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.

A 40-Year-Old Man with Sarcoidosis and Factor V Leiden Thrombophilia Presenting with Deep Vein Thrombosis and Pulmonary Thromboembolism.

BACKGROUND The association between sarcoidosis and pulmonary embolism (PE) has been described in the literature, but little is known about the origin of hypercoagulability and hypofibrinolysis in sarcoidosis. PE is a multifactorial disease that is rarely caused by a single risk factor, and might be expected in disabling sarcoidosis. No data are available, however, about sarcoidosis being a risk factor for venous thromboembolism in factor V Leiden thrombophilia. CASE REPORT We describe a case of a 40-year-old man with asymptomatic sarcoidosis. Diagnosis was based on abnormal chest radiology (enlargement of hilar and mediastinal lymph nodes), confirmed by histopathological examination (noncaseating granulomas involving the mediastinal lymph nodes). No therapy was proposed due to good exercise tolerance, normal pulmonary function test, and absence of extrapulmonary involvement. The patient was followed up for 5 years until he developed progressive exertional dyspnea and chest pain. Plasma D-dimers, serum NT-proBNP, and troponin were increased. A computed tomography angiogram confirmed PE. Factor V Leiden thrombophilia was diagnosed following a search for risk factors for thromboembolism. Spontaneous remission of the chest lymphadenopathy was observed on anticoagulation therapy. Different potential mechanisms that relate sarcoidosis to venous thromboembolism are discussed. CONCLUSIONS PE is a potentially fatal condition and may complicate sarcoidosis, a clinically insignificant condition. Sarcoidosis patients with new symptomatology and PE with a high concentration of plasma D-dimers merit extra consideration. In certain clinical situations, sarcoidosis may be considered as a risk factor for deep vein thrombosis/PE. The anti-inflammatory and anti-fibrotic properties of anticoagulation warrant further study.

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.

Methotrexate treatment efficacy in sarcoidosis might be related to TNF-α polymorphism: real life preliminary study.

INTRODUCTION: Methotrexate therapy improves lung function in selected sarcoidosis patients. Variation in TNF gene was associated with response to treatment. Aim: To determine the predictive role of-308 G/A, -857C/T, -863 C/A and -1031 T/C TNF-α polymorphism in the efficacy of MTX for progressive pulmonary sarcoidosis. MATERIAL AND METHODS: Twenty-eight sarcoidosis patients treated with MTX (6-24 months) were genotyped for TNF-α polymorphisms: -1031 T/C, -857C/T, -308 G/A and -863 C/A. Pulmonary function test (PFT) were performed every 6 months to determine treatment response, until the drug withdrawal. RESULTS: No correlation between the initial clinical presentation of sarcoidosis and TNF α polymorphisms was found, neither for every allele nor for combined genotypes distribution. According to PFT evaluation we have discovered 3 types of response to MTX: early (ER), late (LR) and No-response (NR). TNF-α-308 A allele carriers have got significantly higher chance to be LR, p=0.02, RRI:83%. TNF-α-308 GG genotype transferred the 3-fold higher probability of early vs late response to MTX, p=0.02. Combined genotyping allowed to distinguish LR from ER and NR groups. ER and NR patients are genetically similar (-857CC-308GG). LR are "genetically" different group of patients (-857C/T-308GG or -857CC-308A/G) with 5-fold greater probability to be LR than TNF-α-857CC-308GG patients, p=0,005 sensitivity 85%, specificity: 43%, PPV 58%, NPV 75%. TNF-α-308GG-857CC patients have significantly lower chance to be LR comparing to other response type p=0.03 OR=0,075 95% CI=0.07-0.08. CONCLUSION: Two types of positive response to MTX therapy (early and late) in chronic respiratory sarcoidosis are associated with polymorphic changes in TNF gene.

Does bronchiectasis affect COPD comorbidities?

