The Presence of T Allele (rs35705950) of the MUC5B Gene Predicts Lower Baseline Forced Vital Capacity and Its Subsequent Decline in Patients with Hypersensitivity Pneumonitis.

Hypersensitivity pneumonitis (HP) is an exposure-related interstitial lung disease with two phenotypes-fibrotic and non-fibrotic. Genetic predisposition is an important factor in the disease pathogenesis and fibrosis development. Several genes are supposed to be associated with the fibrosing cascade in the lungs. One of the best-recognized and most prevalent is the common MUC5B gene promoter region polymorphism variant rs35705950. The aim of our study was to establish the frequency of the minor allele of the MUC5B gene in the population of patients with HP and to find the relationship between the MUC5B promoter region polymorphism and the development of lung fibrosis, the severity of the disease course, and the response to the treatment in patients with HP. Eighty-six consecutive patients with HP were tested for the genetic variant rs35705950 of the MUC-5B gene. Demographic, radiological, and functional parameters were collected. The relationship between the presence of the T allele and lung fibrosis, pulmonary function test parameters, and the treatment response were analyzed. The minor allele frequency in the study group was 17%, with the distribution of the genotypes GG in 69.8% of subjects and GT/TT in 30.2%. Patients with the GT/TT phenotype had significantly lower baseline forced vital capacity (FVC) and significantly more frequently had a decline in FVC with time. The prevalence of lung fibrosis in high-resolution computed tomography (HRCT) was not significantly increased in GT/TT variant carriers compared to GG ones. The patients with the T allele tended to respond worse to immunomodulatory treatment and more frequently received antifibrotic drugs. In conclusions: The frequency of MUC5B polymorphism in HP patients is high. The T allele may indicate a worse disease course, worse immunomodulatory treatment response, and earlier need for antifibrotic treatment.

Venous Thromboembolic Disease in COVID-19, Pathophysiology, Therapy and Prophylaxis.

For over two years, the world has been facing the epidemiological and health challenge of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Growing problems are also complications after the development of COVID-19 in the form of post and long- COVID syndromes, posing a challenge for the medical community, both for clinicians and the scientific world. SARS-CoV-2 infection is associated with an increased risk of cardiovascular complications, especially thromboembolic complications, which are associated with both thrombosis of small and very small vessels due to immunothrombosis, and the development of venous thromboembolism. Low molecular wight heparin (LMHW) are the basic agents used in the prevention and treatment of thromboembolic complications in COVID-19. There is still a great deal of controversy regarding both the prevention and treatment of thromboembolic complications, including the prophylaxis dose or the optimal duration of anticoagulant treatment in patients with an episode of venous thromboembolism.

Nontuberculous Mycobacterial Lung Disease in the Patients with Cystic Fibrosis-A Challenging Diagnostic Problem.

BACKGROUND: Cystic fibrosis (CF) is an autosomal, recessive genetic disorder, caused by a mutation in the cystic fibrosis transmembrane conductance receptor regulator (CFTR) gene. Dysregulated mucous production, and decreased bronchial mucociliary clearance, results in increased susceptibility to bacterial and fungal infections. Recently, nontuberculous mycobacteria (NTM) infections were identified as an emerging clinical problem in CF patients. AIM: The aim of the present study was to assess the frequency of NTM isolations in CF patients hospitalized in the pulmonary department, serving as a hospital CF center, and to describe challenges concerning the recognition of NTMLD (nontuberculous mycobacterial lung disease) in those patients. METHODS: Consecutive CF patients, who were hospitalized due to pulmonary exacerbations (PEX), in a single CF center, between 2010 and 2020, were retrospectively assessed for the presence of NTM in respiratory specimens. Clinical and radiological data were retrospectively reviewed. RESULTS: Positive respiratory specimen cultures for NTM were obtained in 11 out of 151 patients (7%), mean age-35.7 years, mean BMI-20.2 kg/m2, mean FEV1-58.6% pred. Cultures and phenotyping revealed the presence of Mycobacterium avium (M. avium)-in six patients, Mycobacterium chimaera (M. chimaera) in two, Mycobacterium kansasii (M. kansasii)-in one, Mycobacterium abscessus (M. abscessus)-in one, Mycobacterium lentifavum (M. lentiflavum)-in one. Simultaneously, respiratory cultures were positive for fungi in 91% of patients: Candida albicans (C. albicans)-in 82%, Aspergillus fumigatus (A. fumigatus)-in 45%. Clinical signs of NTMLD were non-specific, chest CT indicated NTMLD in five patients only. CONCLUSION: Due to non-specific clinical presentation, frequent sputum cultures for NTM and analysis of serial chest CT examinations are crucial for NTMLD recognition in CF patients. Further studies concerning the predictive role of fungal pathogens for NTMLD development in CF patients are needed.

