Carcinogenesis-related changes in iron metabolism in chronic obstructive pulmonary disease subjects with lung cancer.

Chronic obstructive pulmonary disease (COPD) is often accompanied by lung cancer. In our previous work, it was observed that matrix metalloproteinase-3 and haptoglobin (HP) polymorphisms were potential markers of enhanced susceptibility to lung cancer development among male COPD subjects. Here, results are reported on blood serum levels of several proteins involved in iron metabolism, inflammation and the oxidative stress response compared between the same groups of subjects. The blood serum levels of tumor necrosis factor α (TNFα), transferrin, hepcidin, ferritin, soluble transferrin receptor and 8-oxo-2'-deoxyguanosine were compared, as well as total iron-binding capacity (TIBC) and ceruloplasmin ferroxidase activity in two groups of subjects: Male COPD patients (54 subjects) and male COPD patients diagnosed with lung cancer (53 subjects). Statistically significant differences were identified between the two groups in transferrin and TNFα levels, as well as in TIBC; all three parameters were lower in the group consisting of COPD patients diagnosed with lung cancer (P<0.01). It was also revealed that HP genotype 1/2 was concomitant with low transferrin blood level in subjects with COPD; this apparent dependence was absent in the COPD + cancer subjects. The results indicate a role of iron metabolism in the susceptibility to lung cancer in COPD-affected subjects. They also emphasize the importance of individual capacity for an effective response to oxidative stress during the pathogenic process as HP is a plasma protein that binds free hemoglobin and its polymorphism results in proteins with altered hemoglobin-binding capacity and different antioxidant and iron-recycling functions.

Predictors of EGFR mutation and factors associated with clinical tumor stage at diagnosis: Experience of the INSIGHT study in Poland.

Targeted therapy of non-small cell lung cancer (NSCLC) patients with mutations in the epidermal growth factor receptor (EGFR) gene has been associated with improved prognosis. However, there is a shortage on data from real-world clinical practice in management of EGFR-positive NSCLC patients in Poland. The present study retrospectively analyzed data from the INSIGHT study to evaluate the incidence and clinical management of EGFR-positive NSCLC in Poland. The authors additionally aimed to identify predictors of the EGFR mutation and factors associated with clinical stage of the tumor at diagnosis. Incidence of EGFR mutations was 11.8% and the most common mutations were a deletion on exon 19 and an L858R substitution on exon 21. Mutations were strongly associated with female gender [male vs. female odds ratio (OR): 0.51; P=0.004] and never having smoked (current/past smoker vs. never smoked OR: 0.16; P<0.001), and advanced clinical stage (stage IV vs. stage I/II OR: 2.89; P=0.029). Patients with EGFR mutation were also observed to have a greater propensity to develop bone metastasis (OR: 11.62; P=0.008). Multivariate regression analysis demonstrated that patients with past or current smoking history or a poor performance on the Eastern Cooperative Oncology Group (ECOG) scale were less likely to have the EGFR mutation. Furthermore, EGFR-positive patients with greater ECOG scores and a tumor other than adenocarcinoma or squamous cell carcinoma were more likely to present advanced tumors. Early screening for EGFR mutation and the use of EGFR-targeting therapies as first-line agents may lead to better prognosis and successful clinical management of EGFR-positive NSCLC patients.

Fire-eater's lung.

Fire eater's lung (FEL) is an acute hydrocarbon pneumonitis caused by aspiration or inhalation into airways of liquid hydrocarbons. This disorder is classified into distinct form of chemical toxic pneumonitis. An amateur fire-eater is presented in this work. He accidentally aspirated into airways about 1/3 of glass of grill lighter fluid composed of mixture of liquid hydrocarbons. A few hours after this incident he had severe symptoms like weakness, high temperature, midsternal pleuritic chest pain, myalgia of the back, shortness of breath, and dry cough. Radiologic examination revealed consolidations with well-defined cavitary lesions (pneumatoceles) in lower lobes mainly in the left lower lobe. After one week of this event clinical improvement was observed. The lesions resolved nearly completly during three months. The review of the literature connected with fire-eater's lung is also presented.

Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects.

INTRODUCTION AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is often accompanied by lung cancer. Among the genes that may play a role in the occurrence of COPD and lung cancer are those encoding the proteolytic enzymes, such as matrix metalloproteinases (MMPs) and their tissue inhibitors. The objective of this study was to find MMPs-associated markers useful in the identification of COPD subjects with increased susceptibility to developing lung cancer. MATERIALS AND METHODS: We compared the frequency of single nucleotide polymorphisms in genes coding for matrix proteinases (MMP1, MMP2, MMP3, MMP9, MMP12) as well as tissue inhibitor of metalloproteinases (TIMP1) in two groups of subjects: COPD patients (54 subjects) and COPD patients diagnosed for lung cancer occurrence (53 subjects).The levels of the respective proteins in blood serum were also analyzed. RESULTS: The frequencies of 2 genotypes, MMP3 rs3025058 and MMP3 rs678815, were significantly different between the studied groups. In both cases, more heterozygotes and less homozygotes (both types) were observed in the COPD group than in the COPD + cancer group. A significantly higher TIMP1 level in blood serum was observed in the COPD + cancer group than in the COPD group. There were no statistically significant differences in MMPs blood levels between the studied groups. In addition, no genotype-associated differences in TIMP1 or MMPs blood levels were observed. CONCLUSIONS: Homozygocity for MMP3 rs3025058 and rs678815 polymorphisms is a potential marker of enhanced susceptibility to lung cancer development among COPD subjects.

