Characteristics of Interstitial Pneumonia With Autoimmune Features (IPAF): Protocol for a Multicenter Prospective Study.

BACKGROUND: "Interstitial lung disease" (ILD) is a broad term encompassing diseases of different backgrounds. "Interstitial pneumonia with autoimmune features" (IPAF) is a recent term that implies the presence of autoimmunity. OBJECTIVE: This study aims to determine the characteristics of Polish patients with IPAF, compare them with patients with other interstitial pneumonias, and search for the prognostic and diagnostic biomarkers of IPAF in serum and bronchoalveolar lavage fluid (BALF). METHODS: This multicenter prospective study plans to recruit 240 participants divided into 1 study group and 2 control groups. Biological fluid samples will be collected according to Polish Respiratory Society management guidelines and stored at -80°C for further tests. Prospective 5-year observations of 60 newly diagnosed individuals are planned. The study will be divided into subsections. First, we plan to characterize Polish patients with IPAF (study group) against their peers with other ILDs (2 control groups). Control group 1 will comprise patients with idiopathic ILDs, including mainly idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Control group 2 will comprise patients with connective tissue disease-associated interstitial lung diseases, such as rheumatoid arthritis, systemic sclerosis, polymyositis, dermatomyositis, Sjögren's syndrome, mixed connective tissue disease, and systemic lupus erythematosus. Radiological and functional parameters will be analyzed. Patients will be compared in terms of high-resolution computed tomography results, the 6-minute walking test performance, and pulmonary function test parameters. The diagnosis of IPAF will be reassessed on a regular basis through multidisciplinary discussion in order to determine its clinical stability. In the laboratory arm, inflammation and fibrosis pathways will be assessed. Cytokine levels (interleukin 8, transforming growth factor beta 1, chemokine C-C motif ligand [CXCL]18, CXCL1, surfactant protein [SP]-A, SP-D, Krebs von den Lungen-6 protein, and chitinase 1) will be measured in serum and BALF. A comparative analysis of serum and BALF cytokine levels will be performed in order to establish potential differences between systemic and local inflammatory pathways. In the quality of life (QoL) arm of the study, dyspnea and cough and their impact on various aspects of the QoL will be assessed. Depression and anxiety will be measured with the Hospital Anxiety and Depression Modified Scale and the 9-item Patient Health Questionnaire, and potential correlations with symptom prevalence will be assessed. RESULTS: This study will start recruiting patients to phase 1 in October 2023. The final results will be available in 2028. We plan to publish preliminary results after 2-3 years from the start of phase 1. CONCLUSIONS: This study will be a step toward a better understanding of IPAF etiopathogenesis and outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44802.

Expectations, symptoms, and quality of life before and after 1 year of Pirfenidone treatment in patients with idiopathic pulmonary fibrosis: A single-arm, open-label nonrandomized study.

Background and Aims: Antifibrotic therapies reduce lung function decline in patients with idiopathic pulmonary fibrosis (IPF). This single-arm, open-label, nonrandomized study aimed to determine the influence of antifibrotic treatment on patients' reported symptoms and expectations of the therapy. Methods: Fifty-two patients with confirmed IPF at a mean age of 65 ± 8.63 years (73% male) completed the following surveys at baseline and after 12 months of Pirfenidone treatment: Short Form Healthy Survey (SF-36), St. George's Respiratory Questionnaire (SGRQ), Baseline Dyspnea Index (BDI), Fatigue Assessment Scale (FAS), Leicester Cough Questionnaire (LCQ), and Patient's Needs and Expectations Authors' Survey. Results: The most important patients' needs were access to novel therapy, fast and easy access to health centers specializing in IPF treatment, and the improvement of the general condition or the maintenance of its level. These needs did not change with time, except for the significantly more important right of deciding on disease management after 12 months of treatment (p = 0.014). The quality of life per SF-36, after 1 year of Pirfenidone treatment, significantly improved in the physical cumulative score (p = 0.004) and mental cumulative score (p = 0.003). Significant deteriorations were observed in bodily pain and vitality. For the remaining questionnaires (SGRQ, BDI, FAS, and LCQ), no significant changes in the course of the study were noticed. Around one in 10 patients subjected to Pirfenidone therapy had achieved general symptom improvement in all areas; that is, quality of life improvement as well as cough and dyspnea reduction. Conclusions: One year of antifibrotic treatment resulted in a general improvement in the quality of life per the SF-36 questionnaire. Patients' expectations of disease management did not change; also, access to novel therapies and easy access to health centers specializing in IPF management remained their top needs.

