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.

Bronchoalveolar Lavage Cell Count and Lymphocytosis Are the Important Discriminators between Fibrotic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis.

BACKGROUND: Fibrotic hypersensitivity pneumonitis (fHP) shares many features with other fibrotic interstitial lung diseases (ILD), and as a result it can be misdiagnosed as idiopathic pulmonary fibrosis (IPF). We aimed to determine the value of bronchoalveolar lavage (BAL) total cell count (TCC) and lymphocytosis in distinguishing fHP and IPF and to evaluate the best cut-off points discriminating these two fibrotic ILD. METHODS: A retrospective cohort study of fHP and IPF patients diagnosed between 2005 and 2018 was conducted. Logistic regression was used to evaluate the diagnostic utility of clinical parameters in differentiating between fHP and IPF. Based on the ROC analysis, BAL parameters were evaluated for their diagnostic performance, and optimal diagnostic cut-offs were established. RESULTS: A total of 136 patients (65 fHP and 71 IPF) were included (mean age 54.97 ± 10.87 vs. 64.00 ± 7.18 years, respectively). BAL TCC and the percentage of lymphocytes were significantly higher in fHP compared to IPF (p < 0.001). BAL lymphocytosis >30% was found in 60% of fHP patients and none of the patients with IPF. The logistic regression revealed that younger age, never smoker status, identified exposure, lower FEV1, higher BAL TCC and higher BAL lymphocytosis increased the probability of fibrotic HP diagnosis. The lymphocytosis >20% increased by 25 times the odds of fibrotic HP diagnosis. The optimal cut-off values to differentiate fibrotic HP from IPF were 15 × 106 for TCC and 21% for BAL lymphocytosis with AUC 0.69 and 0.84, respectively. CONCLUSIONS: Increased cellularity and lymphocytosis in BAL persist despite lung fibrosis in HP patients and may be used as important discriminators between IPF and fHP.

Factors Predictive for Immunomodulatory Therapy Response and Survival in Patients with Hypersensitivity Pneumonitis-Retrospective Cohort Analysis.

Hypersensitivity pneumonitis (HP) is one of the interstitial lung diseases with clearly established diagnostic criteria. Nevertheless, pharmacologic treatment recommendations are still lacking. Most specialists use steroids as first-line drugs, sometimes combined with an immunosuppressive agent. Aim: The aim of the present retrospective study was to establish predictive factors for treatment success and survival advantage in HP patients. Methods: We analyzed the short-term treatment outcome and overall survival in consecutive HP patients treated with prednisone alone or combined with azathioprine. Results: The study group consisted of 93 HP patients, 54 (58%) with fibrotic HP and 39 (42%) with non-fibrotic HP. Mean (± SD) VCmax % pred. and TL,co % pred. before treatment initiation were 81.5 (±20.8)% and 48.3 (±15.7)%, respectively. Mean relative VCmax and TL,co change after 3−6 months of therapy were 9.5 (±18.8)% and 21.4 (±35.2)%, respectively. The short-term treatment outcomes were improvement in 49 (53%) patients, stabilization in 16 (17%) patients, and progression in 28 (30%) patients. Among those with fibrotic HP, improvement was noted in 19 (35%) cases. Significant positive treatment outcome predictors were fever after antigen exposure, lymphocyte count in broncho-alveolar lavage fluid (BALF) exceeding 54%, RV/TLC > 120% pred., and ill-defined centrilobular nodules in high-resolution computed tomography (HRCT). An increased eosinophil count in BALF and fibrosis in HRCT were significant negative treatment outcome predictors. The presence of fibrosis in HRCT remained significant in a multivariate analysis. A positive response to treatment, as well as preserved baseline VCmax (% pred.) and TLC (% pred.), predicted longer survival, while fibrosis in HRCT was related to a worse prognosis. Conclusion: Immunomodulatory treatment may be effective in a significant proportion of patients with HP, including those with fibrotic changes in HRCT. Therefore, future trials are urgently needed to establish the role of immunosuppressive treatment in fibrotic HP.