INTRODUCTION: COPD and bronchiectasis, chronic inflammation disorders of the bronchial tree through the mechanism of 'spill-over' of inflammatory mediators, may lead to systemic manifestations of illness of the respiratory system and comorbidities. The aim of the study was to evaluate the frequency of coexisting chronic obstructive pulmonary disease and bronchiectasis and influence of bronchiectasis on COPD comorbid diseases. MATERIAL AND METHODS: A post-hoc cross-sectional analysis of cohort study of 288 consecutive patients hospitalized due to acute exacerbation of COPD was performed. RESULTS: 177 males (61.5%) and 111 females (38.5%) with mean age = 71.0 8 ± 8.9 yrs, FEV1 % pred. = 34.6 ± 16.8 with COPD diagnosis were studied. In this group, 29 (10.1%) patients presented with bronchiectasis confirmed by HRCT scan. COPD patients with and without bronchiectasis had similar Charlson index results (2.5 vs 2.1, p=0.05). COPD patients with bronchiectasis required longer hospitalization during exacerbation. COPD patients with bronchiectasis significantly more often than patients without this comorbidity revealed the features of colonization with P. aeruginosa (OR = 4.17, p = 0.02). CONCLUSIONS: Bronchiectasis is a relatively common comorbidity in COPD patients. COPD patients with bronchiectasis are more frequently colonized with P. aruginosa comparing to non-bronchiectasis COPD patients. We did not confirm the influence of bronchiectasis on COPD comorbidities.

The influence of comorbidities on mortality in sarcoidosis: a observational prospective cohort study.

AIM: The aim of this study was to identify the frequency and prevalence of comorbidities in sarcoid patients and to assess their influence on overall mortality in the cohort of patients with sarcoidosis. MATERIALS AND METHODS: A cohort of 557 patients with histologically confirmed sarcoidosis diagnosed between 2007 and 2011 and a group of non-sarcoid controls were observed. All patients were carefully observed for comorbidities and mortality. RESULTS: 291 males (52.2%) and 266 females (47.8%) with mean age 48.4 ± 12.0 years in sarcoidosis group and a group of 100 controls with mean age (49.25 ± 10.3) were observed. The mean number of comorbidities in both groups was similar (0.9 ± 0.99 vs 0.81 ± 0.84 NS). The frequency of thyroid disease was significantly higher in sarcoidosis group comparing to controls at the time of diagnosis (OR = 3.62 P = 0.0144). During the observation period (median 58.0 months), 16 patients died (2.9%). The mean number of comorbidities was significantly higher in the groups of non-survivors as compared to survivors (2.8 ± 1.0, vs 0.8 ± 0.9), P < 0.0001. CONCLUSION: The comorbidity burden has strong impact on mortality in sarcoidosis. Thyroid diseases are more frequent in sarcoidosis than in non-sarcoid controls.

Sarcoidosis as a risk factor for venous thromboembolism.

Sarcoidosis as a chronic condition of immune dysregulation might be associated with increased risk of venous thromboembolism (VTE). In this study we report three cases of sarcoidosis and pulmonary embolism (PE) occurring together, that share common clinical, serological and pathological findings, confirming the diagnosis of active pulmonary sarcoidosis and no others co-existing prothrombotic factors. We hypothesized that the hypercoagulability and increased risk for VTE in sarcoidosis may be attributable to active local and generalized inflammatory process. The possible relation of clinical picture of sarcoidosis that favors thrombus formation and the bidirectional inflammation and coagulation process are discussed. Further investigation of PE in patients with sarcoidosis are required as the co-incidence of both diseases seems to be more frequent than expected. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 170-178).

Pilot program on distance training in spirometry testing - the technology feasibility study.

INTRODUCTION: Office spirometry has been widely used in recent years by general practitioners in primary care setting, thus the need for stricter monitoring of the quality of spirometry has been recognized. MATERIAL AND METHODS: A spirometry counseling network of outpatients clinics was created in Poland using portable spirometer Spirotel. The spirometry data were transferred to counseling centre once a week. The tests sent to the counseling centre were analyzed by doctors experienced in the analysis of spirometric data. In justified cases they sent their remarks concerning performed tests to the centres via e-mail. RESULTS: We received 878 records of spirometry tests in total. Data transmission via the telephone was 100% effective. The quality of spirometry tests performed by outpatients clinics was variable. CONCLUSIONS: The use of spirometers with data transfer for training purposes seems to be advisable. There is a need to proper face-to-face training of spirometry operators before an implementation of any telemedicine technology.