Determinants of daily physical activity limitation in patients with idiopathic pulmonary fibrosis.

The purpose of the study was to determine the level of physical fitness assessed based on the physiological parameters and intensity of daily physical activity (PA) of patients with idiopathic pulmonary fibrosis (IPF). Additionally, we aimed to determine the intensity and duration of exercise that would bring beneficial modifications in the cardio-respiratory system of the patients with IPF. Eighteen patients with IPF (61.7 ± 4.3 years) and fifteen healthy volunteers performed a graded exercise test to exhaustion on a treadmill (Bruce protocol). Spirometry, dyspnea (mMRC, Borg scale) and fatigue (FAS) were measured. Total daily PA (kcal/day, MET) was monitored for seven days. The linear regression of PA (kcal/day) vs. peak oxygen uptake (%pred. peakVO2) was used to determine the intensity of daily PA that should be used in the rehabilitation of the patients with IPF. The average energy expenditure of daily PA of patients with IPF was 147.9 ± 86.4 kcal/day and it was significantly lower compared to healthy individuals. The linear regression indicated that the predicted energy expenditure of daily PA (PAEE) is 280.0 kcal/day, estimated based on VO2peak 100%pred. Therefore, the patients should add about 30 min of exercise of the intensity of 4.5 ± 0.2 kcal (calculated at the anaerobic threshold) or about 3700 steps/day to their daily PA. Diffusion for carbon monoxide and physiological variables of aerobic capacity seem to be the most important determinants of PA limitation in patients with IPF. The method of estimating PAEE should be used to plan training loads in IPF rehabilitation.

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.

Impact of physical functional capacity on quality of life in patients with interstitial lung diseases.

This study aimed to investigate the physical functioning predictors for health-related quality of life (HRQL) decline in patients with idiopathic interstitial fibrosis (IPF), sarcoidosis and other interstitial lung disease (ILD). The study enrolled 52 patients with ILD and 16 healthy individuals. Participants' HRQL was assessed using the 36-item Short-Form Health Survey questionnaire. Spirometry, physical performance, and daily physical activity (PA) were monitored. Patients with IPF showed significantly lower PA compared to patients with other ILD (p = 0.002)and sarcoidosis (p = 0.01). The type of disease aetiology had no significant effect on aerobic capacity, HRQL and fatigue. Patients with ILD showed significant greater fatigue, lower physical functioning and greater physical aspects scores compared to the control group (F=6.0; p = 0.018; F=12.64; p = 0.001, respectively). A significant positive correlation was observed between 6-minute walking distance (6MWD) and the physical domain of HRQL (r = 0.35, p = 0.012) and PA and the physical aspects of HRQL (r = 0.37, p = 0.007). This study revealed that the key predictors for HRQL decline were lower lung function, lower PA and physical performance.

Three Weeks of Pulmonary Rehabilitation Do Not Influence Oscillometry Parameters in Postoperative Lung Cancer Patients.

