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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.

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ., Competing Interests: Conflict of interest: S.A. Papiris reports grants, personal fees and nonfinancial support from La Roche Hoffman and Boehringer Ingelheim, and other support from Savara, outside the submitted work. Conflict of interest: F. Bonella reports grants and personal fees from Savara Pharma outside the submitted work. Conflict of interest: R. Borie has received consulting fees from Boehringer Ingelheim, Roche and Sanofi, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim and Roche, outside the submitted work; support for attending meetings and/or travel received from Boehringer Ingelheim, Roche and Chiesi outside the submitted work; and participation on a data safety monitoring or advisory board for Savara, outside the submitted work. Conflict of interest: M. Molina-Molina reports personal fees and grants from Esteve-Teijin, Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: E. Jouneau reports personal fees and other support from Actelion, AIRB, AstraZeneca, Bellerophon Therapeutics, Biogen, BMS, Boehringer Ingelheim, Chiesi, FibroGen, Galecto Biotech, Genzyme, Gilead, GlaxoSmithKline, LVL, Mundipharma, Novartis, Pharm-Olam, Pfizer, Pliant Therapeutics, F. Hoffmann-La Roche, Ltd, Sanofi and Savara-Serendex, outside the submitted work. Conflict of interest: C. McCarthy is a scientific advisory board member of Savara Inc. unrelated to this work and has not received any payment from Savara Inc. for any work to date. Conflict of interest: E. Bendstrup reports grants and personal fees from Boehringer Ingelheim and Hofmann la Roche, and personal fees from Galapagos, outside the submitted work. Conflict of interest: M. Griese has received grants or contracts from Boehringer Ingelheim, outside the submitted work; has participated on a data safety or advisory board for Boehringer Ingelheim, outside the submitted work; and is the Head of chILD-EU, outside the submitted work. Conflict of interest: E.D. Manali reports personal fees and nonfinancial support from La Roche Hoffman; grants, personal fees and nonfinancial support from Boehringer Ingelheim; and other support from Savara, all outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

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.

Diagnosis of sarcoidosis is mainly based on radiological examinations. The most important one is chest X-ray, which in typical cases reveals bilateral enlarged hilar lymph nodes, in a proportion of patients also concomitant parenchymal changes, rarely isolated parenchymal infiltrations or signs of lung fibrosis. The next step is chest computed tomography (CT), most often of high resolution, although strict indications for CT have been defined. Monitoring of sarcoidosis is based on the assessment of serial chest X-ray examinations. Indications for CT in a patient with completed diagnosis are limited. Positron emission tomography (PET) is a valuable tool for the evaluation of especially difficult diagnostic cases, for the assessment of disease activity, identification of yet unidentified extrapulmonary locations or selection of an optimal place for biopsy. In the present paper you will find how to use these radiological techniques for the diagnosis and monitoring of sarcoidosis., (© 2018 MEDPRESS.)

Sarcoidosis is an inflammatory disease of unknown etiology. Most commonly it results in the formation of non-caseating granulomas in intrathoracic lymph nodes and lung parenchyma, but the clinical course and picture may be complicated by extrapulmonary involvement and many non-respiratory signs and symptoms which are directly related to the disease. In addition, sarcoidosis patients may suffer from a plethora of symptoms of uncertain or unknown origin. Fatigue is one of these symptoms, and according to some authors it is reported by the majority of patients with active sarcoidosis, but also by a smaller proportion of patients with inactive sarcoidosis, or even with complete clinical and radiological remission. Therefore the term fatigue syndrome is frequently used to name this clinical problem. The definition of fatigue syndrome in sarcoidosis is imprecise and the syndrome is usually recognized by use of validated questionnaires. In this review the uptodate knowledge in this field was presented and different challenges connected with this syndrome were described.

Granulomatosis with polyangiitis (GPA) is a multi-organ disease which mostly affects lungs, kidney, and head and neck region. We report a rare case of acute laryngeal dyspnea and rapidly progressive pulmonary changes as first manifestations of disease. A 53 year-old woman presented with symptoms of two-week dyspnea, which aggravated rapidly in the preceding hours. Laryngological examination revealed subglottic infiltrations and vocal fold oedema which required urgent tracheotomy. During few days she developed gingival ulcerations and pulmonary infiltration with negative serum c-ANCA titers. The histopathological examination of subglottic and gingival biopsies and the clinical picture established the diagnosis of GPA. She was treated with prednisone and cyclophosphamide with recovery; however, during over 3 years of follow-up, pulmonary symptoms relapsed and subglottic stenosis persisted. The difficulties in diagnosis and treatment in this unusual presentation of GPA are outlined with conclusion that in patients with subglottic infiltration, which develops rapidly, even when this is a sole presentation of the disease, and when c-ANCA are negative, GPA should always be considered.

