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.

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.

Relationship of emotional distress and physical concerns with fatigue severity in sarcoidosis.

Background: Fatigue is one of the most common and disabling symptoms of sarcoidosis. The cause of fatigue remains unclear and is usually multifactorial. The majority of previous studies evaluated clinical parameters with only few of them including assessment of psychological factors as contributing to the severity of the symptoms. Objective: The aim of this study was to evaluate the relationship of emotional distress, physical concerns, and dyspnea in explaining fatigue in patients with sarcoidosis. Methods: Fifty-seven patients with sarcoidosis were enrolled to the study and filled out measures of fatigue (FAS), dyspnea (MRC), anxiety sensitivity (ASI-3), and anxiety and depression (HADS). Results: Linear regression revealed that distress and physical concerns subscale of ASI are significant predictors of fatigue explaining jointly 53.5% of fatigue variance. Conclusions: The results of the study emphasize the importance of including emotional distress and physical concerns into the diagnostic procedures and management of fatigue in sarcoidosis. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 160-164).

Association of anxiety sensitivity-physical concerns and FVC with dyspnea severity in sarcoidosis.

OBJECTIVE: The purpose of the study was to evaluate the relationship of an objective functional lung parameter (FVC) and a subjective psychological factor (physical symptom concerns) with dyspnea in sarcoidosis. Dyspnea constitutes one of the most common and burdensome symptoms in sarcoidosis, yet little is known about its mechanisms and, in particular, psychological. METHOD: A total of 107 hospitalized sarcoidosis patients (Female=50, Mage=45.3years) volunteered to take part in the correlational research study. Participants underwent spirometry and completed the MRC Dyspnea Scale and the Anxiety Sensitivity Index-3 (ASI) questionnaire. Linear hierarchical regression analysis was used to determine the relationship between the studied predictors and dyspnea severity. RESULTS: The best fitting model predicted 18% of variance in dyspnea severity. Physical symptom concerns subscale of ASI (ß=0.24) and FVC (ß=-0.23) were significantly related to dyspnea MRC severity, but only physical concerns remained significantly related to dyspnea when both predictors were in the model. CONCLUSIONS: The current results suggest that both psychological and physiological factors should be taken into account when explaining subjective dyspnea severity in sarcoidosis. More specifically, these findings call for including cognitive vulnerability factors related to anxiety (physical symptom concerns) into the diagnostic procedures and management of dyspnea in sarcoidosis.

Rounded atelectasis of the lung: A pictorial review.

Rounded atelectasis of the lung is well described in medical literature, but still difficult to diagnose. Since lesions give no clinical symptoms in patients, radiologists are often the first to recognize the round lesion in an X-ray picture or a CT scan. Rounded atelectasis is an atypical form of lung collapse that usually occurs adjacent to scarred pleura and can be mistaken for lung cancer. Patients with rounded atelectasis have a history of asbestos exposure or pleural effusion due to various causes. When characteristic imaging findings are present, the diagnosis is rarely dubious and no further investigation is necessary. However, differential diagnosis of rounded atelectasis poses a challenge to pulmonary specialists and radiologists.

Enhanced expression of Fas Ligand (FasL) in the lower airways of patients with fibrotic interstitial lung diseases (ILDs).

The exact role of FasL, and particularly its soluble and membrane-bound forms, in the development of chronic ILDs and lung fibrosis has not been extensively explored. We aimed at analyzing membrane-bound FasL expression on alveolar macrophages (AM) and lymphocytes (AL) as well as soluble FasL (sFasL) levels in bronchoalveolar lavage (BAL) from ILDs patients, incl. pulmonary sarcoidosis (PS), hypersensitivity pneumonitis (HP), silicosis, asbestosis, idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and healthy subjects (n = 89, 12, 7, 8, 23, 6, 17, respectively). In IPF, significantly increased percentage of AM FasL(+) and CD8(+)FasL(+) cells as well as sFasL levels in BAL were found. Increased sFasL levels were also observed in HP. NSIP and asbestosis were characterized by higher AM FasL(+) relative number; CD8(+)FasL(+) population was expanded in asbestosis only. There was a significant decline in AL FasL(+) percentage in PS and HP. Vital capacity was negatively correlated with sFasL levels, AM FasL(+) and CD8(+)FasL(+) cell relative count. CD4(+)FasL(+) and CD8(+)FasL(+) percentage strongly correlated with BAL neutrophilia, an unfavorable prognostic factor in lung fibrosis. The concurrent comparative BAL analysis of FasL expression indicates that FasL(+) AM and AL (mainly Tc cells) comprise an important element of the fibrotic process, mostly in IPF. FasL might play a crucial role in other fibrosis-complicated ILDs, like NSIP and asbestosis.