Background: Thoracic surgery is a recommended treatment option for non-small cell lung cancer patients. An important part of a patient's therapy, which helps to prevent postoperative complications and improve quality of life, is pulmonary rehabilitation (PR). The aim of this study was to assess whether the implementation of physical activity has an influence on forced oscillation technique (FOT) values in patients after thoracic surgery due to lung cancer. Methods: In this observational study, we enrolled 54 patients after thoracic surgery due to lung cancer, 49 patients with idiopathic interstitial fibrosis (IPF), and 54 patients with chronic obstructive pulmonary disease/asthma−COPD overlap (COPD/ACO). All patients were subjected to three weeks of in-hospital PR and assessed at the baseline as well as after completing PR by FOT, spirometry, grip strength measurement, and the 6-min walk test (6MWT). Results: We observed differences between FOT values under the influence of physical activity in studied groups, mostly between patients after thoracic surgery and COPD/ACO patients; however, no significant improvement after completing PR among FOT parameters was noticed in any group of patients. Improvements in the 6MWT distance, left hand strength, and right hand strength after PR were noticed (p < 0.001, 0.002, and 0.012, respectively). Conclusions: Three weeks of pulmonary rehabilitation had no impact on FOT values in patients after thoracic surgery due to lung cancer. Instead, we observed improvements in the 6MWT distance and the strength of both hands. Similarly, no FOT changes were observed in IPF and COPD/ACO patients after completing PR.

Guidelines of the Polish Respiratory Society on the Diagnosis and Treatment of Progressive Fibrosing Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis.

The recommendations were developed as answers to previously formulated questions concerning everyday diagnostic and therapeutic challenges. They were developed based on a review of the current literature using the GRADE methodology. The experts suggest that PF-ILD be diagnosed based on a combination of different criteria, such as the aggravation of symptoms, progression of radiological lesions, and worsening of lung function test parameters. The experts recommend a precise diagnosis of an underlying disease, with serological testing for an autoimmune disease always being included. The final diagnosis should be worked out by a multidisciplinary team (MDT). Patients with an interstitial lung disease other than IPF who do not meet the criteria for the progressive fibrosis phenotype should be monitored for progression, and those with systemic autoimmune diseases should be regularly monitored for signs of interstitial lung disease. In managing patients with interstitial lung disease associated with autoimmune diseases, an opinion of an MDT should be considered. Nintedanib rather than pirfenidon should be introduced in the event of the ineffectiveness of the therapy recommended for the treatment of the underlying disease, but in some instances, it is possible to start antifibrotic treatment without earlier immunomodulatory therapy. It is also admissible to use immunomodulatory and antifibrotic drugs simultaneously. No recommendations were made for or against termination of anti-fibrotic therapy in the case of noted progression during treatment of a PF-ILD other than IPF. The experts recommend that the same principles of non-pharmacological and palliative treatment and eligibility for lung transplantation should be applied to patients with an interstitial lung disease other than IPF with progressive fibrosis as in patients with IPF.

Guidelines of the Polish Respiratory Society on the Diagnosis and Treatment of Progressive Fibrosing Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis

The recommendations were developed as answers to previously formulated questions concerning everyday diagnostic and therapeutic challenges. They were developed based on a review of the current literature using the GRADE methodology. The experts suggest that PF-ILD be diagnosed based on a combination of different criteria, such as the aggravation of symptoms, progression of radiological lesions, and worsening of lung function test parameters. The experts recommend a precise diagnosis of an underlying disease, with serological testing for an autoimmune disease always being included. The final diagnosis should be worked out by a multidisciplinary team (MDT). Patients with an interstitial lung disease other than IPF who do not meet the criteria for the progressive fibrosis phenotype should be monitored for progression, and those with systemic autoimmune diseases should be regularly monitored for signs of interstitial lung disease. In managing patients with interstitial lung disease associated with autoimmune diseases, an opinion of an MDT should be considered. Nintedanib rather than pirfenidon should be introduced in the event of the ineffectiveness of the therapy recommended for the treatment of the underlying disease, but in some instances, it is possible to start antifibrotic treatment without earlier immunomodulatory therapy. It is also admissible to use immunomodulatory and antifibrotic drugs simultaneously. No recommendations were made for or against termination of anti-fibrotic therapy in the case of noted progression during treatment of a PF-ILD other than IPF. The experts recommend that the same principles of non-pharmacological and palliative treatment and eligibility for lung transplantation should be applied to patients with an interstitial lung disease other than IPF with progressive fibrosis as in patients with IPF.