Sarcoidosis is an orphan inflammatory disorder that can virtually affect any organ or system in the body, although the lungs and lymph nodes are most frequently involved. Sarcoidosis is believed to derive from an interaction between environmental and genetic agents. Many studies emphasize a strong association between certain human leukocyte antigen (HLA) alleles and sarcoidosis susceptibility. Several new insights have allowed the further evaluation of other candidate genes with a potential function in the immunopathogenesis of sarcoidosis. This review summarizes recent advances in the identification of novel molecular markers that may play a role in different stages of disease, such as the acute phase of inflammation, granuloma formation and fibrosis. Furthermore, this article elucidates the role of both TGF-b/Smad and (HIF)-1a-VEGF-ING-4 signaling pathways in the development of sarcoidosis. The potential epigenetic regulation of the processes occurring in sarcoidosis by miRNA is also discussed.

Patient: Male, 26 FINAL DIAGNOSIS: Sarcoidosis Symptoms: Disseminated lung parenchymal changes Medication: - Clinical Procedure: - Specialty: Pulmonology., Objective: Rare disease., Background: Sarcoidosis is a granulomatous inflammatory disease that is induced by unknown antigen(s) in a genetically susceptible host. Although the direct link between Mycobacterium tuberculosis (MTB) infection and sarcoidosis can be excluded on the basis of a current knowledge, the non-infectious mechanisms may explain the causative role of mycobacterial antigens. The co-incidence of tuberculosis (TB) and sarcoidosis, and higher incidence of mycobacterial DNA in biological samples of sarcoid patients, have been reported by many authors., Case Report: We present a case in which MTB infection in 1 family member triggered a sarcoid reaction in the infected subject and 2 other non-infected family members. We discuss different aspects of diagnosis and differentiation, as well as up-to-date hypotheses on the possible mechanisms leading to sarcoid inflammation in patients exposed to MTB., Conclusions: This case series documents the possibility of familial spreading of sarcoidosis, and points to MTB as a potential etiological factor.

Introduction:  Sustained inflammation in sarcoidosis may lead to lung fibrosis. The activity of numerous chemokines responsible for proliferation and activity of T lymphocytes may play a crucial role in this process and may have predictive value. These include cytokines induced by interferon γ, such as CXCL9, 10, and 11-ligands of chemokine receptor CXCR3., Objectives:  The aim of the study was to estimate the role of CXCR3 ligands in the pathogenesis of sarcoidosis and the predictive value of their concentrations in bronchoalveolar lavage (BAL) fluid. , Patients and Methods:  CXCL9, 10, and 11 concentrations in BAL fluid were measured by an enzyme‑linked immunosorbent assay in patients with sarcoidosis (n = 59) and controls (n = 34). A total of 46 patients were followed up for 24 months to compare the results between the subgroups with complete remission and with chronic disease., Results:  Protein-standardized CXCL11 concentrations in BAL fluid from patients with stage II sarcoidosis were higher than in those with stage I (median [interquarile range], 0.95 [0.26-2.39] vs. 0.32 [0.13-0.74] pg/μg protein, P = 0.02). CXCL10 levels in BAL fluid from patients without Löfgren syndrome were higher compared with those the syndrome (0.69 [0.51-1.05] vs. 0.40 [0.27-0.70] pg/μg protein, P = 0.05). None of these markers predicted the chronic course of the disease. CXCL10 levels in BAL fluid correlated with serum angiotensin‑converting enzyme, and CXCL11 levels with parenchymal lesions on high‑resolution computed tomography. Only nonstandardized CXC11 concentrations in BAL fluid were higher in sarcoidosis., Conclusions:  Our results support the hypothesis that cytokines CXCL9, 10, and 11 may be involved in the pathogenesis of chronic sarcoidosis. However, the lack of notable differences between the sarcoidosis and control groups, as well as the lack of associations with the chronic course suggest that they should not be considered as potential prognostic markers.