Venous thromboembolism and sarcoidosis: co-incidence or coexistence?

The association between venous thromboembolism (VTE) and sarcoidosis has been reported recently, nevertheless the true incidence of co-incident sarcoidosis and VTE is unknown. Sarcoidosis as a chronic disease of immune dysregulation might be associated with an increased risk of VTE. The mechanisms responsible for VTE development are not clear and may be influenced by several factors: activity of inflammation, clinical characteristics of sarcoidosis and comorbidities. Pulmonary embolism (PE) as a potentially fatal condition should be considered in all of the patients with sarcoidosis in whom worsening of the respiratory status is diagnosed. A high plasma D-dimers (DD) level may be suggestive of VTE, nevertheless elevated plasma DD should be interpreted with caution, in the context of the active inflammatory process. If sarcoidosis appears to be one of risk factors for VTE development, further investigations are needed to define the pro-thrombotic phenotype of this disease.

Methotrexate as a single agent for treating pulmonary sarcoidosis: a single centre real-life prospective study.

INTRODUCTION: The first-line therapy in chronic sarcoidosis, according to WASOG/ATS/ERS recommendations, is GCS. This therapy is associated with significant adverse effects and finally does not alter the natural history of the disease. The objective of our study was to evaluate the efficacy and safety of monotherapy with MTX, as an alternative to GCS, in progressive pulmonary sarcoidosis. MATERIAL AND METHODS: An open prospective real-life, single-centre trial was performed on 50 patients with biopsy proven sarcoidosis, 28M and 22F, mean age 45.55 ± 8.9 years. The average duration of disease before MTX therapy was 12.34 ± 20.49 years, GCS therapy in the past was applied in 41 patients. All patients received MTX (10 mg or 15 mg weekly) between 2004 and 2013 because of chronic progressive pulmonary sarcoidosis. Therapy was planned for 24 months. Patients underwent regular clinical evaluation, pulmonary function assessment, exercise ability testing (6MWT), and chest radiography for therapy effectiveness every six months and side effects monitoring every 4-6 weeks. Forty-nine patients were included for statistical analysis of treatment efficacy. They were retrospectively allocated to "MTX responder" group if an improvement of 10% of FEV1, FVC, TLC, or 15% of DLCO from the initial value was documented for at least one parameter or "non-responders" if the patient did not meet the above-mentioned criteria. RESULTS: Duration of treatment ranged from 6 to 24 months, mean time 60.75 ± 34.1 weeks. For the whole cohort significant improvement after MTX therapy was observed for minimal SaO2 (%) (p = 0.043) and for decrease of DSaO2 (%) (p = 0.048) in six-minute walk test. The results were significantly better for patients treated with 15 mg than for those treated with 10 mg weekly and for those who obtained a greater total amount of MTX during therapy. Significant difference of DLCO%pred was observed after six months of MTX therapy between groups treated 15 mg vs 10 mg weekly (73.27 ± 12.7% vs. 63.15 ± 16.4%, p = 0.03). Twenty-five patients (55%) met the criteria of "MTX responders" group. Patients who responded well to treatment had significantly lower TLC and FVC initial values comparing to "MTX non-responders". After treatment the only significant difference in PFT between groups was noted for DLCO%pred. Eleven patients (22%) stopped the treatment due to adverse events of MTX, mild hepatic abnormalities were observed in ten patients (20%), and concomitant infection was found in four patients. There were no patients with a fatal outcome. CONCLUSIONS: MTX as a single agent in the treatment of sarcoidosis has proved to be a safe and effective steroid alternative. Selected patients with chronic pulmonary sarcoidosis experience definite PFT improvements after MTX treatment. There is need to search for predictors of MTX treatment effectiveness.

Fatal clinical outcome in a patient with sarcoidosis-lymphoma syndrome.