[Pneumocystis pneumonia in HIV-infected patients with cytomegalovirus co-infection. Two case reports and a literature review]. / Pneumocystozowe zapalenie pluc u zakazonych HIV przy wspólistniejacym zakazeniu cytomegalowirusem. Opis dwóch przypadków i przeglad literatury.

Pneumocystis pneumonia (PCP) is one of the infectious lung diseases diagnosed in HIV-infected patients. The pathogen responsible for the development of this opportunistic infection is an atypical fungus called Pneumocystis jiroveci. PCP remains the most common disorder diagnosed at the onset of acquired immunodeficiency syndrome (AIDS), especially in individuals not aware of their HIV infection. The most important risk factor of PCP development in HIV-infected person is the decrease of T CD4+ cell number below 200/mcL. Clinical symptoms consist of: chronic cough, dyspnoea and weakness. Arterial blood gas analysis often reveals the presence of hypoxaemia, and high-resolution computed tomography imaging shows diffuse ground glass opacities. Treatment is based on intravenous administration of trimetoprim-sulfamethoxasole. In patients with moderate and severe symptoms of PCP it is recommended that corticosteroids are used. Co-infection with cytomegalovirus (CMV) is a poor prognostic sign in PCP. CMV-related organ disease should be suspected in patients with T CD4+ cell number lower than 50/mcL. It is arguable whether CMV infection in symptomatic PCP patients should be treated. There are suggestions that corticosteroids used in PCP patients with CMV co-infection could promote the development of CMV pneumonia. In the present paper we present two patients with PCP, unaware of their HIV infection. In both cases a CMV co-infection was found.

Association of genetic dependences between lung cancer and chronic obstructive pulmonary disease.

INTRODUCTION: Recent studies have shown an increased risk of lung cancer in patients with bronchial obstructive changes, including patients with COPD. It seems that there are common factors of pathogenesis of both diseases associated with oxidative stress. In the present paper the genes linked to the repair of oxidative damage of DNA, associated with cancer, of iron metabolism and coding proteolytic enzymes were assessed. MATERIAL AND METHODS: The study was conducted in two groups of patients: 53 patients with non-small cell lung cancer and chronic obstructive pulmonary disease, and 54 patients only with chronic obstructive pulmonary disease. The polymorphisms of the single nucleotide were determined in the case of the majority of genes using the PCR-RFLP method. The statistical analysis of quantitative variables was executed using the Mann-Withney U-test and the test of medians; the analysis of genetic variables was executed using the chi² test. RESULTS: Regarding the polymorphisms of genes involved in iron metabolism, statistically significant differences between the two groups have been demonstrated only in the case of haptoglobin gene HP1/2. A higher incidence of form 1/1 was found in patients with COPD and a higher incidence of form 1/2 in patients with lung cancer and COPD. Analysis of gene polymorphisms of proteolytic enzymes and inhibitors of the enzyme gene showed statistically significant differences between the two groups only for the MMP3 gene 6A/5A. In the case of the MMP12 gene polymorphism (A-82G) a tendency toward differences in the occurrence of specific alleles was identified. CONCLUSIONS: These results indicate that patients with coincidence of COPD and lung cancer have disorders of the genes involved in iron metabolism, and they have different genetic polymorphisms of proteolytic enzymes comparing to COPD patients.

[Chylothorax in patients with diffuse pulmonary lymphangiomatosis]. / Chlonkotok oplucnowy w przebiegu naczyniakowatosci limfatycznej pluc.

The occurence of chylothorax is uncommon and usually is caused by trauma or neoplastic process of the mediastinum. Primary lymphatic lesions of the lungs are extremly rare. One of them is lymphangiomatosis --diffuse lesions characterized primarily by an increased number of complex anastomosing lymphatic channels in which dilatation is secondary phenomenon. These lesions can involve lungs, mediastinum and pleura. The prognosis for the patients with this disease limited to the thorax is guarded and progressive although some patients have realtively indolent course. We present 2 patients : 18-years old boy and 17-years old girl. admitted to hospital because of chylothorax. The diagnostic did could not allow to discover disruption of thoracic duct, even during thoracoscopy. In material taken from the pleura and mediastinum during exploratory thoracotomy - diffuse pulmonary lymphangiomatosis was found. CT examination of the chest revealed osteolysis of the spine. The girl died after 6 weeks from the first symptoms and boy is observed for 18 months with symptoms of progressive restrictive lung disease.