Forced Oscillation Measurements in Patients with Idiopathic Interstitial Pneumonia Subjected to Pulmonary Rehabilitation.

(1) Background: Pulmonary rehabilitation (PR) plays a significant therapeutic role for patients with idiopathic interstitial pneumonia (IIP). The study assessed the impact of physical activity on lung function measured by forced oscillation technique (FOT). (2) Methods: The study involved 48 patients with IIP subjected to a 3-week inpatient PR. The control group included IIP patients (n = 44) on a 3-week interval without PR. All patients were assessed at baseline and after 3 weeks of PR by FOT, spirometry, plethysmography, grip strength measurement and the 6-minute walk test. (3) Results: There were no significant changes in FOT measurements in the PR group, except for reduced reactance at 11 Hz, observed in both groups (p < 0.05). Patients who completed PR significantly improved their 6-min walk distance (6MWD) and forced vital capacity (FVC). The change in 6MWD was better in patients with higher baseline reactance (p = 0.045). (4) Conclusions: Patients with IIP benefit from PR by an increased FVC and 6MWD; however, no improvement in FOT values was noticed. Slow disease progression was observed in the study and control groups, as measured by reduced reactance at 11 Hz. Patients with lower baseline reactance limitations achieve better 6MWD improvement.

Effect of Apnea-Induced Hypoxia on Cardiovascular Adaptation and Circulating Biomarkers of Oxidative Stress in Elite Breath-Hold Divers.

Given the previous evidence that breath-hold diving is a cause of physiological stress, this study aimed to determine whether a combination static and dynamic apnea would affect total oxidant status, nitric oxide, heat shock proteins and cardiovascular parameters in elite freedivers. Thirteen finalists of the World and European championships in swimming pool breath-hold diving participated in the study. Whole-body plethysmography and electrocardiography was performed to determine the cardiorespiratory variables at baseline and during the simulation static apnea. An assessment of the heart rate, blood oxygen saturation and biochemical variables was performed before and in response to a combination of a static followed by a dynamic apnea. Static and dynamic breath-holding had a significant effect on oxidative stress, as evidenced by an increase in the total oxidant status/capacity (p < 0.001). The post apnea concentrations of heat shock proteins 27 (HSP27) were significantly elevated (p < 0.03, but total antioxidant status (TAS), HSP90, HSP70, and nitric oxide (NO) changes were not significant. levels under the influence of the static and dynamic breath-hold protocol. A significant positive correlation between HSPs and TAS (r = 0.63; p < 0.05) as well as NO levels was associated with beneficial cardiovascular adaptation. An increase in serum HSP27 levels mediated in nitric oxide levels could explain its important role in improving cardiovascular functions in elite freedivers. Further studies are necessary to explain the exact mechanisms of breath holds training of cardiovascular adaptation responsible for maintaining adequate oxygen supply in elite divers.

A prolonged steroid therapy may be beneficial in some patients after the COVID-19 pneumonia.