Dominating Cause of Pulmonary Hypertension May Change Over Time-Diagnostic and Therapeutic Considerations in a Patient with Pulmonary Hypertension Due to Rheumatoid Arthritis with Lung Involvement.

Chronic lung diseases are one of the most frequent causes of pulmonary hypertension (PH). The diagnostic challenge is to differentiate PH due to chronic lung disease from pulmonary arterial hypertension (PAH) with coexisting chronic lung disease. Moreover, the dominating cause of PH may change over time, requiring the implementation of new diagnostic procedures and new treatment modalities. We present a 68-year-old female, initially diagnosed with PH in the course of interstitial lung disease, with restrictive impairment of lung function. Therapy with immunosuppressive drugs resulted in significant clinical, radiological and functional improvement. However, five years later, arthritis symptoms developed, with PH worsening, despite stable lung disease. The patient was diagnosed with PAH in the course of rheumatoid arthritis. The introduction of sildenafil resulted in marked clinical and hemodynamic responses. Long-term survival (eleven years from PH onset and five years from PAH confirmation) has been achieved, and the patient remains in good functional condition. As the differential diagnosis of PH in patients with lung diseases is complex, the cooperation of pulmonologists and cardiologists is mandatory to obtain therapeutic success.

Combined Emphysema and Interstitial Lung Disease as a Rare Presentation of Pulmonary Involvement in a Patient with Chronic Visceral Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B).

BACKGROUND Niemann-Pick disease is a rare genetic disorder caused by mutations in sphingomyelin phosphodiesterase 1 gene. It results in acid sphingomyelinase deficiency (ASMD) and sphingomyelin intracellular accumulation. Lung disease is diagnosed mostly in chronic visceral ASMD. Ground-glass opacities and smooth interlobular septal thickening are described most frequently. They are localized predominantly in the lower parts of both lungs. CASE REPORT The authors describe a rare type of lung involvement, composed of emphysema and interstitial lung disease (ILD), in a nonsmoking adult male with chronic visceral ASMD. Areas of ground-glass opacities and lung fibrosis presenting as reticulation and bronchiectasis have been described in high-resolution computed tomography of the lungs. The radiological findings were localized predominantly in the middle and lower parts of both lungs. Large air spaces of marginal emphysema, localized in the upper lobes, were also demonstrated. Foamy macrophages, staining blue with May-Grünwald-Giemsa, were found in bronchoalveolar lavage, confirming lung involvement in the course of ASMD. The course of disease was stable, with no hypoxemia at rest. Nevertheless, because of markedly decreased lung transfer for carbon monoxide and significant desaturation on exertion, further controls have been planned, with qualification for long-term oxygen therapy in case of deterioration. CONCLUSIONS We present a unique type of lung involvement, combined emphysema and ILD, in a nonsmoking adult patient with chronic visceral ASMD. On such occasion chronic obstructive pulmonary disease coexisting with ILD as well as chronic pulmonary fibrosis and emphysema syndrome should be excluded.

Non-Tuberculous Mycobacteria in Respiratory Specimens of Patients with Obstructive Lung Diseases-Colonization or Disease?

