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.

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.

Therapeutic decisions in a cohort of patients with idiopathic pulmonary fibrosis: a multicenter, prospective survey from Poland.

Background: Pirfenidone and nintedanib are considered as the standard of care in idiopathic pulmonary fibrosis (IPF), but there is no consensus as to which of these two agents should be regarded as first-line treatment. Objective: To provide real-world data on therapeutic decisions of pulmonary specialists, particularly the choice of the antifibrotic drug in patients with IPF. Methods: This was a multicenter, prospective survey collecting clinical data of patients with IPF considered as candidates for antifibrotic treatment between September 2019 and December 2020. Clinical characteristics and information on the therapeutic approach were retrieved. Statistical evaluation included multiple logistic regression analysis with stepwise model selection. Results: Data on 188 patients [74.5% male, median age 73 (interquartile range, 68-78) years] considered for antifibrotic therapy were collected. Treatment was initiated in 138 patients, while 50 patients did not receive an antifibrotic, mainly due to the lack of consent for treatment and IPF severity. Seventy-two patients received pirfenidone and 66 received nintedanib. Dosing protocol (p < 0.01) and patient preference (p = 0.049) were more frequently associated with the choice of nintedanib, while comorbidity profile (p = 0.0003) and concomitant medication use (p = 0.03) were more frequently associated with the choice of pirfenidone. Age (p = 0.002), lung transfer factor for carbon monoxide (TLCO) (p = 0.001), and gastrointestinal bleeding (p = 0.03) were significantly associated with the qualification for the antifibrotic treatment. Conclusion: This real-world prospective study showed that dose protocol and patient preference were more frequently associated with the choice of nintedanib, while the comorbidity profile and concomitant medication use were more frequently associated with the choice of pirfenidone. Age, TLCO, and history of gastrointestinal bleeding were significant factors influencing the decision to initiate antifibrotic therapy.

Sarcoidosis in coexistence with chronic granulomatous disease.

Granulomas formations are present in many lung diseases. Coexistence of one or more of these diseases is very rare. Diagnostics of such cases always poses a challenge. We present a case of coexistence of chronic granulomatous disease (CGD) and sarcoidosis.

Progressive fibrosis in interstitial lung diseases - proposed definition and management.

Interstitial lung diseases may have an unpredictably progressive course, which is manifested as progression of pulmonary fibrosis, causing an increasing impairment of lung function affecting a poor prognosis. The possibility of an effective antifibrotic treatment is a chance for patients to slow down the progression of the disease, perhaps even extend their life. For this reason, standardization of the definition as well as identification criteria for progressive fibrosis interstitial lung disease is a method for optimizing the management in this group of patients.

Diagnosis of sarcoidosis - the updated ATS 2020 recommendations through the prism of everyday clinical practice.

Diagnosis of sarcoidosis is not standardized, but there is a general consensus that it should be based on the following criteria: consistent, adequate clinical presentation, demonstration of the presence of granulomatous lesions in pathomorphological examination (in one or more tissue samples) and the exclusion of alternative causes of granulomatous disease. In this article, the reader will find, briefly presented, the most important position of ATS experts regarding selected aspects of the diagnosis of sarcoidosis, with a comment from the authors of this editorial.

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.

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.

Nintedanib - efficacy, safety and practical aspects of treatment for patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a rare disease with progressive course and a very unfavourable prognosis. Antifibrotic drugs are a chance to reduce the rate of disease progression and extend the life of IPF patients. One of these drugs is nintedanib, an oral tyrosine kinase inhibitor. In the following article, the reader will find a summary of current knowledge on the efficacy and safety of nintedanib treatment of IPF patients. This study uses data from pivotal studies and experience from everyday clinical practice indicating a wide range of possible applications of the drug in IPF patients.

Cardiac sarcoidosis: worse pulmonary function due to left ventricular ejection fraction?: A case-control study.

Dyspnea and exercise intolerance are usually attributed to pulmonary disease in sarcoidosis patients. However, cardiac involvement may also be responsible for these symptoms. Data regarding the impact of heart involvement on lung function in cardiac sarcoidosis (CS) is limited.The aim of study was to compare the results of pulmonary function tests (PFTs) in patients with and without heart involvement. We performed a retrospective analysis of PFTs in a group of sarcoidosis patients both with and without heart involvement evaluated by cardiovascular magnetic resonance (CMR) study. The study was performed in the period between May 2008 and April 2016.We included data of sarcoidosis patients who underwent testing for possible CS (including CMR study) at a national tertiary referral center for patients with interstitial lung diseases. All patients had histopathologicaly confirmed sarcoidosis and underwent standard evaluation with PFTs measurements including spirometry, plethysmography, lung transfer factor (TL,CO), and 6-minute walking test (6MWT) assessed using the most recent predicted values.We identified 255 sarcoidosis patients (93 women, age 42 ±â€Š10.7 y): 103 with CS and 152 without CS (controls). CS patients had significantly lower left ventricular ejection fraction (LVEF; 56.9 ±â€Š7.0 vs 60.4 ±â€Š5.4, P < .001). Any type of lung dysfunction was seen in 63% of CS patients compared with 31% in the controls (P = .005). Ventilatory disturbances (obstructive or restrictive pattern) and low TL,CO were more frequent in CS group (52% vs 23%, P < .001 and 38% vs 18% P < .01 respectively). CS (OR = 2.13, 95% CI: 1.11-4.07, P = .02), stage of the disease (OR = 3.13, 95% CI: 1.4-7.0, P = .006) and LVEF (coefficient = -0.068 ±â€Š0.027, P = .011) were independent factors associated with low FEV1 but not low TL,CO. There was a significant correlation between LVEF and FEV1 in CS group (r = 0.31, n = 89, P = .003). No significant difference in 6MWD between CS patients and controls was observed.Lung function impairment was more frequent in CS. Lower LVEF was associated with decreased values of FEV1. Relatively poor lung function may be an indication of cardiac sarcoidosis.

