Pneumothorax in Patients with Pulmonary Langerhans Cell Histiocytosis.

INTRODUCTION: Pneumothorax often develops in pulmonary Langerhans cell histiocytosis (PLCH), but some patients take a long time to be correctly diagnosed. OBJECTIVES: This study assessed the frequency of pneumothorax in PLCH and analysed the role of chest computed tomography (CT) in the prompt diagnosis. PATIENTS AND MATERIAL: Of the 90 patients with PLCH seen from 2000 to 2015, 29 (32%) had pneumothorax as the initial finding. In this group, 18 (62%) patients were diagnosed within 1 month, whereas the diagnosis was delayed for 4-120 months in 11 (38%) patients. RESULTS: Patients who had pneumothorax as the initial sign of PLCH tended to be younger (mean age 27.7 ± 7.92 vs. 39.9 ± 13.21 years; P = 0.0001), male (69% vs. 43%; P = 0.028), smoked less (mean pack/years 8.4 ± 6.85 vs. 19 ± 17.16; P = 0.003), and had a significantly lower mean FVC (77.96 ± 19.62 vs. 89.47 ± 21.86% pred.; P = 0.015) and FEV1 (68.6 ± 19.93 vs. 79.4 ± 21.48% pred.; P = 0.03 than patients who had no pneumothorax. Recurrent pneumothorax was diagnosed more frequently in the group with a delayed diagnosis (82% vs. 39%; P = 0.02). CT was performed in all of the patients who were diagnosed promptly, but in none of the patients with a delayed diagnosis. CONCLUSIONS: Patients who had pneumothorax as the initial sign of PLCH were younger, more frequently men, and had greater respiratory impairment than those who had no pneumothorax. CT in patients with pneumothorax led to a correct diagnosis of this disease.

Cryptogenic Organizing Pneumonia: IL-1ß, IL-6, IL-8, and TGF- ß1 Serum Concentrations and Response to Clarithromycin Treatment.

Cryptogenic organizing pneumonia (COP) is a distinct clinicopathological entity with unknown etiology. Inflammatory cytokines play a role in the development of the disease. The present study was performed to assess the correlation between concentrations of IL-1ß, IL-6, IL-8, and TGF-ß1 in the serum with response to clarithromycin (CAM) treatment in patients with COP. A total of 39 patients with COP were enrolled in to this study. An oral dose of 500 mg CAM was administered to all of the patients twice daily for 3 months. A complete response was noticed in 31 (80 %) of patients, and 8 (20 %) patients failed to respond to treatment. The concentration of cytokines were assessed by ELISAs before and after treatment. CAM treatment was associated with decreases in serum IL-6 (3.8 pg/mL [IQR 0.9-11.8] vs. 1.1 pg/mL [IQR 0.2-3.1]; p = 0.004), IL-8 (13.6 pg/mL [IQR 9.8-17.5] vs. 8.1 pg/mL [IQR 6.2-13.2]; p = 0.004), and TGF-ß1 (37.1 ng/mL [IQR 31.7-46.2] vs. 25.7 ng/mL [IQR 22-41.7];p = 0.0001), which was particularly notable in the responders. We conclude that IL-6, IL-8, and TGF-ß1 may play a role in the pathogenesis of COP, as their decreased concentrations were associated with a positive response to CAM treatment.

Pulmonary Function Abnormalities in Regard to Age at the Time of Diagnosis of Hypersensitivity Pneumonitis.