INTRODUCTION: This report introduces two cases presenting absorption of considerable radiological changes in the course of the coronavirus pneumonia in patients treated with prolonged oral steroids.CASES: The first case concerns a male receiving steroids only during hospitalisation in the Infectious Disease Hospital. After discharge, the patient experienced increasing dyspnoea resulting in hospitalisation in our Department of Lung Diseases. HRCT revealed progression of a bilateral, middle, and basal ground-glass opacity when compared to the examination performed at the early stage of the disease. The supplementary oxygen therapy and steroids were administered, followed by extended prednisone consumption up to 2 months after discharge. Follow-up HRCT revealed an almost complete absorption of the ground-glass opacity. The second case concerns a male treated with steroids only during hospitalisation in the Infectious Disease Hospital. Chest CT revealed widespread bilateral ground-glass opacities with consolidations. After discharge with no treatment, he suffered from severe dyspnoea and exercise intolerance, resulting in hospitalisation on the 7th day of home stay. Since then, a continued steroid treatment was administered resulting in a clinical, spirometric, and radiological improvement.CONCLUSIONS: Based on these observations, patients after the COVID-pneumonia may derive benefits from a prolonged steroid treatment. Therefore, this class of medications should be considered in SARS-CoV-2 patients, especially in patients with persistent radiological changes and dyspnoea requiring the supplementary oxygen therapy. However, randomised controlled trials are required to establish guidelines for the steroid treatment in this group of patients.

Comparison of the diagnostic effectiveness between an expert and a student in the diagnosis of sarcoidosis by transbronchial biopsy of mediastinal lymph nodes under the control of endosonography.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of mediastinal lymph nodes is currently considered to be the most effective minimally invasive diagnostic method in patients with suspected stage I and II sarcoidosis. However, diagnostic effectiveness depends on the experience and skills of the doctor which is dependent on the number of correctly performed procedures. The aim of the study is to compare the diagnostic effectiveness of the EBUS-TBNA test obtained by an expert in this field vs that of his student. MATERIAL AND METHODS: in patients with a clinical and radiological suspicion of sarcoidosis, EBUS-TBNA procedures were performed by an expert (over 1000 previously performed tests) and by his student who completed basic training (15 procedures performed). In the expert's opinion, the student was experienced enough to perform the EBUS-TBNA on his own. Previously, more than 100 conventional fibreoptic bronchoscopies had been performed by the student. During that time, he had been working in the department of pulmonary diseases and tuberculosis for two years. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and accuracy of the EBUS-TBNA test in diagnosing sarcoidosis were calculated. Statistical evaluation was made using ROC curves for the expert and for the student. RESULTS: The study included 215 patients between 22-68 years of age with suspected sarcoidosis who were diagnosed between 2013-2016. 124 EBUS-TBNA tests were performed by the expert, and 91 procedures were performed by the student. The presence of sarcoid granulomas was confirmed by a biopsy in 165 (76.7%) patients. In terms of the diagnosis of sarcoidosis, a higher sensitivity and accuracy of the EBUS test was found in the procedures done by the expert (76.7% and 95.3%, respectively) as compared to the results obtained by the student (66.1% and 93.1%, respectively). However, these differences were not statistically significant (p = 0.11). All tests were assessed in a hospital pathology unit, but not necessarily by one person, which may be a limitation of our research. In this study, only cytological smears were taken into consideration. CONCLUSIONS: In the diagnosis of sarcoidosis, the student, after appropriate training by an expert, achieved a comparable level of diagnostic effectiveness with EBUS-TBNA after performing 90 tests independently.

The effects of exercise training on lipid profile in patients with sarcoidosis.

This study aimed to determine the use of lipid profiling to assess the effects of moderate intensity exercise training (ET) on patients with sarcoidosis. Fourteen patients with sarcoidosis (mean age, 46.0 ± 9.6 years) were examined before and after 3-week of ET programme in hospital settings. Symptoms (fatigue: FAS, dyspnoea: MRC), lung function tests and physical function tests (6 MWT, muscle force) were measured before and after ET. Proton nuclear magnetic resonance (NMR) spectroscopy combined with orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to determine lipid profile before and after ET. Twenty-five NMR signals from lipid compounds were selected for further analysis as well as serum lipid and inflammatory markers. Three weeks of ET results in improvement of symptoms (FAS: 27.5 vs. 21.0; p < 0.001, MRC: 0.86 vs. 0.14; p = 0.002) and physical function (6MWT: 508.43 vs. 547.29; p = 0.039). OPLS-DA analysis of the lipid profiles of patients with sarcoidosis revealed differences among the samples before and after ET, including decreases in fatty acids (p < 0.017), triglycerides (p < 0.022) and total cholesterol (p < 0.020). Other changes included shifts in fatty acids oxidation products and triacylglycerol esters. A short-time, in-hospital exercise training benefits patients with sarcoidosis by enhancing their physical function. Additionally, positive effect on lipid profile was observed also in this study. It is suggested that lipid profiling could become a new prognostic method to assess effects of pulmonary rehabilitation in patients with sarcoidosis.