Introduction: Discriminating between active and inactive sarcoidosis may be problematic in everyday clinical practice. There are numerous biochemical markers used in the diagnosis and monitoring of sarcoidosis. Somatostatin receptor (SR) scintigraphy with the use of 99mTc-octreotide may be used to estimate disease activity., Objectives: The aim of the paper was to assess the value of traditional biomarkers (serum angiotensin-converting enzyme [SACE], C-reactive protein, markers of calcium metabolism, bronchoalveolar lavage fluid [BALF] lymphocytes) and a novel biomarker, 8-isoprostane (8-IP) in exhaled breath condensate (EBC), in the assessment of sarcoidosis activity in relation to somatostatin receptor scintigraphy., Patients and Methods: The study included 32 patients with sarcoidosis. Scintigraphy was performed using somatostatin analogue, 99mTc-HYNIC-TOC; planar and SPECT/CT images were recorded. The study group was divided into a subgroup with positive radiotracer uptake (n = 20) and without a visible uptake (n = 12). 8-IP levels were measured in EBC by an immunoenzymatic assay. RESULTS We observed a significantly higher EBC 8-IP levels in the subgroup with positive uptake compared with those with negative uptake (19.1 ± 19.8 vs. 5.4 ± 3.5 pg/ml, P = 0.02). The levels of SACE and the percentage of BALF lymphocytes were also nonsignificantly elevated. In the group of patients with positive scintigraphy results, a positive correlation was observed between the uptake ratio and SACE (r = 0.44, P = 0.041)., Conclusions: The results indicate low value of biochemical markers in the assessment of disease activity. SR scintigraphy may have practical usefulness in the monitoring of sarcoidosis.

Introduction: Hepatocyte growth factor (HGF) is a strong mitogen stimulating lung epithelial cell growth. Elevated levels of HGF have been reported in various biological materials of patients with acute respiratory distress syndrome and in patients recovering from pneumonia or pneumonectomy. Sarcoidosis may be complicated by lung fibrosis. Consequently, HGF could be considered a new biomarker identifying patients with a higher risk of lung fibrosis. The aim of the study was to verify whether: 1. HGF is measurable in bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC); 2. HGF in BALF or EBC is impaired in sarcoidosis; and 3. HGF correlates with chosen activity and prognostic markers., Material and Methods: Sixty-four EBC and 30 BALF of sarcoid patients, and 15 and 9 of healthy controls, respectively, were collected for the measurement of HGF using an ELISA test., Results: HGF was detectable in 62% of EBC samples (56% sarcoidosis and 87% of controls) and in all the BALF samples. EBC and BALF concentrations were not different in comparison to the controls. Moreover, no correlation was found between EBC/BALF concentrations and radiological stage, lung function tests, duration of disease, number of relapses, BALF lymphocytes, serum ACE, or serum and urine calcium concentrations., Conclusions: HGF is detectable in BAL and EBC. However, it does not distinguish sarcoidosis patients from healthy subjects. The above, as well as the lack of correlations with various parameters of disease activity and severity rule out EBC/ /BALF HGF as a biomarker for sarcoidosis monitoring.

Introduction: Increased generation of superoxide anion (O(2)(-).) by bronchoalveolar lavage (BAL) cells has been reported in various inflammatory disorders. However, the clinical relevance of this phenomenon is unclear., Objectives: The aim of the study was to investigate whether production of O(2)(-). is enhanced in smoking-related chronic bronchitis and sarcoidosis, and to assess a relationship between O(2)(-). generation and lung function impairment and changes in BAL cellular pattern., Patients and Methods: Forty-two patients with sarcoidosis, 24 smokers with chronic bronchitis, and 17 controls were examined. A number/percentage of BAL cells was calculated. Spontaneous and phorbol myristate acetate (PMA)-stimulated O(2)(-). production was measured in BAL cells. Spirometry was performed., Results: Patients with smoking-related chronic bronchitis produced more O(2)(-). spontaneously (6.42 -/+1.24 vs. 15.39 -/+2.47 nmol/106 cells, P = 0.003) and after stimulation (3.73 -/+1.32 vs. 14.76 -/+2.79 nmol/106 cells; P = 0.001). PMA-stimulated excess production correlated with the percentage of neutrophils (r = 0.66, P = 0.0005). In sarcoidosis, only spontaneous production of O(2)(-). was higher (vs. 18.07 -/+2.49 nmol/106 cells, P = 0.004) and correlated with the percentage of BAL lymphocytes. There was no correlation between O(2)(-). production and lung function parameters., Conclusions: Patients with smoking-related chronic bronchitis produce more O(2)(-)., and this phenomenon is related to BAL neutrophils. In sarcoidosis, spontaneous release of O(2)(-). from BAL cells is related to the extent of lymphocytic alveolitis. Higher O(2)(-). generation did not impair lung function.