Non-tuberculous mycobacteria (NTM) are increasingly a cause of human respiratory tract colonization and mycobacterial lung disease (NTM-LD), especially in patients with chronic lung diseases. The aim of the present study was to find the factors predictive of NTM-LD in patients with obstructive lung diseases and NTM respiratory isolates. A total of 839 isolates of NTM, obtained from 161 patients between 2010 and 2020 in a single pulmonary unit, have been retrospectively reviewed. Of these isolates, 73 concerned 36 patients with obstructive lung diseases (COPD-26, asthma-3, COPD/asthma overlap syndrome-7). NTM-LD was recognized according to the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) criteria in 17 patients, colonization in 19. Lower BMI, elevated body temperature on admission, infiltrative/cavitary lesions on chest CT, and NTM species other than Mycobacterium gordonae were the significant predictors of NTM-LD recognition. Based on the above-mentioned predictive factors, an original scoring system was implemented. The diagnostic utility of the scoring system was higher than that of single parameters. We conclude that NTM-LD prediction in patients with obstructive lung diseases and positive respiratory isolates is difficult. A scoring system based on clinical, radiological and microbiological characteristics was capable of facilitating the differential diagnosis, but it needs further validation in a larger study group.

SARS-CoV-2 lung disease in a patient with pulmonary sarcoidosis - case report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the recently identified cause of the current pandemic. In patients with chronic respiratory lung diseases, SARS-CoV-2 may result in significant morbidity and increased mortality. We present a case of a 69-year-old male with stage II pulmonary sarcoidosis who had been under observation for 30 months without immunosuppressive treatment. He then developed severe SARS-CoV-2 disease with typical radiological and laboratory findings. Therapy with oxygen, antibiotics, low-molecular-weight heparin in a prophylactic dose, and dexamethasone resulted in marked clinical improvement. We will discuss the rationale for corticosteroid use in both SARS-CoV-2 disease and in SARS-CoV-2 disease that is complicating comorbid sarcoidosis.

Interferon Gamma Release Assays in Patients with Respiratory Isolates of Non-Tuberculous Mycobacteria - a Preliminary Study.

Interferon gamma releasing assays (IGRAs) are extensively used in the diagnosis of latent tuberculosis infections. Comparing to tuberculin skin test (TST) they lack false positive results in the populations vaccinated with BCG, and in most non-tuberculous mycobacteria (NTM) infections. Nevertheless, Mycobacterium kansasii, Mycobacterium marinum, and Mycobacterium szulgai may induce positive IGRAs due to RD1 homology with Mycobacterium tuberculosis. The aim of the study was to investigate the possible influence of NTM respiratory isolates on the results of IGRAs. 39 patients (23 females and 16 males) of median age 61 years, with negative medical history concerning tuberculosis, entered the study. Identification of NTM was performed using the niacin test and molecular method GenoType CM test (Hain Lifescience). QFT-Plus was performed in 17 patients, T-SPOT-Tb - in 23 patients. Chest X-rays and a high-resolution computed tomography of the chest have been reviewed by the experienced radiologist blinded to the results of IGRAs, in search of past tuberculosis signs. Positive IGRAs results were obtained in three out of 39 patients (8%): 22% of patients with M. kansasii isolates and 18% of patients with radiological signs on HRCT that might be suggestive of past tuberculosis. Positive IGRAs correlated with radiological signs suggestive of past tuberculosis (r = 0.32, p = 0.04), and on the borderline with isolation of M. kansasii (r = 0.29, p = 0.06). These findings may suggest that a positive IGRAs result, in our material, could depend mostly on asymptomatic past Tb infection. The cross-reactivity of M. kansasii isolates with IGRAs was less probable; nevertheless, it requires further investigations.Interferon gamma releasing assays (IGRAs) are extensively used in the diagnosis of latent tuberculosis infections. Comparing to tuberculin skin test (TST) they lack false positive results in the populations vaccinated with BCG, and in most non-tuberculous mycobacteria (NTM) infections. Nevertheless, Mycobacterium kansasii, Mycobacterium marinum, and Mycobacterium szulgai may induce positive IGRAs due to RD1 homology with Mycobacterium tuberculosis. The aim of the study was to investigate the possible influence of NTM respiratory isolates on the results of IGRAs. 39 patients (23 females and 16 males) of median age 61 years, with negative medical history concerning tuberculosis, entered the study. Identification of NTM was performed using the niacin test and molecular method GenoType CM test (Hain Lifescience). QFT-Plus was performed in 17 patients, T-SPOT-Tb ­ in 23 patients. Chest X-rays and a high-resolution computed tomography of the chest have been reviewed by the experienced radiologist blinded to the results of IGRAs, in search of past tuberculosis signs. Positive IGRAs results were obtained in three out of 39 patients (8%): 22% of patients with M. kansasii isolates and 18% of patients with radiological signs on HRCT that might be suggestive of past tuberculosis. Positive IGRAs correlated with radiological signs suggestive of past tuberculosis (r = 0.32, p = 0.04), and on the borderline with isolation of M. kansasii (r = 0.29, p = 0.06). These findings may suggest that a positive IGRAs result, in our material, could depend mostly on asymptomatic past Tb infection. The cross-reactivity of M. kansasii isolates with IGRAs was less probable; nevertheless, it requires further investigations.