[Hypersensitivity pneumonitis recognised by open lung biopsy in patients at the Institute of Tuberculosis and Lung Diseases]. / Alergiczne zapalenie pecherzyków plucnych rozpoznane przy pomocy otwartej biopsji pluca w materiale Instytutu Gruzlicy i Chorób Pluc.

UNLABELLED: Diagnosis of hypersensitivity pneumonitis (HP) is made on the basis of a combination of clinical features connected with the exposition to organic dusts, radiographic abnormalities, lung function tests and immunological tests. Open lung biopsy (OLB) and histological examination is not necessary and is indicated mainly in chronic and subacute form of HP. In the chronic form of HP symptoms often do not show a temporal relationship with antigen exposure and errors occur especially if specific questions are not asked about exposure to antigen if HP. The aim of this paper was to analyse whether OLB was necessary in all patients in whom HP was recognised just after this procedure. Material included 21 patients in whom microscopic examination suggested HP among 258 pts in whom OLB was performed in the period of 1998-2003. There were 13 men and 8 women at the age of 18 to 65 years, mediana 42 years. RESULTS: We found 3 groups of pts. Group "+" included 9 exposed pts. They were asked and confirmed contact with birds, hay and 7 of them observed correlation between exposition and symptoms. The second Group "-" included 7 pts who were asked about exposition and who answered in the negative. In all of them HRCT scans suggested HP. Restriction was below 70% of VC in 3 pts. The third Group "0" included 5 pts who were not asked about exposition and correlation with symptoms. Two from them lived in the rural area. CONCLUSIONS: Open lung biopsy was not necessary for 6 patients in Group "+", because then had enough symptoms to recognise HP. In 3 patients of Group "+" and in 5 of Group "0" OLB could be not necessary because specific anamnesis and additional examinations were not collected. OLB was necessary method for 7 patients in Group "-".

[Organizing pneumonia--analysis of 18 own cases]. / Organizujace sie zapalenie pluc--analiza 18 przypadków.

Organizing pneumonia (OP) is a rarely diagnosed disease, however the incidence ratio was estimated as 6-7/100000. Disease can occur in cryptogenic form or as a secondary reaction to various noxious agents, drugs, and ionising radiation, as a concomitant disease to infections, lympho- and myeloproliferative disorders, and connective tissue diseases. Symptoms of OP are non-specific therefore lung biopsy and histological examination are necessary for diagnosis. Eighteen cases of OP, 15 women and 3 men, aged 40 to 76 years, are presented with analysis of clinicopathological characteristic and therapeutic problems. In all cases diagnosis was confirmed by open lung biopsy. In one case radiotherapy and in one trastuzumab treatment was the cause of OP. In further 3 women antibodies against Chlamydia pneumoniae and in one--against Mycoplasma pneumoniae were found in serum. Probably Hashimoto disease was the cause of one case. In 12 patients the OP was idiopathic. Majority of patients were treated by prednisone (0.5 mg/kg). In one patient regression without any treatment was noticed and in other one--after cessation of trastuzumab. Five women were treated by clarithromycin. In 3 of them regression was observed but in other 2 corticotherapy was necessary. The observation period ranged from 1 month to 9 years, mean 34 months.

[Invasive treatment of proteinosis]. / Inwazyjne leczenie proteinozy.

The case of alveolar proteinosis successfully treated with whole lung lavage is described. In 40 years old, heavy smoker man disease started with recurrent respiratory tract infections. Disseminated lesions in chest x-ray were found. Patient was treated with antibiotics and corticosteroids without response-respiratory failure was developed. Diagnosis of alveolar proteinosis was confirmed after open lung biopsy. Bronchoalveolar lavage with small amount of 0.9% saline (200 ml) was repeated 7 times without improvement. PaO2 was 48 mmHg. Whole lung lavage with 10 L of 0.9% saline to each lung was repeated 2 times (total amount of liquid equal 40 L). PaO2 after treatment was 64 mmHg and 2 months later-84 mmHg. No complications were observed. Procedure was exactly described with parameters of respiratory system function.

[Purulent lung diseases necessitating surgical treatment--case reports]. / Ropne choroby pluc wymagajace leczenia chirurgicznego--opis przypadków.

Majority of purulent lung diseases are treated with antibiotics. But sometimes this therapy is not successful and surgical treatment is necessary. Two patients are described in this paper. 68 years old woman in whom infiltration in left lung enlarged during antibiotics therapy. CT examination did not allow to differentiate between abscessus and tumor. Results of bacteriologic and cytologic examination of transthoracic biopsy were negative. During thoracothomy abscessus was resected and diagnosis was confirmed by patomorphologic examination. The second case: 16-years old girl was addmitted to hospital because of high temperature and abnormal chest X-ray picture (infiltration and liquid level in lower right lobe). During puncture the pus was evacuated but bacteria were not cultured. Antibiotics were not effective. Thoracothomy was done and large cysta bronchogenes was resected. In both cases surgical treatment was effective.