A single photon emission computed tomography of the chest with the use of receptor radiotracer (Tc-99m-Depreotide) in sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic and multiorgan disease with unknown etiopathogenesis. Granulomas that do not undergo necrosis and caseous degeneration are distinctive for this disease. Mostly it is connected with young adults, more frequently females than males, and changes are mainly situated in the lymph nodes of the pulmonary hilus and pulmonary parenchyma. Somatotropin release inhibiting hormone receptors could be located in epithelioid and giant cells that create sarcoidal tubercles and lymph nodes. Aim of the study was to determine the usefulness of a single photon emission tomography (SPECT) for an evaluation of the range of sarcoidal changes in the chest after using a receptor tracer. An assumption was made that scintigraphy with the use of Tc-99m-Depreotide could help with location of extrapulmonary sarcoidosis focuses. MATERIAL/METHODS: Authors present five patients with clinically recognized and histopathologically confirmed sarcoidosis. Patients were given Tc-99m-Depreotide and underwent SPECT of chest. The results were compared with X-rays of these patients chests and with the accumulation of radiotracer in 2 other patients with carcinoid syndrome without visible pathological changes in examination. Patients got an intravenous injection of 500 MBq (14mCi) Tc-99m-Depreotide. SPECT of chest together with a "whole body" examination, was performed after 2 hours and 24 hours. RESULTS: Higher radiotracer accumulation was observed in all patients in the area of some chest lymph nodes, in pulmonary tissue in 3 patients and in other groups of lymph nodes in 2 patients. CONCLUSIONS: Emission Tomography of the chest with the use of receptor radiotracer (Tc-99m-Depreotide) can be a crucial complement of sarcoidosis diagnostics in an evaluation of the extent of lung changes together with an estimation of chest lymph nodes abnormalities.

A case report of a patient with dermatomyositis as a prodromal sign of lung cancer.

Dermatomyositis (DM) is a connective tissue disease characterized by specific inflammatory lesions in muscle biopsy. It is caused by vasculitis determined by humoral factors with subsequent inflammatory cell accumulation, mainly T CD4+ and B cells, which infiltrate myocytes leading to its vacuolization and degeneration (mainly in the skeletal muscles, rarely in the smooth muscles). The incidence of DM is estimated at 1-10 per million in adults and at 1-3.2 per million in children. The autoimmune mechanism of disease induction is not fully recognized. Several lines of evidence showed the link between DM and neoplastic disease. The first report of dermatomyositis associated with stomach cancer, by Stertz, comes from 1916. In the same time, Kankeleit reported DM associated with breast cancer. Presumably, it is the result of immune reaction against antigens common for muscle and neoplastic cells or some paraneoplastic syndrome underlying mechanism. The report presents the case of a 52-year-old woman with DM (diagnosed according to the Bohan and Peter criteria) and with coexistent squamous lung cancer in situ. The left upper lobectomy was performed. No complications in postoperative period were observed. During more than 2 years of follow-up after the surgery, the patient remained in good condition, without DM symptoms, or cancer relapse. Considering that DM may be associated with lung cancer; extensive diagnostic work-up to exclude neoplastic lesions should be performed. Patients aged 40 years or more should be particularly screened.

[Interferon gamma (IFN-gamma) level in broncholaveolar lavage (BAL) fluid is positively correlated with CD4/CD8 ratio in selected interstitial lung diseases]. / Stezenie interferonu gamma (IFN-gamma) w plynie z plukania oskrzelowo-pqcherzykowego w wybranych chorobach sródmiaqszowych pluc--dodatnio skorelowane z wartoscia stosunku CD4/CD8.

UNLABELLED: IFN-gamma a potent antifibrotic activity in interstitial lung diseases (ILD). T cells, both Th1 and Tc1, are considered to be the main local source of IFN-gamma. MATERIAL AND METHODS: BAL fluids of 98 patients with ILD, incl. idiopathic pulmonary fibrosis (IPF/UIP), sarcoidosis, extrinsic allergic alveolitis (EAA), asbestosis and silicosis (n=16, 49, 7, 10, 16 resp.) were tested with ELISA for IFN-gamma levels. Results were compared with BAL cytoimmunology and patients' clinical data. RESULTS: Significantly increased IFN-gamma levels were found in non-treated patients with EAA (7.8 +/- 2.1), IPF (6.1 +/- 1.8), Loefgren's syndrome, LS (11.9 +/- 2.6) and progressive sarcoidosis, PS (6.4 +/- 1.2, p < 0.05 for all), whereas the results in pneumoconioses were comparable to those obtained in controls (2.0 +/- 1.1 pg/ml, median +/- SEM). IFN-gamma results were positively correlated with total number of CD4+ cells (r(s) = +0.38, p < 0.05), CD4+ cells percentage (r(s) = +0.32, p < 0.005) and CD4+/CD8+ ratio (r(s) = +0.38, p = 0.0007), but negatively correlated with CD8+ cell percentage (r(s) = -0.39, p < 0.0005). In IPF patients with CD4/CD8 < or =1 (n=9) IFN-gamma level was lower as compared with the group with CD4/CD8 >1 (n=7), 2.8 +/- 1.3 vs. 7.3 +/- 1.0 pg/ml. In sarcoidosis, IFN-gamma level did not seem to have a prognostic role, since values obtained in PS did not differ remarkably from those in stable sarcoidosis and LS. Moreover, subsequent steroid treatment in 7 patients with progressive sarcoidosis did not change significantly IFN-gamma levels in BAL fluid. CONCLUSIONS: Increased IFN-gamma level was found in non-treated patients with IPF, Loefgren's syndrome and progressive sarcoidosis. CD4+ (Th1), but neither CD8+ (Tc1) nor NK cells seem to be the main local source of IFN-gamma in ILD. Relatively low CD4/CD8 ratio in ILD may indicate the patients with increased risk of lung fibrosis.