Hypersensitivity pneumonitis (HP) is a complex syndrome caused by exaggerated immune response to inhalation of a variety of organic particles in susceptible individuals. In this study we assessed the relationship between age at the time of diagnosis and the degree of functional and radiological changes in HP. The diagnosis of HP was made on the basis of a combination of clinical symptoms, medical history, serological tests, radiologic evidence of diffuse lung disease, and absence of other identifiable causes of lung disease. We reviewed the records of 111 patients (68 women) diagnosed with HP over a period of 18 years (1995-2013). The patients were stratified into 3 age-groups: <30, 30-49, and ≥50 years old. The commonest cause of HP was avian antigens (56.8 %). Dyspnea was present in 97.3 % of patients, weight loss in 54.7 % of patients, and respiratory insufficiency in 24.3 % of patients. Lung fibrosis in chest computed tomography was found in 35.1 % of patients. Lung function was impaired more seriously in the youngest age-group, with lung diffusing capacity for carbon monoxide (DLCO) <40 % in 69.2 % of these patients. Restrictive pattern was present in 92.3 % of patients in this group, as compared with the 41.0 % in the whole cohort. In this group, desaturation in the six minute walk test also was most notable, amounting to a median of 11 %. In conclusion, diagnosis of HP at young age is predictive of a more severe clinical course of disease, with lung fibrosis and higher disturbances in pulmonary function.

Bronchial hyperreactivity in sarcoidosis patients: correlation with airflow limitation indices.

UNLABELLED: Bronchial hyperreactivity (BHR) in sarcoidosis has been reported in 5 to 83% of patients, but the relationship between BHR and airway functional status being unclear. The aim of the study was to assess the prevalence and degree of BHR in a group of pulmonary sarcoidosis patients and how BHR does relate to the functional status of airways. MATERIAL AND METHODS: 56 consecutive sarcoidosis outpatients (26 f, 30 m) were included. There were 14 (25%) patients in stage I, 32 (57.1%) patients in stage II and 10 (17.9%) patients in stage III. In all patients the standard evaluation included a history, physical examination, chest radiogram, serum ACE activity and lung function assessment were done. The provocation challenge test with doubling concentrations of histamine was performed in all patients using the standardized protocol recommended by the ERS. RESULTS: 4 patients (7%) were restrictive, airway obstruction was detected in 7 (12.5%) cases. Up to 32% of patients had maximal expiratory flows at low lung volumes below the lower limit of normal (LLN). The histamine challenge test results: in 9 cases (16%) the fall in FEV1 was < 20% of the baseline; mean PC20H (n = 47) was 5.7 +/- 5.9 mg/mL, range: 0.56-26.7 mg/mL. The challenge test was regarded as positive (PC20H < or = 8 mg/mL) in 71.4% of the group. BHR expressed as ln(PC20H) correlated weakly but significantly with FEV1, FEV1%VC, MMEF and PEF. CONCLUSION: BHR occurs frequently in sarcoidosis patients and should be considered especially in patients with airflow limitation.

Antineutrophil cytoplasmic antibodies and their relationship with disease activity and presence of staphylococcal superantigens in nasal swabs in patients having granulomatosis with polyangiitis: results of a study involving 115 patients from a single center.

OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCAs) are considered a risk factor for granulomatosis with polyangiitis (GPA) exacerbation, especially when staphylococcal superantigens (SAgs) are present in nasal swabs. Their role in monitoring disease activity remains controversial. This study determined the relationship of ANCAs with disease activity and presence of SAgs in GPA patients. METHODS: Among a total of 115 GPA patients hospitalized in the period 2009-2016, we investigated the presence of SAgs and ANCA concentration. Blood samples and nasal swabs were taken at each visit (referred further to as episodes). Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). RESULTS: We analyzed 362 episodes. ANCAs were detected in 215 (59.4%), while SAgs were detected in 126 (34.8%) episodes. We found a significant correlation between the presence of ANCAs and disease activity (p = 0.0032), as well as between their level and GPA severity (r = 0.25363, p = 0.000001). We also determined that an ANCA values ≥ 138 Ru/ml were an indicator of active disease with high specificity and low sensitivity (84.4% and 37.3%, respectively). The relationship between ANCA presence and the presence of SAgs was not confirmed; however, when SAgs were analyzed based on the different types, ANCA levels were found to be significantly higher in the group with SAg type B (p = 0.031). CONCLUSIONS: There was no detectable evidence for the association between ANCA level and the presence of SAgs. Although monitoring ANCA levels as a marker of disease activity may be clinically relevant, GPA management cannot proceed on the basis of ANCA levels alone. Key Points • ANCA concentration usually correlates with GPA activity, although in half of patients, ANCAs persist despite effective treatment and clinical remission. • ANCA values of 138 Ru/ml seem to be an indicator of active disease with high specificity, but low sensitivity. • Although there is a relevance for ANCA monitoring as a marker of disease activity, GPA management cannot be based on ANCA levels alone. • The suspected clinical correlation between ANCA formation and SAg presence in nasal swabs is not obvious and requires further investigations.