Forced oscillation measurements in patients after lobectomy - A comparative analysis with IPF and COPD patients.

OBJECTIVES: Forced oscillation technique (FOT) is becoming increasingly widespread measurement method used for assessment of lung function. In the present study, we attempted to assess FOT values in patients after lobectomy in comparison with IPF and COPD patients. METHODS: Twenty-two patients after lobectomy due to lung cancer stage I or II, 28 patients with idiopathic pulmonary fibrosis and 17 patients with chronic obstructive pulmonary disease were enrolled in the study. All patients performed spirometry (FEV1 , FVC, FEV1 /FVC, MEF50 , MEF25 , FEF25-75 , MIF50 ), plethysmography (Raw , TLC, RV, RV/TLC) and a test using the forced oscillation technique- resistance (R at 5Hz, 11Hz and 19Hz, inspiratory, expiratory and total), reactance (Xat 5Hz, 11Hz, inspiratory, expiratory and total), Fres and expiratory flow limitation (∆X). The ANOVA Kruskal-Wallis test followed by a multiple comparison test were used to evaluate the differences in oscillatory parameters between-groups. RESULTS: Patients after lobectomy presented reduced X5, X11 and moderately increased R5, R11, R19, R5-19, ∆X and Fres. Rinsp 5 weresignificantly higher when compared with IPF patients (P = 0.001). In lobectomy patients R5, X5, X11, ∆X and Fres were significantly less affected when compared with patients with COPD (P < 0.05 for all values). R5-19, which reflects small airways dysfunction, occurred to be similarly elevated as in COPD patients (0.5 vs 0.6 cmH2 O/L/s).Abnormalities of reactance at 11Hz were observed more frequently than at 5Hz in all groups of patients. CONCLUSION: Patients after lobectomy due to lung cancer presented FOT abnormalities, which could be caused by lung parenchymal abnormalities following recent thoracic surgery.

Prospective Evaluation of the NETest as a Liquid Biopsy for Gastroenteropancreatic and Bronchopulmonary Neuroendocrine Tumors: An ENETS Center of Excellence Experience.