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.

Exogenous lipoid pneumonia induced by nasal instillation of paraffin oil.

Lipoid pneumonia is a rare pulmonary disease, classified in terms of the source of lipid exposure into two variants: exogenous and endogenous. We present a patient with exogenous lipoid pneumonia, acquired after chronic exposure to paraffin oil-containing nasal drops. The diagnosis was established by demonstration of lipid-laden macrophages in bronchoalveolar lavage, chest computed tomography results and a history of lipid exposure.

[Bronchoscopy end endoscopic biopsy techniques in diagnosis of interstitial lung diseases]. / Bronchoskopia i endoskopowe techniki biopsyjne w diagnostyce chorób sródmiazszowych pluc.

The article treats about utility of bronchoscopy and endoscopic biopsy techniques in diagnosis of interstitial lung diseases (ILD). It describes macroscopic changes visible in bronchoscopy in course of particular ILD and biopsy techniques i.e. endobronchial biopsy (EBB), transbronchial lung biopsy (TBLB), transbronchial "blind" needle aspiration (TBNA) and transbronchial needle aspiration under endobronchial ultrasonography (EBUS-TBNA).

[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 lung disease in patients with primary biliary cirrhosis]. / Zmiany sródmiazszowe w plucach u chorych na pierwotna zólciowa marskosc watroby.

Primary biliary cirrhosis (PBC) is a chronic autoimmune disorder of unknown etiology. The disease affects middle-aged women and is characterized by the destruction of the intralobular bile ducts that causes consequent cholestasis. AMA is a hallmark of PBC, composed mostly of IgG and IgM class. The M2 antibody is the most specific one, with sensitivity range of 54-98% depending on type of test used. PBC is often accompanied by other autoimmune diseases, such as Sjögrens syndrome, thyroiditis, rheumatoid arthritis, dermatomyositis, polymyositis. Interstitial lung disease (ILD) has been reported in patients with primary biliary cirrhosis but its frequency and nature are poorly understood. We report pulmonary involvement in the course of PBC in 4 middle-aged women. Histopatological examination of lung specimens was available in three patients: two presented with sarcoid - like granulomas, one with lymphocytic interstitial pneumonia (LIP). In one patient the diagnosis of pulmonary fibrosis was based on clinical and radiological features. Because of abnormal pulmonary function tests (PFT) results all the patients were treated with prednisone, one, additionally with azathioprine. The treatment was successful in all of the patients.

[Virtual bronchoscopy and bronchofiberoscopy--a comparison of diagnostic value in assessment of centrally localized lung tumor]. / Porównanie wartosci diagnostycznej bronchoskopii wirtualneji bronchofiberoskopii w diagnostyce centralnego guza pluca.

INTRODUCTION: Virtual bronchoscopy (VB) is a new, noninvasive diagnostic technique which allows visualizing trachea and bronchi. Virtual images are created on the basis of data derived from helical CT scans using special protocol. A reconstructed, virtual image of the bronchial tree is very similar to that seen during conventional bronchofiberoscopy (FOB). The aim of the study was to compare VB images of the bronchi with those coming from FOB and evaluate diagnostic value of VB in centrally localized lung tumor. MATERIAL AND METHODS: The studied group consisted of 40 patients with suspicion of centrally localized lung cancer. Primary diagnosis was based on the chest X-ray. Each patient underwent CT and bronchofiberoscopy and after those routine procedures the VB analysis was performed. The results of the FOB were not known for radiologist performing VB. In both used methods, FOB and VB, the evaluation and comparison of the features of tumor presence, bronchial stenosis and widening of the carina were performed. In all 40 patients lung cancer was confirmed. The diagnosis was established by histopathologic examination of the tissue biopsy: 32 patients (80%)--non small cell lung cancer, 2 patients (5%)--small cell lung cancer, 5 patients (12.5%)--squamous cell carcinoma, 1 patient (2.5%)--carcinoid. RESULTS: Diagnostic value of VB in assessment of the for presence of the tumor in bronchus was: sensitivity 79.5%, specificity 95.5%, for bronchial stenosis: sensitivity 58.6%, specificity 98.1% and for widening of carina: sensitivity 60.7%, specificity 97.7%. CONCLUSION: The results indicate that virtual bronchoscopy is highly sensitive and specific diagnostic method, a clinically valuable for the evaluation of lung tumor with a central location.