Diagnostic and treatment standards in idiopathic pulmonary fibrosis in the era of antifibrotic drugs in Poland: A real-world practice survey.

Background Currently, only two drugs have been shown to modify the inevitable natural history of idiopathic pulmonary fibrosis (IPF). Changes in the reimbursement policy for antifibrotic drugs in Poland have led to the availability of pirfenidone from January 2017 and nintedanib from March 2018 for the treatment of Polish patients with IPF. This study aimed to evaluate the possible changes and shortcomings in the clinical practice standards in IPF in the era of access to antifibrotic therapy in Poland. Methods A real-world data survey was performed among physicians attending the Polish Respiratory Society Congress held in May 2018. The present survey was a follow-up to the previous survey undertaken in 2016, before the availability of antifibrotics in Poland. Results A total of 99 physicians participated in the survey, among which 80% were pulmonologists. The majority of participants (83%) represented hospital-based clinicians and most of them (93%) were involved in interstitial lung diseases (ILD) management. As many as 63% of the respondents elaborate the final diagnosis of IPF working with the expert radiologist routinely, 47% do that in the cooperation with other pulmonologists, and if a biopsy was performed 39% discuss its results with the expert pathologist. Bronchoalveolar lavage (BAL) and surgical lung biopsy (SLB) would never be recommended in the differential diagnosis of IPF by 9% and 16% of the respondents, respectively. Corticosteroids (CS) or a combination of CS and immunosuppressants (IS) is still recommended by 22% of participants. Proton pump inhibitors (PPI) in the case of symptomatic GERD are prescribed by 44% of the respondents, and 12% prescribe PPI regardless of GERD symptoms. Pirfenidone is used by 70%, and nintedanib by 48% of the respondents. Only 39% of the respondents refer patients with IPF to professional rehabilitation centers. Conclusions The level of cooperation between pulmonologists and other specialists in the diagnostic workup of IPF is unsatisfactory. IPF treatment practices in the era of access to effective drugs in Poland require immediate improvement. There is an urgent need to develop the local Polish practical guidelines to improve the management of IPF.

The presence of staphylococcal superantigens in nasal swabs and correlation with activity of granulomatosis with polyangiitis in own material.

OBJECTIVES: Nasal carriage of Staphylococcus aureus and its superantigens (SAg) seem to be a risk factor disease exacerbation in granulomatosis with polyangiitis (GPA). We investigated the association between the presence of SAg in nasal swabs and activity of disease in GPA patients also taking into account correlation with an antimicrobial treatment. METHODS: In a prospective study of a total of 150 GPA patients hospitalised in the period 2009-2016, nasal swabs were examined for the presence of Staphylococcus aureus and SAg. Subsequently, the association with disease activity was assessed. RESULTS: Of 362 Staphylococcus aureus-positive nasal swab cultures from 115 of the 150 patients, the presence of at least one SAg in 126 samples (34.8%) from 56 patients (48.7%) was found. Among the 17 patients with limited to subglottic stenosis (SGS) disease, SAg were detected in 6 cases (35.3%). We did not find a significant correlation between the presence of SAg and disease activity (p=0.986), although when individual SAg were analysed separatively, SED and TSST-1 were more frequently present in active disease. Additionally, the results of the analysis demonstrated a protective effect of trimethoprim/sulfamethoxazole (T/S) treatment (0R 0.52, p<0.0092) in GPA patients. Interestingly, GPA limited to SGS appeared as an unfavourable factor associated with disease activity (0R 1.84, p=0.05). CONCLUSIONS: The association between staphylococcal SAg in nasal swabs and GPA activity is not evident. Multiple mechanisms that may lead to disease activation still need to be investigated.

A case report of steroid resistant cardiac sarcoidosis successfully managed with methotrexate.

Up to one fourth of sarcoidosis patients may have cardiac involvement, what is potentially a life-threatening condition and requires aggressive treatment. Corticosteroids are generally effective in cardiac sarcoidosis, however may have significant short and long term adverse effects. We present a case of a 42-year-old male, who was diagnosed with pulmonary and cardiac sarcoidosis. He was treated initially with corticosteroids and satisfactory improvement was achieved in the lungs but not in the heart. Methotrexate was added as a second line therapy, being beneficial for the heart as well as steroid sparing agent. Cardiac improvement was documented during serial CMR imaging. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 178-181).