BACKGROUND: There is a substantial unmet clinical need for an accurate and effective blood biomarker for neuroendocrine neoplasms (NEN). We therefore evaluated, under real-world conditions in an ENETS Center of Excellence (CoE), the clinical utility of the NETest as a liquid biopsy and compared its utility with chromogranin A (CgA) measurement. METHODS: The cohorts were: gastroenteropancreatic NEN (GEP-NEN; n = 253), bronchopulmonary NEN (BPNEN; n = 64), thymic NEN (n = 1), colon cancer (n = 37), non-small-cell lung cancer (NSCLC; n = 63), benign lung disease (n = 59), and controls (n = 86). In the GEPNEN group, 164 (65%) had image-positive disease (IPD, n = 135) or were image-negative but resection-margin/biopsy-positive (n = 29), and were graded as G1 (n = 106), G2 (n = 49), G3 (n = 7), or no data (n = 2). The remainder (n = 71) had no evidence of disease (NED). In the BPNEN group, 43/64 (67%) had IPD. Histology revealed typical carcinoids (TC, n = 14), atypical carcinoids (AC, n = 14), small-cell lung cancer (SCLC, n = 11), and large-cell neuroendocrine carcinoma (LCNEC, n = 4). Disease status (stable or progressive) was evaluated according to RECIST v1.1. Blood sampling involved NETest (n = 563) and NETest/CgA analysis matched samples (n = 178). NETest was performed by PCR (on a scale of 0-100), with a score ≥20 reflecting a disease-positive status and >40 reflecting progressive disease. CgA positivity was determined by ELISA. Samples were deidentified and measurements blinded. The Kruskal-Wallis, Mann-Whitney U, and McNemar tests, and the area under the curve (AUC) of the receiver-operating characteristics (ROC) were used in the statistical analysis. RESULTS: In the GEPNEN group, NETest was significantly higher (34.4 ± 1.8, p < 0.0001) in disease-positive patients than in patients with NED (10.5 ± 1, p < 0.0001), colon cancer patients (18 ± 4, p < 0.0004), and controls (7 ± 0.5, p < 0.0001). Sensitivity for detecting disease compared to controls was 89% and specificity was 94%. NETest levels were increased in G2 vs. G1 (39 ± 3 vs. 32 ± 2, p = 0.02) and correlated with stage (localized: 26 ± 2 vs. regional/distant: 40 ± 3, p = 0.0002) and progression (55 ± 5 vs. 34 ± 2 in stable disease, p = 0.0005). In the BPNEN group, diagnostic sensitivity was 100% and levels were significantly higher in patients with bronchopulmonary carcinoids (BPC; 30 ± 1.3) who had IPD than in controls (7 ± 0.5, p < 0.0001), patients with NED (24.1 ± 1.3, p < 0.005), and NSCLC patients (17 ± 3, p = 0.0001). NETest levels were higher in patients with poorly differentiated BPNEN (LCNEC + SCLC; 59 ± 7) than in those with BPC (30 ± 1.3, p = 0.0005) or progressive disease (57.8 ± 7), compared to those with stable disease (29.4 ± 1, p < 0.0001). The AUC for differentiating disease from controls was 0.87 in the GEPNEN group and 0.99 in BPC patients (p < 0.0001). Matched CgA analysis was performed in 178 patients. In the GEPNEN group (n = 135), NETest was significantly more accurate for detecting disease (99%) than CgA positivity (53%; McNemar test χ2 = 87, p < 0.0001). In the BPNEN group (n = 43), NETest was significantly more accurate for disease detection (100%) than CgA positivity (26%; McNemar's test χ2 = 30, p < 0.0001). CONCLUSIONS: The NETest is an accurate diagnostic for GEPNEN and BPNEN. It exhibits tumor biology correlation with grading, staging, and progression. CgA as a biomarker is significantly less accurate than NETest. The NETest has substantial clinical utility that can facilitate patient management.

Severe bronchiectasis and inflammatory lung disease in a patient with anorexia nervosa and severe and enduring malnutrition - a case report.

BACKGROUND: Persistent structural changes of the lungs in anorexia nervosa (AN) patients are rarely described in contemporary medical literature. The objective of our paper is to report a rare case of severe bronchiectasis and inflammatory changes to the lungs resulting from chronic malnutrition in a AN patient. CASE PRESENTATION: We describe a patient with severe inflammatory lung disease caused by malnutrition, resulting in persistent bronchiectasis accompanying AN. We performed an analysis of the patient's medical records including radiological findings and laboratory results. A review of available literature shows very little data available on this topic. CONCLUSION: Bronchiectasis and other structural changes of the lungs are rare, but severe complications of severe, chronic malnutrition. As exemplified by our case report, they may require extensive differential diagnosis and pose a significant clinical challenge due to their non-reversible character. A successful treatment relies heavily on the patient's compliance and may be hard to achieve. Clinicians managing patients with anorexia nervosa should be wary of early respiratory tract dysfunction-related symptoms and always consider malnutrition bronchiectasis as a differential diagnosis option.

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.

Imaging methods for pulmonary sarcoidosis.