[Bacteriologically confirmed pulmonary tuberculosis in a patient with lymphangioleiomyomatosis accompanying tuberous sclerosis syndrome]. / Gruzlica pluc potwierdzona bakteriologicznie u chorejna limfangioleiomiomatoze w przebiegu stwardnienia guzowatego.

Lymphangioleiomyomatosis (LAM) is a rare disease of unknown origin, that may be sporadic or develop in the course of tuberous sclerosis (TS). Patients do not present immune deficiency, but structural changes in the lung parenchyma (cysts) may encourage various infections, for example tuberculosis. Radiologic findings are often difficult to interpret, because of changes related to LAM itself. We present a young women with a history of TS and LAM, in whom protracting respiratory tract infection was finally diagnosed as tuberculosis. Initial diagnosis was based primarily on clinical signs and symptoms and treatment was started despite the negative result of the sputum microscopy for acid fast bacilli. In the course of treatment the diagnosis was supported by positive tuberculin skin test, interferon-gamma release assay and genetic test for M. tuberculosis in bronchoalveolar lavage fluid, and finally, positive sputum culture in liquid medium.

The Cardiac Markers and Oxidative Stress Parameters in Advanced Non-Small Cell Lung Cancer Patients Receiving Cisplatin-Based Chemotherapy.

INTRODUCTION: Cardiotoxicity is a well known long-term consequence of lung cancer chemotherapy, however little is known about early subclinical changes in cardiac function. AIM: The goal of the study was to assess early cardiotoxic effects of cisplatin-containing chemotherapy in stage III and IV lung cancer patients, measuring serum levels of selected cardiac markers in relation to oxidant effects. METHODS: We quantified the immediate impact of chemotherapy on cardiac troponin T (TnT), creatine kinase-myocardial band (CK-MB) and N- terminal pro-brain natriuretic peptide (NT-proBNP) in blood samples obtained from 12 non-small cell lung cancer (NSCLC) patients. All markers were measured using commercially available immunoassays. To investigate the oxidant effects of cisplatin-containing chemotherapy, we evaluated reduced glutathione (GSH), nitrite (NO2), derivatives of reactive oxygen metabolites (d-ROMs) and thiols (SH). Samples were collected prior to chemotherapy and 1 day after the first cycle of cisplatin administration. RESULTS: Chemotherapy did not cause statistically significant elevations in serum CK-MB. Serum TnT levels were undetectable at both time points in 11 out of 12 patients with a threshold of 0.01 ng/ml. In the single patient with undetectable TnT at the baseline, after the first infusion TnT level reversibly rose to 0.03 ng/ml. The pre-treatment value of NT-proBNP was slightly elevated in 7 out of 12 lung cancer patients. In 1 case NT-proBNP level significantly increased after chemotherapy (from 221.8 to 1489.0 pg/ml p<0.001), in the remaining 11 patients it was stable Cisplatin-based combination chemotherapy induced significant nitrite production in 5 patients (p<0.05). The other measured oxidative stress parameters remained unchanged after the first infusion. CONCLUSION: This pilot study demonstrated occasional elevations of cardiac biomarkers during cisplatin administration. Administration of cisplatin-containing chemotherapy caused significant nitroxidative stress in some patients. The relevance of cardiovascular complications in cancer patients and identification individual risk factors of developing cardiovascular toxicity merit further evaluation.