A 62-year-old female suspected of malignant disease underwent a splenectomy that revealed noncaseating granulomas in the histological specimen. Chest X-ray (CXR) and lung CT scans suggested sarcoidosis stage II. TBLB showed noncaseating granulomas. A diagnosis of sarcoidosis was made. Initially no treatment was needed as partial remission on CXR and normal lung function were observed. During the follow up she underwent open lung biopsy and axillary lymph node biopsy because of radiological progression with presence of CXR opacities imitating metastases and recurrent lymphadenopathy. No malignant cells were found. Spontaneous partial resolution of disseminated changes on the CXR was observed. Because of progressive deterioration in lung function and the clinical course of the disease strongly suggesting the progression of systemic sarcoidosis, the patient was given steroid treatment, which initially resulted in partial remission of pulmonary disseminated changes, peripheral lymphadenopathy and improvement in lung function test. Eight months later severe deterioration in general condition, anaemia, leukocytosis, hypoxemia, massive hepatomegaly and recurrence of general lymphadenopathy along with progression of disseminated changes were found. She died before the final diagnosis was established. Post-mortem examination showed a nodal marginal zone B-cell lymphoma with monocytoid B-cells, according to WHO classification. The malignant cells were found in the jugular, mediastinal, paratracheal, paragastric, paraintestinal and retroperitoneal lymph nodes and they infiltrated the lungs, pleura, liver, thyroid gland and pancreas. No sarcoid granulomas were found in the autopsy.

[Six-minute walk test in sarcoidosis patients with cardiac involvement]. / Test 6-minutowego chodu u chorych na sarkoidoze pluc z zajeciem serca.

INTRODUCTION: Cardiac involvement in sarcoidosis is of critical importance, due to the poor prognosis if this organ manifestation is left undiagnosed and untreated. The six-minute walk test (6 MWT) is a useful test to evaluate exercise tolerance of sarcoid patients. We aimed to assess the 6 MWT value in diagnosis, course and treatment monitoring of patients with cardiac sarcoidosis. MATERIAL AND METHODS: 47 patients were included: 22 with pulmonary sarcoidosis and cardiac involvement (13 women, 9 men), 25 with pulmonary sarcoidosis, with no changes in the heart (15 women, 10 men), and 18 healthy volunteers as controls (12 women, 6 men). Out of 22 patients with cardiac involvement 11 were treated for heart sarcoidosis with prednisone (9 pts - initial dose 60 mg daily and 2 pts - 40 mg daily). 11 pts in this group were not treated. In all patients sarcoidosis was confirmed histopatologically. Magnetic resonance imaging was used to diagnose involvement of the heart. In the studied groups we assessed: heart rate (HR), oxygen saturation, and distance in 6 MWT and Borg dyspnea score. RESULTS: Patients with cardiac sarcoidosis desaturated more during exercise (DSaO2max = 3.5 ± 3.2 vs. 0.38 ± 0.69; p = 0.004) and had a lower increase of HR in first minute during the 6 MWT (DHR1 = 21.81 ± 11.72 vs. 50.61 ± 12.35; p = 0.0001) when compared to healthy subjects. Significantly lower increase of HR in first minute of 6 MWT was observed in patients with cardiac sarcoidosis when compared to patients with pulmonary sarcoidosis with no cardiac involvement (DHR1 = 21.81 ± 11.72 vs. 38.8 ± 18.17, p = 0.01). After introduction of treatment in sarcoidosis group, significantly higher (p = 0.02) increase of HR in first minute of 6 MWT as compared to baseline test was observed. CONCLUSIONS: The six-minute walk test is useful in diagnosing cardiac involvement in sarcoidosis. The increase in HR during exercise and decrease degree of desaturation were a good predictors of the response to therapy.

[Prophylaxis in chronic obstructive pulmonary disease]. / Profilaktyka przewleklej obturacyjnej choroby pluc.

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the world, is responsible for considerable morbidity and deterioration of quality of life of patients and their families. Prevention of COPD aims at reducing the burden of the disease. Prevention of COPD includes measures of tobacco control, reduction of the impact of harmful environment and the use of vaccination. However, despite proven efficacy of these methods, they are often inadequately applied.