p53 and HER2/neu expression in relation to chemotherapy response in patients with non-small cell lung cancer.

The aim of the study was to investigate a relation between p53 and HER2/neu expression in resected lung tumors and the response of those tumors to neoadjuvant chemotherapy. The study population included 67 consecutive patients with non-small cell lung cancer (NSCLC) in stage II or III who were operated on at the Institute of Tuberculosis, Warsaw, Poland, between 20 April 2001 and 10 March 2003. All patients received two cycles of chemotherapy consisting of cisplatin and vinorelbine prior to the operation. The response to therapy was assessed as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), on the basis of CT scans performed before and after neoadjuvant chemotherapy. p53 and HER2/neu protein expression were evaluated by immunohistochemistry (IHC) using antibodies against p53 (clone PAb 1801, Novocastra) and against HER2/neu (Dako) in paraffin-embedded specimens of tumors. A response to therapy (CR+PR) was observed in 27 patients, while 40 patients (SD+PD) were regarded as resistant to therapy. Resistance was observed significantly more often in tumors above 3 cm in diameter. p53 expression was found in 16 tumors (23.9%) and HER2/neu in 26 tumors (38.8%). We observed a nonsignificant tendency to chemoresistance in tumors with HER-2/neu overexpression and also in tumors with p53 overexpression. If we consider HER-2/neu and p53 together, chemoresistance was observed statistically significantly more often when one or both markers were positive (p<0.05). This significance was independent of tumor size.

Epirubicin in previously untreated patients with small cell lung cancer: a phase II study by the EORTC Lung Cancer Cooperative Group.

Epirubicin 110 mg/m2 was administered intravenously every 3 weeks to 41 elderly and/or unfit, previously untreated patients with small cell lung cancer (SCLC). There were three complete responses, 16 partial responses and 14 treatment failures, with a response rate of 57% in 33 evaluable patients. The main toxicity was haematological, characterised by leukopenia and, less frequently, thrombocytopenia and anaemia. There were three toxic deaths due to infection occurring during leukopenia. Non-haematological side effects were alopecia, nausea, stomatitis and diarrhoea. WHO grade 2 cardiac toxicity was seen in 3 patients after a cumulative dose of more than 740 mg/m2. In conclusion epirubicin is an active agent in untreated SCLC.

The prognostic significance of bone marrow metastases in small cell lung cancer patients.

One-hundred forty-six SCLC patients were classified as localised (56) or extensive (90) using chest X-ray, bronchoscopy, brain CT, bone scintigraphy, ultrasonography of the abdomen and bilateral bone marrow trephine biopsy. Bone marrow metastases were found in 28 cases. Patients with bone marrow metastases had significantly shorter time to progression (median 20 weeks) and significantly shorter survival time (median 31 weeks) than other patients with extensive disease (medians 30 and 46 weeks). Patients with bone marrow involvement had significantly more often metastases in three or more organs than others with extensive disease. The negative prognostic significance of bone marrow involvement was however independent of the negative prognostic significance of the number of organs with metastases.

Fatal infection in patients treated for small cell lung cancer in the Institute of Tuberculosis and Chest Diseases in the years 1980-1994.