Factors predisposing to non-tuberculous mycobacterial lung disease in the patients with respiratory isolates of non-tuberculous mycobacteria.

INTRODUCTION: An increasing incidence rate of respiratory isolates of non-tuberculous mycobacteria (NTM) has been noted recently in most European countries as well as in the US. Despite many publications, there is no consensus concerning the importance of different factors in promoting NTM lung disease (NTMLD). The aim of the present retrospective study was to analyse patients with positive NTM respiratory isolates in search of factors predisposing to NTMLD. MATERIAL AND METHODS: 73 patients, 23 males, 50 females, median age 62.2 years, in whom NTM have been cultured from respiratory specimen (sputum and/or bronchial washings), in the period 2010-2015, entered the study. RESULTS: NTMLD (according to ATS/IDSA) has been recognised in 36 patients, airways colonisation by NTM - in 37 patients. NTMLD was diagnosed more often in the patients infected with M. kansasii, M. abscessus and M. avium/M. intracellulare comparing to those infected with M.xenopi, M. gordonae and M. fortuitum (p < 0.0001). The proportion of females to males was significantly higher in the NTMLD group comparing to the colonisation group (p < 0.007). Previous tuberculosis or mycobacteriosis were noted significantly more frequently in the group of patients with NTMLD comparing to the colonisation group (28% vs 8%, p = 0.038). Univariate regression analysis revealed M. kansasii, female gender, and previous tuberculosis or mycobacteriosis as significant predictors of NTMLD. CONCLUSIONS: The risk factors of NTMLD recognition in the presented group of patients were the following: female gender, M. kansasii isolation, as well as past tuberculosis or mycobacteriosis.

Nontuberculous mycobacterial lung disease in a patient with COPD and bronchiectasis, with radiological signs of lung tumor.

Mycobacterial lung disease is caused by nontuberculous mycobacteria (NTM), also known as atypical mycobacteria. NTM are widely distributed in the environment, particularly in soil and water; they may colonize the airways, gastrointestinal tract and genitourinary system, without the apparent signs of disease. Nevertheless, in some risk groups such as patients with chronic lung diseases or with immunodeficiency, mycobacterial lung disease is identified. Recently, increased recognition of mycobacterial lung disease in chronic obstructive pulmonary disease (COPD) patients has been observed, especially in those treated with high doses of inhaled corticosteroids. In the present paper, we describe the patient treated for many years due to COPD and bronchiectasis, with clinical and radiological picture suggestive of lung tumor, in whom final diagnosis of mycobacterial lung disease caused by Mycobacterium avium was made.

Non-high risk PE in the patients with acute or exacerbated respiratory disease: the value of the algorithm based on D-dimer evaluation and Revised Geneva Score.

