only in asthma but also in COPD patients. In the COPD group, serum and IS IL-6 concentrations were statistically higher than in the asthma group. The tissue expression of IL-33 and IL-33 concentrations in the investigated biological samples were on a comparable level in both diseases. Our findings may suggest that IL-33 activation is a common pathway in asthma and COPD.

Comparison of Thymic Stromal Lymphopoietin Concentration in Various Human Biospecimens from Asthma and COPD Patients Measured with Two Different ELISA Kits.

Thymic stromal lymphopoietin (TSLP) seems a promising asthma biomarker. In earlier studies, mainly the serum concentration of TSLP was investigated. The aim of the present study was to compare the TSLP concentration measured by two different ELISA kits in the serum, induced sputum, and exhaled breath condensate in asthma, COPD, and control subjects. The study included 24 asthmatics, 36 patients with COPD, and 12 controls. TSLP concentration was measured with the use of R&D and EIAab commercial ELISA kits. The results obtained with the EIAab kit were 3 to even 45-fold higher than those measured with the R&D kit. Significant differences between the investigated groups were found only for the TSLP concentration in induced sputum. When the R&D kit was used, the highest TSLP levels in induced sputum were found in asthmatics, while the EIAab kit showed the highest TSLP levels in controls. The distribution of results in the Bland-Altman plot was typical for a proportional constant error. TSP concentration in induced sputum might be a more reliable asthma biomarker than serum TSLP. We conclude that TSLP level is highly dependent on the ELISA kit used for the measurement. Thus, judgement on TSLP results obtained with different assays might be confusing and lead to wrong conclusions.

Eosinophilic and Neutrophilic Airway Inflammation in the Phenotyping of Mild-to-Moderate Asthma and Chronic Obstructive Pulmonary Disease.

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with different inflammatory phenotypes. Various inflammatory mediators play a role in these diseases. The aim of this study was to analyze the neutrophilic and eosinophilic airway and systemic inflammation as the phenotypic characterization of patients with asthma and COPD. Twenty-four patients with asthma and 33 patients with COPD were enrolled in the study. All the patients were in mild-to-moderate stage of disease, and none of them were treated with inhaled corticosteroids. Concentrations of IL-6, neutrophil elastase (NE), matrix metalloproteinase 9 (MMP-9), eosinophil cationic protein (ECP), and IL-33 and IL-17 in serum and induced sputum (IS) were measured by enzyme-linked immunosorbent assay (ELISA). The cellular composition of blood and IS was evaluated. Hierarchical clustering of patients was performed for the combination of selected clinical features and mediators. Asthma and COPD can be differentiated based on eosinophilic/neutrophilic systemic or airway inflammation with unsatisfactory efficiency. Hierarchical clustering of patients based on blood eosinophil percentage and clinical data revealed two asthma clusters differing in the number of positive skin prick tests and one COPD cluster with two subclusters characterized by low and high blood eosinophil concentrations. Clustering of patients according to IS measurements and clinical data showed two main clusters: pure asthma characterized by high eosinophil/atopy status and mixed asthma and COPD cluster with low eosinophil/atopy status. The neutrophilic phenotype of COPD was associated with more severe airway obstruction and hyperinflation.

How to Enhance the Diagnosis of Early Stages of Chronic Obstructive Pulmonary Disease (COPD)? The Role of Mobile Spirometry in COPD Screening and Diagnosis-A Systematic Review.

COPD is the third leading cause of death worldwide. Its diagnosis can be made with spirometry, which is underused due to its limited accessibility. Portable spirometry holds promise for enhancing the efficacy of COPD diagnoses. The study aimed to estimate COPD prevalence diagnosed with a portable spirometer in high-risk patients and compare it with COPD prevalence based on data from conventional, on-site spirometry. We also evaluated the strategy of a proactive approach to identify COPD in high-risk individuals. We conducted a systematic review of original studies on COPD targeted screening and diagnosis with portable and conventional spirometers selected from 8496 publications initially found in three databases: Cochrane, PubMed, and Embase. The inclusion criteria were met by 28 studies. COPD prevalence evaluated with the use of portable spirometers reached 20.27% and was lower compared to that estimated with the use of conventional spirometers (24.67%). In 11 included studies, postbronchodilator tests were performed with portable spirometers, which enabled a bedside COPD diagnosis. Portable spirometers can be successfully used in COPD targeted screening and diagnosis and thus enhance the detection of COPD at early stages.

Reactions templated by nucleic acids: more ways to translate oligonucleotide-based instructions into emerging function.

The programmability of oligonucleotide recognition offers an attractive platform to direct the assembly of reactive partners that can engage in chemical reactions. Recently, significant progress has been made in both the breadth of chemical transformations and in the functional output of the reaction. Herein we summarize these recent progresses and illustrate their applications to translate oligonucleotide instructions into functional materials and novel architectures (conductive polymers, nanopatterns, novel oligonucleotide junctions); into fluorescent or bioactive molecule using cellular RNA; to interrogate secondary structures or oligonucelic acids; or a synthetic oligomer.

Metabolomic Analysis of Respiratory Epithelial Lining Fluid in Patients with Chronic Obstructive Pulmonary Disease-A Systematic Review.