The study was performed to explore the frequency of infections present at death and infection as the main cause of death (fatal infection - FI) in 845 consecutive patients (pts) treated for small cell lung cancer (SCLC) at the Institute of Tuberculosis and Chest Diseases in Warsaw, in the period 1980-1994. Diagnosis of infection was based on clinical signs and symptoms, the presence of new lesions on the chest X-ray, microbiological tests and/or autopsy examination. All cases of fungal infection, Pneumocystis carinii pneumonia (PCP) and tuberculosis were proved by autopsy and microscopic examination (including special staining). FI was diagnosed if no progression of cancer was noted and no other complications occurred. Infection was present at the time of death in 116 patients (13.7%) and FI was the cause of death in 39 of them (4.6%). Nine patients died from fungal infection, eight from bacterial infection, seven from PCP and two from tuberculosis. In 13 cases the aetiology of infection found at autopsy was not determined. All FI patients received chemotherapy and corticosteroids, 16 of them also had radiotherapy on the tumour and mediastinum. Thirty-two out of 35 patients had leucopenia. The risk of death from infection was greater in patients above 60 years of age. Patients in bad performance status died of infection significantly earlier than others (P<0.05).

Survival of patients with limited small cell lung cancer in whom complete remission was obtained (a non-randomised retrospective study of 124 consecutive patients.

The aim of this study was to assess whether thoracic radiotherapy (TRT) is necessary for those patients (pts) with limited small cell lung cancer (SCLC) who obtained CR after induction chemotherapy (ChT). The analysis include retrospective material of 124 consecutive pts with limited SCLC. All pts had induction ChT (3-5 courses): 78 with CAVE (cyclophosphamide, doxorubicine, etoposide) and 46--with other regimens without etoposide. After induction ChT 55 pts were irradiated on tumor and mediastinum and in 69 the same ChT was continued for 6-8 courses or till progression. After induction ChT CR was obtained in 31 pts, PR in 67 and NR in 26. TRT significantly increased the number of CR among those pts who did not achieve satisfactory tumor response after induction ChT. The median survival was 24 months for those patients who obtained CR, 12 months for those who obtained PR and 9 months for those who did not respond. In the group of patients who obtain CR, survival was the same for those treated with ChT alone and for those treated with ChT and TRT. We conclude that in the treatment of individual patient with limited SCLC TRT is indicated for those who did not obtain CR after ChT. Whether patients in whom CR after chemotherapy was obtained can further gain by application of TRT is worth further randomised studies.

Combination chemotherapy with cyclophosphamide, epirubicin and etoposide in small cell lung cancer.

From March 1987 to February 1991, 136 patients with untreated small cell lung cancer (64 patients with limited disease and 72 with extensive disease), were treated as part of a prospective multi-center study, with a combination of cyclophosphamide 1000 mg/m2 i.v. on day 1, epirubicin 70 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 i.v. on days 1, 3 and 5. Courses were repeated every 3 weeks. One-hundred thirty-four patients were evaluable. There were 42 (31%) complete responses and 66 (49%) partial responses for an overall response rate of 80% (95% confidence interval 71-87%). A complete response was seen in 24 patients (38%) with limited disease and in 18 patients (26%) with extensive disease, while a partial response was observed for 31 (48%) and in 35 (50%) patients, respectively. The median duration of response for all patients was 8.9 months (range, 1-60+ months). The median duration of survival for the entire group was 11.4 months (12.5 months for limited disease and 9.8 months for extensive disease). The 2-year survival rate for the whole group was 13%. The main side-effects were myelosuppression, alopecia, nausea and vomiting. Grade 4 toxicity was seen in 8.5% of patients. In conclusion, the studied regimen was found to be active and well tolerated and may be considered as an alternative to standard chemotherapy combinations in SCLC.

Usefulness of the PAL test in the diagnosis of lung cancer.