Sarcoidosis is achronic systemic granulomatous disease of unknown etiology. In more than 90% of patients with diagnosed sarcoidosis, mediastinal and hilar lymph nodes are affected. The objective of this paper is to discuss the most important chest imaging methods in pulmonary sarcoidosis. Achest X-ray remains the method of choice at both the diagnostic stage and during follow-up of the disease progress. High-resolution computed tomography allows for amore thorough description of lesions in terms of their location. Research demonstrates the superiority of FDG PET over both aforementioned techniques in the assessment of active inflammatory lesions. Magnetic resonance imaging is currently being used in diagnosing cardiac sarcoidosis. Although EBUS constitutes the basic diagnostic tool, the invasiveness of the method results in it not being used when monitoring the activity of the disease.

Guidelines of the Polish Respiratory Society for diagnosis and treatment of idiopathic pulmonary fibrosis.

INTRODUCTION: This document presents the guidelines of the Polish Respiratory Society (PTChP, Polskie Towarzystwo Chorób Pluc) for diagnosis and treatment of idiopathic pulmonary fibrosis (IPF), developed by agroup of Polish experts. MATERIAL AND METHODS: The recommendations were developed in the form of answers to previously formulated questions concer-ning everyday diagnostic and therapeutic challenges. They were developed based on acurrent literature review using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: We formulated 28 recommendations for diagnosis (8), pharmacological treatment (12) as well as non-pharma-cological and palliative therapy (8). The experts suggest that surgical lung biopsy (SLB) not be performed in patients with the probable usual interstitial pneumonia (UIP) pattern, with an appropriate clinical context and unanimous opinion of a multidisciplinary team. The experts recommend using antifibrotic agents in IPF patients and suggest their use irrespective of the degree of functional impairment. As regards non-pharmacological and palliative treatment, strong re-commendations were formulated regarding pulmonary rehabilitation, oxygen therapy (in patients with chronic respiratory failure), preventive vaccinations as well as referring IPF patients to transplant centres. Table 1 presents an aggregate list of recommendations. CONCLUSIONS: The Polish Respiratory Society Working Group developed guidelines for IPF diagnosis and treatment.

Exercise Training in Patients With Non-Small Cell Lung Cancer During In-Hospital Chemotherapy Treatment: A RANDOMIZED CONTROLLED TRIAL.

PURPOSE: The aim of this study was to perform a randomized trial to assess the impact of exercise training in patients with non-small cell lung cancer during chemotherapy on several outcomes in comparison to a control group (CG). METHODS: The exercise training group (ETG) consisted of 20 patients and the CG consisted of 10 patients. In the ETG, a 4-wk in-hospital exercise training program was performed in 2-wk cycles interspersed with consecutive rounds of chemotherapy with cytostatic drugs. The exercise training program was individualized and included warm-up, respiratory muscle exercise, training on a cycle ergometer or treadmill, and Nordic walking. CG participants were assessed before and after 6 wk of chemotherapy alone. RESULTS: Comparing pre- and post-intervention values, the ETG demonstrated an increase in 6-min walk distance (486 ± 92 vs 531 ± 103 m, P = .01). In a battery of physical performance tests: Up and Go Test (6.3 ± 1.0 vs 6.0 ± 1.1 sec, P = .01); chair stand (13.3 ± 2.8 vs 14.3 ± 3.4 repetitions, P = .001); and arm curl (18.4 ± 3.1 vs 20.4 ± 3.5 repetitions, P = .001) all improved significantly. Spirometry values also improved: FEV1 % predicted (76 ± 16 vs 84 ± 15, P = .01), FVC % predicted (87 ± 14 vs 95 ± 13, P = .01), and FEV1/FVC (73 ± 13% vs 76 ± 12%, P = .04). The exercise training was well tolerated, without any adverse events due to exercise. There were no significant improvements in the CG. CONCLUSIONS: This study suggests that planned, individualized, and supervised exercise programs in patients with advanced lung cancer during chemotherapy are a practical and beneficial intervention for enhancing mobility and physical fitness.