Chronic obstructive pulmonary disease (COPD), as the third leading cause of death among adults, is a significant public health problem around the world. However, about 75% of smokers do not develop the disease despite the severe smoking burden. COPD is a heterogeneous disease, and several phenotypes, with differences in their clinical picture and response to treatment, have been distinguished. Metabolomic studies provide information on metabolic pathways, and therefore are a promising tool for understanding disease etiopathogenesis and the development of effective causal treatment. The aim of this systematic review was to analyze the metabolome of the respiratory epithelial lining fluid of patients with COPD, compared to healthy volunteers, refractory smokers, and subjects with other lung diseases. We included observational human studies. Sphingolipids, phosphatidylethanolamines, and sphingomyelins distinguished COPD from non-smokers; volatile organic compounds, lipids, and amino acids distinguished COPD from smokers without the disease. Five volatile organic compounds were correlated with eosinophilia and four were associated with a phenotype with frequent exacerbations. Fatty acids and ornithine metabolism were correlated with the severity of COPD. Metabolomics, by searching for biomarkers and distinguishing metabolic pathways, can allow us to understand the pathophysiology of COPD and the development of its phenotypes.

Blood and Sputum Eosinophils of COPD Patients Are Differently Polarized than in Asthma.

Different eosinophil subpopulations have been identified in asthma and other eosinophilic disorders. However, there is a paucity of data on eosinophil subpopulations in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to compare eosinophil phenotypes in blood and induced sputum in patients with COPD, asthma and controls. Stable patients with mild-to-moderate COPD (n = 15) and asthma (n = 14) with documented blood eosinophilia ≥100 cells/µL in the year prior to the study and the control group (n = 11) were included to the study. The blood and sputum eosinophil phenotypes were analyzed by flow cytometry. IL-5, IL-13, CCL5 and eotaxin-3 levels were measured in the induced sputum. The marker expression on blood eosinophils was similar among control, asthma and COPD groups. The expressions of CD125, CD193, CD14 and CD62L were higher on blood than on sputum eosinophils in all three groups. We found increased levels of CD193+ and CD66b+ sputum eosinophils from COPD patients, and an elevated level of CD11b+ sputum eosinophils in asthma compared to COPD patients. The results of our study suggest that the profile of marker expression on COPD sputum eosinophils differed from other groups, suggesting a distinct phenotype of eosinophils of COPD patients than in asthma or healthy subjects.

Deep learning algorithm for visual quality assessment of the spirograms.

Objective. The quality of spirometry manoeuvres is crucial for correctly interpreting the values of spirometry parameters. A fundamental guideline for proper quality assessment is the American Thoracic Society and European Respiratory Society (ATS/ERS) Standards for spirometry, updated in 2019, which describe several start-of-test and end-of-test criteria which can be assessed automatically. However, the spirometry standards also require a visual evaluation of the spirometry curve to determine the spirograms' acceptability or usability. In this study, we present an automatic algorithm based on a convolutional neural network (CNN) for quality assessment of the spirometry curves as an alternative to manual verification performed by specialists.Approach. The algorithm for automatic assessment of spirometry measurements was created using a set of randomly selected 1998 spirograms which met all quantitative criteria defined by ATS/ERS Standards. Each spirogram was annotated as 'confirm' (remaining acceptable or usable status) or 'reject' (change the status to unacceptable) by four pulmonologists, separately for FEV1 and FVC parameters. The database was split into a training (80%) and test set (20%) for developing the CNN classification algorithm. The algorithm was optimised using a cross-validation method.Main results. The accuracy, sensitivity and specificity obtained for the algorithm were 92.6%, 93.1% and 90.0% for FEV1 and 94.1%, 95.6% and 88.3% for FVC, respectively.Significance.The algorithm provides an opportunity to significantly improve the quality of spirometry tests, especially during unsupervised spirometry. It can also serve as an additional tool in clinical trials to quickly assess the quality of a large group of tests.

A Real-World Multicenter Retrospective Observational Study on Polish Experience with Nintedanib Therapy in Patients with Idiopathic Pulmonary Fibrosis: The PolExNIB Study.

Nintedanib is a disease-modifying agent licensed for the treatment of IPF. Data on Polish experience with nintedanib in IPF are lacking. The present study aimed to describe the safety and efficacy profiles of nintedanib in a large real-world cohort of Polish patients with IPF. This was a multicenter, retrospective, observational study of IPF patients treated with nintedanib between March 2018 and October 2021. Data collection included baseline clinical characteristics, results of pulmonary function tests (PFTs), and a six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), and treatment persistence were also retrieved. A total of 501 patients (70% male) with a median age of 70.9 years (IQR 65-75.7) were included in this study. Patients were followed on treatment for a median of 15 months (7-25.5). The majority of patients (66.7%) were treated with the full recommended dose of nintedanib and 33.3% of patients were treated with a reduced dose of a drug. Intermittent dose reductions or drug interruptions were needed in 20% of patients. Over up to 3 years of follow-up, pulmonary function remained largely stable with the minority experiencing disease progression. The most frequent ADRs included diarrhea (45.3%), decreased appetite (29.9%), abdominal discomfort (29.5%), weight loss (32.1%), nausea (20.8%), fatigue (19.2%), increased liver aminotransferases (15.4%), and vomiting (8.2%). A total of 203 patients (40.5%) discontinued nintedanib treatment due to diverse reasons including ADRs (10.2%), death (11.6%), disease progression (4.6%), patient's request (6.6%), and neoplastic disease (2.2%). This real-world study of a large cohort of Polish patients with IPF demonstrates that nintedanib therapy is safe, and is associated with acceptable tolerance and disease stabilization. These data support the findings of previously conducted clinical trials and observational studies on the safety and efficacy profiles of nintedanib in IPF.