Usefulness of a simple microagglutination test for diagnosis of malignant diseases was evaluated in the diagnosis of lung cancer. The test was not specific, being positive in 82% of malignant and 55% of nonmalignant cases. It was shown that poly-L-lysine-induced agglutination of lymphocytes reflects rather changed serum than cell properties and cannot be taken as a method for detection of sensitized cells.

The role of human chorionic gonadotropin beta subunit elevation in small-cell lung cancer patients.

Human chorionic gonadotropin (HCG)-like immunoreactivity has been found in many non-trophoblastic tumours, but the biological behaviour of HCG-producing cells has not been clarified yet. The aim of the study was to estimate the frequency of serum HCG beta subunit (s beta HCG) elevation in patients with small-cell lung cancer (SCLC) and to assess its possible prognostic role in this type of tumour. An attempt was also made to reclassify the histology in selected cases to see whether the elevated (s beta HCG) level is connected with any special subtype of small-cell lung cancer. A total of 156 SCLC patients entered the study: 93 men, 63 women, median age 58 years. s beta HCG activity was measured by immunoenzyme assay (Abbott EIA beta HCG 15-15) before treatment. s beta HCG elevation (above 5 mIU/ml) was found in 21 of 156 patients (14%). Response to treatment after chemotherapy (complete and partial response) was obtained in only 48% of those patients in whom elevated s beta HCG was found, in comparison to the 73% response rate observed in the remaining patients. Only 5% of patients with elevated s beta HCG survived 2 years, in comparison to 21% surviving for 2 years among the remaining patients. The prognostic significance of elevated s beta HCG and extent of disease were independent of each other (Cox's proportional-hazard model). Thus s beta HCG elevation in SCLC seems to be a marker of more resistant tumours and of poor prognosis. We have not found any connection between the subtype of small-cell lung cancer and elevated s beta HCG. Elevated s beta HCG was found in 2 out of 11 patients with oat-cell carcinoma, in 3 out of 10 patients with an intermediate cell type and in 5 out of 13 patients with small-cell lung cancer in which the assessment of the subtype was not possible.

The clinical value of Cyfra 21-1 estimation for lung cancer patients.

Cytokeratin-19, one of the cytoskeletal proteins, is expressed both in bronchial epithelium and in lung cancer cells. The aim of our study was to establish the value of serum cytokeratin-19 soluble fragment (Cyfra 21-1) measurement in lung cancer patients. Cyfra 21-1 levels were estimated in 35 patients (pts) with benign lung diseases and in 116 lung cancer patients: 55 pts with squamous cell lung cancer, 38 pts with small cell lung cancer and 23 pts with adenocarcinoma. The cutoff level was set at 4 ng/ml with a specificity of 94% and a sensitivity of 40%. Elevated Cyfra 21-1 values were found in 44% of squamous cell lung cancer, 39% of adenocarcinoma and 34% of small cell lung cancer pts (the difference was not significant). In squamous cell lung cancer and in adenocarcinoma elevated Cyfra 21-1 values were observed more often in patients with advanced disease than in patients with limited disease. There was no significant correlation between the initial Cyfra 21-1 level and the response to chemotherapy. Cyfra 21-1 was not a prognostic indicator, although in operable squamous cell lung cancer the proportion of survivors in the second year of observation was higher among the patients with normal preoperative Cyfra 21-1 levels.

[Levels of ferritin in serum of patients with lung cancer]. / Stezenie ferrytyny w surowicy chorych na raka pluca.

Serum ferritin levels using the radiometric method were determined in 161 lung cancer patients and in 50 patients with non-malignant pulmonary disorders. Elevated serum ferritin levels were seen more often in lung cancer patients (82%) than in those with the non-malignant disorders (52%). The levels of ferritin were also affected by the extension of the disease. In patients with stage III and IV serum ferritin levels were more pronounced (median 577 ng/ml) in comparison with stage I and II (300 ng/ml). Determination of serum ferritin levels may help in evaluating disease progression and staging, but can not be used as a screening test due to a low specificity.