[Apoptosis of alveolar lymphocytes in sarcoidosis and in control group is more frequent in smokers than in nonsmoking persons]. / Apoptoza limfocytów pecherzykowych w sarkoidozie i w grupie kontrolnej wystepuje czesciej u palaczy papierosów niz u osób niepalacych.

Cigarette smoking enhances apoptosis rate of alveolar macrophages. However, little is known about the appearance and extension of apoptosis in bronchoalveolar lavage (BAL) lymphocytes originating from smoker individuals, both in pulmonary sarcoidosis (the disease characterized by lymphocytic alveolitis) and in controls. BAL was carried out in 60 nontreated patients with pulmonary sarcoidosis, subdivided acc. smoking status and in 22 control persons, free of any lung pathology. BAL (alveolar) lymphocytes were a) stained for TUNEL; b) permeabilized and stained with PI for late apoptosis/cell cycle analyses; c) immunophenotyped, including CD95, CD95 Ligand, Bcl-2, Bcl-XL, Bak and insulin-like growth factor-I (IGF-I) expression. BD FACSCalibure flow cytometer, PC Lysys and ModFit software were applied. The low number of AL entered apoptosis, which was confirmed by both techniques. Cigarette smokers were characterized by higher AL apoptosis percentage in respective subgroups (sarcoidosis: 0.6 +/- 0.13 in nonsmokers vs 0.9 +/- 0.23 in smokers; controls: 0.85 +/- 0.23 in nonsmokers vs 1.5 +/- 0.35 smokers, median +/- SEM, p < 0.05); the proliferation rate was lower. Decreased IGF-I expression in AL of sarcoidosis smokers was observed (13.5 +/- 9.2 vs 46.0 +/- 6.0 in nonsmokers, p < 0.05). No differences were found between studied groups in expression of Bcl-2, Fas and FasL molecules (except significantly declined ratio of CD8+FasL+ cells in sarcoidosis nonsmokers). AL apoptosis rate was positively correlated with respective alveolar macrophage results (Rs = +0.59, p < 0.00001) and negatively with CD4/CD8 ratio (Rs = -0.32, p < 0.001); no correlation was found with lung function test results and with Bcl-2, Fas and FasL expression in BAL cells. Apoptosis of alveolar lymphocytes was more frequent in nonsmokers both in pulmonary sarcoidosis and in controls; lower AL percentage proliferates. These phenomena seem to participate in lower AL percentage, observed in smoker subgroup of sarcoidosis. Some mechanisms of local apoptosis alterations in smokers may be common for alveolar lymphocytes and macrophages.

Extrapulmonary lymphangioleiomyomatosis presented as the asymptomatic retroperitoneal tumours--two cases report.

Lymphangioleiomyomatosis [LAM] is a rare lung disease affecting women and characterized by abnormal smooth muscle cells (LAM cells) proliferation along lung and lymphatic channels. The frequent occurrence of extrapulmonary LAM [e-LAM] has been reported as abdomen pelvic lymph nodes involvement, angiomyolipomas, lymphangioleiomyomas or lymphangiomas in LAM patients. An extrapulmonary manifestation as the initial LAM presentation preceding pulmonary disorders and as asymptomatic extrapulmonary LAM lesions are unusual. We report two women presented with asymptomatic retroperitoneal cystic masses accidentally found on ultrasound examination. The tumours were surgically removed and diagnosed as: 1-malignant mesothelioma and 2-tymphangiomyoma. The microscopical sections were reviewed and re-diagnosed as e-LAM at advanced pulmonary LAM development. Mesotheliosis present in e-LAM morphology is unique and was misleading for malignancy diagnosis. The second case illustrates the hormone dependent growth of lymphangiomyoma and LAM development in young women. It is difficult to prove the presence of pulmonary LAM at the time of tumours excision but both cases demonstrate importance of appropriate LAM diagnosis and being aware of such diagnosis in cases presenting with extrapulmonary extension of the disease.