INTRODUCTION: The diagnostic algorithm of non-high risk pulmonary embolism (PE) is based on probability scoring systems and plasma D-dimer (DD) assessment. The aim of the present study was to investigate the efficacy of Revised Geneva Scoring (RGS) and DD testing for the excluding of non-high risk PE, in the patients admitted to the hospital due to acute respiratory diseases. MATERIAL AND METHODS: The consecutive patients, above 18 years of age, referred to the department of lung diseases, entered the study. The exclusion criteria were: the pregnancy and the suspicion of high risk PE. Plasma DD was measured with quick ELISA test, VIDAS D-dimer New, bioMerieux, France. Multislice computed tomography angiography was performed in all of the patients. RESULTS: 153 patients, median age 65 (19-88) years entered the study. The probability of PE was: low - in 58 patients (38%), intermediate - in 90 (59%), high - in 5 (3%). DD < 500 ng/ml was found in 12% of patients with low and intermediate probability of PE. PE was recognized in 10 out of 153 patients (7%). None of the patients with DD < 500 ng/ml was diagnosed with PE (NPV 100%). Median DD value was significantly higher in PE patients comparing to non-PE (4500 ng/ml and 1356 ng/ml respectively, p = 0.006). CONCLUSION: In the group of the patients with acute respiratory symptoms, low or intermediate clinical probability scoring combined with normal DD had a high NPV in excluding PE. Nevertheless, such approach was not very effective, as the increased DD was noted in 88% of the examined population.

[Mycobacterial lung disease in patients with cystic fibrosis--report of three cases]. / Mikobakterioza u chorych na mukowiscydoze--opis trzech przypadków.

Mycobacterial lung disease is caused by nontuberculous mycobacteria (NTM), also known as atypical mycobacteria. NTM are widely distributed in the environment, particularly in soil and water. Although generally of low pathogenicity to humans, NTM can affect patients with underlying chronic lung diseases, such as cystic fibrosis, bronchiectasis, pneumoconiosis, or healed tuberculosis. Some patients with cystic fibrosis (CF) have disease progression due to NTM, others can have NTM cultured intermittently from respiratory specimens without a significant decline in lung function. Identifying which patients will worsen from NTM and therefore need treatment remains difficult because of the similarity of symptoms in CF and NTM lung disease. The most common species of NTM isolated in CF patients are Mycobacterium avium complex (MAC) and Mycobacterium abscessus. In this paper, we present three different cases of mycobacterial lung disease in patients with cystic fibrosis.

[Interstitial lung disease in patients with polymyositis and dermatomyositis--report of three cases]. / Zmiany sródmiazszowe w plucach u chorych na zapalenie wielomiesniowe i skórno-miesniowe--prezentacja trzech przypadków.

Polymyositis (PM) and dermatomyositis (DM) are connective tissue diseases (CTD) characterized by proximal muscle weakness along with changes in various internal organs, with the lungs most frequently involved. Presentation of the disease in the lungs comprises diffuse alveolar haemorrhage due to vasculitis and interstitial lung disease (ILD), which is the most frequent manifestation of CTD in the lungs and worsens the outcome and prognosis. The mechanisms involved in the ILD are not fully known, but the role of autoimmune response is unquestioned. No relationship between the severity of CTD and the changes in the lungs was observed. ILD may present at any time in the course of CTD, sometimes before the signs and symptoms of myositis occur. The more accurate imaging methods are, the more frequently changes in the lungs are detected. High resolution computed tomography (HRCT) is a gold standard in ILD imaging. Treatment of PM/DM-related ILD relays on systemic glucocorticosteroids as the first choice drugs. We present three cases of PM/DM-related ILD in middle-aged men, with a different clinical and radiological presentation. In all cases, apart from imaging (plain X-ray and HRCT of the chest) and pulmonary function tests, histological evaluation of lung changes was performed. In two cases non-specific interstitial pneumonitis (NSIP) was diagnosed, and in the third--organizing pneumonia along with sarcoid changes in the lymph nodes. Because of decreased pulmonary function all patients were treated with systemic corticosteroids and two of them additionally with azathioprine or cyclophosphamide, and the outcome was good in all of them.

[Interstitial pneumonia connected with rituximab therapy--case report]. / Sródmiazszowe zapalenie pluc zwiazane z leczeniem rytuksymabem--opis przypadku.

Rituximab (RTX) is a monoclonal antibody against the CD20 antigen found on the surface of B cells. RTX causes cell lysis and is therefore used to treat lymphomas, leukaemias, transplant rejection and certain autoimmune disorders. Pulmonary adverse events associated with RTX have been reported in literature. We describe a patient with follicular lymphoma treated with R-CHOP scheme (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) who had pulmonary symptoms during chemotherapy which were diagnosed as rituximab-induced interstitial pneumonia. Symptoms and radiological changes resolved with prednisone therapy.