[Usefulness of simultaneous antigenic determination of carcinoembryonic antigen (CEA), ferritin and orosomucoid levels in diagnosis of lung neoplasms]. / Przydatnosc jednoczesnego oznaczania antygenu rakowo-plodowego (CEA), ferrytyny i orozomukoidu w diagnostyce raka pluca.

Basing on results of tumor marker levels (CEA, ferritin, orosomucoid) in 271 lung cancer patients and 50 with non-malignant pulmonary diseases the authors found that assessment of different tumor markers is clinically more useful than single marker evaluation. Analysing several markers increases the specificity to almost 100% but decreases the sensitivity. Assessing several markers can help differentiating between malignant and non-malignant pulmonary disorders. It may also help in correctly staging the disease. A 12 month survival rate was seen only in 50% of the patients in whom the levels exceeded the cut-off value of two studied markers, whereas 90% survived 12 months if all marker levels were within normal levels. None of the patients with all markers exceeding the normal values survived one year after surgery. Survival rates of patients treated non-surgically were not influenced by the tumor marker levels.

[Osteochondroplastic tracheobronchopathy--relation to rhinitis atrophica and iron deficiency]. / Tracheobronchopatia osteochondroplastyczna--relacja z ozena i niedokrwistoscia z niedoboru zelaza.

Tracheobronchopathia osteochondroplastica (TO) is a rare disease with accumulation of bony and cartilaginous nodules in the tracheal and bronchial mucosa. In some cases rhinitis atrophica (ozena) has been associated. A case of TO coexisting with ozena and iron deficiency anaemia was described.

[Cytomegalic disease as a cause of disseminated lung lesions in an immunosuppressed patient]. / Cytomegalia jako przyczyna masywnych zmian rozsianych w plucach u chorego w immunosupresji.

A case of disseminated lesions in the lungs was diagnosed just during autopsy as cytomegalic infection. 54-year old patient treated since 10 years because of lymphoplasmacytoid lymphoma of low malignancy was admitted to Institute of Tuberculosis with suspicion of miliary tuberculosis. The high temperature, pemphigus--like skin lesions and disseminated lesions in the chest X-ray appeared immediately after succeeding chemotherapy. Tuberculous bacilli. Aspergillus fumigatus and Pneumocystis carinii were not found in examined materials (BALF, blood, urine, skin and mucous lesions). Patient died after 3 days and typical lesions of cytomegalovirus infection were found only after autopsy in macroscopic picture of the lungs.

[Pulmonary sarcoidosis diagnosed in 2 cases suspected to be neoplasms]. / Sarkoidoza pluc rozpoznana w 2 przypadkach podejrzanych o nowotwór.

Two young patients suspected of neoplasms were admitted to Thoracic Surgery Department of Institute of Tuberculosis in first case (35-years old woman) chest x-ray showed atelectasis of upper right lobe, enlarged lymph nodes of mediastinum and right hillium-lymphoproliferative process was suspected. Repeated bronchoscopies revealed narrowing of upper right bronchus and in biopsy--granulomas with small focus of necrosis were found. Tuberculosis was not excluded. During short antituberculous treatment progression of lung lesions and enlarged supraclavicular lymph node were observed. Following biopsy confirmed sarcoidosis. Treatment with prednisone was successful. In second case the chest x-ray showed large masses in both lungs suspected of seminoma metastases. Lung biopsy made during thoracotomy revealed sarcoidosis.

[Pneumonia and panophthalmitis as first signs of pneumococcal endocarditis]. / Zapalenie pluc i wnetrza galki ocznej jako pierwsze etapy pneumokokowego zapalenia wsierdzia.

A case of pneumonia associated with pneumococcal endocarditis of bicuspid aortic valve complicated by pneumococcal meningitis and panophthalmitis successfully treated by antibiotics and late valve replacement was described.