Introduction: The imbalance between metalloproteinases (MMPs) and their tissue inhibitors TIMPs) may be involved in the pathogenesis of lung sarcoidosis, a granulomatous inflammatory disease which may lead to lung fibrosis., Objectives: The aim of the study was to verify whether the expression of MMP-9, MMP-2, TIMP-1, and TIMP-2 in peripheral lung biopsies of patients with sarcoidosis correlate with lung function tests, radiological pattern, and bronchoalveolar lavage (BAL) cells. We compared the expression of MMPs and TIMPs between patients with sarcoid-positive vs. - negative biopsy and fibrosing vs. non-fibrosing high-resolution computed tomography (HRCT)pattern., Patients and Methods: We examined patients with histologically proven stage II and III sarcoidosis (n = 17). Immunohistochemistry with antibodies against the studied molecules was performed in the lung and bronchial tissue specimens obtained from transbronchial lung biopsies. The radiological pattern was evaluated based on HRCT. The total cell number and percentage of cells were calculated in the BAL samples., Results: MMPs and TIMPs were present in the cells of sarcoid granuloma, and were more prevalent in the parenchyma than in the bronchi. We found no correlation between MMP-9, MMP-2, TIMP-1, TIMP-2 and HRCT pattern or BAL cells. There were inverse associations between MMP-9 and FEV1 (% predicted), and also between MMP-2 and maximal expiratory flow 25-75% (L and % predicted) in patients with sarcoidosis diagnosed by transbronchial lung biopsy. There were no differences in the measured parameters between patients with and without fibrotic changes and between those with negative vs. positive lung biopsy results., Conclusions: Our study provides an indirect evidence for a potential involvement of MMPs/TIMPs in the sarcoid inflammation of the distal airways.

Everyday clinical practice reveals both cases of asthma with non-typical symptoms as well as pseudo-asthmatic syndromes with symptoms typical for asthma. Bronchofiberoscopy is a diagnostic method which may help to overcome many diagnostic problems. Although it is a safe procedure, an increased risk of severe bronchoconstriction exists in patients with asthma. The fear of this complication may cause late diagnosis of some asthma-mimicking diseases and may delay the proper treatment. In the present paper we describe two cases showing the possibility of making diagnostic mistakes, and especially illustrating the role ofbronchoscopy in differential diagnosis of bronchial asthma. The authors remind specific indications for this examination in patients with asthma or those presenting asthma-like symptoms. Safety precautions have been also recollected. If safety rules are met, severe bronchoconstriction in patients with bronchial hyperreactivity can be avoided.

Introduction: Oxidative lung damage may be associated with the destruction of alveolar cells. Type II alveolar epithelial cells (AECs),as progenitors of type I cells, are indispensable for the renovation of alveolar structure after lung injury. Extensive damage to type II cells could be responsible for unfavorable outcome. However, the susceptibility of type II AECs to oxidative stress is unclear., Material/methods: We investigated the susceptibility of freshly isolated and cultured rat type II AECs to oxidative stress (H2O2 and Fe2+). Thiobarbituric acid reactive substances (TBARS)were measured as indices of lipid peroxidation and cytotoxicity was estimated by the MTT test. Aminotriazol (ATZ), an inhibitor of intracellular catalase, was used to estimate the protective role of catalase., Results: TBARS concentration increased significantly in freshly isolated, oxidant-exposed cells (4.0 +/-1.3 vs.8.3 +/-2.2 nmol/g protein, p=0.0313)and insignificantly in cultured cells (1.7 +/-0.4 vs.4.4 +/-1.7 nmol/g protein).ATZ was toxic even to cells not exposed to oxidants. Inhibition of catalase in cells exposed to oxidants resulted in an insignificant increase in TBARs:4.5 +/-1.5 vs.16.2 +/-3.9 nmol/g protein, p=0.0625,and 4.0 +/-0.8 vs.7.6 +/-4.0 for freshly isolated and cultured cells, respectively. Oxidative stress itself did not increase cytotoxicity., Conclusions: Type II AECs are not resistant to oxidative stress. We cannot, however, explain why cells with evidence of lipid peroxidation do not show increased cytotoxicity. The toxicity of ATZ is not related to oxidative cell damage. In cells exposed to oxidants, TBARS may fur-ther increase when catalase is inhibited, which suggests an important protective role for catalase.