Systemic treatment for sarcoidosis was needed for 16% of 1810 Caucasian patients.

INTRODUCTION AND OBJECTIVE: Sarcoidosis is a systemic granulomatous disease predominantly affecting the lungs, although granulomas can also involve all other organs. Fortunately, it is often a self-limiting disease and aggressive treatment is not indicated in majority of cases. However, treatment is recommended when critical organs are affected or the disease is progressive. So far, there is lack of reliable information regarding the frequency of treatment in Caucasian population or data are discordant. The aim of this study was to evaluate the prevalence of systemic immune-modulating treatment in a large cohort of sarcoidosis patients. METHODS: We performed a retrospective analysis of patients discharged from our institution with the final diagnosis 'sarcoidosis' (ICD-10: D86) from January 2010 to December 2013. RESULTS: 1810 sarcoidosis patients were hospitalized during these four years, 47.6% were females, mean age was 43.5 ± 12.2 years. The majority (80.6%) were discharged as pulmonary and/or lymph node sarcoidosis (D86.0, D86.1, D86.2). Only 281 (15.5%) patients were discharged with systemic treatment, 60.1% of them were men (OR 1.5; 95% CI: 1.1-1.9, P = .0047). The 44.8% of patients who had sarcoidosis also involving an organ other than the lungs (D86.8) were much more likely to be treated: OR 5.6; 95% CI: 4.2-7.4, P < .0001). Older age (>50) was also identified as a risk factor for treatment (odds ratio: 1.8; 95% CI: 1.5-2.4). CONCLUSIONS: Less than 16% sarcoidosis patients required systemic treatment. Older men with multiorgan sarcoidosis were more likely to be treated.

Idiopathic pulmonary fibrosis (IPF) - common practice in Poland before the "antifibrotic drugs era".

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and debilitating lung disease with a median survival time of 3-5 years. For now, pirfenidone (PIR) and nintedanib (NTB) are the only drugs that can slow down the disease's progression. In Poland, these drugs, although registered for legal use, had not been reimbursed for IPF patients until the end of the year 2016. Aim of the study was to assess what was common practice in terms of diagnosis and treatment in the period before antifibrotic drugs became available for IPF patients in Poland. MATERIAL AND METHODS: We performed a survey among participants of two nationwide pulmonological congresses held in 2016. RESULTS: One hundred and fifty physicians took part in the study. Only 55% of respondents would reach their final diagnosis in collaboration with a radiologist. Just 40% of those sending patients for surgical lung biopsy (SLB) would discuss the case directly with a pathologist. 22% would never refer the patient suspected of having IPF for SLB. 85% believed that bronchoalveolar lavage (BAL) may be useful for diagnosis. 41% of respiratory professionals would not use any drug for the treatment of IPF patients. 23% of physicians would prescribe corticosteroids in high doses (CS), either in monotherapy or in combination with other drugs. Only 43% of respondents would use antacid drugs in case of symptomatic gastro-oesophageal reflux disease (GERD), and only 11% would prescribe these drugs regardless of GERD diagnosis. CONCLUSIONS: The majority of Polish pulmonologists were not supported by radiologists and pathologists in the diagnostic process. Treatment standards were unsatisfactory, mostly due to a lacking of reimbursement regulations. Further education is necessary to improve management of IPF patients in Poland.

Intratracheal Dilation-injection Technique in the Treatment of Granulomatosis with Polyangiitis Patients with Subglottic Stenosis.

OBJECTIVE: An analysis of subglottic stenosis (SGS) occurrence frequency in patients with granulomatosis with polyangiitis (GPA) based on the time of appearance of clinical symptoms, and an assessment of treatment effectiveness, in particular with the intratracheal dilation-injection technique (IDIT). METHODS: Review and treatment with IDIT of 34 patients with SGS associated with GPA. RESULTS: SGS developed in 34 of 250 patients with GPA (13.6%) and was not reflective of disease activity in the organs in 15 of 34 patients (44%): 11 cases after and 4 cases during immunosuppressive therapy (IST) when patients did not have organ symptoms. All patients underwent IDIT and in total, the treatment resulted in immediate improvement. In addition, in 21 cases, IST was applied because of other organ involvement or of the lack of longterm efficacy of IDIT. The median time of response was 37 months and the median interval between sessions was 5 months. None of the patients required tracheostomy after beginning IDIT in our hospital. CONCLUSION: SGS often occurs independently of other features of active GPA. IDIT is a safe and effective technique in the treatment of GPA-related SGS. It should be performed in all patients with GPA who develop significant SGS and in those with multiorgan disease concomitantly with IST. In patients with isolated SGS, IDIT also makes IST and tracheostomy unnecessary.

Cardiac sarcoidosis - silent destroyer.

We report a case of histologically proven pulmonary sarcoidosis and cardiac involvement in a 53-year old woman with progression leading to the heart failure documented in cardiovascular magnetic resonsnce studies.